Predominant role of reduced beta-cell sensitivity to glucose over insulin resistance in impaired glucose tolerance

E. Ferrannini, A. Gastaldelli, Y. Miyazaki, M. Matsuda, M. Pettiti, A. Natali, A. Mari, R. A. DeFronzo

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93 Scopus citations

Abstract

Aims/hypothesis. Impaired glucose tolerance (IGT) is an insulin-resistant state and a risk factor for Type 2 diabetes. The relative roles of insulin resistance and insulin deficiency in IGT have been disputed. Methods. In 40 IGT subjects and 63 sex-, age-, and weight-matched controls with normal glucose tolerance (NGT), we measured (i) indices of insulin sensitivity of fasting glucose production (by tracer glucose) and glucose disposal (M value on a 240 pmol·min-1·m-2 insulin clamp) and (ii) indices of beta-cell function (glucose sensitivity, rate sensitivity, and potentiation) derived from model analysis (Am J Physiol 283:E1159-E1166, 2002) of the insulin secretory response (by C-peptide deconvolution) to oral glucose. Results. In comparison with NGT, IGT were modestly insulin resistant (M=29±2 vs 35±2 μmol·min-1·kg FFM-1, p=0.01); insulin sensitivity of glucose production also was reduced, in approximate proportion to M. Despite higher baseline insulin secretion rates, IGT was characterized by a 50% reduction in glucose sensitivity [53 (36) vs 102 (123) pmol·min-1·m -2·mM-1, median (interquartile range), p=0.001] and impaired potentiation [1.6 (0.8) vs 2.0 (1.5) units, p<0.04] of insulin release, whereas rate sensitivity [1.15 (1.15) vs 1.38 (1.28) nmol·m -2·mM-1] was not significantly reduced. Glucose sensitivity made the single largest contribution (∼50%) to the observed variability of glucose tolerance. Conclusion/interpretation. In IGT the defect in glucose sensitivity of insulin release quantitatively predominates over insulin resistance in the genesis of the reduced tolerance to oral glucose.

Original languageEnglish (US)
Pages (from-to)1211-1219
Number of pages9
JournalDiabetologia
Volume46
Issue number9
DOIs
StatePublished - Sep 1 2003

Keywords

  • Beta-cell function
  • IGT
  • Insulin resistance
  • Insulin secretion
  • Mathematical modelling

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Ferrannini, E., Gastaldelli, A., Miyazaki, Y., Matsuda, M., Pettiti, M., Natali, A., Mari, A., & DeFronzo, R. A. (2003). Predominant role of reduced beta-cell sensitivity to glucose over insulin resistance in impaired glucose tolerance. Diabetologia, 46(9), 1211-1219. https://doi.org/10.1007/s00125-003-1169-6