Type 2 diabetes and cancer: umbrella review of meta-analyses of observational studies

BMJ. 2015 Jan 2:350:g7607. doi: 10.1136/bmj.g7607.


Objectives: To summarise the evidence and evaluate the validity of the associations between type 2 diabetes and the risk of developing or dying from cancer.

Design: An umbrella review of the evidence across meta-analyses of observational studies of type 2 diabetes with risk of developing or dying from any cancer.

Data sources: PubMed, Embase, Cochrane database of systematic reviews, and manual screening of references.

Eligibility criteria: Meta-analyses or systematic reviews of observational studies in humans that examined the association between type 2 diabetes and risk of developing or dying from cancer.

Results: Eligible meta-analyses assessed associations between type 2 diabetes and risk of developing cancer in 20 sites and mortality for seven cancer sites. The summary random effects estimates were significant at P=0.05 in 20 meta-analyses (74%); and all reported increased risks of developing cancer for participants with versus without diabetes. Of the 27 meta-analyses, eventually only seven (26%) compiled evidence on more than 1000 cases, had significant summary associations at P ≤ 0.001 for both random and fixed effects calculations, and had neither evidence of small study effects nor evidence for excess significance. Of those, only six (22%) did not have substantial heterogeneity (I(2)>75%), pertaining to associations between type 2 diabetes and risk of developing breast, cholangiocarcinoma (both intrahepatic and extrahepatic), colorectal, endometrial, and gallbladder cancer. The 95% prediction intervals excluded the null value for four of these associations (breast, intrahepatic cholangiocarcinoma, colorectal, and endometrial cancer).

Conclusions: Though type 2 diabetes has been extensively studied in relation to risk of developing cancer and cancer mortality and strong claims of significance exist for most of the studied associations, only a minority of these associations have robust supporting evidence without hints of bias.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Diabetes Complications / epidemiology*
  • Diabetes Complications / etiology*
  • Diabetes Mellitus, Type 2 / complications*
  • Female
  • Humans
  • Neoplasms / epidemiology*
  • Neoplasms / etiology*
  • Neoplasms / mortality
  • Reproducibility of Results
  • Risk Factors