The unique variants or biomarkers of individuals help to understand the pathogenesis as well as the potential risk of individuals or patients to diabetic nephropathy (DN). The aim of this study was to investigate the association of a genetic polymorphism of monocyte chemoattractant protein-1 (CCL2-rs3917887), chemokine receptor 5 (CCR5-rs1799987), engulfment and cell mortality (ELMO1-rs74130), and interleukin-8 (IL8-rs4073) with the development of DN among Malaysian type 2 diabetes mellitus (T2DM) patients. More than one thousand diabetic patients were examined and a total of 652 T2DM patients were tested comprising 227 Malays (nonnephrotic=96 and nephrotic=131), 203 Chinese (nonnephrotic=95 and nephrotic=108), and 222 Indians (nonnephrotic=136 and nephrotic=86). DNA Sequenom mass ARRAY was employed to identify polymorphisms in CCL2, CCR5, ELMO1, and IL8 genes. DNA was extracted from the secondary blood samples taken from the T2DM patients. The alleles and genotypes were tested using four genetic models and the best mode of inheritance was chosen. CCR5 rs1799987 (G>A) showed strong association with the development of diabetic nephropathy only among the Chinese with OR=6.71 (2.55-17.68) 95% CI while IL8 rs4073 (T>A) showed association with nephropathy only among the Indians with OR=1.57 (0.66-3.71) 95% CI. The additive model was the best model for the mode of inheritance of all the genes. The contribution of genetic variants differs across ethnic groups or background. Further studies which involve environmental risk factors should be taken into consideration.
Type 2 diabetes mellitus (T2DM) is associated with a high incidence of nephropathy. The aim of this study was to investigate the association of a genetic polymorphism of carnosinase (CNDP1-D18S880 and -rs2346061), endothelial nitric oxide synthase (NOS3-rs1799983), and manganese superoxide dismutase (MnSOD-rs4880) genes with the development of diabetic nephropathy among Malaysian type 2 diabetic patients. A case-control association study was performed using 652 T2DM patients comprising 227 Malays (without nephropathy = 96 and nephropathy = 131), 203 Chinese (without nephropathy = 95 and nephropathy = 108), and 222 Indians (without nephropathy = 136 and nephropathy = 86). DNA sequencing was performed for the D18S880 of CNDP1, while the rest were tested using DNA Sequenom MassARRAY to identify the polymorphisms. DNA was extracted from the secondary blood samples taken from the T2DM patients. The alleles and genotypes were tested using four genetic models, and the best mode of inheritance was chosen based on the least p value. The rs2346061 of CNDP1 was significantly associated with diabetic nephropathy among the Indians only with OR = 1.94 and 95% CI = (1.76–3.20) and fitted best the multiplicative model, while D18S880 was associated among all the three major races with the Malays having the strongest association with OR = 2.46 and 95% CI = (1.48–4.10), Chinese with OR = 2.26 and 95% CI = (1.34–3.83), and Indians with OR = 1.77 and 95% CI = (1.18–2.65) in the genotypic multiplicative model. The best mode of inheritance for both MnSOD and NOS3 was the additive model. For MnSOD-rs4880, the Chinese had OR = 2.8 and 95% CI = (0.53–14.94), Indians had OR = 2.4 and 95% CI = (0.69–2.84), and Malays had OR = 2.16 and 95% CI = (0.54–8.65), while for NOS3-rs1799983, the Indians had the highest risk with OR = 3.16 and 95% CI = (0.52–17.56), followed by the Chinese with OR = 3.55 and 95% CI = (0.36–35.03) and the Malays with OR = 2.89 and 95% CI = (0.29–28.32). The four oxidative stress-related polymorphisms have significant effects on the development of nephropathy in type 2 diabetes patients. The genes may, therefore, be considered as risk factors for Malaysian subjects who are predisposed to T2DM nephropathy.
Background Diabetes is one of the leading cause of chronic kidney disease (CKD) and end stage renal disease. This study aims to develop and validate different risk predictive models for incident CKD and CKD progression in people with type 2 diabetes (T2D). Methods We reviewed a cohort of people with T2D seeking care from two tertiary hospitals in the metropolitan cities of the state of Selangor and Negeri Sembilan from January 2012 to May 2021. To identify the three-year predictor of developing CKD (primary outcome) and CKD progression (secondary outcome), the dataset was randomly split into a training and test set. A Cox proportional hazards (CoxPH) model was developed to identify for predictors of developing CKD. The resultant CoxPH model was compared with other machine learning models on their performance using C-statistic. Results The cohorts included 1 992 participants, of which 295 had developed CKD and 442 reported worsening of kidney function. Equation for the three-year risk of developing CKD included gender, haemoglobin A1c, triglyceride and serum creatinine levels, estimated glomerular filtration rate, history of cardiovascular disease and diabetes duration. For risk of CKD progression, the model included systolic blood pressure, retinopathy and proteinuria. The CoxPH model was better at prediction compared to other machine learning models examined for incident CKD (C-statistic: training 0.826; test 0.874) and CKD progression (C-statistic: training 0.611; test 0.655). Risk calculator can be found at https://rs59.shinyapps.io/071221/. Conclusions The Cox regression model was the best performing modelto predict people with T2D who will develop a 3-year risk of incident CKD and CKD progression in a Malaysian cohort.
AimEvidence from the literature points towards a viable choice of utilizing Labisia pumila to improve the metabolic profile in animal studies. To that end, this prospective study was designed to assess the health impact of the consumption of L. pumila standardized extract (SKF7®) on key parameters of obesity in humans such as body weight (BW), body mass index (BMI), waist circumference (WC) and waist‐to‐height ratio (WHtR).Materials and MethodsA dose‐ranging analysis using SKF7® was conducted through a randomized, double‐blind, multicentre, placebo‐controlled, phase 2 clinical trial involving individuals with obesity (N = 133) between January 2020 and April 2021. The potential percentage of change was assessed in relation to BW, BMI, WC and WHtR.ResultsAverage treatment effect estimates (treatment group vs. placebo) show a statistically significant reduction in the percentage of change for BW (mean = −2.915; CI: −4.546, −1.285), BMI (−2.921; CI: −4.551, −1.291), WC (mean = −2.187; CI: −3.784, −0.589) and WHtR (mean = −2.294, CI: −3.908, −0.681) in the group with a total of 750 mg of SKF7® (p < .01). An incremental reduction in WC and WHtR was consistent with the gradual increase in the total daily concentration of SKF7® from 375 to 750 mg. WC and WHtR had higher effect size (f 2 = 0.11 and f 2 = 0.13 respectively) in comparison with BW and BMI.ConclusionsSKF7® is potentially a novel therapeutic treatment for obesity, reflected by reductions in BW, BMI, WC and WHtR. The use of SKF7® suggests a dose‐dependent reduction in abdominal obesity, exemplified by a decline in WC and WHtR.
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