Programming of adult cardiovascular disease following exposure to late-gestation hyperglycemia
Open accessAbstract
Background: In utero exposure to hyperglycemia is becoming increasingly prevalent as the number of women entering pregnancy with type II diabetes, or developing gestational diabetes, increases. Both animal studies and epidemiologic investigations have found cardiovascular abnormalities in adult offspring of hyperglycemic mothers (OHM). Objective: We hypothesized that adult OHM would have abnormal cardiac function in vivo and increased susceptibility to ischemia. Methods: Pregnant rats were made diabetic on day 12 of gestation. Serum glucose was monitored twice daily and insulin provided to maintain serum glucose at 200–400 mg/dl. Offspring were fostered to normal mothers after birth. Adult OHM were studied at 8–10 months of age with echocardiography to assess in vivo cardiac function and isolated hearts to determine the response to ischemia. Results: Echocardiography found significant diastolic dysfunction in male OHM compared to male controls. In isolated hearts, baseline cardiac function and left ventricular compliance was significantly diminished in male OHM compared to controls. Ischemia caused a significant decline in heart function in controls and female OHM, while function in male OHM remained unchanged. Conclusions: Adult male OHM demonstrate programmed cardiac dysfunction. Given the growing number of pregnancies complicated by hyperglycemia, additional assessment of cardiac function of adults born to diabetic mothers may be warranted.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Fetal hypertrophic cardiomyopathy is a well-recognized feature of gestational diabetes mellitus, though it was believed that this resolved within a few months of birth.
“Fetal hypertrophic cardiomyopathy is a well-recognized feature of GDM, though it was believed that this resolved within a few months of birth [78,79,80,81,82].”
From Recent Experimental Studies of Maternal Obesity, Diabetes during Pregnancy and the Developmental Origins of Cardiovascular Disease (2022) · cites this paper as [80]
The Introduction describes neonatal hypertrophic cardiomyopathy similar to that found in human offspring of diabetic mothers, supporting its association with maternal diabetes. The Discussion says that cardiac changes persisted into adulthood in the study’s rat model, but it does not say that human fetal cardiomyopathy was believed to resolve within a few months of birth. (LLM, conf=0.85)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Lang, R. M., Bierig, M., Devereux, R. B., Flachskampf, F. A., Foster, E., Pellikka, P. A., Picard, M. H., Roman, M. J., Seward, J., Shanewise, J. S., et al. (2005) · Journal of the American Society of Echocardiography · doi:10.1016/j.echo.2005.10.005 · Cited by 11,318 · see citing works
Hyperglycemia and adverse pregnancy outcomes
(2008) · New England Journal of Medicine · doi:10.1056/nejmoa0707943 · Cited by 5,563 · see citing works
WEIGHT IN INFANCY AND DEATH FROM ISCHAEMIC HEART DISEASE
Barker, D. J. P., Osmond, C., Winter, P. D., Margetts, B., & Simmonds, S. J. (1989) · The Lancet · doi:10.1016/s0140-6736(89)90710-1 · Cited by 3,574 · see citing works
Barker, D. J., Osmond, C., Golding, J., Kuh, D., & Wadsworth, M. E. (1989) · BMJ · doi:10.1136/bmj.298.6673.564 · Cited by 2,415 · see citing works
Calvert, H., Horwich, A., Newlands, E. S., Beǵent, R. H. J., Rustin, G. J. S., Kaye, S. B., Harris, A. L., Williams, C. J., & Slevin, M. L. (1988) · The Lancet · doi:10.1016/s0140-6736(88)92709-2 · Cited by 1,183 · see citing works
Increasing Prevalence of Gestational Diabetes Mellitus (GDM) Over Time and by Birth Cohort
Dabelea, D., Snell‐Bergeon, J. K., Hartsfield, C. L., Bischoff, K. J., Hamman, R. F., & McDuffie, R. S. (2005) · Diabetes Care · doi:10.2337/diacare.28.3.579 · Cited by 707 · see citing works
Excessive Obesity in Offspring of Pima Indian Women with Diabetes during Pregnancy
Pettitt, D. J., Baird, H. R., Aleck, K. A., Bennett, P. H., & Knowler, W. C. (1983) · New England Journal of Medicine · doi:10.1056/nejm198302033080502 · Cited by 530 · see citing works
Increasing prevalence of Type II diabetes in American Indian children
Dabelea, D., Hanson, R. L., Bennett, P. H., Roumain, J., Knowler, W. C., & Pettitt, D. J. (1998) · Diabetologia · doi:10.1007/s001250051006 · Cited by 403 · see citing works
The predisposition to obesity and diabetes in offspring of diabetic mothers
Dabelea, D. (2007) · Diabetes Care · doi:10.2337/dc07-s211 · Cited by 384 · see citing works
Diabetes and Obesity in the Offspring of Pima Indian Women With Diabetes During Pregnancy
Pettitt, D. J., Nelson, R. G., Saad, M. F., Bennett, P. H., & Knowler, W. C. (1993) · Diabetes Care · doi:10.2337/diacare.16.1.310 · Cited by 295 · see citing works
Gestational Glucose Tolerance and Risk of Type 2 Diabetes in Young Pima Indian Offspring
Franks, P. W., Looker, H. C., Kobes, S., Touger, L., Tataranni, P. A., Hanson, R. L., & Knowler, W. C. (2006) · Diabetes · doi:10.2337/diabetes.55.02.06.db05-0823 · Cited by 253 · see citing works
Type 2 Diabetes Mellitus in Children and Youth: A New Epidemic
KAUFMAN, F. R. (2002) · Journal of Pediatric Endocrinology and Metabolism · doi:10.1515/jpem.2002.15.s2.737 · Cited by 226 · see citing works
Sex differences in the fetal programming of hypertension
Grigore, D., Ojeda, N. B., & Alexander, B. T. (2008) · Gender Medicine · doi:10.1016/j.genm.2008.03.012 · Cited by 203 · see citing works
Offspring of diabetic pregnancy: Long-term outcomes
Siméoni, U., & Barker, D. J. P. (2009) · Seminars in Fetal and Neonatal Medicine · doi:10.1016/j.siny.2009.01.002 · Cited by 186 · see citing works
Vohr, B. R., & Boney, C. M. (2008) · The Journal of Maternal-Fetal & Neonatal Medicine · doi:10.1080/14767050801929430 · Cited by 184 · see citing works
Cardiovascular and metabolic abnormalities in the offspring of diabetic pregnancy
Manderson, J. G., Mullan, B. A., Patterson, C., Hadden, D. R., Traub, A. I., & McCance, D. R. (2002) · Diabetologia · doi:10.1007/s00125-002-0865-y · Cited by 153 · see citing works
Kozák-Bárány, A., Jokinen, E., Kero, P., Tuominen, J., Rönnemaa, T., & Välimäki, I. A. T. (2004) · Early Human Development · doi:10.1016/j.earlhumdev.2003.11.006 · Cited by 95 · see citing works
Offspring of diabetic pregnancy: Short-term outcomes
Weindling, A. M. (2009) · Seminars in Fetal and Neonatal Medicine · doi:10.1016/j.siny.2008.11.007 · Cited by 92 · see citing works
Streptozotocin diabetes in the pregnant rat induces cardiovascular dysfunction in adult offspring
Holemans, K., Gerber, R. T., Meurrens, K., Clerck, F. D., Poston, L., & Assche, F. A. V. (1999) · Diabetologia · doi:10.1007/s001250051117 · Cited by 85 · see citing works
Fetal programming of appetite by exposure to a maternal low-protein diet in the rat
Bellinger, L., & Langley‐Evans, S. C. (2005) · Clinical Science · doi:10.1042/cs20050127 · Cited by 84 · see citing works
Elmes, M. J., Gardner, D. S., & Langley‐Evans, S. C. (2007) · British Journal Of Nutrition · doi:10.1017/s000711450769182x · Cited by 84 · see citing works
Rocha, S. O., Gomes, G. N., Forti, A. L. L., Franco, M. D. C., Fortes, Z. B., Cavanal, M. F., & Gil, F. Z. (2005) · Pediatric Research · doi:10.1203/01.pdr.0000188698.58021.ff · Cited by 75 · see citing works
Lee, H., Jang, H. C., Park, H. K., & Cho, N. H. (2007) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2007.03.023 · Cited by 72 · see citing works
Nutrient Restriction Impairs Nephrogenesis in a Gender-Specific Manner in the Ovine Fetus
Gilbert, J. S., Ford, S. P., Lang, A. L., Pahl, L. R., Drumhiller, M. C., Babcock, S. A., Nathanielsz, P. W., & Nijland, M. J. (2007) · Pediatric Research · doi:10.1203/01.pdr.0000250208.09874.91 · Cited by 57 · see citing works
Segar, E. M., Norris, A. W., Yao, J., Hu, S., Koppenhafer, S. L., Roghair, R. D., Segar, J. L., & SCHOLZ, T. D. (2009) · Clinical Science · doi:10.1042/cs20080550 · Cited by 43 · see citing works
Self-citationReinking, B. E., Wedemeyer, E. W., Weiss, R. M., Segar, J. L., & SCHOLZ, T. D. (2009) · Cardiovascular Diabetology · doi:10.1186/1475-2840-8-43 · Cited by 37 · see citing works
Self-citationDemirören, K., Çam, L., Oran, B., Koç, H., Başpınar, O., Baysal, T., & Karaaslan, S. (2005) · Journal of Perinatal Medicine · doi:10.1515/jpm.2005.042 · Cited by 26 · see citing works
Myocardial Protection for Neonates and Infants
Jonas, R. A. (1998) · The Thoracic and Cardiovascular Surgeon · doi:10.1055/s-2007-1013087 · Cited by 26 · see citing works
Gerber, R. T., Holemans, K., O'Brien-Coker, I., Mallet, A. I., van Breed, R., Assche, F. A. V., & Poston, L. (2000) · American Journal of Obstetrics and Gynecology · doi:10.1067/mob.2000.107115 · Cited by 25 · see citing works
Elmes, M. J., McMullen, S., Gardner, D. S., & Langley‐Evans, S. C. (2007) · Life Sciences · doi:10.1016/j.lfs.2007.10.022 · Cited by 20 · see citing works
Fetal programming alters reactive oxygen species production in sheep cardiac mitochondria
Bergen, N. H. V., Koppenhafer, S. L., Spitz, D. R., Volk, K. A., Patel, S. S., Roghair, R. D., Lamb, F. S., Segar, J. L., & SCHOLZ, T. D. (2008) · Clinical Science · doi:10.1042/cs20080474 · Cited by 18 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Fetal Programming, Epigenetics, and Adult Onset Disease
Lane, R. H. (2014) · Clinics in Perinatology · doi:10.1016/j.clp.2014.08.006 · Cited by 103 · see citing works
Kereliuk, S. M., & Dolinsky, V. W. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23084467 · Cited by 34 · see citing works
Association of maternal diabetes and child asthma
Azad, M. B., Becker, A. B., & Kozyrskyj, A. L. (2012) · Pediatric Pulmonology · doi:10.1002/ppul.22668 · Cited by 33 · see citing works
Kurepa, D., Pramanik, A. K., Kakkilaya, V., Caldito, G. C., Groome, L. J., Bocchini, J. A., & Jain, S. K. (2012) · Neonatology · doi:10.1159/000339286 · Cited by 31 · see citing works
Rodrigues, A. F. D. A. C., de Lima, I. L. B., Bergamaschi, C. T., Campos, R. R., Hirata, A. E., Schoorlemmer, G. H. M., & Gomes, G. N. (2012) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00241.2012 · Cited by 29 · see citing works
Su, D., Guan, L., Gao, Q., Li, Q., Shi, C., Liu, Y., Sun, L., Lu, C., Ma, X., & Zhao, J. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2017.01.021 · Cited by 26 · see citing works
Jawerbaum, A., & White, V. (2017) · Placenta · doi:10.1016/j.placenta.2017.02.009 · Cited by 25 · see citing works
Armstrong, D. W. J., Tse, M. Y., Wong, P. G., Ventura, N. M., Meens, J., Johri, A. M., Matangi, M. F., & Pang, S. C.-N. (2014) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-014-2003-9 · Cited by 21 · see citing works
Elevated MST1 leads to apoptosis via depletion of YAP1 in cardiomyocytes exposed to high glucose
Su, D., Li, Y., Guan, L., Li, Q., Shi, C., Ma, X., & Song, Y. (2021) · Molecular Medicine · doi:10.1186/s10020-021-00267-6 · Cited by 19 · see citing works
Long-term outcomes and potential mechanisms of offspring exposed to intrauterine hyperglycemia
Yan, Y., Feng, C., Yu, D., Tian, S., Zhou, Y. X., Huang, Y.-T., Cai, Y., Chen, J., Zhu, M., & Jin, M. (2023) · Frontiers in Nutrition · doi:10.3389/fnut.2023.1067282 · Cited by 21 · see citing works
Capobianco, E., Pelesson, M., Careaga, V. P., Fornes, D. D., Canosa, I. S., Higa, R., Maier, M. S., & Jawerbaum, A. (2015) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201500334 · Cited by 18 · see citing works
Cardiovascular Health of Offspring of Diabetic Mothers From the Fetal Through Late-Infancy Stages
Do, V., Al-Hashmi, H., Ojala, T., Jain, V., Colen, T., Goncalvez-Alvarez, S., Davidge, S. T., Al-Rajaa, N., Serrano-Lomelin, J., Stickland, M. K., et al. (2019) · JACC: Cardiovascular Imaging · doi:10.1016/j.jcmg.2018.10.016 · Cited by 17 · see citing works
Gascón, L. M., Ortíz, M. C., Martínez, M. G., Sanchez, J. M., Sancho‐Rodríguez, N., Albaladejo-Otón, M. D., Mulero, M. D. R., & Rodríguez, F. (2022) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00213.2021 · Cited by 16 · see citing works
Persistent Aortic Stiffness and Left Ventricular Hypertrophy in Children of Diabetic Mothers
Do, V., Eckersley, L., Lin, L., Davidge, S. T., Stickland, M. K., Ojala, T., Serrano-Lomelin, J., & Hornberger, L. K. (2021) · CJC Open · doi:10.1016/j.cjco.2020.10.020 · Cited by 15 · see citing works
Blue, E. K., Ballman, K. K., Boyle, F. A., Oh, E., Kono, T., Quinney, S. K., Thurmond, D. C., Evans‐Molina, C., & Haneline, L. S. (2014) · Pediatric Research · doi:10.1038/pr.2014.185 · Cited by 8 · see citing works
Peng, Y., Feng, W. S., Wei, Z., Liao, X., Yang, H., Chang, C., Gan, L., & Zhang, J. (2024) · Early Human Development · doi:10.1016/j.earlhumdev.2024.106168 · Cited by 5 · see citing works
Maternal Hyperglycemia Induces Autonomic Dysfunction and Heart Failure in Older Adult Offspring
Silva, O. A. D., Duarte, G. I. B. P., & Lahlou, S. (2023) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/a-2159-6468 · Cited by 4 · see citing works
The Implications of Maternal Obesity on Offspring Physiology and Behavior in the Nonhuman Primate
Sullivan, E. L., & Kievit, P. (2016) · Springer eBooks · doi:10.1007/978-1-4939-6386-7_10 · Cited by 4 · see citing works
Rigal, E., Josse, M., Greco, C., Rosenblatt‐Velin, N., Rochette, L., Guénancia, C., & Vergely, C. (2024) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.202400136 · Cited by 3 · see citing works
Sommes-nous programmés dès les premiers jours à développer des maladies cardiovasculaires ?
Rigal, E., Josse, M., & Vergely, C. (2023) · Archives des Maladies du Coeur et des Vaisseaux - Pratique · doi:10.1016/j.amcp.2023.09.012
Su, D., Li, Y., Guan, L., Li, Q., Shi, C., Ma, X., & Song, Y. (2021) · Figshare · doi:10.6084/m9.figshare.13888989
Su, D., Li, Y., Guan, L., Li, Q., Shi, C., Ma, X., & Song, Y. (2021) · Figshare · doi:10.6084/m9.figshare.13888983
Su, D., Li, Y., Guan, L., Li, Q., Shi, C., Ma, X., & Song, Y. (2021) · Figshare · doi:10.6084/m9.figshare.13888992
Su, D., Li, Y., Guan, L., Li, Q., Shi, C., Ma, X., & Song, Y. (2021) · Figshare · doi:10.6084/m9.figshare.13888986
Su, D., Li, Y., Guan, L., Li, Q., Shi, C., Ma, X., & Song, Y. (2021) · Figshare · doi:10.6084/m9.figshare.13888998
Su, D., Li, Y., Guan, L., Li, Q., Shi, C., Ma, X., & Song, Y. (2021) · Figshare · doi:10.6084/m9.figshare.13888995
Fang, Y.-J., Gonzalez, K., Konecny, F. A., Chicco, A. J., & Chung, E. (2026) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00277.2026
- Authors
- Agoudemos, M., Reinking, B. E., Koppenhafer, S. L., Segar, J. L., & Scholz, T. D.
- Affiliations
- University of Iowa (US)
- Venue
- Neonatology
- Publisher
- S. Karger AG
- Published
- 2011
- Volume
- 100
- Issue
- 2
- Pages
- 198-205
- ISSN
- 1661-7800 (ISSN-L)
- 1661-7819
- PMC
- PMC3085032
- OpenAlex
- W2077335394
- Cited by
- 27
- References
- 31
- Citations by year
- 2026: 1 · 2024: 2 · 2023: 3 · 2022: 2 · 2021: 7 · 2020: 1 · 2018: 1 · 2017: 2 · 2016: 1 · 2015: 1 · 2014: 3 · 2012: 3
- FWCI
- 1.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neonatology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (T32 HL-07413, T32HL007413, R01HL088883)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Keywords
- gestational diabetes mellitus, cardiac dysfunction, diastolic dysfunction, myocardial ischemia, left ventricular compliance, sex differences, developmental programming, cardiovascular risk, rat model
- MeSH terms
- Animals, Blood Glucose, Cardiovascular Diseases, Diabetes Mellitus, Experimental, Disease Models, Animal, Female, Hyperglycemia, Male, Pregnancy, Prenatal Exposure Delayed Effects, Risk Factors, Streptozocin, Diabetes, Gestational, Rats, Sprague-Dawley, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
