The link associating hypoglycemia to cardiovascular disease (CVD) is controversial among researchers because some believe that severe hypoglycemic events are an indication of a serious comorbid illness, rather than it being the cause of such a condition. In contrast to this notion, a newly conducted meta-analysis reveals that patients with low blood glucose levels requiring emergency medical assistance are at a higher risk for cardiovascular disease (relative risk 2.05; 95% CI 1.74-2.42; p<0.001).
The meta-analysis consisted of 6 cohort studies involving over 900,000 participants with type 2 diabetes. All of the studies selected in the meta-analysis adjusted for participants' age, sex, CVD history, health status, use of diabetes medication, and history of microvascular complications.
Studies included in the analysis all showed an association between hypoglycemia and CVD, which was then tested through a sensitivity analysis to determine any possible confounding by other comorbidities. From the sensitivity analysis, it was deduced that a comorbid illness alone was not enough to explain the association between hypoglycemia and CVD, since the relative risk would have to be significantly greater than what the results indicated.
According to the authors, the increased risk of CVD due to severe hypoglycemia makes biological sense. This is because when a severe hypoglycemic event occurs, the sympathetic nervous system increases catecholamine neurotransmitters in the body and causes adverse effects on the "myocardium and the vascular system." (Wright et al.)
Aside from it being an observational study, limitations of this meta-analysis included selection bias; it lacked individual patient data, and could not be generalized to type-1 diabetic patients.
Due to the results of the analysis, authors of the study suggest using a less strict HbA1c target for individuals that are at a higher risk of hypoglycemia when in combination with proper self-care.
Goto Atsushi, et al "Severe hypoglycemia and cardiovascular disease: systematic review and meta-analysis with bias analysis" BMJ 2013; 347: f4533.
Wright RJ, Frier BM. Vascular disease and diabetes: is hypoglycaemia an aggravating factor? Diabetes Metab Res Rev2008;24:353-63.