Genetic Risk Score for Plasma Uric Acid Levels Is Associated With Early Rapid Kidney Function Decline in Type 2 Diabetes.

CONTEXT: Observational studies have shown that elevated uric acid (UA) is associated with chronic kidney disease (CKD). However, whether the relationship is causal remains unclear. OBJECTIVE: To determine the association of plasma UA and incident CKD and the causal relationship between plasma UA and rapid decline in kidney function (RDKF) in patients with type 2 diabetes (T2D). METHODS: Multivariable Cox regression was conducted to evaluate the hazard ratio (HR) between plasma UA and incident CKD among 1300 normoalbuminuric patients in 2 T2D study cohorts (DN, n = 402; SMART2D, n = 898). A weighted genetic risk score (wGRS) was calculated based on 10 single nucleotide polymorphism (SNPs) identified in genome-wide association studies of UA in East Asians. Mendelian randomization (MR) analysis was performed among 1146 Chinese T2D patients without CKD (estimated glomerular filtration rate [eGFR] > 60 mL/min/1.73m2) at baseline (DN, 478; SMART2D, 668). The wGRS and individual SNPs were used as genetic instruments and RDKF was defined as eGFR decline of 5 mL/min/1.73m2/year or greater. RESULTS: During mean follow-up of 5.2 and 5.4 years, 81 (9%) and 46 (11%) participants in SMART2D and DN developed CKD, respectively. A 1-SD increment in plasma UA conferred higher risk of incident CKD (DN, adjusted-HR = 1.40 [95% CI, 1.02-1.91], P = 0.036; SMART2D, adjusted-HR = 1.31 [95% CI, 1.04-1.64], P = 0.018). Higher wGRS was associated with increased odds for RDKF (meta-adjusted odds ratio = 1.12 [95% CI, 1.01-1.24], P = 0.030, Phet = 0.606). CONCLUSION: Elevated plasma UA is an independent risk factor for incident CKD. Furthermore, plasma UA potentially has a causal role in early eGFR loss in T2D patients.

Study protocol for a nationwide Knowledge, Attitudes and Practices (KAP) survey on diabetes in Singapore's general population.

INTRODUCTION: This study aims to establish the Knowledge, Attitudes and Practices (KAP) of the general population (people with and without diabetes) towards diabetes. The study will examine (a) recognition and understanding of causes, prevention and treatment strategies of diabetes; (b) identify the knowledge gaps and behavioural patterns that may hamper diabetes prevention and control; (c) stigma towards and stigma perceived by people with diabetes and (d) awareness of anti-diabetes campaigns. METHODS AND ANALYSIS: The study is a nationwide, cross-sectional study of Singapore's general population aged 18 years and above (n=3000), comprising Chinese, Malay, Indian and other ethnic groups, who can understand English, Chinese, Malay or Tamil language. The sample was derived using a disproportionate stratified sampling using age and ethnicity. The proportion of respondents in each ethnic group (Chinese, Malay and Indian) was set to approximately 30%, while the proportion of respondents in each age group was set around 20% in order to ensure a sufficient sample size. The respondents will be administered questionnaires on diabetes KAP, stigma towards diabetes, lifestyle, diet and awareness of local anti-diabetes campaigns. The analysis will include descriptive statistics and multiple logistic and linear regression analyses to determine the socio-demographic correlates of correct recognition of diabetes, help-seeking preferences, as well as overall knowledge and attitudes among those with and without diabetes. We will consider a p value ≤0.05 as significant. ETHICS AND DISSEMINATION: This study protocol has been reviewed by the Institutional Research Review Committee and the National Healthcare Group Domain Specific Review Board (NHG DSRB Ref 2018/00430). The results of the study will be shared with policymakers and other stakeholders. There will be a local mass media briefing to disseminate the findings online, in print and on television and radio. The results will be published in peer-reviewed journals and presented in scientific meetings.

Central arterial stiffness is associated with systemic inflammation among Asians with type 2 diabetes.

OBJECTIVE: To examine the relationship between inflammation and central arterial stiffness in a type 2 diabetes Asian cohort. METHOD: Central arterial stiffness was estimated by carotid-femoral pulse wave velocity and augmentation index. Linear regression model was used to evaluate the association of high-sensitivity C-reactive protein and soluble receptor for advanced glycation end products with pulse wave velocity and augmentation index. High-sensitivity C-reactive protein was analysed as a continuous variable and categories (<1, 1-3, and >3 mg/L). RESULTS: There is no association between high-sensitivity C-reactive protein and pulse wave velocity. Augmentation index increased with high-sensitivity C-reactive protein as a continuous variable (ß = 0.328, p = 0.049) and categories (ß = 1.474, p = 0.008 for high-sensitivity C-reactive protein: 1-3 mg/L and ß = 1.323, p = 0.019 for high-sensitivity C-reactive protein: >3 mg/L) after multivariable adjustment. No association was observed between augmentation index and soluble receptor for advanced glycation end products. Each unit increase in natural log-transformed soluble receptor for advanced glycation end products was associated with 0.328 m/s decrease in pulse wave velocity after multivariable adjustment (p = 0.007). CONCLUSION: Elevated high-sensitivity C-reactive protein and decreased soluble receptor for advanced glycation end products are associated with augmentation index and pulse wave velocity, respectively, suggesting the potential role of systemic inflammation in the pathogenesis of central arterial stiffness in type 2 diabetes.

Riboregulators and metabolic disorders: getting closer towards understanding the pathogenesis of diabetes mellitus?

Type 2 Diabetes occurs as a result of defects in insulin secretion and its function. Although mechanisms of disease are not fully elucidated, it is recognized that a progressive decline in insulin secretory capacity is responsible for its occurrence and natural course. Metabolic syndrome, known to be a precursor of Type 2 diabetes, is characterized by a constellation of vascular risk factors, with obesity playing a central role. Obesity contributes to impaired insulin function and abnormal glucose metabolism. MicroRNAs (miRNA) are highly conserved, small, RNA molecules encoded in the genomes of plants and animals and they regulate the expression of many other genes either by RNA interference (RNAi) or RNA activation (RNAa). miRNAs have been found to regulate multiple genes and seem to be crucial factors in many cellular pathways, including development, cell differentiation, proliferation and apoptosis. Pancreatic islet cell specific miRNAs which regulate insulin secretion, and adipocyte specific miRNAs which regulate adipocyte differentiation, are examples of miRNAs that are predicted to have crucial roles in governing glucose homeostasis. Further understanding of the roles of miRNAs in glucose metabolism may unravel better understanding of pancreatic cell biology and diabetes pathophysiology, allowing for newer therapeutic targets and strategies. In this review, we will be discussing about the role/function of miRNAs in insulin secretion and regulation, lipid metabolism and conditions like hypertension and cardiovascular diseases and the potential use of miRNA in therapy.