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


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 (Delta RQ 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.
Galgani
Jose E
JE
Pennington Biomedical Research Center, 6400 Perkins Rd., Baton Rouge, LA 70808, USA.
Heilbronn
Leonie K
LK
Azuma
Koichiro
K
Kelley
David E
DE
Albu
Jeanine B
JB
Pi-Sunyer
Xavier
X
Smith
Steven R
SR
Ravussin
Eric
E
D001692:Biological Transport / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism*; D001823:Body Composition; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology*; D015309:Glucose Clamp Technique; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D010101:Oxygen Consumption / Q000187:drug effects; D012016:Reference Values
D001786:Blood Glucose; D007328:Insulin; D005947:Glucose