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Metabolic Dysfunction in Diabetic Offspring: Deviations in Metabolic Flexibility


Medicine & Science in Sports & Exercise: January 2013 - Volume 45 - Issue 1 - p 8–15
doi: 10.1249/MSS.0b013e31826909d3
Clinical Sciences

In type 2 diabetes (T2D), insulin resistance is related to comorbidities, including high lipotoxicity, poor glucoregulation, and loss of metabolic flexibility. Controversy exists regarding whether reduced metabolic flexibility precedes insulin resistance or vice versa.

Purpose The purpose of this study was to determine whether a family history of T2D leads to metabolic inflexibility.

Methods To examine potential loss of metabolic flexibility at early stages, we used a hooded metabolic cart to compare metabolic characteristics in people with T2D, family history of T2D (FH+), and controls (FH−) 1) at rest, 2) with passive stretching (PS) and recovery, and 3) with oral glucose load. Testing of 9 T2D, 11 FH+, and 9 FH− occurred after a 12-h fast under resting conditions. Expired gas and blood glucose (BG) were measured before and after each condition.

Results PS lowered BG (P < 0.05) in FH− and FH+ (mean ± SD, −2.7 ± 5.9 and −5.8 ± 7.5 mg·mL−1) compared with T2D (−0.9 ± 7.7). CHO use (kcal·min−1) increased with PS in all groups (0.04 ± 0.18, 0.03 ± 0.26, and 0.22 ± 1.6 mg·mL−1 in FH−, FH+, and T2D, respectively). For oral glucose load, different metabolic flexibility existed between FH− as well as FH+ (0.16 ± 0.07) as well as T2D (0.16 ± 0.07), with no difference between FH− and T2D.

Conclusion PS increases glycolytic activity without affecting BG in T2D, and reductions in metabolic flexibility exist in T2D and FH+ without glucoregulatory impairment in FH+, indicating early stage of mitochondrial dysfunction in FH+. Findings indicate PS is an important tool for assessing metabolic flexibility.

1Department of Kinesiology, Louisiana State University, Baton Rouge, LA; 2Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD; and 3Department of Kinesiology and Health Studies, Southeastern Louisiana University, Hammond, LA

Address for correspondence: Ryan D. Russell, Ph.D., Department of Medicine, University of Maryland School of Medicine, 660 W Redwood Street, HH 313-A, Baltimore, MD 21201; E-mail:

Submitted for publication March 2012.

Accepted for publication July 2012.

©2013The American College of Sports Medicine