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

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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 2007

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Type 2 Diabetes Mellitus
Glucose Tolerance Test
Glucose
Insulin Resistance
Glucose Intolerance
Insulin
Waist Circumference
Hyperglycemia
Research Design
Weights and Measures

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Cnop, M., Vidal, J., Hull, R. L., Utzschneider, K. M., Carr, D. B., Schraw, T., ... 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

Progressive loss of β-cell function leads to worsening glucose tolerance in first-degree relatives of subjects with type 2 diabetes. / Cnop, Miriam; Vidal, Josep; Hull, Rebecca L.; Utzschneider, Kristina M.; Carr, Darcy B.; Schraw, Todd; Scherer, Philipp E.; Boyko, Edward J.; Fujimoto, Wilfred Y.; Kahn, Steven E.

In: Diabetes Care, Vol. 30, No. 3, 03.2007, p. 677-682.

Research output: Contribution to journalArticle

Cnop, M, Vidal, J, Hull, RL, Utzschneider, KM, Carr, DB, Schraw, T, Scherer, PE, Boyko, EJ, Fujimoto, WY & Kahn, SE 2007, 'Progressive loss of β-cell function leads to worsening glucose tolerance in first-degree relatives of subjects with type 2 diabetes', Diabetes Care, vol. 30, no. 3, pp. 677-682. https://doi.org/10.2337/dc06-1834
Cnop, Miriam ; Vidal, Josep ; Hull, Rebecca L. ; Utzschneider, Kristina M. ; Carr, Darcy B. ; Schraw, Todd ; Scherer, Philipp E. ; Boyko, Edward J. ; Fujimoto, Wilfred Y. ; Kahn, Steven E. / Progressive loss of β-cell function leads to worsening glucose tolerance in first-degree relatives of subjects with type 2 diabetes. In: Diabetes Care. 2007 ; Vol. 30, No. 3. pp. 677-682.
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