CARING (CAncer Risk and INsulin analoGues): the association of diabetes mellitus and cancer risk with focus on possible determinants - a systematic review and a meta-analysis

Jakob Starup-Linde*, Oystein Karlstad, Stine Aistrup Eriksen, Peter Vestergaard, Heleen K Bronsveld, Frank de Vries, Morten Andersen, Anssi Auvinen, Jari Haukka, Vidar Hjellvik, Marloes T Bazelier, Anthonius de Boer, Kari Furu, Marie L De Bruin

*Corresponding author for this work

Research output: Contribution to journal(Systematic) Review article peer-review


BACKGROUND: Patients suffering from diabetes mellitus (DM) may experience an increased risk of cancer; however, it is not certain whether this effect is due to diabetes per se.

OBJECTIVE: To examine the association between DM and cancers by a systematic review and meta-analysis according to the PRISMA guidelines.

DATA SOURCES: The systematic literature search includes Medline at PubMed, Embase, Cinahl,, Cochrane library, Web of Science and SveMed+ with the search terms: "Diabetes mellitus", "Neoplasms", and "Risk of cancer".

STUDY ELIGIBILITY CRITERIA: The included studies compared the risk of cancer in diabetic patients versus non-diabetic patients. All types of observational study designs were included.

RESULTS: Diabetes patients were at a substantially increased risk of liver (RR=2.1), and pancreas (RR=2.2) cancer. Modestly elevated significant risks were also found for ovary (RR=1.2), breast (RR=1.1), cervix (RR=1.3), endometrial (RR=1.4), several digestive tract (RR=1.1-1.5), kidney (RR=1.4), and bladder cancer (RR=1.1). The findings were similar for men and women, and unrelated to study design. Meta-regression analyses showed limited effect modification of body mass index, and possible effect modification of age, gender, with some influence of study characteristics (population source, cancer- and diabetes ascertainment).

LIMITATIONS: Publication bias seemed to be present. Only published data were used in the analyses.

CONCLUSIONS: The systematic review and meta-analysis confirm the previous results of increased cancer risk in diabetes and extend this to additional cancer sites. Physicians in contact with patients with diabetes should be aware that diabetes patients are at an increased risk of cancer.

Original languageEnglish
Pages (from-to)296-332
Number of pages37
JournalCurrent Drug Safety
Issue number5
Publication statusPublished - Nov 2013
Externally publishedYes


  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Child
  • Child, Preschool
  • Diabetes Complications/epidemiology
  • Diabetes Mellitus/drug therapy
  • Humans
  • Hypoglycemic Agents/adverse effects
  • Infant
  • Insulin/adverse effects
  • Middle Aged
  • Neoplasms/epidemiology
  • Publication Bias
  • Regression Analysis
  • Risk
  • Young Adult

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