Cohort profile: the German Diabetes Study (GDS)

Abstract

Background: The German Diabetes Study (GDS) is a prospective longitudinal cohort study describing the impact of subphenotypes on the course of the disease. GDS aims at identifying prognostic factors and mechanisms underlying the development of related comorbidities.

Study design and methods: The study comprises intensive phenotyping within 12 months after clinical diagnosis, at 5-year intervals for 20 years and annual telephone interviews in between. Dynamic tests, including glucagon, mixed meal, intravenous glucose tolerance and hyperinsulinemic clamp tests, serve to assess beta-cell function and tissue-specific insulin sensitivity. Magnetic resonance imaging and multinuclei spectroscopy allow quantifying whole-body fat distribution, tissue-specific lipid deposition and energy metabolism. Comprehensive analyses of microvascular (nerve, eye, kidney) and macrovascular (endothelial, cardiorespiratory) morphology and function enable identification and monitoring of comorbidities. The GDS biobank stores specimens from blood, stool, skeletal muscle, subcutaneous adipose tissue and skin for future analyses including multiomics, expression profiles and histology. Repeated questionnaires on socioeconomic conditions, patient-reported outcomes as quality of life, health-related behavior as physical activity and nutritional habits are a specific asset of GDS. This study will recruit 3000 patients and a group of humans without familiy history of diabetes. 237 type 1 and 456 type 2 diabetes patients have been already included.

Keywords: Beta cell function; Diabetes comorbidities; Insulin resistance; Magnetic resonance spectroscopy; Metabolic phenotyping.

Fig. 1

Beta-cell function as assessed from increase of C-peptide during the glucagon stimulation test (C-peptide concentration at 6 min after injection minus C-peptide concentration at baseline) (a, n = 216 patients with type 1 DM, n = 374 patients with type 2 DM), insulin sensitivity (M value) as assessed from euglycemic-hyperinsulinemic clamp tests in patients with type 1 DM or type 2 DM (b, n = 204 patients with type 1 DM, n = 351 patients with type 2 DM), high-density lipoprotein levels (HDL, c, n = 236 patients with type 1 DM, n = 448 patients with type 2 DM), low-density lipoprotein levels (LDL, d, n = 236 patients with type 1 DM, n = 448 patients with type 2 DM), systolic blood pressure (e, n = 237 patients with type 1 DM, n = 447 patients with type 2 DM), and diastolic blood pressure (f, n = 237 patients with type 1 DM, n = 447 patients with type 2 DM)