Understanding the impact of hypoglycemia on the cardiovascular system

Abstract

Introduction Hypoglycemia occurs commonly in insulin requiring individuals with either Type 1 or Type 2 Diabetes. Areas Covered This article will review recent information on the pro-inflammatory and pro-atherothrombotic effects of hypoglycemia. Additionally, effects of hypoglycemia on arrhythmogenic potential and arterial endothelial dysfunction will be discussed. Effects of hypoglycemia on cardiovascular morbidity and mortality from large clinical studies in Type 1 and Type 2 DM will also be reviewed. Expert Commentary The relative and absolute risk of severe hypoglycemia leading to death and serious adverse events in both cardiovascular and other organ systems has been highlighted following the publication of recent large clinical trials focused on glucose control and outcomes. It would be helpful if future studies could develop broader end points to include minor and moderate hypoglycemia as well as more robust methods for capturing hypoglycemia contemporaneously with adverse events. In addition, perhaps consideration of including hypoglycemia as a primary outcome, may help identify the possible cause and effect of hypoglycemia on cardiovascular morbidity and mortality.

Hypoglycaemia leads to a delayed increase in platelet and coagulation activation markers in people with type 2 diabetes treated with metformin only: Results from a stepwise hypoglycaemic clamp study

“…[6][7][8][9][10][11] A couple of pathophysiological theories have been put forward to explain the potential harmful atherothrombotic effects of hypoglycaemic events. 12 One was activation of the sympathetic nervous system, which induces the release of counterregulatory hormones (eg, catecholamines) as a response to the hypoglycaemic state, leading to haemodynamic changes with increased cardiac workload as well as derailments of potassium levels and provoking cardiac arrhythmia, QT interval prolongation and sudden cardiac death. [13][14][15] The second explanation frequently mentioned is the activation of platelets and the coagulation system by hypoglycaemic episodes, subsequently increasing the risk of atherothrombotic events.…”

Overexpression of PID1 reduces high density lipoprotein level and functionality in swine

“…Diabetes, a metabolic disorder characterized by hyperglycemia, is an independent risk factor for cardiovascular diseases (CVDs) . The risk of CVD is increased by two to four times in patients with diabetes .…”

Urinary glucose excretion after dapagliflozin treatment: An exposure‐response modelling comparison between Japanese and non‐Japanese patients diagnosed with type 1 diabetes mellitus

“…Frequent episodes of hypoglycaemia negatively impact quality of life, which in turn may lessen patient compliance. Events of severe hypoglycaemia have also been associated with an increased risk of cardiovascular morbidity and mortality, and all‐cause mortality in patients with diabetes . Clearly, adjunct therapies with insulin‐independent mechanisms of action, such as SGLT2 inhibitors, present an opportunity to refine the T1DM treatment paradigm and improve patient outcomes…”

“…Events of severe hypoglycaemia have also been associated with an increased risk of cardiovascular morbidity and mortality, and all-cause mortality in patients with diabetes. 7,8 Clearly, adjunct therapies with insulin-independent mechanisms of action, such as SGLT2 inhibitors, present an opportunity to refine the T1DM treatment paradigm and improve patient outcomes. 6 Phase 3 investigations in patients with T1DM show that dapagliflozin reduces HbA1c over 24 weeks compared with placebo, without increasing the risk of hypoglycaemia.…”