Gong Siqian, Guo Jiandong, Han Xueyao, Li Meng, Zhou Lingli, Cai Xiaoling, Zhu Yu, Luo Yingying, Zhang Simin, Zhou Xianghai, Ma Yumin, Ji Linong
Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing 100044, China.
Peking University Diabetes Center, Beijing 100044, China.
J Clin Endocrinol Metab. 2017 May 1;102(5):1548-1556. doi: 10.1210/jc.2016-2332.
A sodium glucose cotransporter 2 (SGLT2) inhibitor, which increases urinary glucose excretion, was reported to decrease blood glucose levels and deaths among patients with type 2 diabetes mellitus (T2DM) and established cardiovascular disease. SLC5A2 and HNF1A mutations are associated with renal glycosuria, but their contributions to renal glycosuria in patients with T2DM are not well understood.
To assess the clinical features of patients with T2DM and renal glycosuria and those with T2DM and low urinary glucose excretion (LUGE) and identify variants in the exons of SLC5A2 and HNF1A in patients with renal glycosuria and T2DM.
A total of 2044 Chinese patients with T2DM, including 64 patients with renal glycosuria and 58 patients with LUGE, were tested for their plasma and urine glucose concentrations after fasting. SLC5A2 and HNF1A exons were sequenced.
Compared with patients with LUGE, those with renal glycosuria were younger (P = 0.008), had lower body mass index (BMI) (P = 0.002) and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) values (P < 0.0001), and were less likely to have hypertension (P = 0.006). HOMA-IR and BMI were negatively associated with renal glycosuria after adjusting for age, sex, hypertension, and insulin therapy. One novel mutation (V359G) of SLC5A2 in 32 patients with renal glycosuria and one known mutation (R131W) of HNF1A in 28 nonobese patients with renal glycosuria were identified.
These findings suggest that there are subtypes of T2DM characterized by different urinary glucose excretion and cardiovascular risk factors. SLC5A2 and HNF1A mutations partially explain renal glycosuria in patients with T2DM.
据报道，一种钠葡萄糖协同转运蛋白2（SGLT2）抑制剂可增加尿糖排泄，降低2型糖尿病（T2DM）合并已确诊心血管疾病患者的血糖水平和死亡率。溶质载体家族5成员2（SLC5A2）和肝细胞核因子1α（HNF1A）突变与肾性糖尿有关，但它们在T2DM患者肾性糖尿中的作用尚不清楚。
评估T2DM合并肾性糖尿患者和T2DM合并低尿糖排泄（LUGE）患者的临床特征，并鉴定肾性糖尿合并T2DM患者中SLC5A2和HNF1A外显子的变异。
对2044例中国T2DM患者进行空腹血浆和尿葡萄糖浓度检测，其中包括64例肾性糖尿患者和58例LUGE患者。对SLC5A2和HNF1A外显子进行测序。
与LUGE患者相比，肾性糖尿患者更年轻（P = 0.008），体重指数（BMI）更低（P = 0.002），胰岛素抵抗稳态模型评估（HOMA-IR）值更低（P < 0.0001），患高血压的可能性更小（P = 0.006）。校正年龄、性别、高血压和胰岛素治疗后，HOMA-IR和BMI与肾性糖尿呈负相关。在32例肾性糖尿患者中鉴定出1个SLC5A2新突变（V359G），在28例非肥胖肾性糖尿患者中鉴定出1个HNF1A已知突变（R131W）。
这些发现表明，存在以不同尿糖排泄和心血管危险因素为特征的T2DM亚型。SLC5A2和HNF1A突变部分解释了T2DM患者的肾性糖尿。
