Abstract
It is established that high concentrations of High-Density Lipoprotein (HDL) are associated with low risk of type 2 diabetes and posttransplantation diabetes mellitus (PTDM). However, HDL particles vary by size, density, and biological action. The aim of our study was to determine the association between different HDL particles with the development of PTDM in renal transplant recipients (RTRs).
We included 351 stable outpatient adult RTR with a functioning graft ≥1 year from the Tranplantlines Food and Nutrition Study(NCT02811835). HDL particle concentration and size were measured by 1H-NMR spectroscopy using a Vantera® NMR Clinical Analyzer (LabCorp, Raleigh, NC). HDL size was weighted averages derived from the sum of the diameter of each subclass multiplied by its relative mass percentage. Estimated ranges of HDL diameter for the HDL subclasses were as follows: large HDL particles, 9.6–13 nm; medium HDL particles, 8.1–9.5 nm; and small HDL particles, 7.4–8.0 nm. PTDM was defined according the American Diabetes Association’s diagnostic criteria for diabetes. Multivariable-adjusted Cox proportional-hazards regression analyses were performed to assess the prospective association of HDL particles with PTDM.
During 5.2 (IQR, 4.1–5.8) years of follow-up, 39 (11%) RTR developed PTDM. In a multivariable Cox regression analysis, higher HDL cholesterol was associated with a lower risk of PTDM development, after adjustment for age, sex and BMI (hazard ratio[HR] 0.55, 95% CI 0.36-0.83 per 1SD mg/dL; P=0.005). Moreover, among different HDL indices; HDL size, and large HDL were inversely associated with PTDM, after adjustment for age, sex, and BMI ([ HR 0.48, 95% CI 0.31-0.76 per 1SD nm; P=0.002], and [HR 0.63, 95% CI 0.47-0.84 per 1SD µmol/L; P=0.002], respectively ). However medium HDL and small HDL were not associated with risk of developing PTDM ([ HR 0.88, 95% CI 0.64-1.23 per 1SD µmol/L; P=0.48], and [HR 1.14, 95% CI 0.85-1.52 per µmol/L; P=0.37], respectively ). In additional models, the association remained significant for HDL cholesterol, HDL size, and large HDL after adjustment for other confounders including, the lifestyle, use of medication, kidney function and transplantation-specific parameters. In the last model after adjustment for age, sex, BMI, triglycerides, systolic blood pressure, and fasting plasma glucose, association were similar for HDL cholesterol, HDL size, and large HDL ([ HR 0.61, 95% CI 0.40-0.94 per 1SD mg/dL; P=0.024], [HR 0.58, 95% CI 0.36-0.93 per 1SD nm; P=0.025], and [HR 0.68, 95% CI 0.50-0.93 per 1SD µmol/L; P=0.017].
In this study, we found that higher concentrations of HDL cholesterol, large HDL, and higher HDL size were associated with a lower risk of developing PTDM in RTRs, independent of established risk factors for PTDM development.
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