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Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association Hisham Alrefai, MD Cert., Endocrinology & Diabetes Cert., Clinical Lipidology Cert., Bone Densitometry Hypertension Fellowship

Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association Hisham Alrefai, MD Cert.,

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Page 1: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

Applying diabetes guidelines and clinical trials to daily practice

115th Annual Convention of Indiana Osteopathic Association

Hisham Alrefai, MDCert., Endocrinology & Diabetes

Cert., Clinical LipidologyCert., Bone DensitometryHypertension Fellowship

Page 2: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

1999

Page 3: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

2009

Page 4: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

Age-adjusted Percentage of U.S. Adults Who Were Obese or Who Had Diagnosed Diabetes

Obesity (BMI ≥30 kg/m2)

Diabetes

1994

1994

2000

2000

No Data <14.0% 14.0-17.9% 18.0-21.9% 22.0-25.9% >26.0%

No Data <4.5% 4.5-5.9% 6.0-7.4% 7.5-8.9% >9.0%

CDC’s Division of Diabetes Translation. National Diabetes Surveillance System available at http://www.cdc.gov/diabetes/statistics

2009

2009

Page 5: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

I. CLASSIFICATION AND DIAGNOSIS OF DIABETES

Page 6: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

Criteria for the Diagnosis of DiabetesCriteria for the Diagnosis of Diabetes

A1C ≥6.5%OR

Fasting plasma glucose (FPG)≥126 mg/dl (7.0 mmol/l)

OR

Two-hour plasma glucose ≥200 mg/dl (11.1 mmol/l) during an OGTT

OR

A random plasma glucose ≥200 mg/dl (11.1 mmol/l)

ADA. I. Classification and Diagnosis. Diabetes Care 2011;34(suppl 1):S13. Table 2.

Page 7: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

Prediabetes: IFG, IGT, Increased A1CPrediabetes: IFG, IGT, Increased A1C

Categories of increased risk for diabetes (Prediabetes)*

FPG 100-125 mg/dl (5.6-6.9 mmol/l): IFGor

2-h plasma glucose in the 75-g OGTT140-199 mg/dl (7.8-11.0 mmol/l): IGT

or

A1C 5.7-6.4%

*For all three tests, risk is continuous, extending below the lower limit of a range and becoming disproportionately greater at higher ends of the range.

ADA. I. Classification and Diagnosis. Diabetes Care 2011;34(suppl 1):S13. Table 3.

Page 8: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

• A complete medical evaluation should be performed to– Classify the diabetes– Detect presence of diabetes complications– Review previous treatment, glycemic control in patients

with established diabetes– Assist in formulating a management plan– Provide a basis for continuing care

• Perform laboratory tests necessary to evaluate each patient’s medical condition

Diabetes Care: Initial EvaluationDiabetes Care: Initial Evaluation

ADA. V. Diabetes Care. Diabetes Care 2011;34(suppl 1):S16.

Page 9: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

Components of the Components of the Comprehensive Diabetes Comprehensive Diabetes

Evaluation (1)Evaluation (1)Medical history• Age and characteristics of onset of diabetes

(e.g., DKA, asymptomatic laboratory finding)• Eating patterns, physical activity habits,

nutritional status, and weight history; growth and development in children and adolescents•Diabetes education history

• Review of previous treatment regimens and response to therapy (A1C records)

ADA. V. Diabetes Care. Diabetes Care 2011;34(suppl 1):S17. Table 8.

Page 10: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

Components of the Components of the Comprehensive Diabetes Comprehensive Diabetes

Evaluation (2)Evaluation (2)

ADA. V. Diabetes Care. Diabetes Care 2011;34(suppl 1):S17. Table 8.

Current treatment of diabetes, including medications, meal plan, physical activity patterns, and results of glucose monitoring and patient’s use of data (1)• DKA frequency, severity, and cause• Hypoglycemic episodes

– Hypoglycemia awareness

– Any severe hypoglycemia: frequency and cause

Page 11: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

Components of the Components of the Comprehensive Diabetes Comprehensive Diabetes

Evaluation (3)Evaluation (3)

ADA. V. Diabetes Care. Diabetes Care 2011;34(suppl 1):S17. Table 8.

Current treatment of diabetes, including medications, meal plan, physical activity patterns, and results of glucose monitoring and patient’s use of data (2)• History of diabetes-related complications

– Microvascular: retinopathy, nephropathy, neuropathy• Sensory neuropathy, including history of foot lesions• Autonomic neuropathy, including sexual dysfunction and

gastroparesis

– Macrovascular: CHD, cerebrovascular disease, PAD

– Other: psychosocial problems*, dental disease*

*See appropriate referrals for these categories.

Page 12: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

Components of the Components of the Comprehensive Diabetes Comprehensive Diabetes

Evaluation (4)Evaluation (4)

ADA. V. Diabetes Care. Diabetes Care 2011;34(suppl 1):S17. Table 8.

Physical examination (1)•Height, weight, BMI

• Blood pressure determination, including orthostatic measurements when indicated•Fundoscopic examination*•Thyroid palpation

• Skin examination (for acanthosis nigricans and insulin injection sites)

*See appropriate referrals for these categories.

Page 13: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

Components of the Components of the Comprehensive Diabetes Comprehensive Diabetes

Evaluation (5)Evaluation (5)

ADA. V. Diabetes Care. Diabetes Care 2011;34(suppl 1):S17. Table 8.

*See appropriate referrals for these categories.

Physical examination (2)• Comprehensive foot examination

–Inspection

– Palpation of dorsalis pedis and posterior tibial pulses

– Presence/absence of patellar and Achilles reflexes

– Determination of proprioception, vibration, and monofilament sensation

Page 14: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

Laboratory evaluation• A1C, if results not available within past 2–3

months• If not performed/available within past year– Fasting lipid profile, including total, LDL- and HDL-

cholesterol and triglycerides– Liver function tests– Test for urine albumin excretion with spot urine

albumin/creatinine ratio– Serum creatinine and calculated GFR– TSH in type 1 diabetes, dyslipidemia, or women

>50 years of age

ADA. V. Diabetes Care. Diabetes Care 2011;34(suppl 1):S17. Table 8.

Components of the Components of the Comprehensive Diabetes Comprehensive Diabetes

Evaluation (6)Evaluation (6)

Page 15: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

Referrals•Annual dilated eye exam•Family planning for women of reproductive age•Registered dietitian for MNT•Diabetes self-management education

• Dental examination• Mental health professional, if needed

ADA. V. Diabetes Care. Diabetes Care 2011;34(suppl 1):S17. Table 8.

Components of the Components of the Comprehensive Diabetes Comprehensive Diabetes

Evaluation (7)Evaluation (7)

Page 16: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

Glycemic Recommendations for Non-Glycemic Recommendations for Non-Pregnant Adults with Diabetes (1)Pregnant Adults with Diabetes (1)

A1C <7.0%*

Preprandial capillary plasma glucose

70–130 mg/dl* (3.9–7.2 mol/l)

Peak postprandial capillary plasma glucose†

<180 mg/dl* (<10.0 mmol/l)

*Postprandial glucose measurements should be made 1–2 h after the beginning of the meal, generally peak levels in patients with diabetes.

ADA. V. Diabetes Care. Diabetes Care 2011;34(suppl 1):S21. Table 10.

Page 17: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

Recommendations: A1CRecommendations: A1C

• Perform A1C test at least twice yearly in patients meeting treatment goals (and have stable glycemic control) (E)

• Perform A1C test quarterly in patients whose therapy has changed or who are not meeting glycemic goals (E)

• Use of point-of-care testing for A1C allows for timely decisions on therapy changes, when needed (E)

ADA. V. Diabetes Care. Diabetes Care 2011;34(suppl 1):S18.

Page 18: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

Correlation of A1C with Estimated Correlation of A1C with Estimated Average Glucose (eAG)Average Glucose (eAG)

Mean plasma glucose

A1C (%) mg/dl mmol/l

6 126 7.0

7 154 8.6

8 183 10.2

9 212 11.8

10 240 13.4

11 269 14.9

12 298 16.5

ADA. V. Diabetes Care. Diabetes Care 2011;34(suppl 1):S18. Table 9.

These estimates are based on ADAG data of ~2,700 glucose measurements over 3 months per A1C measurement in 507 adults with type 1, type 2, and no diabetes. The correlation between A1C and average glucose was 0.92. A calculator for converting A1C results into estimated average glucose (eAG), in either mg/dl or mmol/l, is available at http://professional.diabetes.org/GlucoseCalculator.aspx.

Page 19: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

Recommendations:Recommendations:Glycemic Goals in Adults (1)Glycemic Goals in Adults (1)

ADA. V. Diabetes Care. Diabetes Care 2011;34(suppl 1):S19.

• Lowering A1C to below or around 7%– Shown to reduce microvascular and neuropathic

complications of diabetes– If implemented soon after diagnosis of diabetes,

associated with long-term reduction in macrovascular disease

• Therefore, a reasonable A1C goal for many non-pregnant adults is <7% (B)

Page 20: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

Intensive Glycemic Control and Intensive Glycemic Control and Cardiovascular Outcomes: ACCORDCardiovascular Outcomes: ACCORD

Gerstein HC, et al, for the Action to Control Cardiovascular Risk in Diabetes Study Group.N Engl J Med 2008;358:2545-2559.

©2008 New England Journal of Medicine. Used with permission.

Primary Outcome: Nonfatal MI, nonfatal stroke, CVD death

HR=0.90 (0.78-1.04)

Page 21: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

Intensive Glycemic Control and Intensive Glycemic Control and Cardiovascular Outcomes: VADTCardiovascular Outcomes: VADT

Duckworth W, et al., for the VADT Investigators. N Engl J Med 2009;360:129-139.

Primary Outcome: Nonfatal MI, nonfatal stroke, CVD death, hospitalization for heart failure, revascularization

HR=0.88 (0.74-1.05)

©2009 New England Journal of Medicine. Used with permission.

Page 22: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

Intensive Glycemic Control and Intensive Glycemic Control and Cardiovascular Outcomes: ADVANCECardiovascular Outcomes: ADVANCE

©2008 New England Journal of Medicine. Used with permission.

Primary Outcome: Microvascular plus macrovascular (nonfatal MI, nonfatal stroke, CVD death)

Patel A, et al,. for the ADVANCE Collaborative Group. N Engl J Med 2008;358:2560-2572.

HR=0.90 (0.82-0.98)

Page 23: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

Recommendations:Recommendations:Glycemic Goals in Adults (2)Glycemic Goals in Adults (2)

ADA. V. Diabetes Care. Diabetes Care 2011;34(suppl 1):S19.

• Additional analysis from several randomized trials suggest a small but incremental benefit in microvascular outcomes with A1C values closer to normal

• Providers might reasonably suggest more stringent A1C goals for selected individual patients, if this can be achieved without significant hypoglycemia or other adverse effects of treatment

– Such patients might include those with short duration of diabetes, long life expectancy, and no significant cardiovascular disease (B)

Page 24: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

Recommendations:Recommendations:Glycemic Goals in Adults (3)Glycemic Goals in Adults (3)

ADA. V. Diabetes Care. Diabetes Care 2011;34(suppl 1):S19.

• Conversely, less stringent A1C goals may be appropriate for patients with– History of severe hypoglycemia, limited life

expectancy, advanced microvascular or macrovascular complications, extensive comorbid conditions

– Those with longstanding 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 (C)

Page 25: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

• Goals should be individualized based on– Duration of diabetes– Age/life expectancy– Comorbid conditions

– Known CVD or advanced microvascular complications

– Hypoglycemia unawareness– Individual patient considerations– Hypoglycemia unawareness– Individual patient considerations

Glycemic Recommendations for Non-Glycemic Recommendations for Non-Pregnant Adults with Diabetes (2)Pregnant Adults with Diabetes (2)

ADA. V. Diabetes Care. Diabetes Care 2011;34(suppl 1):S21. Table 10.

Page 26: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

• Postprandial glucose may be targeted if A1C goals are not met despite reaching preprandial glucose goals

• More or less stringent glycemic goals may be appropriate for individual patients

Glycemic Recommendations for Non-Glycemic Recommendations for Non-Pregnant Adults with Diabetes (3)Pregnant Adults with Diabetes (3)

ADA. V. Diabetes Care. Diabetes Care 2011;34(suppl 1):S21. Table 10.

Page 27: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

A1C 6.5 – 7.5%**

Monotherapy

MET +

GLP-1 or DPP4 1

TZD 2

Glinide or SU 5

TZD + GLP-1 or DPP4 1

MET +Colesevelam

AGI 3

2 - 3 Mos.***

2 - 3 Mos.***

2 - 3 Mos.***

Dual Therapy

MET +

GLP-1 or

DPP4 1+

TZD 2

Glinide or SU 4,7

A1C > 9.0%

No Symptoms

Drug Naive Under Treatment

INSULIN

± Other

Agent(s) 6

Symptoms

INSULIN

± Other

Agent(s) 6

INSULIN

± Other

Agent(s) 6

Triple Therapy

AACE/ACE Algorithm for Glycemic Control Committee

Cochairpersons:Helena W. Rodbard, MD, FACP, MACEPaul S. Jellinger, MD, MACE

Zachary T. Bloomgarden, MD, FACEJaime A. Davidson, MD, FACP, MACEDaniel Einhorn, MD, FACP, FACEAlan J. Garber, MD, PhD, FACEJames R. Gavin III, MD, PhDGeorge Grunberger, MD, FACP, FACEYehuda Handelsman, MD, FACP, FACEEdward S. Horton, MD, FACEHarold Lebovitz, MD, FACEPhilip Levy, MD, MACEEtie S. Moghissi, MD, FACP, FACEStanley S. Schwartz, MD, FACE

* May not be appropriate for all patients** For patients with diabetes and A1C < 6.5%,

pharmacologic Rx may be considered*** If A1C goal not achieved safely

† Preferred initial agent

1 DPP4 if PPG and FPG or GLP-1 if PPG

2 TZD if metabolic syndrome and/or nonalcoholic fatty liver disease (NAFLD)

3 AGI if PPG

4 Glinide if PPG or SU if FPG

5 Low-dose secretagogue recommended

6 a) Discontinue insulin secretagoguewith multidose insulin

b) Can use pramlintide with prandial insulin

7 Decrease secretagogue by 50% when added to GLP-1 or DPP-4

8 If A1C < 8.5%, combination Rx with agents that cause hypoglycemia should be used with caution

9 If A1C > 8.5%, in patients on Dual Therapy,insulin should be considered

MET +

GLP-1

or DPP4 1 ± SU 7

TZD 2

GLP-1

or DPP4 1 ± TZD 2

A1C 7.6 – 9.0%

Dual Therapy 8

2 - 3 Mos.***

2 - 3 Mos.***

Triple Therapy 9

INSULIN

± Other

Agent(s) 6

MET +

GLP-1 or DPP4 1

or TZD 2

SU or Glinide 4,5

MET +

GLP-1

or DPP4 1+ TZD 2

GLP-1

or DPP4 1 + SU 7

TZD 2

MET † DPP4 1 GLP-1 TZD 2 AGI 3

Available at www.aace.com/pub© AACE December 2009 Update. May not be reproduced in any form without express written permission from AACE

Page 28: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

A1C 6.5 – 7.5%**A1C 6.5 – 7.5%**

Monotherapy

MET +

GLP-1 or DPP4 1

TZD 2

Glinide or SU 5

TZD + GLP-1 or DPP4 1

MET +Colesevelam

AGI 3

2 - 3 Mos.***

Dual Therapy

MET +

GLP-1 or DPP4 1

+

TZD 2

Glinide or SU 4,7

INSULIN

± Other Agent(s) 6

Triple Therapy

MET † DPP4 1 GLP-1 TZD 2 AGI 3

2 - 3 Mos.***

2 - 3 Mos.***

*** If A1C goal not achieved safely

† Preferred initial agent

1 DPP4 if PPG and FPG or GLP-1if PPG

2 TZD if metabolic syndrome and/or nonalcoholic fatty liver disease (NAFLD)

3 AGI if PPG

4 Glinide if PPG or SU if FPG

5 Low-dose secretagogue recommended

6 a) Discontinue insulin secretagogue with multidose insulin

b) Can use pramlintide with prandial insulin

7 Decrease secretagogue by 50% when added to GLP-1 or DPP-4

Available at www.aace.com/pub© AACE December 2009 Update. May not be reproduced in any form without express written permission from AACE

LIFESTYLE MODIFICATION

AACE/ACE DIABETES ALGORITHM FOR

GLYCEMIC CONTROL

Page 29: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

MET +

GLP-1

or DPP4 1+ TZD 2

GLP-1

or DPP4 1 + SU 7

TZD 2

A1C 7.6 – 9.0%A1C 7.6 – 9.0%LIFESTYLE MODIFICATION

AACE/ACE DIABETES ALGORITHM FOR

GLYCEMIC CONTROL

Available at www.aace.com/pub© AACE December 2009 Update. May not be reproduced in any form without express written permission from AACE

Dual Therapy 8

MET +

GLP-1 or DPP4 1

or TZD 2

SU or Glinide 4,5

2 - 3 Mos.***

Triple Therapy 9

2 - 3 Mos.***

INSULIN

± Other Agent(s) 6

*** If A1C goal not achieved safely

† Preferred initial agent

1 DPP4 if PPG and FPG or GLP-1if PPG

2 TZD if metabolic syndrome and/or nonalcoholic fatty liver disease (NAFLD)

4 Glinide if PPG or SU if FPG

5 Low-dose secretagogue recommended

6 a) Discontinue insulin secretagogue with multidose insulin

b) Can use pramlintide with prandial insulin

7 Decrease secretagogue by 50% when added to GLP-1 or DPP-4

8 If A1C < 8.5%, combination Rx with agents that cause hypoglycemia should be used with caution

9 If A1C > 8.5%, in patients on Dual Therapy, insulin should be considered

Page 30: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

No Symptoms

Drug Naive Under Treatment

Symptoms

MET +

GLP-1 or DPP4 1

± SU 7

TZD 2

GLP-1 or DPP4 1 ± TZD 2

A1C > 9.0%A1C > 9.0%LIFESTYLE MODIFICATION

AACE/ACE DIABETES ALGORITHM FOR

GLYCEMIC CONTROL

Available at www.aace.com/pub© AACE December 2009 Update. May not be reproduced in any form without express written permission from AACE

INSULIN

± Other Agent(s) 6

INSULIN

± Other Agent(s) 6

1 DPP4 if PPG and FPG or GLP-1if PPG

2 TZD if metabolic syndrome and/or nonalcoholic fatty liver disease (NAFLD)

6 a) Discontinue insulin secretagogue with multidose insulin

b) Can use pramlintide with prandial insulin

7 Decrease secretagogue by 50% when added to GLP-1 or DPP-4

Page 31: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

* The abbreviations used here correspond to those used on the algorithm (Fig. 1).** The term ‘glinide’ includes both repaglinide and nateglinide.

Benefits are classified according to major effects on fasting glucose, postprandial glucose, and nonalcoholic fatty liver disease (NAFLD). Eightbroad categories of risks are summarized. The intensity of the background shading of the cells reflects relative importance of the benefit or risk.*

Available at www.aace.com/pub© AACE December 2009 Update. May not be reproduced in any form without express written permission from AACE

Page 32: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

Recommendations: Bariatric SurgeryRecommendations: Bariatric Surgery

• Consider bariatric surgery for adults with BMI >35 kg/m2 and type 2 diabetes (B)

• After surgery, life-long lifestyle support and medical monitoring is necessary (E)

• Insufficient evidence to recommend surgery in patients with BMI <35 kg/m2 outside of a research protocol (E)

• Well-designed, randomized controlled trials comparing optimal medical/lifestyle therapy needed to determine long-term benefits, cost-effectiveness, risks (E)

ADA. V. Diabetes Care. Diabetes Care 2011;34(suppl 1):S26.

Page 33: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

Recommendations: ImmunizationRecommendations: Immunization

• Provide an influenza vaccine annually to all diabetic patients ≥6 months of age (C)

• Administer pneumococcal polysaccharide vaccine to all diabetic patients ≥2 years

• One-time revaccination recommended for those >64 years previously immunized at <65 years if administered >5 years ago

• Other indications for repeat vaccination: nephrotic syndrome, chronic renal disease, immunocompromised states (C)

ADA. V. Diabetes Care. Diabetes Care 2011;34(suppl 1):S27.

Page 34: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

Recommendations: Recommendations: Hypertension/Blood Pressure ControlHypertension/Blood Pressure Control

Treatment (2)• Patients with more severe hypertension

(systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg) at diagnosis or follow-up– Should receive pharmacologic therapy in addition

to lifestyle therapy (A)

ADA. VI. Prevention, Management of Complications. Diabetes Care 2011;34(suppl 1):S27.

Page 35: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

Recommendations:Recommendations:Dyslipidemia/Lipid ManagementDyslipidemia/Lipid Management

Screening• In most adult patients

– Measure fasting lipid profile at least annually• In adults with low-risk lipid values (LDL

cholesterol <100 mg/dl, HDL cholesterol >50 mg/dl, and triglycerides <150 mg/dl)– Lipid assessments may be repeated every 2 years

(E)

ADA. VI. Prevention, Management of Complications. Diabetes Care 2011;34(suppl 1):S29.

Page 36: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

Recommendations: Glycemic, Blood Recommendations: Glycemic, Blood Pressure, Lipid Control in AdultsPressure, Lipid Control in Adults

A1C <7.0%*

Blood pressure <130/80 mmHg†

LipidsLDL cholesterol <100 mg/dl

(<2.6 mmol/l)‡

*More or less stringent glycemic goals may be appropriate for individual patients. Goals should be individualized based on: duration of diabetes, age/life expectancy, comorbid conditions, known CVD or advanced microvascular complications, hypoglycemia unawareness, and individual patient considerations.

†Based on patient characteristics and response to therapy, higher or lower systolic blood pressure targets may be appropriate.

‡In individuals with overt CVD, a lower LDL cholesterol goal of <70 mg/dl (1.8 mmol/l), using a high dose of statin, is an option.

ADA. VI. Prevention, Management of Complications. Diabetes Care 2011;34(suppl 1):S31. Table 12.

Page 37: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

Recommendations:Recommendations:Antiplatelet Agents (1)Antiplatelet Agents (1)

• Consider aspirin therapy (75–162 mg/day) (C)– As a primary prevention strategy in those with type 1 or type 2

diabetes at increased cardiovascular risk (10-year risk >10%)– Includes most men >50 years of age or women >60 years of age

who have at least one additional major risk factor• Family history of CVD• Hypertension• Smoking• Dyslipidemia• Albuminuria

ADA. VI. Prevention, Management of Complications. Diabetes Care 2011;34(suppl 1):S31.

Page 38: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

Recommendations:Recommendations:Antiplatelet Agents (2)Antiplatelet Agents (2)

• Aspirin should not be recommended for CVD prevention for adults with diabetes at low CVD risk, since potential adverse effects from bleeding likely offset potential benefits (C)• 10-year CVD risk <5%: men <50 and women <60 years

of age with no major additional CVD risk factors • In patients in these age groups with multiple

other risk factors (e.g., 10-year risk 5%-10%) clinical judgment is required (E)

ADA. VI. Prevention, Management of Complications. Diabetes Care 2011;34(suppl 1):S31.

Page 39: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

Recommendations:Recommendations:Antiplatelet Agents (3)Antiplatelet Agents (3)

• Use aspirin therapy (75–162 mg/day)– Secondary prevention strategy in those with diabetes with a

history of CVD (A)• For patients with CVD, documented aspirin allergy

– Clopidogrel (75 mg/day) should be used (B)• Combination therapy with ASA (75–162 mg/day) and

clopidogrel (75 mg/day)– Reasonable for up to a year after an acute coronary

syndrome (B)

ADA. VI. Prevention, Management of Complications. Diabetes Care 2011;34(suppl 1):S31.

Page 40: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

Recommendations:Recommendations:Nephropathy ScreeningNephropathy Screening

• Assess urine albumin excretion annually (E)– In type 1 diabetic patients with diabetes duration of 5

years– In all type 2 diabetic patients at diagnosis

• Measure serum creatinine at least annually (E)– In all adults with diabetes regardless of degree of urine

albumin excretion– Serum creatinine should be used to estimate GFR and

stage level of chronic kidney disease, if present

ADA. VI. Prevention, Management of Complications. Diabetes Care 2011;34(suppl 1):S33.

Page 41: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

Definitions of Abnormalities in Definitions of Abnormalities in Albumin ExcretionAlbumin Excretion

Category

Spot collection (µg/mg creatinine)

Normal <30

Microalbuminuria 30-299

Macroalbuminuria (clinical)

≥300

ADA. VI. Prevention, Management of Complications. Diabetes Care 2011;34(suppl 1):S34. Table 13.

Page 42: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

Recommendations:Recommendations:Nephropathy Treatment (1)Nephropathy Treatment (1)

• Nonpregnant patient with micro- or macroalbuminuria– Either ACE inhibitors or ARBs should be used

(A)

ADA. VI. Prevention, Management of Complications. Diabetes Care 2011;34(suppl 1):S33.

Page 43: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

Recommendations:Recommendations:Nephropathy Treatment (2)Nephropathy Treatment (2)

• In patients with type 1 diabetes, hypertension, and any degree of albuminuria– ACE inhibitors have been shown to delay

progression of nephropathy (A)• In patients with type 2 diabetes,

hypertension, and microalbuminuria– Both ACE inhibitors and ARBs have been shown to

delay progression to macroalbuminuria (A)

ADA. Prevention, Management of Complications. Diabetes Care 2011;34(suppl 1):S33.

Page 44: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

Recommendations:Recommendations:Nephropathy Treatment (3)Nephropathy Treatment (3)

• In patients with type 2 diabetes, hypertension, macroalbuminuria, and renal insufficiency (serum creatinine >1.5 mg/dl)– ARBs have been shown to delay progression of

nephropathy (A)

• If one class is not tolerated, the other should be substituted (E)

ADA. VI. Prevention, Management of Complications. Diabetes Care 2011;34(suppl 1):S33.

Page 45: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

Recommendations: RetinopathyRecommendations: Retinopathy

• To reduce risk or slow progression of retinopathy– Optimize glycemic control (A)– Optimize blood pressure control (A)

ADA. VI. Prevention, Management of Complications. Diabetes Care 2011;34(suppl 1):S35.

Page 46: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

Recommendations:Recommendations:Retinopathy Screening (1)Retinopathy Screening (1)

• Initial dilated and comprehensive eye examination by an ophthalmologist or optometrist– Adults and children aged 10 years or older with

type 1 diabetes• Within 5 years after diabetes onset (B)

– Patients with type 2 diabetes• Shortly after the diagnosis of diabetes (B)

ADA. VI. Prevention, Management of Complications. Diabetes Care 2011;34(suppl 1):S35.

Page 47: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

Recommendations:Recommendations:Retinopathy Screening (2)Retinopathy Screening (2)

• Subsequent examinations for type 1 and type 2 diabetic patients– Should be repeated annually by an ophthalmologist or

optometrist • Less frequent exams (every 2–3 years)

– May be considered following one or more normal eye exams

• More frequent examinations required if retinopathy is progressing (B)

ADA. VI. Prevention, Management of Complications. Diabetes Care 2011;34(suppl 1):S35.

Page 48: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

Recommendations:Recommendations:Retinopathy Treatment (1)Retinopathy Treatment (1)

• Promptly refer patients with any level of macular edema, severe NPDR, or any PDR– To an ophthalmologist knowledgeable and experienced

in management, treatment of diabetic retinopathy (A)• Laser photocoagulation therapy is indicated

– To reduce risk of vision loss in patients with• High-risk PDR• Clinically significant macular edema• Some cases of severe NPDR (A)

ADA. VI. Prevention, Management of Complications. Diabetes Care 2011;34(suppl 1):S35.

Page 49: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

Recommendations:Recommendations:Retinopathy Treatment (2)Retinopathy Treatment (2)

• Presence of retinopathy– Not a contraindication to aspirin therapy for

cardioprotection, as this therapy does not increase the risk of retinal hemorrhage (A)

ADA. VI. Prevention, Management of Complications. Diabetes Care 2011;34(suppl 1):S35.

Page 50: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

Recommendations:Recommendations:Neuropathy Screening, Treatment (1)Neuropathy Screening, Treatment (1)

• All patients should be screened for distal symmetric polyneuropathy (DPN)– At diagnosis– At least annually thereafter using simple clinical

tests (B)• Electrophysiological testing rarely needed

– Except in situations where clinical features are atypical (E)

ADA. VI. Prevention, Management of Complications. Diabetes Care 2011;34(suppl 1):S36.

Page 51: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

Recommendations:Recommendations:Neuropathy Screening, Treatment (2)Neuropathy Screening, Treatment (2)

• Screening for signs and symptoms of cardiovascular autonomic neuropathy– Should be instituted at diagnosis of type 2 diabetes and 5

years after the diagnosis of type 1 diabetes– Special testing rarely needed; may not affect management

or outcomes (E)• Medications for relief of specific symptoms related to

DPN, autonomic neuropathy are recommended– Improve quality of life of the patient (E)

ADA. VI. Prevention, Management of Complications. Diabetes Care 2011;34(suppl 1):S36.

Page 52: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

Recommendations: Foot Care (1)Recommendations: Foot Care (1)

• For all patients with diabetes, perform an annual comprehensive foot examination to identify risk factors predictive of ulcers and amputations– Inspection– Assessment of foot pulses– Test for loss of protective sensation: 10-g monofilament plus

testing any one of• Vibration using 128-Hz tuning fork• Pinprick sensation• Ankle reflexes• Vibration perception threshold (B)

ADA. VI. Prevention, Management of Complications. Diabetes Care 2011;34(suppl 1):S37.

Page 53: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

Recommendations:Recommendations:Diabetes Care in the Hospital (1)Diabetes Care in the Hospital (1)

• All patients with diabetes admitted to the hospital should have– Their diabetes clearly identified in the medical

record (E)– An order for blood glucose monitoring, with

results available to the health care team (E)

ADA. VIII. Diabetes Care in Specific Settings. Diabetes Care. 2011;34(suppl 1):S43.

Page 54: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

Recommendations:Recommendations:Diabetes Care in the Hospital (2)Diabetes Care in the Hospital (2)

• Goals for blood glucose levels– Critically ill patients: 140-180 mg/dl

(10 mmol/l) (A)– More stringent goals, such as 110-140 mg/dl (6.1-

7.8 mmol/l) may be appropriate for selected patients, if achievable without significant hypoglycemia (C)

– Non-critically ill patients: base goals on glycemic control, severe comorbidities (E)

ADA. VIII. Diabetes Care in Specific Settings. Diabetes Care. 2011;34(suppl 1):S43.

Page 55: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

Number and Percentage of U.S. Population with Diagnosed Diabetes, 1958-2009

CDC’s Division of Diabetes Translation. National Diabetes Surveillance System available at http://www.cdc.gov/diabetes/statistics

Page 56: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

Recommendations: Testing for Recommendations: Testing for Diabetes in Asymptomatic PatientsDiabetes in Asymptomatic Patients• Consider testing overweight/obese adults with

one or more additional risk factors– In those without risk factors, begin testing at age

45 years (B)

• If tests are normal– Repeat testing at least at 3-year intervals (E)

• Use A1C, FPG, or 2-h 75-g OGTT (B)• In those with increased risk for future

diabetes– Identify and, if appropriate, treat other CVD risk

factors (B)

ADA. II. Testing in Asymptomatic Patients. Diabetes Care 2011;34(suppl 1):S13-S14.

Page 57: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

Criteria for Testing for Diabetes in Criteria for Testing for Diabetes in Asymptomatic Adult Individuals (1)Asymptomatic Adult Individuals (1)

•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 were diagnosed with GDM

•Hypertension (≥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 polycystic ovarian syndrome (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

*At-risk BMI may be lower in some ethnic groups.

1. Testing should be considered in all adults who are overweight (BMI ≥25 kg/m2*) and have additional risk factors:

ADA. Testing in Asymptomatic Patients. Diabetes Care 2011;34(suppl 1):S14. Table 4.

Page 58: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

2. In the absence of criteria (risk factors on previous slide), testing for diabetes should begin at age 45 years

3. If results are normal, testing should be repeated at least at 3-year intervals, with consideration of more frequent testing depending on initial results and risk status

ADA. Testing in Asymptomatic Patients. Diabetes Care 2011;34(suppl 1):S14. Table 4.

Criteria for Testing for Diabetes in Criteria for Testing for Diabetes in Asymptomatic Adult Individuals (2)Asymptomatic Adult Individuals (2)

Page 59: Applying diabetes guidelines and clinical trials to daily practice 115th Annual Convention of Indiana Osteopathic Association  Hisham Alrefai, MD Cert.,

Recommendations:Recommendations:Prevention/Delay of Type 2 DiabetesPrevention/Delay of Type 2 Diabetes• Refer patients with IGT (A), IFG (E), or A1C 5.7-

6.4% (E) to support program– Weight loss 7% of body weight– At least 150 min/week moderate activity

• Follow-up counseling important (B);third-party payors should cover (E)

• Consider metformin if multiple risk factors, especially if hyperglycemia (e.g., A1C>6%) progresses despite lifestyle interventions (B)

• In those with prediabetes, monitor for development of diabetes annually (E)

ADA. IV. Prevention/Delay of Type 2 Diabetes. Diabetes Care 2011;34(suppl 1):S16.