High-Density Lipoprotein Particles and Their Relationship to Posttransplantation Diabetes Mellitus in Renal Transplant Recipients.

Sara Sokooti,Jenny E Kootstra-Ros,Jose L Flores-Guerrero,Maryse C J Osté,Stephan J L Bakker,Tamas Szili-Torok,Hiddo J.L Heerspink,Margery A Connelly,Robin P F Dullaart,António W Gomes-Neto

doi:10.3390/biom10030481

Abstract

High concentrations of high-density lipoprotein (HDL) cholesterol are likely associated with a lower risk of posttransplantation diabetes mellitus (PTDM). However, HDL particles vary in size and density with yet unestablished associations with PTDM risk. The aim of our study was to determine the association between different HDL particles and development of PTDM in renal transplant recipients (RTRs). We included 351 stable outpatient adult RTRs without diabetes at baseline evaluation. HDL particle characteristics and size were measured by nuclear magnetic resonance (NMR) spectroscopy. During 5.2 (IQR, 4.1‒5.8) years of follow-up, 39 (11%) RTRs developed PTDM. In multivariable Cox regression analysis, levels of HDL cholesterol (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.40–0.94 per 1SD increase; p = 0.024) and of large HDL particles (HR 0.68, 95% CI 0.50–0.93 per log 1SD increase; p = 0.017), as well as larger HDL size (HR 0.58, 95% CI 0.36–0.93 per 1SD increase; p = 0.025) were inversely associated with PTDM development, independently of relevant covariates including, age, sex, body mass index, medication use, transplantation-specific parameters, blood pressure, triglycerides, and glucose. In conclusion, higher concentrations of HDL cholesterol and of large HDL particles and greater HDL size were associated with a lower risk of PTDM development in RTRs, independently of established risk factors for PTDM development.

Highlights

Posttransplantation diabetes mellitus (PTDM) is one of the major complications following renal transplantation
The distribution of high-density lipoprotein (HDL) particles is altered from large HDL particles which are rich in cholesteryl esters to small HDL particles in type 2 diabetes mellitus (T2DM) [18]
Among HDL particles, measured by nuclear magnetic resonance (NMR) spectroscopy, lower levels of large HDL particles and smaller HDL particle size were associated with the development of insulin resistance and T2DM, often independently of typical diabetes risk factors [19,20,21,22,23]

Summary

Introduction

Posttransplantation diabetes mellitus (PTDM) is one of the major complications following renal transplantation. There are similarities between the pathogenesis of PTDM and type 2 diabetes mellitus (T2DM) [6] Alternations in both insulin secretion and insulin resistance may be considered as risk factor for developing PTDM [7]. HDL particles vary in size, density, and function, causing various HDL particles to differ in their associations with insulin secretion, resistance, and incident diabetes [14,15]. Among HDL particles, measured by nuclear magnetic resonance (NMR) spectroscopy, lower levels of large HDL particles and smaller HDL particle size were associated with the development of insulin resistance and T2DM, often independently of typical diabetes risk factors [19,20,21,22,23]

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