Metabolic Flexibility in Response to Glucose Is Not Impaired in People With Type 2 Diabetes After Controlling for Glucose Disposal Rate
- Jose E. Galgani1,
- Leonie K. Heilbronn1,2,
- Koichiro Azuma3,
- David E. Kelley3,
- Jeanine B. Albu4,
- Xavier Pi-Sunyer4,
- Steven R. Smith1,
- Eric Ravussin1 and
- and the Look AHEAD Adipose Research Group*
- 1Pennington Biomedical Research Center, Baton Rouge, Louisiana
- 2Garvan Institute of Medical Research, New South Wales, Australia
- 3Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
- 4New York Obesity Research Center, St. Luke's Roosevelt Hospital Center, New York, New York
- Address correspondence and reprint requests to Eric Ravussin, PhD, Pennington Biomedical Research Center, 6400 Perkins Rd., Baton Rouge, LA 70808. E-mail:
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/m2 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 (R2 = 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 (ΔRQ 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.
- Received January 11, 2008.
- Accepted January 12, 2008.