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We used the insulin-perfused human forearm model to assess the effects of vasoconstriction induced with norepinephrine on the extraction of glucose in the forearm in two groups of healthy young volunteers. The norepinephrine findings were compared with a previously studied group in which vasoconstriction had been caused by reflex activation of the sympathetic nervous system. The aim of the study was to determine the relative importance of hemodynamic and receptor-mediated mechanisms of insulin resistance. Plasma insulin, arterial and venous glucose samples, and forearm blood flow were measured at 10-minute intervals during a 30-minute baseline, a 60-minute intra-arterial insulin infusion, and during 30 minutes of insulin infusion plus vasoconstriction. Group 1 (n=14) had physiological vasoconstriction induced by inflation of bilateral thigh cuffs to 40 mm Hg to cause pooling of blood in the lower extremities and reflex vasoconstriction in the forearm; group 2 (n=8) had intra-arterial infusion of norepinephrine to achieve the same degree of vasoconstriction as seen with inflation of thigh cuffs in group 1. Subjects in A frequent association of tissue insulin insensitivity and blood pressure in humans has been ob-L. served in several clinical surveys.17 Recent investigations have focused on a possible pressor effect of insulin through sympathetic nervous system tone, 811 an increase in the intravascular volume, 12 -13 or through the effect of insulin on vascular smooth muscle.14 ' 15 It has been speculated that high insulin in insulin-resistant states may cause the increase of blood pressure in hypertension through these various pressor mechanisms. 16 In contrast to the insulinogenic hypothesis of the blood pressure elevation, the infusion of insulin into humans has been repeatedly associated with vasodilation or attenuation of vasoconstrictive stimuli instead of a pressor effect.11 . 1719In a recent review we offered an alternative explanation for the frequent association between elevated blood pressure and insulin resistance. 20 ' 21 We proposed that vascular changes in the microcirculation secondary to long-standing elevations in blood pressure may alter the delivery of insulin and glucose to tissues and may thereby, in part, cause insulin resistance. Our hypothesis suggests that the primary defect may be vascular in nature, from elevation in blood pressure, and not in tissue sensitivity to the effects of insulin. A first step group 3 (n=7) had infusion of intra-arterial norepinephrine to achieve a twofold increase in physiological vasoconstriction. With a physiological decrease in forearm blood flow (group 1), there was a 19% decrease in forearm blood flow resulting in a 23% reduction in glucose uptake in the forearm (P<.03). The same degree of reduction in forearm blood flow with a predominantly a-adrenergic agonist, norepinephrine (group 2), causes much less insulin resistance (a decrease in utilization of 13%) (P

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Seventy percent of the residents studied in Tecumseh are physically inactive and have a less favorable cardiac risk profile. Enhancement of exercise habits may beneficially affect cardiovascular status and, presumably, the prognosis.

Background: Theory-based methods to support the uptake of evidence-based practices (EBPs) are critical to improving mental health outcomes. Implementation strategy costs can be substantial, and few have been rigorously evaluated. The purpose of this study is to conduct a cost-effectiveness analysis to identify the most cost-effective approach to deploying implementation strategies to enhance the uptake of Life Goals, a mental health EBP. Methods: We used data from a previously conducted randomized trial to compare the cost-effectiveness of Replicating Effective Programs (REP) combined with external and/or internal facilitation among sites non-responsive to REP. REP is a low-level strategy that includes EBP packaging, training, and technical assistance. External facilitation (EF) involves external expert support, and internal facilitation (IF) augments EF with protected time for internal staff to support EBP implementation. We developed a decision tree to assess 1-year costs and outcomes for four implementation strategies: 1) REP only, 2) REP+EF 3) REP+EF add IF if needed, 4) REP+EF/IF. The analysis used a 1-year time horizon and assumed a health payer perspective. Our outcome was quality-adjusted life years (QALYs). The economic outcome was the incremental cost-effectiveness ratio (ICER). We conducted deterministic and probabilistic sensitivity analysis (PSA). Results: Our results indicate that REP+EF add IF is the most cost-effective option with an ICER of $593/QALY. The REP+EF/IF and REP+EF only conditions are dominated (i.e., more expensive and less effective than comparators). One-way sensitivity analyses indicate that results are sensitive to utilities for REP+EF and REP+EF add IF. The PSA results indicate that REP+EF, add IF is the optimal strategy in 30% of iterations at the threshold of $100,000/QALY. Conclusions: Our results suggest that the most cost-effective implementation support begins with a less intensive, less costly strategy initially and increases as needed to enhance EBP uptake. Using this approach, implementation support resources can be judiciously allocated to those clinics that would most benefit. Our results were not robust to changes in the utility measure. Research is needed that incorporates robust and relevant utilities in implementation studies to determine the most cost-effective strategies. This study advances economic evaluation of implementation by assessing costs and utilities across multiple implementation strategy combinations.