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 journalArticle

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Abstract

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
JournalDiabetes
Volume57
Issue number4
DOIs
Publication statusPublished - 2008 Apr
Externally publishedYes

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Type 2 Diabetes Mellitus
Glucose
Insulin
Weight Loss
Fasting
Photon Absorptiometry
Body Composition
Nonesterified Fatty Acids
Life Style
Research Design
Obesity
Fats
Carbohydrates

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Galgani, J. E., Heilbronn, L. K., Azuma, K., Kelley, D. E., Albu, J. B., Pi-Sunyer, X., ... Ravussin, E. (2008). Metabolic flexibility in response to glucose is not impaired in people with type 2 diabetes after controlling for glucose disposal rate. Diabetes, 57(4), 841-845. https://doi.org/10.2337/db08-0043

Metabolic flexibility in response to glucose is not impaired in people with type 2 diabetes after controlling for glucose disposal rate. / Galgani, Jose E.; Heilbronn, Leonie K.; Azuma, Koichiro; Kelley, David E.; Albu, Jeanine B.; Pi-Sunyer, Xavier; Smith, Steven R.; Ravussin, Eric.

In: Diabetes, Vol. 57, No. 4, 04.2008, p. 841-845.

Research output: Contribution to journalArticle

Galgani, JE, Heilbronn, LK, Azuma, K, Kelley, DE, Albu, JB, Pi-Sunyer, X, Smith, SR & Ravussin, E 2008, 'Metabolic flexibility in response to glucose is not impaired in people with type 2 diabetes after controlling for glucose disposal rate', Diabetes, vol. 57, no. 4, pp. 841-845. https://doi.org/10.2337/db08-0043
Galgani, Jose E. ; Heilbronn, Leonie K. ; Azuma, Koichiro ; Kelley, David E. ; Albu, Jeanine B. ; Pi-Sunyer, Xavier ; Smith, Steven R. ; Ravussin, Eric. / Metabolic flexibility in response to glucose is not impaired in people with type 2 diabetes after controlling for glucose disposal rate. In: Diabetes. 2008 ; Vol. 57, No. 4. pp. 841-845.
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AU - Kelley, David E.

AU - Albu, Jeanine B.

AU - Pi-Sunyer, Xavier

AU - Smith, Steven R.

AU - Ravussin, Eric

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N2 - 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.

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