Insulin resistance: comparison of the role in onset and progression of type 2 diabetes, atherosclerotic vascular disease and neurodegenerative disorders

Previous findings suggested that insulin resistance (IR) is underlying pathogenesis of diverse diseases such as type 2 diabetes (T2D), atheroclerotic vascular disease (AVD) and neurodegenerative disorders (NDDs). Thus, primary objective of this project is to perform a comparative analysis of relationship between IR levels and onset and progression of (1) T2D (high-risk individuals, gestational diabetes, overt T2D) (2) AVD (ischemic heart and brain diseases) and (3) NDDs (Alzheimer and Parkinson diseases) during 2yr follow up. The analysis includes testing of IR levels (euglycemic hyperinsulinemic clamp), oxidative vs non-oxidative glucose disposal (indirect calorimetry) and insulin receptor content and autophosphorylation capacity in muscle bioptate. Secondary objectives will comprise comparative analyses of changes in IR levels and other disease determinants: (a) insulin secretion capacity; (b) insulin and energy homeostasis regulating hormones (leptin, resistin, adiponectin and GLP 1); (c) dyslipidemia, hypofibrinolysis, oxidative stress and inflammation mediators; (d) total and abdominal obesity; (e) endothelial disfunction, vascular stenosis, plaque stability and arterial pressure and (f) cognitive function impairments. In general, the results of this project should contribute to evaluation of the hypothesis that IR exerts its effect through the same or similar mechanisms in the settings of different pathogenetic templates resulting in development of T2D, AVD and NDDs.