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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
Open accessAbstract
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.
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“although admittedly, atypical diabetes is becoming increasingly dif fi cult to precisely de fi ne in the absence of a de fi nitive set of tests for either type of diabetes (158 -160,163 -169)”
From 2. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes—2024 (2024) · cites this paper as [167]
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The Evolving Spectrum of Pediatric Non-Type 1 Diabetes: A Clinical and Genetic StudyPreprint
Acar, M. I., Boztepe, K., Gol, N. K., Ozkan, N. Z., & Pirgon, Ö. (2026) · Research Square · doi:10.21203/rs.3.rs-11154820/v1
Metadata
- Authors
- Pihoker, C., Gilliam, L. K., Ellard, S., Dabelea, D., Davis, C., Dolan, L. M., Greenbaum, C. J., Imperatore, G., Lawrence, J. M., Marcovina, S. M., Mayer-Davis, E., Rodriguez, B. L., Steck, A. K., Williams, D. E., Hattersley, A. T., & for the SEARCH for Diabetes in Youth Study Group
- Affiliations
- Seattle Children's Hospital (US)
- University of Washington (US)
- University of Exeter (GB)
- Wake Forest University Health Sciences (US)
- Cincinnati Children's Hospital Medical Center (US)
- Benaroya Research Institute (US)
- Centers for Disease Control and Prevention (US)
- Kaiser Permanente (US)
- Colorado School of Public Health (US)
- Corresponding author
- Pihoker, Catherine
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2013-10
- Volume
- 98
- Issue
- 10
- Pages
- 4055-4062
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC3790621
- OpenAlex
- W2062206625
- Cited by
- 397
- References
- 34
- Citations by year
- 2026: 20 · 2025: 22 · 2024: 30 · 2023: 43 · 2022: 46 · 2021: 28 · 2020: 41 · 2019: 29 · 2018: 43 · 2017: 29 · 2016: 24 · 2015: 23 · 2014: 16 · 2013: 3
- FWCI
- 14.60
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs (HIR 10-001)
- National Institute for Health and Care Research (NF-SI-0611-10219)
- National Institutes of Health (5ul1rr026314-03, UL1TR001082, UL1TR000077)
- U.S. Public Health Service (PAS 00097, U58/CCU919256, U48/CCU519239, U48/CCU419249, U48/CCU819241-3, U48/CCU919219, U58 CCU019235-4)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK057516, P30 DK 57516)
- National Center for Research Resources (UL1RR029882, M01 RR00069, UL1-RR026314, M01-RR 00037, UL1RR02631401, M01RR000069, M01RR000037)
- National Center for Chronic Disease Prevention and Health Promotion (U01 DP-000247, U18 DP-002709, U18 DP-002708-01, U18-DP-002708, U01-DP000246, U01-DP-000250, U18 DP-000247-06A1, U01-DP-000254, U18 DP002714, U01DP000245, U18DP002710-01, U01 DP000248, DP-05069, U01DP000244, U18 DP002710, 1U18-DP-002709, DP-10001)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- maturity-onset diabetes of the young, HNF1A, HNF4α, glucokinase, pediatric diabetes, misdiagnosis, insulin therapy, fasting C-peptide, SEARCH for Diabetes in Youth
- MeSH terms
- Adolescent, Child, Child, Preschool, Diabetes Mellitus, Type 2, DNA Mutational Analysis, Female, Glucokinase, Humans, Male, Mutation, Prevalence, Age of Onset, Hepatocyte Nuclear Factor 1-alpha, Hepatocyte Nuclear Factor 4, Young Adult
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