ACUTE HYPERINSULINEMIA DECREASES CHOLESTEROL-SYNTHESIS LESS IN SUBJECTS WITH NON-INSULIN-DEPENDENT DIABETES-MELLITUS THAN IN NONDIABETIC SUBJECTS

To investigate the effect of insulin on cholesterol synthesis in vivo we measured plasma mevalonic acid (MVA) concentrations using gas chrom atography-mass spectrometry in six non-obese patients with non-insulin -dependent diabetes mellitus (NIDDM) [four men, two women: age 57 . 5 +/- 2 . 2 years (mean +/- SEM); glycated haemoglobin (HbA1) 8 . 5 +/- 0 . 5%; total cholesterol (TC) 5 . 7 +/- 0 . 5 mmol L(-1), triglycerid e (TG) 3 . 8 +/- 0 . 9 mmol L(-1)] and six non-diabetic, sex- and age- matched control subjects (age 55 . 7 +/- 2 . 8 years; HbA1 6 . 5 +/- 0 . 1%: TC 5 . 4 +/- 0 . 3 mmol L, TG 1 . 2 +/- 0 . 1 mmol L(-1)). Subj ects were studied twice: during 13-h hyperinsulinaemic (1 mu kg(-1) mi n(-1)), euglycaemic (5 mmol L(-1)) clamp and during a saline infusion. Baseline MVA concentration was significantly higher in diabetic patie nts than in control subjects (9 . 8 +/- 0 . 7 ng mL(-1). 5 . 6 +/- 0 . 9 ng mL(-1), P = 0 . 004). At the end of each study, MVA concentratio n, expressed as a percentage of baseline, was significantly lower duri ng the hyperinsulinaemic, euglycaemic clamp than during the saline stu dy in both the diabetic (54 . 4 +/- 5 . 3% vs. 69 . 6 +/- 6 . 3%, P = 0 . 036) and control subjects (30 . 5 +/- 3 . 4% vs. 61 . 7 +/- 6 . 0% , P = 0 . 01). However, the decrease in MVA during the hyperinsulinaem ic clamp study was more marked in the control subjects than in the dia betic subjects (P = 0 . 03). A significant positive correlation was fo und between percentage decrease of MVA and non-esterified fatty acids following the insulin clamp in NIDDM (r = 0 . 83, P = 0 . 04). We conc lude that acute hyperinsulinaemia decreases cholesterol synthesis less in subjects with NIDDM than in non-diabetic subjects and that this ph enomenon, together with increased basal cholesterol synthesis in NIDDM , may in part be due to insulin resistance.