Raising HDL Cholesterol in Patients With Diabetes

Question: What are the best methods for clinicians to use to raise HDL in patients with type 2 diabetes?

Answer: To arrive at an answer, we should ask ourselves several key questions. First, what constitutes a low level of HDL cholesterol? If the definition is based on the 2001 National Cholesterol Education Program Adult Treatment Panel III guidelines, levels of HDL cholesterol <40 mg/dl are considered a risk factor for coronary heart disease, with <40 mg/dl for men and <50 mg/dl for women a component of metabolic syndrome—a clustering of risk factors linked to cardiovascular disease (CVD) and diabetes that includes a large waist size, hypertension, impaired glucose metabolism, and dyslipidemia.¹

Next, why is the HDL cholesterol reduced? Assuming the patient has type 2 diabetes, obesity is likely present. Obesity reduces levels of HDL cholesterol independent of diabetes.^2,3

Third, hypertriglyceridemia is often present in patients with type 2 diabetes and obesity, and the inverse relationship between hypertriglyceridemia and HDL cholesterol is well established. If both reduced HDL cholesterol and hypertriglyceridemia are present, then the patient with diabetes must have metabolic syndrome.⁴

Fourth, what is the current level of glycemia? In general, with increasing levels of glycated hemoglobin (A1C), fasting triglycerides increase with associated decreases in HDL cholesterol.⁵

Fifth, are there genetic and/or other acquired causes of low HDL cholesterol that need to be considered—for example, cigarette smoking, sedentary behavior, proteinuria, or hypogonadism? Is the patient using medications such as beta-blockers or diuretics?

Finally, what are the goals for patients with or even without diabetes and low levels of HDL cholesterol, and what are the therapeutic options? Presently, no evidence exists that increasing HDL cholesterol independent from other risk factor modification reduces CVD risk. For patients with metabolic syndrome, the focus should remain on reducing LDL cholesterol.⁶ To increase HDL cholesterol, lifestyle modification should be emphasized. Of course, smoking cessation is the place to start.⁷

For most patients with diabetes, weight loss is most important. A 10% weight reduction is recommended, with fasting lipids not reexamined until several months of stability at the reduced weight.⁸ Quitting smoking and losing weight at the same time are nearly impossible, so I suggest that smoking cessation be the first step.

Dietary macronutrient content also can influence levels of HDL cholesterol. However, mixed messages about dietary macronutrient composition are prevalent. One of the best ways for people to raise HDL cholesterol is to consume more saturated fats, but this increase keeps bad company, as it raises LDL cholesterol as well. The modest fall in HDL cholesterol during active dieting with higher carbohydrate feeding should not be viewed as harmful—once weight stability has ensued at the reduced weight, HDL cholesterol levels will increase.

Then there's glycemia. Typically with hypoglycemic therapy, the impact on HDL cholesterol is minimal, although there is some evidence that insulin may be more effective here than a sulfonylurea.⁹ Increases in physical activity—especially aerobic exercise—increase HDL cholesterol in patients with and without diabetes.^10,11

What about medications? The pharmaceutical class with by far the greatest impact on HDL cholesterol is the cholesteryl ester transfer protein (CETP) inhibitors. However, the recent experience with torcetrapib, a CETP inhibitor that raised HDL cholesterol by 60% and even lowered LDL cholesterol but failed to decrease the progression of coronary atherosclerosis, indicates that levels of HDL cholesterol per se may not be sufficiently informative.¹² Although fibrates and statins all increase HDL cholesterol modestly (typically 5–10%), the drug of choice to raise HDL cholesterol is niacin. Here an increase in HDL cholesterol in the range of 15–30% often is experienced. For most patients with diabetes, glycemia is unaffected, but sometimes increases in glycemia may follow.¹³

In summary, the following approach is recommended for raising HDL in patients with diabetes:

1. Consider acquired causes of reduced HDL cholesterol and modify when possible.

2. Improve glycemia, e.g., A1C <7%.

3. Reduce LDL cholesterol to <70 mg/dl.

4. Improve lifestyle through smoking cessation, weight loss, and exercise—mostly aerobic.

5. Prescribe niacin and monitor glycemia. ▪