People with T1D have higher HDL cholesterol (HDLc) yet are more insulin resistant and have increased cardiovascular disease (CVD) risk than people without diabetes. We hypothesized that HDL is dysfunctional in people with T1D, explaining this paradox. We examined the association between eIS, serum HDL CEC, and HDL subspecies in adults with T1D. This study was conducted in a sub-cohort (N=134) randomly selected from the Coronary Artery Calcification in type 1 diabetes study (N=652). eIS was calculated using a validated equation that includes waist circumference, triglycerides, adiponectin, diastolic blood pressure and insulin dose. We quantified CEC from a macrophage cell line (J774) and through the cholesterol transport proteins ABCA1 and ABCG1 and HDL particle concentration and size using calibrated ion mobility analysis. The analyzed HDLs were extra small (XS-HDL), small (S-HDL), medium (M-HDL) and large (L-HDL) populations. Associations were assessed by multivariable linear regression. J774 and ABCA1 CEC were negatively associated with eIS, as was S-HDL (Table). eIS positively associated with L-HDL, whereas other HDL metrics were not associated with eIS. Higher eIS associated with fewer S-HDL particles and reduced macrophage- and ABCA1-mediated CEC, suggesting novel interactions among insulin sensitivity and HDL metrics, which may contribute to CVD risk in T1D.
T. Buckner: None. K. Bornfeldt: None. J. Heinecke: None. T. Vaisar: Consultant; Self; MedImmune. Research Support; Self; MedImmune. J.K. Snell-Bergeon: None.
American Diabetes Association (7-13-CD-10 to J.K.S-B.)