Hypoglycemia and Cardiovascular Risks

TLDR: The effects of hypoglycemia on the CV system is reviewed, how this major metabolic stress could precipitate major vascular events such as myocardial infarction and stroke, and its potential role in these recent clinical studies are reviewed.

Abstract: Although hypoglycemia is the most common side effect of insulin therapy in diabetes and its morbidity is well known, for many years, the potentially life-threatening effects of hypoglycemia on the cardiovascular (CV) system have either been overlooked or have been dismissed as inconsequential to people with insulin-treated type 2 diabetes. This scenario may possibly be a consequence of the persisting misconception that this population is seldom exposed to severe hypoglycemia, defined as any episode that requires external assistance for recovery, whereas self-treated events are classified as “mild” (1). This myth was firmly repudiated by the findings of the large prospective study by the U.K. Hypoglycemia Study Group (2), which demonstrated that severe hypoglycemia is a common problem in insulin-treated type 2 diabetes and that the incidence increases with duration of insulin therapy. However, evidence for CV morbidity associated with hypoglycemia has been predominantly hypothetical and anecdotal (1,3). The potential dangers of intensive treatment regimens and strict glycemic control in people with type 2 diabetes who have CV disease (CVD) have now been highlighted by the disconcerting outcomes of recent studies (4–6), in which hypoglycemia was implicated in the excess mortality that was observed in some of these trials. It is therefore timely to review the effects of hypoglycemia on the CV system, how this major metabolic stress could precipitate major vascular events such as myocardial infarction and stroke, and its potential role in these recent clinical studies. In the adult human, acute hypoglycemia causes pronounced physiological responses as a consequence of autonomic activation, principally of the sympatho-adrenal system, and results in end-organ stimulation and a profuse release of epinephrine (adrenaline). This profound autonomic stimulus provokes hemodynamic changes, the important consequences of which are to maintain the supply of glucose to the brain and promote the hepatic …