title: Severe hypoglycemia and hip fracture in patients with type 2 diabetes: a nationwide population-based cohort study.
abstract: Hypoglycemia is a major concern in glycemic control. Using the Taiwan National Health Insurance Research Database, we found that the risk of hip fracture was associated with emergency or hospitalization visits of severe hypoglycemia in patients with type 2 diabetes; greater visits were associated with higher incidence of hip fracture.
  
  
  
  The objective of the study was to assess the risk of hip fracture among patients with type 2 diabetes mellitus (T2DM) and severe hypoglycemia.
  
  
  
  Using the National Health Insurance Research database in Taiwan, we identified 2588 patients with T2DM who had developed severe hypoglycemia from 2001 to 2009. A comparison cohort who had never developed severe hypoglycemia was frequency matched at a ratio of approximately 1:2. Multivariate Cox proportional hazard regression analysis was used to evaluate the risk of hip fracture.
  
  
  
  During a median follow-up period of 3.9 years, there were 219 hip fracture events in 5173 comparison cohorts and 148 hip fracture events in 2588 hypoglycemia cohorts. The incidence of hip fracture was higher in patients with severe hypoglycemia than without severe hypoglycemia (17.19 vs. 8.83 per 1000 person-years; adjusted HR 1.71, 95% CI = 1.35-2.16). Approximately half of the individuals developed hip fracture within 2 years from the first occurrence of severe hypoglycemia. There was a significant associated trend towards increased hip fracture risk with increasing average visit of severe hypoglycemia per year (p for trend <0.001). Medication analysis showed that patients taking sulfonylurea alone, insulin alone, and insulin secretagogues combined with insulin had a higher associated risk to develop hip fracture.
  
  
  
  Severe hypoglycemia was associated with a higher risk to develop hip fracture. The more the visits of severe hypoglycemia per year indicated the higher associated risk in patients with T2DM. Fall is likely an important reason for severe hypoglycemia in relation to increased risk of hip fracture.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, China Medical University Hospital, 2, Yuh-Der Road, Taichung, 40447, Taiwan.|Department of Medicine, China Medical University, Taichung, 40402, Taiwan.
authors.forename: Y C
authors.initials: YC
authors.lastname: Hung
authors.affiliation: Management Office for Health Data, China Medical University Hospital, Taichung, 40447, Taiwan.|Veterans General Hospital, Taichung, Taiwan.
authors.forename: C C
authors.initials: CC
authors.lastname: Lin
authors.affiliation: Management Office for Health Data, China Medical University Hospital, Taichung, 40447, Taiwan.
authors.forename: H J
authors.initials: HJ
authors.lastname: Chen
authors.affiliation: Department of Nursing, School of Health, National Taichung University of Science and Technology, Taichung, 40343, Taiwan.
authors.forename: M P
authors.initials: MP
authors.lastname: Chang
authors.affiliation: Department of Integration of Traditional Chinese and Western Medicine, China Medical University Hospital, Taichung, 40447, Taiwan.|School of Chinese Medicine, China Medical University, Taichung, 40402, Taiwan.
authors.forename: K C
authors.initials: KC
authors.lastname: Huang
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, China Medical University Hospital, 2, Yuh-Der Road, Taichung, 40447, Taiwan.|Department of Medicine, China Medical University, Taichung, 40402, Taiwan.
authors.forename: Y H
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, China Medical University Hospital, 2, Yuh-Der Road, Taichung, 40447, Taiwan. chingchu@ms15.hinet.net.|School of Chinese Medicine, China Medical University, Taichung, 40402, Taiwan. chingchu@ms15.hinet.net.
authors.forename: C C
authors.initials: CC
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D015897:Comorbidity; D016208:Databases, Factual; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000188:drug therapy / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006620:Hip Fractures / Q000453:epidemiology / Q000209:etiology*; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced / Q000150:complications* / Q000453:epidemiology; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use; D015994:Incidence; D008297:Male; D008875:Middle Aged; D058866:Osteoporotic Fractures / Q000453:epidemiology / Q000209:etiology*; D018570:Risk Assessment / Q000379:methods; D013624:Taiwan / Q000453:epidemiology
chemical_list: D007004:Hypoglycemic Agents
keywords: Assessment; Diabetes; Fracture; Hypoglycemia; Insulin; Sulfonylurea