{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T19:36:00Z","timestamp":1790019360604,"version":"4.0.1"},"reference-count":90,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical University of Bialystok","award":["B.SUB.23.502"],"award-info":[{"award-number":["B.SUB.23.502"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Gestational diabetes mellitus (GDM) is a common metabolic complication of pregnancy associated with significant short- and long-term risks for both mother and offspring. Increasing evidence indicates that genetic susceptibility plays a central role in GDM pathogenesis, particularly through variants affecting insulin secretion and pancreatic \u03b2-cell function. This narrative review integrates molecular, clinical, and epidemiological perspectives, highlighting population-specific effects and gene\u2013environment interactions. Improved understanding of the genetic risk architecture may support earlier risk stratification and enable the future development of personalized strategies for GDM prevention and management, with particular emphasis on genetic polymorphisms in SLC30A8, CDKAL1, and HHEX genes consistently implicated in glucose homeostasis and \u03b2-cell integrity. These genes contribute to distinct but complementary molecular pathways underlying GDM, including impaired insulin biosynthesis, defective zinc transport within insulin granules, and altered paracrine regulation within pancreatic islets. While associations between these variants and GDM have been repeatedly demonstrated, their clinical relevance and mechanistic impact remain incompletely understood. Available evidence suggests that CDKAL1 represents the strongest genetic determinant, followed by SLC30A8, while HHEX appears to play a modulatory role. This review summarizes current findings on the molecular functions and clinical significance of these polymorphisms, highlighting population-specific effects and gene\u2013environment interactions. Improved understanding of genetic risk architecture may support earlier risk stratification and enable future development of personalized strategies for GDM prevention and management.<\/jats:p>","DOI":"10.3390\/ijms27021121","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T09:16:59Z","timestamp":1769159819000},"page":"1121","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Molecular Genetics of \u03b2-Cell Compensation in Gestational Diabetes Mellitus: Insights from CDKAL1, SLC30A8 and HHEX"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3894-3218","authenticated-orcid":false,"given":"Justyna","family":"Hryniewicka","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, ul. M. Sklodowskiej-Curie 24a, 15-276 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7403-6928","authenticated-orcid":false,"given":"Angelika","family":"Buczy\u0144ska-Backiel","sequence":"additional","affiliation":[{"name":"Clinical Research Centre, Medical University of Bialystok, ul. M. Sk\u0142odowskiej-Curie 24a, 15-276 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Zbucka-Kr\u0119towska","sequence":"additional","affiliation":[{"name":"Department of Gynecological Endocrinology and Adolescent Gynecology, Medical University of Bialystok, ul. M. Sk\u0142odowskiej-Curie 24a, 15-276 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4522-4978","authenticated-orcid":false,"given":"Adam Jacek","family":"Kr\u0119towski","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, ul. M. Sklodowskiej-Curie 24a, 15-276 Bialystok, Poland"},{"name":"Clinical Research Centre, Medical University of Bialystok, ul. M. Sk\u0142odowskiej-Curie 24a, 15-276 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma\u0142gorzata","family":"Szelachowska","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, ul. M. Sklodowskiej-Curie 24a, 15-276 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S105","DOI":"10.2337\/dc07-s201","article-title":"What Is Gestational Diabetes?","volume":"30","author":"Buchanan","year":"2007","journal-title":"Diabetes Care"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"American Diabetes Association (2013). Diagnosis and Classification of Diabetes Mellitus. Diabetes Care, 36, S67\u2013S74.","DOI":"10.2337\/dc13-S067"},{"key":"ref_3","first-page":"CD011624","article-title":"Different intensities of glycaemic control for women with gestational diabetes mellitus","volume":"10","author":"Hofer","year":"2023","journal-title":"Cochrane Database Syst. 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