Cholesterol Absorption, Synthesis, and LDL Metabolism in NIDDM

Abstract

OBJECTIVE Cholesterol and lipoprotein metabolism was studied in mildly hypercholesterolemic nonobese men with NIDDM to find out which metabolic parameters regulate serum cholesterol level in these NIDDM subjects. RESEARCH DESIGN AND METHODS Nonobese NIDDM subjects (n = 13) and control subjects (n = 18) with serum cholesterol ≥ 6.0 and triglycerides ≤ 2.5 mmol/l were studied on a similar monoene-enriched diet. Cholesterol absorption was studied with peroral double isotopes and by measuring serum plant sterols with gas-liquid chromatography; cholesterol synthesis was studied by measuring sterol balance and by measuring serum cholesterol precursor sterols; and LDL kinetics was measured with 131I-labeled autologous apoprotein (apo) B. RESULTS Cholesterol absorption was significantly lower in NIDDM subjects than in the control subjects, as detected by low serum plant sterol levels and absorption percentage (23 vs. 29%, P < 0.05). Cholesterol synthesis was significantly higher in NIDDM subjects than in the control subjects, as detected by precursor sterols or balance data (18 vs. 12 mg · kg−1 · day−1, P < 0.01), cholesterol turnover (19 vs. 13 mg · kg−1 · day−1, P < 0.01), and LDL apo B removal (0.343 vs. 0.267 pools/day, P < 0.01). Serum total and LDL cholesterol levels were inversely correlated with cholesterol synthesis, which was positively related to the catabolism of LDL apo B and negatively related to cholesterol absorption efficiency. CONCLUSIONS In this small selected group of mildly hypercholesterolemic nonobese NIDDM subjects, the regulation of serum cholesterol levels was achieved by the homeostasis between cholesterol absorption, synthesis, and LDL fractional catabolism. Cholesterol turnover and removal of LDL apo B were high in NIDDM subjects, compared with the control subjects, whereas cholesterol absorption efficiency was abnormally low Because of the relatively small number of selected subjects, the present results are not directly applicable to the overall NIDDM population.