Hypoglycemia Predicts CV Events in Type 1 and 2 Diabetes

Liam Davenport

December 22, 2014

Insulin-treated diabetes patients who experience hypoglycemia face an increased and ongoing risk for cardiovascular events and all-cause mortality, regardless of whether they have type 1 or type 2 diabetes, a new study has found.

The investigators, led by Kamlesh Khunti, MD, from Leicester Diabetes Centre, University of Leicester, United Kingdom, found that the risks were increased substantially in patients both with and without a history of cardiovascular disease (CVD), with events occurring a median of 1.5 years after the index hypoglycemia event.

"This is the first study of its kind to analyze real-world data combining both type 1 and type 2 diabetes patients from a representative population from primary care," senior author Sanjay Paul, PhD, head of the clinical trials and biostatistics unit at the QIMR Berghofer Medical Research Institute, Brisbane, Australia, told Medscape Medical News.

The findings confirm the results from the ACCORD study in people with type 2 diabetes and add to the evidence for a link between hypoglycemia and cardiovascular events in people with type 1 diabetes, the researchers say.

"This will help clinicians, caregivers, and patients to improve blood sugar management and reduce complications from this complex disease," Dr Paul said.

"The large number of patients requiring insulin therapy means even a small increase in risk could have major clinical and public-health implications," he added. "Both health workers and patients need to be aware that failure to properly manage diabetes could cause potentially fatal CVD."

The research was published online on December 9 in Diabetes Care.

Study Used Real-Life Data on Those With Type 1 and 2 Diabetes

The work was prompted by a number of studies that have examined a possible link between glycemic control and an increased risk of CVD or mortality in type 2 diabetes. For example, the ACCORD study was stopped early due to a higher death rate associated with intensive glycemic control among type 2 diabetes patients with a high risk of heart disease, suggesting a possible association between hypoglycemia and cardiovascular disease.

"Keeping that in mind, [we] thought it would be a good idea to use real-life data to see if hypoglycemia would be associated with the risk of myocardial infarction, stroke, or microvascular events, and, of course, mortality," Dr Paul commented.

This, he said, was all the more important given the lack of studies examining the risk of hypoglycemia in both type 1 and type 2 diabetes.

The team conducted a retrospective analysis of data from the UK Clinical Practice Research Datalink, which includes 265,868 insulin-treated patients aged over 30 years who had received a diagnosis of diabetes between 2001 and 2007.

Of these, 3260 patients with type 1 diabetes and 10,422 patients with type 2 diabetes were included, and their records linked to the Hospital Episode Statistics database, which details all hospital admissions, outpatient appointments, and emergency attendances at National Health Service hospitals in England.

During a median follow-up of 5.0 years for type 1 diabetes patients and 4.8 years for those with type 2 diabetes, hypoglycemia was experienced by 573 (18%) and 1463 (14%) of patients, respectively.

Compared with patients who did not experience hypoglycemia, the hazard ratio (HR) for CV events among type 1 diabetes patients who experienced hypoglycemia was 1.51 (not significant) and 1.61 for those with and without a history of CVD. For type 2 diabetes patients, the respective HRs were 1.60 and 1.49.

The HR for all-cause mortality among patients who experienced hypoglycemia was 1.98 and 2.03 among type 1 diabetes patients with and without a history of CVD, while the respective HRs among type 2 diabetes patients were 1.74 and 2.48.

The team also calculated that the median time interval between the first hypoglycemia event and the first CV event was 1.5 years in both type 1 and type 2 diabetes patients.

"The results of this retrospective cohort analysis demonstrate that, in a nationally representative contemporary population, hypoglycemia is associated with an increased risk of CV events and all-cause mortality in insulin-treated patients with type 1 and type 2 diabetes," the researchers say.

The analysis also reconfirms that the increased risk of CV events after a hypoglycemic episode "persists over a period of months and years," they add.

"Based on the results of our analysis and previously published studies, we recommend that special attention should be paid to insulin-treated patients who experience a hypoglycemic event — especially those who are at elevated risk for CV events — and an effort should be made to reduce the incidence of future hypoglycemic events," the team concludes.

Dr Paul said he is now conducting an investigation in which data from continuous blood glucose monitoring systems are being used to develop a statistical method to predict incipient hypoglycemia in type 1 and type 2 diabetes patients. This, he hopes, will allow doctors to be able to take precautionary measures when treating diabetes patients.

This work was supported by both the East Midlands National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research & Care (CLAHRC) and the NIHR CLAHRC for Northwest London; the Leicester–Loughborough Diet, Lifestyle, and Physical Activity Biomedical Research Unit; the Imperial NIHR Biomedical Research Centre; the Imperial Centre for Patient Safety and Service Quality; and received infrastructure support from Therapeutic Innovations Australia. Dr Paul has acted as a consultant and speaker for Novartis and Amylin Pharmaceuticals and has received grants  from Merck Sharp & Dohme, Novo Nordisk, Pfizer, Amylin Pharmaceuticals, Bristol-Myers Squibb, and Hospira. Disclosures for the coauthors are listed in the article.

Diabetes Care. Published onlineDecember 9, 2014. Abstract


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