Association of Clinical Symptomatic Hypoglycemia With Cardiovascular Events and Total Mortality in Type 2 Diabetes

A nationwide population-based study

  1. Shao-Yuan Chuang, PHD10
  1. 1Healthcare and Management Center, Taipei Veterans General Hospital, Taipei, Taiwan
  2. 2Department of Medicine, National Yang-Ming University, Taipei, Taiwan
  3. 3Institute of Public Health and Community Medicine Research Center, National Yang-Ming University, Taipei, Taiwan
  4. 4Cardiology Division, Internal Medicine Department, Taipei Veterans General Hospital, Taipei, Taiwan
  5. 5The Joanna Briggs Institute, Faculty of Health Sciences, The University of Adelaide, Adelaide, Australia
  6. 6Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan
  7. 7Cardiology Division, Internal Medicine Department, Taipei Medical University Wan-Fang Hospital, Taipei, Taiwan
  8. 8Department of Medicine, Taipei Medical University, Taipei, Taiwan
  9. 9The Skirball Center for Cardiovascular Research, Cardiovascular Research Foundation, Orangeburg, New York
  10. 10Institute of Population Health Sciences, National Health Research Institutes, Miaoli, Taiwan
  1. Corresponding author: Shao-Yuan Chuang, chuangsy{at}
  1. P.-F.H. and S.-H.S. contributed equally to this work.


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.

RESEARCH DESIGN AND 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.


  • The interpretation and conclusions contained herein do not represent those of the Bureau of National Health Insurance, Department of Health, or National Health Research Institutes.

  • This article contains Supplementary Data online at

  • A slide set summarizing this article is available online.

  • Received May 11, 2012.
  • Accepted September 10, 2012.

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