Increased Prevalence of Beta-Cell Dysfunction despite Normal HbA1c in Youth and Young Adults with Turner Syndrome
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INTRODUCTION: Adult women with Turner syndrome (TS) have a high prevalence of diabetes and β-cell dysfunction that increases morbidity and mortality, but it is unknown if there is β-cell dysfunction present in youth with TS. This study aimed to determine the prevalence of β-cell dysfunction in youth with TS and the impact of traditional therapies on insulin sensitivity (SI) and insulin secretion. METHODS: Cross-sectional, observational study recruited 60 girls with TS and 60 healthy controls (HC) matched on pubertal status. Each subject had a history, physical exam, and oral glucose tolerance test (OGTT). Oral glucose and c-peptide minimal modeling was used to determine β-cell function. RESULTS: Twenty-one TS girls (35%) met criteria for prediabetes. Impaired fasting glucose was present in 18% of girls with TS and 3% HC (p value = 0.02). Impaired glucose tolerance was present in 23% of TS girls and 0% HC (p value <0.001). The hemoglobin A1c was not different between TS and HC (median 5%, p = 0.42). Youth with TS had significant reductions in SI, β-cell responsivity (Φ), and disposition index (DI) compared to HC. These differences remained significant when controlling for body mass index z-score (p values: 0.0006, 0.002, <0.0001 for SI, Φ total, DI, respectively). CONCLUSIONS: β-Cell dysfunction is present in youth with TS compared to controls. The presence of both reduced insulin secretion and SI suggest a unique TS-related glycemic phenotype. Based on the data from this study, we strongly suggest that providers employ serial OGTT to screen for glucose abnormalities in TS youth.
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Multiple studies demonstrate impaired beta cell function as well as reduced insulin sensitivity are involved in the development of diabetes in TS, while one study found glucose intolerance despite apparently normal beta cell function.
“Furthermore, multiple studies demonstrate impaired beta cell function as well as reduced insulin sensitivity are involved in the development of diabetes in TS ,227,229,384,705,707,708 while one study found glucose intolerance despite apparently normal beta cell function.709”
From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [708]
Several studies have demonstrated that fasting glucose and hemoglobin A1c can be normal even in the setting of impaired glucose tolerance in individuals with TS.
“Several studies have demonstrated that fasting glucose and hemoglobin A1c can be normal even in the setting of impaired glucose tolerance in individuals with TS.704,708”
From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [708]
Several studies support that diabetes occurs at an earlier age and is less likely to involve the usual risk factors (BMI, body composition, and family history) in TS compared to the general population.
“Several studies support that diabetes occurs at an earlier age384,708 and is less likely to involve the usual risk factors (BMI, body composition, and family history) in TS compared to the general population.704”
From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [708]
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- Authors
- Sheanon, N., Elder, D., Khoury, J., Casnellie, L., Gutmark-Little, I., Cernich, J., & Backeljauw, P. F.
- Affiliations
- Cincinnati Children's Hospital Medical Center (US)
- Children's Mercy Hospital (US)
- Venue
- Hormone Research in Paediatrics
- Publisher
- S. Karger AG
- Published
- 2021
- Volume
- 94
- Issue
- 7-8
- Pages
- 297-306
- ISSN
- 1663-2818 (ISSN-L)
- 1663-2826
- PMC
- PMC8678339
- OpenAlex
- W3206168900
- Cited by
- 12
- References
- 34
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 3 · 2023: 4 · 2022: 1
- FWCI
- 1.88
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Hormone Research in Paediatrics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (UL1TR001425)
- National Institute of Diabetes and Digestive and Kidney Diseases (T32DK063929)
- National Institute of Environmental Health Sciences (T32ES010957)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- Turner syndrome, beta-cell dysfunction, insulin sensitivity, insulin secretion, prediabetes, impaired glucose tolerance, impaired fasting glucose, HbA1c, youth, young adults, oral glucose tolerance test, disposition index, diabetes screening
- MeSH terms
- Adolescent, Blood Glucose, C-Peptide, Cross-Sectional Studies, Diabetes Mellitus, Female, Glucose Tolerance Test, Glycated Hemoglobin, Humans, Insulin Resistance, Phenotype, Prediabetic State, Turner Syndrome, Body Mass Index, Prevalence, Glucose Intolerance
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