title: Hypoglycemia and risk of cardiovascular disease and all-cause mortality in insulin-treated people with type 1 and type 2 diabetes: a cohort study.
abstract: OBJECTIVE
  Hypoglycemia has been associated with an increased risk of cardiovascular (CV) events and all-cause mortality. This study assessed whether, in a nationally representative population, there is an association between hypoglycemia, the risk of CV events, and all-cause mortality among insulin-treated people with type 1 diabetes or type 2 diabetes.
  
  
  METHODS
  This retrospective cohort study used data from the Clinical Practice Research Datalink database and included all insulin-treated patients (≥30 years of age) with a diagnosis of diabetes.
  
  
  RESULTS
  In patients who experienced hypoglycemia, hazard ratios (HRs) for CV events in people with type 1 diabetes were 1.51 (95% CI 0.83, 2.75; P = ns) and 1.61 (1.17, 2.22), respectively, for those with and without a history of CV disease (CVD) before the index date. In people with type 2 diabetes, the HRs for patients with and without a history of CVD were 1.60 (1.21, 2.12) and 1.49 (1.23, 1.82), respectively. For all-cause mortality, HRs in people with type 1 diabetes were 1.98 (1.25, 3.17), and 2.03 (1.66, 2.47), respectively, for those with and without a history of CVD. Among people with type 2 diabetes, HRs were 1.74 (1.39, 2.18) and 2.48 (2.21, 2.79), respectively, for those with and without a history of CVD. The median time (interquartile range) from first hypoglycemia event to first CV event was 1.5 years (0.5, 3.5 years) and 1.5 years (0.5, 3.0 years), respectively, for people with type 1 and type 2 diabetes.
  
  
  CONCLUSIONS
  Hypoglycemia is associated with an increased risk of CV events and all-cause mortality in insulin-treated patients with diabetes. The relationship between hypoglycemia and CV outcomes and mortality exists over a long period.
authors.affiliation: Leicester Diabetes Centre, University of Leicester, Leicester, U.K. Leicester Clinical Trials Unit, University of Leicester, Leicester, U.K. kk22@leicester.ac.uk.
authors.forename: Kamlesh
authors.initials: K
authors.lastname: Khunti
authors.affiliation: Leicester Diabetes Centre, University of Leicester, Leicester, U.K. Leicester Clinical Trials Unit, University of Leicester, Leicester, U.K.
authors.forename: Melanie
authors.initials: M
authors.lastname: Davies
authors.affiliation: Department of Primary Care and Public Health, Imperial College London, London, U.K.
authors.forename: Azeem
authors.initials: A
authors.lastname: Majeed
authors.affiliation: Novo Nordisk A/S, Bagsværd, Denmark.
authors.forename: Brian Larsen
authors.initials: BL
authors.lastname: Thorsted
authors.affiliation: Novo Nordisk A/S, Bagsværd, Denmark.
authors.forename: Michael Lyng
authors.initials: ML
authors.lastname: Wolden
authors.affiliation: Clinical Trials and Biostatistics Unit, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Sanjoy K
authors.initials: SK
authors.lastname: Paul
mesh_terms: D000328:Adult; D000368:Aged; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000188:drug therapy / Q000401:mortality; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000188:drug therapy / Q000401:mortality; D003925:Diabetic Angiopathies / Q000150:complications* / Q000401:mortality; D004739:England / Q000453:epidemiology; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D007003:Hypoglycemia / Q000209:etiology*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D061385:Insulins / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged
chemical_list: D007004:Hypoglycemic Agents; D061385:Insulins