Body weight modulates cholesterol metabolism in non-insulin dependent type 2 diabetics.

Abstract

Cholesterol metabolism was studied in 64 subjects with type 2 diabetes who had body weight ranging from normal to obese, to find out whether weight interferes with cholesterol metabolism in diabetes. Cholesterol absorption was measured with peroral isotopes and by assaying serum plant sterol and cholestanol to cholesterol ratios, cholesterol synthesis with sterol balance, and measuring serum cholesterol precursor ratios. The study population was divided into normal-weight (body mass index, 24.1 +/- 0.4 kg/m2; mean +/- SEM; n = 20) and obese (31.0 +/- 0.5 kg/m2; n = 44) groups. Despite similar serum cholesterol and blood glucose values, fecal neutral sterol excretion, cholesterol and bile acid synthesis, cholesterol turnover (1649 +/- 78 vs. 1077 +/- 52 mg/d; p < 0.001), and serum cholesterol precursors were higher, and cholesterol absorption % (32 +/- 1 vs. 40 +/- 2%; p < 0.05), serum cholestanol, and plant sterols were lower in the obese vs. the non-obese groups. Serum sex hormone-binding globulin was positively associated with variables of cholesterol absorption, whereas blood glucose, serum insulin, and body mass index were associated with variables of cholesterol synthesis. In multiple stepwise regression analysis, cholesterol absorption percentage (R2 = 24%) and body mass index (R2 = 15%) were the only variables explaining the variability of cholesterol synthesis. Body weight, through its entire range, regulates cholesterol metabolism in type 2 diabetes such that with increasing insulin resistance, cholesterol absorption is lowered and cholesterol synthesis increased.