Distinct β-cell defects in impaired fasting glucose and impaired glucose tolerance

Mustafa Kanat, Andrea Mari, Luke Norton, Diedre Winnier, Ralph A. DeFronzo, Chris Jenkinson, Muhammad Abdulghani

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Abstract

To characterize the defects in β-cell function in subjects with impaired fasting glucose (IFG) and compare the results to impaired glucose tolerance (IGT) and normal glucose tolerance (NGT) subjects, β-cell glucose sensitivity and rate sensitivity during the oral glucose tolerance test were measured with the model by Mari in 172 Mexican Americans. A subgroup (n = 70) received a 2-h hyperglycemic clamp (+125 mg/dL), and first- and second-phase insulin secretion were quantitated. Compared with NGT, subjects with IFG and IGT manifested a decrease in β-cell glucose sensitivity; IFG subjects, but not IGT subjects, had decreased β-cell rate sensitivity. In IFG subjects, the defect in β-cell glucose sensitivity was time dependent, began to improve after 60 min, and was comparable to NGT after 90 min. The incremental area under the plasma C-peptide concentration curve during the first 12 min of the hyperglycemic clamp (ΔC-pep [AUC] 0-12) was inversely related with the increase in FPG concentration (r = -36, r = 0.001), whereas ΔC-pep[AUC] 15-120 positively correlated with FPG concentration (r = 0.29, r < 0.05). When adjusted for the prevailing level of insulin resistance, first-phase insulin secretion was markedly decreased in both IFG and IGT, whereas second-phase insulin secretion was decreased only in IGT. These results demonstrate distinct defects in β-cell function in IFG and IGT.

Original languageEnglish
Pages (from-to)447-453
Number of pages7
JournalDiabetes
Volume61
Issue number2
DOIs
Publication statusPublished - 1 Feb 2012

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Kanat, M., Mari, A., Norton, L., Winnier, D., DeFronzo, R. A., Jenkinson, C., & Abdulghani, M. (2012). Distinct β-cell defects in impaired fasting glucose and impaired glucose tolerance. Diabetes, 61(2), 447-453. https://doi.org/10.2337/db11-0995