Inflammatory biomarkers in the health to disease transition: NAKO data contributes to IMMEDIATE project
After the list of observational cohorts used in the previous IMMEDIATE insights blog post, today we dive into the German National Cohort (NAKO). Another contribution to the IMMEDIATE insight blog series comes from Solange Gonzalez Chiappe, a post-doctoral fellow from the Max Delbrück Center.
Long periods of chronic subclinical inflammation may precede organ damage, eventually leading to clinical manifestation of chronic diseases such as cardiovascular disease, chronic kidney disease, type 2 diabetes, or brain damage. However, the complexity of these relationships and, in particular, the processes preceding organ dysfunction are insufficiently understood. With the EU-funded IMMEDIATE project (Imminent Disease Prediction and Prevention at the Environment Host Interface), data from the German National Cohort (NAKO) will be used to unravel shared and non-shared inflammation signatures in the transition from health to disease in the domains of metabolic, cardiovascular, kidney and brain function.
The “NAKO Gesundheitsstudie” is well suited to address IMMEDIATE research questions. Indeed, it is a large-scale, nationwide, long-term population-based cohort study that aims to investigate the causes of widespread diseases, identify risk factors, and highlight effective forms of early detection and prevention of disease. For this purpose, a total of 205,217 individuals aged between 20 and 69 from across Germany were medically examined and questioned on their living habits (including MRI measurements among 30.861 persons) between 2014 and 2019. All volunteers were recruited in 18 study centres and examined by using the same protocols and equipment. All participants supplied blood samples, which are stored in a central biobank as well as in decentral biorepositories at the study centres for later research projects. Participants are followed up for incident diseases via questionnaires (every 2-3 years) and use of secondary data, including information from health and pension insurance companies, cancer registries and mortality registries. In addition, as a unique point in this large cohort, it is planned to invite all participants to re-examinations every 4-5 years, which will allow us to measure changes in risk factors and phenotypes and thus the transition from health to disease in detail.
For IMMEDIATE purposes, a NAKO subset from Berlin-North participants will be sampled and their inflammation profiles will be deeply characterized by a variety of inflammation-related proteins in baseline blood samples. This data will be related to prospective changes between the baseline and first follow-up examination (approximately 5 years apart) in intermediary outcome variables (HbA1c, blood pressure, arterial stiffness, and glomerular filtration rate) in order to identify domain-specific and overarching inflammation signatures. In addition, baseline inflammation profiles will be related to the progression of brain damage as evidenced by neuroimaging which enables comprehensive quantitative assessment of brain white matter damage, grey and white matter atrophy, and changes in functional connectivity over time. Lifestyle (anthropometry, physical activity, alcohol consumption, diet, smoking) and other (medical history, well-being, quality of life) factors associated with the identified shared and non-shared inflammation signatures will be investigated in order to explore the potential of personalized prevention. Finally, the gut microbiome profile will be quantified in stool samples and metabolomics profiling will be performed in blood samples for an integrative analysis of systems-overarching modulation pathways of chronic inflammation. Together, we will seize this opportunity of using multi-modality datasets to evaluate how the diet-microbiome-metabolite-immune axis influences health conditions as well as structural and homeostatic changes in the brain.
For more details on NAKO please visit their website https://nako.de/