phosphocreatine and Diabetic-Angiopathies

To identify differences in postexercise phosphocreatine (PCr) recovery, an index of mitochondrial function, in diabetic patients with and without lower extremity complications.. 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.. 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.. 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.

Topics: Adult; Aged; Aged, 80 and over; Case-Control Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Neuropathies; Exercise; Female; Granulocyte Colony-Stimulating Factor; Humans; Inflammation Mediators; Magnetic Resonance Spectroscopy; Male; Middle Aged; Mitochondria; Muscle Contraction; Muscle, Skeletal; Osteoprotegerin; Oxidative Phosphorylation; Peripheral Arterial Disease; Phosphocreatine; Time Factors; Tumor Necrosis Factor-alpha

This study was performed to assess left ventricular (LV) energy metabolism and function in patients with type 1 diabetes with or without overt microvascular complications.. We performed cardiac Magnetic Resonance Imaging (MRI) and (31)P spectroscopy (MRS) in 24 patients with overt microvascular complications and in 15 carefully selected patients without complications in spite of a long duration of the disease (>20 years) and matched for anthropometric features. 31 healthy subjects served as a control group.. Systolic function was preserved in all study subjects. Patients with overt complications showed a higher LV wall mass/end diastolic volume ratio and altered parameters of diastolic function when compared to patients without complications and to controls. They were also characterized by lower PCr/ATP ratio (a recognized marker of energy metabolism). No effect of HbA1c was detected within groups.. In patients with type 1 diabetes 1) overt microvascular complications were associated with altered LV geometry, diastolic function and energy metabolism 2) in patients without complications and duration of disease >20 years no association with these alterations were found despite poor glycemic control. The features of this highly selected subgroup of patients demonstrated that long lasting chronic hyperglycemia per se is not sufficient to induce abnormality of cardiac energy metabolism and that additional yet to be identified (metabolic or genetic) factors must be important contributing factors.

Topics: Adenosine Triphosphate; Adult; Blood Glucose; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diastole; Energy Metabolism; Fatty Acids; Female; Homeostasis; Humans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Microcirculation; Middle Aged; Phosphocreatine; Systole; Ventricular Function, Left

We have demonstrated that food restriction that is associated with weight loss can produce a type of cardiac dysfunction similar to that produced by diabetes. As in diabetic atria, the food-restricted atria had a 2-fold increase in contraction force, rate of force development, and rate of force decline compared with controls. Both food-restricted and diabetic atria could tolerate anoxia better than controls. The contractile function of the whole perfused heart from the food-restricted rat was reduced, as in the case of the diabetic heart. As the left ventricular volume was increased, the left ventricular developed pressure and the rate of rise and fall in pressure were significantly reduced in both food-restricted and diabetic hearts, compared with those of age- and weight-matched controls. The positive inotropic responses of atria and whole perfused heart to increasing concentrations of extracellular calcium were similarly altered in food-restricted and diabetic hearts. The possible molecular mechanisms of these findings and some of the differences observed between food-restricted and diabetic hearts are discussed.

Topics: Adenosine Triphosphate; Animals; Blood Glucose; Calcium; Cardiomyopathies; Diabetes Mellitus, Experimental; Diabetic Angiopathies; Diet, Reducing; Insulin; Male; Myocardial Contraction; Phosphocreatine; Rats; Rats, Sprague-Dawley; Ventricular Function, Left

Topics: Adenosine Triphosphate; Arterial Occlusive Diseases; Diabetic Angiopathies; Energy Metabolism; Humans; Intermittent Claudication; Magnetic Resonance Spectroscopy; Male; Middle Aged; Muscles; Phosphates; Phosphocreatine; Prospective Studies