Lower total and percent of high-molecular-weight adiponectin concentration in South Asian kidney transplant recipients

Prasad, G. V. Ramesh; Vorobeichik, Leon; Nash, Michelle M.; Huang, Michael; Rapi, Lindita; Maguire, Graham F.; Mamdani, Muhammad; Yan, Andrew T.; Connelly, Philip W.

doi:10.1093/ckj/sfs033

Cited by 5 publications

(5 citation statements)

References 32 publications

(37 reference statements)

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“… 16 Decreased adiponectin concentrations have been demonstrated in KTR who are ethnically already at higher risk of type 2 diabetes. 17 Adiponectin gene variants also associate with PTDM. 18 Conversely, adjusting for adiponectin did not alter the relationship between BCAA and insulin resistance in 70 subjects.…”

Section: Discussionmentioning

confidence: 99%

Plasma Branched-Chain Amino Acid Concentrations and Glucose Homeostasis in Kidney Transplant Recipients and Candidates

Prasad

Nash

Yuan

et al. 2023

Can J Kidney Health Dis

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Background: Post-transplant diabetes mellitus (PTDM) encompasses new-onset and previously unrecognized type 2 diabetes. Kidney failure masks type 2 diabetes. Branched-chain amino acids (BCAA) are closely associated with glucose metabolism. Therefore, understanding BCAA metabolism both in kidney failure and after kidney transplantation may inform PTDM mechanisms. Objective: To understand the impact of present or absent kidney function on plasma BCAA concentrations. Design: Cross-sectional study of kidney transplant recipients and kidney transplant candidates. Setting: Large kidney transplant center in Toronto, Canada. Measurements: We measured plasma BCAA and aromatic amino acid (AAA) concentrations in 45 pre-kidney transplant candidates (15 with type 2 diabetes, 30 without type 2 diabetes) and 45 post-kidney transplant recipients (15 PTDM, 30 non-PTDM), along with insulin resistance and sensitivity by 75 g oral glucose loading for those in each group without type 2 diabetes. Methods: Plasma AA concentrations were analyzed using MassChrom AA Analysis and compared between groups. The insulin sensitivity for oral glucose tolerance tests or Matsuda index (a measure of whole-body insulin resistance), Homeostatic Model Assessment for Insulin Resistance (a measure of hepatic insulin resistance), and Insulin Secretion-Sensitivity Index-2 (ISSI-2, a measure of pancreatic β-cell response) was calculated from fasting insulin and glucose concentrations, and compared with BCAA concentrations. Results: Each BCAA concentration was higher in post-transplant subjects than pre-transplant subjects ( P < .001 for leucine, isoleucine, valine). In post-transplant subjects, each BCAA concentration was higher in PTDM versus non-PTDM (odds ratio for PTDM 3-4 per 1 SD increase in BCAA concentration, P < .001 for each). Tyrosine concentrations were also higher in post-transplant subjects than pre-transplant subjects, but tyrosine did not differ by PTDM status. By contrast, neither BCAA nor AAA concentrations were different in pre-transplant subjects with or without type 2 diabetes. Whole-body insulin resistance, hepatic insulin resistance, and pancreatic β-cell response did not differ between nondiabetic post-transplant and pre-transplant subjects. Branched-chain amino acid concentrations correlated with the Matsuda index and Homeostatic Model Assessment for Insulin Resistance ( P < .05 for each) only in nondiabetic post-transplant subjects—not in nondiabetic pre-transplant subjects. Branched-chain amino acid concentrations did not correlate with ISSI-2 in either pre-transplant or post-transplant subjects. Limitations: The sample size was small, and subjects were not studied prospectively for the development of type 2 diabetes. Conclusions: Plasma BCAA concentrations are higher post-transplant in type 2 diabetic states, but do not differ by diabetes status in the presence of kidney failure. The association of BCAA with measures of hepatic insulin resistance among nondiabetic post-transplant patients is consistent with impaired BCAA metabolism as a characteristic of kidney transplantation.

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Section: Discussionmentioning

confidence: 99%

Plasma Branched-Chain Amino Acid Concentrations and Glucose Homeostasis in Kidney Transplant Recipients and Candidates

Prasad

Nash

Yuan

et al. 2023

Can J Kidney Health Dis

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“…A total of 60 Caucasian males, 30 South Asian males, 26 Caucasian females, and 13 South Asian females were studied, slightly exceeding the study design target sample of 120 subjects. A complete description of the subjects can be found in Prasad et al [ 2 ].…”

Section: Methodsmentioning

confidence: 99%

“…The current study was designed to compare two novel risk factors, adiponectin and paraoxonase 1 (PON1), as candidates for differing risk between South Asian and Caucasian KTR. We observed significantly lower total and high molecular weight adiponectin in South Asian KTR [ 2 ]. Stage 3 chronic renal disease, defined as cystatin C-based estimated glomerular filtration rate (eGFR) less than 60, was associated with lower PON1 mass in subjects with diabetes [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Paraoxonase 1 Phenotype and Mass in South Asian versus Caucasian Renal Transplant Recipients

et al. 2012

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South Asian renal transplant recipients have a higher incidence of cardiovascular disease compared with Caucasian renal transplant recipients. We carried out a study to determine whether paraoxonase 1, a novel biomarker for cardiovascular risk, was decreased in South Asian compared with Caucasian renal transplant recipients. Subjects were matched two to one on the basis of age and sex for a total of 129 subjects. Paraoxonase 1 was measured by mass, arylesterase activity, and two-substrate phenotype assay. Comparisons were made by using a matched design. The frequency of PON1 QQ, QR and RR phenotype was 56%, 37%, and 7% for Caucasian subjects versus 35%, 44%, and 21% for South Asian subjects (χ 2 = 7.72, P = 0.02). PON1 mass and arylesterase activity were not significantly different between South Asian and Caucasian subjects. PON1 mass was significantly associated with PON1 phenotype (P = 0.0001), HDL cholesterol (P = 0.009), LDL cholesterol (P = 0.02), and diabetes status (P < 0.05). Arylesterase activity was only associated with HDL cholesterol (P = 0.003). Thus the frequency of the PON1 RR phenotype was higher and that of the QQ phenotype was lower in South Asian versus Caucasian renal transplant recipients. However, ethnicity was not a significant factor as a determinant of PON1 mass or arylesterase activity, with or without analysis including PON1 phenotype. The two-substrate method for determining PON1 phenotype may be of value for future studies of cardiovascular complications in renal transplant recipients.

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“…The correlation between decreased adiponectin and increased insulin resistance is particularly strong for SA[ 100 ]. Both total and high molecular weight adiponectin levels are lower in SA KTR[ 101 ]. KTR with metabolic syndrome have significantly lower serum adiponectin levels than those without metabolic syndrome.…”

Section: Individual Cardiovascular Risk Factorsmentioning

confidence: 99%

Managing cardiovascular disease risk in South Asian kidney transplant recipients

Prasad¹,

Bhamidi²

2021

WJT

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South Asians (SA) are at higher cardiovascular risk than other ethnic groups, and SA kidney transplant recipients (SA KTR) are no exception. SA KTR experience increased major adverse cardiovascular events both early and late post-transplantation. Cardiovascular risk management should therefore begin well before transplantation. SA candidates may require aggressive screening for pre-transplant cardiovascular disease (CVD) due to their ethnicity and comorbidities. Recording SA ethnicity during the pre-transplant evaluation may enable programs to better assess cardiovascular risk, thus allowing for earlier targeted peri- and post-transplant intervention to improve cardiovascular outcomes. Diabetes remains the most prominent post-transplant cardiovascular risk factor in SA KTR. Diabetes also clusters with other metabolic syndrome components including lower high-density lipoprotein cholesterol, higher triglycerides, hypertension, and central obesity in this population. Dyslipidemia, metabolic syndrome, and obesity are all significant CVD risk factors in SA KTR, and contribute to increased insulin resistance. Novel biomarkers such as adiponectin, apolipoprotein B, and lipoprotein (a) may be especially important to study in SA KTR. Focused interventions to improve health behaviors involving diet and exercise may especially benefit SA KTR. However, there are few interventional clinical trials specific to the SA population, and none are specific to SA KTR. In all cases, understanding the nuances of managing SA KTR as a distinct post-transplant group, while still screening for and managing each CVD risk factor individually in all patients may help improve the long-term success of all kidney transplant programs catering to multi-ethnic populations.

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Lower total and percent of high-molecular-weight adiponectin concentration in South Asian kidney transplant recipients

Cited by 5 publications

References 32 publications

Plasma Branched-Chain Amino Acid Concentrations and Glucose Homeostasis in Kidney Transplant Recipients and Candidates

Plasma Branched-Chain Amino Acid Concentrations and Glucose Homeostasis in Kidney Transplant Recipients and Candidates

Paraoxonase 1 Phenotype and Mass in South Asian versus Caucasian Renal Transplant Recipients

Managing cardiovascular disease risk in South Asian kidney transplant recipients

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