Maternal diabetes programs sexually dimorphic early-onset cardiovascular dysfunction in metabolically healthy offspring
Year: 2025
Type: article
Abstract: The incidence of cardiovascular disease (CVD) in young individuals is increasing. This alarming trend underscores the need to identify at-risk groups for preventive measures. Emerging evidence suggests that maternal diabetes increases the risk for metabolic diseases and early-onset CVDs in their offspring. However, the evidence is largely observational, limited by confounding factors, and lacks crucial mechanistic insight. Here, we combine experimental, epidemiological, and clinical approaches to disentangle the effects of maternal diabetes on offspring metabolism and endothelial function. In mice, we find that maternal hyperglycemia induces early-onset endothelial dysfunction specifically in male offspring, independent of metabolic disease. In humans, a case-control study and an epidemiological study confirm elevated risk of early-onset endothelial dysfunction and related CVDs in metabolically healthy sons of mothers with type 1 diabetes. Our findings identify an underrecognized risk group for early-onset CVDs and emphasize the importance of maternal conditions in shaping the cardiovascular health of future generations.
Source: Cell Reports Medicine
Authors: Allan Zhao, Yuxia Wei, Eftychia Kontidou, Ali Mahdi, Paulo R. Jannig, Sara Torstensson, Hong Jiang, Alice Larsson, Aida Collado, Rawan Humoud, Jacob Grünler, David Ersgård, Buket Öztürk Esen, Xiaowei Zheng, Haojiang Lu, Eva Lindgren, Sanjiv Risal, Jian Zhao, Elisabet Stener-Victorin, Henrik Toft Sørensen, Lars Pedersen, John Pernow, Zhichao Zhou, Sofia Carlsson, Sergiu-Bogdan Catrina, Qiaolin Deng
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,620
Funders: European Foundation for the Study of Diabetes, Fondation pour la Recherche Médicale, Hjärt-Lungfonden, Karolinska Institutet, Knut och Alice Wallenbergs Stiftelse, Novo Nordisk, Stockholms Läns Landsting, Vetenskapsrådet, China Scholarship Council, Barndiabetesfonden, Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse, Diabetesfonden, Novo Nordisk Fonden
Awards: The red blood cell: Mediator of cardiovascular disease and novel target for treatments, G1599799803, G2232524611, The red blood cell as a mediator and therapeutic target in cardiovascular disease, G3806585397, G4313440097, A programming perspective of the germline cycle on origin of germ cell tumors and epigenetic inheritance of diseases, G4585358754, Erythrocyte-derived non-coding RNAs: new mediators of vascular injury in diabetes, G4811698461, G5598530166, Autoimmune diabetes in adults and Type 2 diabetes subtypes-risk factors and prognosis- precision medicine in diabetes, G597141605, G6156220506, Migration towards the next generation-a better understanding of mammalian germ cells and germ cell tumors, Towards targeted treatment of polycystic ovary syndrome by dissecting its molecular mechanisms and inheritance, G6802557554, G712881263, G718169693, G7592473672, G8875775068
OpenAlex ID: W4416329877