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HDL Cholesterol Efflux Predicts Incident New-Onset Diabetes After Transplantation (NODAT) in Renal Transplant Recipients Independent of HDL Cholesterol Levels
- Source :
- Diabetes, 68(10), 1915-1923. AMER DIABETES ASSOC
- Publication Year :
- 2019
- Publisher :
- AMER DIABETES ASSOC, 2019.
-
Abstract
- In renal transplant recipients (RTRs), new-onset diabetes after transplantation (NODAT) is a frequent and serious complication limiting survival of graft and patient. However, the underlying pathophysiology remains incompletely understood. In vitro and in preclinical models, HDL can preserve β-cell function, largely by mediating cholesterol efflux, but this concept has not been evaluated in humans. This study investigated whether baseline cholesterol efflux capacity (CEC) in RTRs is associated with incident NODAT during follow-up. This prospective longitudinal study included 405 diabetes-free RTRs with a functioning graft for >1 year. During a median (interquartile range) follow-up of 9.6 (6.6–10.2) years, 57 patients (14.1%) developed NODAT. HDL CEC was quantified using incubation of human macrophage foam cells with apolipoprotein B–depleted plasma. Baseline CEC was significantly lower in patients developing NODAT during follow-up (median 6.84% [interquartile range 5.84–7.50%]) compared with the NODAT-free group (7.44% [6.46–8.60%]; P = 0.001). Kaplan-Meier analysis showed a lower risk for incident NODAT with increasing sex-stratified tertiles of HDL efflux capacity (P = 0.004). Linear regression analysis indicated that CEC is independently associated with incident NODAT (P = 0.04). In Cox regression analyses, CEC was significantly associated with NODAT (hazard ratio 0.53 [95% CI 0.38–0.76]; P < 0.001), independent of HDL cholesterol levels (P = 0.015), adiposity (P = 0.018), immunosuppressive medication (P = 0.001), and kidney function (P = 0.01). Addition of CEC significantly improved the predictive power of the Framingham Diabetes Risk Score (P = 0.004). This study establishes HDL CEC as a strong predictor of NODAT in RTRs, independent of several other recognized risk factors.
- Subjects :
- 0301 basic medicine
Adult
Male
medicine.medical_specialty
Diabetes risk
KIDNEY-TRANSPLANTATION
Endocrinology, Diabetes and Metabolism
TACROLIMUS
030209 endocrinology & metabolism
Lower risk
Gastroenterology
INSULIN-SECRETION
CAPACITY
03 medical and health sciences
chemistry.chemical_compound
MELLITUS
0302 clinical medicine
High-density lipoprotein
Postoperative Complications
BETA-CELLS
Interquartile range
Risk Factors
Diabetes mellitus
Internal medicine
Internal Medicine
medicine
Diabetes Mellitus
Humans
Longitudinal Studies
Prospective Studies
RISK
business.industry
Cholesterol
Hazard ratio
Cholesterol, HDL
GLUCOSE-METABOLISM
Middle Aged
ER STRESS
medicine.disease
Kidney Transplantation
Transplant Recipients
Transplantation
030104 developmental biology
chemistry
Female
business
HIGH-DENSITY-LIPOPROTEIN
Subjects
Details
- Language :
- English
- ISSN :
- 1939327X and 00121797
- Volume :
- 68
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Diabetes
- Accession number :
- edsair.doi.dedup.....aa5a1fc41c34ca23210ac3dcbed5d5eb