Human insulin does not increase bladder cancer risk.
BACKGROUND
Whether human insulin can induce bladder cancer is rarely studied.


METHODS
The reimbursement databases of all Taiwanese diabetic patients from 1996 to 2009 were retrieved from the National Health Insurance. An entry date was set at 1 January 2004 and a total of 785,234 patients with type 2 diabetes were followed up for bladder cancer incidence until the end of 2009. Users of pioglitazone were excluded and the period since the initiation of insulin glargine (marketed after the entry date in Taiwan) was not included in the calculation of follow-up. Incidences for ever-users, never-users and subgroups of human insulin exposure (using tertile cutoffs of time since starting insulin, duration of therapy and cumulative dose) were calculated and the hazard ratios were estimated by Cox regression.


RESULTS
There were 87,940 ever-users and 697,294 never-users, with respective numbers of incident bladder cancer of 454 (0.52%) and 3,330 (0.48%), and respective incidence of 120.49 and 94.74 per 100,000 person-years. The overall hazard ratios (95% confidence intervals) indicated a significant association with insulin in the age-sex-adjusted models [1.238 (1.122-1.366)], but not in the model adjusted for all covariates [1.063 (0.951-1.187)]. There was also a significant trend for the hazard ratios for the different categories of the dose-response parameters in the age-sex-adjusted models, which became insignificant when all covariates were adjusted.


CONCLUSIONS
This study relieves the concern of a bladder cancer risk associated with human insulin. Appropriate adjustment for confounders is important in the evaluation of cancer risk associated with a medication.
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 of the National Health Research Institutes, Taipei, Taiwan.
Chin-Hsiao
CH
Tseng
D000328:Adult; D000367:Age Factors; D000368:Aged; D016208:Databases, Factual; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000188:drug therapy; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D015994:Incidence; D061386:Insulin, Regular, Human / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012307:Risk Factors; D012737:Sex Factors; D013624:Taiwan / Q000453:epidemiology; D001743:Urinary Bladder / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology
D007004:Hypoglycemic Agents; D061386:Insulin, Regular, Human