Insulin therapy and the risk of colorectal cancer in patients with type 2 diabetes: a meta-analysis of observational studies

Br J Clin Pharmacol. 2014 Aug;78(2):301-9. doi: 10.1111/bcp.12350.

Abstract

Aims: Several epidemiological studies have reported inconsistent associations between insulin therapy and the risk of colorectal cancer (CRC) in patients with type 2 diabetes mellitus. We performed this meta-analysis of observational studies to evaluate the effect of insulin therapy on the risk of CRC.

Methods: We carried out a systematic search of PubMed, Embase and the Cochrane Library Central database between January 1966 and August 2013. Fixed-effects and random-effects models were used to estimate the pooled relative risk (RR) and corresponding 95% confidence interval (CI).

Results: A total of 12 epidemiological studies were included in the present meta-analysis, involving a total of 7947 CRC cases and 491 384 participants. There was significant heterogeneity among the studies, but no publication bias. Insulin therapy significantly increased the risk of CRC [RR = 1.69, 95% CI (1.25, 2.27)]. When the various studies were stratified by study design, we found that insulin use was associated with a statistically significant 115% higher risk of CRC among case-control studies [RR = 2.15, 95% CI (1.41, 3.26)], but not among cohort studies [RR = 1.25, 95% CI (0.95, 1.65)]. Furthermore, a significant association was noted among studies conducted in USA [RR = 1.73, 95% CI (1.15, 2.60)] and Asia [RR = 2.55, 95% CI (2.14, 3.04)], but not in Europe [RR = 1.20, 95% CI (0.92, 1.57)].

Conclusions: The present meta-analysis suggests that insulin therapy may increase the risk of CRC. More prospective cohort studies with longer follow-up durations are warranted to confirm this association. Furthermore, future studies should report results stratified by gender and race and should adjust the results by more confounders.

Keywords: colorectal cancer; epidemiology; insulin; meta-analysis.

Publication types

  • Meta-Analysis

MeSH terms

  • Colorectal Neoplasms / chemically induced*
  • Data Interpretation, Statistical
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects*
  • Hypoglycemic Agents / therapeutic use
  • Insulin / administration & dosage
  • Insulin / adverse effects*
  • Insulin / therapeutic use
  • Observational Studies as Topic
  • Risk

Substances

  • Hypoglycemic Agents
  • Insulin