Effect of excessive weight gain with intensive therapy of type 1 diabetes on lipid levels and blood pressure: results from the DCCT. Diabetes Control and Complications Trial

Abstract

Context: Intensive treatment of type 1 diabetes results in greater weight gain than conventional treatment.

Objective: To determine the effect of this weight gain on lipid levels and blood pressure.

Design: Randomized controlled trial; ancillary study of the Diabetes Control and Complications Trial (DCCT).

Setting: Twenty-one clinical centers.

Participants: The 1168 subjects enrolled in DCCT with type 1 diabetes who were aged 18 years or older at baseline.

Intervention: Randomized to receive either intensive (n = 586) or conventional (n = 582) diabetes treatment with a mean follow-up of 6.1 years.

Main outcome measures: Plasma lipid levels and blood pressure in each treatment group categorized by quartile of weight gain.

Results: With intensive treatment, subjects in the fourth quartile of weight gain had the highest body mass index (BMI) (a measure of weight adjusted for height), blood pressure, and levels of triglyceride, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B compared with the other weight gain quartiles with the greatest difference seen when compared with the first quartile (mean values for the highest and lowest quartiles: BMI, 31 vs 24 kg/m2; blood pressure, 120/77 mm Hg vs 113/73 mm Hg; triglyceride, 0.99 mmol/L vs 0.79 mmol/L [88 mg/dL vs 70 mg/dL]; LDL-C, 3.15 mmol/L vs 2.74 mmol/L [122 mg/dL vs 106 mg/dL]; and apolipoprotein B, 0.89 g/L vs 0.78 g/L; all P<.001). In addition, the fourth quartile group had a higher waist-to-hip ratio; more cholesterol in the very low density lipoprotein, intermediate dense lipoprotein, and dense LDL fractions; and lower high-density lipoprotein cholesterol and apolipoprotein A-I levels compared with the first quartile. Baseline characteristics were not different between the first and fourth quartiles of weight gain with intensive therapy except for a higher hemoglobin A1c in the fourth quartile. Weight gain with conventional therapy resulted in smaller increases in BMI, lipids, and systolic blood pressure.

Conclusions: The changes in lipid levels and blood pressure that occur with excessive weight gain with intensive therapy are similar to those seen in the insulin resistance syndrome and may increase the risk of coronary artery disease in this subset of subjects with time.

Figure 1

Increases in body mass index (BMI) (a measure of weight in kilograms divided by the square of height in meters) and the equivalent weight in kilograms from baseline to follow-up in the quartiles of weight gain in the conventionally and intensively treated groups.

Figure 2

Distribution of lipoprotein cholesterol across nonequilibrium density gradient (from very low-density lipoprotein [VLDL], intermediate density lipoprotein [IDL], low-density lipoprotein [LDL], to high-density lipoprotein [HDL]) ultracentrifugation comparing the fourth quartile with the first quartile of weight gain with conventional therapy (A) and difference plot of mean cholesterol levels of each fraction with 95% confidence interval (B).

Figure 3

Distribution of lipoprotein cholesterol across nonequilibrium density gradient (from very low-density lipoprotein [VLDL], intermediate density lipoprotein [IDL], low-density lipoprotein [LDL], to high-density lipoprotein [HDL]) ultracentrifugation comparing the fourth quartile with the first quartile of weight gain with intensive therapy (A) and difference plot of mean cholesterol levels of each fraction with 95% confidence interval (B).