Metabolic Inflexibility: The link Connecting Diabetics with First and Second Degree Offspring of Diabetes?

In type 2 diabetes (T2D), insulin resistance (IR) is related to co‐morbidities including high lipotoxicity, poor glucoregulation, and loss of metabolic flexibility (MF). Controversy exists over whether declining MF precedes IR, or vice versa. To examine potential loss of MF at early stages, we used a hooded metabolic cart to compare metabolic trends in people with T2D, family history of T2D (FH), and controls (Con) 1) at rest, 2) with passive stretching (PS) and recovery, and 3) with oral glucose tolerance test (OGTT). Testing of 9 T2D, 11 FH, and 9 Con occurred after a 12 hour fast under resting conditions. Expired gas, and blood‐glucose (BG) were measured before and after each stage. PS lowered BG (p < .05) in Con and FH (mean ± SD, −2.7 ± 5.9, −5.8 ± 7.5mg/mL) compared to T2D (−0.9 ± 7.7). CHO use (kcal/min) increased (p < 0.05) with PS in all groups (0.04 ± 0.18, 0.03 ± 0.26, 0.22 ±1.6mg/mL) (Con, FH, T2D respectively). For OGTT, different MF (Δ RER from fasting to OGTT) exists between Con and T2D (0.16 ± 0.07) as well as FH (0.16 ± 0.07)] with no difference between FH and T2D. Data suggest PS increases glycolysis without affecting BG in T2D, and that similar reductions in MF exist in T2D and FH without glucoregulatory impairment in FH, indicating very early stage mitochondrial dysfunction in FH.