Type 2 Diabetes Mellitus Treatment & Management

HKDU⠀ Published at 2021-10-27

Management of Coronary Heart Disease

There is contradictory epidemiologic evidence as to whether diabetes is in fact a CHD risk equivalent. For the present, however, that is the position adopted by most groups, such as the National Cholesterol Education Program (NCEP) and the ADA. [342]

Although the risk for CHD is 2-4 times greater in patients with diabetes than it is in individuals without diabetes, control of conventional risk factors is probably more important in event reduction than is glycemic control. Control of hypertension, aspirin therapy, and lowering of LDL cholesterol levels are vitally important in reducing CHD risk.

Aspirin

The ADA recommends that patients with diabetes who are at high risk for cardiovascular events receive primary preventive therapy with low-dose, enteric-coated aspirin. For patients with aspirin hypersensitivity or intolerance, clopidogrel is recommended. [344]

However, a randomized, controlled trial from Japan found that using low-dose aspirin as primary prevention did not reduce the risk of cardiovascular events in patients with type 2 diabetes. [345These investigators subsequently reported that low-dose aspirin therapy reduces cardiovascular risk only in patients with a glomerular filtration rate (GFR) of 60-89 mL/min; low-dose aspirin had no beneficial impact if the GFR was above 90 mL/min or below 60 mL/min. [346]

A study by Okada et al reported that low-dose aspirin therapy (81-100 mg) in patients with diabetes who are taking insulin or oral hypoglycemic agents does not reduce atherosclerotic events. [347This is yet another argument against using low-dose aspirin for primary prevention of cardiovascular disease in patients with moderate or severe diabetes.

Statins

The Scandinavian Simvastatin Survival Study (4S) showed a 42% reduction in CHD events in diabetic patients with simvastatin therapy (mean dose 27 mg daily, with LDL reduction approximately 35%). Participants in 4S had known CHD and very high LDL cholesterol levels. [348]

A smaller reduction was seen in the Heart Protection Study (HPS) in patients with CHD or other vascular disease and diabetes. [349Patients in the HPS treatment arm received simvastatin 40 mg daily. Lesser degrees of risk reduction have been shown in other secondary prevention studies in patients treated with pravastatin with mild to moderate LDL cholesterol elevation at baseline.

Atorvastatin, 10 mg daily, did not reduce CHD risk among diabetic patients with hypertension and no previous CHD who were enrolled in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). [350In contrast, the Collaborative Atorvastatin Diabetes Study (CARDS) showed a significant reduction in CHD risk in patients with type 2 diabetes mellitus and 1 other risk factor when treated with atorvastatin 10 mg daily. [351]

Some studies have suggested that statin therapy may be associated with an increased risk of developing diabetes. In a pooled analysis of data from five statin trials, intensive-dose statin therapy was associated with increased risk of new-onset diabetes compared with moderate dose statins. [352]

A study by Ahmadizar et al of subjects over age 45 years who had no diabetes at baseline reported that compared with individuals who have never used statins, the risk of incident type 2 diabetes development in persons who have ever taken statins is 38% greater, with the likelihood being particularly high in persons with impaired glucose homeostasis and in individuals who are overweight/obese. However, analyses stratified at baseline for gender and body mass index (BMI) indicated that statin use was not significantly associated with type 2 diabetes in women or in persons with a normal body mass index (BMI). [353354]

The American Diabetes Association (ADA) provided recommendations on the use of statins in patients with diabetes to align with those of the American College of Cardiology and the American Heart Association. [355]

  • The ADA recommends statin use for nearly everyone with diabetes.

  • The ADA guidelines divide diabetes patients by 3 age groups:

    • Younger than 40 years: No statins for those with no cardiovascular disease (CVD) risk factors other than diabetes; moderate intensity or high-intensity statin doses for those with additional CVD risk factors (baseline LDL cholesterol 100 or greater, high blood pressure, smoking, and overweight/obesity); and high-intensity statin doses for those with overt CVD (including previous cardiovascular events or acute coronary syndrome).

    • Age 40-75 years: Moderate-intensity statins for those with no additional risk factors, and high-intensity statins for those with either CVD risk factors or overt CVD.

    • Older than 75 years: Moderate-intensity statins for those with CVD risk factors; and high-intensity statins for those with overt CVD.

  • Lipid monitoring for adherence is recommended as needed, and annual monitoring is advised for patients younger than 40 years who have not yet started on statins.

  • There is a new BMI cut point of 23 kg/m2 (instead of 25 kg/m2) for screening Asian Americans for prediabetes and diabetes, based on evidence that Asian populations are at increased risk at lower BMIs relative to the general population.

  • The premeal glucose target of 70-130 mg/dL was changed to 80-130 mg/dL to better reflect new data that compared average glucose levels with HbA1c targets.

  • The goal for diastolic blood pressure was raised to 90 mm Hg from 80 mm Hg to better reflect data from randomized clinical trials. (This follows ADA's 2013 shift from a systolic target of 130 mm Hg to 140 mm Hg.)

  • With regard to physical activity, the document now advises limiting the time spent sitting to no longer than 90 min.

  • The ADA does not support e-cigarettes as alternatives to smoking or to facilitate smoking cessation.

  • Immunization against pneumococcal disease is recommended.

  • A new HbA1c target of less than 7.5% for children is now recommended.

HDL cholesterol therapy

The benefits of raising HDL cholesterol levels in patients with type 2 diabetes remains uncertain. Some of the statin trials suggest that statin therapy eliminates some of the excess risk from low HDL cholesterol levels in patients with LDL cholesterol elevation at baseline.

The Veterans Administration HDL Intervention Trial (VA-HIT) showed an approximately 22% reduction in CHD events in patients with diabetes and known CHD when HDL cholesterol levels were increased by approximately 6% by gemfibrozil. [356This was a population with low LDL cholesterol levels, however, so whether these same benefits would accrue in patients with elevated LDL cholesterol who are treated with a statin before their low HDL cholesterol is addressed is unclear.

Triglyceride therapy

An elevated triglyceride level is a common abnormality in type 2 diabetes mellitus. However, whether therapy to reduce triglycerides helps to reduce CHD events has not been determined from clinical end-point trials.

Revascularization

The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) study, which was conducted in 2368 patients with type 2 diabetes mellitus and heart disease, showed no significant difference in the rates of death and major cardiovascular events between patients undergoing prompt revascularization and those undergoing medical therapy with insulin or insulin-sensitizing drugs. [357These data emphasize the need to customize therapy to the patient’s circumstances and therapeutic goals.