Insulin resistance and stroke: mechanisms and therapeutic approaches

Abstract

The review analyzed literature data on the epidemio­logy, risk factors, and mechanisms of acute cerebrovascular accident (ACVA) in patients with diabetes mellitus. The role of insulin resistance and the effectiveness of therapeutic approaches to its correction in cerebral stroke are considered. Diabetes mellitus is recognized as an independent modifiable risk factor for ACVA. In people with diabetes of different age, the risk of stroke is increased by 2–6 times, and the indicators are especially high in patients of young working age. The presence of diabetes mellitus is associated with more severe symptoms, increased risk of complications, longer hospitalization, and higher mortality. Research results show that insulin resistance is one of the main triggers for the development of ischemic stroke due to embolism caused by oxidative stress, endothelial dysfunction and platelet hyperactivation, as well as due to atherosclerotic changes caused by inflammation, proliferation of smooth muscle cells of the vascular wall, dyslipidemia and hypertension on the background of hyperglycemia and hyperinsulinemia. It has been proven that insulin resistance not only provokes ACVA, but also negatively affects their prognosis. Metformin is a key drug for improving insulin sensitivity and is recognized as one of the most important first-line therapeutic agents to achieve and maintain treatment goals in patients with type 2 diabetes. The results of expe­rimental and clinical studies proved that this agent has a whole range of neuroprotective properties, which generally prevent the development of cerebral ischemia and reduce the negative consequences in case of its occurrence. Animals with experimental acute cerebral ischemia who have been treated with metformin had a better overall neurological score, significantly smaller infarct size, better coordination scores, and higher numbers of neurons and microglia. The neuroprotective effect of metformin in stroke is realized through the AMPK (5’AMP-activated protein kinase) signaling pathway with reduction of oxidative stress, neuroinflammation, stimulation of angiogenesis and neurogenesis, autophagy, and inhibition of apoptosis. According to data from cohort and randomized clinical trials, the use of metformin is associated with a significantly lower risk of developing ACVA. Long-term use of this drug in type 2 diabetes contributes to a milder course of stroke, is associated with better functional recovery, and a decrease in disability and mortality rates.