Pleiotropic effects of statins are more pronounced in conditions of chronic hyperglycemia?
In a retrospective cohort study of patients aged 75 or more, Ramos and colleagues found reduction in CVD in those without diabetes using statin treatment for primary prevention. In the presence of diabetes, statin use was associated with reductions in the incidence of CVD and in total mortality . The fact that the effect of statin treatment in the primary prevention in the older population varies depending on the presence of type 2 diabetes seems to us very interesting in connection with the results of the ACCORD study. This RCT study showed that aggressive blood glucose control in patients with type 2 diabetes can increase mortality, including death from CVD . The reason for this unexpected finding is still unknown. Many years the main doctrine has been that insulin resistance is the only pathological characteristic. However, in response to overfeeding skeletal and cardiac muscle develops insulin resistance, which promotes diversion of excess nutrients to adipose tissue for safe storage. Therefore some authors have proposed that this induction of insulin resistance protects important tissues from nutrient-induced dysfunction . For example, we were able to show that the lowest total and CVD mortality in type 2 diabetes patients is associated with overweight or even light obesity . The decrease in GLUT4 and caveolin-1 associated with statins treatment results in decreased glucose uptake and increased insulin resistance in adipose tissue as well as in muscle and liver, which may leads to hyperglycemia and hyperinsulinemia, early markers of type 2 diabetes . Possible explanations for the so-called "reverse epidemiology" in the context of chronic heart failure are presented back in 2004  and include not only the category of "reverse causation".
It can be assumed that non-lipid-related (pleiotropic) effects of statins are more pronounced in conditions of chronic hyperglycemia.
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Competing interests: No competing interests