Intensive Therapy of Type I Diabetes May Increase the Risk of Coronary Artery Disease
ABSTRACT & COMMENTARY
Synopsis: Intensive treatment of Type I diabetes results in greater weight gain and changes in lipid levels and blood pressure that are similar to those seen in the insulin resistance syndrome and may increase the risk of coronary artery diseases.
Source: Purnell JO, et al. JAMA 1998;280:140-146.
Purnell et al demonstrated in an ancillary study of the Diabetes Control and Complications Trial (DCCT) that intensive treatment resulted in greater weight gain than conventional treatment. Subjects were randomized to receive either intensive (n = 586) or convention (n = 582) diabetes treatment with a mean follow up of 6.1 years. All subjects were 18 years or older. With intensive treatment, subjects in the fourth quartile of weight gain had the highest body mass index (BMI), blood pressure, and levels of triglyceride, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B as compared with the other weight gain quartiles. The mean value for the highest and lowest quartiles were as follows: BMI, 31 vs. 24 kg/m2; blood pressure, 120/77 mmHg vs. 113/73 mmHg; and apolipoprotein B, 0.89 g/L vs. 0.78 g/L (all P < 0.001). In addition, the fourth quartile group had higher waist-to-hip ratio; more cholesterol in the very low density lipoprotein, intermediate density lipoprotein (IDL-C), and dense LDL fractions; and lower high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-1 levels compared with the first quartile.
The changes in lipid levels and blood pressure that occur with excessive weight gain during intensive therapy are similar to those seen in the insulin resistance syndrome and may increase the risk of coronary artery disease (CAD) in this subset of subjects.
COMMENT BY RALPH R. HALL, MD, FACP
This is a particularly disturbing article in that Lamarche et al have shown in their studies that the apolipoprotein B levels and LDL particle size may identify those at risk for CAD more effectively than changes in the cholesterol levels. They remind us that patients who achieve significant reductions in LDL-C still develop CAD.1,2
These findings indicate that there is not only a need to lower LDL-C, but also to alter the quality of the lipoproteins. Only recently that have we understood that these qualitative features of plasma lipoproteins are important in predicting the risk of CAD. Dense lipoproteins derive their atherogenic properties because of their low binding affinity for the LDL receptors, a decreased resistance to oxidative stress, and a prolonged plasma half life.3
Haffner et al have shown that type II diabetics who have the lipoprotein pattern similar to these type I patients who have gained weight with their treatment have as high a risk for myocardial infarction (MI) as nondiabetics with a previous MI.4
So, what are we to do with type I diabetics who have a tendency to gain weight? The statins decrease the LDL-C, but they do not alter their small, dense quality. On the other hand, metformin, the fibrates, troglitazone, and exercise affect the changes in lipoproteins that increase their size and their affinity for LDL receptor sites and render them less atherogenic.3-5
Perhaps combining insulin with metformin or the fibrates may prevent these unfavorable changes in the lipid profiles and, in the case of metformin, may make weight gain less likely just as they do in type II diabetics. Definitive studies to support these concepts are urgently needed.
References
1. Lamarche B, et al. JAMA 1998;279:1955-1961.
2. Superko HR, et al. Circulation 1996;94:2351-2354.
3. Chapman, et al. EurHeart J 1998;19 (Suppl A):A-24- A-30.
4. Haffner SM, et al. N Engl J Med 1998;339:229-234.
5. Hirano T, et al. Ann Intern Med 1998;129:162.
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