Development and validation of risk assessment models for diabetes-related complications based on the DCCT/EDIC data

Aim: To derive and validate a set of computational models able to assess the risk of developing complications and experiencing adverse events for patients with diabetes. The models are developed on data from the Diabetes Control and Complications Trial (DCCT) and the Epidemiology of Diabetes Interventions and Complications (EDIC) studies, and are validated on an external, retrospectively collected cohort. Methods: We selected fifty-one clinical parameters measured at baseline during the DCCT as potential risk factors for the following adverse outcomes: Cardiovascular Diseases (CVD), Hypoglycemia, Ketoacidosis, Microalbuminuria, Proteinuria, Neuropathy and Retinopathy. For each outcome we applied a data-mining analysis protocol in order to identify the best-performing signature, i.e., the smallest set of clinical parameters that, considered jointly, are maximally predictive for the selected outcome. The predictive models built on the selected signatures underwent both an interval validation on the DCCT/EDIC data and an external validation on a retrospective cohort of 393 diabetes patients (49 Type I and 344 Type II) from the Chorleywood Medical Center, UK. Results: The selected predictive signatures contain five to fifteen risk factors, depending on the specific outcome. Internal validation performances, as measured by the Concordance Index (CI), range from 0.62 to 0.83, indicating good predictive power. The models achieved comparable performances for the Type I and, quite surprisingly, Type II external cohort. Conclusions: Data-mining analyses of the DCCT/EDIC data allow the identification of accurate predictive models for diabetes-related complications. We also present initial evidences that these models can be applied on a more recent, European population.