Risk of malignancies in patients with insulin-treated diabetes mellitus -: Results of a population-based trial with 10-year follow-up (JEVIN)

Background: Studies involving diabetes mellitus and malignancies show contradictory results: Many of them have found incidences of malignancies that are comparable or lower, other studies have found higher rates than those of non-diabetic subjects. Hence, the goal of the present trial was to study the possible association between diabetes mellitus and the incidence of malignancies and its outcome in a selection-free population over a longer period of time. Patients and methods: All the patients (n = 291) who participated in the JEVIN (Jena's St. Vincent)- trial (a prospective, 10 year follow-up, population-based intervention survey of all insulin-treated patients with type I and type 2 diabetes mellitus aged 16 to 60 years and living in the city of Jena [about 100,000 inhabitants], Thuringia, Germany) were assessed. The baseline examination took place in 1989/90, follow-up examinations were performed in 1994/95 and 1999/2000. Results: Up to 1999/2000, 2 patients with type 1 and 5 patients with insulin-treated type 2 diabetes mellitus developed a malignancy (incidence 0.0241). The most frequent malignancies were cancer of the colon and rectum (3 of 291 patients, incidence 0.0103). Comparing these data with the incidence of carcinoma of the colon and rectum reported by the Robert-Koch-Institrite of Germany (incidence 0.0012) diabetic patients showed a 9.9-fold increased risk (p = 0.042). There were no significant differences regarding incidence of total malignancies or carcinoma of the breast, the lung, renal cells or gonads. Correlation and multivariate analyses revealed no associations between the development of malignancies and patients' outcome and diabetes duration, the duration of insulin therapy, insulin dosage, the quality of diabetes control or the presence of diabetes-related long-term complications. Conclusions: Conclusive to other data derived from selected cohorts, population-based the JEVIN-trial demonstrate an increased incidence of malignancies of the colon and rectum in insulin-treated patients with diabetes mellitus. However, for further confirmation of these interesting results more studies in larger populations over longer periods of time are necessary to explain the heterogeneous findings in patients with diabetes mellitus of an increased incidence for some cancer entities, but not for others. Knowledge of these mechanisms should have important implications for the direction of strategies to prevent the development of malignancies, or to enhance ability to make an earlier diagnosis and more effective therapies.