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.
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.
Authors: Alexandra K Lee; John W McEvoy; Ron C Hoogeveen; Christie M Ballantyne; Elizabeth Selvin Journal: J Am Coll Cardiol Date: 2016-09-20 Impact factor: 24.094
Authors: Andrew J Karter; Kasia J Lipska; Patrick J O'Connor; Jennifer Y Liu; Howard H Moffet; Emily B Schroeder; Jean M Lawrence; Gregory A Nichols; Katherine M Newton; Ram D Pathak; Jay Desai; Beth Waitzfelder; Melissa G Butler; Abraham Thomas; John F Steiner Journal: J Diabetes Complications Date: 2017-02-21 Impact factor: 2.852