Madras Diabetes Research Foundation, Chennai, India; Deakin University, School of Medicine, IMPACT, Institute for Innovation in Physical and Mental Health and Clinical Translation, Geelong, Australia.
Deakin University, School of Medicine, IMPACT, Institute for Innovation in Physical and Mental Health and Clinical Translation, Geelong, Australia.
Prim Care Diabetes. 2023 Aug;17(4):401-407. doi: 10.1016/j.pcd.2023.04.004. Epub 2023 Apr 11.
Maturity Onset Diabetes of the Young (MODY) is a form of monogenic diabetes caused by mutations in single genes, affecting adolescents or young adults. MODY is frequently misdiagnosed as type 1 diabetes (T1). Though several studies from India have reported on the genetic aspects of MODY, the clinical profile, complications and treatments given have not been reported so far, nor compared with T1D and type 2 diabetes (T2D).
To determine the prevalence, clinical features, and complications of common forms of genetically proven MODY seen at a tertiary diabetes centre in South India and compare them with matched individuals with T1D and T2D.
Five hundred and thirty individuals identified as 'possible MODY' based on clinical criteria, underwent genetic testing for MODY. Diagnosis of MODY was confirmed based on pathogenic or likely pathogenic variants found using Genome Aggregation Database (gnomAD) and American College of Medical Genetics (ACMG) criteria. The clinical profile of MODY was compared with individuals with type 1 (T1D) and type 2 (T2D) diabetes, matched for duration of diabetes. Retinopathy was diagnosed by retinal photography; nephropathy by urinary albumin excretion > 30 µg/mg of creatinine and neuropathy by vibration perception threshold > 20 v on biothesiometry.
Fifty-eight patients were confirmed to have MODY (10.9%). HNF1A-MODY (n = 25) was the most common subtype followed by HNF4A-MODY (n = 11), ABCC8-MODY (n = 11), GCK-MODY (n = 6) and HNF1B-MODY (n = 5). For comparison of clinical profile, only the three 'actionable' subtypes - defined as those who may respond to sulphonylureas, namely, HNF1A, HNF4A and ABCC8-MODY, were included. Age at onset of diabetes was lower among HNF4A-MODY and HNF1A-MODY than ABCC8-MODY, T1D and T2D. Prevalence of retinopathy and nephropathy was higher among the three MODY subtypes taken together (n = 47) as compared to T1D (n = 86) and T2D (n = 86).
This is one of the first reports of MODY subtypes from India based on ACMG and gnomAD criteria. The high prevalence of retinopathy and nephropathy in MODY points to the need for earlier diagnosis and better control of diabetes in individuals with MODY.
青年发病的成年型糖尿病（MODY）是一种由单个基因突变引起的单基因糖尿病，影响青少年或年轻人。MODY 常被误诊为 1 型糖尿病（T1）。尽管印度的几项研究报告了 MODY 的遗传方面，但迄今为止，尚未报告其临床特征、并发症和治疗方法，也未与 T1D 和 2 型糖尿病（T2D）进行比较。
确定在印度南部一家三级糖尿病中心发现的常见遗传证实的 MODY 形式的患病率、临床特征和并发症，并将其与匹配的 T1D 和 T2D 个体进行比较。
根据临床标准，530 名被确定为“可能的 MODY”的个体接受了 MODY 的基因检测。根据使用基因组聚集数据库（gnomAD）和美国医学遗传学学院（ACMG）标准发现的致病性或可能致病性变体，确认 MODY 的诊断。MODY 的临床特征与 1 型（T1D）和 2 型（T2D）糖尿病患者进行比较，这些患者的糖尿病病程相匹配。视网膜病变通过视网膜摄影诊断；肾病通过尿白蛋白排泄量>30μg/mg 肌酐和神经病变通过生物感觉计的振动感觉阈值>20v 来诊断。
58 名患者被证实患有 MODY（10.9%）。HNF1A-MODY（n=25）是最常见的亚型，其次是 HNF4A-MODY（n=11）、ABCC8-MODY（n=11）、GCK-MODY（n=6）和 HNF1B-MODY（n=5）。为了比较临床特征，仅包括三种“可操作”亚型——定义为可能对磺脲类药物有反应的亚型，即 HNF1A、HNF4A 和 ABCC8-MODY。与 ABCC8-MODY、T1D 和 T2D 相比，HNF4A-MODY 和 HNF1A-MODY 的糖尿病发病年龄更低。三种 MODY 亚型（n=47）的视网膜病变和肾病患病率均高于 T1D（n=86）和 T2D（n=86）。
这是根据 ACMG 和 gnomAD 标准报告的印度 MODY 亚型的首批报告之一。MODY 中视网膜病变和肾病的高患病率表明需要更早地诊断并更好地控制 MODY 患者的糖尿病。
