Scientific Concept of the National Cohort (status ... - Nationale Kohorte

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A.3 Study design
dictive value of structural alterations and tissue composition for the development of metabolic
and inflammatory disorders. Thus, we hypothesize, for example, that early changes
in lung and airway structure are strong predictors for inflammatory disease and that early
changes in kidney structure are strong predictors of cardiovascular and metabolic diseases.
Metabolism / energy balance
MRI can explicitly distinguish between body fat compartments, including fat in subcutaneous,
visceral, intrahepatic, intrapancreatic, and intraskeletal localizations. Particularly with
respect to the risk of future cardiovascular and metabolic diseases – including insulin resistance,
beta cell dysfunction, and type 2 diabetes – the dedicated predictive value of volume
of each of these compartments can be assessed. Thus, we will determine which specific fat
compartment has the strongest predictive value for incident cardiometabolic diseases and
hypothesize that the volume of visceral fat and the amount of liver fat are stronger predictors
for incident type 2 diabetes and CVD than are other fat compartments or somatometric
measurements. In addition to the specific role of each of the fat compartments, fat-to-muscle
ratio may add further predictive value to the risk of cardiometabolic diseases. By using
this database, investigations can be conducted on the interactions of genetic factors with
nutrition and physical activity and predict the fat-to-muscle ratio and changes over time.
Overview
A.3.4.4 Study population, imaging methods, and planned study logistics
The comprehensive native MRI scans will be performed at dedicated imaging sites in close
proximity to the study centers. These imaging facilities will be uniformly equipped with identical
3-Tesla MRI technology and adequately trained and certified staff will ensure high standardization
and internal validity of the acquired MRI data sets. Upon completion of the examination,
data will be transferred to a centralized reading core at the competence center on
imaging for a ”first-line” reading to determine the presence of relevant (major) incidental findings
and for quality control. It is planned that serious incidental findings will be reported immediately
to the imaging site, which will initiate appropriate algorithms to manage conditions
that have been detected; the latter procedures, however, are still subject to feasibility studies.
Data will also be transferred to an integration center for long-term archiving and so that they
are available for subsequent ”second-line” reading and scientific analysis. Using similar
technical equipment, a follow-up examination is scheduled after 5 years.
Study population
Anticipated subresponse: Currently, no final decision has been reached concerning how
to design the invitation procedure at the MRI sites. The two variants under discussion are:
1) To treat the MRI examination as a substudy. Here, all participants to be examined at
the site are offered to participate in the MRI examination on a voluntary basis. According
to the SHIP experience, a subresponse (participation rate) of up to 60% can be expected.
This would have the consequence that only National Cohort study centers or regions with
>15,000 participants will be qualified as a MRI site; 2) only those subjects are included at
MRI sites who are not only willing to participate in Level 1 and 2 examinations, but also in
the MRI examination. At present, the first variant is favored. However, currently, too few
study centers exist to examine >10,000 subjects.
A.3