Metabolic dysfunction in diabetic offspring:  deviations in metabolic flexibility.
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.


OBJECTIVE
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.


CONCLUSIONS
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.
Department of Kinesiology, Louisiana State University, Baton Rouge, LA, USA. rrussell@medicine.umaryland.edu
Ryan D
RD
Russell
Robert R
RR
Kraemer
Arnold G
AG
Nelson
D000328:Adult; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D002153:Calorimetry, Indirect; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D004734:Energy Metabolism / Q000235:genetics / Q000502:physiology*; D005260:Female; D005951:Glucose Tolerance Test; D040941:Heredity; D006801:Humans; D008297:Male; D052580:Muscle Stretching Exercises
D015415:Biomarkers; D001786:Blood Glucose