Failure of hyperglycemia and hyperinsulinemia to compensate for impaired metabolic response to an oral glucose load

M. Hussain, M. Janghorbani, S. Schuette, R. V. Considine, R. L. Chisholm, K. J. Mather

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Objective To evaluate whether the augmented insulin and glucose response to a glucose challenge is sufficient to compensate for defects in glucose utilization in obesity and type 2 diabetes, using a breath test measurement of integrated glucose metabolism. Methods Non-obese, obese normoglycemic and obese type 2 diabetic subjects were studied on 2 consecutive days. A 75 g oral glucose load spiked with 13C-glucose was administered, measuring exhaled breath 13CO2 as an integrated measure of glucose metabolism and oxidation. A hyperinsulinemic euglycemic clamp was performed, measuring whole body glucose disposal rate. Body composition was measured by DEXA. Multivariable analyses were performed to evaluate the determinants of the breath 13CO2. Results Breath 13CO2 was reduced in obese and type 2 diabetic subjects despite hyperglycemia and hyperinsulinemia. The primary determinants of breath response were lean mass, fat mass, fasting FFA concentrations, and OGTT glucose excursion. Multiple approaches to analysis showed that hyperglycemia and hyperinsulinemia were not sufficient to compensate for the defect in glucose metabolism in obesity and diabetes. Conclusions Augmented insulin and glucose responses during an OGTT are not sufficient to overcome the underlying defects in glucose metabolism in obesity and diabetes.

Original languageEnglish (US)
Pages (from-to)238-244
Number of pages7
JournalJournal of Diabetes and its Complications
Issue number2
StatePublished - Mar 1 2015



  • Breath test
  • Compensation
  • Glucose oxidation
  • Hyperglycemia
  • Hyperinsulinemia
  • Insulin resistance

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine

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