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

Abstract

Background: Hypoglycaemia 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.

Methods: This 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.

Results: Six 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.

Conclusions: Emerging 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.

Figure 1

Flow diagram of the study identification process.

Figure 2

Effect of experimental hypoglycaemia on QT interval. Typical QT measurement with a screen cursor placement from a subject during euglycaemia (a), showing a clearly defined T wave, and hypoglycaemia (b), showing prolonged repolarization and a prominent U wave. Horizontal: 799 ms epoch, vertical: 1.33 mV full scale (adapted from Marques et al. [55]).

Figure 3

“Dead in bed” syndrome (adapted from Tanenberg et al. [[17]]). Glucose levels captured by the retrospective continuous subcutaneous glucose monitoring system (CGMS) for the evening before and the morning of the patient’s death. The calibrations measured and entered by the patient are represented by the 4 circles. The timing of the patient’s meals, exercise, and correction insulin boluses are represented by the bars along the bottom of the graph. The precipitous decrease in glucose level after the correction doses can be observed to start just after midnight, and possible counterregulatory efforts are noted once the glucose level declined to below 30 mg/dL shortly after 2 am.