Prevalence, Characteristics and Clinical Diagnosis of Maturity Onset Diabetes of the Young Due to Mutations in HNF1A, HNF4A, and Glucokinase: Results From the SEARCH for Diabetes in Youth
Year: 2013
Type: article
Abstract: AIMS: Our study aims were to determine the frequency of MODY mutations (HNF1A, HNF4A, glucokinase) in a diverse population of youth with diabetes and to assess how well clinical features identify youth with maturity-onset diabetes of the young (MODY). METHODS: The SEARCH for Diabetes in Youth study is a US multicenter, population-based study of youth with diabetes diagnosed at age younger than 20 years. We sequenced genomic DNA for mutations in the HNF1A, HNF4A, and glucokinase genes in 586 participants enrolled in SEARCH between 2001 and 2006. Selection criteria included diabetes autoantibody negativity and fasting C-peptide levels of 0.8 ng/mL or greater. RESULTS: We identified a mutation in one of three MODY genes in 47 participants, or 8.0% of the tested sample, for a prevalence of at least 1.2% in the pediatric diabetes population. Of these, only 3 had a clinical diagnosis of MODY, and the majority was treated with insulin. Compared with the MODY-negative group, MODY-positive participants had lower FCP levels (2.2 ± 1.4 vs 3.2 ± 2.1 ng/mL, P < .01) and fewer type 2 diabetes-like metabolic features. Parental history of diabetes did not significantly differ between the 2 groups. CONCLUSIONS/INTERPRETATION: In this systematic study of MODY in a large pediatric US diabetes cohort, unselected by referral pattern or family history, MODY was usually misdiagnosed and incorrectly treated with insulin. Although many type 2 diabetes-like metabolic features were less common in the mutation-positive group, no single characteristic identified all patients with mutations. Clinicians should be alert to the possibility of MODY diagnosis, particularly in antibody-negative youth with diabetes.
DOI: 10.1210/jc.2013-1279
Authors: Catherine Pihoker, Lisa K. Gilliam, Sian Ellard, Dana Dabelea, Cralen Davis, Lawrence M. Dolan, Carla J. Greenbaum, Giuseppina Imperatore, Jean M. Lawrence, Santica M. Marcovina, Elizabeth Mayer-Davis, Beatriz L. Rodriguez, Andrea K. Steck, Desmond E. Williams, Andrew T. Hattersley, for the SEARCH for Diabetes in Youth Study Group
Institutions: Seattle Children's Hospital, University of Washington, University of Exeter, Wake Forest University Health Sciences, Wake Forest University, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Benaroya Research Institute, Centers for Disease Control and Prevention, Kaiser Permanente, University of North Carolina at Chapel Hill, Kuakini Medical Center, Colorado School of Public Health, University of Colorado Denver
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Funders: U.S. Department of Veterans Affairs, National Institute for Health and Care Research, National Institutes of Health, U.S. Public Health Service, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Research Resources, National Center for Chronic Disease Prevention and Health Promotion, National Center for Advancing Translational Sciences
Awards: G1061576540, G1092462818, South Carolina Clinical & Translational Research Institute (SCTR), G142556933, G1518032353, G1841928114, UCHSC Diabetes and Endocrinology Research Center, G2027946723, G2091809135, G22646245, G2320993242, Cincinnati Center for Clinical and Translational Sciences and Training, G248045910, G249568976, G2698360221, G278975345, G2962638713, G3146357332, G325765397, G3437629819, G3753588054, G3798223455, G386564605, G4526474293, G4976965329, G5105936691, G561931883, Colorado Clinical and Translational Sciences Institute, General Clinical Research Center, NIHR Senior Investigator Award, General Clinical Research Center, G8005556827, G822274331, G832786732, Cincinnati Center for Clinical and Translational Sciences and Training, G874743574, G891215646, G951231213
OpenAlex ID: W2062206625