Cardiac implications of hypoglycaemia in patients with diabetes – a systematic review

Abstract

BackgroundHypoglycaemia has been associated with increased cardiovascular (CV) risk and mortality in a number of recent multicentre trials, but the mechanistic links driving this association remain ill defined. This review aims to summarize the available data on how hypoglycaemia may affect CV risk in patients with diabetes.MethodsThis was a systematic review of available mechanistic and clinical studies on the relationship between hypoglycaemia and cardiovascular risk. Study outcomes were compiled from relevant articles, and factors contributing to hypoglycaemia-mediated CVD and its complications are discussed.ResultsSix recent comprehensive clinical trials have reinforced the critical importance of understanding the link between hypoglycaemia and the CV system. In addition, 88 studies have indicated that hypoglycaemia mechanistically contributes to CV risk by increasing thrombotic tendency, causing abnormal cardiac repolarization, inducing inflammation, and contributing to the development of atherosclerosis. These hypoglycaemia-associated risk factors are conducive to events such as unstable angina, non-fatal and fatal myocardial infarction, sudden death, and stroke in patients with diabetes.ConclusionsEmerging data suggest that there is an impact of hypoglycaemia on CV function and mechanistic link is multifactorial. Further research will be needed to ascertain the full impact of hypoglycaemia on the CV system and its complications.

Severe Hypoglycemia and Mortality After Cardiovascular Events for Type 1 Diabetic Patients in Sweden

“…This study could not account for hypoglycemia-associated mechanisms such as release of glucagon and catecholamines (epinephrine), enhanced platelet aggregation, cardiac autonomic neuropathy, or QTc interval changes, which lead to life-threatening cardiac arrhythmias that could explain the increased risk of mortality after a major CVD event in type 1 diabetic patients with histories of severe hypoglycemia (21).…”

“…A recent systematic review of cardiac implications of hypoglycemia in patients with diabetes identified only one study of type 2 diabetic patients (ADVANCE) that could determine a clear association between prior severe hypoglycemia and increased risk of death from any cause (HR 2.69 [95% CI 1.97-3.67]) (21). We have estimated a lower association in type 1 diabetes, with an HR of 1.79 (95% CI 1.37-2.35) in the first 28 days after a CVD event and an HR of 1.25 (95% CI 1.02-1.53) after 28 days post CVD event.…”

Effects of glucose-lowering agents on vascular outcomes in type 2 diabetes: A critical reappraisal

“…A similar relationship between severe hypoglycaemia and the risk of death was shown in both arms (glargine and standard care) of the ORIGIN study evaluating patients with prediabetes or mild T2DM [33]. A systematic review indicates that hypoglycaemia mechanistically contributes to cardiovascular risk by increasing thrombotic tendency, causing abnormal cardiac repolarization, inducing inflammation, and contributing to the development of atherosclerosis and to severe events such as unstable angina, non-fatal and fatal myocardial infarction, sudden death, and stroke in patients with diabetes [34].…”

Hypoglycaemia, thrombosis and vascular events in diabetes

“…Low blood glucose levels trigger an acute, compensatory catecholamine response which along with a concomitant drop in potassium levels affects cardiac depolarization prolonging the QT interval generating a proarrhythmogenic environment. During sleep, it is likely that exaggerated sympathoadrenal activation, with or without electrolyte disturbances, leads to more lethal ventricular arrhythmias and is thought to be the cause of the so-called 'dead in bed' scenario whereby young T1DM patients are found dead in an undisturbed bed [15,16]. Acute, insulin-induced hypoglycemia has been shown in numerous studies to induce a proinflammatory state.…”