Department of Endocrinology, Metabolism and Diabetes, Faculty of Medicine, Kindai University, Osaka-sayama, Osaka, Japan.
J Diabetes Investig. 2021 May;12(5):728-737. doi: 10.1111/jdi.13417. Epub 2020 Oct 27.
AIMS/INTRODUCTION: Glucosuria is a representative symptom in diabetes patients with poor glycemic control and in those treated with sodium-glucose cotransporter 2 inhibitors. Renal threshold levels of glucose excretion are known to vary among individuals, but factors contributing to glucosuria are not well characterized. The present study aimed to clarify clinical and genetic determinants of glucosuria in individuals with diabetes mellitus.
The 24-h urinary glucose excretion was measured in 135 hospitalized patients on admission, with continuous measurement for five consecutive days in 75 patients. Genetic and clinical factors contributing to glucosuria were studied. As a genetic factor, SLC5A2 polymorphism was genotyped. A total of 476 participants (266 participants with type 2 diabetes and 210 healthy controls) were additionally genotyped for the association study of SLC5A2 with type 2 diabetes. A meta-analysis was carried out with the present study and previous association studies.
Multiple regression analysis showed that the independent variables of average blood glucose (β = 0.41, P = 1.4 × 10 ), estimated glomerular filtration rate (β = 0.28, P = 6.0 × 10 ), sex (β = 0.28, P = 5.7 × 10 ) and SLC5A2 rs9934336 polymorphism (β = 0.17, P = 0.02) were significantly correlated with urinary glucose excretion. The frequency of the A allele of rs9934336 tended to be lower in participants with type 2 diabetes than in controls (odds ratio 0.78, 95% confidence interval 0.53-1.13, not significant), and meta-analysis showed a significant association between the A allele and type 2 diabetes (summary odds ratio for minor allele [A] 0.86, 95% confidence interval 0.78-0.94, P < 0.002).
Blood glucose, estimated glomerular filtration rate, sex and SLC5A2 polymorphism were independent determinants of glucosuria in diabetes mellitus.
目的/引言：糖尿病人血糖控制不佳或使用钠-葡萄糖共转运蛋白 2 抑制剂时，会出现糖尿症状。已知个体的肾糖阈水平存在差异，但导致糖尿的因素尚未得到很好的描述。本研究旨在阐明糖尿病患者糖尿的临床和遗传决定因素。
对 135 名住院患者入院时的 24 小时尿葡萄糖排泄量进行了测量，其中 75 名患者连续测量了 5 天。研究了导致糖尿的遗传和临床因素。作为遗传因素，对 SLC5A2 多态性进行了基因分型。另外，对 476 名参与者（266 名 2 型糖尿病患者和 210 名健康对照者）进行了 SLC5A2 与 2 型糖尿病关联研究的基因分型。本研究与之前的关联研究进行了荟萃分析。
多元回归分析显示，平均血糖（β=0.41，P=1.4×10-4）、估算肾小球滤过率（β=0.28，P=6.0×10-6）、性别（β=0.28，P=5.7×10-6）和 SLC5A2 rs9934336 多态性（β=0.17，P=0.02）是与尿糖排泄显著相关的独立变量。与对照组相比，2 型糖尿病患者 rs9934336 的 A 等位基因频率较低（比值比 0.78，95%置信区间 0.53-1.13，无统计学意义），荟萃分析显示 A 等位基因与 2 型糖尿病显著相关（次要等位基因 A 的汇总比值比 0.86，95%置信区间 0.78-0.94，P<0.002）。
血糖、估算肾小球滤过率、性别和 SLC5A2 多态性是糖尿病患者糖尿的独立决定因素。
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