Impact of nicotinic acid treatment on insulin secretion and insulin sensitivity in low and high insulin responders

Abstract

The aim of the study was to evaluate the effect of nicotinic acid (NA) on glucose tolerance, insulin secretion and sensitivity in relation to perturbations of non-esterified fatty acids (NEFA) and previously characterized insulin responses. Healthy subjects (n= 12) were treated for 14 days with incremental doses of NA reaching 2 g day⁻¹. Before NA and on day 14 a hyperglycaemic clamp (11 mmoll⁻¹) was performed with arginine (5g i.v.) stimulation before and during the clamp.

Fasting serum levels of NEFA were evanescently decreased on day 3 (-38%; p<0.01) and day 7 (-33%; p<0.05), but not on day 14 (-14%; NS). NA treatment did not significantly affect levels of fasting blood glucose, insulin, C-peptide, proinsulin or glucagon. NA treatment lowered the amount of infused glucose necessary to achieve clamp levels 48 (8) vs. 61 (10) μmol kg⁻¹ min⁻¹ (p<0.01). Incremental increases in fasting NEFA levels correlated (r = -0.72) with decreased insulin sensitivity as reflected by M/I ratios (the amount of glucose infused, minus glucosuria, divided by the mean insulin level) (p<0.01). Insulin and glucagon responses to arginine and glucose were similar before and after NA in subgroups with initially low and high insulin responses to glucose.

NA-induced insulin resistance in this study is (a) less than previously reported; (b) not associated with changes in insulin secretory responsiveness, but is (c) influenced by an individually variable NA effect on fasting NEFA levels. Our results do not indicate that NA treatment can be used to test the capacity of B cells to cope with insulin resistance.

Key Words:

• insulin secretion
• insulin sensitivity
• nicotinic acid
• non-esterified fatty acids