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

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.

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P1650HIGH-DENSITY LIPOPROTEIN PARTICLES AND THEIR RELATIONSHIP TO POSTTRANSPLANTATION DIABETES IN RENAL TRANSPLANT RECIPIENTS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p1650 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Sara Sokooti Oskooei ◽

Tamas Szili-Torok ◽

Jose L Flores-Guerrero ◽

Maryse C.J. Osté ◽

António W Gomes-Neto ◽

...

Keyword(s):

Renal Transplant ◽

Lower Risk ◽

Cox Regression ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

Cox Proportional Hazards ◽

Relative Mass ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Cox Regression Analysis

Abstract Background and Aims 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). Method 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. Results 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]. Conclusion 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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Characteristics of low-density and high-density lipoprotein subclasses in pediatric renal transplant recipients

Transplant International ◽

10.1111/j.1432-2277.2011.01313.x ◽

2011 ◽

Vol 24 (11) ◽

pp. 1094-1102 ◽

Cited By ~ 10

Author(s):

Aleksandra Zeljkovic ◽

Jelena Vekic ◽

Vesna Spasojevic-Kalimanovska ◽

Zorana Jelic-Ivanovic ◽

Amira Peco-Antic ◽

...

Keyword(s):

Renal Transplant ◽

High Density Lipoprotein ◽

Density Lipoprotein ◽

High Density ◽

Renal Transplant Recipients ◽

Low Density ◽

Transplant Recipients ◽

Lipoprotein Subclasses ◽

Pediatric Renal Transplant ◽

Pediatric Renal Transplant Recipients

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Abstract P175: High-density Lipoprotein Cholesterol and Mortality Prior to Age 90 in a Cohort of Male Physicians

Circulation ◽

10.1161/circ.125.suppl_10.ap175 ◽

2012 ◽

Vol 125 (suppl_10) ◽

Author(s):

Catherine Rahilly-Tierney ◽

Howard D Sesso ◽

J. Michael Gaziano ◽

Luc Djousse

Keyword(s):

High Density Lipoprotein ◽

Lower Risk ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

Cox Proportional Hazards ◽

High Density ◽

Health Study ◽

Inverse Association ◽

Cvd Mortality

BACKGROUND: Few studies have examined prospectively the relationship between baseline high-density lipoprotein (HDL) cholesterol and longevity. OBJECTIVES: We sought to examine whether higher HDL levels were associated with lower risk of all-cause, cardiovascular (CVD), and non-CVD mortality prior to age 90 in the Physicians’ Health Study (PHS). METHODS: We considered a baseline cohort of 1351 PHS participants who provided bloods between 1997 and 2001 and were old enough to reach age 90 by March 4, 2009. Included subjects had complete baseline data on HDL and total cholesterol; lifestyle factors including smoking, exercise, alcohol consumption, and BMI; and comorbidities including hypertension, diabetes mellitus, congestive heart failure, cancer, and stroke. We used Cox proportional hazards to determine the HRs and 95% CIs for all-cause, CVD, and non-CVD mortality prior to age 90, adjusting for baseline age, co-morbidities, and non-HDL cholesterol. RESULTS: At baseline, the cohort had a mean (SD) age of 81.9 (2.9) years and a mean (SD) HDL cholesterol of 44.8(16.5) mg/dL. After a mean follow-up of 6.8 years (maximum 12.3 years), 501 (37.1%) of men died prior to age 90. In multi-variable adjusted analyses, men in the highest HDL-C quartile (≥54.1 mg/dL) had a 28% lower risk (HR 0.72, 95% CI 0.55-0.95) of all-cause mortality prior to age 90 compared to men in the lowest HDL-C quartile (<32.8 mg/dL). From the lowest to highest HDL quartile, age-adjusted HR(95%CI) for CVD mortality prior to age 90 were 0.66 (0.44-0.99), 0.58 (0.38-0.90), and 0.53 (0.34-0.82) (p for trend 0.004). There was no significant association between baseline HDL cholesterol and non-CVD death. CONCLUSION: In a cohort of older male physicians with long-term follow-up, baseline HDL cholesterol was inversely associated with the risk of dying prior to age 90, largely explained by an inverse association between HDL and CVD mortality.

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Higher High Density Lipoprotein 2 (HDL2) to Total HDL Cholesterol Ratio Is Associated with a Lower Risk for Incident Hypertension

Diabetes & Metabolism Journal ◽

10.4093/dmj.2018.0053 ◽

2019 ◽

Vol 43 (1) ◽

pp. 114 ◽

Cited By ~ 1

Author(s):

You-Cheol Hwang ◽

Wilfred Y. Fujimoto ◽

Steven E. Kahn ◽

Donna L. Leonetti ◽

Edward J. Boyko

Keyword(s):

High Density Lipoprotein ◽

Lower Risk ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

High Density ◽

Incident Hypertension ◽

Cholesterol Ratio

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Alcohol Intake and Incident Myocardial Infarction: The Role of High-density Lipoprotein Cholesterol (P18-020-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz039.p18-020-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Shue Huang ◽

Zhe Huang ◽

Gregory Shearer ◽

Shanshan Li ◽

Shuohua Chen ◽

...

Keyword(s):

Myocardial Infarction ◽

Alcohol Consumption ◽

High Density Lipoprotein ◽

Lower Risk ◽

Alcohol Intake ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

High Density ◽

Penn State

Abstract Objectives The aim of this study is to test the hypothesis that the lower risk of myocardial infarction (MI) associated with alcohol intake is through its effect on raising high-density lipoprotein (HDL) cholesterol. Methods This study included 81,827 Chinese men and women (mean age: 51 ± 12 yr.) from the Kailuan Study who were free of cardiovascular disease in 2006 (at baseline) and were followed up to Dec. 2016. At baseline, alcohol consumption was assessed via a questionnaire and the concentration of HDL cholesterol was measured. Incident MI at follow up was a first MI event, confirmed by medical record review. Multivariable Cox regression was used to model the association between habitual alcohol intake and risks of MI, adjusting for potential covariates including age, sex, education, monthly income, occupation, smoking status, physical activity, body mass index, waist circumferences, hypertension, diabetes and total cholesterol. Mediated effect through HDL cholesterol was assessed using a causal mediating analysis (SAS macro). Results During an average of 9.6 years of follow-up, we documented 1095 incident cases. The adjusted hazard ratio (HR) for MI was 0.64 (95% confidence interval (CI), 0.54–0.76) for current alcohol drinkers compared with never or former. The ratio changed very slightly, to 0.65 (95% CI, 0.55–0.76) after further adjustment of HDL cholesterol concentration. Mediation analysis showed that HDL cholesterol concentrations mediated a small, non-significant proportion (1.8%) of the effect of alcohol on MI. Conclusions Alcohol consumption was associated with a lower risk for MI incidence in a large Chinese cohort. Our results suggest that the benefits associated with moderate alcohol consumption is not related to the effects of alcohol on HDL cholesterol. Funding Sources Start-up grant from Penn State College of Health and Human Development, and Penn State CyberScience Seed Grant Program.

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Low levels of high-density lipoprotein cholesterol: an independent risk factor for late adverse cardiovascular events in renal transplant recipients

Transplant International ◽

10.1111/j.1432-2277.2009.01021.x ◽

2009 ◽

Vol 23 (6) ◽

pp. 574-579 ◽

Cited By ~ 8

Author(s):

Kulpreet Barn ◽

Mark Laftavi ◽

Drew Pierce ◽

Chin Ying ◽

William E. Boden ◽

...

Keyword(s):

Risk Factor ◽

Renal Transplant ◽

High Density Lipoprotein ◽

High Density Lipoprotein Cholesterol ◽

Cardiovascular Events ◽

Independent Risk Factor ◽

Density Lipoprotein ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Low Levels

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High Density Lipoprotein Cholesterol Efflux Capacity and Atherosclerosis in Cardiovascular Disease: Pathophysiological Aspects and Pharmacological Perspectives

Cells ◽

10.3390/cells10030574 ◽

2021 ◽

Vol 10 (3) ◽

pp. 574

Author(s):

Maria Pia Adorni ◽

Nicoletta Ronda ◽

Franco Bernini ◽

Francesca Zimetti

Keyword(s):

High Density Lipoprotein ◽

Cholesterol Efflux ◽

Current Knowledge ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

High Density ◽

Current Evidence ◽

Endocrine Disorders ◽

Lifestyle Modifications ◽

Cholesterol Efflux Capacity

Over the years, the relationship between high-density lipoprotein (HDL) and atherosclerosis, initially highlighted by the Framingham study, has been revealed to be extremely complex, due to the multiple HDL functions involved in atheroprotection. Among them, HDL cholesterol efflux capacity (CEC), the ability of HDL to promote cell cholesterol efflux from cells, has emerged as a better predictor of cardiovascular (CV) risk compared to merely plasma HDL-cholesterol (HDL-C) levels. HDL CEC is impaired in many genetic and pathological conditions associated to high CV risk such as dyslipidemia, chronic kidney disease, diabetes, inflammatory and autoimmune diseases, endocrine disorders, etc. The present review describes the current knowledge on HDL CEC modifications in these conditions, focusing on the most recent human studies and on genetic and pathophysiologic aspects. In addition, the most relevant strategies possibly modulating HDL CEC, including lifestyle modifications, as well as nutraceutical and pharmacological interventions, will be discussed. The objective of this review is to help understanding whether, from the current evidence, HDL CEC may be considered as a valid biomarker of CV risk and a potential pharmacological target for novel therapeutic approaches.

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Post-Transplant Diabetes Mellitus and Prediabetes in Renal Transplant Recipients: An Update

Nephron ◽

10.1159/000514288 ◽

2021 ◽

pp. 1-13

Author(s):

Ana Elena Rodríguez-Rodríguez ◽

Esteban Porrini ◽

Mads Hornum ◽

Javier Donate-Correa ◽

Raúl Morales-Febles ◽

...

Keyword(s):

Diabetes Mellitus ◽

Renal Transplant ◽

Cell Function ◽

Cell Damage ◽

Current Evidence ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Post Transplant ◽

Β Cell Function

Post-transplant diabetes mellitus (PTDM) is a frequent and relevant complication after renal transplantation: it affects 20–30% of renal transplant recipients and increases the risk for cardiovascular and infectious events. Thus, understanding pathogenesis of PTDM would help limiting its consequences. In this review, we analyse novel aspects of PTDM, based on studies of the last decade, such as the clinical evolution of PTDM, early and late, the reversibility rate, diagnostic criteria, risk factors, including pre-transplant metabolic syndrome and insulin resistance (IR) and the interaction between these factors and immunosuppressive medications. Also, we discuss novel pathogenic factors, in particular the role of β-cell function in an environment of IR and common pathways between pre-existing cell damage and tacrolimus-induced toxicity. The relevant role of prediabetes in the pathogenesis of PTDM and cardiovascular disease is also addressed. Finally, current evidence on PTDM treatment is discussed.

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