A new diagnosis of type 2 diabetes may be linked to a subsequent increased risk of developing some obesity-related cancers, according to new findings presented at the European Congress on Obesity (ECO) 2025.
Background
Previous research has uncovered associations between type 2 diabetes and a higher risk of several obesity-related cancers. However, it remains unclear whether these associations are causal, the result of confounding factors; immortal time bias, caused by the combination of prevalent and new-onset type 2 diabetes; or time detection bias, such as the co-diagnosis of two relatively common conditions simultaneously.
Study Methods and Results
Investigators aimed to address these previous methodological flaws in a new study. They used UK Biobank data to match 23,750 patients with new-onset type 2 diabetes (defined by the date of first reported non–insulin-dependent diabetes) with 71,123 controls on the basis of body mass index (BMI), age, and sex. The primary outcome of the study was incident obesity-related cancer—encompassing hepatic, pancreatic, colorectal, postmenopausal breast, endometrial, renal, esophageal, gastric, multiple myeloma, gallbladder, thyroid, meningioma, and ovarian cancers.
Where case numbers permitted, the investigators also examined the risk of site-specific cancers. They used statistical modeling to calculate the increased risk of cancer outcomes among patients with type 2 diabetes and adjusted for alcohol consumption, smoking status, and the influx of cancer diagnoses shortly following diabetes diagnosis as a result of increased medical surveillance.
After a median follow-up of 5 years, the investigators identified 2,431 new primary cancers among the patients with type 2 diabetes and 5,184 new primary cancers among matched controls. They found that new-onset type 2 diabetes was associated with a 48% and 24% increased risk of obesity-related cancers in male and female patients, respectively, an effect independent of BMI. Nonetheless, there were no associations with several site-specific obesity-related cancers, notably, endometrial and postmenopausal breast cancers.
Additionally, new-onset type 2 diabetes increased the risk of colorectal cancer by 27% in male patients and 34% in female patients. The risk of pancreatic cancer was elevated by 74% in male patients and nearly double among female patients with new-onset type 2 diabetes. For hepatic cancer, new-onset type 2 diabetes was associated with a near-quadrupling of the risk in male patients and near fivefold increased risk in female patients.
Conclusions
“At this stage, we are unsure whether these differences in [male] and [female patients are resultant from] a sex-dependent biological pathway such as hormone levels, insulin sensitivity, body fat composition, or … a simple difference in the number of cancers found in [male] and [female patients] within UK Biobank by chance,” the study authors indicated. “Having accounted for key biases found in previous research in this field, and confounding [factors] (by adjusting for BMI, smoking, alcohol, and detection-time bias), our findings indicate that new-onset [type 2 diabetes] is associated with some but not all site-specific obesity-related cancers. In turn, the pathways through which [type 2 diabetes] may affect obesity-related cancer require further investigation,” they underscored.
The investigators are currently exploring several mechanisms, including hyperinsulinemia, hyperglycemia, and chronic inflammation.
“Hyperinsulinemia has the strongest evidence for a plausible mechanism [because of] its ability to stimulate cell growth and proliferation,” the study authors concluded.
