title: Postexercise phosphocreatine recovery, an index of mitochondrial oxidative phosphorylation, is reduced in diabetic patients with lower extremity complications.
abstract: OBJECTIVE
  To identify differences in postexercise phosphocreatine (PCr) recovery, an index of mitochondrial function, in diabetic patients with and without lower extremity complications.
  
  
  METHODS
  We enrolled healthy control subjects and three groups of patients with type 2 diabetes mellitus: without complications, with peripheral neuropathy, and with both peripheral neuropathy and peripheral arterial disease. We used magnetic resonance spectroscopic measurements to perform continuous measurements of phosphorous metabolites (PCr and inorganic phosphate [Pi]) during a 3-minute graded exercise at the level of the posterior calf muscles (gastrocnemius and soleus muscles). Micro- and macrovascular reactivity measurements also were performed.
  
  
  RESULTS
  The resting Pi/PCr ratio and PCr at baseline and the maximum reached during exercise were similar in all groups. The postexercise time required for recovery of Pi/PCr ratio and PCr levels to resting levels, an assessment of mitochondrial oxidative phosphorylation, was significantly higher in diabetic patients with neuropathy and those with both neuropathy and peripheral arterial disease (P < .01 for both measurements). These two groups also had higher levels of tumor necrosis factor-α (P < .01) and granulocyte colony-stimulating factor (P < .05). Multiple regression analysis showed that only granulocyte colony-stimulating factor, osteoprotegerin, and tumor necrosis factor-α were significant contributing factors in the variation of the Pi/PCr ratio recovery time. No associations were observed between micro- and macrovascular reactivity measurements and Pi/PCr ratio or PCr recovery time.
  
  
  CONCLUSIONS
  Mitochondrial oxidative phosphorylation is impaired only in type 2 diabetes mellitus patients with neuropathy whether or not peripheral arterial disease is present and is associated with the increased proinflammatory state observed in these groups.
authors: Joslin-Beth Israel Deaconess Foot Center and Microcirculation Lab, Beth Israel Deaconess Medical Center, and Harvard Medical School, Boston, MA, USA.
authors: Francesco
authors: F
authors: Tecilazich
authors: Thanh
authors: T
authors: Dinh
authors: Thomas E
authors: TE
authors: Lyons
authors: Julie
authors: J
authors: Guest
authors: Rosemond A
authors: RA
authors: Villafuerte
authors: Christos
authors: C
authors: Sampanis
authors: Charalambos
authors: C
authors: Gnardellis
authors: Chun S
authors: CS
authors: Zuo
authors: Aristidis
authors: A
authors: Veves
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D015444:Exercise; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism*; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000503:physiopathology; D053244:Osteoprotegerin / Q000097:blood; D010085:Oxidative Phosphorylation; D058729:Peripheral Arterial Disease / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D010725:Phosphocreatine / Q000378:metabolism*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D018836:Inflammation Mediators; D053244:Osteoprotegerin; C506030:TNFRSF11B protein, human; D014409:Tumor Necrosis Factor-alpha; D010725:Phosphocreatine; D016179:Granulocyte Colony-Stimulating Factor