Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jul;68(7):1574-1584.
doi: 10.1007/s00125-025-06421-7. Epub 2025 Apr 5.

Cardiac remodelling, recognition memory deficits and accelerated ageing in a rat model of gestational diabetes

Sathya Velmurugan #  1 , Vivek K Pandey #  1 , Nirmal Verma  1 , Deepak Kotiya  1 , Florin Despa  1 , Sanda Despa  2
Affiliations

Cardiac remodelling, recognition memory deficits and accelerated ageing in a rat model of gestational diabetes

Sathya Velmurugan et al. Diabetologia. 2025 Jul.

Abstract

Aims/hypothesis: Women with prior gestational diabetes mellitus (GDM) have higher incidence of age-associated diseases, including type 2 diabetes, CVD and cognitive impairment. Human studies cannot readily determine whether GDM causes these conditions or the underlying mechanisms. Here we used a well-validated rat model of GDM to address these questions.

Methods: Rats with beta cell-specific expression of human amylin, a pancreatic hormone, were used as a GDM model. Five-month-old female rats were randomly assigned to no-pregnancy, one-pregnancy and two-pregnancies experimental groups. GTTs and transthoracic echocardiography were performed at baseline and during the postpartum period. At 18 months of age, the novel object recognition test was administered, followed by euthanasia and organ collection.

Results: All female rats developed glucose intolerance and showed cardiac remodelling and impaired left ventricular relaxation with ageing. Glucose intolerance was exacerbated in rats with prior GDM pregnancies compared with nulliparous rats, with significant differences starting at 9 months of age. However, blood glucose levels were comparable in the three groups during the course of the study. Rats with two GDM-complicated pregnancies had increased left ventricular mass compared with the other groups following the second pregnancy and until the end of the study. At 18 months of age, rats with prior GDM pregnancies presented aggravated demyelination, particularly in the hippocampus and mid-brain region, oxidative stress and neuroinflammation, and had a lower recognition index in the novel object recognition test compared with nulliparous rats. Higher parity exacerbated these effects. Shorter telomeres and reduced mitochondrial DNA content, two hallmarks of biological ageing, were found in the brain, heart and pancreas of rats with prior GDM.

Conclusions/interpretation: These findings support the concept that GDM is a sex-specific risk factor for ageing-related diseases, and point to accelerated cellular ageing as a contributing mechanism.

Data availability: Cardiac echocardiography and GTT data are available at Dataverse under the identifier https://doi.org/10.7910/DVN/R2HITG.

Keywords: Cardiac hypertrophy; Cellular ageing; Cognitive impairment; Gestational diabetes.

PubMed Disclaimer

Conflict of interest statement

Data availability: Cardiac echocardiography and GTT data are available at Dataverse under the identifier https://doi.org/10.7910/DVN/R2HITG . All other raw data are available from the corresponding author upon reasonable request. Funding: This work was supported by NIH grants HL148443 and HL135000 to SD, NIH grants NS116058 and AG057290 to FD, and American Heart Association grant 19TPA34850094 to SD. Authors’ relationships and activities: The authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work. Contribution statement: SV and VKP contributed to the experimental design, data acquisition and analysis, and editing and final approval of the manuscript. NV and DK participated in data acquisition, analysis and interpretation, and editing and final approval of the manuscript. FD contributed to the overall design of the project, data analysis and interpretation, and editing and final approval of the manuscript. SD contributed to the overall design of the project, data analysis and interpretation, writing, editing and final approval of the manuscript. SD is the guarantor.

References

    1. Bellamy L, Casas JP, Hingorani AD, Williams D. (2009) Type 2 diabetes mellitus after gestational diabetes: a systematic review and meta-analysis. Lancet 373:1773–1779. - PubMed
    1. Kim C, Newton KM, Knopp RH. (2002) Gestational diabetes and the incidence of type 2 diabetes: a systematic review. Diabetes Care 25:1862–1868. - PubMed
    1. Daly B, Toulis KA, Thomas N, et al. (2018) Increased risk of ischemic heart disease, hypertension, and type 2 diabetes in women with previous gestational diabetes mellitus, a target group in general practice for preventive interventions: A population-based cohort study. PLoS Med 15(1):e1002488. - PMC - PubMed
    1. Shah BR, Retnakaran R, Booth GL. (2008) Increased risk of cardiovascular disease in young women following gestational diabetes mellitus. Diabetes Care 31:1668–1669. - PMC - PubMed
    1. Gunderson EP, Chiang V, Pletcher MJ, et al. (2014) History of gestational diabetes mellitus and future risk of atherosclerosis in mid-life: the Coronary Artery Risk Development in Young Adults study. J Am Heart Assoc 3:e000490. - PMC - PubMed

LinkOut - more resources