Mild age-related diabetes (MARD) – mechanisms and pathways

This work package focuses on diabetes-driven cardiovascular disease (CVD). The mild age-related diabetes (MARD) cluster, together with the mild obesity-related diabetes (MOD) and the severe insulin-resistant diabetes (SIRD) has the highest risk of developing CVD.

Central to the studies in this work package are a number of well-characterised cohorts, extensively phenotyped for CVD relevant parameters and with long follow-up, including the Malmö Diet Cancer study (MDC), the Malmö Offspring Study (MOS), the Carotid Plaque Imaging Project (CPIP), the SUrrogate markers for Micro- and Macro-vascular hard endpoints for Innovative diabetes Tools (SUMMIT-CVD), the Malmö part of the Swedish CardioPulmunary BioImage Study (SCAPIS), and the Malmö AMI in the elderly (MAMI-Y) studies. 

Among other activities, we focus on the role of immune responses against modified self-antigens and on developing therapies targeting these immune processes. We also work on developing imaging techniques and identifying biomarkers that can identify subjects with high-risk for CVD and vascular injury.

Objectives

• To identify targetable mechanisms and pathways underlying initiation and progression of MARD and CVD.

Selected publications

• Title: Plaque characteristics and biomarkers predicting regression and progression of carotid atherosclerosis
  Reference: Cell Reports Medicine, 3, 100676 (2022)
• Title: Interferon regulatory factor-5-dependent CD11c+ macrophages contribute to the formation of rupture–prone atherosclerotic plaques 
  Reference: European Heart Journal, 43, 1864-1877 (2022)
• Title: Evidence for a protective role of placental growth factor in cardiovascular disease
  Reference: Science Translational Medicine, 12, eabc8587 (2020)
• Title: Pathogenic mtDNA variants, in particular single large-scale mtDNA deletions, are strongly associated with post-lingual onset sensorineural hearing loss in primary mitochondrial disease
  Reference: Molecular Genetics and Metabolism, 137, 230-238 (2022)
• Title: The association between plasma metabolites and future risk of all-cause mortality
  Reference: Journal of Internal Medicine, 292 (5), 804-815 (2022)
• Title: A healthy dietary metabolic signature is associated with a lower risk for type 2 diabetes and coronary artery disease
  Reference: BMC Medicine, 20:122, (2022)