Introducing a new component of the metabolic syndrome: low cholesterol absorption

Abstract

Weight reduction is the recommended treatment of obese type 2 diabetes, but the effects of weight reduction on cholesterol metabolism are poorly understood. We investigated glucose, cholesterol, and lipoprotein metabolism at baseline and 2 y after weight reduction in obese patients with type 2 diabetes consuming an isoenergetic diet. Sixteen subjects were randomly chosen to consume a very-low-energy or low-energy diet for 3 mo, after which they consumed a weight-maintenance diet for up to 2 y. Cholesterol absorption and metabolism, LDL and HDL kinetics, and variables of glucose metabolism were studied at baseline and 2 y. Baseline serum sex hormone binding globulin (SHBG) was significantly related to cholesterol absorption efficiency, and serum glucose and insulin concentrations were associated with cholesterol synthesis. After 2 y, body weight was reduced by 6 +/- 1 kg (P < 0.01), body mass index by 6% (P < 0.05), and blood glucose by 14% (P < 0.01); the ratio of serum SHBG to insulin increased by 66% (P < 0.05). Serum and VLDL, LDL, and HDL triacylglycerol were significantly reduced by 13-24%. Despite unchanged serum concentrations of cholesterol, cholesterol absorption efficiency and the ratio of serum plant sterols to cholesterol-indicators of cholesterol absorption-increased by 28% (P < 0.01) and 20-31% (P < 0. 05 for both), respectively; the fractional removal of LDL apolipoprotein B decreased. Fecal excretion of cholesterol as neutral sterols decreased significantly by 11%. Changes in body weight were significantly negatively correlated with changes in ratios of cholesterol to serum plant sterols and cholestanol. Baseline cholesterol absorption and synthesis were related to respective serum SHBG, glucose, and insulin values. Weight reduction increased cholesterol absorption and improved variables of glucose metabolism. These results suggest that low cholesterol absorption and high synthesis may be part of the insulin resistance syndrome.