INCREASED HEPATIC SECRETION OF VERY-LOW-DENSITY LIPOPROTEIN APOLIPOPROTEIN B-100 IN NIDDM

We measured the hepatic secretion of very-low-density lipoprotein apol ipoprotein B-100 (VLDL apoB) using a stable isotope gas-chromatography mass-spectrometry method in six patients with non-insulin-dependent d iabetes mellitus (NIDDM) (four males, two females, age 57.5+/-2.2 year s (mean+/-SEM), weight 88.2+/-5.5 kg, glycated haemoglobin (HbA(1)) 8. 5+/-0.5%, plasma total cholesterol concentration 5.7+/-0.5 mmol/l, tri glyceride 3.8+/-0.9 mmol/l, high-density lipoprotein (HDL) cholesterol 1.0+/-0.1 mmol/l) and six non-diabetic subjects matched for age, sex and weight (four males, two females, age 55.7+/-2.8 years, weight 85.8 +/-5.6 kg, HbA(1) 6.5+/-0.1%,plasma total cholesterol concentration 5. 7+/-0.5 mmol/l, triglyceride 1.2+/-0.1 mmol/l, HDL cholesterol 1.4+/-0 .1 mmol/l). HbA(1), plasma triglyceride and mevalonic acid (an index o f cholesterol synthesis in vivo) concentrations were significantly hig her in the diabetic patients than in the non-diabetic subjects (p = 0. 006, p = 0.02 and p = 0.004, respectively), VLDL apoB absolute secreti on rate was significantly higher in the diabetic patients compared wit h the non-diabetic subjects (2297+/-491 vs 921+/-115 mg/day, p < 0.05) , but there was no significant difference in the fractional catabolic rate of VLDL apoB. There was a positive correlation between VLDL apoB secretion rate and (i) fasting C-peptide (r = 0.84, p = 0.04) and (ii) mevalonic acid concentration (r = 0.83, p < 0.05) in the diabetic pat ients but not in the non-diabetic subjects. There was also a significa nt positive association between plasma mevalonic acid and plasma C-pep tide (r = 0.82, p < 0.05) concentrations in the diabetic patients. We conclude that in NIDDM, there is increased hepatic secretion of VLDL a poB which may partly explain the dyslipoproteinaemia seen in this cond ition. We suggest that increased secretion of this apolipoprotein may be a consequence of resistance to the inhibitory effect of insulin on VLDL apoB secretion. Insulin resistance may also be the mechanism by w hich cholesterol synthesis, a regulator of apoB secretion, is increase d in NIDDM.