Cardiovascular Importance of Hyperglycemia and Hypoglycemia

Abstract

For addressing the question of cardiovascular importance of hypoglycemia, it is important to clarify its context. First, hypoglycemia is a result of treatment of hyperglycemia by oral insulin secretagogues or insulin. Chronic hyperglycemia usually expressed by HbA1c level is considered a risk factor for cardiovascular disease, although this epidemiological association does not necessarily mean the existence of causal association, so the possibility cannot be excluded that HbA1c may be only a marker of atherosclerotic vascular disease. Thus, in the present review the evidence related to hyperglycemia and hypoglycemia as factors contributing to the development of cardiovascular events will be discussed and the main following issues will be addressed: The relationship of hyperglycemia to cardiovascular disease will be documented based on analysis of epidemiological and clinical interventional studies. Furthermore, the evidence will be summarized that hypoglycemic episodes contribute to the development of cardiovascular events in patients with type 2 diabetes treated by hypoglycemia-inducing drugs. Finally, it will be demonstrated how the conclusions from the described studies translated in practical recommendations for personalized treatment of type 2 diabetes. ### Is hyperglycemia related to cardiovascular disease? The evidence about a relationship between hyperglycemia and cardiovascular disease comes from epidemiological studies and epidemiological post hoc analyses of clinical trials. For consideration of a biological variable, e.g., HbA1c, as a cardiovascular risk factor, it is important to analyze its relationship with cardiovascular disease also outside the diabetic range. The epidemiological study European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk) included 4,662 men and 5,570 women. Relative risks for cardiovascular disease (nonfatal or fatal coronary heart disease and strokes) adjusted for age and risk factors were calculated after 6-year follow-up period. An increase in HbA1c of 1% (11 mmol/mol) was associated with relative risk for cardiovascular disease of 1.21 (95% CI 1.13–1.29 for males and 1.11–1.31 for females; …