遗传性肾性糖尿和糖尿病对SGLT2抑制剂的反应

Aims To present the clinical features of two rare cases with hereditary renal glycosuria and diabetes, explore their responses to sodium‐glucose cotransporter 2 (SGLT2) inhibitor, and summarize the reported solute carrier family 5 member 2 (SLC5A2) mutations and related phenotypes. Methods Two patients were followed up for 6.5 and 3 years respectively. SLC5A2 and hepatocyte nuclear factor 1‐alpha (HNF1A) gene were sequenced. We used the flash glucose monitoring system to evaluate the efficacy of SGLT2 inhibitor treatment. Then we retrieved all the literature and analyzed SLC5A2 gene mutations and the phenotypes. Results During long‐time follow up, the two patients had frequent unproportional renal glycosuria in the morning even when their fasting serum glucose was only slightly increased. A novel rare mutation V359G and a pathogenic rare mutation ivs7 + 5G > A in SLC5A2 gene were found respectively. In Case 1, the 24 h glucose excretion was 2.2 g/d and increased to 103 g/d after dapaglifozin treatment, whereas the average glucose (6.33 ± 1.56 vs. 6.28 ± 1.74 mmol/L), and time in range (TIR) (95% vs. 93%) were similar. In Case 2, the 24 h glycosuria was 121.4 g/d and increased to 185.8 g/day after dapaglifozin add‐on therapy, with a further reduction of average glucose (9.11 ± 2.63 vs. 7.54 ± 2.39 mmol/L, p  < 0.001) and better TIR (70% vs. 84%). We reviewed 139 cases with hereditary renal glycosuria and SLC5A2 gene mutation. The urine glucose was highest in patients with homozygous mutations [64.0(36.6–89.6)g/24 h] compared with compound heterozygous mutations [25.9(14.4–41.2)g/24 h] and heterozygous mutations [3.45(1.41–7.50)g/24 h] ( p  < 0.001). Conclusions Genetic renal glycosuria could not protect individuals completely from developing diabetes. Patients with SGLT2 gene mutations are still responsive to the SGLT2 inhibitor treatment.