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

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

doi:10.3390/biom10030481

Cited by 9 publications

(9 citation statements)

References 66 publications

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“…Furthermore, the association between the larger subspecies H6P and H7P and incident T2D were independent of metabolic factors but not of HOMA-IR, triglycerides, and LDL-C. In comparison, we recently documented an inverse association of H6P with development of posttransplantation diabetes in renal transplant recipients ( 22 ).…”

Section: Discussionmentioning

confidence: 92%

“…Lipoprotein parameters were measured by NMR spectroscopy at LabCorp (Morrisville, NC, formerly LipoScience) using an optimized version of the NMR LipoProfile test (LP4 algorithm) on plasma EDTA specimens ( 20 , 22 , 33 ). Total cholesterol, triglycerides, and HDL cholesterol (HDL-C) were measured using Vantera Clinical NMR Analyzer platform using Partial Least-Squares (PLS) regression models.…”

Section: Methodsmentioning

confidence: 99%

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

Sokooti

Flores‐Guerrero

Kieneker

et al. 2021

The Journal of Clinical Endocrinology &Amp; Metabolism

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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.

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Section: Discussionmentioning

confidence: 92%

Section: Methodsmentioning

confidence: 99%

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

Sokooti

Flores‐Guerrero

Kieneker

et al. 2021

The Journal of Clinical Endocrinology &Amp; Metabolism

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“…Lipoprotein parameters were measured by NMR spectroscopy at Labcorp on plasma EDTA specimens [ 43 , 44 , 45 ]. Total cholesterol, HDL-C, triglycerides, apoB, and apoA-I were measured employing the LP4 algorithm [ 29 , 30 , 46 ]. The %CV for apoB ranges from 1.1 to 2.4 and for apoA-I ranges from 1.4 to 2.2.…”

Section: Methodsmentioning

confidence: 99%

“…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 ].…”

Section: Introductionmentioning

confidence: 99%

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

Berg

Flores‐Guerrero

Gruppen

et al. 2022

JCM

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Detailed information regarding lipoprotein concentrations and subfractions in cirrhotic patients before and after orthotopic liver transplantation (OLT) is lacking. Lipoprotein-Z (LP-Z) is a recently characterised abnormal, hepatotoxic free cholesterol-rich low-density lipoprotein (LDL)-like lipoprotein. We determined the lipoprotein profiles, including LP-Z, in cirrhotic patients and OLT recipients and assessed the prognostic significance of LP-Z on the OLT waiting list. We performed analyses in cirrhotic transplant candidates and non-cirrhotic OLT recipients. A population-based cohort was used as reference. The setting was a University hospital. Lipoprotein particle concentrations and subfractions were measured by nuclear magnetic resonance spectroscopy. In the cirrhotic patients (N = 130), most measures of triglyceride-rich lipoproteins (TRL), LDL, and high-density lipoproteins (HDL) were much lower compared to the OLT recipients (N = 372) and controls (N = 6027) (p < 0.01). In the OLT recipients, many lipoprotein variables were modestly lower, but HDL-cholesterol, triglycerides, and TRL and HDL size were greater vs. the control population. LP-Z was measurable in 40 cirrhotic patients and 3 OLT recipients (30.8% vs. 0.8%, p < 0.001). The cirrhotic patients with measurable LP-Z levels had profoundly lower HDL-cholesterol and particle concentrations (p < 0.001), and worse Child Pugh Turcotte classifications and MELD scores. The presence of LP-Z (adjusted for age, sex, and MELD score) predicted worse survival in cirrhotic patients (HR per 1 LnSD increment: 1.11, 95%CI 1.03–1.19, p = 0.003). In conclusion, cirrhotic patients have considerably lower plasma concentrations of all major lipoprotein classes with changes in lipoprotein subfraction distribution. After OLT, these lipoprotein abnormalities are in part reversed. LP-Z is associated with cirrhosis. Its presence may translate in disturbed HDL metabolism and worse survival.

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“…Serum creatinine was measured by using an enzymatic isotope dilution assay, traceable on mass spectrometry, on a Roche P-Modulator automated analyzer (Roche Diagnostics, Basel, Switzerland), and kidney function was assessed by using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula for creatinine in order to calculate the estimated glomerular filtration rate (eGFR) [31]. HDL-cholesterol was derived from lipoprotein measures assessed on a Vantera Clinical NMR Analyzer platform [32]. Other serum and urine variables were assessed using standard laboratory methods.…”

Section: Clinical Parametersmentioning

confidence: 99%

Low Circulating Concentrations of Very Long Chain Saturated Fatty Acids Are Associated with High Risk of Mortality in Kidney Transplant Recipients

et al. 2021

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Kidney transplant recipients (KTR) are at increased risk of mortality, particularly from infectious diseases, due to lifelong immunosuppression. Although very long chain saturated fatty acids (VLSFA) have been identified as crucial for phagocytosis and clearance of infections, their association with mortality in immunocompromised patient groups has not been studied. In this prospective cohort study we included 680 outpatient KTR with a functional graft ≥1 year and 193 healthy controls. Plasma VLSFA (arachidonic acid (C20:0), behenic acid (C22:0) and lignoceric acid (C24:0)) were measured by gas chromatography coupled with a flame ionization detector. Cox regression analyses was used to prospectively study the associations of VLSFA with all-cause and cause-specific mortality. All studied VLSFA were significantly lower in KTR compared to healthy controls (all p < 0.001). During a median (interquartile range) follow-up of 5.6 (5.2–6.3) years, 146 (21%) KTR died, of which 41 (28%) died due to infectious diseases. In KTR, C22:0 was inversely associated with risk of all-cause mortality, with a HR (95% CI) per 1-SD-increment of 0.79 (0.64–0.99), independent of adjustment for potential confounders. All studied VLSFA were particularly strongly associated with mortality from infectious causes, with respective HRs for C20:0, C22:0 and C24:0 of 0.53 (0.35–0.82), 0.48 (0.30–0.75), and 0.51 (0.33–0.80), independent of potential confounders. VLSFA are inversely associated with infectious disease mortality in KTR after adjustment, including HDL-cholesterol. Further studies are needed to assess the effect of VLSFA-containing foods on the risk of infectious diseases in immunocompromised patient groups.

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

Cited by 9 publications

References 66 publications

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

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

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

Low Circulating Concentrations of Very Long Chain Saturated Fatty Acids Are Associated with High Risk of Mortality in Kidney Transplant Recipients

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