Yoshimura Kai, Hirota Yushi, Hamaguchi Tetsushi, Takeuchi Takehito, Takayoshi Tomofumi, Saito Shuichiro, Ueda Mariko, Nishikage Seiji, Yamamoto Akane, Hashimoto Naoko, Ogawa Wataru
Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Division of Diabetes and Endocrinology, Konan Medical Center, Kobe, Japan.
J Diabetes Investig. 2025 Sep;16(9):1663-1669. doi: 10.1111/jdi.70105. Epub 2025 Jun 30.
Genetic insulin resistance syndrome is characterized by severe insulin resistance due to functional abnormalities of the insulin receptor or downstream signaling molecules. Treatment typically includes insulin formulations and oral hypoglycemic agents such as metformin and sodium-glucose cotransporter 2 (SGLT2) inhibitors. However, achieving adequate glycemic control remains challenging. Moreover, given its rarity, reports on perinatal glycemic management in affected pregnancies remain scarce.
We describe prenatal care for two cases of genetic insulin resistance syndrome: a case of type A insulin resistance syndrome attributed to a heterozygous variant (Asn462Ser) of INSR (case 1) and a case of genetic insulin resistance syndrome due to a heterozygous variant (Arg649Trp) of PIK3R1 (case 2). We also review the literature for metformin treatment of gestational diabetes mellitus (GDM) or type 2 diabetes during pregnancy.
In case 1, perinatal glycemic management during three pregnancies was achieved with metformin alone, resulting in deliveries without any adverse events for both mother and infants. In case 2, administration of metformin during pregnancy initially reduced daily insulin requirements from 230 to 50 U/day, with a predelivery insulin dose of 112 U/day. At 34 weeks of gestation, a cesarean section was performed because of intractable uterine contractions. The child was diagnosed as small for gestational age and harbored the same genetic variant as the mother.
The present cases suggest that metformin administration during pregnancy can be beneficial in cases of genetic insulin resistance syndrome, similar to its use in pregnancies associated with T2D or GDM.
遗传性胰岛素抵抗综合征的特征是由于胰岛素受体或下游信号分子的功能异常导致严重的胰岛素抵抗。治疗通常包括胰岛素制剂以及口服降糖药，如二甲双胍和钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂。然而，实现充分的血糖控制仍然具有挑战性。此外，鉴于其罕见性，关于受影响妊娠围产期血糖管理的报道仍然很少。
我们描述了两例遗传性胰岛素抵抗综合征的产前护理情况：一例A型胰岛素抵抗综合征归因于INSR的杂合变异（Asn462Ser）（病例1），另一例遗传性胰岛素抵抗综合征归因于PIK3R1的杂合变异（Arg649Trp）（病例2）。我们还回顾了关于二甲双胍治疗妊娠期糖尿病（GDM）或妊娠期间2型糖尿病的文献。
在病例1中，仅使用二甲双胍就实现了三次妊娠期间的围产期血糖管理，母婴分娩均无任何不良事件。在病例2中，孕期使用二甲双胍最初将每日胰岛素需求量从230单位降至50单位/天，分娩前胰岛素剂量为112单位/天。妊娠34周时，因难治性子宫收缩行剖宫产。该儿童被诊断为小于胎龄儿，且携带与母亲相同的基因变异。
目前的病例表明，孕期使用二甲双胍对遗传性胰岛素抵抗综合征病例可能有益，类似于其在与2型糖尿病或妊娠期糖尿病相关的妊娠中的应用。
