Association between severe hypoglycemia, adverse macrovascular events, and inflammation in the Edinburgh Type 2 Diabetes Study


Bedenis R, Price AH, Robertson CM, et al. Association between severe hypoglycemia, adverse macrovascular events, and inflammation in the Edinburgh Type 2 Diabetes Study. Diabetes Care. 2014. [ePub ahead of print] doi: 10.2337/dc14-0908.

This prospective evaluation of subjects in the Edinburgh Type 2 Diabetes Study (n=1,066) investigated whether an association exists between severe hypoglycemia and macrovascular outcomes in type 2 diabetes, and whether that association is mediated by an inflammatory mechanism.

  

Commentary Thumb Inzucchi Severe Hypoglycemia 

Severe hypoglycemia was defined as any episode of hypoglycemia that required external assistance for recovery. The primary outcomes were fatal or nonfatal myocardial infarction, angina, transient ischemic attack, or fatal or nonfatal stroke over 4 years.

History of Severe Hypoglycemia Assocated With Increased Macrovascular Disease Risk 

After 4 years of follow-up, 99 participants (9.3%) reported the occurrence of one or more macrovascular events since baseline. Coronary heart events were reported in 64 participants (6.0%), of whom 36 (3.6%) had an MI. Cerebrovascular events occurred in 42 participants (3.9%), of whom 32 (3.0%) had a stroke.

 
Adjusting for possible confounders, statistically significant increased odds were observed for the composite macrovascular event outcome, coronary heart events, and MI. Compared with those with no history of severe hypoglycemia at baseline, subjects who reported at least one episode of hypoglycemia were ~1.1 times more likely to experience a macrovascular event, 1.4 times more likely to experience a coronary heart event, and 3 times more likely to experience an MI at follow-up.
 
No significant association was found between severe hypoglycemia and cerebrovascular events or stroke.

Severe Hypoglycemia Linked With Inflammation 

Inflammation markers were evaluated at baseline and not during, or soon after, a hypoglycemic episode to determine whether increased risk for macrovascular events associated with severe hypoglycemia was mediated by a proinflammatory state. A history of severe hypoglycemia was associated with statistically significant higher levels of all five inflammatory markers.

After controlling for possible cardiometabolic confounders, a statistically significant association was observed for tumor necrosis factor-α (TNF-α) and the general inflammation factor.

Proinflammatory State Does Not Influence Severe Hypoglycemia & Macrovascular Risk 

Iinflammation markers were evaluated at baseline and not during, or soon after, a hypoglycemic episode to determine whether increased risk for macrovascular events associated with severe hypoglycemia was mediated by a proinflammatory state. There was no evidence that a proinflammatory state influences the association between severe hypoglycemia and increased risk for macrovascular events.

Clinical Significance for HCPs 

  • In patients with type 2 diabetes, a history of severe hypoglycemia is strongly associated with subsequent macrovascular morbidity, principally related to MI
    • Careful consideration should be given to appropriate A1C targets in patients with long durations of diabetes, and older patients who are at greater risk of hypoglycemia
    • Strict glycemic control may not be advisable in patients who already have a degree of underlying macrovascular disease
     
  • The association between hypoglycemia and macrovascular events does not appear to be mediated by inflammation
 
All slides available for download in the slide library. 
 

Related content: 

For more content on hypoglycemia, click here. 

For more content on inflammation, click here. 

For more content on macrovascular complications of diabetes, click here. 

  

Any pharmacologic agents discussed are approved for use in the United States by the U.S. Food and Drug Administration (FDA) unless otherwise noted. Consult individual prescribing information for approved uses outside of the United States. 

October 2014 

This overview was created by KnowledgePoint360 Group, LLC, and was not associated with funding via an educational grant or a promotional/commercial interest.  

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Last Modified: 12/9/2014