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Diabetologia. 2003 Sep;46(9):1211-9. Epub 2003 Jul 23.

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

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1
Metabolism Unit, C.N.R. Institute of Clinical Physiology and Department of Internal Medicine, University of Pisa School of Medicine, Pisa, Italy. ferranni@ifc.cnr.it

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 x min(-1) x 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 micromol x min(-1) x 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 x min(-1) x m(-2) x 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 x m(-2) x mM(-1)] was not significantly reduced. Glucose sensitivity made the single largest contribution (approximately 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.

PMID:
12879253
DOI:
10.1007/s00125-003-1169-6
[Indexed for MEDLINE]
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