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-C-13]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.