{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T05:28:38Z","timestamp":1792042118041,"version":"4.4.0"},"reference-count":35,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,6,13]],"date-time":"2022-06-13T00:00:00Z","timestamp":1655078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Gestational diabetes mellitus (GDM) is a pregnancy complication characterized by second trimester hyperglycemia. Untreated, GDM is related to an increased risk for adverse pregnancy outcomes. Both beta cell dysfunction and insulin resistance underlie impaired glucose tolerance. Understanding the dominant mechanism predisposing to GDM may be important to provide effective treatment in order to improve perinatal outcomes. We hypothesize that insulin resistance rather that beta cell dysfunction predisposes to GDM. Methods: A 75g oral glucose tolerance test (OGTT) was performed on 2112 second-trimester pregnant women to determine the relationship between insulin resistance (HOMA-IR), beta cell function (HOMA-\u03b2), and the prevalence of abnormal glucose handling. Results: High insulin resistance raised the risk of GDM (relative risk (RR) 6.1, 95% confidence interval (CI) (4.4\u20138.5)), as did beta cell dysfunction (RR 3.8, 95% CI (2.7\u20135.4)). High insulin resistance, but not beta cell function, enhances the necessity for additional glucose lowering medication on top of a low carbohydrate diet in women diagnosed with GDM. Conclusions: Both high insulin resistance and beta cell dysfunction increase the risk of GDM. As increased insulin resistance, rather than beta cell function, is related to an insufficient response to a low carbohydrate diet, we speculate that insulin sensitizers rather than insulin therapy may be the most targeted therapeutic modality in diet-insensitive GDM.<\/jats:p>","DOI":"10.3390\/nu14122444","type":"journal-article","created":{"date-parts":[[2022,6,13]],"date-time":"2022-06-13T22:00:38Z","timestamp":1655157638000},"page":"2444","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Role of Beta Cell Function and Insulin Resistance in the Development of Gestational Diabetes Mellitus"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6142-3777","authenticated-orcid":false,"given":"Jonas","family":"Ellerbrock","sequence":"first","affiliation":[{"name":"School for Oncology and Developmental Biology (GROW), Maastricht University, 6229 ER Maastricht, The Netherlands"},{"name":"Department of Obstetrics and Gynecology, Zuyderland Medical Center, 6419 PC Heerlen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benthe","family":"Spaanderman","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joris van","family":"Drongelen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Mulder","sequence":"additional","affiliation":[{"name":"School for Oncology and Developmental Biology (GROW), Maastricht University, 6229 ER Maastricht, The Netherlands"},{"name":"Department of Obstetrics and Gynecology, Maastricht University Medical Center, 6229 ER Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Lopes van Balen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Maastricht University Medical Center, 6229 ER Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronique","family":"Schiffer","sequence":"additional","affiliation":[{"name":"School for Oncology and Developmental Biology (GROW), Maastricht University, 6229 ER Maastricht, The Netherlands"},{"name":"Department of Obstetrics and Gynecology, Maastricht University Medical Center, 6229 ER Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4513-163X","authenticated-orcid":false,"given":"Laura","family":"Jorissen","sequence":"additional","affiliation":[{"name":"School for Oncology and Developmental Biology (GROW), Maastricht University, 6229 ER Maastricht, The Netherlands"},{"name":"Department of Obstetrics and Gynecology, Maastricht University Medical Center, 6229 ER Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4478-7207","authenticated-orcid":false,"given":"Robert-Jan","family":"Alers","sequence":"additional","affiliation":[{"name":"School for Oncology and Developmental Biology (GROW), Maastricht University, 6229 ER Maastricht, The Netherlands"},{"name":"Department of Obstetrics and Gynecology, Maastricht University Medical Center, 6229 ER Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanine","family":"Leenen","sequence":"additional","affiliation":[{"name":"Department of Finance, Zuyderland Medical Center, 6419 PC Heerlen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chahinda","family":"Ghossein-Doha","sequence":"additional","affiliation":[{"name":"School for Oncology and Developmental Biology (GROW), Maastricht University, 6229 ER Maastricht, The Netherlands"},{"name":"Department of Cardiology, Maastricht University Medical Center, 6229 HX Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Spaanderman","sequence":"additional","affiliation":[{"name":"School for Oncology and Developmental Biology (GROW), Maastricht University, 6229 ER Maastricht, The Netherlands"},{"name":"Department of Obstetrics and Gynecology, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands"},{"name":"Department of Obstetrics and Gynecology, Maastricht University Medical Center, 6229 ER Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,13]]},"reference":[{"key":"ref_1","unstructured":"Association, A.D. (2004). Gestational Diabetes Mellitus, American Diabetes Association."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Plows, J.F., Stanley, J.L., Baker, P.N., Reynolds, C.M., and Vickers, M.H. (2018). The Pathophysiology of Gestational Diabetes Mellitus. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19113342"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1097\/MED.0b013e32834c800d","article-title":"Placental hormones and the control of maternal metabolism and fetal growth","volume":"18","author":"Newbern","year":"2011","journal-title":"Curr. Opin. Endocrinol. Diabetes Obes."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1186\/s12967-018-1666-5","article-title":"Heterogeneity of insulin resistance and beta cell dysfunction in gestational diabetes mellitus: A prospective cohort study of perinatal outcomes","volume":"16","author":"Liu","year":"2018","journal-title":"J. Transl. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/j.ajog.2004.11.039","article-title":"Gestational diabetes: The consequences of not treating","volume":"192","author":"Langer","year":"2005","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Ju, H., Rumbold, A.R., Willson, K.J., and Crowther, C.A. (2008). Borderline gestational diabetes mellitus and pregnancy outcomes. BMC Pregnancy Childbirth, 8.","DOI":"10.1186\/1471-2393-8-31"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1016\/j.cmet.2014.09.018","article-title":"Metformin: From Mechanisms of Action to Therapies","volume":"20","author":"Foretz","year":"2014","journal-title":"Cell Metab."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1007\/BF00280883","article-title":"Homeostasis model assessment: Insulin resistance and \u03b2-cell function from fasting plasma glucose and insulin concentrations in man","volume":"28","author":"Matthews","year":"1985","journal-title":"Diabetologia"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1177\/1932296818805074","article-title":"Insulin Units and Conversion Factors: A Story of Truth, Boots, and Faster Half-Truths","volume":"13","author":"Knopp","year":"2019","journal-title":"J. Diabetes Sci. Technol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1089\/met.2009.0017","article-title":"\u03b2-Cell Function and Insulin Resistance in Pregnancy and Their Relation to Fetal Development","volume":"8","author":"Das","year":"2010","journal-title":"Metab. Syndr. Relat. Disord."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1080\/09513590.2017.1369516","article-title":"Homeostatic model assessment of beta cell function predicting abnormal oral glucose tolerance testing in pregnancy: A systematic review and meta-analysis","volume":"33","author":"Ellerbrock","year":"2017","journal-title":"Gynecol. Endocrinol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"676","DOI":"10.2337\/dc10-0719","article-title":"International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hypergly-cemia in pregnancy","volume":"33","author":"Metzger","year":"2010","journal-title":"Diabetes Care"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1016\/S0140-6736(07)61602-X","article-title":"The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: Guidelines for reporting observational studies","volume":"370","author":"Altman","year":"2007","journal-title":"Lancet"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2533","DOI":"10.2337\/dc14-0573","article-title":"Different Associations of Diabetes With \u03b2-Cell Dysfunction and Insulin Resistance Among Obese and Nonobese Chinese Women with Prior Gestational Diabetes Mellitus","volume":"37","author":"Li","year":"2014","journal-title":"Diabetes Care"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1172\/JCI10842","article-title":"Obesity and insulin resistance","volume":"106","author":"Kahn","year":"2000","journal-title":"J. Clin. Investig."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.it.2003.10.013","article-title":"Inflammation: The link between insulin resistance, obesity and diabetes","volume":"25","author":"Dandona","year":"2004","journal-title":"Trends Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1007\/s11886-001-0059-0","article-title":"Pathophysiology and treatment of the dyslipidemia of insulin resistance","volume":"3","author":"Cohn","year":"2001","journal-title":"Curr. Cardiol. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/S0889-8529(03)00073-2","article-title":"Obesity and dyslipidemia","volume":"32","author":"Howard","year":"2003","journal-title":"Endocrinol. Metab. Clin. N. Am."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.arcmed.2005.01.005","article-title":"Regulation of Plasma Triglycerides in Insulin Resistance and Diabetes","volume":"36","author":"Ginsberg","year":"2005","journal-title":"Arch. Med. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1007\/s00125-015-3525-8","article-title":"Pathophysiology of diabetic dyslipidaemia: Where are we?","volume":"58","year":"2015","journal-title":"Diabetologia"},{"key":"ref_21","first-page":"600","article-title":"The Effects of Carbohydrate Restriction in Patients with Diet-Controlled Gestational Diabetes","volume":"91","author":"Major","year":"1998","journal-title":"Obstet. Gynecol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Gui, J., Liu, Q., and Feng, L. (2013). Metformin vs Insulin in the Management of Gestational Diabetes: A Meta-Analysis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0064585"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.diabres.2013.12.056","article-title":"Metformin vs insulin in the management of gestational diabetes: A systematic review and meta-analysis","volume":"104","author":"Su","year":"2014","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"9804708","DOI":"10.1155\/2019\/9804708","article-title":"Comparative Efficacy and Safety of Metformin, Glyburide, and Insulin in Treating Gestational Diabetes Mellitus: A Meta-Analysis","volume":"2019","author":"Guo","year":"2019","journal-title":"J. Diabetes Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.diabres.2015.05.017","article-title":"Metformin for the treatment of gestational diabetes: An updated meta-analysis","volume":"109","author":"Kitwitee","year":"2015","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1056\/NEJMoa0707193","article-title":"Metformin versus Insulin for the Treatment of Gestational Diabetes","volume":"358","author":"Rowan","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1111\/dom.12893","article-title":"The emerging role of metformin in gestational diabetes mellitus","volume":"19","author":"Gray","year":"2017","journal-title":"Diabetes Obes. Metab."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1007\/s13300-018-0479-0","article-title":"Long-Term Effects of Oral Antidiabetic Drugs During Pregnancy on Offspring: A Systematic Review and Meta-analysis of Follow-up Studies of RCTs","volume":"9","author":"Wekker","year":"2018","journal-title":"Diabetes Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1111\/j.1365-3016.2010.01140.x","article-title":"Disparities in the risk of gestational diabetes by race-ethnicity and country of birth","volume":"24","author":"Hedderson","year":"2010","journal-title":"Paediatr. P\u00e9rinat. Epidemiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1530\/EJE-12-0452","article-title":"Failure to increase insulin secretory capacity during pregnancy-induced insulin resistance is associated with ethnicity and gestational diabetes","volume":"167","author":"Jenum","year":"2012","journal-title":"Eur. J. Endocrinol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"294","DOI":"10.3904\/kjim.2013.28.3.294","article-title":"\u03b2-Cell dysfunction and insulin resistance in gestational glucose intolerance","volume":"28","author":"Jang","year":"2013","journal-title":"Korean J. Intern. Med."},{"key":"ref_32","first-page":"1","article-title":"Risks for Gestational Diabetes Mellitus and Pregnancy-Induced Hypertension Are Increased in Polycystic Ovary Syndrome","volume":"2013","author":"Wang","year":"2013","journal-title":"BioMed Res. Int."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"E1","DOI":"10.1530\/EJE-14-0429","article-title":"PCOS: A heterogeneous condition with multiple faces for multiple doctors","volume":"171","author":"Bouchard","year":"2014","journal-title":"Eur. J. Endocrinol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.ics.2005.01.002","article-title":"PCOS: Backgrounds, evidence and problems in diagnosing the syndrome","volume":"1279","author":"Laven","year":"2005","journal-title":"Int. Congr. Ser."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1093\/humrep\/deh137","article-title":"Is insulin resistance an essential component of PCOS? The influence of confounding factors","volume":"19","author":"Cibula","year":"2004","journal-title":"Hum. Reprod."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/12\/2444\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:30:23Z","timestamp":1760139023000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/12\/2444"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,13]]},"references-count":35,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["nu14122444"],"URL":"https:\/\/doi.org\/10.3390\/nu14122444","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,13]]}}}