New research to be presented at this year's European Congress on Obesity (ECO 2025, Malaga, Spain, 11-14 May) shows that a new diagnosis of type 2 diabetes is linked to a subsequent increase in the risk of developing some, but not all, obesity related cancers. The study is by Owen Tipping, University of Manchester, UK, and Professor Andrew Renehan, National Institute for Health Research (NIHR) Manchester Biomedical Research Centre, Manchester, UK, and colleagues.
Previous research has described associations between type 2 diabetes mellitus (T2D) and higher risk of several obesity-related cancers (ORCs). However, it remains unclear whether these associations are causal, due to confounding (e.g their mutual risk factor of obesity); immortal time bias (many studies combine prevalent and new-onset T2D); or time detection bias (for example, the co-diagnosis of two relatively common conditions at the same time). In this study, the authors aimed to address these previous methodological flaws.
They performed a matched cohort control study within UK Biobank of new-onset T2D (defined by date of first reported non-insulin dependent diabetes) versus unexposed individuals matched (1 participant to 3 controls) on body mass index (BMI), age, and sex The primary outcome was incident ORC encompassing liver, pancreatic, bowel, post-menopausal breast, endometrial, kidney, oesophageal, stomach, multiple myeloma, gallbladder, thyroid, meningioma, and ovarian cancer.
Where case numbers permitted, the authors also investigated the risk of site-specific cancers. Statistical modelling was used to calculate the increased risk of cancer outcomes among participants with T2D, and was adjusted for alcohol consumption, smoking, and the influx of cancer diagnoses shortly following diabetes diagnosis due to increased medical surveillance.
A total of 23,750 participants with T2D were matched with 71,123 controls. Over a median follow-up time of 5 years, there were 2431 new primary cancers among T2D participants and 5184 new primary cancers among matched controls.
The data analysis showed new-onset T2D was associated with a 48% increased risk of ORC in men and a 24% increased risk in women – an effect independent of BMI. However, there were no associations with several site-specific ORCs – notably, endometrial, and post-menopausal breast cancer in women
There were positive associations found – new onset T2D increased the risk for bowel cancer by 27% in men and 34% in women; for pancreatic cancer by 74% in men and a near-doubling of risk in women. For liver cancer new onset T2D was associated with a near-quadrupling of risk in men and near 5-fold increased risk in women.
The authors explain: "At this stage we are unsure whether these differences in men and women are due to a sex-dependent biological pathway such as hormone levels, insulin sensitivity, body fat composition, or due to a simple difference in the number of cancers found in men and women within UK Biobank by chance."
The authors conclude: "Having accounted for key biases found in previous research in this field, and confounding (by adjusting for BMI, smoking, alcohol, and detection-time bias), our findings indicate that new-onset T2DM is associated with some but not all site-specific obesity-related cancers. In turn, the pathways through which T2DM may affect obesity-related cancer require further investigation."
The add that several mechanisms are under investigation – high levels of insulin (hyperinsulinaemia), high levels of glucose (hyperglycaemia), and chronic inflammation. The authors say: "Hyperinsulinemia has the strongest evidence for a plausible mechanism due to its ability to stimulate cell growth and proliferation."
