Maternal diabetes programs sexually dimorphic early-onset cardiovascular dysfunction in metabolically healthy...

Area of Science:

• Cardiovascular Science
• Endocrinology
• Developmental Biology

Background:

• Cardiovascular disease (CVD) incidence is rising in young individuals.
• Maternal diabetes is linked to increased offspring risk for metabolic diseases and early-onset CVDs.
• Existing evidence is observational, lacking mechanistic insight and controlling for confounding factors.

Purpose of the Study:

• To investigate the mechanistic link between maternal diabetes and offspring cardiovascular health.
• To determine if maternal diabetes impacts offspring metabolism and endothelial function.
• To identify specific at-risk groups for early-onset CVDs.

Main Methods:

• Combined experimental (mouse models), epidemiological, and clinical studies.
• Investigated endothelial function and metabolic parameters in offspring.
• Analyzed human case-control and epidemiological data.

Main Results:

• Maternal hyperglycemia in mice induced early-onset endothelial dysfunction in male offspring, independent of metabolic status.
• Human studies confirmed an elevated risk of early-onset endothelial dysfunction and CVDs in metabolically healthy sons of mothers with type 1 diabetes.
• Identified a specific underrecognized risk group for early-onset CVD.

Conclusions:

• Maternal diabetes, particularly hyperglycemia, is a significant risk factor for early-onset endothelial dysfunction in male offspring.
• This risk is present even in metabolically healthy individuals, highlighting a non-metabolic pathway.
• Maternal health conditions play a crucial role in shaping the long-term cardiovascular health of offspring.