糖尿病人如何提高HDL?

Raising HDL Cholesterol in Patients WithDiabetes

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

Answer:To arrive at an answer, we should ask ourselves severalkey questions. First, what constitutes a low level of HDL cholesterol?If the definition is based on the 2001 National CholesterolEducation Program Adult Treatment Panel III guidelines, levelsof HDL cholesterol <40 mg/dl are considered a risk factorfor coronary heart disease, with <40 mg/dl for men and <50mg/dl for women a component of metabolic syndrome—a clusteringof risk factors linked to cardiovascular disease (CVD) anddiabetesthatincludes a large waist size, hypertension, impaired glucosemetabolism, and dyslipidemia.¹

Next, why is the HDL cholesterol reduced? Assuming the patienthas type 2diabetes, obesity is likely present. Obesity reduceslevels of HDL cholesterol independent ofdiabetes.^2,3

Third, hypertriglyceridemia is often present in patients withtype 2diabetesand obesity, and the inverse relationship between hypertriglyceridemiaand HDL cholesterol is well established. If both reduced HDLcholesterol and hypertriglyceridemia are present, then the patientwithdiabetesmust have metabolic syndrome.⁴

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

Fifth, are there genetic and/or other acquired causes of lowHDL 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 withoutdiabetesand low levels of HDL cholesterol, and what are thetherapeutic options? Presently, no evidence exists that increasingHDL cholesterol independent from other risk factor modificationreduces CVD risk. For patients with metabolic syndrome, thefocus should remain on reducing LDL cholesterol.⁶To increaseHDL cholesterol, lifestyle. modification should be emphasized.Of course, smoking cessation is the place to start.⁷

For most patients withdiabetes, weight loss is most important.A 10% weight reduction is recommended, with fasting lipids notreexamined until several months of stability at the reduced weight.⁸Quitting smoking and losing weight at the same time are nearlyimpossible, so I suggest that smoking cessation be the firststep.

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

Then there's glycemia. Typically with hypoglycemic therapy,the impact on HDL cholesterol is minimal, although there issome evidence that insulin may be more effective here than a sulfonylurea.⁹Increasesin physical activity—especially aerobicexercise—increaseHDL cholesterol in patients with and withoutdiabetes.^10,11

What about medications? The pharmaceutical class with by farthe greatest impact on HDL cholesterol is the cholesteryl estertransfer protein (CETP) inhibitors. However, the recent experiencewith torcetrapib, a CETP inhibitor that raised HDL cholesterolby 60% and even lowered LDL cholesterol but failed to decreasethe progression of coronary atherosclerosis, indicates thatlevels of HDL cholesterol per se may not be sufficiently informative.¹²Althoughfibrates and statins all increase HDL cholesterol modestly (typically 5–10%),the drug of choice to raise HDL cholesterol is niacin. Herean increase in HDL cholesterol in the range of 15–30%often is experienced. For most patients withdiabetes, glycemiais unaffected, but sometimes increases in glycemia may follow.¹³

In summary, the following approach is recommended for raisingHDL in patients withdiabetes:

• Consider acquired causes of reduced HDL cholesterol and modifywhen possible.
  
• Improve glycemia, e.g., A1C <7%.
  
• ReduceLDL cholesterol to <70 mg/dl.
  
• Improve lifestyle. throughsmoking cessation, weight loss, andexercise—mostlyaerobic.
  
• Prescribe niacin and monitor glycemia.
  

Footnotes

Robert H. Eckel, MD, isCharles A. Boettcher II Chair in Atherosclerosis at Universityof Colorado at Denver and Health Sciences Center

References

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11.Di Loreto C, Fanelli C, Lucidi P, et al: Make your diabetic patients walk: Long-term impact of different amounts of physical activity on type 2diabetes.DiabetesCare28: 1295–1302, 2005.[Abstract/Free Full Text]

12.Nissen SE, Tardif JC, Nicholls SJ, et al.: Effect of torcetrapib on the progression of coronary atherosclerosis.N Engl J Med356:1304–1316, 2007.[Abstract/Free Full Text]

13.Grundy SM, Vega GL, McGovern ME, et al.: Efficacy, safety, and tolerability of once-daily niacin for the treatment of dyslipidemia associated with type 2diabetes: Results of the Assessment ofDiabetesControl and Evaluation of the Efficacy of Niaspan Trial.Arch Intern Med162:1568–1576, 2002.[Abstract/Free Full Text]