The following examinations are performed at time points indicated above and are described in more detail in our standard operating procedures (Appendix 1). Briefly, blood samples are obtained from an arm vein after a 12-h overnight fast. Triglycerides (TG), glucose, insulin, high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), total cholesterol, C-reactive protein (CRP), glycosylated hemoglobin (HbA
1c), and C-peptide are measured using standard procedures at respective hospitals or centers with high standard of accuracy. Serum and EDTA plasma are centrifuged at 2500 rpm for 10 min at 20 °C. Aliquots are stored at −80°C in case new blood markers will be analyzed later. In addition, whole blood from an EDTA tube is taken and stored (at Regional Biobank) at −80°C for later analysis of DNA and other blood markers. Blood pressure is measured after a 12-h overnight fast and following 15 min of seated quiet rest. Testing of cardiorespiratory fitness (peak oxygen uptake, V̇O
2peak) is performed on a treadmill or cycle ergometers identical to that in previous studies in our group [
11]. Ergometer selected for testing is dependent upon preferred type of exercise during the intervention, as well as physical limitations presented by participants. Participants with previous heart diseases are tested under electrocardiograph (ECG) monitoring, and the ACC/AHA-guidelines for exercise testing of patients with known cardiovascular disease is followed [
12]. Body composition and weight are measured using bioelectrical impedance (Inbody 720, BIOSPACE, Seoul, Korea). Physical activity is measured via SenseWear Armband activity monitor (BodyMedia 7, Pittsburgh, PA, USA) or by Actigraph (GT3X, Manufactering Technology Inc., Florida, USA). After the clinical test at the hospital, all participants are given either SenseWear or Actigraph monitor. The participants are instructed to wear it for seven days continuously (24 h), except when in contact with water (shower/bath/swim). Novel genetic biomarkers (DNA and RNA) will be analyzed using high-throughput OMICS technology (genotyping or exome sequencing, DNA methylation, RNA sequencing, microRNA screening, MS-based proteomics, and MR metabolomics) using validated methods established at the Norwegian University of Science and Technology’s Genomics, Proteomics and Metabolomics Core Facilities. Health economic analysis will be calculated as the sum of hospital cost (inpatient, day care, and outpatient care), use of general physician, and primary health care (rehabilitation, nursing homes, home care etc.). Five different questionnaires are used in this study: Questionnaire 1 consisted of questions about specific aspects of physical activity history. The short form health survey SF-8 (1-wk recall version) is used to describe quality of life and chronic pain (Q3). The questions from Q1, Q2 and Q3 are the same questions that have been used in the Nord-Trøndelag Health Study (HUNT) [
13‐
15]. Medications were monitored throughout the study.