The Danish Centre for Strategic Research in Type 2 Diabetes (DD2) Project: rationale and planned nationwide studies of genetic predictors, physical exercise, and individualized pharmacological treatment

Charlotte Steffensen,¹ Reimar W Thomsen,² Allan Vaag,³ Henning Beck-Nielsen,⁴ Jens Sandahl Christiansen,¹ Torben Hansen,^5,6 Oluf Borbye Pedersen,^5,6 Jørgen Rungby<sup>1

1</sup>Aarhus University Hospital, Department of Medicine, Aarhus, ²Aarhus University Hospital, Institute of Clinical Medicine, Department of Clinical Epidemiology, Aarhus, ³Copenhagen University Hospital "Rigshospitalet", Department of Endocrinology, Copenhagen, ⁴Odense University Hospital, Department of Endocrinology, Odense, ⁵The Novo Nordisk Foundation Centre for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, ⁶Faculty of Health Sciences, University of Aarhus, Aarhus, Denmark

Abstract: Here we provide an overview of the rationale and methods of a series of planned population based studies within the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) Project. The project aims to support and evaluate ongoing political and administrative efforts to implement nationwide guidelines for maintaining metabolic control in newly diagnosed type 2 diabetes (T2D) patients to prevent diabetic complications and improve quality of life. The DD2 is designed as a prospective cohort study (collection of epidemiological data) supplemented by randomized clinical intervention trials (on physical exercise and individualized pharmacological treatment) and the establishment of a biobank comprised of material from a large number of newly diagnosed T2D patients. Inclusion of the majority of newly diagnosed T2D patients as they are diagnosed at their general practitioner or diabetes hospital outpatient clinics and entered into the DD2 cohort will establish a nationwide database comprising a large number of future incident cases of T2D in Denmark. These cases will form the project cohort of the DD2. Within the first 6 months of diagnosis, all patients will be invited to contribute to a biobank of DNA, plasma, urine, and tissue sampling. The DNA biobank will enable future studies of the effect of pharmacological treatment and outcome in subsets of patients with specific genetic risk profiles covering disease etiology and specific drug kinetics and metabolism. We will also perform two clinical intervention trials examining: the effectiveness of physical exercise on diabetes-related outcomes and the impact of trial outcomes on individualized pharmacological treatment. Moreover, the DD2 will serve as a platform for testing and developing new antidiabetic drugs. All together, we expect this study to contribute to substantially improved diabetes care in T2D patients locally and abroad.

Keywords: type 2 diabetes, prognosis, intervention, physical exercise