Year: 2026
Type: dissertation
Study design: Observational Study
Abstract: BackgroundAdrenomedullin (ADM) is a vasoactive neurohormonal peptide involved in vascular integrity and fluid homeostasis. Even if elevated ADM is an established marker of acute vascular stress, it remains unclear how the ADM system should be measured and interpreted in the general population. In particular, it is uncertain which components of the pathway are most informative, when they should be measured, and how differences in ADM concentrations should be understood. Addressing these questions may help clarify why the same biological system is associated with both acute vascular dysfunction and longer term metabolic risk. This thesis therefore examined the ADM system across acute clinical and population-based settings using molecular epidemiological methods.MethodsFour studies were conducted using observational clinical and population-based cohorts. Paper I evaluated ADM in patients presenting to the emergency department with acute dyspnea, with 90-day mortality and hospitalization as outcomes. Papers II and IV examined ADM and related precursor peptides glycine-extended ADM, stable prohormone fragment midregional-proADM and peptidylglycine α-amidating monooxygenase (PAM) activity, in relation to diabetes, insulin resistance and adiposity. Paper III used loss of function genetic variants to investigate associations between genetically impaired PAM function and metabolic and body-composition traits.ResultsIn the clinical setting of acute dyspnea, higher circulating ADM concentrations were associated with greater risks of 90-day mortality and hospitalization. In the population-based setting ADM was associated with metabolic dysfunction and prospectively with incident diabetes mellitus. Genetically impaired PAM function was associated with worse glucose tolerance and lower muscle mass. Longitudinal analyses suggested that the ADM-system primarily reflected current adiposity and metabolic dysfunction, rather than future changes in weight.ConclusionCollectively, the findings support ADM as a context-dependent marker of vascular and metabolic stress, whose triggers and consequences vary across clinical settings and tissues. The predominant observational design does not establish causality.
Author: Bronton, Kevin
Institution: Lund University
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7213219545