title: A Population-Based Study of All-Cause Mortality and Cardiovascular Disease in Association With Prior History of Hypoglycemia Among Patients With Type 1 Diabetes.
abstract: This study investigated the effects of severe hypoglycemia on risks of all-cause mortality and cardiovascular disease (CVD) incidence in patients with type 1 diabetes mellitus (T1DM).
  
  
  
  Two nested case-control studies with age- and sex-matched control subjects and using the time-density sampling method were performed separately within a cohort of 10,411 patients with T1DM in Taiwan. The study enrolled 564 nonsurvivors and 1,615 control subjects as well as 743 CVD case subjects and 1,439 control subjects between 1997 and 2011. History of severe hypoglycemia was identified during 1 year, 1-3 years, and 3-5 years before the occurrence of the study outcomes. Conditional logistic regression analyses were performed to estimate the odds ratio (OR) and 95% CI of the study outcomes.
  
  
  
  Prior severe hypoglycemic events within 1 year were associated with higher risks of all-cause mortality and CVD (adjusted OR 2.74 [95% CI 1.96-3.85] and 2.02 [1.35-3.01], respectively). Events occurring within 1-3 years and 3-5 years before death were also associated with adjusted ORs of 1.94 (95% CI 1.39-2.71) and 1.68 (1.15-2.44), respectively. Significant dose-gradient effects of severe hypoglycemia frequency on mortality and CVD were observed within 5 years.
  
  
  
  Although the CVD incidence may be associated with severe hypoglycemic events occurring in the previous year, the risk of all-cause mortality was associated with severe hypoglycemic events occurring in the preceding 5 years. Exposure to repeated severe hypoglycemic events can lead to higher risks of mortality and CVD.
authors.affiliation: Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Chin-Li
authors.initials: CL
authors.lastname: Lu
authors.affiliation: Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan Department of Intensive Care Medicine, Chi Mei Medical Center, Tainan, Taiwan.
authors.forename: Hsiu-Nien
authors.initials: HN
authors.lastname: Shen
authors.affiliation: Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Susan C
authors.initials: SC
authors.lastname: Hu
authors.affiliation: Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan Departments of Internal Medicine and Occupational and Environmental Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Jung-Der
authors.initials: JD
authors.lastname: Wang
authors.affiliation: Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan cyli99@mail.ncku.edu.tw.
authors.forename: Chung-Yi
authors.initials: CY
authors.lastname: Li
mesh_terms: D000328:Adult; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D016022:Case-Control Studies; D002423:Cause of Death; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000453:epidemiology; D005260:Female; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced / Q000453:epidemiology*; D007004:Hypoglycemic Agents / Q000009:adverse effects; D015994:Incidence; D007328:Insulin / Q000009:adverse effects; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009026:Mortality; D016017:Odds Ratio; D012306:Risk; D012307:Risk Factors; D012720:Severity of Illness Index; D013624:Taiwan / Q000453:epidemiology; D055815:Young Adult
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin