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An important unanswered question is whether more significant weight loss, such as that reported by Zaccardi et al., might itself produce improvements in vascular function. It is possible that the modest weight loss reported in the present study did not attain a critical threshold in correcting the underlying metabolic state as it impacts the vasculature. For example, insulin resistance was not formally measured in the present study. Both groups exhibited an ~30 percent reduction in circulating insulin levels, but this simple measure might obscure a subtle difference in the alteration in metabolic state between the groups (owing, presumably, to the drug), which itself contributed to the observed effects on vascular function. Similarly, a number of unmeasured but potentially relevant factors can be put forward that might have contributed to the beneficial effect on endothelial function. These could include other metabolic variables such as free fatty acids or homocysteine, measures of oxidative state, adipocyte products such as TNF-[alpha], leptin, or adiponectin, or measures of systemic inflammation such as C-reactive protein. In this context, the observed correlation of the vascular effect with change in LDL cholesterol is of interest, but far from conclusive. These issues notwithstanding, the present study suggests that modest weight loss alone does not sufficiently correct the mechanism by which obesity impacts vascular function.

In summary, the present study found that modest weight loss alone failed to improve endothelial function in obesity, while weight loss plus orlistat improved vascular function, at least in part by improving endothelium-dependent vasodilation. This latter effect was statistically correlated with an improvement in LDL cholesterol, suggesting that the effects of this classical risk factor on endothelial function in obesity dominated other more direct effects of obesity such as insulin resistance. Further studies will be needed to confirm this group's findings, and to extend the study of the metabolic effects of weight loss to include other classical and nonclassical variables with potential impact on vascular function. Such studies will both extend our understanding of the pathogenesis of obesity-associated endothelial dysfunction and support therapeutic decision-making that includes among its targets a reduction in adverse cardiovascular outcomes.

Source: Diabetes Care - June 2003

See also:

1. Weight Loss and Endothelial Function in Obesity
2. Affects of Weight Loss on Endothelial Function in Obesity
3. Endothelial Function & Weight Loss Study
4. Responses to Obesity Treatment
5. Other Weight Loss-Endolthelial Function Studies
6. Weight Loss Issues

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