Tags

Type your tag names separated by a space and hit enter

Progressive loss of beta-cell function leads to worsening glucose tolerance in first-degree relatives of subjects with type 2 diabetes.
Diabetes Care. 2007 Mar; 30(3):677-82.DC

Abstract

OBJECTIVE

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

Authors+Show Affiliations

Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, VA Puget Sound Health Care System and University of Washington, Seattle, Washington 98108, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

17327340

Citation

Cnop, Miriam, et al. "Progressive Loss of Beta-cell Function Leads to Worsening Glucose Tolerance in First-degree Relatives of Subjects With Type 2 Diabetes." Diabetes Care, vol. 30, no. 3, 2007, pp. 677-82.
Cnop M, Vidal J, Hull RL, et al. Progressive loss of beta-cell function leads to worsening glucose tolerance in first-degree relatives of subjects with type 2 diabetes. Diabetes Care. 2007;30(3):677-82.
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 beta-cell function leads to worsening glucose tolerance in first-degree relatives of subjects with type 2 diabetes. Diabetes Care, 30(3), 677-82.
Cnop M, et al. Progressive Loss of Beta-cell Function Leads to Worsening Glucose Tolerance in First-degree Relatives of Subjects With Type 2 Diabetes. Diabetes Care. 2007;30(3):677-82. PubMed PMID: 17327340.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Progressive loss of beta-cell function leads to worsening glucose tolerance in first-degree relatives of subjects with type 2 diabetes. 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, PY - 2007/3/1/pubmed PY - 2007/4/28/medline PY - 2007/3/1/entrez SP - 677 EP - 82 JF - Diabetes care JO - Diabetes Care VL - 30 IS - 3 N2 - OBJECTIVE: The relative roles of insulin resistance and beta-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, beta-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, beta-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 beta-cell function. Thus, early interventions to slow the decline in beta-cell function should be considered in high-risk individuals. SN - 1935-5548 UR - https://www.unboundmedicine.com/medline/citation/17327340/Progressive_loss_of_beta_cell_function_leads_to_worsening_glucose_tolerance_in_first_degree_relatives_of_subjects_with_type_2_diabetes_ L2 - http://care.diabetesjournals.org/cgi/pmidlookup?view=long&amp;pmid=17327340 DB - PRIME DP - Unbound Medicine ER -