Online quiz 1.docx

Question: Which factor does not predict relapse of diabetes in obese patients with DM2, whom have experienced remission of diabetes following gastric bypass surgery?

Pre-operative glycemic control

Insulin therapy before surgery

Pre-operative BMI values

Pre-operative diabetes duration

Older age at surgery

Answer: The correct answer is pre-operative BMI values. Data was collected in a retrospective cohort study of 4,434 adults with type 2 diabetes who underwent gastric bypass from 1995 to 2008. Diabetes remission and relapse events were recorded.Multivariate analysis showed older age at surgery was associated with higher risk of relapse (HR for 5-year increase in age, 1.07; 95 % CI, 1.01 to 1.14). Subjects with poor preoperative glycemic control (HbA1c ≥6.5 %) were significantly more likely to experience relapse than those with good preoperative control, (HR for HbA1c 6.5-8% 1.34; 95% CI 1.04-1.71, HR for HbA1c 8-9% 1.43; 95% CI 1.03-1.97, HR for HbA1c 9-10% 1.95; 95% CI, 1.34-2.84). Subjects treated with insulin were significantly more likely to experience relapse than diabetic subjects not using insulin before surgery (HR for patients on oral medication at surgery 1.37; 95% CI 1.10-1.70 and HR for patients on insulin at surgery 1.91; 1.48-2.45). Longer diabetes duration was significantly associated with higher relapse rate (HR for each additional year of diabetes, 1.13; 95 % CI, 1.09 to 1.17). However, pre-operative BMI values were not significantly different (p = 0.93) between patients who never completely remitted their diabetes (BMI 45.5 kg/m2), patients who completely remitted but relapsed (BMI 45.8 kg/m2), and patients who durably remitted their diabetes (BMI 45.6 kg/m2). Arterburn D, et al. A Multisite Study of Long-term Remission and Relapse of Type 2 Diabetes Mellitus Following Gastric Bypass. Obesity Surgery 2012

Question 1: Clinical characteristics of obese, ketosis-prone diabetes include which of the following:

Preserved beta cell function Age at onset < 40 years Presence of islet cell specific autoantibodies Female sex predominance DKA provoked by significant precipitating stress

Answer: The correct answer is preserved beta cell function. Other clinical characteristics of obese, ketosis-prone diabetes are; absence of islet cell autoantibodies, male sex preponderance, DKA that is unprovoked by any significant precipitating stress, and age at onset usually > 40 years. The Endocrine Society; 2011:43.

Question 2: The most commonly reported adverse event with Janumet in the treatment of type 2 diabetes is:

Abdominal Pain Nausea Diarrhea Upper respiratory infection Headache

Answer: The correct answer is diarrhea. In clinical studies, the most common adverse reactions reported with Janumet in ≥ 5% of patients and more commonly than in patients treated with placebo were as follows: diarrhea > upper respiratory tract infection > headache. Inc. DIAB-1002314-0000-05/11

Question 3: What is the best screening test for cystic fibrosis-related diabetes (CFRD)?

Urine glucose HbA1c

Fructosamine Oral glucose tolerance test (OGTT) Fasting plasma glucose

Answer: The correct answer is OGTT. The American Diabetes Association and The Cystic Fibrosis Foundation recommend the oral glucose tolerance test (OGTT) as the screening test of choice for CFRD. Although it is an imperfect test due to the variability observed in individual CF patients over time, longitudinal studies demonstrate that a diabetes diagnosis by OGTT correlates with clinically important CF outcomes including the rate of lung function decline over the next 4 years, the risk of microvascular complications, and the risk of early death. The committee concluded that HbA1c is not sufficiently sensitive for diagnosis of CFRD and should not be used as a screening test. Fasting plasma glucose does not identify those patients without fasting hyperglycemia, and will miss the diagnosis of diabetes in approximately half of CF patients. Fructosamine and urine glucose have low sensitivity in the CF population. Diabetes Care. 2010;33(12):2697-2708.

Question 4: Patients with maturity-onset diabetes of the young (MODY )3 may respond to which of the following agents:

Glipizide Pioglitazone Metformin Sitagliptin Exenatide

Answer: The correct answer is glipizide. Patients with maturity-onset diabetes of the young (MODY)3 have a mutation in TCF/HNF-alpha. Mutations of this gene lead to reduced beta cell mass or impaired function. About 70% of people develop this type of diabetes by age 25 years, but it occurs at much later ages in a few. This type of diabetes can often be treated with sulfonylureas with excellent results for decades. Diabetes Res Clin Pract. 2008;81(1):e1-e3

Question 5: The American Association of Clinical Endocrinologist (AACE) recommends personal continuous glucose monitoring for patients with type 1 diabetes and the following characteristics:

Hypoglycemic unawareness or frequent hypoglycemia During preconception and pregnancy All answer choices are correct HbA1c over target Excess glycemic variability

Answer: The correct answer is all answer choices are correct. The American Association of Clinical Endocrinologists (AACE) recommends personal CGM for those with type 1 DM and the following characteristics: Hypoglycemic unawareness or frequent hypoglycemia, HbA1c over target, excess glycemic variability (eg, hypoglycemia judged to be excessive, potentially disabling, or life- threatening), requiring HbA1c lowering without increased hypoglycemia, and during preconception and pregnancy. Endocrine Practice. 2010;16(5):730-745.

Question : A randomized, double-blind, multicenter trial was conducted to investigate whether patients taking metformin for type 2 diabetes mellitus (T2DM) have improved glycemic control without compromising tolerability by adding saxagliptin vs. uptitrating metformin. Which of the following best describes the results?

Reduction in 120-minute Post Prandial Glucose (PPG) was not significantly greater with saxagliptin + metformin XR than with uptitrated metformin XR

Reduction in Fasting Plasma Glucose (FPG) was significantly greater with uptitrated metformin XR than with saxagliptin + metformin XR

The proportion of patients experiencing ≤1 adverse events was greater with saxagliptin + metformin XR than with uptitrated metformin XR

Decreases in mean HbA1c were similar in patients receiving saxagliptin + metformin XR to those receiving uptitrated metformin XR

The percentage of patients achieving HbA1c <7.0% was significantly greater with saxagliptin + metformin XR than with uptitrated metformin XR

Answer: The correct answer is the percentage of patients achieving HbA1c <7.0% was significantly greater with saxagliptin + metformin XR than with uptitrated metformin XR. Adults with T2DM and HbA1c between 7.0 and 10.5% receiving metformin extended release (XR) 1500 mg/day for ≤8 weeks were randomized to receive saxagliptin 5 mg added to metformin XR 1500 mg (n = 138) or metformin XR uptitrated to 2000 mg/day (n = 144). At week 18, the adjusted mean reduction from baseline HbA1c was ?0.88% for saxagliptin + metformin XR and ?0.35% for uptitrated metformin XR (difference, ?0.52%; p < 0.0001). For 120-min PPG and FPG, differences in adjusted mean change from baseline between saxagliptin + metformin XR and uptitrated metformin XR were ?1.3 mmol/l (?23.32 mg/dl) (p = 0.0013) and ?0.73 mmol/l (?13.18 mg/dl) (p = 0.0030), respectively. More patients achieved HbA1c <7.0% with saxagliptin + metformin XR than with uptitrated metformin XR (37.2 vs. 26.1%; p = 0.0459). The proportions of patients experiencing any adverse events (AEs) were generally similar between groups; neither group showed any notable difference in hypoglycemia or gastrointestinal AEs. Adding saxagliptin to metformin XR provided superior glycemic control compared with uptitrating metformin XR without the emergence of additional safety concerns Fonseca V, et al. Adding saxagliptin to extended-release metformin vs. uptitrating metformin dosage. Diabetes, Obesity and Metabolism. 2012;14(4):365-371.

Question: Diabetes is the leading cause of new blindness among people ages 20-74 years. Which of the following statements is false regarding ranibizumab injection, (Lucentis)?

It’s a promising therapy for DM macular edema, but isn’t approved by FDA It is used to treat age related macular degeneration It is an anti-angiogenic VEGF inhibitor The most common side effectis bleeding of the conjunctiva

Answer: The correct answer is: It’s a promising therapy for DM macular edema, but isn’t approved by FDA is false. In August 2012, the Food and Drug Administration approved ranibizumab for the treatment of diabetic macular edema (DME). The drug’s safety and effectiveness to treat DME were established in two clinical studies involving 759 patients who were treated and followed for three years. Patients were randomly assigned to receive monthly injections of Lucentis or no injections for 24 months. Results showed that between 34 - 45 % of those treated withLucentis gained at least three lines of vision compared with 12 -18 % of those who did not. The most common side effects of the drug were bleeding of the conjunctiva, eye pain, and increased intraocular pressure.The FDA previously had approved Lucentis to treat age-related macular degeneration and macular edema following retinal vein occlusion. Ranibizumab is an monoclonal antibody fragment which inhibits a number of subtypes of vascular endothelial growth factors. VEGF increases retinal vascular permeability, thereforeblocking VEGF in the eye may prevent and reverse vision loss caused by macular degeneration. Ip MS, Domalpally A, et al. Long-term effects of intravitreal ranibizumab (RBZ) on diabetic retinopathy severity and progression. Presented at the 2012 Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO); May 6–10, 2012; Fort Lauderdale, Florida. Abstract 1336. Nguyen Q, et al.Ranibizumab for diabetic macular edema results from 2 phase III randomized trials: RISE and RIDE. Ophthalmology.2012;119:789–801.

Question 1: Which of the following best describes the results of a recent cross-sectional study investigating the impact of body mass index (BMI) status on the relationship of serum 25-hydroxyvitamin D (25OHD) concentration with insulin sensitivity?

The correlation of serum 25OHD with insulin sensitivity was much stronger in the overweight group than in the normal weight group.

The correlation of serum 25OHD with insulin sensitivity was similar in both the overweight and normal weight group

The optimal serum 25OHD concentration for insulin sensitivity is about 46 ng mL?1. The optimal serum 25OHD concentration for insulin sensitivity is about 34 ng mL?1.

Answer: The correct answer is the correlation of serum 25OHD with insulin sensitivity was much stronger in the overweight group than in the normal weight group. Obesity is a risk factor for hypovitaminosis D, insulin resistance and type 2 diabetes. This cross-sectional study enrolled 126 healthy and glucose-tolerant subjects. The participants were divided into two groups based on BMI: normal weight (n = 68) and overweight (n = 58). Insulin sensitivity index (ISI) was assessed by using hyperglycemic clamps. Serum 25OHD concentration was determined in the fasting samples. The correlation of serum 25OHD with ISI was much stronger in the overweight group (r = 0•5271, P < 0•0001) than in the normal weight group (r = 0•2836, P = 0•002). The correlation remained significant in the overweight group (r = 0•3620, P = 0•002), but not in normal weight group after adjusting for age, gender, BMI, season of study, ethnicity and exercise.

Nonlinear regression analysis revealed that when serum 25OHD concentration was > 40 ng mL?1, the association between serum 25D concentrations and insulin sensitivity plateaued. The results of this study suggested that overweight subjects with hypovitaminosis D may benefit more from vitamin D replacement than normal weight subjects. Furthermore, the optimal serum 25OHD concentration for insulin sensitivity is about 40 ng mL?1. Horng-Yih Ou, et al Eur J Clin Invest 2011; 41 (11): 1195–1201

Question: The recommended glucose target for diabetic patients admitted to the intensive care unit (ICU) is:

100-140 mg/dl140-180 mg/dl120-160 mg/dl80-110 mg/dl

Answer: The correct answer is 140-180 mg/dl. The American Association of Clinical Endocrinologists and the American Diabetes Association recommends a glucose range of 140-180 mg/dl for critically ill diabetic patients. Although a very tight glucose target 80–110 mg/dl was beneficial in a predominantly surgical ICU population (Leuven trial-2001), this target has been difficult to achieve in subsequent studies. Several randomized controlled trials (RCT’s) investigating the effect of intensive insulin therapy (IIT) on mortality with sub-analyses for patients with diabetes were performed at mixed surgical and medical ICU’s, without making distinction between surgical and medical patients. In all these studies IIT did not show survival benefit over conventional glucose control in patients with diabetes. Also when analyzing pooled data from both Leuven trials no benefit of IIT was seen in the diabetic patients. The achieved glucose levels in the IIT group of the pooled analysis ranged from 104 to 117 mg/dl and in the conventional group from 144 mg/dl to 171 mg/dl. The NICE-SUGAR trial published in 2009 included the largest population of diabetes patients (n= 1211) and achieved mean (SD) glucose values of 108 mg/dl and 144 mg/dl in the total population. In this subgroup the benefit tended towards the conventional treatment, just like the overall outcome. The negative results in the mixed populations are supported by analyses comparing mortality rates before and after the implementation of an IIT protocol showing no significant decrease in mortality with IIT in patients with diabetes. S.E. Siegelaar 826 et al. Best Practice & Research Clinical Endocrinology & Metabolism 25 (2011) 825–834 Research Clinical Endocrinology

Question 1: True or False: In a randomized trial, duloxetine was found to be inferior to pregabalin for the treatment of pain in patients with diabetic peripheral neuropathy (DPN) who had an inadequate pain response to gabapentin. (True or False)?

TrueFalse

Answer: The correct answer is False. The primary objective of this 12–week,open-label, noninferiority study was to determine whether treatment with duloxetine was at least as good as pregabalin in reducing pain associated with DPN in patients who had an inadequate pain response to treatment with gabapentin. (≥900 mg/d) (defined as a daily pain score of ≥4 on a numerical rating scale [0–10 points]). The mean change in the pain rating at end point was -2.6 for duloxetine and -2.1 for pregabalin. The 97.5% lower confidence limit was a -0.05 difference in means, establishing noninferiority. Tanenberg RJ et al. Mayo Clin Proc. • July 2011,•86(7):615-624

Question: Which of the following statements is true regarding the FREEDOM (Future Revascularization Evaluation in Patients With Diabetes Mellitus: Optimal Management of Multivessel cardiac Disease) trial?

CABG was associated with a lower risk of stroke

Patients in the PCI group had higher rates of acute renal failure

CABG was associated with a significant reduction in all-cause mortality

PCI was associated with a significant reduction in the risk of MI

Repeat revascularization was higher in the CABG treated patients

Answer: The correct answer is: CABG was associated with a significant reduction in all-cause mortality is false. FREEDOM enrolled 1900 patients with diabetes and coronary artery disease, a majority of whom had three-vessel disease, to treatment with CABG surgery or PCI with drug eluting stents. Dual antiplatelet therapy was recommended for at least 12 months, and patients were followed for a minimum of two years. The primary outcome measure was a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke. The 5-year event rates were 26.6% in the PCI group, as compared with 18.7% in the CABG group, for an absolute difference of 7.9 percentage points (95% confidence interval [CI], 3.3 to 12.5, P=0.005). There was increased all-cause mortality in the PCI group (P = 0.049), with 5-year rates of 16.3% in the PCI group versus 10.9% in the CABG group, for an absolute difference of 5.4 percentage points (95% CI, 1.5 to 9.2). There were fewer strokes in the PCI group with the 5-year rates being 2.4% in the PCI group and 5.2% in the CABG group (P = 0.03). The excess of strokes in the CABG group occurred in the first 30 days after randomization. The repeat revascularization rate after 1 year was 12.6% in the PCI group, compared with 4.8% in the CABG group(hazard ratio, 2.74; 95% CI, 1.91 to 3.89; P<0.001). Acute renal failure requiring hemodialysis within 30 days after revascularization was observed in 1 patient in the PCI group and 8 patients in the CABG group (P=0.02). Farkouh ME, Domanski M, Sleep LA, et al. Strategies for multivesselrevascularization in patients with diabetes. N Engl J Med 2012.

Question: A comparative trial was performed between once-daily liraglutide and once-weekly exenatide in patients with type 2 diabetes. Which of the following statements is false regarding the trial results?

More nausea, diarrhea, and vomiting occurred with liraglutide

Injection-site nodules were more common with liraglutide

There were more serious adverse events in the exenatide group

The liraglutide group lost more weight, irrespective of BMI

Decrease in fasting glucose was greater in the liraglutide group

Answer: The correct answer is: Injection-site nodules were more common with liraglutide is false.The trial was a 26 week, open-label, randomized, parallel-group study at 105 sites in 19 countries between Jan 2010, and Jan 2011. Type II diabetic patients on oralantihyperglycaemic drugs were randomly assigned (1:1) to receive injections of once-daily liraglutide (1.8 mg) or once-weekly exenatide (2 mg). The primary endpoint was change in HbA from baseline to week 26. Both drugs were associated with a decrease in HbA1, but was greater in patients taking liraglutide (-1.28% vs. -1.48%). However, the treatment difference (0.21%; 95% CI, 0.083-0.33) did not meet the predefined noninferiority criteria. At 26 weeks, fasting serum glucose significantly decreased in both groups (p<0.0001), but the decrease was greater in patients in the liraglutide group (-2.12 vs – 1.76) with a treatment difference (0.36; 95% CI, 0.05-0.66). Both treatments were associated with progressive decreases in bodyweight, but patients taking liraglutide lost more weight (-3.57 vs -2.68) irrespective of BMI, with a treatment difference (0.9; 95% CI, 0.39-1.40). The most common adverse events were mainly gastrointestinal in both groups, with a greater frequency of nausea, diarrhea, and vomiting in patients in the liraglutide group. Injection-site nodules were more common with exenatide than with liraglutide. There were more serious adverse events in the exenatide group (3% vs 2%) (including acute cholecystitis, myocardial infarction, pancreatitis and prostate cancer) but with no identifiable pattern of events.Buse JB. Exenatide once weekly versus liraglutide once daily in patients with type 2 diabetes (DURATION-6): a randomised, open-label study. Published online November7, 2012

Question 1: A retrospective study found that implementing a mandatory, comprehensive protocol for treating adult patients with diabetic ketoacidosis (DKA) resulted in:

Shorter time to clearance of the anion gap and ketonesAll answer choices are correctShorter ICU and hospital lengths of stayNo difference in the percentage of patients developing hypoglycemic episodes

Fewer recurrences of an anion gap acidosis.

Answer: The correct answer is all answer choices are correct. To determine the effect of a mandatory protocol for treating DKA, a chart review was conducted, which included a total of 241 consecutive nonpregnant patients >18 yrs old admitted to a medical intensive care unit for DKA between January 2000 and January 2005. The mandatory treatment protocol was implemented in May 2003. Before protocol implementation, the mean &elusmn;SD ICU and hospital lengths of stay were 44 &elusmn; 28 hrs and 91 &elusmn; 73 hrs, respectively. After implementation, ICU and hospital lengths of stay decreased 23% and 30%, to 34 &elusmn;18 hrs and 64 &elusmn;41 hrs, respectively (both p < .007). Time to anion gap closure and ketone clearance also decreased (both p < .05). No difference in the number of hypoglycemic episodes was observed. This was the first report of a protocol for DKA decreasing the rate of anion gap recurrence after discontinuation of an insulin infusion. Protocol-driven care can decrease intensive care unit (ICU) morbidity, mortality, length of stay, errors, and costs. Several DKA treatment guidelines exist, but previous studies of their effectiveness show no or limited benefit, perhaps because care was standardized for some but not all aspects of DKA or because their use was not mandatory. Bull, SV et al. Crit Care Med 2007 Vol. 35, No. 1

Question : A 52-year-old male with DM2 on insulin, reportsdysesthesia, numbness and tingling of extremities, and poor sleep quality. You diagnosediabetic peripheral neuropathic pain. Which therapy would you prescribe for analgesia and improved sleep?

AmitriptylineDuloxetinePregabalinVitamin B12

Answer: The correct answer is pregabalin. A recently published, double-blind, randomized trial compared amitriptyline, duloxetine and pregabalin in 104 diabetics with peripheral neuropathic pain. Subjective pain and sleep quality (using polysomnography sleep records) were assessed over 28 days. Amitriptyline, duloxetine, and pregabalin, all reduced subjective pain with no one drug being superior to another. Subjective pain ratings showed ∼50% improvement, in line with previous studies. For sleep, pregabalin improvedsleep continuity (P< 0.001), reducing wake after sleep onset, in line with previous reports. Duloxetine increased wake and reduced total sleep time (P< 0.01 and P< 0.001) and substantially reduced REM sleep. Previous literature suggests that amitriptyline promotes sleep initiation and sleep continuity, however there may be less impact of amitriptyline on sleep in patients with diabetic peripheral neuropathic pain. Research has shown that people who take metformin may be at risk for developing vitamin B12 deficiency associated peripheral neuropathy, however this patient is on insulin. Boyle J, et al. Randomized, Placebo-Controlled Comparison of Amitriptyline, Duloxetine, and Pregabalin in Patients with Chronic Diabetic Peripheral Neuropathic Pain. Impact on pain, polysomnographic sleep, daytime functioning, and quality of life. Diabetes CareDecember 2012 vol. 35 no. 12 2451-2458

Question: Clinical characteristics of obese, ketosis-prone diabetes include which of the following: Correct! Female sex predominanceDKA provoked by significant precipitating stressPreserved beta cell functionAge at onset < 40 yearsPresence of islet cell specific autoantibodies


Question: A randomized trial assessed the efficacy and safety of L-methylfolate calcium 3 mg, pyridoxal-5´-phosphate 35 mg, and methylcobalamin 2 mg (LMF-MC-PP; Metanx ®) in patients with diabetic peripheral neuropathy (DPN). Which of the following best describes the results?

The rate of adverse events was significantly higher in the Metanx ® group compared to placeboThere was no significant improvement in inflammatory biomarkers in the Metanx ® group compared to placeboThere was no significant difference in the quality of life survey between the Metanx ® and placebo groups

The neuropathy total symptom score-6 (NTSS-6) improved significantly in the Metanx ® group compared to placebo.There was a significant improvement in vibratory perception threshold (VPT) in the Metanx ® group compared to placebo.

Answer: The correct answer is the neuropathy total symptom score-6 (NTSS-6) improved significantly in the Metanx ® group compared to placebo. DPN affects at least 1 in 5 persons with diabetes causing debilitating neuropathic pain or partial to complete loss of sensation in the extremities. The cause is multifactorial and likely involves oxidative stress. Unfortunately, the treatment options are limited. The effects of the B vitamins, L-methylfolate calcium 3 mg, pyridoxal-5´-phosphate 35 mg, and methylcobalamin 2 mg (LMF-MC-PP; Metanx ®) on signs, symptoms, and biomarkers associated with DPN were assessed in a 24-week, multicenter, randomized, double-blind, placebo-controlled trial involving 214 patients with DPN (baseline vibration perception threshold [VPT]: 25-45 volts) but without peripheral vascular disease. Patients who had had previous surgery with residual neurologic deficit, or A1C >9% were excluded. Concomitant opiate use was not permitted, but other DPN medications could be used as long as doses were kept constant during the study. The mean patient age was 62.6 &elusmn; 8.9 years, and there were no differences between the LMF-MC-PP and placebo groups at baseline in age, race, ethnicity, duration of diabetes or neuropathy, or baseline outcome measures. At 24 weeks, change in VPT, the primary outcome, did not differ between the LMF-MC-PP and placebo groups (Table 1). In terms of secondary outcomes, a significant difference in mean neuropathy total symptom score-6 (NTSS-6) was observed with LMF-MC-PP vs. placebo, and the mental component scale (MCS) of the short form 36 (SF-36, a validated quality of life survey) improved significantly. Homocysteine, an inflammatory factor associated with diabetic complications including DPN was also significantly reduced in the Metanx group compared to placebo [(-2.7 &elusmn;3.0) vs (0.5 &elusmn;2.4) P=0.0001] Adverse events were infrequent, occurring in <2% of all subjects; none were considered serious. These findings suggest that LMF-MC-PP may be a safe and effective symptomatic therapy for patients with DPN, leading to improvement in components of quality of life and inflammatory biomarkers, despite a lack of change in vibration sensation. Fonseca, V.A. et al., Abstract 1053-P. American Diabetes Association 71st Scientific Sessions June 24 - 28, 2011 San Diego, California

Question : Which of the following best describes the results of the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial?

The rates of death and major cardiovascular events were significantly greater in patients undergoing prompt revascularization compared to those undergoing medical therapy.

None of the answers are correct The survival rates in the insulin-sensitization group were significantly higher compared to the insulin-provision

group. The survival rates in the insulin-provision group were significantly higher than in the insulin-sensitization group. The rates of major cardiovascular events were significantly higher in the medical-therapy group compared to the

revascularization group

Answer: The correct answer choice is none of the answers are correct. The Bypass Angioplasty Revascularization Investigation (BARI2D) trial was conducted to determine optimal treatments to prevent mortality and major cardiovascular events in patients with T2DM and stable ischemic heart disease. Both prompt revascularization compared with intensive medical therapy alone or with delayed revascularization, and insulin-sensitization compared with insulin-provisional therapeutic strategies were evaluated in 2368 patients over 5 years with the use of a 2×2 randomized factorial trial design. At 5 years, rates of survival did not differ significantly between the revascularization group (88.3%) and the medical-therapy group (87.8%, P=0.97) or between the insulin-sensitization group (88.2%) and the insulin-provision group (87.9%, P=0.89). The rates of freedom from major cardiovascular events also did not differ significantly among the groups: 77.2% in the revascularization group and 75.9% in the medical-treatment group (P=0.70) and 77.7% in the insulin-sensitization group and 75.4% in the insulin-provision group (P=0.13). In the PCI stratum, there was no significant difference in primary end points between the revascularization group and the medical-therapy group. In the CABG stratum, the rate of major cardiovascular events was significantly lower in the revascularization group (22.4%) than in the medical-therapy group (30.5%, P=0.01; P=0.002 for interaction between stratum and study group). Of note, in secondary analysis, insulin-sensitization therapies appeared to enhance the benefit of revascularization in the higher-risk subgroup of patients selected for CABG. Additionally, insulin sensitization was associated with lower body mass index, higher high-density lipoprotein cholesterol level, and lower rates of severe hypoglycemia.

Goldfine AB, Fonseca V. Management of diabetes mellitus in patients with cardiovascular disease in the bypass angioplasty revascularization investigation 2 diabetes (BARI 2D) trial. Circulation. 2010;121(22):2447-2449.

Question: A case series was conducted to evaluate the role of continuous subcutaneous insulin infusion (CSII) therapy in patients with symptomatic diabetic gastroparesis and unstable glycemic control. Compared with multiple–dose insulin (MDI) regimens, the use of CSII resulted in:

A higher median median capillary blood glucose (CBG)A reduction in length of hospital stay related to gastroparesis and glycemic instabilityNo change in glycemic variabilityNo statistically significant reduction in HbA1cAll of the answer choices are correct

Answer: A reduction in length of hospital stay related to gastroparesis and glycemic instability. Following initiation of CSII, the median length of inpatient bed days associated with hospital admissions related to gastroparesis and glycemic instability was reduced from 8.5 (range 0–144) days patient –1year –1 prior to CSII to 0 (range 0–15) days patient –1year –1. (p<0.05). The median HbA1c reduction with CSII was 1.8% (22 mmol/mol; p<0.05). The median capillary blood glucose (CBG) with CSII was significantly lower than with MDI: 7.7 mmol/l (range 3.8–15.4 mmol/l) vs 9.8 mmol/l (range 2.3–27 mmol/l), respectively, (p <0.001) Glycemic variability with CSII was significantly reduced compared with MDI: (p<0.001). The initial costs of CSII therapy are relatively high, but overall reduction in length of hospital stay may prove it to be cost effective. Sharma D et al. Diabetologia. Published online August 14, 2011

Question 1: A recent analysis of the HAPO study showed that measuring Hemoglobin A1c is a useful alternative to an oral glucose tolerance test OGTT for assessing the risk of adverse outcomes in pregnant woman. (True or False)?

False

True

Answer: The correct answer is false. The objective of this study was to compare associations of maternal glucose and A1C with adverse outcomes in the multinational Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study and determine, based on those comparisons, if A1C measurement can provide an alternative to an oral glucose tolerance test (OGTT) in pregnant women. Eligible pregnant women underwent a 75-g OGTT at 24–32weeks’ gestation. A sample for A1C was also collected. Neonatal anthropometrics and cord serum C-peptide were measured. Associations with outcomes were assessed using multiple logistic regression with adjustment for potential confounders. Among the 23,316 HAPO Study participants with glucose levels blinded to caregivers, 21,064 had a nonvariant A1C result. The mean ±SD A1C was 4.7960 ±40%. Associations were significantly stronger with glucose measures than with A1C for birth weight, sum of skin folds, and percent body fat > 90th percentile and for fasting and 1-h glucose for cord C-peptide (all P < 0.01). For example, in fully adjusted models, odds ratios (ORs) for birth weight > 90th percentile. For each measure higher by 1 SD were 1.39, 1.45, and 1.38, respectively, for fasting, 1- and 2-h plasma glucose and 1.15 for A1C. ORs for cord C-peptide > 90th percentile were 1.56, 1.45, and 1.35 for glucose, respectively, and 1.32 for A1C. ORs were similar for glucose and A1C for primary cesarean section, preeclampsia, and preterm delivery. On the basis of associations with adverse outcomes, these findings suggest that A1C measurement is not a useful alternative to an OGTT in pregnant women. The correct answer is false. The objective of this study was to compare associations of maternal glucose and A1C with adverse outcomes in the multinational Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study and determine, based on those comparisons, if A1C measurement can provide an alternative to an oral glucose tolerance test (OGTT) in pregnant women. Eligible pregnant women underwent a 75-g OGTT at 24–32weeks’ gestation. A sample for A1C was also collected. Neonatal anthropometrics and cord serum C-peptide were measured. Associations with outcomes were assessed using multiple logistic regression with adjustment for potential confounders. Among the 23,316 HAPO Study participants with glucose levels blinded to caregivers, 21,064 had a nonvariant A1C result. The mean ±SD A1C was 4.7960 ±40%. Associations were significantly stronger with glucose measures than with A1C for birth weight, sum of skin folds, and percent body fat Lowe LP, et al. Hyperglycemia and adverse pregnancy outcome (HAPO) study: Associations of maternal A1C and glucose with pregnancy outcomes. Diabetes Care.

Question: Which of the following best describes the results of a recent study evaluating the long-term safety, tolerability and efficacy of linagliptin?

Incidence of adverse events leading to discontinuation was highSignificant weight loss was achieved with linagliptin.Largest observed reduction of HbA1c with linagliptin was noted for those receiving the initial combination of linagliptin plus metforminHbA1c change from baseline to week 102 was 0.5% with linagliptin monotherapy.

Answer: The correct answer is: HbA1c change from baseline to week 102 was 0.5% with linagliptin monotherapy. The aim of this 78-week open-label extension study was to evaluate the long-term safety, tolerability and efficacy of the dipeptidyl peptidase-4 inhibitor linagliptin given either alone or in combination with other oral glucose-lowering agents in persons with type 2 diabetes. Subjects participated in one of four preceding 24-week, randomized, double-blind, placebo-controlled parent trials and who received linagliptin, linagliptin + metformin, linagliptin + metformin + a sulfonylurea or linagliptin + pioglitazone (all with linagliptin administered orally once daily). Individuals receiving one of these treatments during a previous trial continued the same treatment (n = 1532) for up to a total of 102 weeks, whereas those previously receiving placebo were switched to linagliptin (n = 589). All 2121 participants received at least one dose of the trial medication and were included in the primary safety analysis. In subjects previously receiving active treatment, the A1c reduction achieved during the 24-week parent trials was sustained through the 78-week extension period (change from baseline to week 102:) 0.8%). In participants randomized to linagliptin in the four previous trials (group A), the glucose-lowering effect of linagliptin achieved during the initial 24 weeks of treatment (mean change from baseline to week 24: - 0.8% was maintained over the 78 weeks of the extension phase (change from baseline to week 102: - 0.8%). Coefficient of durability per 78 weeks, 0.14% (p < 0.0001, non-inferiority 0.3%). The largest observed reduction of HbA1c with linagliptin was noted for those receiving the initial combination of linagliptin plus pioglitazone (change from baseline to week 102: -1.5%), followed by those receiving metformin background. Most AEs were mild or moderate and the incidence of severe AEs was low (3.8%). The incidence of AEs leading to discontinuation also was low (3.4%). Drug-related adverse events were experienced by 14.3% of participants. Hypoglycemia occurred in 13.9% of participants and was similar between those previously receiving treatment (13.6%) and those switching from placebo to linagliptin (14.6%). Hypoglycemia occurred most frequently with the use of metformin + a sulfonylurea background therapy (11%). Overall, no clinically relevant changes in body weight were observed. In conclusion Long-term treatment with linagliptin was well tolerated with no change in the safety profile observed during the extension study. Sustained long-term glycemic control was maintained for up to 102 weeks with either linagliptin monotherapy or linagliptin in combination with other oral glucose-lowering agents. Gomis R., Owens D. R., Taskinen, M.R., et al. Int J Clin Pract, August 2012, 66, 8, 731–740

Question: The results from a 26 week randomized trial, comparing the efficacy and safety between liraglutide once a day versus exenatide twice a day for type 2 diabetes showed:

Overall treatment satisfaction was significantly better in the exenatide group than in the liraglutide groupReduction of HbA1c values with liraglutide was statistically superior to that seen with exenatidePatients receiving exenatide experienced less persistent nausea.Patients receiving liraglutide experienced more episodes of hypoglycemiaWeight loss was greater in patients receiving liraglutide.

Answer: The correct answer is reduction of HbA1c values with liraglutide was statistically superior to that seen with exenatide. The mean change in HbA1c from baseline to week 26 (-1•12% vs -0•79% p<0•0001); Minor hypoglycemia was less frequent with liraglutide than with exenatide. Liraglutide and exenatide were associated with similar weight losses. Overall treatment satisfaction was significantly better in the liraglutide group (n=161) than in the exenatide group (n=143) (p=0•0004). The incidence of nausea was similar initially, but it was less persistent with liraglutide (estimated treatment rate ratio 0•448 for liraglutide vs exenatide; proportion of participants with nausea at week 26, 5 of 202 [3%] vs 16 of 186 [9%]/sub/sub The Lancet. 2009;374(9683):39-47

Question: BC is a 47-year-old male non-smoker with T2DM, hypertension, and obesity. He is taking metformin 1000 mg twice daily, lisinopril 40 mg each morning, and amlodipine 10 mg each morning. His blood pressure is 132/70 mm Hg. Which of the following would you do next?

Add a beta-blocker

Change his lisinopril or amlodipine dose to the eveningAdd a thiazide diuretic

Answer: The correct answer is: change his lisinopril or amlodipine dose to the evening. The benefits of lowering BP in diabetes to <140 mm Hg systolic and <80 mm Hg diastolic have been established in randomized control trials. However, the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial demonstrated that, in patients with T2DM, intensive BP lowering to <120 mm Hg systolic yielded no significant differences in fatal and nonfatal cardiovascular events compared with BP maintained between 130 and 140 mm Hg. Moreover, aggressive BP lowering may be associated with serious adverse events. The 2012 ADA guidelines state that a systolic BP goal of <130 mm Hg is appropriate for most patients; however, higher or lower BP targets may be individualized.If a patient is taking multiple BP medications, one or more should be taken at bedtime. Administering an antihypertensive at night results in better ambulatory BP control and reduces cardiovascular mortality. BC is on maximal doses of 2 antihypertensive agents, and his BP is 132/70 mm Hg. His physician must individualize care and decide If adding a third agent is worth the risk of another medication when clear benefit has not been demonstrated. It is reasonable to continue his current regimen with the exception of changing either his lisinopril or amlodipine dose to the evening and reassessing his BP control at his next visit. Cusbman WC, Evans GW, Byington RP, et al. ACCORD Study Group. Effects of intensive blood-pressure control in type 2 diabetes mellitus. NEngUMed. 2010;362:15?5-1585.

Question: 1 A recent study has shown that the administration of glutamic acid decarboxylase formulated with aluminium hydroxide (GAD-alum) preserves insulin production in patients with recent-onset type 1 diabetes (True or False)

False

True

Answer: The correct answer is false. Glutamic acid decarboxylase (GAD) is a major target of the autoimmune response that occurs in type 1 diabetes mellitus. In animal models of autoimmunity, treatment with a target antigen can modulate aggressive autoimmunity. This study assessed whether immunisation with GAD formulated with aluminum hydroxide (GAD-alum) would preserve insulin production in recent-onset type 1 diabetes. A total of 145 patients, aged 3–45 years, who had been diagnosed with type 1 diabetes for less than 100 days were enrolled from 15 sites in the USA and Canada, and randomly assigned to receive one of three treatments: three injections of 20 ?g GAD-alum, two injections of 20 ?g GAD-alum and one of alum, or 3 injections of alum. Injections were given subcutaneously at baseline, 4 weeks later, and 8 weeks after the second injection. At 1 year, the 2-h AUC of C-peptide, adjusted for age, sex, and baseline C-peptide value, was 0•412 nmol/L (95% CI 0•349–0•478) in the GAD-alum group, 0•382 nmol/L (0•322–0•446) in the GAD-alum plus alum group, and 0•413 nmol/L (0•351–0•477) in the alum group. The ratio of the population mean of the adjusted geometric mean 2-h AUC of C-peptide was 0•998 (95% CI 0•779–1•22; p=0•98) for GAD-alum versus alum, and 0•926 (0•720–1•13; p=0•50) for GAD-alum plus alum versus alum. HbA1c, insulin use, and the occurrence and severity of adverse events did not differ between groups. Antigen-based immunotherapy therapy does not alter the course of loss of insulin secretion during 1 year in patients with recently diagnosed type 1 diabetes. Although antigen-based therapy is a highly desirable treatment and is effective in animal models, translation to human autoimmune disease remains a challenge. Wherrett DK, Bundy B, Becker DJ, et al. Antigen-based therapy with glutamic acid decarboxylase (GAD) vaccine in patients with recent-onset type 1 diabetes: A randomised double-blind trial.

Question: 2 A randomized clinical trial was conducted to assess the efficacy of a self-monitoring-based disease management strategy in patients with type 2 diabetes treated with oral agent monotherapy. After 6 months, mean HbA1c reduction in the intervention group was:

0.7%

0.5%

1.2%

1.6%

1.9%

Answer: The correct answer is 1.2%. This was an open-label, randomized, pilot study, primarily led by diabetes nurses. Patients were randomly allocated to either a self-monitoring-based disease management strategy or usual care and followed up for 6 months. Self-monitoring of blood glucose results were discussed during monthly telephone contact. Patients were instructed how to modify lifestyle based on blood glucose readings. The primary endpoint was mean change in HbA1c levels. After 6 months, mean HbA1c reduction was 1.2 &elusmn; 0.1% (–13 &elusmn; 1 mmol/mol) in the intervention group and 0.7 &elusmn; 0.2 (–8 &elusmn; 2 mmol/mol) in the control group, with an absolute mean difference between groups of –0.5% (95% CI ?0.9 to ?0.0%; P = 0.04) (?5 mmol/mol, 95% CI ?10 to 0). Franciosi M, et al. Diabetic Medicine: (2011) 28: 789–796

Question: 3 BC is a 47-year-old male non-smoker with T2DM, hypertension, and obesity. He is current on his influenza and pneumococcal vaccinations. Should BC receive any other vaccinations?

Yes, he should receive the hepatitis B virus vaccine

No

Yes, he should receive the chickenpox/varicella vaccine

Yes, he should receive the shingles/herpes zoster vaccine Answer: The correct answer is: Yes, he should receive the hepatitis B virus vaccine. The ADA states that unless there are contraindications, all diabetics should receive the pneumococcal and annual influenza vaccines. The Advisory Committee on Immunization Practices of the CDC, as well as the most recent ADA guidelines, also recommend hepatitis B virus (HBV) vaccinefor unvaccinated adults with diabetes from ages 19 to 59. Unvaccinated adults with diabetes ?60 should be vaccinated at the discretion of the provider after assessing risk and likelihood of an adequate immune response. Diabetic patients may be at risk of contracting HBV in long-term care facilities where assisted blood sugar monitoring commonly occurs. Studies have shown that diabetics may progress to chronic hepatitis B infection more often than patients without diabetes, and are at higher risk for nonalcoholic liver disease and hepatocellular carcinoma. The shingles vaccine is recommended for individuals over the age of 50, whether or not they have diabetes. The varicella vaccine is recommend in adults who have never had chicken pox, regardless if they have diabetes or not. American Diabetes Association. Standards of medical care in diabetes-2013.

Question: 4 The most commonly reported adverse event with Janumet in the treatment of type 2 diabetes is:

Upper respiratory infection

Abdominal Pain

Nausea

Headache

Diarrhea Answer: The correct answer is diarrhea. In clinical studies, the most common adverse reactions reported with Janumet in ≥ 5% of patients and more commonly than in patients treated with placebo were as follows: diarrhea > upper respiratory tract infection > headache. Inc. DIAB-1002314-0000-05/11

Question: 5 A recent study was conducted to assess the long-term effects of post-transplant glycemia on long-term survival in renal transplant recipients without pre-existing diabetes. Which of the following variables was found to be superior for predicting all-cause and cardiovascular (CV) mortality after renal transplantation?

Hypertension

Fasting Plasma Glucose (FPG)

2-hr plasma glucose after an oral glucose tolerance test (OGTT)

LDL-cholesterol

HbA1c

Answer: The correct answer is 2-hr plasma glucose after an oral glucose tolerance test (OGTT). The main finding of this large single-centre study of renal transplant recipients without pre-existing diabetes was that as a predictor of long-term mortality, post-challenge 2hPG measured early after renal transplantation was superior to, and independent of, FPG, even after adjustments for confounding risk factors. Each 18 mg/dl increment in 2hPG was associated with a 5% (95% CI 1%, 9%) increased risk of death from any cause and 6% (95% CI 1%, 12%) increased risk of death from CV disease. Furthermore, the findings in this study first to indicate that renal transplant recipients with impaired glucose tolerance have lower long-term chance of survival than those with normal glucose tolerance. Valderhaug T. G., et al.

Question: A post hoc analysis of data from the DURABLE clinical trial was performed to compare outcomes in patients with type 2 diabetes initiating Humalog 75/25 or insulin glargine therapy, stratified by baseline oral antihyperglyce¬mic agent (OHA). Which of the following OHA treatment groups had the greatest improvement in HbA1c?

Metformin/thiazolidinedioneMetformin/sulfonylurea/thiazolidinedioneSulfonylurea/thiazolidinedioneMetformin/sulfonylurea

Answer: The correct answer is metformin/thiazolidinedione. A significantly greater proportion of patients in the metformin/thiazolidinedione group achieved an A1C value less than 7.0% in comparison with the cor¬responding proportion in the metformin/sulfonylurea group. In both insulin treatment groups, metformin/thiazolidinedione-treated patients had significantly greater improvement in A1C levels (-2.19% to -2.36%) and lower end point A1C values, in comparison with metformin/sulfonyl¬urea-treated patients (all P<.05). Patients treated with sulfonylurea/thiazolidinedione or metformin/sulfonylurea/thiazolidinedione did not differ significantly from metfor¬min/sulfonylurea-treated patients in A1C change (-1.56% to -1.84%). Although the analysis did not specificallycompare outcomes between insulin treatment groups, both insulin treatment groups had relatively similar A1C reductions with metformin/thiazolidinedione therapy. Herman WH, et al. Concomitant oral antihyperglycemic agent use and associated treatment outcomes after initiation of insulin therapy.

Question 1: Which factor is associated with an increased risk of diabetic ketoacidosis (DKA) at the time of initial diagnosis of type 1 diabetes mellitus (T1DM)?Younger ageClose family history of diabetesHigher BMIAnswer: Younger age. Children and adolescents presenting with a new diagnosis of T1DM were more likely to have DKA if they were younger, especially below the age of 2 years. Thinner children also have a higher likelihood of DKA at initial presentation. Having first or second degree relatives with T1DM reduced the likelihood of DKA at time of initial diagnosis, suggesting that awareness of diabetes and its symptoms may lead to earlier diagnosis. de Vries L, et al. Diabet Med. 2013;30(11):1360-1366.

Question 2: Which endpoint would significantly decrease in pediatric patients with type 1 diabetes who were using once-daily insulin detemir compared to twice-daily insulin detemir?Frequency of severe hypoglycemic episodesHbA1cNocturnal hypoglycemic events/weekAll of the answers are correctAnswer: Nocturnal hypoglycemic events/weeks. Though these did decrease with both treatments, the decrease was significant only with the once-daily regimen. No clinical advantage was found for twice-daily detemir vs once-daily detemir, though younger children and those in active puberty may need twice-daily therapy. Nimri R, et al. Pediatr Diabetes. 2013;14(3):196-202.

Question 3: For children with type 1 diabetes mellitus (T1DM) who also have idiopathic growth hormone deficiency (IGHD), what is the impact of growth hormone treatment?Higher hemoglobin A1c levelsIncreased insulin requirementIncreased insulin requirement and higher hemoglobin A1c levels

No difference in insulin requirement or hemoglobin A1c levelsAnswer: Increased insulin requirement. A group of 37 children with T1DM were found to also have IGHD. When treated with growth hormone, the daily insulin requirement was increased (1.0 units/kg/day in the T1DM and IGHD group compared to 0.85 units/kg/day in controls with just T1DM). However, there was no significant difference in glycemic control, assessed by hemoglobin A1c levels. Bonfig W, et al. J Pediatr. 2013;163(4):1095-1098.e4.

Question 1: In the NAVIGATOR trial, participants who received nateglinide had a reduction in:The incidence of diabetes, but not in cardiovascular outcomes.The incidence of cardiovascular outcomes, but not in diabetesThe incidence of diabetes and in cardiovascular outcomesNeither the incidence of diabetes nor in cardiovascular outcomes

Answer: The correct answer is neither the incidence of diabetes nor in cardiovascular outcomes. The results of the NAVIGATOR trial (Long-term Study of Nateglinide+Valsartan to Prevent or Delay Type II Diabetes Mellitus and Cardiovascular Complications) show that among persons with impaired glucose tolerance and cardiovascular disease or cardiovascular risk factors, assignment to nateglinide, at a dose of 60 mg three times daily, as compared with placebo, in addition to a lifestyle modification program, did not reduce the incidence of diabetes or cardiovascular outcomes. N Engl J Med. 2010;362(16):1463-1476

Question 2: A recent analysis of the HAPO study showed that measuring Hemoglobin A1c is a useful alternative to an oral glucose tolerance test OGTT for assessing the risk of adverse outcomes in pregnant woman. (True or False)?

False

True

Answer: The correct answer is false. The objective of this study was to compare associations of maternal glucose and A1C with adverse outcomes in the multinational Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study and determine, based on those comparisons, if A1C measurement can provide an alternative to an oral glucose tolerance test (OGTT) in pregnant women. Eligible pregnant women underwent a 75-g OGTT at 24–32weeks’ gestation. A sample for A1C was also collected. Neonatal anthropometrics and cord serum C-peptide were measured. Associations with outcomes were assessed using multiple logistic regression with adjustment for potential confounders. Among the 23,316 HAPO Study participants with glucose levels blinded to caregivers, 21,064 had a nonvariant A1C result. The mean ±SD A1C was 4.7960 ±40%. Associations were significantly stronger with glucose measures than with A1C for birth weight, sum of skin folds, and percent body fat > 90th percentile and for fasting and 1-h glucose for cord C-peptide (all P < 0.01). For example, in fully adjusted models, odds ratios (ORs) for birth weight > 90th percentile. For each measure higher by 1 SD were 1.39, 1.45, and 1.38, respectively, for fasting, 1- and 2-h plasma glucose and 1.15 for A1C. ORs for cord C-peptide > 90th percentile were 1.56, 1.45, and 1.35 for glucose, respectively, and 1.32 for A1C. ORs were similar for glucose and A1C for primary cesarean section, preeclampsia, and preterm delivery. On the basis of associations with adverse outcomes, these findings suggest that A1C measurement is not a useful alternative to an OGTT in pregnant women. The correct answer is false. The objective of this study was to compare associations of maternal glucose and A1C with adverse outcomes in the multinational Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study and determine, based on those comparisons, if A1C measurement can provide an alternative to an oral glucose tolerance test (OGTT) in pregnant women. Eligible pregnant women underwent a 75-g OGTT at 24–32weeks’ gestation. A sample for A1C was also collected. Neonatal anthropometrics and cord serum C-peptide were measured. Associations with outcomes were assessed using multiple logistic regression with adjustment for potential confounders. Among the 23,316 HAPO Study participants with glucose levels blinded to caregivers, 21,064 had a nonvariant A1C result. The mean ±SD A1C was 4.7960 ±40%. Associations were significantly stronger with glucose measures than with A1C for birth weight, sum of skin folds, and percent body fat Lowe LP, et al. Hyperglycemia and adverse pregnancy outcome (HAPO) study: Associations of maternal A1C and glucose with pregnancy outcomes. Diabetes Care.

Question 3: In a randomized, active-control trial, a comparative evaluation of amitriptyline and duloxetine in painful diabetic neuropathy (PDN) demonstrated:

Duloxetine was superior in efficacy to Amitriptyline

More patients preferred Amitriptyline over DuloxetineThe number of moderate to severe adverse events was higher with DuloxetineAmitriptyline was superior in efficacy to DuloxetineBoth agents were similar in efficacy

Answer: Both agents were similar in efficacy. More patients preferred duloxetine over preferred amitriptyline, but it was not statistically significant (P = 0.18). Moderate to severe averse events were more common with amitriptyline compared with duloxetine (51 vs. 24% of patients; P < 0.01). Diabetes Care. 2011;34(4):818-822.

Question 4: A case series was conducted to evaluate the role of continuous subcutaneous insulin infusion (CSII) therapy in patients with symptomatic diabetic gastroparesis and unstable glycemic control. Compared with multiple–dose insulin (MDI) regimens, the use of CSII resulted in:

No statistically significant reduction in HbA1cNo change in glycemic variabilityA reduction in length of hospital stay related to gastroparesis and glycemic instabilityAll of the answer choices are correctA higher median median capillary blood glucose (CBG)


Question 5: A comparative trial was performed between once-daily liraglutide and once-weekly exenatide in patients with type 2 diabetes. Which of the following statements is false regarding the trial results?

The liraglutide group lost more weight, irrespective of BMIThere were more serious adverse events in the exenatide groupMore nausea, diarrhea, and vomiting occurred with liraglutideDecrease in fasting glucose was greater in the liraglutide groupInjection-site nodules were more common with liraglutide

Answer: The correct answer is: Injection-site nodules were more common with liraglutide is false.The trial was a 26 week, open-label, randomized, parallel-group study at 105 sites in 19 countries between Jan 2010, and Jan 2011. Type II diabetic patients on oralantihyperglycaemic drugs were randomly assigned (1:1) to receive injections of once-daily liraglutide (1.8 mg) or once-weekly exenatide (2 mg). The primary endpoint was change in HbA from baseline to week 26. Both drugs were associated with a decrease in HbA1, but was greater in patients taking liraglutide (-1.28% vs. -1.48%). However, the treatment difference (0.21%; 95% CI, 0.083-0.33) did not meet the predefined noninferiority criteria. At 26 weeks, fasting serum glucose significantly decreased in both groups (p<0.0001), but the decrease was greater in patients in the liraglutide group (-2.12 vs – 1.76) with a treatment difference (0.36; 95% CI, 0.05-0.66). Both treatments were associated with progressive decreases in bodyweight, but patients taking liraglutide lost more weight (-3.57 vs -2.68) irrespective of BMI, with a treatment difference (0.9; 95% CI, 0.39-1.40). The most common adverse events were mainly gastrointestinal in both groups, with a greater frequency of nausea, diarrhea, and vomiting in patients in the liraglutide group. Injection-site nodules were more common with exenatide than with liraglutide. There were more serious adverse events in the exenatide group (3% vs 2%) (including acute cholecystitis, myocardial infarction, pancreatitis and prostate cancer) but with no identifiable pattern of events.Buse JB. Exenatide once weekly versus liraglutide once daily in patients with type 2 diabetes (DURATION-6): a randomised, open-label study. Published online November7, 2012

Question: The most significant reason for improved adherence/compliance with use of metformin XR is:

Decrease in incidence of diarrheaLess frequent dosingDecrease in incidence of nauseaAll of the answer choices are correct

Answer: The correct answer is: All of the answer choices are correct. Patients with T2DM have comorbidities and are on multiple medications besides medications for treatment of diabetes. In a study done to address the compliance of anti-diabetic medications, A1C level was positively related with frequency of anti-diabetic medications dosing. Only 46% patients were reported to be optimally compliant with oral medications and there was A1C difference of 1.4% between compliant and noncompliant group. GI side effects related to immediate-release formulation of metformin have shown to have negative impact on health-related quality of life which leads to non-adherence and poor glycemic control. Incidence of GI side effect with Metformin 1500mg IR; [Diarrhea 10.4%, Nausea 8.2%] vs. Metformin XR (AM/PM) [Diarrhea 8.3%, Nausea 3.9%]. Discontinuation of Metformin IR treatment in first week of treatment; [due to diarrhea: 1.2%, due to nausea 1.7%]. Discontinuation of Metformin XR treatment in first week of treatment was 0% for both diarrhea and nausea. Incidence of GI side effects on Metformin IR: [Diarrhea 58%, Nausea 18%]. At 6 months after switchover to XR. [Diarrhea 14%, Nausea 6%]. Metformin IR is recommended 2 to 3 times a day. Once-daily dosing with Metformin XR simplifies treatment regimen and improves compliance, which results in improved glycemic control that would decrease the risk of long-term complications of diabetes. Ali S & Fonseca V. Expert Opin. Pharmacother. (2012) 13(12)

Question: The EUREXA trial compared add-on exenatide with glimepiride for durability of glycemic control in patients with type 2 diabetes inadequately controlled by metformin alone. Which of the following best describes the results?

Reduction in bodyweight in the exenatide group was not statistically significantSignificantly more patients attained an A1C level of < 7% in the glimepiride group than in the exenatide groupThere was no significant difference in A1C reduction between glimepiride and exenatideFasting plasma glucose concentration significantly lower in exenatide groupSymptomatic hypoglycemia were similar between both groups

Answer: The correct answer is: Fasting plasma glucose concentration significantly lower in exenatide group. Exenatide twice daily versus glimepiride for prevention of glycemic deterioration in patients with type 2 diabetes with metformin failure (EUREXA) trial is the longest randomized controlled study of a GLP-1 receptor agonist reported to date—with comparative treatment for up to 4.5 years. 515 patients were randomly assigned to the exenatide group and 514 to the glimepiride group, of whom 490 versus 487 were the intention-to-treat population. 203 (41%) patients had treatment failure in the exenatide group compared with 262 (54%) in the glimepiride group (risk difference 12•4 [95% CI 6•2–18•6], hazard ratio 0•748 [0•623–0•899]; p=0•002). 218 (44%) of 490 patients in the exenatide group, and 150 (31%) of 487 in the glimepiride group achieved an HbA1c concentration of less than 7% (p <0•0001), and 140 (29%) versus 87 (18%) achieved concentrations of 6•5% and less (p=0•0001). Fasting plasma glucose concentration was significantly lower in the exenatide group after years 1 (p=0.048), 2 (p=0.004), and 3 (p <00001) of treatment. A significantly greater decrease in bodyweight in patients given exenatide than in those given glimepiride (p <0•0001) was noted. Significantly fewer patients in the exenatide group than in the glimepiride group reported documented symptomatic (p <0•0001), nocturnal (p=0•007), and non-nocturnal (p <0•0001) hypoglycemia. Discontinuation because of adverse events (mainly gastrointestinal) was significantly higher (p=0•0005) in the exenatide group than in the glimepiride group in the first 6 months of treatment, but not thereafter. Gallwitz B, Guzman J, Dotta F, et al. Lancet 2012; 379: 2270–78

Question: Albuminuria and estimated glomerular filtration rate are independent risk factors for cardiovascular events and death in type 2 diabetes mellitus.

TrueFalse

Answer: The correct answer is true. Albuminuria is an independent risk marker for all-cause mortality and adverse cardiovascular events, including myocardial infarction, stroke, hospitalization for congestive heart failure, and peripheral vascular disease. Cardiovascular risk also increases proportionally and independently as the GFR declines in patients with type 2 diabetes mellitus. Mayo Clin Proc. May 2011 ;86(5):444-456

Question: A retrospective cohort study was conducted to investigate the risk of all-cause mortality associated with individual glucose-lowering treatment regimens in heart failure patients with diabetes? Patients using ___ had a significantly lower risk of death from diabetes or cardiovascular causes.

Insulin monotheraphySulfonylurea monotherapyMetformin + insulinMetformin + sulfonylureaMetformin monotherapy

Answer: The correct answer is metformin monotherapy. This study was conducted in Denmark in patients who were hospitalized with heart failure for the first time during 1997–2006 and treated with metformin, sulfonylureas and/or insulin. Compared with patients using sulfonylurea monotherapy, patients using metformin as monotherapy had a significantly lower risk of death from diabetes or cardiovascular causes while the risk was significantly higher in patients using insulin as monotherapy. Andersson C, et al. Diabetologia (2010) 53:2546–2553

Question: A retrospective cohort study was conducted to investigate health care utilization, cost, and clinical outcomes among non-insulin treated patients with type 2 diabetes mellitus (T2DM) initiating insulin glargine using either disposable pen or vial and syringe. The patients initiating insulin glargine with a disposable pen experienced:

Lower discontinuation ratesAll answer choices are correctFewer hypoglycemic eventsFewer diabetes-related inpatient hospitalizationsA significantly larger decrease from baseline in A1C

Answer: The correct answer is all answer choices are correct. Patients initiating insulin glargine treatment with the disposable pen were significantly less likely to discontinue or switch treatment during the 12-month follow-up period than were patients who initiated treatment with the vial and syringe (42.4% vs. 50.8%, P<0.001) the proportion of patients who experienced a hypoglycemic event was 6.35% in the disposable pen group versus 8.47% in the vial group (P=0.012). Fewer diabetes-related inpatient hospitalizations were noted in the disposable pen group (P=0.04). Despite having a higher mean baseline A1C, patients who initiated insulin glargine with the disposable pen experienced a significantly larger decrease from baseline in A1C than those initiating insulin glargine with the vial (?1.3±2.1 vs ?0.8±2.1, P=0.01). Davis S et al. Endocr Pract. 2011:1-27

Question : BC is a 47-year-old male non-smoker with T2DM, hypertension, and obesity. He is taking metformin 1000 mg twice daily, lisinopril 40 mg each morning, and amlodipine 10 mg in the evening. His blood pressure is 138/76 mm Hg. Which of the following would you do next?

Add a thiazide diureticMake no anti-HTN medication changesAdd a vasodilatorAdd a beta-blocker

Answer: The correct answer is: Make no anti-HTN medication changes. The new ADA guidelines raise the target for systolic blood pressure from <130 mm Hg to <140 mm Hg based on evidence that there is not a great deal of additional value in aiming for the lower target, but there is an increase in risk in pushing systolic pressure lower than 140 mm Hg. The primary data for that recommendation came from a meta-analysis that demonstrated that although the use of intensive versus standard blood-pressure targets in patients with type 2 diabetes was associated with a small reduction in the risk for stroke, there was no evidence for decreased mortality or MI, but an increased risk for hypotension and other adverse events. The previous target of <130 mm Hg had not been derived from randomized, controlled trials, but from observational studies that seemed to suggest lower is better for blood pressure in those with diabetes. However, the new ADA recommendations state lower targets (such as <130 mm Hg) may be appropriate in certain patients (such as younger individuals) if target can be achieved without treatment burden. American Diabetes Association.Standards of medical care in diabetes-2013. Diabetes Care. January 2013.

Question : The ORIGIN trial evaluated the effect of insulin glargine in patients with diabetes mellitus and prediabetes. Based on the results of the trial, which of the following statements is true regarding insulin glargine?

It decreased the incidence of colon cancerIt slowed the progression of atherosclerosisIt reducedthe risk of developing DM2 by 28% in prediabetes patientsIt slowed the progression of microalbuminuria

Answer: The correct answer is: It reducedthe risk of developing DM2 by 28% in prediabetes patients is true. Glargine reduced the risk of developing type 2 diabetes by 28% among patients with prediabetes. 12,537 patients (mean age of 63.5) with cardiovascular risk factors plus impaired fasting glucose, impaired glucose tolerance, or DM2were randomly assigned to receive insulin glargine or standard care. Patients were followed for an average of 6 years. Glargine did not slow the progression of atherosclerosis and had a neutral effect on cardiovascular outcomes with rates of incident cardiovascular outcomes being similar in the glargine and standard-care groups: 2.94 and 2.85 per 100 person-years, respectively, (hazard ratio, 1.02; 95% confidence interval [CI], 0.94 to 1.11; P=0.63).Glargine slowed the progression of dysglycemia; patients who were assigned to glargine were 28% less likely to have diabetes develop from the time of randomization until the first oral glucose-tolerance test than were participants assigned to standard care. Insulin glargine also had a neutral effect on cancers (colon, prostate, melanoma, breast, lung) with hazard ratio for colon cancer of 1.09;95% CI, 0.79 to 1.51; P=0.61.There was also no significant difference microvascular events, (including microalbuminuria[hazard ratio, 0.97; 95% CI, 0.90 to 1.05; P=0.43]). The Origin Trial Investigators. Basal Insulin and Cardiovascular and Other Outcomes in Dysglycemia.N Engl J Med 2012; 367:319-398 July 26, 2012.

Question : A randomized, double-blind, placebo-controlled study was conducted to compare the efficacy and safety of initial combination therapy with linagliptin and pioglitazone in patients with inadequately controlled type 2 diabetes. What was the mean change in HbA1c for patients with a baseline HbA1c ? 9.0%?

- 0.56%- 0.9%- 1.23%- 1.49%- 0.72%

Answer: The correct answer is - 1.49%. The reduction in HbA1c was greatest for patients with higher baseline HbA1c. Linagliptin plus pioglitazone patients with a baseline HbA1c ≥9.0% had a larger reduction in HbA1c (?1.49%) than seen in the overall patient group receiving linagliptin plus pioglitazone (?0.90%). The placebo corrected adjusted mean change from baseline at 24 weeks for this subgroup was?0.65% (95% CI?1.02,?0.28; p = 0.0008). For the subgroups of patients with baselineHbA1c 7.5 to<8.0 and 8.0 to<9.0%, the placebo-corrected adjusted mean changes from baseline at week 24 were ?0.48% (95% CI ?0.95, ?0.01; p = 0.048) and ?0.49% (95% CI ?0.82, ?0.16; p = 0.0031), respectively. Gomis R et al.Diabetes, Obesity and Metabolism 13: 653–661, 2011

Question : An open-label trial was conducted to assess the efficacy and safety of switching from sitagliptin to liraglutide in metformin-treated adults with type 2 diabetes. Conversion to liraglutide was associated with which of the following?

Significant reduction in body weightSignificant reduction in fasting plasma glucoseAll of the answer choices are correctImprovement in treatment satisfactionIncreased proportion of patients reaching A1C <7%

Answer: The correct answer is: All of the answer choices are correct. In an open-label trial, participants randomized to receive either liraglutide (1.2 or 1.8 mg/day) or sitagliptin (100 mg/day), each added to metformin, continued treatment for 52 weeks. In a 26-week extension, sitagliptin-treated participants were randomly allocated to receive instead liraglutide at either 1.2 or 1.8 mg/day, while participants originally randomized to receive liraglutide continued unchanged. Although 52 weeks of sitagliptin changed glycosylated hemoglobin (HbA1c) by -0.9% from baseline, additional decreases occurred after switching to liraglutide (1.2 mg/day, -0.2%, P = 0.006; 1.8 mg/day, -0.5%, P = 0.0001). Conversion to liraglutide was associated with reductions in fasting plasma glucose (FPG) (1.2 mg/day, -0.8 mmol/L, P = 0.0004; 1.8 mg/day, -1.4 mmol/L, P < 0.0001) and body weight (1.2 mg/day, -1.6 kg; 1.8 mg/day, -2.5 kg; both P < 0.0001) and with an increased

proportion of patients reaching A1C <7% (from ∼30% to ∼50%). Overall treatment satisfaction, assessed by the Diabetes Treatment Satisfaction Questionnaire, improved after switching to liraglutide (pooled 1.2 and 1.8 mg/day, 1.3; P = 0.0189). Following changing over, mostly transient nausea occurred in 21% of participants, and minor hypoglycemia remained low (3–4% of participants). Continuing liraglutide treatment at 1.2 mg/day and 1.8 mg/day for 78 weeks reduced HbA1c (baseline 8.3 and 8.4%, respectively) by -0.9 and -1.3%, respectively; FPG by -1.3 and -1.7 mmol/L, respectively; and weight by -2.6 and -3.1 kg, respectively, with 9–10% of participants reporting minor hypoglycemia. Glycemic control, weight, and treatment satisfaction improved after switching from sitagliptin to liraglutide, even though there was a transient increase in gastrointestinal reactions. Pratley RE, Nauck MA, Bailey T, et al. Efficacy and safety of switching from the DPP-4 inhibitor sitagliptin to the human GLP-1 analog liraglutide after 52 weeks in metformin-treated patients with type 2 diabetes. Diabetes Care. 2012.

Question : True or False: In a randomized trial, duloxetine was found to be inferior to pregabalin for the treatment of pain in patients with diabetic peripheral neuropathy (DPN) who had an inadequate pain response to gabapentin. (True or False)?

FalseTrue


Question: A variant in which of the following genes has been found to cause susceptibility to type 2 diabetes?

LYP/PTPN22CTLA-4CDKAL1insVNTR

Answer: The correct answer is CDKAL1. Type 2 diabetes mellitus is caused by a combination of genetic and environmental factors that result in decreased insulin function at sites of insulin action and a reduced ability of pancreatic beta cells to elevate insulin secretion in response to increased blood glucose levels. The company, deCODE Genetics confirmed previous genomewide studies and identified an association with variant CDKAL1. The production of mature insulin takes place within the beta cell and depends on the cleavage of the preproinsulin and proinsulin molecules. The cleavage site at the junction of the A chain and the C-peptide contains a lysine residue, which is critical for cleavage. The gene, CDKAL1 plays a critical role in the production of lysine. Failure to incorporate lysine resulting in the misfolding of proinsulin and thus preventing proteolytic processing. In addition, there are now many associations between oxidative stress and beta-cell failure. CDKAL1 may be exquisitely sensitive to oxidation. As the molecular mechanisms of CDKAL1 are revealed, researchers may consider small-molecule mediators to prevent the progression of type 2 diabetes in patients who carry CDKAL1 risk variants. LYP/PTPN22, insVNTR and CTLA-4 are all non-HLA genetic susceptibility genes for type 1 diabetes. Kaufman, R.J. N Engl J Med 2011; 365:1931-1933

Question: What are the recommended glucose level targets (whole blood) during pregnancy for women with gestational diabetes?

All answer choices are correctFasting ≤100 mg/dL1-hour postprandial ≤150 mg/dLNone of the answer choices are correct2-hour postprandial ≤120 mg/dL

Answer: The correct answer is 2-hour postprandial ≤120 mg/dL. Additional target glucose levels recommended by the American College of Obstetrics and Gynecology (ACOG) and American Diabetes Association (ADA) are fasting ≤ 95 mg/dL and 1-hour postprandial ≤130–140 mg/dL . Int J Womens Health. 2010;2:339-351

Question: The risk of developing type 1 diabetes in the offspring of a mother with type 1 diabetes is:

1.5%8%6%3%

Answer: The correct answer is 3%. The offspring of a mother with type 1 DM have a 3% risk of developing type 1 diabetes. David G. Gardner, Dolores Shoback, ed. Greenspan's Basic & Clinical Endocrinology. Ninth ed.; 2011:589.

Question: A post-hoc analysis of pooled data from three pivotal studies evaluated the glucose and lipid-altering efficacy of colesevelam HCl when added to background metformin therapy in patients with inadequately controlled type 2 diabetes mellitus (T2DM). The results showed that colesevelam HCl:)

Significantly increased high-density lipoprotein cholesterol (HDL-C)Did not significantly reduce hemoglobin A1c (HbA1Significantly reduced fasting plasma glucoseSignificantly reduced triglyceride levelsDid not significantly reduce low-density lipoprotein cholesterol (LDL-C)

Answer: The correct answer choice is significantly reduced fasting plasma glucose. In this pooled analysis of 696 T2DM patients receiving metformin monotherapy or metformin combined with other antidiabetes therapies, 355 were randomized to colesevelam HCl and 341 to placebo. Compared to placebo, colesevelam HCl significantly reduced hemoglobin A1c (HbA1c) and fasting plasma glucose (mean treatment difference: –0.50% and –15.7 mg/dL, respectively; P<.001 for both), as well as significantly reduced levels of LDL-C; mean treatment difference: –16.5% P<.0001). Median triglyceride levels were increased with colesevelam HCl (treatment difference: +12.8%; P<.0001). The mean increase in HDL-C with colesevelam HCl was not significant. Colesevelam HCl therapy was generally well tolerated. Bays HE. Endocrine Practice, 2011

Question: Which of the following findings from the Look AHEAD trial is true?

Intensive lifestyle intervention (ILI) group experienced significantly greater average improvements in all risk factors except LDL-C levels compared to DSE (the control group)Intensive lifestyle intervention (ILI) group maintained greater improvements than DSE participants in body weight, fitness, but not HbA1CIntensive lifestyle intervention (ILI) group experienced significantly greater average improvements in all risk factors except HDL-C levels compared to DSE (the control group)There was no difference between intensive lifestyle intervention (ILI) and diabetes support and education (DSE; the control group) on the incidence of major CVD events

Answer: The correct answer is Intensive lifestyle intervention (ILI) group experienced significantly greater average improvements in all risk factors except LDL-C levels compared to DSE (the control group). The Look AHEAD (Action for Health in Diabetes) trial is a multicenter randomized clinical trial comparing the effects of an intensive lifestyle intervention (ILI) and diabetes support and education (DSE; the control group) on the incidence of major CVD events in 5145 overweight or obese individuals (59.5% female; mean age,58.7 years) with type 2 diabetes mellitus. Averaged across 4 years, ILI participants had a greater percentage of weight loss than DSE participants (?6.15% vs ?0.88%; P_.001) and greater improvements in treadmill fitness (12.74% vs 1.96%; P_.001), hemoglobin A1c level (?0.36% vs ?0.09%; P_.001), systolic(?5.33 vs ?2.97 mm Hg; P_.001) and diastolic (?2.92 vs ?2.48mmHg; P=.01) blood pressure, and levels of high-density lipoprotein cholesterol (3.67 vs 1.97 mg/dL; P_.001) and triglycerides (?25.56 vs ?19.75 mg/dL; P_.001). Reductions in low-density lipoprotein cholesterol levels were greater in DSE than ILI participants (?11.27 vs ?12.84 mg/dL; P=.009) owing to greater use of medications to lower lipid levels in the DSE group. At 4 years, ILI

participants maintained greater improvements than DSE participants in weight, fitness, hemoglobin A1c levels, systolic blood pressure, and highdensity lipoprotein cholesterol levels. The Look AHEAD Research Group. Arch Intern Med. 2010;170(17):1566-1575

Question : Your patient and his wife disagree about how much coffee he should drink each day and want your opinion. With a family history of diabetes, he feels the more coffee the better, according to information he has read. She says he should stick to only one cup of coffee a day, if that. What do you tell them?

Coffee has nothing to do with his risk of diabetesHis risk of diabetes will be reduced by coffeeHis risk of diabetes will be increased by coffee

Answer: His risk of diabetes will be reduced by coffee. A recent meta-analysis of more than 1 million participants and 45,000 cases of diabetes found that coffee consumption was inversely associated with the risk of type 2 diabetes in a dose-response manner. Ding M, et al. Diabetes Care. 2014;37(2):569-586.

Question : Which type of coffee would reduce his risk of diabetes?

Caffeinated onlyDecaffeinated onlyBoth caffeinated and decaffeinated

Answer: Both caffeinated and decaffeinated. In the same meta-analysis, both caffeinated and decaffeinated coffee were associated with reduced diabetes risk. The relative risk of diabetes for a 1 cup/day increase was 0.91 for caffeinated coffee consumption and 0.94 for decaffeinated coffee consumption. Ding M, et al. Diabetes Care. 2014;37(2):569-586.

Question 1: The EUREXA trial compared add-on exenatide with glimepiride for durability of glycemic control in patients with type 2 diabetes inadequately controlled by metformin alone. Which of the following best describes the results?

Fasting plasma glucose concentration significantly lower in exenatide groupSignificantly more patients attained an A1C level of < 7% in the glimepiride group than in the exenatide groupReduction in bodyweight in the exenatide group was not statistically significantSymptomatic hypoglycemia were similar between both groupsThere was no significant difference in A1C reduction between glimepiride and exenatide

Answer: The correct answer is: Fasting plasma glucose concentration significantly lower in exenatide group. Exenatide twice daily versus glimepiride for prevention of glycemic deterioration in patients with type 2 diabetes with metformin failure (EUREXA) trial is the longest randomized controlled study of a GLP-1 receptor agonist reported to date—with comparative treatment for up to 4.5 years. 515 patients were randomly assigned to the exenatide group and 514 to the glimepiride group, of whom 490 versus 487 were the intention-to-treat population. 203 (41%) patients had treatment failure in the exenatide group compared with 262 (54%) in the glimepiride group (risk difference 12•4 [95% CI 6•2–18•6], hazard ratio 0•748 [0•623–0•899]; p=0•002). 218 (44%) of 490 patients in the exenatide group, and 150 (31%) of 487 in the glimepiride group achieved an HbA1c concentration of less than 7% (p <0•0001), and 140 (29%) versus 87 (18%) achieved concentrations of 6•5% and less (p=0•0001). Fasting plasma glucose concentration was significantly lower in the exenatide group after years 1 (p=0.048), 2 (p=0.004), and 3 (p <00001) of treatment. A significantly greater decrease in bodyweight in patients given exenatide than in those given glimepiride (p <0•0001) was noted. Significantly fewer patients in the exenatide group than in the glimepiride group reported documented symptomatic (p <0•0001), nocturnal (p=0•007), and non-nocturnal (p <0•0001) hypoglycemia. Discontinuation because of adverse events (mainly gastrointestinal) was significantly higher (p=0•0005) in the exenatide group than in the glimepiride group in the first 6 months of treatment, but not thereafter. Gallwitz B, Guzman J, Dotta F, et al. Lancet 2012; 379: 2270–78

Question: Which of the following statements is false regarding Qsymia (phentermine/topiramate ER)?

Post-marketing studies are under way to look for evidence of ↑ heart dzWomen on this medication are required to take monthly pregnancy tests

It was approved by the US FDA in 2012Induced myopia and angle-closure glaucoma are adverse effectsIt helps people lose about 5% of their body weight

Answer: The correct answer is: It helps people lose about 5% of their body weight. Once-daily Qsymia combines the appetite suppressant phentermine with the seizure medication topiramate. The US FDA approved the prescription drug in July 2012 as an adjunct to a reduced-calorie diet and exercise for chronic weight management in obese (body mass index [BMI] >30 kg/m2) or overweight (BMI >27 kg/m2) adults with at least one weight-related co-morbidity, such as hypertension, type 2 diabetes mellitus or dyslipidemia. The drug is expected to help obese patients drop about 10% of their weight, more than any other approved obesity drug. Women are urged to use contraception, because fetal exposure to topiramate has been linked to an increased risk for cleft lip, with or without cleft palate. Induced myopia and angle-closure glaucoma are the two main adverse ophthalmic effects of topiramate. Qsymia is not recommended for people with recent or unstable heart disease or stroke and post-marketing studies are under way to look for increased evidence of these diseases in patients taking this medication. Cameron, Fiona. Phentermine and Topiramate Extended Release (Qsymia): First Global Approval. Drugs, 2012; 72, 15, 2033-2042

Question: What does not need to be considered when evaluating for individualized glycemic goals in type 2 diabetics?

Life expectancyHistory of hypoglycemiaEthnicityAge of the patientSignificant comorbidities

Answer: The correct answer is: Ethnicity. Ethnicity does not play a role when evaluating for individualized glycemic goals. The ADA guidelines state that goals for glycemic control should be based upon the individual's overall health and projected period of survival, since the risk of complications is duration-dependent.A reasonable A1C goal for most non-pregnant adults is <7%. However, providers can reasonably suggest more stringent A1C goals (such as < 6.5%) for selected individual patients (such as those with short duration of diabetes, long life expectancy, and no significant CVD). Less stringent A1C goals (such as <8%) may be appropriate for patients with a history of severe hypoglycemia, limited life expectancy, extensive comorbid conditions, and those with long-standing diabetes in whom the general goal is difficult to attain despite diabetes self-management education, appropriate glucose monitoring, and effective doses of multiple glucose-lowering agents including insulin.American Diabetes Association. Standards of medical care in diabetes-2013.

Question : Which of the following best describes results from the Stop Atherosclerosis in Native Diabetics Study (SANDS) trial?

Baseline A1c was related to the effects of lipid and BP lowering on carotid intima medial thickness (CIMT)Baseline A1c predicted the progression of carotid intima medial thickness (CIMT) and left ventricular mass indexThe degree of baseline glycemia was negatively correlated with the ability to achieve SBP, LDL-C and non-HDL-C targetsIntensive lipid and BP treatment worsened glycemic control

Answer: The correct answer is the degree of baseline glycemia was negatively correlated with the ability to achieve SBP, LDL-C and non-HDL-C targets. The Stop Atherosclerosis in Native Diabetics Study (SANDS) compared the effects of reducing systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) to standard targets of 130 mmHg, 100 mg/dl and 130 mg/dl versus aggressive targets of 115 mmHg, 70 mg/dl and 100 mg/dl on preclinical atherosclerosis in diabetic adults from a population with high rates of diabetes and diabetes-associated CVD. In the group treated to lower targets, there was a reduction in carotid intima medial thickness (CIMT) and a greater reduction in left ventricular (LV) mass. Glycemia control, however, varied widely among the study participants. Therefore, the relation between baseline glycemia and ability to achieve the blood pressure (BP), LDL-C and non-HDL-C targets and whether glycemia control affected the ability of lipid and BP lowering to influence changes in carotid atherosclerosis and cardiac structure, as measured by CIMT and LV mass index (LVMI). The SANDS trial is unique in that rather than comparing two pharmacologic regimens, it compared two cohorts treated to aggressive versus standard targets for SBP and lipid control, including non-HDL-C, in diabetic individuals. The degree of

baseline glycemia was negatively correlated with the ability to achieve SBP, LDL-C and non-HDL-C targets, and the likelihood of reaching these targets declined significantly in both groups with increasing tertile of baseline A1c. Although carotid atherosclerosis, indexed by CIMT, was significantly and directly related to baseline A1c, A1c did not influence the effects of lipid and SBP lowering on carotid atherosclerosis. These findings are noteworthy for several reasons. First, they suggest that the improvements in subclinical measures of atherosclerosis and cardiac function observed in SANDS did not differ as a result of differences in glycemia control. They also suggest that the treatment strategies used to achieve the BP and lipid targets did not affect glycemia control, eliminating potential negative consequences of treatment regimens. Thiazide diuretics and ?-blockers, which were steps 2 and 3 of the algorithm for BP control in SANDS (Weir et al., 2009), have known potential adverse effects on glycemia management, whereas ACE inhibitors may have beneficial effects. Had intensive lipid and BP treatment worsened glycemia control, that finding would have complicated clinical decision making because of the known benefits of glycemia control on microvascular complications. Although a direct relationship was observed between baseline glycemia and CIMT, as seen in other studies ( [McNeely et al., 2009] and [Selvin et al., 2005] ), the degree of baseline glycemia did not significantly influence change in CIMT or LVMI over 36 months. This observation reinforces the need to focus on lipid and BP control in diabetes regardless of glycemia status, with the implication that improvements in CVD risk are possible despite level of glycemia. Mete M, et al. Journal of diabetes and its complications. 2011 vol:25 iss:6 pg:362 -367

Question: A recent study showed that ?-Cell function can be preserved for at least 3.5 years with early and intensive therapy for type 2 diabetes. (True or False)

FalseTrue

Answer: The correct answer is: True. A randomized trial of 58 patients with treatment-naïve newly diagnosed type 2 diabetes was conducted to assess β-cell function preservation after 3.5 years of intensive therapy with: Insulin plus metformin (INS group) vs. Triple oral therapy (TOT group) with metformin, glyburide, and pioglitazone. All patients were treated with insulin and metformin for a 3-month lead-in period followed by random assignment to the INS or TOT group. β-Cell function was assessed using a mixed-meal challenge test at randomization and 6, 12, 18, 30, and 42 months. Analyses were intention to treat and performed with repeated-measures models. Completion rates at 3.5 years were 83% in the insulin group and 72% in the TOT group, with good compliance in both groups (87 6 20% in the INS group vs. 90 6 15% in the TOT group). β-Cell function was preserved at 3.5 years after diagnosis, with no significant change from baseline or difference between the two groups as measured by area under the curve (AUC) of C-peptide (P = 0.14) or the ratio of C-peptide to glucose AUC (P = 0.7). Excellent glycemic control was maintained in both groups (end-of-study HbA1c 6.35 ± 0.84% in the INS group vs. 6.59 ± 1.94% in the TOT group). Weight increased in both groups over time (from 102.2 ± 24.9 kg to 106.2 ± 31.7 kg in the INS group and from100.9 ± 23.0 kg to 110.5 ± 31.8 kg in the TOT group), with no significant difference between groups (P = 0.35). Hypoglycemic events decreased significantly over time (P = 0.01) but did not differ between groups (P = 0.83). This study concluded that β-Cell function can be preserved for at least 3.5 years with early and intensive therapy for type 2 diabetes with either insulin plus metformin or triple oral therapy after an initial 3-month insulin-based treatment period. Harrison L et al. Diabetes Care 2012;35:1406-1412

Question: The TIMES2 Study evaluated the effects of testosterone replacement therapy (TRT) on Insulin resistance, cardiovascular risk factors, and symptoms in hypogonadal men with type 2 diabetes and/or metabolic syndrome. Transdermal TRT was associated with which of the following?

Reduction in homeostasis model assessment of insulin resistance (HOMA-IR)Increase in Non-fatal Cardiovascular EventsIncrease in HDL cholesterolIncrease in LDL cholesterolIncrease in lipoprotein a (Lpa)

Answer: Reduction in homeostasis model assessment of insulin resistance (HOMA-IR). There were Improvements in total and LDL cholesterol, and Lpa. HDL cholesterol decreased from baseline significantly more with TRT than placebo. There were no significant differences between groups in the frequencies of adverse events (AEs) or serious AEs. The majority of AEs (>95%) were mild or moderate. Diabetes Care. 2011;34(4):828-837.

Question: A mutation in the gene encoding the transcription factor HNF-1beta (HNF1B) in a young patient with diabetes and early-onset kidney disease is associated with which monogenic form of diabetes?

MODY2MODY3MODY5MODY1MODY4

Answer: MODY5. Mutations in the hepatocyte nuclear factor?1? (HNF1B) account for approximately 2% of cases of maturity-onset diabetes of the young (MODY). MODY5 has a progressive clinical course in terms of hyperglycemia, with increasing treatment requirements. Additional clinical features include; presence of renal cysts and other renal abnormalities as well as genital abnormalities and abnormal liver function. MODY2 involves mutations in glucokinase and is associated with a mild form of nonprogressive hyperglycemia that is usually asymptomatic at diagnosis and is treated with diet alone. MODY1 is due to mutations in HNF-4alpha. MODY3 is due to mutations in HNF1alpha. MODY4 is due to a frame-shift mutation in the gene encoding a ?-cell transcription factor, Insulin promoter factor 1/ Pancreas?duodenum homeobox protein 1(IPF1/PDX1 ). Genetic testing will disclose whether MODY is present and will distinguish between subtypes of MODY, and thereby give clues to prognosis and treatment. Stefan SF et al. MODY: History, genetics, pathophysiology, and clinical decision making Diabetes Care August 2011 34:1878-1884

Question: A retrospective chart review was conducted to determine the effect of metformin on 25-OH vitamin D and B12 levels in patients with diabetes mellitus type 2. What were the findings from this study?

Patients on metformin had statistically significant lower vitamin B12 levels than those not on metforminNo statistically significant difference was shown between users and nonusers of metformin in regard to vitamin B12 levelsMetformin use did adversely affect successful treatment of vitamin D deficiency in the subgroup with osteoporosisPatients on metformin had statistically significant lower 25-OH vitamin D than those not on metformin

Answer: The correct answer is patients on metformin had statistically significant lower vitamin B12 levels than those not on metformin. The effect of metformin on vitamin B12 levels in diabetic patients has been studied for decades, noting that on average 10-30% of patients show a malabsorptive deficiency of vitamin B12. This study was a retrospective chart review of patients treated between 2003-2009 at Loyola University Medical Center in both ambulatory primary care and endocrinology clinics. 706 patients aged 20-93 with diabetes mellitus type 2 were included with a mean age of 63 &elusmn; 13 years and a mean BMI of 33.1 kg/m2. 34% of these patients used metformin, and 35% of these patients had been diagnosed with osteoporosis/osteopenia. Patients on metformin had statistically significant lower vitamin B12 levels than those not on metformin (p<0.0001, 95% CI = (-220, -84)). No statistically significant difference was shown between users and nonusers of metformin in regard to vitamin D levels when adjusted for variables (p=0.297, 95% CI for mean difference = (-0.7, 2.2)). Metformin use did not adversely affect successful treatment of vitamin D deficiency in this population as a whole, nor did it affect the subgroup with osteoporosis (p =0.956). Those with osteoporosis did have statistically significant lower baseline vitamin D levels compared to those without when adjusted for all variables (p=0.002, 95% CI = (0.8, 3.9)). This study confirms the higher prevalence of vitamin B12 deficiency in metformin treated type 2 diabetic patients. This study also suggests that vitamin D deficiency is not a clinical concern among metformin treated type 2 diabetics, and metformin does not negatively impact treatment of vitamin D deficiency in these patients. Kos E et al. The effect of metformin therapy on vitamin D and B12 levels in patients with diabetes mellitus type 2. Endocr Pract. 2011:1-16.

Question: BC is a 47-year-old male non-smoker with T2DM, hypertension, and obesity. He is taking metformin 1000 mg twice daily, lisinopril 40 mg each morning, and amlodipine 10 mg each morning. His blood pressure is 132/70 mm Hg. Which of the following would you do next?

Change his lisinopril or amlodipine dose to the eveningAdd a thiazide diureticAdd a beta-blocker

Answer: The correct answer is: change his lisinopril or amlodipine dose to the evening. The benefits of lowering BP in diabetes to <140 mm Hg systolic and <80 mm Hg diastolic have been established in randomized control trials. However,

the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial demonstrated that, in patients with T2DM, intensive BP lowering to <120 mm Hg systolic yielded no significant differences in fatal and nonfatal cardiovascular events compared with BP maintained between 130 and 140 mm Hg. Moreover, aggressive BP lowering may be associated with serious adverse events. The 2012 ADA guidelines state that a systolic BP goal of <130 mm Hg is appropriate for most patients; however, higher or lower BP targets may be individualized.If a patient is taking multiple BP medications, one or more should be taken at bedtime. Administering an antihypertensive at night results in better ambulatory BP control and reduces cardiovascular mortality. BC is on maximal doses of 2 antihypertensive agents, and his BP is 132/70 mm Hg. His physician must individualize care and decide If adding a third agent is worth the risk of another medication when clear benefit has not been demonstrated. It is reasonable to continue his current regimen with the exception of changing either his lisinopril or amlodipine dose to the evening and reassessing his BP control at his next visit. Cusbman WC, Evans GW, Byington RP, et al. ACCORD Study Group. Effects of intensive blood-pressure control in type 2 diabetes mellitus. NEngUMed. 2010;362:15?5-1585.

Question: Which of the following best describes the results of a recent cross-sectional study investigating the impact of body mass index (BMI) status on the relationship of serum 25-hydroxyvitamin D (25OHD) concentration with insulin sensitivity?

The optimal serum 25OHD concentration for insulin sensitivity is about 46 ng mLThe correlation of serum 25OHD with insulin sensitivity was much stronger in the overweight group than in the normal weight group.The optimal serum 25OHD concentration for insulin sensitivity is about 34 ng mL

Answer: The correct answer is the correlation of serum 25OHD with insulin sensitivity was much stronger in the overweight group than in the normal weight group. Obesity is a risk factor for hypovitaminosis D, insulin resistance and type 2 diabetes. This cross-sectional study enrolled 126 healthy and glucose-tolerant subjects. The participants were divided into two groups based on BMI: normal weight (n = 68) and overweight (n = 58). Insulin sensitivity index (ISI) was assessed by using hyperglycemic clamps. Serum 25OHD concentration was determined in the fasting samples. The correlation of serum 25OHD with ISI was much stronger in the overweight group (r = 0•5271, P < 0•0001) than in the normal weight group (r = 0•2836, P = 0•002). The correlation remained significant in the overweight group (r = 0•3620, P = 0•002), but not in normal weight group after adjusting for age, gender, BMI, season of study, ethnicity and exercise. Nonlinear regression analysis revealed that when serum 25OHD concentration was > 40 ng mL?1, the association between serum 25D concentrations and insulin sensitivity plateaued. The results of this study suggested that overweight subjects with hypovitaminosis D may benefit more from vitamin D replacement than normal weight subjects. Furthermore, the optimal serum 25OHD concentration for insulin sensitivity is about 40 ng mL?1. Horng-Yih Ou, et al Eur J Clin Invest 2011; 41 (11): 1195–1201

Question: The EUREXA trial compared add-on exenatide with glimepiride for durability of glycemic control in patients with type 2 diabetes inadequately controlled by metformin alone. Which of the following best describes the results?

Significantly more patients attained an A1C level of < 7% in the glimepiride group than in the exenatide groupReduction in bodyweight in the exenatide group was not statistically significantThere was no significant difference in A1C reduction between glimepiride and exenatideFasting plasma glucose concentration significantly lower in exenatide groupSymptomatic hypoglycemia were similar between both groups

Answer: The correct answer is: Fasting plasma glucose concentration significantly lower in exenatide group. Exenatide twice daily versus glimepiride for prevention of glycemic deterioration in patients with type 2 diabetes with metformin failure (EUREXA) trial is the longest randomized controlled study of a GLP-1 receptor agonist reported to date—with comparative treatment for up to 4.5 years. 515 patients were randomly assigned to the exenatide group and 514 to the glimepiride group, of whom 490 versus 487 were the intention-to-treat population. 203 (41%) patients had treatment failure in the exenatide group compared with 262 (54%) in the glimepiride group (risk difference 12•4 [95% CI 6•2–18•6], hazard ratio 0•748 [0•623–0•899]; p=0•002). 218 (44%) of 490 patients in the exenatide group, and 150 (31%) of 487 in the glimepiride group achieved an HbA1c concentration of less than 7% (p <0•0001), and 140 (29%) versus 87 (18%) achieved concentrations of 6•5% and less (p=0•0001). Fasting plasma glucose concentration was significantly lower in the exenatide group after years 1 (p=0.048), 2 (p=0.004), and 3 (p <00001) of treatment. A significantly greater decrease in bodyweight in patients given exenatide than in those given glimepiride (p <0•0001) was noted. Significantly fewer

patients in the exenatide group than in the glimepiride group reported documented symptomatic (p <0•0001), nocturnal (p=0•007), and non-nocturnal (p <0•0001) hypoglycemia. Discontinuation because of adverse events (mainly gastrointestinal) was significantly higher (p=0•0005) in the exenatide group than in the glimepiride group in the first 6 months of treatment, but not thereafter. Gallwitz B, Guzman J, Dotta F, et al. Lancet 2012; 379: 2270–78

Question 1: True or False: In a randomized trial, duloxetine was found to be inferior to pregabalin for the treatment of pain in patients with diabetic peripheral neuropathy (DPN) who had an inadequate pain response to gabapentin. (True or False)?

TrueFalse


Question : What were the findings from a recent prospective study aimed to examine vitamin D status as a determinant for development of type 2 diabetes and deterioration of glucose homeostasis?

Low 25(OH) D status was significantly associated with an increase in fasting blood glucoseLow 25(OH) D status was significantly associated with an increase in HbA1c.Low 25 (OH) D status was significantly associated with incident diabetes after adjustment for confounders.Low 25(OH) D status was not significantly associated with an increase in 2-hour glucose

Answer: The correct answer is: Low 25(OH) D status was significantly associated with an increase in fasting blood glucose. This was population-based randomized controlled Trial which was conducted in Copenhagen, Denmark. It included 6,405 men and women aged 30–65 years at baseline (1999–2001), with 4,296 participating in the follow-up examination 5 years later (2004–2006). Vitamin D was determined at baseline as serum 25-hydroxyvitamin D [25(OH) D]. Diabetes was defined based on an oral glucose tolerance test and HbA1c. Secondary outcomes included continuous markers of glucose homeostasis. The risk of incident diabetes associated with a 10 nmol/L increase in 25(OH) D was OR) 0.91 (95% CI 0.84–0.97) in crude analyses. The association became statistically nonsignificant after adjustment for confounders, with an OR per 10 nmol/L of 0.94 (0.86–1.03). Low 25(OH)D status was significantly associated with unfavorable longitudinal changes in continuous markers of glucose homeostasis after adjustment for confounders. Fasting and 2-h glucose and insulin as well as the degree of insulin resistance increased significantly more during follow-up among those with low 25(OH)D levels compared with those with higher levels. In conclusion, Low 25(OH)D status was not significantly associated with incident diabetes after adjustment for confounders. However, it was significantly associated with unfavorable longitudinal changes in continuous markers of glucose homeostasis, indicating that low vitamin D status could be related to deterioration of glucose homeostasis. Husemoen LLN, et al. Serum 25(OH)D and type 2 diabetes association in a general population. Diabetes Care. 2012.

Question: A retrospective cohort study was conducted to assess the relationship of individual sulfonylureas and the risk of overall mortality in a large cohort of patients with type 2 diabetes. What were the findings in patients with underlying coronary artery disease (CAD)?

Decreased overall mortality risk with glipizide versus glyburideNo statistically significant difference in the risk of overall mortalityIncreased overall mortality risk with glimepiride versus glipizideIncreased overall mortality risk with glyburide versus glimepiride

Answer: The correct answer is increased overall mortality risk with glyburide versus glimepiride. This study was conducted using an academic health center enterprise-wide electronic health record (EHR) system to identify 11,141 patients with type 2 diabetes (4,279 initiators of monotherapy with glyburide, 4,325 initiators of monotherapy with glipizide, and 2,537 initiators of monotherapy with glimepiride), ≥18 years of age with and without a history of coronary

artery disease (CAD) and not on insulin or a noninsulin injectable at baseline. No statistically significant difference in the risk of overall mortality observed among the individual sulfonylureas in the entire cohort. However, in the subanalysis of patients with documented CAD, a trend toward an increased overall mortality risk with glyburide versus glimepiride (hazard ratio 1.36 [95% CI 0.96 –1.91]), and a trend toward an increased risk of mortality with the glipizide versus glimepiride (1.39 [0.99 –1.96]), were observed, suggesting that glimepiride may be the preferred sulfonylurea in those with underlying CAD. Pantalone K et al. Diabetes Care 33:1224–1229, 2010

Question 1: A 52-year-old male with DM2 on insulin, reportsdysesthesia, numbness and tingling of extremities, and poor sleep quality. You diagnosediabetic peripheral neuropathic pain. Which therapy would you prescribe for analgesia and improved sleep?

Vitamin B12DuloxetineAmitriptylinePregabalin

Answer: The correct answer is pregabalin. A recently published, double-blind, randomized trial compared amitriptyline, duloxetine and pregabalin in 104 diabetics with peripheral neuropathic pain. Subjective pain and sleep quality (using polysomnography sleep records) were assessed over 28 days. Amitriptyline, duloxetine, and pregabalin, all reduced subjective pain with no one drug being superior to another. Subjective pain ratings showed ∼50% improvement, in line with previous studies. For sleep, pregabalin improvedsleep continuity (P< 0.001), reducing wake after sleep onset, in line with previous reports. Duloxetine increased wake and reduced total sleep time (P< 0.01 and P< 0.001) and substantially reduced REM sleep. Previous literature suggests that amitriptyline promotes sleep initiation and sleep continuity, however there may be less impact of amitriptyline on sleep in patients with diabetic peripheral neuropathic pain. Research has shown that people who take metformin may be at risk for developing vitamin B12 deficiency associated peripheral neuropathy, however this patient is on insulin. Boyle J, et al. Randomized, Placebo-Controlled Comparison of Amitriptyline, Duloxetine, and Pregabalin in Patients with Chronic Diabetic Peripheral Neuropathic Pain. Impact on pain, polysomnographic sleep, daytime functioning, and quality of life. Diabetes CareDecember 2012 vol. 35 no. 12 2451-2458

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Question: What is the best screening test for cystic fibrosis-related diabetes (CFRD)?

Correct! (Correct answer is highlighted below)

Fructosamine

Urine glucose

Fasting plasma glucose

Oral glucose tolerance test (OGTT)

HbA1c

Answer: Oral glucose tolerance test (OGTT). The American Diabetes Association and The Cystic Fibrosis Foundation recommend the OGTT as the screening test of choice for CFRD. Although it is an imperfect test due to the variability observed in individual CF patients over time, longitudinal studies demonstrate that a diabetes diagnosis by OGTT correlates with clinically important CF outcomes including the rate of lung function decline over the next 4 years, the risk of microvascular complications, and the risk of early death. The committee concluded that HbA1c is not sufficiently sensitive for diagnosis of CFRD and should not be used as a screening test. Fasting plasma glucose does not identify those patients without fasting hyperglycemia, and will miss the diagnosis of diabetes in approximately half of CF patients. Fructosamine and urine glucose have low sensitivity in the CF population. Diabetes Care. 2010;33(12):2697-2708.

Question: A prospective intervention study was conducted to analyze glucostatic parameters in obese subjects with T2DM before and after an equivalent amount of weight loss induced by either a low calorie diet (LCD) or Roux-en-Y gastric bypass (RYGB).Which of the following findings of this study is correct?

The improvement in insulin sensitivity (Si) was similar between RYGB and LCDThe disposition index (DI) was significantly greater in RYGB compared with LCD subjectsThe acute C-peptide response to glucose was significantly greater in LCD compared with RYGB subjects.The equivalent weight loss was achieved in the same time in both groups

Answer: The correct answer is the disposition index (DI) was significantly greater in RYGB compared with LCD subjects. A significant improvement in insulin secretion normalized to the degree of insulin resistance (disposition index) was observed in both groups, but the mean increase was substantially greater in RYGB compared with LCD subjects (258.2 &elusmn; 86.6 vs. 55.9 &elusmn; 19.9; P = 0.04). Insulin sensitivity (Si) markedly improved only in the RYGB group (P = 0.002), but no significant change was detected in the LCD group (P = 0.30). When adjusted for baseline (Si), the change remained significant in the RYGB group (P = 0.02) but still did not reach statistical significance in the LCD group (P = 0.09). Changes in acute C-peptide response to glucose (ACPRg) was not statistically significant in LCD group (P = 0.46), but remained significant in RYGB group (P = 0.008). The equivalent weight loss was achieved in less than half the time after RYGB as compared to LCD. Plum L, et al. Obesity (2011)

Question: A recent study has shown that the administration of glutamic acid decarboxylase formulated with aluminium hydroxide (GAD-alum) preserves insulin production in patients with recent-onset type 1 diabetes (True or False)

TrueFalse

Answer: The correct answer is false. Glutamic acid decarboxylase (GAD) is a major target of the autoimmune response that occurs in type 1 diabetes mellitus. In animal models of autoimmunity, treatment with a target antigen can modulate aggressive autoimmunity. This study assessed whether immunisation with GAD formulated with aluminum hydroxide (GAD-alum) would preserve insulin production in recent-onset type 1 diabetes. A total of 145 patients, aged 3–45 years, who had been diagnosed with type 1 diabetes for less than 100 days were enrolled from 15 sites in the USA and Canada, and randomly assigned to receive one of three treatments: three injections of 20 ?g GAD-alum, two injections of 20 ?g GAD-alum and one of alum, or 3 injections of alum. Injections were given subcutaneously at baseline, 4 weeks later, and 8 weeks after the second injection. At 1 year, the 2-h AUC of C-peptide, adjusted for age, sex, and baseline C-peptide value, was 0•412 nmol/L (95% CI 0•349–0•478) in the GAD-alum group, 0•382 nmol/L (0•322–0•446) in the GAD-alum plus alum group, and 0•413 nmol/L (0•351–0•477) in the alum group. The ratio of the population mean of the adjusted geometric mean 2-h AUC of C-peptide was 0•998 (95% CI 0•779–1•22; p=0•98) for GAD-alum versus alum, and 0•926 (0•720–1•13; p=0•50) for GAD-alum plus alum versus alum. HbA1c, insulin use, and the occurrence and severity of adverse events did not differ between groups. Antigen-based immunotherapy therapy does not alter the course of loss of insulin secretion during 1 year in patients with recently diagnosed type 1 diabetes. Although antigen-based therapy is a highly desirable treatment and is effective in animal models, translation to human autoimmune disease remains a challenge. Wherrett DK, Bundy B, Becker DJ, et al. Antigen-based therapy with glutamic acid decarboxylase (GAD) vaccine in patients with recent-onset type 1 diabetes: A randomised double-blind trial.

Question: Which of the following best describes the results of a study assessing the efficacy and safety of sitagliptin (SITA) monotherapy and SITA/metformin (MET) vs. pioglitazone (PIO) in patients with type 2 diabetes and moderate-to-severe hyperglycemia (A1C = 7.5–12.0%)?

Improvement in 2-h postmeal glucose was similar in both groups.There was no change in body weight with SITA/METImprovement in fasting plasma glucose was significantly greater with PIOImprovement in A1C was significantly greater with PIOImprovement in A1C was significantly greater with SITA/MET

Answer: The correst answer is improvement in A1C was significantly greater with SITA/MET. In an initial 12-week phase (Phase A), 492 patients (aged ≥18 to ≤ 78 years) with T2DM were who were drug naïve [not taking an antihyperglycaemic agent (AHA) within the previous 3 months and not more than 4 weeks cumulatively in the previous 3 years] were randomized 1:1 in a double-blind fashion to SITA (100 mg qd) or PIO (15 mg qd, up-titrated to 30 mg after 6 weeks). In Phase B (28 additional weeks), the SITA group was switched to SITA/MET (up-titrated to 50/1000 mg bid over 4 weeks) and the PIO group was up-titrated to 45 mg qd. At the end of Phase A, mean changes from baseline were -1.0% and -0.9% for A1C; -26.6 mg/dl and -28.0 mg/dl for fasting plasma glucose; and -52.8 mg/dl and -50.1 mg/dl for 2-h post-meal glucose for SITA and PIO, respectively. At the end of Phase B, improvements in glycemic parameters were greater with SITA/MET vs. PIO: -1.7% vs. -1.4% for A1C (p = 0.002); -45.8 mg/dl vs. -37.6 mg/dl for fasting plasma glucose (p = 0.03); -90.3 mg/dl vs. -69.1 mg/dl for 2-h post meal glucose (p = 0.001); and 55.0% vs. 40.5% for patients with A1C < 7% (p = 0.004). A numerically higher incidence of gastrointestinal adverse events and a significantly lower incidence of edema were observed with SITA/MET vs. PIO. The incidence of hypoglycemia was similarly low in both groups. Body weight decreased with SITA/MET and increased with PIO (-1.1 kg vs. 3.4 kg; p < 0.001). Perez-Monteverde A et al. International Journal of Clinical Practice Vol 65, Issue 9;930–938, September 2011

Question: A randomized placebo-controlled trial was conducted to investigate whether treatment with salsalate, an anti–inflammatory medication, improves glycemia in a group of newly diagnosed drug–naive patients with type 2 diabetes mellitus (T2DM). Which of the following best describes the results?

Salsalate reduced fasting glucoseSalsalate did not reduce HbA1cFasting insulin levels were decreased in the salsalate group, while they increased in the placebo group.None of the answer choices are correctHOMA–IR did not change but HOMA–B increased in the salsalate group.

Answer: The correct answer choice is salsalate reduced fasting glucose. There is a large body of evidence that suggest that chronic inflammation plays a role in the pathogenesis of type 2 diabetes and that that anti-inflammatory therapy may therefore be useful for treating diabete. Previous studies have shown that salicylate, a traditional anti-inflammatory agent, inhibits activity of the transcription factor NF-?B, which regulates the production of multiple inflammatory mediators. The TINSAL-T2D trial showed that salsalate was well tolerated in patients with T2DM and it improved measures of glycemic control over a 3-month trial. The study in question was a randomized, double-blind, placebo-controlled trial. Diagnosis of T2DM was made within 2 months of enrollment, and participants had not received any anti–glycemic agent. Sixty adults were randomized to receive salsalate (3 g/day) or placebo for 12 weeks. Salsalate reduced fasting glucose from 6.3 &elusmn; 0.2 mmol/l to 5.4 &elusmn; 0.2 mmol/l (P < 0.01). Fasting insulin levels were increased in the salsalate group from 18.8 &elusmn; 1.6 to 21.6 &elusmn; 3.9, while they decreased in the placebo group. HbA1c rose in the placebo group from 6.2% &elusmn; 0.2 to 7.9% &elusmn; 1.1 mmol/mol, but decreased in the intervention group from 6.1% &elusmn; 0.5 to 5.6% &elusmn; 0.2 mmol/mol (P < 0.04 for between–group comparison). HOMA–IR did not change but HOMA–B increased ˜1.7–fold (P = 0.06) in the salsalate group . HOMA-IR, an indirect measure of insulin resistance, was calculated as the product of FPG (mmol/l) and insulin (lIU/ml) divided by 22.5. HOMA-B, an indirect estimate of b-cell function, was calculated as fasting insulin (lIU/ ml) 9 20/[FPG (mmol/l) - 3.5]. Consistent with the TINSAL-T2D trial, this study demonstrated the positive effect of salsalate on control of hyperglycemia in patients with T2DM. The optimal duration of treatment with salsalate and sustainability of its effect requires further study. elusmn; 1.6 to 21.6 Faghihimani E et al. Acta Diabetol. 2011 Sep 22

Question : A study was conducted to examine whether the effects of intensive glycemic control on major outcomes in the ADVANCE trial differ between participants among different demographic regions. Which region had the highest mortality?

AsiaNorth AmericaEastern Europe.None of the answers are correctEstablished market economies (EMEs)

Answer: The correct answer choice is none of the answers are correct. The ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release (MR) Controlled Evaluation) trial had the broadest worldwide coverage of patients of any trial of diabetes yet conducted, although relatively few participants (4%) came from North America. Participants in ADVANCE were drawn from 20 different countries. A study was conducted to determine whether the effects of intensive glycemic control on major outcomes in ADVANCE differ between participants from Asia, established market economies (EMEs), and eastern Europe. Demographic and clinical characteristics were compared across regions using generalized linear and mixed models. Effects on outcomes of the gliclazide modified release–based intensive glucose control regimen, targeting an AlC ≥ 6.5%, were compared across regions using Cox proportional hazards models and revealed the effects of intensive glycemic control were not significantly different (P≤0.23) between regions for any outcome, including mortality, vascular end points, and severe hypoglycemic episodes. This is evident, regardless of differences in health care systems, clinical practice, and use of medications (including statins and blood pressure–lowering medication). Hence, according to this study the methods of glycemic control used in ADVANCE can be safely recommended for Caucasian and Asian patients with type 2 diabetes in all three regions studied who are at moderate to high risk of cardiovascular disease. Woodward M, Patel A, Zoungas S, et al. Does glycemic control offer similar benefits among patients with diabetes in different regions of the world? Diabetes Care.


No statistically significant reduction in HbA1cAll of the answer choices are correctNo change in glycemic variabilityA reduction in length of hospital stay related to gastroparesis and glycemic instabilityA higher median median capillary blood glucose (CBG)


Question : Which of the following best describes the results of the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial

The survival rates in the insulin-sensitization group were significantly higher compared to the insulin-provision group.The rates of death and major cardiovascular events were significantly greater in patients undergoing prompt revascularization compared to those undergoing medical therapy.The rates of major cardiovascular events were significantly higher in the medical-therapy group compared to the revascularization groupNone of the answers are correctThe survival rates in the insulin-provision group were significantly higher than in the insulin-sensitization group.

Answer: The correct answer choice is none of the answers are correct. The Bypass Angioplasty Revascularization Investigation (BARI2D) trial was conducted to determine optimal treatments to prevent mortality and major cardiovascular events in patients with T2DM and stable ischemic heart disease. Both prompt revascularization compared with intensive medical therapy alone or with delayed revascularization, and insulin-sensitization compared with insulin-

provisional therapeutic strategies were evaluated in 2368 patients over 5 years with the use of a 2×2 randomized factorial trial design. At 5 years, rates of survival did not differ significantly between the revascularization group (88.3%) and the medical-therapy group (87.8%, P=0.97) or between the insulin-sensitization group (88.2%) and the insulin-provision group (87.9%, P=0.89). The rates of freedom from major cardiovascular events also did not differ significantly among the groups: 77.2% in the revascularization group and 75.9% in the medical-treatment group (P=0.70) and 77.7% in the insulin-sensitization group and 75.4% in the insulin-provision group (P=0.13). In the PCI stratum, there was no significant difference in primary end points between the revascularization group and the medical-therapy group. In the CABG stratum, the rate of major cardiovascular events was significantly lower in the revascularization group (22.4%) than in the medical-therapy group (30.5%, P=0.01; P=0.002 for interaction between stratum and study group). Of note, in secondary analysis, insulin-sensitization therapies appeared to enhance the benefit of revascularization in the higher-risk subgroup of patients selected for CABG. Additionally, insulin sensitization was associated with lower body mass index, higher high-density lipoprotein cholesterol level, and lower rates of severe hypoglycemia. Goldfine AB, Fonseca V. Management of diabetes mellitus in patients with cardiovascular disease in the bypass angioplasty revascularization investigation 2 diabetes (BARI 2D) trial. Circulation. 2010;121(22):2447-2449.

Question: A retrospective cohort study was conducted to investigate the risk of all-cause mortality associated with individual glucose-lowering treatment regimens in heart failure patients with diabetes? Patients using ___ had a significantly lower risk of death from diabetes or cardiovascular causes.

Metformin + insulinSulfonylurea monotherapyMetformin + sulfonylureaInsulin monotheraphyMetformin monotherapy

Answer: The correct answer is metformin monotherapy. This study was conducted in Denmark in patients who were hospitalized with heart failure for the first time during 1997–2006 and treated with metformin, sulfonylureas and/or insulin. Compared with patients using sulfonylurea monotherapy, patients using metformin as monotherapy had a significantly lower risk of death from diabetes or cardiovascular causes while the risk was significantly higher in patients using insulin as monotherapy. Andersson C, et al. Diabetologia (2010) 53:2546–2553

Question: A study aimed to determine the effects on glycemic control after the implementation of a dedicated hospital subcutaneous insulin prescription chart found:

A decrease in the use of supplemental insulinNo reduction in hypoglycemic eventsAn increase in the proportion of blood glucose levels within the ideal rangeAll answer choices are correctNone of the answer choices are correct

Answer: The correct answer is an increase in the proportion of blood glucose levels within the ideal range. A dedicated subcutaneous insulin prescription chart incorporating glucose monitoring results and management guidelines was introduced to facilitate better hospital diabetes control. Point of care capillary blood glucose monitoring charts for 99 people with diabetes from the period before the introduction of the new chart, and106 after its introduction were reviewed. A total of 12,649 blood glucose levels (BGLs) were collected for glucometric analysis. Following the introduction of the chart, there was an increase in the number of BGLs performed daily from 4.5 &elusmn; 1.2 to 4.9 &elusmn; 1.3 (p = 0.05). There was an increase in the proportion of BGLs within the ideal range (51.8% vs. 54.1%, p = 0.01). There was a reduction in hypoglycemic events (proportion of BGLs <70 mg/dl in the whole population decreased from 5.2% to 3.4% (p < 0.001), proportion of BGLs < 70 mg/dl for each patient decreased from 5.6 &elusmn; 9.2% to 2.9 &elusmn; 5.4% (p = 0.01), proportion of days where patient had a BGL < 70 mg/dl decreased from 17.6 &elusmn; 22.6% to 11.4 &elusmn; 18.8% (p = 0.03)), despite an increase in the use of supplemental insulin (14.2 &elusmn; 35.7 vs. 29.4 &elusmn; 51.4 units/patient, p = 0.02). This study concluded that the use of a dedicated hospital subcutaneous insulin prescription chart can reduce hypoglycemia and improve some measures of glycemic control. Cheung N.W. et al. Diabetes Research and Clinical Practice 92 (2011) 337–341

Question: The American Diabetes Association recommends that testing to detect type 2 diabetes and assess risk for future diabetes in asymptomatic people should be considered in adults of any age who are overweight or obese (BMI ?25 kg/m2*) and who have one or more of the following additional risk factors:

Women who delivered a baby weighing > 10 lbsSmokingWomen who delivered a baby weighing > 10 lbsHigh-risk race/ethnicitySecond-degree relative with diabetes

Answer: The correct answer is: High-risk race/ethnicity. According to the American Diabetes Association’s (ADA) most recent position statement (Standards of Medical Care in Diabetes - released in January, 2012) testing should be considered in all adults who are overweight (BMI ≥25 kg/m2*) and who have one or more additional risk factors: Physical inactivity; First-degree relative with diabetes, high-risk race/ethnicity (e.g., African American, Latino, Native American, Asian American, Pacific Islander); Women who delivered a baby weighing >9 lb or who were diagnosed with GDM; Hypertension (blood pressure ≥140/90 mmHg or on therapy for hypertension); HDL cholesterol level <35 mg/dL (0.90 mmol/L) and/or a triglyceride level >250 mg/dL (2.82 mmol/L), women with PCOS; A1C ≥5.7%, IGT, or IFG on previous testing; Other clinical conditions associated with insulin resistance (e.g., severe obesity, acanthosis nigricans), history of CVD, In the absence of the above criteria, testing for diabetes should begin at age 45 years. If results are normal, testing should be repeated at least at 3-year intervals, with consideration of more-frequent testing depending on initial results (e.g., those with prediabetes should be tested yearly) and risk status. Diabetes Care. 2012;35:S11-S63

Question: Diabetes is the leading cause of new blindness among people ages 20-74 years. Which of the following statements is false regarding ranibizumab injection, (Lucentis)?

It is used to treat age related macular degenerationThe most common side effectis bleeding of the conjunctivaIt is an anti-angiogenic VEGF inhibitorIt’s a promising therapy for DM macular edema, but isn’t approved by FDA

Answer: The correct answer is: It’s a promising therapy for DM macular edema, but isn’t approved by FDA is false. In August 2012, the Food and Drug Administration approved ranibizumab for the treatment of diabetic macular edema (DME). The drug’s safety and effectiveness to treat DME were established in two clinical studies involving 759 patients who were treated and followed for three years. Patients were randomly assigned to receive monthly injections of Lucentis or no injections for 24 months. Results showed that between 34 - 45 % of those treated withLucentis gained at least three lines of vision compared with 12 -18 % of those who did not. The most common side effects of the drug were bleeding of the conjunctiva, eye pain, and increased intraocular pressure.The FDA previously had approved Lucentis to treat age-related macular degeneration and macular edema following retinal vein occlusion. Ranibizumab is an monoclonal antibody fragment which inhibits a number of subtypes of vascular endothelial growth factors. VEGF increases retinal vascular permeability, thereforeblocking VEGF in the eye may prevent and reverse vision loss caused by macular degeneration. Ip MS, Domalpally A, et al. Long-term effects of intravitreal ranibizumab (RBZ) on diabetic retinopathy severity and progression. Presented at the 2012 Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO); May 6–10, 2012; Fort Lauderdale, Florida. Abstract 1336. Nguyen Q, et al.Ranibizumab for diabetic macular edema results from 2 phase III randomized trials: RISE and RIDE. Ophthalmology.2012;119:789–801.

Question: Results from a post hoc analysis evaluating the efficacy of colesevelam when added to metformin, insulin or sulfonyureas in patients with inadequately controlled type 2 diabetes showed:

A reduction in HbA1c levels by 0.5%All answer choices are correctA reduction in fasting plasma glucose levels by a median of 15.7 mg/dLA reduction in LDL-C by 16.5%

Answer: The correct answer is all answer choices are correct. The Post hoc analysis evaluated the results from 3 randomized, double-blind, placebo-controlled studies over the course of 16 or 26 weeks. Medscape Medical News, May 9, 2011

Question: BC is a 47-year-old male non-smoker with T2DM, hypertension, and obesity. He is taking metformin 1000 mg twice daily, lisinopril 40 mg daily, and amlodipine 10 mg every evening. His lipid profile reveals the following:Total cholesterol 185 mg/dL; HDL 40 mg/dL; TG 145 mg/dL; LDL 90 mg/dL.Should BC be started on a statin?

Physician dependentYesNoOnly after a 3 month trial of lifestyle changes

Answer: The correct answer is: Yes. In addition to lifestyle changes, statins are the primary means of achieving LDL goals. Since BC is over 40 without known CVD and has a cardiac risk factor of hypertension, he should be started on statin therapy regardless of his baseline LDL (90 mg/dL), which is already at goal (<100 mg/dL). The American Diabetes Association recommends that all patients with overt coronary vascular disease (CVD) should receive a statin. Statins should also be prescribed for patients with diabetes who do not have CVD, but who are older than 40 and have one or more cardiac risk factors (family history of CVD, hypertension, smoking, dyslipidemia, or albuminuria) regardless of their baseline LDL cholesterol. The recommended LDL goal in type II diabetics continues to be <100 mg/dL. However, <70 mg/dL is a reasonable goal for those with known CVD. American Diabetes Association. Standards of medical care in diabetes-2013.

Question: A randomized trial was conducted to evaluate the efficacy and safety of initial combination therapy with metformin plus colesevelam in patients with early type 2 diabetes. In post hoc analyses, what percentage of patients achieved the composite dual goal of A1C <7.0% + LDL-C <100 mg/dl with metformin/colesevelam versus metformin/placebo.

25%56%12%40%

Answer: The correct answer is 40%. In post hoc analyses, composite dual glycemic and lipid goals achieved with metformin/colesevelam versus metformin/placebo were: A1C <7.0% + LDL-C <100 mg/dL (40% versus 12% [P<.0001]). In this study, initial treatment with the combination of metformin/colesevelam in patients with type 2 diabetes provided synergistic effects, lowering both A1C and LDL-C levels. Safety and tolerability were similar between the treatment groups. This combination therapy may be particularly beneficial for patients with recently diagnosed type 2 diabetes, helping them to achieve the glycemic and lipid goals associated with overall risk reduction. Additional studies are needed, however, to evaluate whether colesevelam preserves b-cell function in patients with type 2 diabetes and whether it improves cardiovascular outcomes in these patients. Rosenstock J, Fonseca VA, et al. Endocr Pract. 2010 Jul-Aug;16(4):629-40.

Question: Vegetarian diets were found to be associated with a substantial and independent reduction in diabetes incidence. (True or False)

FalseTrue

Answer: The correct answer is True. To evaluate the relationship of diet to incident diabetes among non-Black and Black participants in the Adventist Health Study-2. Participants were 15,200 men and 26,187 women (17.3% Blacks) across the U.S. and Canada who were free of diabetes and who provided demographic, anthropometric, lifestyle and dietary data. Participants were grouped as vegan, lacto ovo vegetarian, pesco vegetarian, semi-vegetarian or non-vegetarian (reference group). A follow-up questionnaire after two years elicited information on the development of diabetes. Cases of diabetes developed in 0.54% of vegans, 1.08% of lacto ovo vegetarians, 1.29% of pesco vegetarians, 0.92% of semi-vegetarians and 2.12% of non-vegetarians. Blacks had an increased risk compared to non-Blacks (odds ratio [OR] 1.364; 95% confidence interval [CI], 1.093-1.702). In multiple logistic regression analysis controlling for age, gender, education, income, television watching, physical activity, sleep, alcohol use, smoking and BMI, vegans (OR 0.381; 95% CI 0.236-0.617), lacto ovo vegetarians (OR 0.618; 95% CI 0.503-0.760) and semi-vegetarians (OR 0.486, 95% CI 0.312-0.755) had a lower risk of diabetes than non-vegetarians. In non-Blacks vegan, lacto ovo and semi-vegetarian diets were protective against diabetes (OR 0.429, 95% CI 0.249-0.740; OR 0.684, 95% CI 0.542-0.862; OR 0.501, 95% CI 0.303-0.827); among Blacks vegan and lacto ovo vegetarian diets were protective (OR 0.304, 95% CI

0.110-0.842; OR 0.472, 95% CI 0.270-0.825). These associations were strengthened when BMI was removed from the analyses.Vegetarian diets (vegan, lacto ovo, semi-) were associated with a substantial and independent reduction in diabetes incidence. In Blacks the dimension of the protection associated with vegetarian diets was as great as the excess risk associated with Black ethnicity. Tonstad S et al. Vegetarian diets and incidence of diabetes in the Adventist Health Study–2. Nutr Metab Cardiovasc Dis. 2011 Oct 7.

Question: Clinical characteristics of obese, ketosis-prone diabetes include which of the following:

DKA provoked by significant precipitating stressPresence of islet cell specific autoantibodiesFemale sex predominancePreserved beta cell functionAge at onset < 40 years


Question: Which of the following statements is false regarding a recently published randomized trial compared insulin degludec verses glargine?

Rates of confirmed hypoglycemia were similar in both groupsThere was significantly more weight gain in the degludec groupDegludec achieved overall glycemic control similar to that of glargineSimilar percentages of pts in both groups achieved A1C levels <7%Degludec had lower nocturnal hypoglycemia rates

Answer: The correct answer is: There was significantly more weight gain in the degludec group is false. In this 1-year, parallel-group, randomized, open-label, treat-to-target trial, insulin naive adults with type 2 diabetes with A1C of 7-10% were randomized to receive once daily degludec or glargine, both with metformin. There were 1,030 participants (degludec 773, glargine 257) with mean age 59 years; baseline A1C 8.2%. Reduction of A1C from baseline to end of trial was similar between treatments; mean A1C decreased by 1.06 to 7.1% with degludec and by 1.19 to 7.0% with glargine. Rates of overall confirmed hypoglycemic episodes were similar (P = 0.106) between treatments. The rate of nocturnal confirmed hypoglycemic episodes was significantly lower (by 36%) with degludec; the estimated rate ratio of degludec to glargine was 0.64 (95% CI 0.42–0.98; P = 0.038). Observed mean weight gain at the end of the trial was similar between degludec and glargine groups (2.4 and 2.1 kg; P = 0.28). End-of-trial mean daily insulin doses were 0.59 and 0.60 units/kg for degludec and glargine, respectively. Degludec is a long acting insulin developed by Novo Nordisk and is currently under review by the FDA, although in Nov 2012, an advisory panel to the U.S. FDA, voted to recommend approval.Combined data from 16 studies suggest degludec may trend toward higher incidence of cardiovascular events compared to standard insulins (difference is not statistically significant and completed trials have not enrolled enough patients, or lasted long enough, to ascertain heart risks). ZinmanB, et al. Insulin Degludec Versus Insulin Glargine in Insulin-Naive Patients With Type 2 Diabetes.Diabetes Care December 2012 vol. 35 no. 12 2464-2471

Question: A randomized clinical trial was conducted to assess the efficacy of a self-monitoring-based disease management strategy in patients with type 2 diabetes treated with oral agent monotherapy. After 6 months, mean HbA1c reduction in the intervention group was:

1.2%1.6%0.5%1.9%0.7%

Answer: The correct answer is 1.2%. This was an open-label, randomized, pilot study, primarily led by diabetes nurses. Patients were randomly allocated to either a self-monitoring-based disease management strategy or usual care and

followed up for 6 months. Self-monitoring of blood glucose results were discussed during monthly telephone contact. Patient Franciosi M, et al. Diabetic Medicine: (2011) 28: 789–796

Question: BC is a 57-year-old male non-smoker with T2DM, hypertension, and obesity. He has recently moved into the neighborhood and this is his first physician encounter with you. He has made numerous lifestyle changes over the last 8 months including diet and exercise. He is taking metformin 1000 mg twice daily, aspirin 81 mg daily, lisinopril 40 mg daily, amlodipine 10 mg every evening, and simvastatin 40 mg every evening. His Hem A1C is 6.9%, BP 128/76 mm Hg and lipid profile: Total cholesterol 185 mg/dL; HDL 40 mg/dL; TG 145 mg/dL; LDL 110 mg/dL.Comprehensive metabolic panel is normal. The patient feels well, has no complaints and reports no hypoglycemia. What is your next step?

Stop aspirin therapy.Increase simvastatin to 80 mg daily.Stop simvastatin and start atorvastatin.Make no medication changes on this visit.Decrease metformin to 500 mg twice daily.

Answer: The correct answer is: Stop simvastatin and start atorvastatin. The ADA recommends the low-density lipoprotein-cholesterol (LDL-C) goal in patients with diabetes with no overt CVD to be <100 mg/dL (2.6 mmol/L). This patient does not currently meet this goal, therefore choice A is incorrect. Simvastatin 80 mg is limited to patients that have been taking this dose for >12 consecutive months without evidence of myopathy and are not currently taking or beginning to take a simvastatin dose-limiting or contraindicated interacting medications.It is recommended that patients who are unable to achieve LDL-C goal using the 40 mg dose of simvastatin, be switched to an alternative LDL-C-lowering treatment that provides greater LDL-C reduction, than increasing the simvastatin dose to 80 mg. This patient’s A1c is at goal, he is tolerating metformin without issue, and has no renal or liver dysfunction (normal CMP), therefore there is no indication to decrease or stop metformin. The ADA currently recommends aspirin 75–162 mg/day in patients with DM2 at increased CVD risk (10-yr risk >10%). This patients Framingham risk score is 10%, thereforediscontinuing aspirin therapy is incorrect.

FDA Drug Safety Communication: Restrictions, contraindications, and dose limitations for Zocor (simvastatin) to reduce the risk of muscle injury. Based on FDA's review of the Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) trial.

Question: The risk of developing type 1 diabetes in the offspring of a mother with type 1 diabetes is:

1.5%3%8%6%

Answer: The correct answer is 3%. The offspring of a mother with type 1 DM have a 3% risk of developing type 1 diabetes. David G. Gardner, Dolores Shoback, ed. Greenspan's Basic & Clinical Endocrinology. Ninth ed.; 2011:589.

Question: The TIMES2 Study evaluated the effects of testosterone replacement therapy (TRT) on Insulin resistance, cardiovascular risk factors, and symptoms in hypogonadal men with type 2 diabetes and/or metabolic syndrome. Transdermal TRT was associated with which of the following?

Increase in Non-fatal Cardiovascular Events Increase in LDL cholesterol Increase in HDL cholesterol Increase in lipoprotein a (Lpa) Reduction in homeostasis model assessment of insulin resistance (HOMA-IR)

Answer: Reduction in homeostasis model assessment of insulin resistance (HOMA-IR). There were Improvements in total and LDL cholesterol, and Lpa. HDL cholesterol decreased from baseline significantly more with TRT than placebo. There were no significant differences between groups in the frequencies of adverse events (AEs) or serious AEs. The majority of AEs (>95%) were mild or moderate. Diabetes Care. 2011;34(4):828-837.

Question: Which of the following best describes the principal findings of SOLVE: Study of Once Daily Levemir: insights into the timing of insulin initiation in people with poorly controlled type 2 diabetes in routine clinical practice?Metformin, sulfonylurea and dual OAD (metformin plus sulfonylurea), remain the most common treatments prior to insulin initiation.All of the answer choices are correct.The majority of patients with T2DM were poorly controlled at the point at which the decision was taken to initiate basal insulin treatment.Considerable regional differences exist in the timing of insulin initiation and in the use of OADs.

Answer: The correct answer is: All of the answer choices are correct. The aim of this analysis was to determine the timing of insulin initiation in routine clinical practice, especially in relation to glycemic control and use of oral antidiabetic drugs (OADs). Study of Once Daily Levemir was a 24-week international observational study involving 10 countries (Canada, China, Germany, Israel, Italy, Poland, Portugal, Spain, Turkey and the UK). which evaluated the safety and effectiveness of initiating once-daily insulin detemir in people with T2DM being treated with one or more OADs. A total of 17,374 participants were enrolled in the study: aged 62 ± 12 years, 53% male, T2DM duration 10 ± 7 years, body mass index 29.3 ± 5.4 kg/m2 Pre-insulin HbA1c was 8.9 ± 1.6%. The proportion of patients with HbA1c ≥9.0% ranged from 64% (UK) to 23% (Poland). Pre-insulin OAD treatment included metformin (81%), sulfonylureas (59%), glinides (16%), thiazolidinediones (TZD) (12%), α-glucosidase inhibitors (12%) and dipeptidyl peptidase (DPP)-IV inhibitors (7%). The mean starting dose of insulin detemir for the total cohort was 0.16 ± 0.09 U/kg. Differences in OAD use and insulin doses at initiation were evident among participating countries. The largest proportional changes in OAD prescribing at insulin initiation were seen with glinides (+15%), sulfonylureas (-19%), TZD (-31%) and DPP-IV inhibitors (-28%). Despite the well-documented benefits of timely blood glucose control and the availability of consensus guidelines encouraging the earlier use of insulin replacement, a substantial delay remains with respect to the appropriate initiation of insulin treatment in routine clinical practice. Nearly half of the patients had HbA1c ≥9.0% despite prolonged treatment with multiple OADs. Considerable regional differences exist in both the timing of insulin initiation and in the use of OADs. SOLVE provides an opportunity to better understand global and regional trends in the intensification of treatment in patients with T2DM. These findings should facilitate the development of targeted treatment strategies in order to achieve improved glycemic control earlier in the course of T2DM.alpha;-glucosidase inhibitors (12%) and dipeptidyl peptidase (DPP)-IV inhibitors (7%). The mean starting dose of insulin detemir for the total cohort was 0.16 ± 0.09 U/kg. Differences in OAD use and insulin doses at initiation were evident among participating countries. The largest proportional changes in OAD prescribing at insulin initiation were seen with glinides (+15%), sulfonylureas (-19%), TZD (-31%) and DPP-IV inhibitors (-28%). Despite the well-documented benefits of timely blood glucose control and the availability of consensus guidelines encouraging the earlier use of insulin replacement, a substantial delay remains with respect to the appropriate initiation of insulin treatment in routine clinical practice. Nearly half of the patients had HbA1c alpha;-glucosidase inhibitors (12%) and dipeptidyl peptidase (DPP)-IV inhibitors (7%). The mean starting dose of insulin detemir for the total cohort was 0.16 ± 0.09 U/kg. Differences in OAD use and insulin doses at initiation were evident among participating countries. The largest proportional changes in OAD prescribing at insulin initiation were seen with glinides (+15%), sulfonylureas (-19%), TZD (-31%) and DPP-IV inhibitors (-28%). Despite the well-documented benefits of timely blood glucose control and the availability of consensus guidelines encouraging the earlier use of insulin replacement, a substantial delay remains with respect to the appropriate initiation of insulin treatment in routine clinical practice. Nearly half of the patients had HbA1c Khunti K et al. Diabetes, Obesity and Metabolism, 2012 Jul;14(7):654-61.

Question 1: A 52-year-old male with DM2 on insulin, reportsdysesthesia, numbness and tingling of extremities, and poor sleep quality. You diagnosediabetic peripheral neuropathic pain. Which therapy would you prescribe for analgesia and improved sleep?

Duloxetine

Vitamin B12

Amitriptyline

Pregabalin

Answer: The correct answer is pregabalin. A recently published, double-blind, randomized trial compared amitriptyline, duloxetine and pregabalin in 104 diabetics with peripheral neuropathic pain. Subjective pain and sleep quality (using polysomnography sleep records) were assessed over 28 days. Amitriptyline, duloxetine, and pregabalin, all reduced subjective pain with no one drug being superior to another. Subjective pain ratings showed ∼50% improvement, in line with previous studies. For sleep, pregabalin improvedsleep continuity (P< 0.001), reducing wake after sleep onset, in line with previous reports. Duloxetine increased wake and reduced total sleep time (P< 0.01 and P< 0.001) and substantially

reduced REM sleep. Previous literature suggests that amitriptyline promotes sleep initiation and sleep continuity, however there may be less impact of amitriptyline on sleep in patients with diabetic peripheral neuropathic pain. Research has shown that people who take metformin may be at risk for developing vitamin B12 deficiency associated peripheral neuropathy, however this patient is on insulin. Boyle J, et al. Randomized, Placebo-Controlled Comparison of Amitriptyline, Duloxetine, and Pregabalin in Patients with Chronic Diabetic Peripheral Neuropathic Pain. Impact on pain, polysomnographic sleep, daytime functioning, and quality of life. Diabetes CareDecember 2012 vol. 35 no. 12 2451-2458

Question: A post hoc analysis of data from the DURABLE clinical trial was performed to compare outcomes in patients with type 2 diabetes initiating Humalog 75/25 or insulin glargine therapy, stratified by baseline oral antihyperglycemic agent (OHA). Which of the following OHA treatment groups had the greatest improvement in HbA1c?

Metformin/sulfonylurea/thiazolidinedione

Metformin/thiazolidinedione

Sulfonylurea/thiazolidinedione

Metformin/sulfonylurea

Answer: The correct answer is metformin/thiazolidinedione. A significantly greater proportion of patients in the metformin/thiazolidinedione group achieved an A1C value less than 7.0% in comparison with the cor¬responding proportion in the metformin/sulfonylurea group. In both insulin treatment groups, metformin/thiazolidinedione-treated patients had significantly greater improvement in A1C levels (-2.19% to -2.36%) and lower end point A1C values, in comparison with metformin/sulfonyl¬urea-treated patients (all P<.05). Patients treated with sulfonylurea/thiazolidinedione or metformin/sulfonylurea/thiazolidinedione did not differ significantly from metfor¬min/sulfonylurea-treated patients in A1C change (-1.56% to -1.84%). Although the analysis did not specificallycompare outcomes between insulin treatment groups, both insulin treatment groups had relatively similar A1C reductions with metformin/thiazolidinedione therapy. Herman WH, et al. Concomitant oral antihyperglycemic agent use and associated treatment outcomes after initiation of insulin therapy.

Question : A 26-year-old male with DM1 has an insulin regimen that includes insulin glargine26 units at bedtime and insulin aspart1 unit per 16 g carbohydrate for breakfast and lunch, and 1 unit per 13 g carbohydrate for dinner. He has a correction dose of 1 unit per 45 mg/dL, with a glucose goal of less than 120 mg/dL for corrections. He has normal renal and liver function. His Hem A1c is 7.8%. The patient reports that his fasting glucose numbers are within goal. However, he is using correction doses before bedtime as he has noticed high glucose levels at that time. He reports his evening glucose levels rise even with initial response to the aspart dose he gives himself at dinner. What changes to his insulin regimen is the most appropriate?

Split glargine into 13 units in the morning and 13 units in the evening

Change glargine from bedtime to morning

Increase glargine to 28 units at bedtime

Increase carbohydrate ratio to 1 unit per 10g of carbohydrate for dinner

Answer: The correct answer is: Split glargine into 13 units in the morning and 13 units in the evening. The patient is having insufficient basal insulin late in the 24-hour dosing period. This is an issue for up to 20% of patients with once daily glargine dosing. An overlapping effect is created by splitting the basal insulin into 2 doses, which would reduce any decrease in the insulin level. Choice A is incorrect as changing the timing to the morning would shift the glucose rise to another part of the day (before breakfast). The patients’ basal insulin dose is greater than 50% of the total daily insulin dosage, and his fasting numbers are at goal, therefore increasing the glarginedose would not be helpful (choice B). The patients dinner carbohydrate counting ratio is already more intense that the ratio he uses for breakfast and lunch. Increasing it would decrease the glucose peak after dinner, but would not prevent the glucose rise later in the evening (choice D).

Roach P 2008 New insulin analogues and routes of delivery: Pharmacodynamics and clinical considerations. ClinPharmacokinet 47:595-610.

Question: The ACCORD Study Group investigated whether combination therapy with a statin plus a fibrate, as compared with statin monotherapy, would reduce the risk of cardiovascular disease in patients with type 2 diabetes mellitus who were at high risk for cardiovascular disease. Which of the following best describes the results?

The combination of fenofibrate and simvastatin reduced the rate of fatal nonfatal myocardial infarction only, as compared

with simvastatin alone.

Women seemed to benefit from fenofibrate therapy, whereas there was a trend toward harm among men.

The combination of fenofibrate and simvastatin did not reduce the rate of fatal cardiovascular events, nonfatal

myocardial infarction, or nonfatal stroke, as compared with simvastain alone

The combination of fenofibrate and simvastatin did reduce the rate of fatal cardiovascular events, nonfatal myocardial

infarction, and nonfatal stroke, as compared with simvastatin alone.

Answer: The combination of fenofibrate and simvastatin did not reduce the rate of fatal cardiovascular events, nonfatal myocardial infarction, or nonfatal stroke, as compared with simvastain alone. The rates of the primary outcome did not differ significantly between the fenofibrate group and the placebo group during 4.7 years of treatment and follow-up. The annual rate of the primary outcome was 2.2% in the fenofibrate group and 2.4% in the placebo group (hazard ratio in the fenofibrate group, 0.92; 95% confidence interval [CI], 0.79 to 1.08; P = 0.32). Prespecified subgroup analyses suggested heterogeneity in treatment effect according to sex, with a benefit for men and possible harm for women. The primary outcome for men was 11.2% in the fenofibrate group versus 13.3% in the placebo group, whereas the rate for women was 9.1% in the fenofibrate group versus 6.6% in the placebo group (P = 0.01 for interaction). ACCORD Study Group, Ginsberg HN, Elam MB, et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med. 2010;362(17):1563-1574.

Question : The ORIGIN trial evaluated the effect of insulin glargine in patients with diabetes mellitus and prediabetes. Based on the results of the trial, which of the following statements is true regarding insulin glargine?

It decreased the incidence of colon cancer

It reducedthe risk of developing DM2 by 28% in prediabetes patients

It slowed the progression of microalbuminuria

It slowed the progression of atherosclerosis

Answer: The correct answer is: It reducedthe risk of developing DM2 by 28% in prediabetes patients is true. Glargine reduced the risk of developing type 2 diabetes by 28% among patients with prediabetes. 12,537 patients (mean age of 63.5) with cardiovascular risk factors plus impaired fasting glucose, impaired glucose tolerance, or DM2were randomly assigned to receive insulin glargine or standard care. Patients were followed for an average of 6 years. Glargine did not slow the progression of atherosclerosis and had a neutral effect on cardiovascular outcomes with rates of incident cardiovascular outcomes being similar in the glargine and standard-care groups: 2.94 and 2.85 per 100 person-years, respectively, (hazard ratio, 1.02; 95% confidence interval [CI], 0.94 to 1.11; P=0.63).Glargine slowed the progression of dysglycemia; patients who were assigned to glargine were 28% less likely to have diabetes develop from the time of randomization until the first oral glucose-tolerance test than were participants assigned to standard care. Insulin glargine also had a neutral effect on cancers (colon, prostate, melanoma, breast, lung) with hazard ratio for colon cancer of 1.09;95% CI, 0.79 to 1.51; P=0.61.There was also no significant difference microvascular events, (including microalbuminuria[hazard ratio, 0.97; 95% CI, 0.90 to 1.05; P=0.43]). The Origin Trial Investigators. Basal Insulin and Cardiovascular and Other Outcomes in Dysglycemia.N Engl J Med 2012; 367:319-398 July 26, 2012.

Question: A 52-year-old male with DM2 on insulin, reportsdysesthesia, numbness and tingling of extremities, and poor sleep quality. You diagnosediabetic peripheral neuropathic pain. Which therapy would you prescribe for analgesia and improved sleep?Duloxetine

Amitriptyline

Vitamin B12

Pregabalin

Answer: The correct answer is pregabalin. A recently published, double-blind, randomized trial compared amitriptyline, duloxetine and pregabalin in 104 diabetics with peripheral neuropathic pain. Subjective pain and sleep quality (using polysomnography sleep records) were assessed over 28 days. Amitriptyline, duloxetine, and pregabalin, all reduced subjective pain with no one drug being superior to another. Subjective pain ratings showed ∼50% improvement, in line with previous studies. For sleep, pregabalin improvedsleep continuity (P< 0.001), reducing wake after sleep onset, in line

with previous reports. Duloxetine increased wake and reduced total sleep time (P< 0.01 and P< 0.001) and substantially reduced REM sleep. Previous literature suggests that amitriptyline promotes sleep initiation and sleep continuity, however there may be less impact of amitriptyline on sleep in patients with diabetic peripheral neuropathic pain. Research has shown that people who take metformin may be at risk for developing vitamin B12 deficiency associated peripheral neuropathy, however this patient is on insulin. Boyle J, et al. Randomized, Placebo-Controlled Comparison of Amitriptyline, Duloxetine, and Pregabalin in Patients with Chronic Diabetic Peripheral Neuropathic Pain. Impact on pain, polysomnographic sleep, daytime functioning, and quality of life. Diabetes CareDecember 2012 vol. 35 no. 12 2451-2458

Question 1: Which of the following statements is true regarding the risk of coronary artery disease (CAD) in a patient with T2DM and no known history of cardiovascular disease (CVD)?

About the same as that of a nondiabetic individual with CAD

About twice that of a nondiabetic individual with CAD

About the same as that of a nondiabetic individual without CAD

About half that of a nondiabetic individual with CAD

Answer: The correct answer is: About the same as that of a nondiabetic individual with CAD. Research has substantiated that patients with type 2 diabetes mellitus are at increased risk for cardiovascular (CV) disease. The hazard ratio for death from CAD for diabetic subjects without prior myocardial infarction was no different than in nondiabetic subjects with prior MI, even correcting for other baseline risk factors. Diabetes is a risk factor for CVD, equivalent to smoking and hyperlipidemia. More recent studies suggest that both early and late onset of diabetes are associated with increased risk of major CVD events and mortality, but only early onset of diabetes (associated with >10 years' duration) appears to be a CVD equivalent. The risk is about 2-3 times that of non-diabetic individuals without CAD. Wannamethee SG, et al. Arch Intern Med. 2011;171(5):404-410.

Question: Which factor does not predict relapse of diabetes in obese patients with DM2, whom have experienced remission of diabetes following gastric bypass surgery?

Pre-operative diabetes duration

Older age at surgery

Pre-operative glycemic control

Pre-operative BMI values

Insulin therapy before surgery

Answer: The correct answer is pre-operative BMI values. Data was collected in a retrospective cohort study of 4,434 adults with type 2 diabetes who underwent gastric bypass from 1995 to 2008. Diabetes remission and relapse events were recorded.Multivariate analysis showed older age at surgery was associated with higher risk of relapse (HR for 5-year increase in age, 1.07; 95 % CI, 1.01 to 1.14). Subjects with poor preoperative glycemic control (HbA1c ≥6.5 %) were significantly more likely to experience relapse than those with good preoperative control, (HR for HbA1c 6.5-8% 1.34; 95% CI 1.04-1.71, HR for HbA1c 8-9% 1.43; 95% CI 1.03-1.97, HR for HbA1c 9-10% 1.95; 95% CI, 1.34-2.84). Subjects treated with insulin were significantly more likely to experience relapse than diabetic subjects not using insulin before surgery (HR for patients on oral medication at surgery 1.37; 95% CI 1.10-1.70 and HR for patients on insulin at surgery 1.91; 1.48-2.45). Longer diabetes duration was significantly associated with higher relapse rate (HR for each additional year of diabetes, 1.13; 95 % CI, 1.09 to 1.17). However, pre-operative BMI values were not significantly different (p = 0.93) between patients who never completely remitted their diabetes (BMI 45.5 kg/m2), patients who completely remitted but relapsed (BMI 45.8 kg/m2), and patients who durably remitted their diabetes (BMI 45.6 kg/m2). Arterburn D, et al. A Multisite Study of Long-term Remission and Relapse of Type 2 Diabetes Mellitus Following Gastric Bypass. Obesity Surgery 2012

Question: Exenatide once weekly (EQW) was compared to with insulin detemir in patients with type 2 diabetes inadequately controlled with metformin. Which of the following statements is false regarding the trial results?

A1c targets were not different between the EQW and detemir groups

Injection site–related adverse events occurred more often with EQW

GI-related adverse events occurred more frequently with EQW

Patients who received EQW had more weight loss

Patients who received EQW had a low risk of hypoglycemia

Answer: The correct answer is: A1c targets were not different between the EQW and detemir groups. A multicenter, open-label, parallel-arm study compared the efficacy and safety of exenatide once weekly (EQW) with titrated insulin detemir in 216 patients with type 2 diabetes inadequately controlled with metformin. Patients were randomized to EQW (2 mg) or detemironce or twice daily, titrated to achieve target fasting plasma glucose for 26 weeks. The primary outcome was proportion of patients achieving A1C?7.0% and weight loss ?1.0 kg. Therapy with EQW provided better glycemic and weight control compared with detemir. Patients who received EQW were 6.6-times more likely to achieve A1C ? 7.0% with weight loss ?1.0 kg than patients who received detemir. Overall, 44.1% (95% CI, 34.7–53.9) of EQW-treated patients compared with 11.4% (6.0–19.1) of detemir-treated patients achieved the primary outcome (P < 0.0001). Treatment with EQW resulted in significantly greater reductions than detemir inweight (-2.7 +/- 0.3 kg vs. +0.8 +/- 0.4 kg; P < 0.0001). Gastrointestinal-related and injection site–related adverse events occurred more frequently with EQW than with detemir. There was no major hypoglycemia in either group. Five (6%) patients in the EQW group and six (7%) patients in the detemir group experienced minor hypoglycemia. Melanie Davies, MD et. al. Once-Weekly Exenatide Versus Once- or Twice-Daily Insulin Detemir. Randomized, open-label, clinical trial of efficacy and safety in patients with type 2 diabetes treated with metformin alone or in combination with sulfonylureas.Diabetes Care,December 2012.


All of the answer choices are correct

No change in glycemic variability

A reduction in length of hospital stay related to gastroparesis and glycemic instability

No statistically significant reduction in HbA1c

A higher median median capillary blood glucose (CBG)


Question: A Japanese study recently assessed 35 type 1 diabetic patients without detectable C–peptide using the insulin pump and found that the basal insulin requirement of the total daily insulin dose was approximately:

35%

50%

40%

30%

45%

Answer: The correct answer is 30%. This study was done during 2–3 weeks of hospitalization in patients on diabetic diets. Total daily insulin dose was 31.6 ± 8.5 units, and total basal insulin requirement was 8.7 6 ± 2.9 units, which was 27.7 ± 6.9% of the total daily dose (TDD). In addition, the maximal basal insulin requirement in all patients was 43.8% TDD, and no patients required 50% TDD. Kuroda A, et al. Diabetes Care. 2011; 34(5):1089-1090

Question: Which of the following groups of patients is the least likely to need diabetic screening?

Patients with psoriasis

African American patients who are overweight (BMI ≥ 25)

Patients with crohn's disease

Patients who are ≥ 45 years old

Overweight females (BMI ≥ 25) with polycystic ovary syndrome

Answer: The correct answer is: Patients with crohn's disease are least likely to need diabetic screening. The ADA recommends testing for diabetes in all adults with BMI ≥25kg/m2 and one or more additional risk factors for diabetes (family history diabetes mellitus in a first-degree relative, habitual physical inactivity, belonging to a high-risk ethnic or racial group [eg, African-American, Hispanic, Native American, Asian-American, and Pacific Islanders], history of delivering a baby weighing >4.1 kg or >9 lb, or of gestational diabetes mellitus, hypertension, dyslipidemia, polycystic ovary syndrome, history of vascular disease). In individuals without risk factors, testing should begin at age 45 ≥ years. Patients withchronicdiseases such as psoriasis and crohn's may be on long term steroids that American Diabetes Association. Standards of medical care in diabetes--2012. Diabetes Care 2012; 35 Suppl 1:S11.

Question: BC is a 47-year-old male non-smoker with T2DM, hypertension, and obesity. He is taking metformin 1000 mg twice daily, lisinopril 40 mg daily, and amlodipine 10 mg every evening. His lipid profile reveals the following:Total cholesterol 185 mg/dL; HDL 40 mg/dL; TG 145 mg/dL; LDL 90 mg/dL.Should BC be started on a statin?

No

Only after a 3 month trial of lifestyle changes

Physician dependent

Yes

Answer: The correct answer is: Yes. In addition to lifestyle changes, statins are the primary means of achieving LDL goals. Since BC is over 40 without known CVD and has a cardiac risk factor of hypertension, he should be started on statin therapy regardless of his baseline LDL (90 mg/dL), which is already at goal (<100 mg/dL). The American Diabetes Association recommends that all patients with overt coronary vascular disease (CVD) should receive a statin. Statins should also be prescribed for patients with diabetes who do not have CVD, but who are older than 40 and have one or more cardiac risk factors (family history of CVD, hypertension, smoking, dyslipidemia, or albuminuria) regardless of their baseline LDL cholesterol. The recommended LDL goal in type II diabetics continues to be <100 mg/dL. However, <70 mg/dL is a reasonable goal for those with known CVD. American Diabetes Association. Standards of medical care in diabetes-2013.

Question: Results from a pooled analysis evaluating the benefits of initiating insulin to metformin at an earlier versus later treatment stage, with or without sulfonylurea showed:

Patients taking metformin in combination with a sulfonylurea experienced the greatest HbA1c reductions after the

addition of basal insulin

Weight gain was significantly higher when basal insulin was added to a sulfonylurea alone

Patients taking metformin alone experienced the greatest HbA1c reductions after the addition of basal insulin

Answer: Patients taking metformin alone experienced the greatest HbA1c reductions after the addition of basal insulin. In this large, pooled analysis of prospective, randomized, controlled clinical trials in patients with type 2 diabetes, more than half of the patients previously uncontrolled on 0, 1 or 2 oral antidiabetic drugs (OADs) with baseline HbA1c of 8.7–

9.1% achieved a target HbA1c ≤7.0% after 24 weeks of treatment with the addition of basal insulin, while continuing the oral agent(s). Patients taking metformin (MET) alone before the initiation of basal insulin had the greatest HbA1c reductions and the largest proportion of patients achieving glycemic goal at week 24 compared with patients taking an sulfonylurea (SU) alone or in combination with MET. Of patients failing MET/SU monotherapy and MET + SU in combination, 68.1, 50.4 and 56.4% achieved HbA1c ≤ 7.0%, respectively (p = 0.0006). Weight gain from baseline to week 24 was not significantly different, based on either the number or type of OAD therapy at baseline However, the MET-only group had the numerically lowest weight gain over 24 weeks (1.6 vs. 2.3 k in the SU-only group and 2.0 kg in the combination group, p = 0.1830) after basal insulin initiation.These findings suggest that some patients may benefit from the initiation of basal insulin to MET monotherapy earlier in the management of type 2 diabetes than often occurs in this clinical practice, which supports the inclusion of insulin as a second step in the American Diabetes Association/European Association for the Study of Diabetes treatment algorithm. Fonseca V et al. Diabetes, Obesity and Metabolism 13: 814–822, 2011.

Question: A randomized trial was conducted to evaluate the efficacy and safety of initial combination therapy with metformin plus colesevelam in patients with early type 2 diabetes. In post hoc analyses, what percentage of patients achieved the composite dual goal of A1C <7.0% + LDL-C <100 mg/dl with metformin/colesevelam versus metformin/placebo.

25%

12%

56%

40%

Answer: The correct answer is 40%. In post hoc analyses, composite dual glycemic and lipid goals achieved with metformin/colesevelam versus metformin/placebo were: A1C <7.0% + LDL-C <100 mg/dL (40% versus 12% [P<.0001]). In this study, initial treatment with the combination of metformin/colesevelam in patients with type 2 diabetes provided synergistic effects, lowering both A1C and LDL-C levels. Safety and tolerability were similar between the treatment groups. This combination therapy may be particularly beneficial for patients with recently diagnosed type 2 diabetes, helping them to achieve the glycemic and lipid goals associated with overall risk reduction. Additional studies are needed, however, to evaluate whether colesevelam preserves b-cell function in patients with type 2 diabetes and whether it improves cardiovascular outcomes in these patients. Rosenstock J, Fonseca VA, et al. Endocr Pract. 2010 Jul-Aug;16(4):629-40.

Question: Clinical characteristics of obese, ketosis-prone diabetes include which of the following:

Preserved beta cell function

Female sex predominance

DKA provoked by significant precipitating stress

Age at onset < 40 years

Presence of islet cell specific autoantibodies


Question: Which of the following mechanisms by which hypoglycemia may indirectly affect cardiovascular events is correct?

Hypoglycemia is associated with QTC prolongation

All of the answer choices are correct.

None of the answer choices are correct

Hypoglycemia causes an increase in inflammatory cytokine secretion

Hypoglycemia induces abnormalities in platelet function and activation of the fibrinolytic system

Answer: The correct answer is: All of the answer choices are correct. Hypoglycemia induces several counterregulatory responses. They include a decrease in pancreatic β-cell insulin secretion, an increase in pancreatic α -cell glucagon secretion, an increased sympathoadrenal response with acute plasma increase in adrenaline and norepinephrine (in addition to its elevated tissue turnover),

as well as an increased secretion of ACTH/glucocorticoids. Besides these classical responses, there are several indirect changes induced by hypoglycemia that affect inflammatory cytokine secretion, endothelial function, coagulation, and fibrinolysis. Several studies have shown that hypoglycemia is associated with a significant lengthening of the corrected QT interval (QTC) in subjects with and without diabetes. Other electrocardiographic abnormalities observed during hypoglycemia include a decrease in PR interval and moderate ST segment depression. These changes are likely seen because of increased catecholamine release during hypoglycemia, and QTC prolongation in particular could lead to a high risk of ventricular tachycardia and sudden death. Inflammation has been associated with cardiovascular disease and diabetes. Several inflammatory markers including C-reactive protein, interleukin IL-6, IL-8, tumor necrosis factor (TNF)- α and endothelin-1 have been shown to be increased during hypoglycemia. This increase in inflammatory cytokines could result in endothelial injury and abnormalities in coagulation, resulting in increased risk for cardiovascular events. Certain growth factor levels such as vascular endothelial growth factor are also increased locally and in circulation after an episode of hypoglycemia. Furthermore, some cytokines such as IL-1 have been shown to increase the severity of hypoglycemia, thus perpetuating a positive feedback cycle. Hypoglycemia induces abnormalities in platelet function and activation of the fibrinolytic system. Increased epinephrine levels lead to an increase in platelet activation, leukocyte mobilization, and blood coagulability. Desouza CV, Bolli GB, Fonseca VA. Diabetes Care, 2010;33:1389-1391.

Question: Patients with metabolic syndrome and type 2 diabetes have an exacerbated vascular smooth muscle dysfunction in micro- and macrocirculation compared to those with metabolic syndrome but without type 2 diabetes. True or False?FalseTrueAnswer: True. Metabolic syndrome is associated with endothelial-dependent and endothelial-independent dysfunction, affecting both the macro- and the microvascular systems. Walther G, et al. Arterioscler Thromb Vasc Biol . 2015;35(4):1022-1029.

Question: In those same patients, indices of micro- and macrocirculation are predominantly inversely related to:Inflammatory markersNeither answer is correct – positively associatedAbdominal fatBoth answers are correctAnswer: Both answers are correct. The presence of central abdominal fat and systemic inflammation seems implicated in the pathogenesis of vascular dysfunctions in metabolic syndrome. Walther G, et al. Arterioscler Thromb Vasc Biol . 2015;35(4):1022-1029.

Question: Anthocyanin supplementation in patients with type 2 DIABETES would significantly improve:Serum adiponectinNone of the answers is correctAll of the answers are correctFasting plasma glucose

Serum LDL-CAnswer: All of the answers are correct. Study results suggest that anthocyanin supplementation exerts beneficial metabolic effects in patients with type 2 DIABETES by improving dyslipidemia, enhancing antioxidant capacity and preventing insulin resistance. Li D, et al. J Nutr . 2015;145(4):742-748.

Question: Which outcome is observed when switching from insulin glargine to NPN insulin?Higher frequencies of severe hypoglycemiaIncreased rates of symptomatic hypoglycemiaIncreased metabolic controlGreater treatment satisfactionAnswer: Higher frequencies of severe hypoglycemia. Switching to NPH insulin doubled the rate of severe hypoglycemias and led to decreased metabolic control in the ACCORD trial. Berard L, et al. Can J Diabetes . 2015 Mar 24. [Epub ahead of print]

Question: The major allele rs2431332 at the DMG-dehydrogenase-locus is significantly associated with:None of the answers is correctAll of the answers are correctHigher plasma insulinIncreased insulin resistanceIncreased risk of incident DIABETES

http://www.mdlinx.com/endocrinology/smartestdoc/quizResults.cfm?qeid=EED901FD18A04817BF968A5F888691F1

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Answer: All of the answers are correct. Study results are consistent with a possible causal role of DMG deficiency in DIABETES development. Magnusson M, et al. Diabetes . 2015 Mar 20. [Epub ahead of print] The answers represent the best choice, based on the information provided in the question, generally referring to a specific indicated study.

Question: Which variable is associated with increased odds of malignancy in patients with thyroid follicular neoplasm?

None of the answers is correct

Multinodularity on physical examination

Concomitant hyperthyroidism

History of head and neck radiation

All of the answers are correctAnswer: History of head and neck radiation. Male sex and family history of thyroid cancer were also associated with increased odds of malignancy. Najafian A, et al. Ann Surg Oncol . 2015 Jan 7. [Epub ahead of print]

Question: Which variable is associated with increased odds of a benign lesion in patients with thyroid follicular neoplasm?

Age >45 years

Dysphagia or pressure sensation


All of the answers are correct

Nodules ≥4 cmAnswer: All of the answers are correct. Independent clinical predictors exist that might be helpful in preoperative differentiation of benign and malignant follicular neoplasms. Najafian A, et al. Ann Surg Oncol . 2015 Jan 7. [Epub ahead of print]

Question 3: Testosterone regulates thyroid cancer progression by reducing tumor-suppressor-gene expression and tumor immunity. True or False?

True

FalseAnswer: True. This according to a recent study. Thyroid cancer has a higher incidence in women but more aggressive disease in men. Zhang LJ, et al. Carcinogenesis . 2015;36(4):420-428.

Question: Dabrafenib can stimulate radioiodine uptake in patients with metastatic BRAF V600E-mutant iodine-refractory papillary thyroid cancer (PTC). True or False?

True

FalseAnswer: True. Thus representing a potential new therapeutic approach for these patients. Rothenberg SM, et al. Clin Cancer Res . 2015;21(5):1028-1035.

Question: Which variable is associated with a higher risk of lateral neck recurrence in patients with papillary thyroid carcinoma (PTC) with no ultrasonographic and/or cytological evidence of lymph node metastasis at diagnosis?

Central neck metastasis

Aggressive histological variants

Neither answer is correct

Both answers are correctAnswer: Both answers are correct. In these patients, a closer postsurgical ultrasound surveillance of the lateral neck compartments seems worthwhile. Giordano D, et al. Laryngoscope . 2014 Dec 15. [Epub ahead of print] The answers represent the best choice, based on the information provided in the question, generally referring to a specific indicated study.








Question: Which characteristic differs between patients age 21 years and younger with papillary thyroid carcinomas ≤10 mm and older patients with papillary thyroid microcarcinomas?

Neither answer is correct

Both answers are correct

Rate of lymph node metastases

Tumor sizeAnswer: Both answers are correct. In a recent study, mean tumor size was larger and the frequency of lymph node metastases greater in the younger patients. Pazaitou-Panayiotou K, et al. J Pediatr . 2015;166(2):451-456.e2.

Question: Exposure to which factor in the second or third trimester of pregnancy is associated with a higher risk of childhood obesity?

Antibiotics

Cesarean section

Both answers are correct

Neither answer is correctAnswer: Both answers are correct. The risk of childhood obesity was 84% higher after prenatal exposure to antibiotics and 46% higher after cesarean section. Mueller NT, et al. Int J Obes (Lond) . 2015;39(4):665-670.

Question: True or false: Children with type 1 diabetes have impaired school performance compared with their nondiabetic peers.

True

FalseAnswer: False. In a recent analysis, there were no differences between the groups for any of the educational outcome domains tested. However, poorer glycemic control was associated with lower test scores and school attendance. Cooper MN, et al. Pediatr Diabetes . 2014 Nov 25. [Epub ahead of print]

Question: True or false: Migraine and tension headache are associated with childhood obesity.

False

TrueAnswer: False. In a recent study, frequency and duration of headache attacks did not differ across BMI categories in children. Eidlitz-Markus T, et al. J Child Neurol . 2015;30(4):445-450.

Question: Atorvastatin therapy improves which lipid parameter in children with type 1 diabetes and elevated LDL-

All of the answers are correct

Apolipoprotein B


LDL-C

Lipoprotein subparticlesAnswer: All of the answers are correct. In addition to each answer choice, atorvastatin therapy also improved total cholesterol and non-HDL-C in a placebo-controlled trial. Insulin sensitivity remained unchanged. Canas JA, et al. Pediatr Diabetes . 2015;16(2):79-89.






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