Early kinetic abnormalities of apoB-containing lipoproteins in insulin-resistant women with abdominal obesity.

OBJECTIVE The kinetic abnormalities of apolipoprotein B (apoB)-containing lipoproteins in abdominally obese insulin-resistant individuals remain poorly understood. To determine the influence of insulin resistance, linked with abdominal obesity, on apoB metabolism at an early stage, we performed a stable isotope kinetic study of apoB in very low density lipoproteins (VLDLs), intermediate density lipoproteins (IDLs), and low density lipoproteins (LDLs) in 5 abdominally obese insulin-resistant women with normal fasting triglyceride levels and without impaired glucose tolerance and in 5 age-matched control women. METHODS AND RESULTS Each subject received an intravenous injection of a 0.7 mg/kg bolus of L-[1-(13)C]leucine, immediately followed by a 16-hour constant infusion at 0.7 mg/kg per hour. Compared with control women, insulin-resistant women with abdominal obesity showed a significant 84% increase of the VLDL apoB production rate (27.18+/-11.53 versus 14.80+/-1.94 [control] mg/kg per day, P=0.009), a significant 54% increase of the IDL apoB production rate (20.63+/-3.66 versus 13.39+/-3.99 [control] mg/kg per day, P=0.009), and a significant 63% increase of the LDL apoB production rate (18.49+/-1.70 versus 11.33+/-3.79 [control] mg/kg per day, P=0.009), leading to significantly higher VLDL, IDL, and LDL apoB concentrations. The fractional catabolic rates of VLDL, IDL, and LDL apoB were not significantly different between abdominally obese insulin-resistant women and control women. CONCLUSIONS Our study shows that patients at an early stage of insulin resistance linked with abdominal obesity (without glucose intolerance or fasting hypertriglyceridemia) already have an altered metabolism of the VLDL-IDL-LDL cascade (increased VLDL, IDL, and LDL apoB production rates), which is consistent with the augmented risk of atherosclerosis observed in this population.