Association of Type 2 Diabetes With Cancer: A Meta-analysis With Bias Analysis for Unmeasured Confounding in 151...

Whether the association between type 2 diabetes (T2D) and cancer is causal remains controversial. The goal of this work is to assess the robustness of the observational associations between T2D and cancer to unmeasured confounding.

PubMed, Web of Science, and the Cochrane library were systematically searched on 10 January 2019 for observational studies investigating associations between T2D and cancer incidence or mortality.

Cohort-level relative risk (RR) was extracted. RRs were combined in random-effects meta-analyses and pooled estimates used in bias analyses. A total of 151 cohorts (over 32 million people, 1.1 million cancer cases, and 150,000 cancer deaths) were included. In meta-analyses, T2D was associated with incidence of several cancers, from prostate (RR 0.83; 95% CI 0.79, 0.88) to liver (2.23; 1.99, 2.49), and with mortality from pancreatic cancer (1.67; 1.30, 2.14). In bias analyses, assuming an unmeasured confounding associated with both T2D and cancer with a RR of 1.5, the proportion of studies with a true effect size larger than a RR of 1.1 (i.e., 10% increased risk in individuals with T2D) was nearly 100% for liver, pancreatic, and endometrial, 86% for gallbladder, 67% for kidney, 64% for colon, 62% for colorectal, and <50% for other cancer incidences, and 92% for pancreatic cancer mortality.

Biases other than unmeasured confounding were not analytically assessed.

Our findings strongly suggest a causal association between T2D and liver, pancreatic, and endometrial cancer incidence, and pancreatic cancer mortality. Conversely, associations with other cancers were less robust to unmeasured confounding.