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BMJ. 2013 Jul 29;347:f4533. doi: 10.1136/bmj.f4533.

Severe hypoglycaemia and cardiovascular disease: systematic review and meta-analysis with bias analysis.

Author information

1
Department of Diabetes Research, Diabetes Research Center, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan.

Abstract

OBJECTIVES:

To provide a systematic and quantitative summary of the association between severe hypoglycaemia and risk of cardiovascular disease in people with type 2 diabetes and to examine the sensitivity of the association to possible uncontrolled confounding by unmeasured comorbid severe illness using a bias analysis.

DESIGN:

Meta-analysis of observational studies.

DATA SOURCES:

Medline, Embase, the Cochrane Library, and Web of Science databases were searched to February 2013, without any language restrictions.

ELIGIBILITY CRITERIA:

Two independent reviewers selected cohort studies that evaluated the association of severe hypoglycaemia with cardiovascular events in people with type 2 diabetes; we excluded studies from acute hospital settings. We extracted descriptive and quantitative data.

RESULTS:

Of 3443 citations screened, six eligible studies with 903, 510 participants were identified. In the conventional random effects meta-analysis, severe hypoglycaemia was strongly associated with a higher risk of cardiovascular disease (relative risk 2.05, 95% confidence interval 1.74 to 2.42; P<0.001). The excess fraction of cardiovascular disease incidence that was attributable to severe hypoglycaemia (the population attributable fraction) was 1.56% (95% confidence interval 1.32% to 1.81%; P<0.001). Although moderate heterogeneity across the studies was suggested (I(2)=73.1%; P=0.002 for heterogeneity), most subgroups showed similar results in stratified analyses. The bias analysis indicated that comorbid severe illness alone may not explain the association between hypoglycaemia and cardiovascular disease; to explain this association, comorbid severe illness would have had to be extremely strongly associated with both severe hypoglycaemia and cardiovascular disease.

CONCLUSION:

Our findings suggest that severe hypoglycaemia is associated with a higher risk of cardiovascular disease; they also support the notion that avoiding severe hypoglycaemia may be important to prevent cardiovascular disease in people with type 2 diabetes.

Comment in

PMID:
23900314
DOI:
10.1136/bmj.f4533
[Indexed for MEDLINE]
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