title: Association of clinical symptomatic hypoglycemia with cardiovascular events and total mortality in type 2 diabetes: a nationwide population-based study.
abstract: OBJECTIVE
  Hypoglycemia is associated with serious health outcomes for patients treated for diabetes. However, the outcome of outpatients with type 2 diabetes who have experienced hypoglycemia episodes is largely unknown.
  
  
  METHODS
  The study population, derived from the National Health Insurance Research Database released by the Taiwan National Health Research Institutes during 1998-2009, comprised 77,611 patients with newly diagnosed type 2 diabetes. We designed a prospective study consisting of randomly selected hypoglycemic type 2 diabetic patients and matched type 2 diabetic patients without hypoglycemia. We investigated the relationships of hypoglycemia with total mortality and cardiovascular events, including stroke, coronary heart disease, cardiovascular diseases, and all-cause hospitalization.
  
  
  RESULTS
  There were 1,844 hypoglycemic events (500 inpatients and 1,344 outpatients) among the 77,611 patients. Both mild (outpatient) and severe (inpatient) hypoglycemia cases had a higher percentage of comorbidities, including hypertension, renal diseases, cancer, stroke, and heart disease. In multivariate Cox regression models, including diabetes treatment adjustment, diabetic patients with hypoglycemia had a significantly higher risk of cardiovascular events during clinical treatment periods. After constructing a model adjusted with propensity scores, mild and severe hypoglycemia still demonstrated higher hazard ratios (HRs) for cardiovascular diseases (HR 2.09 [95% CI 1.63-2.67]), all-cause hospitalization (2.51 [2.00-3.16]), and total mortality (2.48 [1.41-4.38]).
  
  
  CONCLUSIONS
  Symptomatic hypoglycemia, whether clinically mild or severe, is associated with an increased risk of cardiovascular events, all-cause hospitalization, and all-cause mortality. More attention may be needed for diabetic patients with hypoglycemic episodes.
authors.affiliation: Healthcare and Management Center, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Pai-Feng
authors.initials: PF
authors.lastname: Hsu
authors.forename: Shih-Hsien
authors.initials: SH
authors.lastname: Sung
authors.forename: Hao-Min
authors.initials: HM
authors.lastname: Cheng
authors.forename: Jong-Shiuan
authors.initials: JS
authors.lastname: Yeh
authors.forename: Wen-Ling
authors.initials: WL
authors.lastname: Liu
authors.forename: Wan-Leong
authors.initials: WL
authors.lastname: Chan
authors.forename: Chen-Huan
authors.initials: CH
authors.lastname: Chen
authors.forename: Pesus
authors.initials: P
authors.lastname: Chou
authors.forename: Shao-Yuan
authors.initials: SY
authors.lastname: Chuang
mesh_terms: D000368:Aged; D002318:Cardiovascular Diseases / Q000097:blood* / Q000209:etiology / Q000401:mortality*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications / Q000401:mortality*; D005260:Female; D006760:Hospitalization; D006801:Humans; D007003:Hypoglycemia / Q000097:blood* / Q000150:complications / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors