Clinical Aspects of Glucose Metabolism and Chronic Disease.

The burden of chronic disease is an emerging world health problem. Advances made in the treatment of individual disease states often fail to consider multimorbidity patterns in clinical research models. Adjusting for age as a confounder ignores its contribution as a powerful risk factor for most chronic diseases. Sarcopenia is an age-related loss of skeletal muscle mass, which is accelerated by chronic inflammation and its resulting cascade of cytokines. Skeletal muscle loss results in insulin resistance, hyperglycemia, and altered mitochondrial glucose signaling pathways. Vascular disease in the brain may alter blood-brain barrier function, allowing transport of substances into the brain which adversely affect the "astrocyte-centric" subunit. Neurogenesis that provides neuronal plasticity is impaired in the diabetic brain, while insulin resistance markers such as insulin-like growth factor (IGF-1) and insulin receptor substrate (IRS-1) are associated with poor cognitive performance. Advanced glycation end products generated by chronic hyperglycemia are found in postmortem AD brain. Intranasal insulin administration, a preferential route for CNS delivery, improved cognitive function in healthy adults, without affecting circulating levels of insulin or glucose. Exercise has demonstrated a neuroprotective effect through induction of antioxidative enzymes, neurotrophic, and vascular endothelial growth factors. Sarcopenia appears to be a dynamic process and is potentially reversible with attention to nutrition and cardiovascular fitness. Early detection and intervention may slow the progression of multimortality disease states and should be a focus of worldwide health systems.

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