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Hypoglycemia Linked to Increased Risk of Cardiovascular Dysfunction

Severe hypoglycemia in type 2 diabetes was found to be associated with increased cardiac failure and mortality.

Previous research has suggested that hypoglycemia may in fact increase the risk of developing cardiovascular disease, but the mechanism behind this has yet to be discovered. There are various potential pathways in which hypoglycemia can result in arrhythmias and atherosclerosis but they are not definite. Low blood sugar has also been linked to respiratory, digestive, and skin conditions. Severe hypoglycemia may just be a parameter used to measure susceptibility of cardiac dysfunction or it could have a direct impact on cardiovascular disease progression. It has also been proposed that hypoglycemia may help determine the severity of diabetes. The association between hypoglycemia and cardiovascular disease has been analyzed in several clinical trials but results are usually not applicable to the general population as they have not been conducted in a community-based setting.

The following prospective cohort analysis was conducted to determine whether severe hypoglycemia in type 2 diabetes patients is linked to cardiovascular events such as coronary heart disease, stroke, heart failure, atrial fibrillation, and peripheral artery disease. The study also aimed to determine the relation between hypoglycemia and causes of mortality. Data was analyzed from 1,209 participants in The Atherosclerosis Risk in Communities (ARIC) study over a 15.3-year period beginning from the years 1996 to 1998. Patients were included in the study if they stated that they had a diabetes diagnosis or if they were on diabetes medications. ICD-9 codes from patient ambulance calls, and visits to the hospital and emergency department were utilized to identify severe hypoglycemic events experienced up until the year of 2013.

Cardiovascular events and mortalities were also determined through use of ICD-9 codes up until the year of 2013.

Patients were categorized as having diabetes for less than 9 years or greater than or equal to 9 years depending on if they had diabetes at baseline because exact onset of diabetes was unavailable. Patient medications were analyzed at every follow-up visit throughout the ARIC study. Parameters evaluated include estimated glomerular filtration rate (eGFR), albuminuria, blood pressure, HDL and LDL cholesterol, and fasting total cholesterol. Patients were also categorized as having low or high cardiovascular risk depending on specific criteria. Researchers further examined whether severe hypoglycemia had any association to cancer and its severity through use of ARIC hospitalization surveillance and cancer registries.

Cox regression models were used to identify the relation between severe hypoglycemia and cardiovascular dysfunction and mortality risk. It was found that a total of 186 participants experienced severe hypoglycemia at least one time throughout the follow-up period. A total of 195 patients had severe hypoglycemia and 118 of these cases resulted in mortality. Three years following initial severe hypoglycemic episode, total mortality was 28.3% and onset of coronary heart disease was 10.8%. Following final adjustment of confounders, severe hypoglycemia was found to be significantly related to coronary heart disease (hazard ratio (HR) 2.02, 95% CI 1.27-3.20). It was also linked to all-cause mortality (HR 1.73, 95% CI 1.38-2.17) and cardiovascular mortality (HR 1.64, 95% CI 1.15-2.34) and cancer mortality (HR 2.49 95% CI 1.46-4.24). However, after final adjustments, severe hypoglycemia was not significantly linked to stroke, heart failure, and atrial fibrillation.

The study suggests that in patients with type 2 diabetes, severe hypoglycemia leads to an increased risk of cardiovascular events and even mortality. Although, after adjustments, hypoglycemia was only significantly linked to coronary heart disease or atherosclerosis. The study demonstrates that severe hypoglycemia is a major risk factor for a decline in overall health even when independent of diabetes and cardiovascular risk factors. It was also found that the greatest cardiovascular incidence and mortality risk was within the first year following onset of severe hypoglycemia. This is an important clinical finding for physicians in that they can anticipate higher complications after a patient’s first hyperglycemic episode and more closely monitor them. Also, it is important that elevated-risk patients be identified early.

There were limitations to the study, however. Only data on severe hypoglycemic episodes that required medical attention were available, therefore other hypoglycemic episodes may have been missed. Exact onset of diabetes diagnoses was unavailable. Changes in factors such as diabetes medications and kidney function were not considered. Also, results were less accurate because some measured outcomes had very few events.

Practice Pearls:

  • Severe hypoglycemia increased cardiovascular dysfunction and mortality risk in type 2 diabetes patients.
  • Severe hypoglycemia was only significantly related to coronary heart disease when compared to other cardiovascular events such as stroke, heart failure, and atrial fibrillation.
  • The greatest cardiovascular dysfunction and mortality risk was seen within the first year following onset of the first severe hypoglycemic event.


Lee AK, Warren B, Lee CJ, et al. The Association of Severe Hypoglycemia With Incident Cardiovascular Events and Mortality in Adults With Type 2 Diabetes. Diabetes Care. 2017; 0:1-8.

Graciela Nieto, Pharm. D. Candidate 2018, LECOM School of Pharmacy