Metabolic flexibility in response to glucose is not impaired in people with type 2 diabetes after controlling for glucose disposal rate

Jose E. Galgani, Leonie K. Heilbronn, Koichiro Azuma, David E. Kelley, Jeanine B. Albu, Xavier Pi-Sunyer, Steven R. Smith, Eric Ravussin

Research output: Contribution to journalArticlepeer-review

93 Citations (Scopus)


OBJECTIVE-Compared with nondiabetic subjects, type 2 diabetic subjects are metabolically inflexible with impaired fasting fat oxidation and impaired carbohydrate oxidation during a hyperinsulinemic clamp. We hypothesized that impaired insulin-stimulated glucose oxidation is a consequence of the lower cellular glucose uptake rate in type 2 diabetes. Therefore, we compared metabolic flexibility to glucose adjusted for glucose disposal rate in nondiabetic versus type 2 diabetic subjects and in the latter group after 1 year of lifestyle intervention (the Look AHEAD [Action For Health in Diabetes] trial). RESEARCH DESIGN AND METHODS-Macronutrient oxidation rates under fasting and hyperinsulinemic conditions (clamp at 80 mU/m 2 per min), body composition (dual-energy X-ray absorptiometry), and relevant hormonal/metabolic blood variables were assessed in 59 type 2 diabetic and 42 nondiabetic individuals matched for obesity, sex, and race. Measures were repeated in diabetic participants after weight loss. RESULTS-Metabolic flexibility to glucose (change in respiratory quotient [RQ]) was mainly related to insulin-stimulated glucose disposal rate (R 2 = 0.46, P < 0.0001) with an additional 3% of variance accounted for by plasma free fatty acid concentration at the end of the clamp (P = 0.03). The impaired metabolic flexibility to glucose observed in type 2 diabetic versus nondiabetic subjects (ARQ 0.06 ± 0.01 vs. 0.10 ± 0.01, respectively, P < 0.0001) was no longer observed after adjusting for glucose disposal rate (P = 0.19). Additionally, the increase in metabolic flexibility to glucose after weight loss was accounted for by the concomitant increase in insulin-stimulated glucose disposal rate. CONCLUSIONS-This study suggests that metabolic inflexibility to glucose in type 2 diabetic subjects is mostly related to defective glucose transport.

Original languageEnglish
Pages (from-to)841-845
Number of pages5
Issue number4
Publication statusPublished - 2008 Apr
Externally publishedYes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism


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