title: Insulin use increases risk of asthma but metformin use reduces the risk in patients with diabetes in a Taiwanese population cohort.
abstract: OBJECTIVE
  Recent reports have suggested that insulin promotes airway smooth muscle contraction and enhances airway hyperresponsiveness, which are cardinal features of asthma. In contrast, metformin can reduce both airway inflammatory and remodeling properties. However, these results are all from in vitro and animal studies. This study investigated whether diabetes and various antidiabetic agents associate with the risk of asthma.
  
  
  METHODS
  We used a retrospective population-based cohort study using Taiwan's National Health Insurance claim database from 2000 to 2010 and a Cox proportional hazards regression model to compare the incidence of asthma between patients with diabetes (n = 19,428) and a matched non-diabetic group (n = 38,856). We also used a case-control study nested from the above cohort including 1,982 incident cases of asthma and 1,982 age- and sex-matched controls. A time density sampling technique was used to assess the effects of various antidiabetic agents on the risk of asthma.
  
  
  RESULTS
  The incidence of asthma was significantly higher in the diabetic cohort than that in the non-diabetic cohort after adjustment for age, sex, and obesity, with a hazard ratio of 1.30 (95% confidence interval [CI]: 1.24-1.38). Insulin was found to increase the risk of asthma among diabetic patients (odds ratio [OR] 2.23; 95% CI: 1.52-3.58). In contrast, the use of metformin correlated with a decreased risk of asthma (OR 0.75; 95% CI: 0.60-0.95).
  
  
  CONCLUSIONS
  Individuals with diabetes are at an increased risk of asthma. Insulin may further increase the risk of asthma, but the risk could possibly be reduced by using metformin.
authors.affiliation: a Division of Chest Medicine, Department of Internal Medicine , National Cheng Kung University Medical College and Hospital , Tainan , Taiwan.
authors.forename: Chiung-Zuei
authors.initials: CZ
authors.lastname: Chen
authors.affiliation: a Division of Chest Medicine, Department of Internal Medicine , National Cheng Kung University Medical College and Hospital , Tainan , Taiwan.
authors.forename: Chih-Hui
authors.initials: CH
authors.lastname: Hsu
authors.affiliation: b Institute of Public Health, National Cheng Kung University Medical College , Tainan , Taiwan.
authors.forename: Chung-Yi
authors.initials: CY
authors.lastname: Li
authors.affiliation: a Division of Chest Medicine, Department of Internal Medicine , National Cheng Kung University Medical College and Hospital , Tainan , Taiwan.
authors.forename: Tzuen-Ren
authors.initials: TR
authors.lastname: Hsiue
mesh_terms: D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D001249:Asthma / Q000453:epidemiology*; D016022:Case-Control Studies; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000453:epidemiology*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D015994:Incidence; D007328:Insulin / Q000008:administration & dosage* / Q000627:therapeutic use; D007345:Insurance Claim Review / Q000706:statistics & numerical data; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000627:therapeutic use; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology; D016017:Odds Ratio; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D017678:Sex Distribution; D013624:Taiwan / Q000453:epidemiology
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin
keywords: Asthma; diabetes; insulin; metformin; population cohort