Diagnosis and treatment of neonatal diabetes: an United States experience†

Støy, Julie; Greeley, Siri Atma W; Paz, Veronica P; Ye, Honggang; Pastore, Ashley N; Skowron, Kinga B; Lipton, Rebecca B; Cogen, Fran R; Bell, Graeme I; Philipson, Louis H; United States Neonatal Diabetes Working Group

doi:10.1111/j.1399-5448.2008.00433.x

Cited by 126Diabetes and associated disordersPancreatic function and diabetesGenomics and Rare Diseases

Diagnosis and treatment of neonatal diabetes: an United States experience†

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Støy, Julie, Greeley, Siri Atma W, Paz, Veronica P, Ye, Honggang, Pastore, Ashley N, Skowron, Kinga B, Lipton, Rebecca B, Cogen, Fran R +3 more·2008·Pediatric Diabetes

DOI 10.1111/j.1399-5448.2008.00433.xPMC PMC2574846

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BACKGROUND/OBJECTIVE: Mutations in KCNJ11, ABCC8, or INS are the cause of permanent neonatal diabetes mellitus in about 50% of patients diagnosed with diabetes before 6 months of age and in a small fraction of those diagnosed between 6 and 12 months. The aim of this study was to identify the genetic cause of diabetes in 77 consecutive patients referred to the University of Chicago with diabetes diagnosed before 1 yr of age. METHODS: We used Oragene DNA Self-Collection kit to obtain a saliva sample for DNA. We sequenced the protein-coding regions of KCNJ11, ABCC8, and INS using standard methods. RESULTS: We enrolled 32 patients diagnosed with diabetes before 6 months of age and 45 patients diagnosed between 6 and 12 months. We identified a mutation in KCNJ11 in 14 patients from 12 families and in INS in 7 patients from 4 families. Three of the patients with an INS mutation were diagnosed with diabetes between 6 and 12 months of age. Finally, we found that two patients had an abnormality of chromosome 6q24 associated with transient neonatal diabetes mellitus. CONCLUSIONS: We were able to establish a genetic cause of diabetes in 63% of patients diagnosed with diabetes before 6 months of age and in 7% of patients diagnosed between 6 and 12 months. Genetic testing, which is critical for guiding appropriate management, should be considered in patients diagnosed with diabetes before 1 yr of age, especially if they are autoantibody negative, although the presence of autoantibodies does not rule out a monogenic cause.

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Mutational analyses are established for classification of diabetes in the neonate as well as in young individuals with a dominant family history of diabetes (MODY).
“However, an exception is the mutational analyses established for classification of diabetes in the neonate (381-384) as well as in young individuals with a dominant family history of diabetes, often referred to as maturityonset diabetes of the young (MODY) (384,385) (Table 8).”
From Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus (2023) · cites this paper as [382]
The Conclusions state that testing for genetic defects in neonatal diabetes is critical for guiding management, and the Results report genetic diagnoses in 20 of 32 patients diagnosed before six months of age. The paper describes a family with MODY-type diabetes in the Discussion (Variable phenotype), but does not establish mutational analysis as a classification method for young people with a dominant family history of diabetes. Page numbers are unavailable in our copy. (LLM, conf=0.86)
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Infants with neonatal diabetes due to a mutation in the KCNJ11 (Kir6.2) gene may be treated with a sulfonylurea rather than with insulin.
“For example, infants with neonatal diabetes due to a mutation in the KCNJ11 (Kir6.2) gene may be treated with a sulfonylurea rather than with insulin (382,384,398).”
From Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus (2023) · cites this paper as [382]
Genetic markers have limited current clinical value in diabetes evaluation and management, but mutation analysis is emerging for classifying neonatal diabetes and MODY in young patients with dominant family history.
“Genetic markers are currently of limited clinical value in evaluating and managing patients with diabetes; however, mutational analysis is rapidly emerging for classifying diabetes in the neonate (258-260) and in young patients with a dominant family history of diabetes, often referred to as “maturityonset diabetes of the young” (MODY) (261).”
From Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus (2011) · cites this paper as [260]

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Authors: Støy, J., Greeley, S. A. W., Paz, V. P., Ye, H., Pastore, A. N., Skowron, K. B., Lipton, R. B., Cogen, F. R., Bell, G. I., Philipson, L. H., & United States Neonatal Diabetes Working Group
Affiliations: Aarhus University (DK)
University of Chicago (US)
Children's National (US)
Corresponding author: Philipson, Louis H
ORCID: Støy, Julie
Greeley, Siri Atma W
Paz, Veronica P
Ye, Honggang
Lipton, Rebecca B
Philipson, Louis H
Venue: Pediatric Diabetes
Publisher: Wiley
Published: 2008-10
Volume: 9
Issue: 5
Pages: 450-459
ISSN: 1399-543X (ISSN-L)
1399-5448
DOI: 10.1111/j.1399-5448.2008.00433.x
PMC: PMC2574846
OpenAlex: W2086980078
Semantic Scholar: 653208934b302ba8ede75f376f2a8ae1c1220f10
Cited by: 126
References: 36
Citations by year: 2025: 2 · 2024: 4 · 2023: 5 · 2022: 4 · 2021: 8 · 2020: 7 · 2019: 4 · 2018: 6 · 2017: 4 · 2016: 11 · 2015: 12 · 2014: 7 · 2013: 7 · 2012: 8
FWCI: 7.05
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: doi.wiley.com/10.1002/tdm_license_1.1 (tdm, 2526 d)
Locations: Pediatric Diabetes (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute of Diabetes and Digestive and Kidney Diseases (DK-44752, DK 20595, R01DK044752, R29DK044752, P60DK020595, P30DK020595)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
Keywords: neonatal diabetes, permanent neonatal diabetes, transient neonatal diabetes, KCNJ11 mutation, ABCC8 mutation, genetic testing, monogenic diabetes, genetic diagnosis
MeSH terms: Kcnj11 Channel, Adolescent, Adult, Child, Child, Preschool, Diabetes Mellitus, Type 1, Female, Glyburide, Humans, Infant, Infant, Newborn, Insulin, Learning Disabilities, Male, Pedigree, Receptors, Drug, United States, ATP-Binding Cassette Transporters, Potassium Channels, Inwardly Rectifying, Diabetes Complications, Sulfonylurea Receptors

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Diagnosis and treatment of neonatal diabetes: an United States experience†

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