Abstract

BackgroundElevated serum uric acid concentration is an independent risk factor and predictor of type 2 diabetes (T2D). Whether the uric acid-associated genes have an impact on T2D remains unclear. We aimed to investigate the effects of the uric acid-associated genes on the risk of T2D as well as glucose metabolism and insulin secretion.MethodWe recruited 2,199 normal glucose tolerance subjects from the Shanghai Diabetes Study I and II and 2,999 T2D patients from the inpatient database of Shanghai Diabetes Institute. Fifteen single nucleotide polymorphisms (SNPs) mapped in or near 11 loci (PDZK1, GCKR, LRP2, SLC2A9, ABCG2, LRRC16A, SLC17A1, SLC17A3, SLC22A11, SLC22A12 and SF1) were genotyped and serum biochemical parameters related to uric acid and T2D were determined.Results SF1 rs606458 showed strong association to T2D in both males and females (p = 0.034 and 0.0008). In the males, LRRC16A was associated with 2-h insulin and insulin secretion (p = 0.009 and 0.009). SLC22A11 was correlated with HOMA-B and insulin secretion (p = 0.048 and 0.029). SLC2A9 rs3775948 was associated with 2-h glucose (p = 0.043). In the females, LRP2 rs2544390 and rs1333049 showed correlations with fasting insulin, HOMA-IR and insulin secretion (p = 0.028, 0.033 and 0.052 and p = 0.034, 0.047 and 0.038, respectively). SLC2A9 rs11722228 was correlated with 2-h glucose, 2-h insulin and insulin secretion (p = 0.024, 0.049 and 0.049, respectively).ConclusionsOur results indicated that the uric acid-associated genes have an impact on the risk of T2D, glucose metabolism and insulin secretion in a Chinese population.

Highlights

  • The prevalence of type 2 diabetes (T2D) is increasing exponentially worldwide, promoted by multifactorial genetic or environmental factors

  • SLC2A9 rs11722228 was correlated with 2-h glucose, 2-h insulin and insulin secretion (p = 0.024, 0.049 and 0.049, respectively)

  • Our results indicated that the uric acid-associated genes have an impact on the risk of T2D, glucose metabolism and insulin secretion in a Chinese population

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Summary

Introduction

The prevalence of type 2 diabetes (T2D) is increasing exponentially worldwide, promoted by multifactorial genetic or environmental factors. Glucose-induced insulin secretion was inhibited by uric acid, which further elevated serum glucose levels. In the residual β-cells in T2D patients, uric acid enhanced the ability of insulin secretion to compensate for the lack of insulin action [10, 11]. We selected 2,999 T2D patients and 2,199 normal glucose tolerance (NGT) subjects to explore whether uric acid-associated genes affect the T2D risk, glucose metabolism and insulin secretion. Elevated serum uric acid concentration is an independent risk factor and predictor of type 2 diabetes (T2D). We aimed to investigate the effects of the uric acid-associated genes on the risk of T2D as well as glucose metabolism and insulin secretion

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