Maturity-onset diabetes of the young (MODY) is a genetically and clinically heterogeneous group of disorders characterised by early onset, lean, non-autoimmunity mediated, non-insulin-dependent diabetes often with autosomal-dominant inheritance and specific pharmaco-genetic response. We describe two siblings with HNF1A-MODY (MODY3) due to a novel germline variant p.(His126Asp) which segregates with diabetes in the family. However, contrary to anticipated therapeutic response, blood glucose in this sib-pair did not respond to sulphonylureas (both low and high dose), dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors), and glucagon-like peptide-1 receptor agonists (GLP-1RA), also known as incretin mimetics. The unexpected limited pharmaco-therapeutic response could potentially be unique to this specific variant and/or progressive pancreatic β-cell failure associated with long-standing disease duration, higher BMI and glucose-toxicity. Therefore, we report a novel-variant MODY3 sib-pair with atypical pharmaco-therapeutic response i.e. resistant to multiple anti-diabetes agents namely sulphonylurea, DPP-4 inhibitors and GLP-1RA treatment.

中文翻译：

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对具有新型 HNF1α (MODY3) 变体的同胞对中的多种降糖剂的反应。

青年成人型糖尿病 (MODY) 是一组遗传和临床异质性疾病，其特征是早发、瘦弱、非自身免疫介导的非胰岛素依赖型糖尿病，通常具有常染色体显性遗传和特定的药物遗传反应。我们描述了两个具有 HNF1A-MODY (MODY3) 的兄弟姐妹，这是由于一种新的种系变体 p.(His126Asp) 与家族中的糖尿病分离。然而，与预期的治疗反应相反，这对同胞对中的血糖对磺脲类药物（低剂量和高剂量）、二肽基肽酶 4 抑制剂（DPP-4 抑制剂）和胰高血糖素样肽 1 受体激动剂没有反应。 GLP-1RA)，也称为肠促胰岛素模拟物。出乎意料的有限药物治疗反应可能是这种特定变异和/或与长期疾病持续时间、更高的 BMI 和葡萄糖毒性相关的进行性胰腺 β 细胞衰竭所特有的。因此，我们报告了具有非典型药物治疗反应的新型变体 MODY3 同胞对，即对多种抗糖尿病药物即磺脲类药物、DPP-4 抑制剂和 GLP-1RA 治疗具有抗性。