Pharmacological Interventions

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There are three pharmacological agents often referred to as "insulin sensitizers"; two thiazoli-denedione (TZD) compounds (rosiglitazone and pioglitazone) and metformin. Despite the frequency with which this term is applied to metformin, in the absence of weight loss, insulin-stimulated glucose disposal does not increase in metformin-treated individuals [59-61]. It is outside the province of this chapter to discuss the mechanism of action of met-formin, nor its use as an effective treatment of type 2 diabetes or PCOS, but the clinical utility of metformin does not seem to reside in its ability to enhance insulin-stimulated glucose uptake.

In contrast, there is no question that TZD compounds will enhance insulin-stimulated glucose uptake in insulin-resistant, nondiabetic individuals, associated with a decrease in daylong plasma insulin and FFA concentrations [62,63]. In addition, there is evidence that TZD compounds have potentially clinically beneficial effects, independent of their ability to enhance insulin sensitivity, for example, decreasing circulating inflammatory markers and increases in plasma adiponectin concentrations [62,64].

In addition to their clinically useful metabolic benefits, TZD compounds are approved for treatment of type 2 diabetes, and have been shown to decrease hepatic steatosis in patients with nonalcoholic fatty liver disease [65] and result in pregnancy when given to women with PCOS [66]. In light of this appealing clinical profile, the possibility that these compounds might be particularly effective in reducing CVD, and preventing the development of type 2 diabetes in particularly susceptible individuals, that is, insulin resistant, but without known disease. At the present time there are no data indicating that the development of CVD can be decreased when a TZD compound is given to insulin-resistant, nondiabetic individuals, with no evidence of CVD. On the other hand, there is information concerning the use of "insulin sensitizers" in delaying the progression to type 2 diabetes of individuals classified as having prediabetes.

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