title: Hypoglycemia and risk of vascular events and mortality: a systematic review and meta-analysis.
abstract: OBJECTIVE
  Hypoglycemia has been associated with adverse outcomes in patients with diabetes and critical illness. However, such associations in these populations have not been systematically examined.
  
  
  METHODS
  We conducted a systematic review and meta-analysis of longitudinal follow-up cohort studies to investigate the associations between hypoglycemia and various adverse outcomes.
  
  
  RESULTS
  After removing duplicates and critically appraising all screened citations, a total of 19 eligible studies were included. As demonstrated by random-effects meta-analysis, hypoglycemia was strongly associated with a higher risk of adverse events (HR 1.90, 95 % CI 1.63-2.20; P < 0.001). Comparable risk ratios were shown in prespecified stratified analyses investigating above association for different study endpoints, in patients with or without critical illness, in patients with and without diabetes (from 1.47 to 3.31; p for interaction or heterogeneity >0.1). Additionally, a dose-dependent relationship between the severity of hypoglycemia and adverse vascular events and mortality (HR for mild hypoglycemia: 1.68, 95 % CI 1.25-2.26; P < 0.001 and HR for severe hypoglycemia: 2.33, 95 % CI 2.07-2.61; P < 0.001; p for trend 0.02) was observed. Suggested by a bias analysis, the above observations were unlikely to have resulted from unmeasured confounding parameters.
  
  
  CONCLUSIONS
  This is the first study demonstrating that hypoglycemia was associated with comparable risk ratios in different study populations and various study endpoints, and a trend of a dose-dependent relationship between hypoglycemia severity and adverse events. The findings of this systematic review support the speculation that hypoglycemia is a risk factor for adverse vascular events and mortality.
authors: Cardiology Division, Internal Medicine Department, Taipei Medical University Wan-Fang Hospital, Taipei, Taiwan.
authors: Jong Shiuan
authors: JS
authors: Yeh
authors: Division of Cardiology, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.|Institute of Public Health and Community Medicine Research Center, National Yang-Ming University, Taipei, Taiwan.|Department of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors: Shih-Hsien
authors: SH
authors: Sung
authors: Nursing Department, Taipei Veterans General Hospital, Taipei, Taiwan.
authors: Hui-Mei
authors: HM
authors: Huang
authors: Nursing Department, Taipei Veterans General Hospital, Taipei, Taiwan.
authors: Huei-Ling
authors: HL
authors: Yang
authors: Department of Medical Education, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Road, Beitou District, Taipei, 111, Taiwan, Roc.
authors: Li-Kai
authors: LK
authors: You
authors: Division of Preventive Medicine and Health Service, Research Institute of Population Health Sciences, National Health Research Institutes, Miaoli, Taiwan.
authors: Shao-Yuan
authors: SY
authors: Chuang
authors: Department of Medical Education, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Road, Beitou District, Taipei, 111, Taiwan, Roc.
authors: Po-Chieh
authors: PC
authors: Huang
authors: Healthcare and Management Center, Taipei Veterans General Hospital, Taipei, Taiwan.|Institute of Public Health and Community Medicine Research Center, National Yang-Ming University, Taipei, Taiwan.|Department of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors: Pai-Feng
authors: PF
authors: Hsu
authors: Department of Medical Education, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Road, Beitou District, Taipei, 111, Taiwan, Roc. hmcheng@vghtpe.gov.tw.|Institute of Public Health and Community Medicine Research Center, National Yang-Ming University, Taipei, Taiwan. hmcheng@vghtpe.gov.tw.|Department of Medicine, National Yang-Ming University, Taipei, Taiwan. hmcheng@vghtpe.gov.tw.
authors: Hao-Min
authors: HM
authors: Cheng
authors: Department of Medical Education, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Road, Beitou District, Taipei, 111, Taiwan, Roc.|Institute of Public Health and Community Medicine Research Center, National Yang-Ming University, Taipei, Taiwan.|Department of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors: Chen-Huan
authors: CH
authors: Chen
mesh_terms: D000328:Adult; D006801:Humans; D007003:Hypoglycemia / Q000453:epidemiology*; D012307:Risk Factors; D014652:Vascular Diseases / Q000453:epidemiology* / Q000401:mortality
keywords: Hypoglycemia; Mortality; Risk factor; Vascular events