scholarly journals Association of leukocyte telomere length with chronic kidney disease in East Asians with type 2 diabetes: A Mendelian randomization study

2021 ◽  
Author(s):  
Resham L Gurung ◽  
Rajkumar Dorajoo ◽  
Yiamunaa M ◽  
Ling Wang ◽  
Sylvia Liu ◽  
...  

Abstract Background Chronic kidney disease (CKD) is common among type 2 diabetes (T2D) and increases the risk of kidney failure and cardiovascular diseases. Shorter leukocyte telomere length is associated with CKD in patients with T2D. We previously reported single nucleotide polymorphisms (SNPs) associated with leukocyte telomere length in Asian population. In this study, we elucidated the association of these SNPs with CKD in patients with T2D using Mendelian randomization (MR) approach. Methods The cross-sectional association of 16 leukocyte telomere length SNPs with CKD, defined as an estimated glomerular filtration rate of less than 60 ml/min/1.73m2 was assessed among 4,768 (1,628 cases, 3,140 controls) participants in the Singapore Study of Macro-angiopathy and Micro-vascular Reactivity in Type 2 Diabetes and Diabetic Nephropathy cohorts. MR analysis was performed using the random-effect inverse-variance weighted (IVW) method, the weighted median, MR-Egger and Radial MR adjusted for age and sex-stratified by cohorts and ethnicity (Chinese and Malays), then meta-analysed. Results Genetically determined shorter leukocyte telomere length was associated with increased risk of CKD in patients with T2D (meta-IVW adjusted odds ratio = 1.51 [95% confidence interval, 1.12 - 2.12; P = 0.007; Phet= 0.547]). Similar results were obtained following sensitivity analysis. MR-Egger analysis (intercept) suggested no evidence of horizontal pleiotropy (β  =  0.010, P = 0.751). Conclusions Our findings suggest that genetically determined leukocyte telomere length is associated with CKD in patients with T2D. Further studies are warranted to elucidate the causal role of telomere length in CKD progression.

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1467-1467
Author(s):  
Andrew Odegaard ◽  
David Jacobs ◽  
Lyn Steffen ◽  
Casey Rebholz ◽  
Katherine Tucker ◽  
...  

Abstract Objectives Diet beverages are calorie free beverages sweetened with non-nutritive sweeteners. People with diabetes are the highest per-capita consumers of diet beverages, tending to consume them as a replacement for sugar sweetened beverages. This behavior is endorsed by dietetic and scientific organizations and diet beverages are marketed synonymously with better health. The underlying concern is the lack of data to support or refute this concept. To begin addressing this gap we examined the association between diet beverage intake and incident chronic kidney disease (CKD) in a population at high risk for CKD. Methods We pooled data from the Atherosclerosis Risk in Communities study (years 1987–2014), Cardiovascular Health Study (1989–2014), Jackson Heart Study (2000–2012), and Multi-Ethnic Study of Atherosclerosis (2000–2013) to conduct a prospective study of the association of diet beverage intake with the incidence of CKD among participants with clinically ascertained type 2 diabetes (T2D) without prevalent CKD and with valid dietary data (n = 3250). CKD was defined using serum creatinine to define estimated glomerular filtration (eGFR) via the CKD-EPI creatinine equation. Incident CKD was defined as (eGFR <60 ml/min/1.73 m2). We carried out a 2-step meta-analysis using individual level, cohort-specific regression analyses with identical adjustment for demographic, lifestyle, overall diet quality (Alternative Healthy Eating Index), energy intake, and clinical risk factors (baseline eGFR, total cholesterol, blood pressure, fasting glucose) to generate effect estimates that were pooled together using fixed and random effects meta-analysis. Results 1018 participants developed CKD during follow-up. There was a positive association between diet beverage intake and risk of CKD. Compared to individuals reporting no intake of diet beverages, those consuming >0 and <1 diet beverage per day had a pooled relative risk and 95% confidence interval (RR, 95% CI) of 1.03 (0.87–1.22) and those consuming ≥1 beverage per day had a pooled RR (95% CI) of 1.20 (1.02–1.41). Conclusions Diet beverage intake was associated with an increased risk of CKD in a diverse population with T2D. These results suggest the need to further examine the role of diet beverages in this high risk population. Funding Sources AHA.


2016 ◽  
Vol 62 (5) ◽  
pp. 11-12
Author(s):  
Anna V. Zheleznyakova ◽  
Olga K. Vikulova ◽  
Svetlana A. Savelyeva ◽  
Valeriy V. Nosikov ◽  
Marina V. Shestakova

Background. Chronic kidney disease is one of the most serious diabetic complications, which end-stage leads to a dramatic decline of renal function and needs for renal replacement therapy. Due to the progressive nature of CKD and the limited efficacy of treatment for advanced stages the prediction of risks and diagnostics on preclinical stage are of great importance. All of the above determines the high relevance of search for genetic markers predict the chronic kidney disease (CKD) development.The aim of our study was to investigate association between polymorphic marker (PM) of gene involved in insulin secretion with development of CKD in type 2 diabetic (T2D) patients. Polymorphism of KCNJ11 gene is associated with different phenotypes of glycemic disorders: neonatal diabetes, hyperinsulinemia, reduced insulin secretion and increased risk of type 2 diabetes. This gene coding Kir6.2 subunit of ATP-dependent potassium channels. The pathogenesis of it’s involvement in renal damage development referred to the fact that this type of potassium channels found not only in the beta- cells, but also in smooth muscle cells of blood vessels, and therefore might have an effect on risk of vascular complications, including CKD.Materials and methods. We enrolled 444 T2D patients. PM rs5219 in KCNJ11 gene was analysed among patients divided in 2 groups: with and without CKD (n=123/321) based on glomerular filtration rate (GFR) < and ≥ 60 ml/min/1,73m2 calculated by MDRD formula. PM studied using PCR. Differences in alleles/genotypes frequencies were assessed by χ² and odds ratio (OR) were calculated. The study was approved by local ethical committee; informed concern was obtained from all the patients.Results. We studied the main clinical parameters: age, HbA1c, serum levels of cholesterol and triglycerides, BP between the groups. We observed significant differences in alleles/genotypes distribution of rs5219 in KCNJ11 gene between groups with and without CKD: the prevalence of allele C and genotype CC in patients without CKD: OR=0,53, 95%CI: 0,40-0,72 and OR=0,46, 95%CI: 0,27-0,79, respectively; while allele T and genotype TT did as risk factors: χ²=17,33; р=0,0002; OR=1,87, 95%CI: 1,39-2,53; genotype TT OR=2,39, 95%CI: 1,52-3,76.Conclusions. We conclude that T2D patients might have genetic susceptibility to CKD development caused by polymorphism rs5219 of KCNJ11 gene with protective role of allele C and genotype CC and risk allelе/genotype is T/TT.


2019 ◽  
Vol 51 (4) ◽  
pp. 707-712
Author(s):  
I-Kuan Wang ◽  
Tsung-Hsun Tsai ◽  
Yi-Chih Hung ◽  
Tzu-Yuan Wang ◽  
Tzung-Hai Yen ◽  
...  

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
William P. Martin ◽  
Colm Tuohy ◽  
Alison Doody ◽  
Sabrina Jackson ◽  
Ronan J. Canavan ◽  
...  

Abstract Identification of people with diabetes and chronic kidney disease at high-risk of early mortality is a priority to guide intensification of therapy. We aimed to investigate the complementary prognostic value of baseline urine albumin-to-creatinine ratio (uACR) and plasma soluble tumour necrosis factor receptor-1 (sTNFR1) with respect to early mortality and renal functional decline in a population with type 2 diabetes and advanced chronic kidney disease. We measured plasma sTNFR1 in people with type 2 diabetes (HbA1c ≥ 48 mmol/mol) at 2 hospital sites in Dublin between October 15th, 2014 and July 17th, 2015. In a subgroup of patients with advanced chronic kidney disease at baseline (estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/BSA) (n = 118), we collected clinical and longitudinal laboratory data to investigate relationships between sTNFR1 and renal and mortality endpoints by multivariable linear mixed-effects models and Cox proportional hazards regression models. The cohort was 64% male and 97% Caucasian. Mean age was 74 years, with a median type 2 diabetes duration of 16 years. Mean CKD-EPI eGFR was 42 mL/min/BSA and median [IQR] uACR was 3 [11] mg/mmol. Twenty-three (39%) people in quartiles 3 and 4 for plasma sTNFR1 died over 4-year follow-up. After adjustment for clinical variables, annual CKD-EPI eGFR decreased by − 0.56 mL/min/BSA/year for each logarithm unit increase in baseline uACR, corresponding to an annual loss of renal function of 3% per year. Furthermore, elevated uACR, but not sTNFR1, increased the risk of ≥ 40% decline in CKD-EPI eGFR (HR 1.5, p = 0.001) and doubling of serum creatinine (HR 2.0, p < 0.001). Plasma sTNFR1 did not predict a more negative trajectory in eGFR slope. However, for those people in quartiles 3 and 4 for plasma sTNFR1, an increased risk of incident mortality was detected (HR 4.9, p = 0.02). No such association was detected for uACR. In this elderly cohort of patients with type 2 diabetes and chronic kidney disease, sTNFR1 predicted short-to-medium term mortality risk but not risk of progressive renal functional decline. In contrast, parallel assessment of uACR predicted renal functional decline but not mortality, highlighting the complementary prognostic information provided by both parameters.


2021 ◽  
Author(s):  
Da Hea Seo ◽  
Young Ju Suh ◽  
Yongin Cho ◽  
Seong Hee Ahn ◽  
Seongha Seo ◽  
...  

Abstract The causal relationship between low muscle mass and development of chronic kidney disease (CKD) is uncertain in patients with type 2 diabetes mellitus (T2DM). We aimed to investigate the association between low muscle mass or sarcopenic obesity and the risk of incident CKD in patients with T2DM. A total of 3,123 patients with T2DM with preserved renal function were followed up for incident CKD. Skeletal muscle mass was estimated from bioelectrical impedance analysis. CKD was defined as an estimated glomerular filtration rate < 60 mL/min/1.73m2. Sarcopenic obesity was defined as the coexistence of sarcopenia and abdominal obesity. During 8.9 years of follow-up, 530 (17.0%) patients developed incident CKD. When subjects were divided into three groups based on sex-specific tertiles, lower muscle mass was not associated with an increased risk of incident CKD after adjustment for risk factors. However, when patients were divided into four groups according to the presence of sarcopenia and obesity, sarcopenic obesity was associated with an increased risk of incident CKD (adjusted hazard ratio 1.77; 95% confidence interval 1.24-2.51; p=0.001) compared to the other groups. Sarcopenic obesity, but not low muscle mass alone, may increase the risk of CKD in patients with T2DM.


Diabetes ◽  
2021 ◽  
Vol 70 (Supplement 1) ◽  
pp. 404-P
Author(s):  
DA HEA SEO ◽  
YONGIN CHO ◽  
SEONG HEE AHN ◽  
SEONG HA SEO ◽  
SEONGBIN HONG ◽  
...  

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