Severe hypoglycemia increased risk for major macrovascular, microvascular events

Zoungas S. N Engl J Med. 2010;363:1410-1418.

Issue: November 2010

Patients with severe hypoglycemia experienced increased risks for a range of adverse clinical outcomes, including macrovascular and microvascular events, and CV and all-cause mortality, according to findings presented in The New England Journal of Medicine.

Researchers involved in the study examined 11,140 patients with type 2 diabetes to determine the relationship between severe hypoglycemia and the risks for macrovascular and microvascular events. Patients were at least 55 years of age and were recruited from 215 centers in 20 countries between June 2001 and March 2003. Researchers split patients into two arms — intensive glucose control (n=5,571) and standard glucose control (n=5,569) — and followed them for a median of 5 years.

During follow-up, 231 patients (2.1%) had at least one severe hypoglycemic episode, 150 in the intensive glucose group (2.7%) and 81 in the standard glucose group (1.5%). Severe hypoglycemia was associated with the following increases in adjusted risks: major macrovascular events (HR=2.88; 95% CI, 2.01-4.12), major microvascular events (HR=1.81; 95% CI, 1.19-2.74), death from a CV cause (HR=2.68; 95% CI, 1.72-4.19) and death from any cause (HR=2.69; 95% CI, 1.97-3.67).

In the concluding remarks of their study, the researchers commented that although their findings cannot exclude the possibility that severe hypoglycemia has a direct causal link with these outcomes, the findings suggest that it is as likely to be a marker of vulnerability to a wide range of adverse clinical outcomes.

“In either case, the presence of severe hypoglycemia should raise clinical suspicion of the patient’s susceptibility to adverse outcomes and prompt action to address this possibility,” they added. – By Brian Ellis

This is an extremely important study in the field of diabetes. It shows the strong association between hypoglycemia and the risk of CV events and death. That itself is a very interesting observation. Even more interesting, nonvascular adverse events were also significantly increased in those with hypoglycemia. This finding raises the possibility that hypoglycemia is a marker of increased risk in general, more so than directly causing CV events. Future studies will need to examine if the findings regarding hypoglycemia noted here are consistent in other diabetic populations.

– Deepak Bhatt, MD
Cardiology Today Editorial Board

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