Professor Karl Otfried Schwab
Head of Pediatric Endocrinology, Diabetology and Lipidology
E: karl.otfried.schwab@uniklinik-freiburg.de
Medical Center – University of Freiburg
Center for Pediatrics
Department of General Pediatrics, Adolescent Medicine and Neonatology
Mathildenstraße 1
79106 Freiburg
Germany
Our research focuses on three main themes:
1. We would like to identify children and adolescents with advanced atherosclerosis and quantify the degree of atherosclerosis. We intend to prevent their progression by treatment of cardiovascular risk factors.
2. By analysing substances in the subcutaneous tissue fluid, we aim to avoid repetitive intravenous blood taking and enable pharmacokinetic studies.
3. We would like to understand the influences on physical fitness in 3-6 year old children.
TEAM
- PD Dr. Andreas Krebs, specialist in child and adolescent medicine, pediatric endocrinology and diabetology as well as laboratory medicine, works on clinical microdialysis and the atherosclerosis prevention.
- Dr. Corinna Brichta, postdoc and specialist in child and adolescent medicine, has been working on microdialysis since her doctoral thesis. Currently she is working on hypophosphatasia- and SGA-projects and additionally on the atherosclerosis project.
- Dr. Jürgen Doerfer is working on clinical microdialysis and the atherosclerosis prevention and additionally works in a further book project.
- Dagmar Eckert is a documentation officer working mainly in the field of clinical research.
RESEARCH THEMES
Identifying and quantifying atherosclerosis in children
In order to quantify early subclinical atherosclerosis in children with danger of advanced atherosclerosis, we use a high-resolution ultrasound device to determine intima-media thickness (IMT) by using an ECG-triggered automatic contour recognition analysing mean and maximal IMT from 200 pictures (Schwab et al. 2007, Krebs et al. 2012). Moreover, semi-automatic non-mydriatic detection of retinal vessel diameter is carried out by using a fundus camera with validated software (Wurm et al. 2019). Finally, non-invasive oscillometric detection of pulse pressure (PP), pulse-wave-velocity (PWV) and central blood pressure (cRR) are implemented by using several MobilOGraph-devices.
We would like to characterize the normal progression of atherosclerosis as the yearly thickening of IMT, the yearly change of retinal vessel parameters and yearly acceleration of PWV and increase of PP. The individual values should be measured in follow-up with and without therapeutical intervention and compared with the values of healthy children and adolescents
Clinical microdialysis
Clinical microdialysis is a minimally-invasive sampling technique that allows continous measurement of biological molecules, drugs and other substances in the extracellular, interstitial fluid and organs. Microdialysis can be used to investigate tissue pharmacokinetics and pharmacodynamics of glucose and lactate (Enderle et al. 2018) or glycerol as a parameter of lipolysis as the result of subcutaneous injection of human growth hormone (Krebs et al. 2019).
Moreover, microdialysis sampling in interstitial subcutaneous tissue can be used for the assessment of cutaneously penetrated testosterone following transdermal administration of testosterone (Krebs et al. 2019). Clinical microdialysis can be used to understand intra-organ substance metabolism and third space substance metabolism.
Physical fitness in preschoolers (3-6 year olds)
The preschool years are an important period of psychomotor development. During this time important processes of brain development occur and the children learn motor skills. We would like to find out the psychosocial, nutritional and environmental factors that lead to obesity. Moreover, we examine the influence of migration background and stress on physical fitness.
SELECTED RECENT PUBLICATIONS
- Krebs A, Doerfer J, ….Brichta C and Schwab KO. (2019) Short-term effects of growth hormone on lipolysis, glucose and amino acid metabolism assessed in serum and microdialysate of healthy young men. Exp Clin Endocrinol Diabetes. https://doi.org/10.1055/a-1027-6620
- Krebs A, … Doerfer J, Brichta C, and Schwab KO. (2019) Transfer of topical testosterone to subcutaneous microdialysate, blood and saliva in healthy young men. Exp Clin Endocrinol Diabetes, 127(5), 289-294. https://doi.org/10.1055/a-0650-4115
- Wurm M, …Brichta C and Schwab KO. (2019) Hemoglobin A1c and retinal arteriolar narrowing in children with type 1 diabetes: the diagnostics of early atherosclerosis risk in kids study. Pediatr. Diabetes, 20(5), 622-628. https://doi.org/10.1111/pedi.12858
- Enderle B, …and Schwab KO. (2018). Interstitial glucose and lactate levels are inversely correlated with the body mass index: Need for in vivo calibration of glucose sensor results with blood values in obese patients. J Diabetes Sci Technol, 12(2), 341-348. https://doi.org/10.1177/1932296817730377
- Pol A,… Schwab KO, et al. (2018) Mutations in SELENBP1, encoding a novel human methanethiol oxidase, cause extraoral halitosis. Nature Genetics, 50(1), 120-129. https://doi.org/10.1038/s41588-017-0006-7
- Burton BK,…Schwab KO, et al. (2015) A phase 3 trial of sebelipase alfa in lysosomal acid lipase deficiency. N Engl J Med, 373(11), 1010-20. https://doi.org/10.1056/NEJMoa1501365
COLLABORATIONS, CO-OPERATIONS AND NETWORKS
- Prof. Ursula Witwer-Backofen, Biological Anthropology, Freiburg
- Prof. Arno Schmidt-Trucksäß und Prof. Henner Hansen, Basel
- Dr. Michael Wurm, Regensburg
- Dr. Axel Dost, Jena
- The urban health project is included in a “German Hub”, an association of researchers in the field of the “Urban Health Hub Germany” (BMBF, https://www.globalhealthhub.de ) and the German Universities Global Health Alliance.
FUNDING
Atherosclerosis project:
IIT: The “DEAR-kids study” is funded by Pfizer Deutschland GmbH (WI204856).
IIT: “Cardiovascular risk factors in patients with GHD, SGA, UTS and PWS” is funded by Sandoz-Hexal, Studiennummer: DRKS00005984.
Clinical microdialysis:
IIT: “Short-term effects of growth hormone on lipolysis, glucose and amino acid metabolism assessed in serum and microdialysate of healthy young men” was funded by Novo Nordisk, Studiennummer: DRKS00001099.
IIT: „Transfer of topical testosterone to subcutaneous microdialysate, blood and saliva in healthy young men” was funded by Ipsen Deutschland GmbH (Studien-Nr.: ZKS000331, EudraCT-number 2006-0025533-20).
Urban Health:
“German Alliance for Global Health Research” within the BMBF program “Forschung für Globale Gesundheit”
Hypophophatasia-project is supported by a grant from Alexion.