title: Failure of hyperglycemia and hyperinsulinemia to compensate for impaired metabolic response to an oral glucose load.
abstract: 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 75g 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.
authors.affiliation: Indiana University School of Medicine, Indianapolis, IN.
authors.forename: M
authors.initials: M
authors.lastname: Hussain
authors.affiliation: BioChemAnalysis Inc., Chicago IL; Center for Stable Isotope Research Inc, Chicago IL.
authors.forename: M
authors.initials: M
authors.lastname: Janghorbani
authors.affiliation: BioChemAnalysis Inc., Chicago IL.
authors.forename: S
authors.initials: S
authors.lastname: Schuette
authors.affiliation: Indiana University School of Medicine, Indianapolis, IN.
authors.forename: R V
authors.initials: RV
authors.lastname: Considine
authors.affiliation: Indiana University School of Medicine, Indianapolis, IN.
authors.forename: R L
authors.initials: RL
authors.lastname: Chisholm
authors.affiliation: Indiana University School of Medicine, Indianapolis, IN. Electronic address: kmather@iu.edu.
authors.forename: K J
authors.initials: KJ
authors.lastname: Mather
mesh_terms: D000328:Adult; D052636:Allostasis; D015992:Body Mass Index; D001944:Breath Tests; D002245:Carbon Dioxide / Q000032:analysis / Q000378:metabolism; D002250:Carbon Radioisotopes; D002952:Citric Acid Cycle; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism*; D005260:Female; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006019:Glycolysis; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism*; D006946:Hyperinsulinism / Q000378:metabolism*; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009765:Obesity / Q000097:blood / Q000378:metabolism*
chemical_list: D002250:Carbon Radioisotopes; D002245:Carbon Dioxide
keywords: Breath test; Compensation; Glucose oxidation; Hyperglycemia; Hyperinsulinemia; Insulin resistance