Central obesity, hepatic lipase activity and dyslipidemia in type 1 diabetes

Excessive weight-gain in a subset of the intensively treated cohort of the Diabetes Control and Complications Trial (DCCT) was associated with insulin resistance, high waist-to-hip ratio and blood pressure, and an atherogenic dyslipidemia with elevations in triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (apoB) in the presence of small-dense LDL, and decreased high-density lipoprotein subclass 2 cholesterol (HDL₂-C) suggesting that intensive therapy unmasked the central obesity syndrome in some insulin resistant subjects. In studies of subjects who do not have type 1 diabetes, higher intraabdominal fat (IAF) is associated with higher hepatic lipase activity (HL) and high HL is associated with a similar atherogenic dyslipidemia. The purpose of this study was to investigate the relationship between IAF, HL, and dyslipidemia in subjects with type 1 diabetes. Twenty-one subjects from the Seattle cohort of the Epidemiology of Diabetes Intervention and Complications Trial (EDIC) (15 males and 6 females) have completed baseline IAF (via CT at the umbilicus), HL, standard serum lipids, and lipoprotein measures. In these subjects, a significant positive relationship exists between IAF and HL (r=0.597, p=0.004), A significant positive relationship exists between IAF and log TG (r=0.726, p<0,001), apoB (r=0.718, p=0.001) and LDL relative flotation rate (LDL-Rf) (r=0.646, p=0.002) which is a measure of LDL-C buoyancy, and a significant negative relationship exists between IAF and HDL₂-C (r=0.570, p=0.007). HL was positively related to apoB (r=0.613, p=0.009) and LDL-Rf (r=0.776, p<0.001) and negatively related to HDL₂-C (r=0.510, p=0.018). When HDL₂-C is adjusted for HL, it is no longer significantly related to IAF. These data suggest that in an unselected group of subjects with type 1 diabetes, increased IAF is strongly and directly related to increased HL which may be a mediator of the dyslipidemia.