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

Miriam Cnop, Josep Vidal, Rebecca L. Hull, Kristina M. Utzschneider, Darcy B. Carr, Todd Schraw, Philipp E. Scherer, Edward J. Boyko, Wilfred Y. Fujimoto, Steven E. Kahn

Research output: Contribution to journalArticle

111 Scopus citations

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 tolbutamidemodified 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.

Original languageEnglish (US)
Pages (from-to)677-682
Number of pages6
JournalDiabetes care
Volume30
Issue number3
DOIs
StatePublished - Mar 1 2007

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing

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    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. (2007). Progressive loss of β-cell function leads to worsening glucose tolerance in first-degree relatives of subjects with type 2 diabetes. Diabetes care, 30(3), 677-682. https://doi.org/10.2337/dc06-1834