Although it has long been proposed that HDL is dysfunctional in type 1 diabetes (T1D), this hypothesis has not been formally tested in large cohorts using validated functional and biochemical HDL metrics. We therefore determined whether HDL particle concentration (HDL-P) and function differed between 187 middle-aged adults with childhood-onset T1D (mean age 51 years, T1D duration 43 years, 53% women) and 200 individuals with normal glucose tolerance (NGT) of similar age and sex distribution. HDL-P was assessed by calibrated ion mobility analysis. HDL function, i.e., serum HDL cholesterol efflux capacity, was quantified in J774 cells using a validated assay. Separate stepwise linear regression models were constructed for each HDL metric, allowing for T1D status and potential confounding factors, including HDL cholesterol (HDL-C). The presence of significant effect modification by sex was evaluated. After adjustment, the concentrations of total (T-HDL-P; β=-0.44, p=0.09) and medium-sized (M-HDL-P; β=-0.84, p<0.0001) HDL particles were lower in the T1D compared with the NGT group. In contrast, T1D status was not significantly associated with small (S-HDL-P) and large-sized (L-HDL-P) HDL-P. A significant sex by T1D status interaction term was observed for M-HDL-P (p=0.03), indicating that women had higher M-HDL-P only in NGT; M-HDL-P did not differ by sex in T1D. Moreover, a marginally significant sex by T1D status interaction was observed for L-HDL (p=0.08), suggesting that women had higher L-HDL-P only in T1D. Unexpectedly, serum HDL cholesterol efflux capacity was higher in the T1D compared with the NGT group (β=0.29, p<0.0001).

In conclusion, lower levels of T-HDL-P and M-HDL-P in T1D may explain in part the higher cardiovascular risk in T1D, as these metrics were recently shown to be associated with protection from vascular complications. The lack of a difference in M-HDL-P by sex in T1D may contribute to the loss of cardioprotection associated with female sex.


T. Costacou: None. T. Vaisar: Consultant; Self; AstraZeneca. J. Ju: None. K. Bornfeldt: None. T.J. Orchard: None. J. Heinecke: None.


National Institutes of Health (HL130153, DK34818)

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