Association between serum vitamin D, insulin resistance (HOMA-IR), and gestational diabetes mellitus

Authors

  • Z. Kirovakov Faculty of Public Health and Health Care, Burgas State University "Prof. Dr. Asen Zlatarov” – Burgas, Bulgaria Author https://orcid.org/0009-0003-7643-5879
  • M. Obreykova Faculty of Public Health and Health Care, Burgas State University "Prof. Dr. Asen Zlatarov” – Burgas, Bulgaria Author
  • N. Kostadinov Faculty of Public Health and Health Care, Burgas State University "Prof. Dr. Asen Zlatarov” – Burgas, Bulgaria Author
  • A. Jovanovska-Kirovakova Faculty of Public Health and Health Care, Burgas State University "Prof. Dr. Asen Zlatarov” – Burgas, Bulgaria Author
  • E. Gyokova Department of Obstetrics and Gynecology, “Sv. Marina” University Hospital – Pleven, Bulgaria; Faculty of Medicine, Medical University – Pleven, Bulgaria Author

DOI:

https://doi.org/10.2478/AMB-2026-0072

Keywords:

gestational diabetes mellitus, insulin resistance, HOMA-IR, vitamin D, pregnancy

Abstract

Abstract. Aim. To investigate whether early pregnancy serum vitamin D levels and insulin resistance (HOMA-IR) are associated with the development of gestational diabetes mellitus (GDM). Materials and methods. This prospective cohort study was conducted between 2023 and 2025 and included 850 pregnant women enrolled during early gestation. Baseline serum Vitamin D concentrations were measured. Fasting plasma glucose and fasting insulin were determined, and HOMA-IR was calculated. Participants were followed until 24–28 weeks of gestation, when GDM was diagnosed using a standardized 75 g oral glucose tolerance test. Correlation analysis and multivariate logistic regression were performed to determine associations and predictive relationships. Results. Women who developed GDM had significantly higher pre-pregnancy BMI (M = 29.8, SD = 5.1) compared to non-GDM women (M = 26.4, SD = 4.7), t(848) = 7.5, p < .001. Similarly, HOMA-IR was significantly elevated in the GDM group (M = 4.3, SD = 1.5) compared to the non-GDM group (M = 3.1, SD = 1.1), t(848) = 9.8, p <0.001. Fasting plasma glucose and fasting insulin were also higher among women with GDM (glucose: M = 5.2, SD = 0.5 vs. M = 4.9, SD = 0.4, t(848) = 5.8, p < .001; insulin: M = 18.5, SD = 5.6 vs. M = 14.3, SD = 4.8, t(848) = 9.2, p < 0.001). There were no statistically significant differences in maternal age (t(848) = 1.8, p = 0.07) or serum vitamin D levels (M = 23.6, SD = 7.2 vs. M = 24.1, SD = 6.8, t(848) = 0.9, p = 0.36) between the groups. Conclusions. The Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) was independently associated with increased risk of gestational diabetes mellitus, while serum vitamin D levels showed no significant relationship, and HOMA-IR demonstrated excellent predictive accuracy for GDM.

References

Dłuski DF, Ruszała M, Rudziński G, et al. Evolution of gestational diabetes mellitus across continents in the 21st century. Int J Environ Res Public Health. 2022;19(23):15804. doi:10.3390/ijerph192315804

Mittal R, Prasad K, Lemos JRN, et al. Unveiling gestational diabetes: an overview of pathophysiology and management. Int J Mol Sci. 2025;26(5):2320. doi:10.3390/ijms26052320

Lin C, Liu H. Relationship between vitamin D deficiency and gestational diabetes: a narrative review. Front Endocrinol (Lausanne). 2024;15:1504930. doi:10.3389/fendo.2024.1504930

American Diabetes Association Professional Practice Committee. Management of diabetes in pregnancy: standards of medical care in diabetes—2022. Diabetes Care. 2022;45(Suppl 1):S232-S243. doi:10.2337/dc22-S015

Zhang T, Yang L, Yang S, Gao S. Vitamin D on the susceptibility of gestational diabetes mellitus: a mini-review. Front Nutr. 2025;12:1514148. doi:10.3389/fnut.2025.1514148

Hod M, Kapur A, Sacks DA, et al. The International Federation of Gynecology and Obstetrics (FIGO) initiative on gestational diabetes mellitus: a pragmatic guide for diagnosis, management, and care. Int J Gynaecol Obstet. 2015;131(Suppl 3):S173-S211. doi:10.1016/S0020-7292(15)30007-2

Maghbooli Z, Hossein-Nezhad A, Karimi F, Shafaei A, Larijani B. Correlation between vitamin D3 deficiency and insulin resistance in pregnancy. Diabetes Metab Res Rev. 2008;24(1):27-32. doi:10.1002/dmrr.737

Choudhury AA, Devi Rajeswari V. Gestational diabetes mellitus: a metabolic and reproductive disorder. Biomed Pharmacother. 2021;143:112183. doi:10.1016/j.biopha.2021.112183

Leoni M, Padilla N, Fabbri A et al. Mechanisms of insulin resistance during pregnancy. In: Infante M, editor. Evolving concepts in insulin resistance. London: IntechOpen; 2022. doi:10.5772/intechopen.107907

Lee J, Lee NK, Moon JH. Gestational diabetes mellitus: mechanisms underlying maternal and fetal complications. Endocrinol Metab (Seoul). 2025;40(1):10-25. doi:10.3803/EnM.2024.2264

Li J, Zhang Q, Wang X et al. Association between inflammatory biomarkers and gestational diabetes mellitus in women aged 20–44: a cross-sectional analysis of NHANES 2007-2018. Gynecol Endocrinol. 2025;41(1):2487492. doi:10.1080/09513590.2025.2487492

Kim KS, Park SW, Cho YW, Kim SK. Vitamin D deficiency at mid-pregnancy is associated with a higher risk of postpartum glucose intolerance in women with gestational diabetes mellitus. Endocrinol Metab (Seoul). 2020;35(1):97-105. doi:10.3803/EnM.2020.35.1.97

Fuentes-Barría H, Aguilera-Eguía R, Flores-Fernández C, et al. Vitamin D and type 2 diabetes mellitus: molecular mechanisms and clinical implications – a narrative review. Int J Mol Sci. 2025;26(5):2153. doi:10.3390/ijms26052153

Kirovakov Z, Petkova E. Impact of vitamin D deficiency on pregnancy outcomes: can we manage it effectively? J Biol Clin Res. 2025;18:271-281. doi:10.3897/jbcr.e166383

Argano C, Mirarchi L, Amodeo S et al. The role of vitamin D and its molecular bases in insulin resistance, diabetes, metabolic syndrome, and cardiovascular disease: state of the art. Int J Mol Sci. 2023;24(20):15485. doi:10.3390/ijms242015485

Taneera J, Yaseen D, Youssef M, et al. Vitamin D augments insulin secretion via calcium influx and upregulation of voltage-gated calcium channels: findings from INS-1 cells and human islets. Mol Cell Endocrinol. 2025;599:112472. doi:10.1016/j.mce.2025.112472

Calle C, Maestro B, García-Arencibia M. 1,25-dihydroxyvitamin D3 effects on the regulation of the insulin receptor gene in the hind limb muscle and heart of streptozotocin-induced diabetic rats. Am J Mol Biol. 2013;3(2):87-97. doi:10.4236/ajmb.2013.32012

Wu J, Atkins A, Downes M, Wei Z. Vitamin D in diabetes: uncovering the sunshine hormone’s role in glucose metabolism and beyond. Nutrients. 2023;15(8):1997. doi:10.3390/nu15081997

Diniz MDFHS, Beleigoli AMR, Schmidt MI, et al. Homeostasis model assessment of insulin resistance (HOMA-IR) and metabolic syndrome at baseline of a multicentric Brazilian cohort: ELSA-Brasil study. Cad Saude Publica. 2020;36(8):e00072120. doi:10.1590/0102-311X00072120.

Silva CM, Arnegard ME, Maric-Bilkan C. Dysglycemia in pregnancy and maternal/fetal outcomes. J Womens Health (Larchmt). 2021;30(2):187-193. doi:10.1089/jwh.2020.8853

Lee JH, Jeon S, Joung B, et al. Associations of homeostatic model assessment for insulin resistance trajectories with cardiovascular disease incidence and mortality. Arterioscler Thromb Vasc Biol. 2023;43(9):1719-1728. doi:10.1161/ATVBAHA.123.319200

Nasser A, Papandreou D, Papadopoulou SK, Cheikh Ismail L. The role of vitamin D supplementation in type 1, type 2, and gestational diabetes: a comprehensive updated narrative review. Clin Pract (Basel). 2025;15(8):148. doi:10.3390/clinpract15080148

Chen W, Luo M, Guo J, et al. Metabolic pathways mediating insulin resistance and gestational diabetes mellitus discovered by high-dimensional systematic Mendelian randomization. Cardiovasc Diabetol. 2025;24(1):195. doi:10.1186/s12933-025-02746-0

Zhang L, Yan X, Zheng W, et al. Assessment of first-trimester insulin resistance indices for gestational diabetes mellitus: a prospective cohort study. J Endocrinol Invest. 2025;48(9):2167-2176. doi:10.1007/s40618-025-02630-4

Ellerbrock J, Spaanderman B, van Drongelen J, et al. Role of beta-cell function and insulin resistance in the development of gestational diabetes mellitus. Nutrients. 2022;14(12):2444. doi:10.3390/nu14122444

Eleftheriades M, Chatzakis C, Papachatzopoulou E, et al. Prediction of insulin treatment in women with gestational diabetes mellitus. Nutr Diabetes. 2021;11(1):30. doi:10.1038/s41387-021-00173-0

Wu H, Chen D, Li X, et al. A novel single-test approach for GDM diagnosis: identification and prediction of high-risk postprandial hyperglycemia. Metabolites. 2025;16(1):27. doi:10.3390/metabo16010027

Kanwar JB, Manglunia A, Mangaraj S, et al. Clinical and biochemical markers in early pregnancy for prediction of gestational diabetes mellitus. Indian J Endocrinol Metab. 2025;29(1):108-115. doi:10.4103/ijem.ijem_492_23

Balogh Z, Csehely S, Orosz M, et al. Relations of insulin resistance, body weight, vitamin D deficiency, SHBG and androgen levels in PCOS patients. Biomedicines. 2025;13(8):1803. doi:10.3390/biomedicines13081803

Trimarco V, Manzi MV, Mancusi C, et al. Insulin resistance and vitamin D deficiency: a link beyond the appearances. Front Cardiovasc Med. 2022;9:859793. doi:10.3389/fcvm.2022.859793

Mohd Ghozali N, Giribabu N, Salleh N. Mechanisms linking vitamin D deficiency to impaired metabolism: an overview. Int J ndocrinol. 2022;2022:1-16. doi:10.1155/2022/6453882

Ehrampoush E, Mirzay Razzaz J, Arjmand H, et al. The association of vitamin D levels and insulin resistance. Clin Nutr ESPEN. 2021;42:325-332. doi:10.1016/j.clnesp.2021.01.012

Genova M, Atanasova B, Ivanova I, et al. Trace elements and vitamin D in gestational diabetes. Acta Med Bulg. 2018;45(1):45–49. doi:10.2478/amb-2018-0009

Kirovakov Z, Stoilov B, Anzaar A. Predictive power of biomarkers in preeclampsia in singleton pregnancies: a comprehensive review of current evidence and future directions. Acta Med Bulg. 2025;52(4):90–98. doi:10.2478/amb-2025-0082

Downloads

Published

08.09.2026

Issue

Section

ORIGINAL ARTICLES

How to Cite

Kirovakov, Z., Obreykova, M., Kostadinov, N., Jovanovska-Kirovakova, A., & Gyokova, E. (2026). Association between serum vitamin D, insulin resistance (HOMA-IR), and gestational diabetes mellitus. Acta Medica Bulgarica, 53(3), 48-54. https://doi.org/10.2478/AMB-2026-0072

Similar Articles

1-10 of 43

You may also start an advanced similarity search for this article.