Type 2 diabetes is a common illness where individuals with the disease are at increased risk of developing significant vascular disease. One possible contributor to vascular disease in these individuals is impaired vasodilatation in response to insulin. In this study we are studying the effects of, and mechanisms of, the drug insulin+s action on forearm blood flow in subjects with the insulin resistant state of type 2 diabetes and non-diabetic control subjects. One effect of insulin is directly vasodilatation and another is reduction in the extent to which norepinephrine (NE), a hormone causing vasoconstriction, decreases blood flow. We have purposefully not eliminated subjects from either group who have hypertension, another state of insulin resistance as it commonly coexists with type 2 diabetes. We intend to study twenty subjects with type 2 diabetes mellitus and 20 subjects without diabetes. Subjects will be males and females between 50-80 years of age with or without mild to moderate hypertension and in good overall medical health. Subjects who are on medications will need to remain without symptoms of hyperglycemia and if hypertensive will need to maintain a blood pressure of < 185/105 mm Hg during the two week withdrawal of medication phase in order to be included. Diabetic subjects will not be eligible to participate if they require insulin for diabetes control. Non-diabetic subjects will be eligible to participate if they do not meet American Diabetes Association criteria for diabetes during a screening oral glucose tolerance test. The goal of this pilot project is to test if impairments in the vasomotor effects of insulin exist in a cohort of older subjects with type 2 diabetes and characterize factors affecting the variability of these vasomotor effects. We will identify any interactions with clinical characteristics of the subjects and whether insulin infusion in this population induces the production of detectable levels of nitric oxide biomarkers as the mechanism of accomplishing vasodilatation. Finally, whether there are any differences in these responses between type 2 diabetes subjects with and without hypertension will be characterized. This information will ultimately be used to design an intervention study to determine whether any improvement in vascular insulin resistance would accompany an intervention resulting in improvement in metabolic insulin sensitivity.
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