Elevated plasma non-esterified fatty acid levels and insulin secretion in non-diabetic relatives of type 2 diabetic patients

OBJECTIVE: High non-esterified fatty acid (NEFA) levels impair glucose-stimulated insulin secretion from islets derived from non-diabetic Zucker rats that are genetically predisposed to diabetes. We therefore examined the effect of elevated plasma NEFA levels on insulin secretion in non-diabetic first-degree relatives of type 2 diabetic patients who are at increased risk of developing diabetes. SUBJECTS AND STUDY DESIGN: Normal glucose tolerant relatives (n = 9) and control subjects with no family history of diabetes were pair-matched for age, sex, body mass index (BMI), insulin sensitivity and early insulin response during an oral glucose tolerance test (OGTT). Plasma NEFA levels were raised from 0 to 340 minutes by the infusion of 20% Intralipid and heparin. From 180 minutes, insulin secretion rates (IRSs) were assessed by stepped low-dose glucose infusion. RESULTS: The mean (geometric mean +/- 95% CI) NEFA levels were comparable between relatives and control subjects (2.7 [2.1-3.6] and 2.1 [1.7-2.7] mmol/l, paired analysis, NS). Similarly, plasma glucose levels achieved at each glucose infusion step were comparable between the groups. However, there were no significant differences between the groups for ISR throughout the study. CONCLUSIONS: Sustained elevation of plasma non-esterified fatty acid levels does not decrease insulin secretion in non-diabetic relatives of type 2 diabetic patients, and is therefore unlikely to be important in the development of the impaired pancreatic beta-cell function in type 2 diabetes mellitus.