"Background: The human micro- and macrocirculation have distinct vital roles in the homeostasis of the cardiovascular system. There is a cross-talk between the two circuits to achieve the adequate vascular adaptations. Reciprocal transduction of ills signal between the micro- and macrocirculation may impair their optimal coupling and further accelerate vascular disease. In Europe the prevalence of insulin resistance (IR) (obesity and diabetes type 2) states and the related vascular damage and mortality is increasing rapidly. Main Scientific objective: to identify the early events in the natural history of chronic vascular disease of the micro- and macrocirculation in IR states and to investigate of the adaptive process of each circuit to the other in order to maintain optimal coupling. Specific scientific objectives: investigation of the cross-talk between wave reflections, pressure amplification, blood pressure phenotypes and blood flow patterns (conduit arteries, skin, muscle, retina) and their relation to the function and structure of large/small arteries, arterioles and cappilaries, endothelial function. Main training Objective: trained-through-research under supervision and hands-on training on microcirculation novel techniques; supervision of the investigations on macrocirculation. Study design: observational, population-based cross sectional study. Study population: random sample (1200 subjects) of Maastricht's area population with and without IR states, age 40-75. Microcirculation: skin videomicroscopy, retinamicroscopy, skin laser doppler and fourier analyses, muscle contrast-enhanced ultrasound,Macrocirculation: pulse wave analysis (mathematic applications-wave separation analysis), pulse wave velocity, carotid/brachial ultrasound, Other methods: All participants will be phenotyped by means of questionnaire, biood, urine, anthropometry, electrocardiogran and echocardiography.Expected results: to identify the very early events and the adaptive processes"