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Progressive Loss of β-Cell Function Leads to Worsening Glucose Tolerance in First-Degree Relatives of Subjects With Type 2 Diabetes
Open accessAbstract
OBJECTIVE—The relative roles of insulin resistance and β-cell dysfunction in the pathogenesis of impaired glucose tolerance (IGT) and type 2 diabetes are debated. First-degree relatives of individuals with type 2 diabetes are at increased risk of developing hyperglycemia. RESEARCH DESIGN AND METHODS—We evaluated the evolution of insulin sensitivity, β-cell function, glucose effectiveness, and glucose tolerance over 7 years in 33 nondiabetic, first-degree relatives of type 2 diabetic individuals using frequently sampled tolbutamide-modified intravenous and oral glucose tolerance tests. RESULTS—Subjects gained weight, and their waist circumference increased (P < 0.05). Insulin sensitivity, the acute insulin response to glucose, and glucose effectiveness did not change significantly. However, when we accounted for the modulating effect of insulin sensitivity on insulin release, β-cell function determined as the disposition index decreased by 22% (P < 0.05). This decrease was associated with declines in intravenous and oral glucose tolerance (P < 0.05 and P < 0.001, respectively). Of the subjects with normal glucose tolerance at the first assessment, we compared those who progressed to IGT with those who did not. The disposition index was 50% lower in the progressors than in the nonprogressors at follow-up (P < 0.05). CONCLUSIONS—The decline in glucose tolerance over time in first-degree relatives of type 2 diabetic individuals is strongly related to the loss of β-cell function. Thus, early interventions to slow the decline in β-cell function should be considered in high-risk individuals.
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“Diminished β-cell function is already present in groups known to be at increased risk of diabetes including first-degree relatives of individuals with diabetes12, women with gestational diabetes13 or polycystic ovary syndrome14 and older individuals15 and underlies the progression to diabetes.”
From Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future (2014) · cites this paper as [12]
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Metadata
- Authors
- Cnop, M., Vidal, J., Hull, R. L., Utzschneider, K. M., Carr, D. B., Schraw, T., Scherer, P. E., Boyko, E. J., Fujimoto, W. Y., & Kahn, S. E.
- Affiliations
- Université Libre de Bruxelles (BE)
- Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, VA Puget Sound Health Care System and University of Washington, Seattle, Washington
- University of Washington (US)
- Albert Einstein College of Medicine (US)
- ORCID
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2007-03-01
- Volume
- 30
- Issue
- 3
- Pages
- 677-682
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- OpenAlex
- W2057730437
- Cited by
- 174
- References
- 35
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 6 · 2023: 7 · 2022: 12 · 2021: 12 · 2020: 7 · 2019: 5 · 2018: 7 · 2017: 13 · 2016: 7 · 2015: 8 · 2014: 10 · 2013: 8 · 2012: 16
- FWCI
- 12.29
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes Care (publishedVersion)
- PubMed (publishedVersion)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
- Funders
- American Diabetes Association
- U.S. Department of Veterans Affairs
- Belgian American Educational Foundation
- Ministerio de Ciencia y Tecnología
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (K24DK002654, DK 02654, DK-17047, DK026687, P30DK026687, P30DK017047)
- National Center for Research Resources (K23RR016066, RR 16066, RR 37)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- type 2 diabetes, first-degree relatives, beta-cell dysfunction, impaired glucose tolerance, insulin sensitivity, disposition index, glucose tolerance, insulin resistance, glucose effectiveness, insulin secretion, disease progression, high-risk individuals
- MeSH terms
- Adult, Blood Glucose, Diabetes Mellitus, Type 2, Family, Follow-Up Studies, Glucose Tolerance Test, Humans, Insulin, Insulin Resistance, Middle Aged, Prediabetic State, Risk Factors, Sensitivity and Specificity, Weight Gain, Body Mass Index, Glucose Intolerance, Body Size, Insulin-Secreting Cells, Adiponectin
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