Abstract 593: ApoB-Lipoprotein Association With Insulin Resistance and Hyperinsulinemia: is Activation of the IL-1ß System Involved?

Abstract

INTRODUCTION: Elevated apoB-lipoproteins is reported to predict type 2 diabetes (T2D) development in postmenopausal women. Low insulin sensitivity (IS) and compensatory hyperinsulinemia is believed to lead to β-cell exhaustion and increase T2D risk. Also, activation of the interleukin-1β (IL-1β) system, a novel inflammatory pathway, is known to predict the development of T2D. We thus aimed to investigate whether plasma apoB associates with low IS and hyperinsulinemia and whether this is via an activation of the IL-1β system. METHODOLOGY: 47 non-diabetic overweight and obese postmenopausal women and 28 men, aged 45 to 74 years old, underwent a modified Botnia clamp, in which 1 st and 2 nd phase insulin secretion were measured during a 1 hour intravenous glucose tolerance test (IVGTT). Following that, a 3 hour hyperinsulinemic-euglycemic clamp (HEIC, insulin infusion rate of 75 mU/m 2 /min) was conducted to measure IS during the last 30 minutes (steady state). IS was expressed as steady state glucose infusion rate (GIR) alone or divided over steady state plasma insulin (M/I). RESULTS: In women, fasting plasma apoB correlated positively with 2 nd phase (r=0.202), total insulin secretion (r=0.168) and with total C-peptide secretion (r=0.204) and negatively with IS (r: GIR= -0.299 and M/I =-0.180) independent of adiposity. Similar to plasma apoB, fasting plasma IL-Ra (indicator of activated IL-1β system) correlated positively with 2 nd phase and total insulin secretion and with total C-peptide secretion (r=0.217; r=0.154; r=0.198 respectively) and negatively with IS (GIR r=-0.304; M/I r=-0.214). Fasting plasma IL-Ra also correlated with apoB r=0.352). Once corrected for IL-1Ra, all associations between apoB and the indexes of IS and insulin secretion were lost. Plasma apoB did not correlate with any indices of insulin secretion or IS in men. The strongest correlate of insulin secretion and IS was adiposity, particularly central. CONCLUSION: ApoB is associated with hyperinsulinemia and low IS in non-diabetic overweight and obese women, which may be mediated through activation of the IL-1β system. Gender differences may need to be considered in exploring the pathophysiology of T2D in humans.