HDL Particle Subspecies and Their Association With Incident Type 2 Diabetes: The PREVEND Study

Abstract

Background and aims High-density lipoproteins (HDL) may be protective against type 2 diabetes (T2D) development, but HDL particles vary in size and function which could lead to differential associations with incident T2D. A newly developed nuclear magnetic resonance (NMR)-derived algorithm provides concentrations for seven HDL subspecies. We aimed to investigate the association of HDL particle subspecies with incident T2D in the general population. Materials and methods Among 4828 subjects of the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study without T2D at baseline. HDL subspecies with increasing size from H1P to H7P were measured by NMR (LP4 algorithm of the Vantera NMR platform). Results 265 individuals developed T2D (median follow-up of 7.3 years). In Cox regression models, HDL size and H4P [HR per 1 SD increase 0.83 (95% CI, 0.69-0.99) and 0.85 (95% CI, 0.75-0.95), respectively] were inversely associated with incident T2D, after adjustment for relevant covariates. Oppositely, levels of H2P were positively associated with incident T2D (HR 1.15 (95% CI, 1.01-1.32)). In secondary analyses, associations with large HDL particles and H6P were modified by BMI in such a way that they were particularly associated with a lower risk of incident T2D, in subjects with BMI < 30 kg/m 2. Conclusion Greater HDL size and lower levels of H4P were associated with a lower risk, whereas higher levels of H2P were associated with a higher risk of developing T2D. In addition, large HDL particles and H6P were inversely associated with T2D in non-obese subjects.

Triglyceride-rich lipoprotein and LDL particle subfractions and their association with incident type 2 diabetes: the PREVEND study

“…Furthermore, HDL particles are able to affect β-cell function [20,73], and HDL-C makes part of established diabetic risk models [74,75]. Recently, HDL size was found to be associated with incident T2D even independent of HDL-C [26]. In the current study, we therefore adjusted HDL-C or alternatively for HDL size.…”

“…Lipoprotein parameters were measured by NMR LipoProfile ® testing at Labcorp (Morrisville, NC). NMR spectra were collected on an optimized version of the NMR LipoProfile test (LP4 algorithm) [22,26,30]. Very large, large, medium, small, and very small triglyceride rich lipoprotein particles (TRLP) and large, medium, and small LDL particles (LDLP) were quantified using the conventional deconvolution method and the amplitudes of their spectroscopically distinct lipid methyl group NMR signals [31].…”

“…By contrast, concentrations of small VLDL and large LDL particles as well as LDL size were inversely associated with incident T2D, independent of established risk factors including glucose and insulin resistance [23][24][25]. Although evidence is mounting that HDL cholesterol and HDL subfractions predict incident T2D even independent of homeostasis model assessment of insulin resistance (HOMA-IR) [26], the association of TRL and LDL particle and subfraction concentrations with β-cell function, estimated as homeostasis model assessment of β-cell function (HOMA-β) have not been determined in a population-based cohort so far.…”

Metabolomics in Diabetes and Diabetic Complications: Insights from Epidemiological Studies

“…Over the past two decades, metabolomics has been widely utilized in large epidemiological studies, and some metabolites/pathways have been identified and validated to be associated with insulin metabolism or being predictive of diabetes across different studies [ 35 ]. Table 2 summarizes the findings from some of key prospective studies [ 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 ].…”

Mahalanobis distance, a novel statistical proxy of homeostasis loss is longitudinally associated with risk of type 2 diabetes

“…Twenty-three out of the thirty-two biomarkers have already been reported to be useful in the calculation of MD as proxy of homeostasis loss (Supplemental Table 2) [16]. We replaced HDL cholesterol, used in a previous report [16], with seven HDL subspecies that have lately been reported to be differently associated with the risk of T2D [32]. Additionally, BCAA (valine, leucine, isoleucine) were included in the analysis because of their association with T2D [15], which has been shown to be causal [33].…”