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

Abstract

Background Triglyceride-rich lipoproteins particles (TRLP) and low density lipoprotein particles (LDLP) vary in size. Their association with β-cell function is not well described. We determined associations of TRLP and LDLP subfractions with β-cell function, estimated as HOMA-β, and evaluated their associations with incident T2D in the general population. Methods We included 4818 subjects of the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study without T2D at baseline. TRLP and LDLP subfraction concentrations and their average sizes were measured using the LP4 algorithm of the Vantera nuclear magnetic resonance platform. HOMA-IR was used as measure of insulin resistance. HOMA-β was used as a proxy of β-cell function. Results In subjects without T2D at baseline, very large TRLP, and LDL size were inversely associated with HOMA-β, whereas large TRLP were positively associated with HOMA-β when taking account of HOMA-IR. During a median follow-up of 7.3 years, 263 participants developed T2D. In multivariable-adjusted Cox regression models, higher concentrations of total, very large, large, and very small TRLP (reflecting remnants lipoproteins) and greater TRL size were associated with an increased T2D risk after adjustment for relevant covariates, including age, sex, BMI, HDL-C, HOMA-β, and HOMA-IR. On the contrary, higher concentrations of large LDLP and greater LDL size were associated with a lower risk of developing T2D. Conclusions Specific TRL and LDL particle characteristics are associated with β-cell function taking account of HOMA-IR. Moreover, TRL and LDL particle characteristics are differently associated with incident T2D, even when taking account of HOMA-β and HOMA-IR.

Profoundly Disturbed Lipoproteins in Cirrhotic Patients: Role of Lipoprotein-Z, a Hepatotoxic LDL-like Lipoprotein

“…Despite many studies on lipoprotein abnormalities in severe chronic liver disease, no data have been currently reported concerning nuclear magnetic resonance (NMR)-determined alterations in lipoprotein subfractions in patients with liver cirrhosis or in OLT recipients. Availability of such data is clinically relevant in view of differential associations of LDL, VLDL, and HDL subfractions and particle concentrations with incident atherosclerotic cardiovascular disease and T2D [ 26 , 27 , 28 , 29 , 30 , 31 , 32 ]. Of particular relevance, an abnormal LDL-like lipoprotein, designated Lipoprotein-Z (LP-Z), has been recently characterised using NMR methodology [ 33 ].…”

Lipoprotein particle sizes and incident type 2 diabetes: the PREVEND cohort study

“…We have reported that, in the Prevention of Renal and Vascular End-Stage Disease (PREVEND) cohort, TRL size was positively associated, whereas LDL size was inversely associated, with incident type 2 diabetes [ 3 ]. Notably, in the same population, we also found that HDL particle size and the concentration of large HDL particles were both inversely associated with incident type 2 diabetes [ 4 ], consistent with a protective effect of HDL on beta cell function [ 5 ].…”

“…Here, we present novel data from our recent studies [ 3 , 4 ], aiming to investigate whether, and to what extent, the size of TRL, LDL and HDL particles, and the ratios and combinations of these lipoprotein particle sizes, are independently associated with incident type 2 diabetes. Furthermore, we question whether the addition of LDL and/or HDL size to risk prediction models improves type 2 diabetes risk prediction over the inclusion of TRL size alone.…”

“…After exclusion of participants with missing data, a total of 4818 participants of the PREVEND study without type 2 diabetes at baseline were included in this study [ 3 , 4 ]. After a median follow-up of 7.3 years, 263 participants had developed type 2 diabetes, which was determined if one or more of the following criteria were met: (1) fasting plasma glucose (FPG) ≥7.0 mmol/l; (2) random sample plasma glucose ≥11.1 mmol/l; (3) self-report of a physician diagnosis of type 2 diabetes; and (4) initiation of glucose-lowering medication use, retrieved from a central pharmacy registry.…”

“…After an overnight fast, EDTA anti-coagulated plasma samples were obtained, and lipoprotein variables were measured by NMR LipoProfile testing at Labcorp (Morrisville, NC, USA). Lipoprotein variables were reported using an optimised version of the NMR LipoProfile test (LP4 algorithm) [ 3 , 4 , 6 ]. Mean TRL, LDL and HDL sizes were calculated using the weighted mean derived from the sum of the diameters of each subfraction.…”