To compare metabolic dysfunction-associated profiles between patients with diabetes who developed different obesity-related site-specific cancers and those who remained free of cancer during follow-up.

Retrospective cohort study.

Public general outpatient clinics in Hong Kong.

Patients with diabetes without a history of malignancy (n=391 921).

The outcomes of interest were diagnosis of site-specific cancers (colon and rectum, liver, pancreas, bladder, kidney and stomach) during follow-up. Cox proportional hazards regression was applied to assess the associations between metabolic dysfunction and other clinical factors with each site-specific cancer.

Each 0.1 increase in waist-to-hip ratio was associated with an 11%–35% elevated risk of colorectal, bladder and liver cancers. Each 1% increase in glycated haemoglobin was linked to a 4%–9% higher risk of liver and pancreatic cancers. While low-density lipoprotein cholesterol and triglycerides were inversely associated with the risk of liver and pancreatic cancers, high-density lipoprotein cholesterol was negatively associated with pancreatic, gastric and kidney cancers, but positively associated with liver cancer. Furthermore, liver cirrhosis was linked to a 56% increased risk of pancreatic cancer. No significant association between hypertension and cancer risk was found.

Metabolic dysfunction-associated profiles contribute to different obesity-related cancer outcomes differentially among patients with diabetes. This study may provide evidence to help identify cancer prevention targets during routine diabetes care.