Progressive Loss of ß-Cell Function Leads to Worsening Glucose Tolerance in First-Degree Relatives of Subjects With Type 2 Diabetes  

Oleh:

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.

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Diabetes Care vol. 30 no. 03 (Mar. 2007), page 677.

Ketersediaan

Perpustakaan FK Nomor Panggil: D05.K.2007.01 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

OBJECTIVE—The relative roles of insulin resistance and ß-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, ß-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, ß-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 ß-cell function. Thus, early interventions to slow the decline in ß-cell function should be considered in high-risk individuals.

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