Murat Karaoglan1, Gulper Nacarkahya2. 1. Department of Pediatric Endocrinology, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey. 2. Department of Molecular Biology, Faculty of Medicine Gaziantep/Turkey, Gaziantep University, Gaziantep, Turkey.
Abstract
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.
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.
Authors: Haichen Zhang; Jeffrey W Kleinberger; Kristin A Maloney; Yue Guan; Trevor J Mathias; Katharine Bisordi; Elizabeth A Streeten; Kristina Blessing; Mallory N Snyder; Lee A Bromberger; Jessica Goehringer; Amy Kimball; Coleen M Damcott; Casey O Taylor; Michaela Nicholson; Devon Nwaba; Kathleen Palmer; Danielle Sewell; Nicholas Ambulos; Linda J B Jeng; Alan R Shuldiner; Philip Levin; David J Carey; Toni I Pollin Journal: Diabetes Care Date: 2022-08-01 Impact factor: 17.152