Sex Differences in Glycolipidic Disorders After Exposure to Maternal Hyperglycemia During Early Development

Overview

Journal J Endocrinol Invest

Publisher Springer

Specialty Endocrinology

Date 2023 Mar 28

PMID 36976483

Authors

S-S Luo

H Zhu

H-F Huang

G-L Ding

Affiliations

Soon will be listed here.

Abstract

Purpose: The aim of this review was to summarize sex differences in glycolipid metabolic phenotypes of human and animal models after exposure to maternal hyperglycemia and overview the underlying mechanisms, providing a new perspective on the maternal hyperglycemia-triggered risk of glycolipidic disorders in offspring.

Methods: A comprehensive literature search within PubMed was performed. Selected publications related to studies on offspring exposed to maternal hyperglycemia investigating the sex differences of glycolipid metabolism were reviewed.

Results: Maternal hyperglycemia increases the risk of glycolipid metabolic disorders in offspring, such as obesity, glucose intolerance and diabetes. Whether with or without intervention, metabolic phenotypes have been shown to exhibit sex differences between male and female offspring in response to maternal hyperglycemia, which may be related to gonadal hormones, organic intrinsic differences, placenta, and epigenetic modifications.

Conclusion: Sex may play a role in the different incidences and pathogenesis of abnormal glycolipid metabolism. More studies investigating both sexes are needed to understand how and why environmental conditions in early life affect long-term health between male and female individuals.

Citing Articles

Gestational diabetes induces autistic-like behaviors in offspring by disrupting the GABAergic system.

Liu X, Huang T, Zhang S, Huang Y, Mo J, Yan Y Front Neurosci. 2025; 19:1538115.

PMID: 40012680 PMC: 11861160. DOI: 10.3389/fnins.2025.1538115.

References

Sun H, Saeedi P, Karuranga S, Pinkepank M, Ogurtsova K, Duncan B . IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract. 2021; 183:109119. PMC: 11057359. DOI: 10.1016/j.diabres.2021.109119. View

Lowe Jr W, Scholtens D, Kuang A, Linder B, Lawrence J, Lebenthal Y . Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study (HAPO FUS): Maternal Gestational Diabetes Mellitus and Childhood Glucose Metabolism. Diabetes Care. 2019; 42(3):372-380. PMC: 6385693. DOI: 10.2337/dc18-1646. View

Boerschmann H, Pfluger M, Henneberger L, Ziegler A, Hummel S . Prevalence and predictors of overweight and insulin resistance in offspring of mothers with gestational diabetes mellitus. Diabetes Care. 2010; 33(8):1845-9. PMC: 2909075. DOI: 10.2337/dc10-0139. View

Vaarasmaki M, Pouta A, Elliot P, Tapanainen P, Sovio U, Ruokonen A . Adolescent manifestations of metabolic syndrome among children born to women with gestational diabetes in a general-population birth cohort. Am J Epidemiol. 2009; 169(10):1209-15. DOI: 10.1093/aje/kwp020. View

Ding G, Wang F, Shu J, Tian S, Jiang Y, Zhang D . Transgenerational glucose intolerance with Igf2/H19 epigenetic alterations in mouse islet induced by intrauterine hyperglycemia. Diabetes. 2012; 61(5):1133-42. PMC: 3331740. DOI: 10.2337/db11-1314. View

Zhu H, Chen B, Cheng Y, Zhou Y, Yan Y, Luo Q . Insulin Therapy for Gestational Diabetes Mellitus Does Not Fully Protect Offspring From Diet-Induced Metabolic Disorders. Diabetes. 2019; 68(4):696-708. DOI: 10.2337/db18-1151. View

van Dijk S, Tellam R, Morrison J, Muhlhausler B, Molloy P . Recent developments on the role of epigenetics in obesity and metabolic disease. Clin Epigenetics. 2016; 7:66. PMC: 4940755. DOI: 10.1186/s13148-015-0101-5. View

Perng W, Kelsey M, Sauder K, Dabelea D . How does exposure to overnutrition in utero lead to childhood adiposity? Testing the insulin hypersecretion hypothesis in the EPOCH cohort. Diabetologia. 2021; 64(10):2237-2246. DOI: 10.1007/s00125-021-05515-2. View

Hockett C, Harrall K, Moore B, Starling A, Bellatorre A, Sauder K . Persistent effects of in utero overnutrition on offspring adiposity: the Exploring Perinatal Outcomes among Children (EPOCH) study. Diabetologia. 2019; 62(11):2017-2024. PMC: 7593989. DOI: 10.1007/s00125-019-04981-z. View

10.

Lefebvre P, Staels B . Hepatic sexual dimorphism - implications for non-alcoholic fatty liver disease. Nat Rev Endocrinol. 2021; 17(11):662-670. DOI: 10.1038/s41574-021-00538-6. View

11.

Shaheen M, Schrode K, Pan D, Kermah D, Puri V, Zarrinpar A . Sex-Specific Differences in the Association Between Race/Ethnicity and NAFLD Among US Population. Front Med (Lausanne). 2021; 8:795421. PMC: 8674562. DOI: 10.3389/fmed.2021.795421. View

12.

Cooper A, Gupta S, Moustafa A, Chao A . Sex/Gender Differences in Obesity Prevalence, Comorbidities, and Treatment. Curr Obes Rep. 2021; 10(4):458-466. DOI: 10.1007/s13679-021-00453-x. View

13.

Tsai S, Rodriguez A, Dastidar S, Del Greco E, Carr K, Sitzmann J . Increased 4E-BP1 Expression Protects against Diet-Induced Obesity and Insulin Resistance in Male Mice. Cell Rep. 2016; 16(7):1903-14. PMC: 4988876. DOI: 10.1016/j.celrep.2016.07.029. View

14.

Gao A, Su J, Liu R, Zhao S, Li W, Xu X . Sexual dimorphism in glucose metabolism is shaped by androgen-driven gut microbiome. Nat Commun. 2021; 12(1):7080. PMC: 8648805. DOI: 10.1038/s41467-021-27187-7. View

15.

Pettersson U, Walden T, Carlsson P, Jansson L, Phillipson M . Female mice are protected against high-fat diet induced metabolic syndrome and increase the regulatory T cell population in adipose tissue. PLoS One. 2012; 7(9):e46057. PMC: 3458106. DOI: 10.1371/journal.pone.0046057. View

16.

Barker D . The origins of the developmental origins theory. J Intern Med. 2007; 261(5):412-7. DOI: 10.1111/j.1365-2796.2007.01809.x. View

17.

Lowe Jr W, Lowe L, Kuang A, Catalano P, Nodzenski M, Talbot O . Maternal glucose levels during pregnancy and childhood adiposity in the Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study. Diabetologia. 2019; 62(4):598-610. PMC: 6421132. DOI: 10.1007/s00125-018-4809-6. View

18.

Gillman M, Oakey H, Baghurst P, Volkmer R, Robinson J, Crowther C . Effect of treatment of gestational diabetes mellitus on obesity in the next generation. Diabetes Care. 2010; 33(5):964-8. PMC: 2858199. DOI: 10.2337/dc09-1810. View

19.

Lusis A, Attie A, Reue K . Metabolic syndrome: from epidemiology to systems biology. Nat Rev Genet. 2008; 9(11):819-30. PMC: 2829312. DOI: 10.1038/nrg2468. View

20.

Mauvais-Jarvis F . Sex differences in metabolic homeostasis, diabetes, and obesity. Biol Sex Differ. 2015; 6:14. PMC: 4559072. DOI: 10.1186/s13293-015-0033-y. View