Individual with cardiovascular disease at the time of type ... · Individual with cardiovascular disease at the time of type 2 diabetes diagnosis Authored by Lawrence Blonde and Richard

Case study: Individual with cardiovascular disease at the time of type 2 diabetes diagnosis

Authored by Lawrence Blonde and Richard Nesto on behalf of the Global Partnership for Effective Diabetes Management.

The Global Partnership for Effective Diabetes Management is supported by an unrestricted educational grant from Bristol-Myers Squibb, AstraZeneca LP.

• This case study outlines the treatment of an adult individual with cardiovascular disease who is newly diagnosed with type 2 diabetes

• The case reflects a full range of treatment and management tools available in the European/US context*

*The management of any patient is subject to social, economic, gender, age, co-morbidity and ethnic variables, and is dependent on the range of treatment options available in specific regions or countries.

Case study: 62-year-old female presenting with NSTEMI

• Sunita, 62 years old, married, two adult sons

• Developed anginal pain that worsened over 20 minutes

• Difficulty breathing, agitated, anxious

• Diagnosed with a NSTEMI at the hospital

• History of hypertension that is well-controlled with an ACE inhibitor and thiazide diuretic

• 62 years old

• NSTEMI

• Hypertension (8 years)

• Current medication: – Lisinopril 20 mg o.d.

– HCTZ 50 mg o.d.

• Weight: 67 kg (147.7 lbs)

• Height: 163 cm (5 ft 4 in)

ACE, angiotensin-converting enzyme; HCTZ, hydrochlorothiazide; NSTEMI, non-ST-elevation myocardial infarction; o.d., once daily.

Management in the emergency department

• At the emergency department:

– Blood pressure: 150/88 mmHg

– Heart rate: 108 beats per minute

• Administered aspirin 325 mg, sublingual nitroglycerin, supplemental oxygen

• Chest pain subsided after second nitroglycerin dose

– BP and HR returned towards normal

• ECG consistent with non-STE acute coronary syndrome with isolated T-wave inversion

• On admission, Sunita’s blood glucose level is 12.8 mmol/l (230 mg/dl)

ECG, electrocardiogram; STE, ST elevation.

Hyperglycaemia on admission

Question Which of the following statements best describes the possible cause of Sunita’s elevated blood glucose levels?

Sunita has diabetes that was present before the acute coronary event but had not been diagnosed

The hyperglycaemia is stress-related; it will resolve once the patient is stabilized and is unrelated to the presence of diabetes

The hyperglycaemia could be a result of stress-related hyperglycaemia, previously undiagnosed diabetes or a combination of the two

Hyperglycaemia on admission

• Hyperglycaemia on admission for ACS is common

– Occurs in 25–58% of cases1 and in almost 90% of people with a history of diabetes2

• Stress-related hyperglycaemia can occur in the absence of diabetes

– BG levels return to normal following the acute crisis

– ~30% of people presenting with ACS have a history of diabetes

– A further 20% are newly diagnosed with diabetes following the ACS event

• The relative contributions of either persistent hyperglycaemia associated with undiagnosed diabetes or that resulting from acute stress-related hyperglycaemia can not be determined

Answer

The hyperglycaemia could be a result of stress-related hyperglycaemia, previously undiagnosed diabetes or a combination of the two

1. Deedwania P et al. Circulation 2008;117:16101619. 2. Pinto DS et al. J Am Coll Cardiol 2005;46:178180.

ACS, acute coronary syndrome; BG, blood glucose.

Question How should Sunita’s hyperglycaemia be treated in the critical care setting?

Test HbA1c and, if elevated (>6.5%; 48 mmol/mol), initiate antihyperglycaemic therapy with oral agents

Controlling hyperglycaemia is not an immediate priority and can wait until Sunita is stabilized

Initiate treatment immediately with IV insulin

Initiate treatment immediately with SC insulin

Management of acute hyperglycaemia

HbA1c, glycosylated haemoglobin; IV, intravenous; SC, subcutaneous.

Treatment selected: Treatment not an immediate priority

• Acute hyperglycaemia is associated with increased risk of adverse short- and long-term outcomes following acute MI, regardless of whether individuals have a history of diabetes1,2,3

• Establishing glycaemic control is, therefore, important for all individuals presenting with acute MI and hyperglycaemia1,2,3

Please select another option 1. Angeli F et al. Curr Diabetes Rev 2010;6:102−110. 2. Meier JJ et al. Diabetes Care 2005;28:2551−2553. 3. Gholap, NN et al. BMJ Open. 2012; 2: e001596.

Error bars: 95% CI; p<0.0001 for all comparisons. *Up to 108 months.

Increased mortality following new-onset hyperglycaemia in patients presenting with ACS and no prior diagnosis of diabetes1

Odds ratio with versus without new-onset hyperglycaemia

1 10

In-hospital mortality

30-day mortality

Long-term mortality*

Increasing mortality risk

ACS, acute coronary syndrome; CI, confidence interval; MI, myocardial infarction.

Figure adapted with permission from Angeli F et al. Curr Diabetes Rev 2010;6:102−110.1

Please select another option

Treatment selected: Treat with oral agents only if HbA1c elevated


• In a study of people admitted to hospital with acute MI,1 for each 2.77 mmol/l (50 mg/dl) incremental increase in admission BG the relative risk of mortality increased by:

– 42% in those with history of type 2 diabetes (p<0.0001)

– 54% in those without history of type 2 diabetes (p=0.0024)


• Oral antihyperglycaemic drugs are not appropriate treatment for acute hyperglycaemia in critically ill people,3 as they do not provide a fast and effective response to the unpredictable changes in glucose levels that occur in critical care

1. Angeli F et al. Curr Diabetes Rev 2010;6:102−110. 2. Meier JJ et al. Diabetes Care 2005;28:2551−2553. 3. Gholap, NN et al. BMJ Open. 2012; 2: e001596. 4. Moghissi ES et al. Diabetes Care 2009;32:1119–1131.

BG, blood glucose; HbA1c, glycosylated haemoglobin; MI, myocardial infarction.


Treatment selected: Subcutaneous insulin



• However, SC insulin is not recommended for glycaemic control in critically ill individuals4

– Critical care setting is highly dynamic; SC insulin does not provide a fast and effective response to unpredictable changes in glucose levels

– Rate of SC absorption of insulin is highly variable in critically ill patients

1. Angeli F et al. Curr Diabetes Rev 2010;6:102−110. 2. Meier JJ et al. Diabetes Care 2005;28:2551−2553. 3. Gholap, NN et al. BMJ Open. 2012; 2: e001596. 4. American Diabetes Association. Diabetes Care 2013;36:S11−S66.

MI, myocardial infarction; SC, subcutaneous.

Treatment selected: Intravenous insulin

• Acute hyperglycaemia is associated with increased risk of adverse short- and long-term outcomes following acute MI, regardless of whether patients have a history of diabetes1,2,3

• Establishing glycaemic control is, therefore, a priority for all individuals presenting with acute MI and hyperglycaemia1,2,3

• IV insulin has a rapid onset/offset of action, and can be adjusted to the rapid/unpredictable changes in BG levels that occur in critical care

• IV insulin therapy is recommended for critically ill people with hyperglycaemia at a threshold of ≤10 mmol/l (180 mg/dl)3

• For most critically ill individuals, target BG range is 7.810 mmol/l (140180 mg/dl)3

• More stringent targets down to 6.1 mmol/l (110 mg/dl) may be appropriate, if achievable without hypoglycaemia, but their clinical benefit is uncertain3,4

• Values below 6.1 mmol/l (110 mg/dl) should be specifically avoided4

1. Angeli F et al. Curr Diabetes Rev 2010;6:102−110. 2. Meier JJ et al. Diabetes Care 2005;28:2551−2553. 3. Gholap, NN et al. BMJ Open. 2012; 2: e001596. 4. American Diabetes Association. Diabetes Care 2013;36:S11−S66. 5. The NICE-SUGAR study investigators. N Engl J Med 2009;360:1283‒1297.

BG, blood glucose; IV, intravenous; MI, myocardial infarction.

• Sunita’s condition has stabilized

• Her BG is now stable and controlled

• HbA1c on admission and follow-up

indicate presence of previously

undiagnosed type 2 diabetes

• Echocardiography indicates normal global left ventricular systolic function with anterior wall motion abnormality

• An invasive strategy is pursued based on the diagnosis of NSTEMI

• Angiography revealed a single lesion in the proximal left anterior descending artery

– Leading to placement of a drug-eluting stent

Status

• BP: 123/82 mmHg

• HR: 75 bpm

• Current BG: stable at 7.6 mmol/l (137 mg/dl)

• HbA1c:

– On admission: 7.8% (62 mmol/mol)

– Following stabilization: 7.9% (63 mmol/mol)

• Insulin infusion rate: ~2 U/hour

• LVEF: 60%

• Elevated troponin and CK-MB

Invasive versus conservative management

Treatments initiated

• Aspirin 100 mg/day

• Prasugrel 10 mg/day

• Fondaparinux 5 mg/day

• Atorvastatin 80 mg/day

BG, blood glucose; BP, blood pressure; CK-MB, creatine kinase-MB; HbA1c, glycosylated haemoglobin; HR, heart rate; LVEF, left ventricular ejection fraction; NSTEMI, non-ST elevation myocardial infarction; U, units.

Question What antihyperglycaemia management would you now propose for Sunita?

Discontinue IV insulin on discharge and advise patient to make an appointment with their family doctor to discuss long-term glucose control

Transition from IV to SC insulin

Transition from IV insulin to oral antidiabetic therapy

Glucose control: next steps • Sunita returns to the cardiology ward following PCI

• She is comfortable, mobile and eating normally

• Her condition continues to be stable, with blood glucose controlled in the target range at an insulin infusion rate of ~2 U/hour

IV, intravenous; MI, myocardial infarction; PCI, percutaneous coronary intervention; SC, subcutaneous; U, units.


Treatment selected: Defer decision on long-term management

• Discontinuing IV insulin and deferring initiation of long-term glycaemic control until after discharge would put Sunita at risk of hyperglycaemia and its associated dangers

– Even short periods of hyperglycaemia increase the risk of vascular complications

• Sunita is at particularly high risk given she has established CAD

• Transition from acute management of hyperglycaemia in the critical care setting, through stabilization in hospital and on to long-term management post-discharge, should be coordinated and seamless

CAD, coronary artery disease; IV, intravenous.

Treatment selected: Transition from IV to SC insulin

• Most individuals should be transitioned from IV insulin to SC insulin following the acute crisis and when their condition has improved/stabilized1

• First basal SC insulin dose usually administered 2−3 hour before discontinuing IV infusion to ensure maintenance of glycaemic control throughout the transition period1

• Total daily dose when transitioning to SC insulin is usually calculated as 80% of the estimated 24-hour insulin requirement based on the insulin infusion rate over the preceding 6−8 hours1

• Blood glucose should be closely monitored over the next few days and doses adjusted according to response

– As Sunita is eating relatively normally, a 50:50 basal/bolus split of the total daily dose is likely to be appropriate1

1. Moghissi ES et al. Diabetes Care 2009;32:1119‒1131.

IV, intravenous; SC, subcutaneous.

Treatment selected: Transition from IV insulin to oral therapy

• Transition from acute treatment of hyperglycaemia during critical care to long-term glucose control should be carefully managed

• All people with type 1 diabetes and many patients with type 2 diabetes should be transitioned from IV to SC insulin following the acute crisis1

• Possible exceptions include those with type 2 diabetes who have near to normal HbA1c or blood glucose under control using low insulin infusion rates. Typical cut-offs are:

– History of, or actual, type 2 diabetes: <0.5 U/hour

– Newly diagnosed type 2 diabetes: <1 U/hour

• For these exceptions, resuming or initiating oral antidiabetic therapy after discontinuing IV insulin may be appropriate; generally, use of oral antihyperglycaemic agents in the hospital setting is problematic1

• Sunita’s HbA1c is 7.9% (63 mmol/mol) and she required an insulin infusion rate of 2 U/hour; thus, the decision was made to transition her from IV to SC insulin

1. Moghissi ES et al. Diabetes Care 2009;32:1119‒1131. HbA1c, glycosylated haemoglobin;

IV, intravenous; SC, subcutaneous; U, units.

Discharge from hospital • Sunita is discharged from hospital 2 days later with instructions to continue

treatment with SC insulin and to closely monitor her blood glucose

• Before discharge she is seen by a specialist diabetes nurse/certified diabetes educator* who discusses with her:

– The causes and consequences of type 2 diabetes

– Diet, meal-planning and exercise

– Insulin administration and glucose self-monitoring techniques

• She is instructed how to adjust the insulin dose to achieve blood glucose levels:

– Before meals: 3.9−7.2 mmol/l (70−130 mg/dl)1,2

– Peak post-prandial (measured 1–2 hours after beginning the meal): <10.0 mmol/l (<180 mg/dl)1,2

Question How soon after discharge should Sunita visit her primary care physician?

<1 month 2 months 6 months Only if problems

*Or equivalent.

1. Inzucchi SE et al. Diabetes Care 2012;35:13641379. 2. American Diabetes Association. Diabetes Care 2013;36:S11S66.

SC, subcutaneous.

Follow-up after discharge

• Maintaining glycaemic control in the transition from in-hospital to outpatient or family practice care can be difficult, but is essential to reduce the risk of further complications/rehospitalization

• Without appropriate education and follow-up, >22% of people with diabetes and cardiac disease are rehospitalized within 30 days of discharge1

• Careful and close coordination between in-hospital specialties and general practice in a multidisciplinary team approach is important for optimized care2

<1 month 2 months 6 months Only if problems

1. Wu CJ & Chang AM. Int Nurs Rev 2008;55:327‒332. 2. Moghissi ES et al. Diabetes Care 2009;32:1119‒1131.

A comprehensive approach to type 2 diabetes management

• Establishing glycaemic control is a priority for all newly diagnosed individuals. However, this should always be pursued within a multifactorial risk-reduction framework that includes appropriate lifestyle interventions1

Baseline examinations to be performed in all people newly diagnosed with type 2 diabetes:

• Eye exam (refer to ophthalmologist): for signs of retinopathy

• Serum creatinine (to calculate eGFR) and 24 hour urine test:† to assess kidney function

• Comprehensive foot exam: for signs of neuropathy

In addition to antihyperglycaemic medication, consider the following for all people newly diagnosed with type 2 diabetes:2

• ACE inhibitors/ARBs (or alternative if contraindications exist) if SBP ≥140 mmHg, DBP >80

mmHg or if ACR is ≥2.5 mg/mmol (≥30 mg/g) • Statin drugs for those: – With LDL cholesterol >2.6 mmol/l (>100 mg/dl) OR

– With overt CVD (LDL cholesterol target <1.8 mmol/l; <70 mg/dl)2,3 OR

– Aged >40 years with at least one additional CVD risk factor*

• Aspirin for secondary prevention of CVD or for those with high CVD risk

1. Inzucchi SE et al. Diabetes Care 2012;35:13641379. 2. American Diabetes Association. Diabetes Care 2013;36:S11S66. 3. Ryden L et al. Eur Heart J 2007;28:88–136.

*Family history of CVD, hypertension, smoking, dyslipidaemia or albuminuria. †24 hour urine test may not always be required. ACR could also be obtained to assess kidney function.

ACE, angiotensin-converting enzyme; ACR, albumin:creatinine ratio; ARB, angiotensin II receptor blocker; CVD, cardiovascular disease; DBP, diastolic blood pressure; eGFR, estimated glomerular filtration rate; LDL, low-density lipoprotein; SBP, systolic blood pressure.

Follow-up visit at family practice • Sunita visits her primary care physician approximately 1 month after

discharge from hospital

• Together they review her BG monitoring diary

• The diary shows that Sunita has done well in controlling her BG levels, with very few glucose values above target or excessive glycaemic excursions, and no problems with hypoglycaemia

• The doctor discusses with Sunita her long-term goals for glycaemic control

Question What should be the target HbA1c

* for Sunita?

<6.0% 6.0–6.5% 6.5–7.0% 7.0–7.5% 7.5–8.0%

*Equivalent values: 6.0% = 42 mmol/mol, 6.5% = 48 mmol/mol, 7.0% = 53 mmol/mol, 7.5% = 58 mmol/mol and 8.0% = 64 mmol/mol.

Target for glycaemic control*

• Guidelines recommend the individualization of glycaemic targets according to a range of characteristics and factors1,2

• Factors favouring a more stringent target of 6.0−6.5% for Sunita include:

– Recently diagnosed diabetes

– Motivated patient with good initial adherence

– 62 years old

• Factors favouring a less stringent target for Sunita (i.e. 7.5−8.0%) include:

– Presence of important comorbidities

– Established CVD

– Risk of hypoglycaemia

• For newly diagnosed people with CVD, who are not elderly or frail, a target HbA1cof 6.5−7.0% is recommended if this can be achieved safely and without delay1

• Less stringent targets (7.0–7.5%) may be indicated for elderly patients, where hypoglycaemia is a concern or where co-morbidities impede use, or full titration, of certain therapies1

1. Bailey CJ et al. Diab Vasc Dis Res 2013;DOI 10.1177/1479164113490765. 2. Inzucchi SE et al. Diabetes Care 2012;35:1364−1379.

<6.0% 6.0–6.5% 6.5–7.0% 7.0–7.5% 7.5–8.0%

*Equivalent values: 6.0% = 42 mmol/mol, 6.5% = 48 mmol/mol, 7.0% = 53 mmol/mol, 7.5% = 58 mmol/mol and 8.0% = 64 mmol/mol.

CVD, cardiovascular disease.

Two months later… • 3 months have elapsed since Sunita was discharged from hospital and

she visits her doctor for a check-up

• She has had no further ischaemia or other events

• Her HbA1c is 6.8% (51 mmol/mol) and her blood glucose monitoring diary continues to show excellent control on low doses of insulin

• However, Sunita tells the doctor that the frequent insulin injections are a major inconvenience

– She feels her quality of life has declined

– She has avoided a number of social engagements due to the complications/embarrassment of injecting

– She has gained weight despite good adherence to dietary advice

• Sunita asks her doctor if any non-injectable treatments are available

HbA1c, glycosylated haemoglobin.

Alternative treatment?

Question What alternative treatment strategies would you propose for Sunita?

None – the insulin therapy is working and Sunita should continue on it

Transition to a trial of metformin monotherapy, monitor closely and review

Transition to a trial of sulphonylurea monotherapy, monitor closely and review


Alternative treatment selected: None − insulin therapy is working

• The antihyperglycaemic efficacy of insulin is excellent

– However, it has a number of drawbacks, such as hypoglycaemic risk and weight gain,1 and many individuals strongly dislike the need for frequent injections

• Many people are only able to achieve adequate glycaemic control with the use of insulin

• Patient preference is a critical consideration when selecting treatment and should not be ignored or neglected

• Given that Sunita is well controlled on low doses of insulin and that her admission HbA1c was not severely elevated, a trial of oral antidiabetic therapy might be effective

1. Inzucchi SE et al. Diabetes Care 2012;35:1364−1379.


Alternative treatment selected: Trial of metformin monotherapy

• Metformin monotherapy might be adequate for Sunita:

– Good glycaemic control on a low dose of insulin

– HbA1c at diagnosis was not severely elevated

• Patient preference is important when selecting therapy and Sunita has a strong desire to stop insulin treatment if possible

Metformin1,2

HbA1c efficacy: High

Hypoglycaemia risk: Low

Weight effect: Neutral/loss

Major side effects: GI Lactic acidosis

Cost: Low

• Metformin is the first-line treatment of choice for most patients with type 2 diabetes,1,2 with extensive experience of its use (also potential CV benefits)

• Dosing of insulin and metformin can be overlapped, with the insulin dose tapered off over time to avoid hyperglycaemia in the period needed for metformin to achieve its full therapeutic effect

• Sunita should be closely monitored and additional oral agents introduced or insulin restarted if metformin alone fails to maintain adequate glycaemic control

1. Bailey CJ et al. Diab Vasc Dis Res 2013;DOI 10.1177/1479164113490765. 2. Inzucchi SE et al. Diabetes Care 2012;35:13641379.

CV, cardiovascular; GI, gastrointestinal; HbA1c, glycosylated haemoglobin.


Alternative treatment selected: Trial of sulphonylurea monotherapy

• Sunita has good glycaemic control on a low dose of insulin and her HbA1c at diagnosis was not severely elevated

• A trial of oral antidiabetic therapy therefore seems reasonable

• Patient preference is important when selecting therapy and Sunita has a strong desire to stop insulin treatment if possible

1. Del Prato SD et al. Int J Clin Pract 2010;64:295−304.

2. Inzucchi SE et al. Diabetes Care 2012;35:1364−1379. 3. Bailey CJ et al. Diab Vasc Dis Res 2013;DOI 10.1177/1479164113490765.

Sulphonylurea2,3

HbA1c efficacy: High

Hypoglycaemia risk: Moderate

Weight effect: Gain

Major side effects: Hypoglycaemia Cost: Low

• However, a sulphonylurea is not generally recommended as first-line oral therapy for patients with type 2 diabetes1,2

• Although sulphonylureas have good efficacy, they are associated with hypoglycaemia risk and weight gain2

• Consequently, use of sulphonylureas should generally be restricted to a component of combination therapy


Status on oral therapy

• 3 months have elapsed since Sunita switched to oral therapy with metformin

• Her HbA1c is 6.9% (52 mmol/mol)

• She is much happier now that she doesn’t have to inject herself every day

• On the other hand, she admits to her doctor that – because it is easier to take a tablet rather than administer and injection – she sometimes forgets to do it

• The doctor reminds her about the importance of taking her medication regularly and asks her to return for another appointment in 3 months time


10 Steps to get more type 2 diabetes patients

to goal

10 Steps to get more people with type 2 diabetes to goal: • Aim for an appropriate individualized glycaemic target, e.g. HbA1c 6.5–7% (48–53 mmol/mol)

(or fasting/preprandial plasma glucose 110–130 mg/dl [6.0–7.2 mmol/l] where assessment of HbA1c is not possible) when safe and appropriate.

• Monitor HbA1c every 3 months in addition to appropriate glucose self-monitoring.

• Appropriately manage all cardiovascular risk factors.

• Refer all newly diagnosed patients to a unit specializing in diabetes care where possible.

• Address the underlying pathophysiology of diabetes, including the treatment of β-cell dysfunction and insulin resistance.

• Treat to achieve appropriate target HbA1c within 6 months of diagnosis.

• After 3 months, if patients are not at the desired target HbA1c, consider combination therapy.

• Consider initiating combination therapy or insulin for patients with HbA1c ≥9% (≥75 mmol/mol).

• Use combinations of antihyperglycaemic agents with complementary mechanisms of action.

• Implement a multidisciplinary team approach that encourages patient self-management, education and self-care, with shared responsibilities to achieve goals.

The Global Partnership for Effective Diabetes Management recommends:1

1. Bailey CJ et al. Diab Vasc Dis Res 2013;DOI 10.1177/1479164113490765.


For more case studies visit www.effectivediabetesmanagement.com

© 2013 International Medical Press. All rights reserved. No responsibility is assumed by the Global Partnership for Effective Diabetes Management or International Medical Press for any injury and/or damage to persons or property through negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein. Due to rapid advances in the medical sciences, the Global Partnership and International Medical Press recommend that independent verification of diagnoses and drug dosages should be made. Neither the Global Partnership for Effective Diabetes Management or International Medical Press assume liability for any material contained herein.

http://www.effectivediabetesmanagement.com/

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Individual with cardiovascular disease at the time of type ... · Individual with cardiovascular disease at the time of type 2 diabetes diagnosis Authored by Lawrence Blonde and Richard