Cited by 174Pancreatic function and diabetesDiabetes, Cardiovascular Risks, and LipoproteinsDiabetes Treatment and Management

Progressive loss of β-cell function leads to worsening glucose tolerance in first-degree relatives of subjects with type 2 diabetes

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Cnop, Miriam, Vidal, Josep, Hull, Rebecca L., Utzschneider, Kristina M., Carr, Darcy B., Schraw, Todd, Scherer, Philipp E., Boyko, Edward J. +2 more·2007·Diabetes Care

Abstract

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 at increased risk of diabetes, including first-degree relatives, women with gestational diabetes or PCOS, and older individuals.

    “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.”

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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)
Venue
Diabetes Care
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
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 › Surgery › 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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