Is Glucose Control Important for Prevention of Cardiovascular Disease in Diabetes?

Abstract

Patients affected by diabetes show an increased risk of cardiovascular disease (CVD) and mortality that reduces their life expectancy by 5–15 years (depending on the age at diagnosis). An 18-year follow-up study from Finland demonstrated a similar impact of type 1 and type 2 diabetes on cardiovascular mortality, with an increased risk of 5.2 and 4.9 times for type 1 and type 2 diabetes, respectively (1). In type 1 diabetes, follow-up results from a large randomized clinical trial suggest that the improvement of metabolic control, obtained through intensive insulin treatment, can prevent CVD in the long term. On the other hand, despite some encouraging results (2,3), the results of trials assessing the long-term cardiovascular effects of improving metabolic control in type 2 diabetes are controversial. Here, we will present the main points supporting and will illustrate the main counterpoints challenging the importance of glucose control for prevention of CVD in diabetic patients. ### Pros #### Pathophysiological effects of hyperglycemia on cardiovascular system. There is convincing evidence from epidemiological and pathophysiological studies that hyperglycemia has a detrimental effect on cardiovascular risk profile in its own right. It is well known that among patients with type 2 diabetes, those with higher levels of blood glucose and HbA1c are at greater risk for CVD. Glycemic fluctuations and chronic hyperglycemia are triggers for inflammatory responses via increased endoplasmic reticulum stress and mitochondrial superoxide production. The molecular pathways underlying hyperglycemia, low-grade inflammation, and oxidative stress have been widely recognized in the pathogenesis of endothelial dysfunction, which represents the first step of atherogenesis. Through this pathway, hyperglycemia-induced early atherogenesis may lead to an increased probability of cardiovascular events later in life. Direct effects of glucose toxicity, oxidative stress, and low-grade inflammation act in a vicious cycle that determines impaired insulin sensitivity, β-cell loss, and endothelial dysfunction, thus leading to micro- and macrovascular complications …