Mitochondrial dysregulation in the pathogenesis of diabetes: potential for mitochondrial biogenesis-mediated interventions.

Muscle mitochondrial metabolism is a tightly controlled process that involves the coordination of signaling pathways and factors from both the nuclear and mitochondrial genomes. Perhaps the most important pathway regulating metabolism in muscle is mitochondrial biogenesis. In response to physiological stimuli such as exercise, retrograde signaling pathways are activated that allow crosstalk between the nucleus and mitochondria, upregulating hundreds of genes and leading to higher mitochondrial content and increased oxidation of substrates. With type 2 diabetes, these processes can become dysregulated and the ability of the cell to respond to nutrient and energy fluctuations is diminished. This, coupled with reduced mitochondrial content and altered mitochondrial morphology, has been directly linked to the pathogenesis of this disease. In this paper, we will discuss our current understanding of mitochondrial dysregulation in skeletal muscle as it relates to type 2 diabetes, placing particular emphasis on the pathways of mitochondrial biogenesis and mitochondrial dynamics, and the therapeutic value of exercise and other interventions.

Recent evolution in demographic and clinical characteristics and in-hospital morbidity in patients undergoing coronary surgery.

BACKGROUND: Over the last 12 years, the demographic and clinical characteristics of patients undergoing myocardial revascularization surgery have evolved rapidly. The goal of our study was to analyze the evolution of these trends and the results of these surgical interventions. METHODS: We identified patients who underwent a first or second myocardial revascularization between 1993 and 2004, and we arbitrarily divided them into 2 groups: 1 cohort of patients who underwent surgery between 1993 and 1998 and 1 cohort of patients who underwent surgery between 1999 and 2004. We compared demographic and clinical characteristics between the 2 cohorts and determined which variables were significant predictors of morbidity and mortality. RESULTS: From 1993 to 2004, 12 202 patients underwent a first (95.5%) or second (4.5%) myocardial revascularization. Patients in the later cohort presented with a high-risk profile. They were older and had metabolic syndrome or diabetes and peripheral vascular disease. On the other hand, there were fewer active smokers in this group. Whereas the rate of postoperative infarction and renal insufficiency was higher in the second cohort, this group had a lower incidence of stroke and prolonged mechanical ventilation and shorter hospital stays. Overall, observed mortality decreased in spite of a steady increase in predicted mortality. Identified predictors of mortality were age, stroke, female sex, nonelective surgery, renal insufficiency, peripheral vascular disease, chronic obstructive pulmonary disease, ventricular dysfunction and stenosis of the left main trunk. CONCLUSION: Our study confirmed current trends that show an increase in the at-risk population with dysmetabolic syndrome in cardiac surgery, as well as constant improvements in tertiary care in anesthesia and coronary surgery.