Acute lowering of fatty acids improves insulin secretion in a subset of type II diabetes subjects

We tested the effects of acute perturbations of elevated fatty acids (FA) on insulin secretion in type II diabetes. Twenty-one type II diabetes subjects with hypertriglyceridemia (triacylglycerol > 2.2mmol/l) and ten age-matched non-diabetic subjects participated. Glucose-stimulated insulin secretion was monitored during hyperglycemic clamps for 120 min. An infusion of Intralipid and heparin was added during min 60-120. In one of two tests, the subjects ingested 250mg of Acipimox 60 min before the hyperglycemic clamp. A third test (also with Acipimox) was performed in seventeen of the diabetic subjects after three days of a low-fat diet. Acipimox lowered FA levels and enhanced insulin sensitivity in non-diabetic diabetic and diabetic subjects alike. Acipimox administration failed to affect insulin secretion rates in non-diabetic subjects and in the group of diabetic subjects as a whole. However, in the diabetic subjects Acipimox increased integrated insulin secretion rates during min 60-120 min in the 50% having the lowest levels of hemoglobin A1c (379 ± 34 with vs. 326 ± 30 pmol·kg-1·min-1 without Acipimox, P