Recent evidence suggests that HDL particle concentration (HDL-P) and cholesterol efflux capacity (CEC) are better predictors of coronary artery disease than HDL-C in type 1 diabetes (T1D) . We hypothesized that these novel HDL markers also predict all-cause mortality better than HDL-C in T1D. HDL-P (calibrated ion mobility analysis) and CEC (validated cell-based assay) were quantified in the first available stored sample from 550 Epidemiology of Diabetes Complications study participants with childhood onset (<17 years) T1D (baseline mean age 27.8 years and T1D duration, 19.6 years) . Vital status was assessed as of September 30, 2019. During a median follow-up of 26 years, there were 167 deaths. At analytic baseline, deceased were older, with longer T1D duration and a worse cardiovascular risk factor profile compared with survivors. In Cox proportional hazards models, after multivariable adjustments including for HDL-C, the concentration of total HDL-P (T-HDL-P, HR=0.90, 95% CI: 0.84-0.96) and that of three of the four major HDL subpopulations - extra small (XS-HDL-P, HR=0.44, 0.21-0.90) , small (S-HDL-P, HR=0.74, 0.60-0.93) and medium (M-HDL-P, HR=0.80, 0.70-0.91) particles - were associated with a lower mortality risk. Marginal protective associations were also observed for the concentration of large-sized particles (L-HDL-P, HR=0.84, 0.68-1.06) , as well as for CEC (HRs per SD was 0.86 (0.74-1.00) and 0.86 (0.73-1.01) for overall J774 and ABCA1-specific CEC, respectively) . These results remained largely unchanged by further adjustment for HDL-P (in the case of HDL-C and CEC) or APOA1 and triglyceride concentrations (for HDL-P) and were similar by sex. HDL-C was not a significant predictor of mortality in either univariate or multivariable analyses. Our findings show that higher HDL-P concentrations are negatively associated with mortality in T1D independent of other risk factors.
T.Costacou: None. R.G.Miller: Stock/Shareholder; Becton, Dickinson and Company. T.J.Orchard: None. T.Vaisar: Consultant; AstraZeneca.
National Institutes of Health (R01HL130153 and R01DK034818) and the Rossi Memorial Fund.