Clinical and Genetic Features of Patients With Type 2 Diabetes and Renal Glycosuria.
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.
Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing 100044, China.|Peking University Diabetes Center, Beijing 100044, China.
Siqian
S
Gong
Department of Medicine, Beijing Yanqing Hospital, Beijing 102100, China.
Jiandong
J
Guo
Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing 100044, China.
Xueyao
X
Han
Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing 100044, China.|Peking University Diabetes Center, Beijing 100044, China.
Meng
M
Li
Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing 100044, China.
Lingli
L
Zhou
Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing 100044, China.
Xiaoling
X
Cai
Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing 100044, China.
Yu
Y
Zhu
Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing 100044, China.
Yingying
Y
Luo
Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing 100044, China.
Simin
S
Zhang
Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing 100044, China.
Xianghai
X
Zhou
Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing 100044, China.
Yumin
Y
Ma
Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing 100044, China.
Linong
L
Ji
D000328:Adult; D017677:Age Distribution; D000368:Aged; D044466:Asian People / Q000235:genetics; D015992:Body Mass Index; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000378:metabolism*; D005260:Female; D014644:Genetic Variation; D006030:Glycosuria, Renal / Q000453:epidemiology / Q000235:genetics*; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D006973:Hypertension / Q000453:epidemiology; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology; D017422:Sequence Analysis, DNA; D051297:Sodium-Glucose Transporter 2 / Q000235:genetics*
C496487:HNF1A protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2