E11
Conditions
Interventions
Group 1: Newly diagnosed T2D
Visit 1:
indirect calorimetry, blood pressure measurement, blood sampling,
MRI and spectroscopy to assess the entire body.
Anthropometry, bioimpedance analysis and plethys
Sponsors
Deutsches Luft- und Raumfahrtzentrum, Institut für Luft- und Raumfahrtmedizin
Eligibility
Sex/Gender
All
Age
24 Years to 69 Years
Inclusion criteria
Inclusion criteria: Individuals with T2D: • Female and male individuals with T2D diagnosis according to ADA criteria • No participation in structured exercise programs for =6 months • BMI between 19 and 35 kg/m2 • Age between 24 and 69 years • Signed informed consent Overweight-toobese individuals: • Female and male participants with normal glucose tolerance • Sex-, age- and physical activity levelmatched to individuals with T2 • No participation in structuredexercise programs for =6 months • BMI between 25 to 40 kg/m2 • Signed informed consent Normal-weight individuals: • Metabolically healthy female and male participants with normal glucose tolerance • Sex-, age- and physical activity levelmatched to individuals with T2D • No participation in structured exercise programs for =6 months • BMI between 19 to 24.9 kg/m2 • Signed informed consent
Exclusion criteria
Exclusion criteria: • Contra-indications against biopsy (e.g. impaired hemostasis, keloidosis, history of adverse reactions to local anesthesia or to surgical procedures) • Contra-indications against magnetic resonance imaging, including metal implants or other osteosynthesis material, not MRI compatible stents, clips etc., pacemakers, infusion pumps, claustrophobia • neurological conditions including strokes, brain hemorrhage, aneurysms, brain tumors, neurodegenerative diseases, seizures, head trauma based on medical history • Cardiovascular conditions including acute coronary artery disease with coronary angina or myocardial infarction in the last 6 months, heart failure (NYHA III-IV), ventricular or atrial arrhythmias, pacemaker, recurrent syncope, • Autonomic disorders • Chronic pulmonary diseases (COPD, severe asthma, pulmonary fibrosis) • Sleep apnea, insomnia or narcolepsy based on medical history • Any other medical condition that the investigators consider contraindication to the study procedures that would make it unsafe or confound the measurements, e.g. medication with insulin, sulfonylurea, glinide,medication influencing hemostasis (e.g. ASS, anticoagulants)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Metabolic in vivo analyses: - Insulin sensitivity via hyperinsulinemic euglycemic clamp (HEC) - Maximal aerobic capacity and detailed muscle function (strength, jump height) - Liver and muscle lipid content via non-invasive 1H-magenitic resonance spectroscopy (MRS) - Liver volume and liver glycogen via non-invasive 13C-MRS - Abdominal fat 6-point Dixon magnetic resonance imaging (MRI) - Energy expenditure and substrate utilization (carbohydrate and fat) via indirect calorimetry at rest and during insulin-stimulated conditions Mechanical in vivo analyses: - Maximal aerobic capacity and maximal muscle force production - Grip strength - Body composition via body plethysmography and bio-electrical impedance analysis | — |
Secondary
| Measure | Time frame |
|---|---|
| From muscle biopsy - Insulin signaling - Mitochondrial function via Polarography - Muscle ultrastructure and fibro-fatty degeneration from histology - Fate of fibro-adipogenic progenitor cells from muscle samples - Myopathological analysis via light microscopy and electron microscopy - Mitochondrial content via citrate synthase activity and mitochondrial DNA copy number - Oxidative stress via mitochondrial and plasma oxidation-reduction potential - Proteomics - Intramyocellular neutral fat content - RNA sequencing From blood samples - routine laboratory blood parameters (glucose, insulin, lactate, pyruvate, free-fatty acids, total cholesterol, LDL-C, HDL-C, creatinine, AST, ALT, gammaGT, hsCRP, fT3, fT4, TSH, HbA1c, albumin, electrolytes, glucagon, CK, LDH, troponin, BNP) - Carnitine and acylcarnitine profiles (mass spec analysis via dried blood sample cards) - markers of biological age: “DNAge” based on CpG DNA methylation pattern of 6 selected genes - blood circulating myo-microRNAs. - blood gas analysis | — |
Countries
Germany
Contacts
Public ContactDominik Pesta
Deutsches Zentrum für Luft- und Raumfahrt - Institut für Luft- und Raumfahrtmedizin
Outcome results
None listed