Impact of family history on relations between insulin resistance, LDL cholesterol and carotid IMT in healthy adults.

Abstract

Insulin resistance (IR) is implicated as an independent risk factor for vascular disease. The aim of this study was to assess the impact of family history (FH) of type 2 diabetes (T2DM) and/or cardiovascular disease (CVD) on the associations between IR, low-density-lipoprotein cholesterol (LDL-C) and subclinical atherosclerosis (common and internal carotid artery intima media thickness (IMT)) in healthy European adults. Participants (n=1048) in the Relationship between Insulin Sensitivity and Cardiovascular disease (RISC) study were grouped according to family history of: (i) type 2 diabetes (FH-T2DM); (ii) cardiovascular disease (FH-CVD); (iii) both (FH-BOTH); or (iv) neither (CON). Insulin resistance (M-value, hyperinsulinaemic euglycaemic clamp), LDL-C and IMT were examined in relation to FH in all available participants, and then within subcohorts (highest quintiles) with higher LDL-C (>3.5 mmol/l (>135 mg/dl), n=252) or greater IR (M-value<5 mg/min/kg, n=299). Carotid IMTs were comparable across the four FH groups, but insulin sensitivity (M-value) was lower (p<0.01) in FH-T2DM (6.1+/-2.6 mg/min/kg than in either CON (6.9+/-2.9 mg/min/kg) or FH-CVD (7.1+/-2.7 mg/min/kg). Within the highest LDL-C quintile, those with FH-CVD (or FH-BOTH) had higher common and internal carotid IMT (6-12%, p<0.05 vs CON). In contrast, within the most IR quintile, FH-CVD was not associated with IMT. In this cross-sectional analysis, family history of T2DM (but not of CVD) was associated with IR. In the presence of elevated LDL-C, FH-CVD (but not FH-T2DM) was associated with increased carotid IMT.