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The Impact of Hypoglycemia on Cardiovascular Risk/Mortality

Dec 6, 2013

Intensive blood sugar goal may not be the answer…. 

High blood sugars can damage vessels leading to cardiovascular disease (CVD) but several recent studies have implicated hypoglycemia as well in cardiovascular (CV) risks and mortality. Researchers recently completed a systematic review of medical literature through November 2012 that included clinical trials related to patients with type 1 or type 2 diabetes who were under intensive blood glucose control and in which the study reported CV complications; it also included studies that looked at the mechanisms linking hypoglycemia to CV risk. A total of 93 studies were included in the review, 5 clinical trials and 88 mechanistic studies.

The large scale trials that look at intensive glucose control have varying findings, some suggest that intensive glucose control leads to improvements in CV outcomes and others suggest that intensive treatment may in fact increase CV risks and mortality due to hypoglycemia. There has been a push toward understanding the impact of hypoglycemia on CV risks and a multifactorial link has been suggested. The analysis of these studies point toward several mechanisms that may increase cardiovascular risk. 1) Catecholamine release in response to hypoglycemia, while intended to be protective, may cause harm in some diabetic patients who already have endothelial dysfunction/ischemia type heart disease due to epinephrine effects such as increased heart rate, increased systolic BP, increased peripheral resistance, etc. 2) Increased platelet aggregation has been identified as a potential result of hypoglycemia; impaired coagulation may lead to MI and CVA 3) Increases in QTc interval and arrhythmias have been associated with hypoglycemia which is thought be a result of "hypoglycemia-induced sympatho-adrenal changes" leading to hypokalemia and direct catecholamine effects on the myocardium. 4) Occurrences of nocturnal hypoglycemia have been linked to QTc prolongation, cardiac arrhythmia and death also known as "dead in bed" syndrome. 5) And insulin induced hypoglycemia has been correlated with increased vascular inflammation/atherosclerosis as noted by increased expression of pro-inflammatory markers during hypoglycemia.

Due to these new insights of CV risks driven by hypoglycemia, what blood glucose levels should we target? We know high blood glucose can be detrimental on the CV system but now we are also discovering that low blood glucose levels may also increase CV risk and mortality. There remains a lot of unanswered questions surrounding this debate and future research is needed to better define a safe blood glucose target as well as the implications of hypoglycemia on the CV system.

Practice Pearls:
  • Uncontrolled plasma glucose can lead to CV damage and CV risk as well as mortality; however recent studies show that CV risk and mortality may also be related to hypoglycemia.
  • Hypoglycemia may have negative impacts on the CV system such as increase catecholamine release, increased platelet aggregation, prolonged QTc interval/arrhythmias and increased inflammation.
  • Patients should be educated on both signs, symptoms and treatment options for hyperglycemia and hypoglycemia as well as educated on safe blood glucose target ranges to help with prevention of CV risk development.

Hanefeld, M. et al. Cardiac implications of hypoglycaemia in patients with diabetes – a systematic review. Cardiovascular Diabetology 2013, 12:135