title: Cancer specific mortality in insulin-treated type 2 diabetes patients.
abstract: OBJECTIVE
  To test the hypothesis that cumulative exposure to insulin and long-acting insulin analogs might be associated with cancer mortality in diabetes patients.
  
  
  METHODS
  All consecutive diabetes patients aged over 40 years, residing in a major urban area were screened at their first diabetes outpatient visit between 01/01/2001-12/31/2008 (n = 79869). Exclusion criteria were insulin treatment at screening, no insulin treatment until 12/31/2008, less than 6 months of glucose-lowering treatment alone before insulin initiation, insulin prescription before glargine became available, age <40/≥ 80 years at first insulin prescription, and <6 months of insulin exposure. A total 4990 subjects were followed-up for death based on death certificate, until 12/31/2011. Adjusted time-dependent competing risk regression analysis, with daily updates of treatment modalities was performed. Results are expressed for every 10,000 IU of cumulative dose or one year of cumulative time exposure to insulin.
  
  
  RESULTS
  Mean baseline age was 62 ± 9 years, and follow-up 4.7 ± 1.9 years. Glargine cumulative dose was associated with lower cancer mortality risk (subhazard ratio, SHR: 0.94 (95%CI 0.89-0.99, p = 0.033)). Cumulative exposure limited to that attained one year prior to death revealed lower SHRs for cumulative time (0.94 (95%CI 0.89-0.99, p = 0.018)) and cumulative dose of glargine (0.92 (95%CI 0.86-0.98, p = 0.014)). Glargine cumulative time and cumulative dose were significant predictors for lower pancreatic and breast cancer mortality, but not for deaths from lung, colorectal, female genital, liver, and urinary tract cancer. No increased hazards were found for any other subtypes of insulins.
  
  
  CONCLUSIONS
  The cumulative dose exposure to insulin glargine was associated with a lower risk of cancer mortality in general, and of breast and pancreatic cancer in particular. This effect remained even after additional "fixed" cohort or propensity score analyses.
authors.affiliation: "Elias" Hospital, Bucharest, Romania; "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania.
authors.forename: Sorin
authors.initials: S
authors.lastname: Ioacara
authors.affiliation: "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania; "N. Paulescu" National Institute of Diabetes, Nutrition and Metabolic Diseases, Bucharest, Romania.
authors.forename: Cristian
authors.initials: C
authors.lastname: Guja
authors.affiliation: "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania; "N. Paulescu" National Institute of Diabetes, Nutrition and Metabolic Diseases, Bucharest, Romania.
authors.forename: Constantin
authors.initials: C
authors.lastname: Ionescu-Tirgoviste
authors.affiliation: "Elias" Hospital, Bucharest, Romania; "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania.
authors.forename: Simona
authors.initials: S
authors.lastname: Fica
authors.affiliation: Department of Endocrinology and Diabetology, Heinrich-Heine University, Düsseldorf, Germany; Institute for Clinical Diabetology, German Diabetes Center, Düsseldorf, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Roden
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007328:Insulin / Q000009:adverse effects* / Q000627:therapeutic use*; D049528:Insulin, Long-Acting / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications* / Q000401:mortality*; D018570:Risk Assessment
chemical_list: D007328:Insulin; D049528:Insulin, Long-Acting