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

Background: Weight reduction is the recommended treatment of obese type 2 d iabetes, but the effects of weight reduction on cholesterol metabolism are poorly understood. Objective: We investigated glucose, cholesterol, and lipoprotein metabolism at baseline and 2 y after weight reduction in obese patients with type 2 d iabetes consuming an isoenergetic diet. Design: 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 kin etics, and variables of glucose metabolism were studied at baseline and 2 y . Results: Baseline serum sex hormone binding globulin (SHBC) was significant ly related to cholesterol absorption efficiency, and serum glucose and insu lin concentrations were associated with cholesterol synthesis. After 2 y, b ody 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 ins ulin increased by 66% (P < 0.05). Serum and VLDL, LDL, and HDL triacylglyce rol were significantly reduced by 13-24%. Despite unchanged serum concentra tions of cholesterol, cholesterol absorption efficiency and the ratio of se rum plant sterols to cholesterol-indicators of cholesterol absorption-incre ased by 28% (P < 0.01) and 20-31% (P < 0.05 for both), respectively; the fr actional removal of LDL apolipoprotein B decreased. Fecal excretion of chol esterol 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. Conclusions: Baseline cholesterol absorption and synthesis were related to respective serum SHBG, glucose, and insulin values. Weight reduction increa sed cholesterol absorption and improved variables of glucose metabolism. Th ese results suggest that low cholesterol absorption and high synthesis may be part of the insulin resistance syndrome.