title: Treatment with human insulin does not increase thyroid cancer risk in patients with type 2 diabetes.
abstract: BACKGROUND
  Whether human insulin therapy may increase thyroid cancer risk in patients with type 2 diabetes mellitus (T2DM) has not been investigated.
  
  
  METHODS
  The reimbursement databases of all Taiwanese diabetic patients from 1996 to 2009 were retrieved from the Bureau of National Health Insurance. The entry date was set at 1 January 2004, and 968,384 patients with T2DM were followed up for thyroid cancer incidence until the end of 2009. Ever-users, never-users and subgroups of human insulin exposure (using tertile cut-offs of time since starting insulin, duration of therapy and cumulative dose) at entry date were calculated for thyroid cancer incidence. Insulin glargine was not marketed until after the entry date. Therefore, to exclude the potential contamination of insulin glargine, patients who happened to use insulin glargine were censored at the time of its initiation when calculating the period of follow-up. Hazard ratios were estimated by Cox regression.
  
  
  RESULTS
  There were 111,121 ever-users and 857,263 never-users of human insulin, with respective numbers of incident thyroid cancer of 118 (0·11%) and 1047 (0·12%), and respective incidences of 23·9 and 23·8 per 100,000 person-years. The overall hazard ratios (95% confidence intervals) did not show a significant association with human insulin in either the age-sex-adjusted or the fully adjusted model: 0·942 (0·778-1·141) and 1·096 (0·888-1·353), respectively. When categorized into tertiles of the dose-response parameters, none of the hazard ratios was significant.
  
  
  CONCLUSIONS
  This study does not support the role of human insulin therapy in increasing the risk of thyroid cancer in patients with T2DM.
authors.affiliation: Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Taipei, Taiwan.
authors.forename: Chin-Hsiao
authors.initials: CH
authors.lastname: Tseng
mesh_terms: D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D061386:Insulin, Regular, Human / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D013964:Thyroid Neoplasms / Q000139:chemically induced*
chemical_list: D007004:Hypoglycemic Agents; D061386:Insulin, Regular, Human
keywords: Diabetes; Taiwan; epidemiology; insulin; thyroid cancer