Clinical and laboratory clues of maturity‐onset diabetes of the young and determination of association with molecular diagnosis

Background/Aim Maturity‐onset diabetes of the young (MODY) is often misdiagnosed as other types of diabetes because it is overlooked due to atypical clinical presentations. This study aims to reveal the clinical and laboratory clues and examine their compatibility with MODY genotypes. Methods Participants consisted of 230 children with atypical presentations for type1(T1DM) and type2 diabetes mellitus (T2DM). MODY‐causing mutations were screened in the following genes:GCK‐HNF1A‐HNF4A‐HNF1B‐PDX1‐NEUROD1‐KLF11‐CEL‐PAX4‐INS‐BLK. Clinical and laboratory features were compared between children with MODY and children without MODY. Results The most common reasons for MODY screening were as follows (n/%):low daily dose of insulin (DDI) requirement (122/53%), absence of beta‐cell antibodies(58/25.3%), coincidental hyperglycemia(26/11.3%), family history of diabetes (12/5.2%), hypoglycemia/hyperglycemia episodes(7/3%), hyperglycemia related to steroids(3/1.4%) and renal glycosuria(2/0.8%). The markers with the most likelihood to distinguish MODY from T1DM were determined as follows: measurable C‐peptide in follow‐up, family history of early‐onset diabetes and low DDI requirement (odds ratio:12.55, 5.53 and 3.43, respectively). The distribution of the most common causative genes in children with MODY(n = 24) is as follows (n/%):GCK(15/62.5%), HNF4A(7/29.1%), HNF1A(1/9.2%) and PDX1(1/9.2%).All children(n = 12) with GCK‐MODY(MODY2) were screened for low DDI requirement, while beta‐cell negativity was more common in HNF4A‐MODY(MODY1). Conclusion The study shows that measurable C‐peptide in follow‐up, family history of early‐onset diabetes, and low DDI are still remarkable clues to predict MODY in children with misdiagnosed T1DM. In addition, the most common mutations were found in the GCK and HNF4A genes. Among children misdiagnosed with T1DM, a low DDI requirement was found more frequently in MODY2, whereas beta‐cell antibody negativity was more common in MODY1. 摘要 背景/目的 由于青少年发病的成人型糖尿病(MODY)的非典型临床表现，该病经常被忽略。这项研究旨在揭示临床和实验室线索，并分析其与MODY基因型的匹配度。 方法 受试者由230名非典型表现为1型(T1DM)和2型糖尿病(T2DM)的儿童组成。在以下基因中筛选引起MODY的突变:GCK‐HNF1A‐HNF4A‐HNF1BPDX1‐NEUROD1‐KLF11‐CEL‐PAX4‐INS‐BLK。研究比较MODY患儿和非MODY患儿的临床和实验室特征。 结果 进行MODY筛查的最常见原因如下(n /%):每日低剂量胰岛素(DDI)需求量(122/53%)、无β细胞抗体(58 / 25.3%)、偶发高血糖(26 / 11.3%)、糖尿病家族史(12 / 5.2%)、低血糖/高血糖发作(7/3%)、与类固醇有关的高血糖症(3 / 1.4%)和肾性糖尿(2 / 0.8%)。最有可能作为MODY与T1DM区分的标志物如下:随访中可测量的C肽、早发型糖尿病家族病史和DDI低需求(比值比分别为:12.55、5.53和3.43)。 儿童中MODY(n = 24)最常见的致病基因分布如下(n /%):GCK(15 / 62.5%)、H