Gitelman syndrome (GS) is an autosomal recessive tubulopathy caused by mutations of the SLC12A3 gene. It is characterized by hypokalemic metabolic alkalosis, hypomagnesemia and hypocalciuria. It is universally known that both hypokalemia and hypomagnesemia can influence insulin secretion and insulin resistance, but the exact mechanisms require further study. We identified a novel deletion variant of the SLC12A3 gene and discussed the appropriate hypoglycemic drugs in Gitelman syndrome (GS) patients with type 2 diabetes. A 55-year-old diabetic female patient was hospitalized for evaluation because of paroxysmal general weakness and numbness of extremities for one year. We suspected that she was suffering from GS by initial estimation. Direct Sanger sequencing was used to analyze the causative gene SLC12A3 of GS. Oral glucose tolerance test (OGTT) was carried out to assess the glucose metabolism and insulin resistance status. Genetic analysis revealed that she was a compound heterozygote for a recurrent missense mutation c.179C > T and a novel deletion c.1740delC in SLC12A3, thus her diagnosis of GS was confirmed. The patient was treated with potassium chloride (3.0 g/d) and magnesium chloride (element magnesium 350 mg/d) on the basis of initial treatment of diabetes with hypoglycemic drug (Repaglinide, 3.0 mg/day). However, she developed frequent hypoglycemia after one week. OGTT showed that her glucose metabolism and insulin resistance much improved after potassium and magnesium supplemental therapy. Then we changed the hypoglycemic agent to a dipeptidyl peptidase-4 (DPP-4) inhibitor (Trajenta 5 mg/d), since then her blood glucose level remained normal during two-year of follow-up. We have identified a novel deletion of the SLC12A3 gene and discussed the appropriate hypoglycemic drugs in Gitelman syndrome (GS) patients with type 2 diabetes. We suggested that attention need to be paid to blood glucose monitoring in GS patients, especially when hypokalemia and hypomagnesemia are corrected. Besides, the insufficient blood volume and serum electrolyte disturbance should also be taken into consideration in the selecting hypoglycemic drugs for GS patients.

中文翻译：

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糖尿病Gitelman综合征中SLC12A3基因的新型复合杂合变异及合适降糖药物的选择：病例报告


Gitelman 综合征 (GS) 是一种由 SLC12A3 基因突变引起的常染色体隐性肾小管病。其特点是低钾性代谢性碱中毒、低镁血症和低钙尿症。众所周知，低钾血症和低镁血症都会影响胰岛素分泌和胰岛素抵抗，但具体机制有待进一步研究。我们鉴定了 SLC12A3 基因的一种新的缺失变异，并讨论了患有 2 型糖尿病的 Gitelman 综合征 (GS) 患者的适当降血糖药物。一名55岁糖尿病女性患者因阵发性全身无力、四肢麻木一年入院评估。我们初步判断她患有GS。采用直接Sanger测序分析GS的致病基因SLC12A3。进行口服葡萄糖耐量试验（OGTT）以评估葡萄糖代谢和胰岛素抵抗状态。遗传分析显示，她是重复性错义突变 c.179C > T 和 SLC12A3 中新的 c.1740delC 缺失的复合杂合子，从而证实了她的 GS 诊断。患者在降糖药（瑞格列奈，3.0 mg/天）初始治疗糖尿病的基础上，加用氯化钾（3.0 g/d）和氯化镁（元素镁350 mg/d）治疗。然而，一周后，她频繁出现低血糖。 OGTT显示，补充钾和镁治疗后，她的糖代谢和胰岛素抵抗明显改善。随后我们将降糖药改为二肽基肽酶4（DPP-4）抑制剂（Trajenta 5 mg/d），此后两年的随访期间，她的血糖水平一直保持正常。 我们发现了 SLC12A3 基因的新缺失，并讨论了患有 2 型糖尿病的 Gitelman 综合征 (GS) 患者的适当降血糖药物。我们建议GS患者需要重视血糖监测，特别是在纠正低钾血症和低镁血症时。此外，GS患者选择降糖药物时还应考虑血容量不足和血清电解质紊乱的情况。