To determine the role of waist circumference and metabolic dysfunction in the risk of cancer in individuals with type 2 diabetes (T2D) and to compare this to individuals without T2D.

Individuals with (n = 1925) and without T2D (n = 10,204) were included from the UCC-SMART cohort. Incident cancer diagnoses were obtained by linkage with the Netherlands Cancer Registry. Metabolic dysfunction was defined as ≥ 3 adapted NCEP ATP-III metabolic syndrome criteria. The effects of waist circumference and metabolic dysfunction on cancer were assessed using Cox proportional hazards models, adjusted for confounders.

During a median follow-up of 8.3 years (IQR 4.2–13.1), 1740 individuals were diagnosed with cancer. Incidence rates of total cancer were 19.3 and 15.5/1000 person-years for individuals with and without T2D, respectively. In individuals without T2D, a higher waist circumference was associated with an increased risk of colorectal (per standard deviation: HR 1.23; 95%CI 1.03–1.46), urinary tract (HR 1.28; 95%CI 1.05–1.56) and total cancer (HR 1.06; 95%CI 1.02–1.13). Metabolic dysfunction was related to an increased risk of colorectal (HR 1.35; 95%CI 1.01–1.82), lung (HR 1.37; 95%CI 1.07–1.75) and total cancer (HR 1.13; 95%CI 1.01–1.25) in individuals without T2D. In individuals with T2D, no significant associations were found.

Incidence rates of cancer are higher among individuals with T2D. However, higher waist circumference and metabolic dysfunction are only associated with an increased cancer risk in patients without T2D. These findings provide novel insights into the role of metabolic dysfunction in the occurrence of cancer.