PT  - JOURNAL ARTICLE
AU  - Cnop, Miriam
AU  - Vidal, Josep
AU  - Hull, Rebecca L.
AU  - Utzschneider, Kristina M.
AU  - Carr, Darcy B.
AU  - Schraw, Todd
AU  - Scherer, Philipp E.
AU  - Boyko, Edward J.
AU  - Fujimoto, Wilfred Y.
AU  - Kahn, Steven E.
TI  - Progressive Loss of β-Cell Function Leads to Worsening Glucose Tolerance in First-Degree Relatives of Subjects With Type 2 Diabetes
AID  - 10.2337/dc06-1834
DP  - 2007 Mar 01
TA  - Diabetes Care
PG  - 677--682
VI  - 30
IP  - 3
4099  - http://care.diabetesjournals.org/content/30/3/677.short
4100  - http://care.diabetesjournals.org/content/30/3/677.full
SO  - Diabetes Care2007 Mar 01; 30
AB  - 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.