Gestational diabetes mellitus (GDM) is among the most common metabolic complications of pregnancy, although its prevalence varies considerably across populations and diagnostic criteria. It develops when pancreatic β-cell compensation is insufficient to overcome the progressive insulin resistance of pregnancy. Maternal glycaemia, even below the threshold for overt diabetes, is continuously associated with adverse outcomes such as large-for-gestational-age birth, primary caesarean delivery, neonatal hypoglycaemia and fetal hyperinsulinaemia. Furthermore, women affected by GDM have an increased long-term risk of developing type 2 diabetes mellitus.[1–3]

Oxidative stress and low-grade inflammation are increasingly recognised as contributors to the pathophysiology of GDM. Excessive reactive oxygen species generation, together with impaired antioxidant defence, may aggravate insulin resistance, β-cell dysfunction and placental abnormalities.[4] Selenium is an essential trace element incorporated into antioxidant selenoproteins, including glutathione peroxidases and thioredoxin reductases. Through these proteins, selenium may influence cellular redox balance, inflammatory responses and glucose metabolism; however, its biological effects are dependent on dose and baseline selenium status, and excessive exposure may be harmful.[5] Meta-analytic evidence has suggested that women with GDM may have lower circulating selenium concentrations than normoglycaemic pregnant women, although heterogeneity among observational studies limits causal interpretation.[6]

Clinical evidence regarding selenium supplementation in GDM remains limited and inconsistent. A randomised trial using 200 µg/day for six weeks reported improvements in fasting glucose, insulin resistance, inflammation and oxidative-stress biomarkers,[7] whereas supplementation with 100 µg/day for 12 weeks did not significantly improve fasting glucose, postprandial glucose or glycated haemoglobin.[8] More recently, a four-week trial of 200 µg/day demonstrated greater reductions in fasting and post-load glucose levels than dietary treatment alone.[9] Differences in selenium dose, intervention duration, sample size and background treatment leave uncertainty regarding its clinical effectiveness and safety. Therefore, the present prospective comparative interventional study evaluated whether adding selenium-enriched yeast providing 200 µg elemental selenium daily to standard GDM care for six weeks or until delivery improves fasting plasma glucose, postprandial plasma glucose and glycated haemoglobin, reduces insulin requirements, and influences maternal and neonatal outcomes.

Study design and setting This prospective comparative interventional study was conducted in the Department of Obstetrics and Gynaecology, Basaveshwara Medical College and Hospital, Chitradurga, Karnataka, from November 2025 to April 2026. Pregnant women with newly diagnosed gestational diabetes mellitus were enrolled and followed until delivery. Participants Women aged ≥18 years with a singleton pregnancy, gestational age of 24–32 weeks and newly diagnosed gestational diabetes mellitus were eligible. Women with pre-existing or overt diabetes, multiple pregnancy, major systemic illness, uncontrolled endocrine disease, selenium supplementation or hypersensitivity, major fetal anomaly, severe obstetric complications, or inability to complete follow-up were excluded. Written informed consent was obtained from all participants. A total of 200 women were included: 100 received selenium supplementation with standard treatment and 100 received standard treatment alone. Intervention and standard management Women in the intervention group received selenium-enriched yeast providing 200 µg elemental selenium orally once daily after a meal for six weeks or until delivery, whichever occurred first. The control group received no additional selenium supplementation. Both groups received standard management comprising individualized medical nutrition therapy, physical activity advice, glucose monitoring and insulin when clinically indicated. Routine antenatal iron, folic acid and calcium supplementation was continued. Data collection and follow-up Baseline data included maternal age, gestational age, gravidity, parity, body mass index, obstetric history, family history of diabetes, blood pressure, medication use and nutritional supplementation. Fasting plasma glucose, postprandial plasma glucose and glycated haemoglobin were recorded at enrolment and after the intervention period. Insulin initiation, dose escalation and final insulin requirement were documented during follow-up. Adherence to selenium supplementation was assessed using tablet counts and participant interviews. Consumption of at least 80% of the prescribed tablets was considered satisfactory adherence. Outcome measures The primary outcomes were changes in fasting plasma glucose, postprandial plasma glucose and glycated haemoglobin from baseline to the end of the intervention period. Secondary maternal outcomes included achievement of glycaemic targets, insulin initiation or escalation, gestational hypertension or pre-eclampsia, gestational age at delivery, induction of labour, mode of delivery and supplementation-related adverse effects. Neonatal outcomes included birth weight, macrosomia or large-for-gestational-age birth, preterm birth, neonatal hypoglycaemia, respiratory distress, neonatal intensive care unit admission, stillbirth and neonatal death. Statistical analysis Continuous variables were summarized as mean ± standard deviation or median [interquartile range], and categorical variables as n (%). Baseline comparisons used Welch independent-samples t tests, Mann–Whitney U tests, Pearson chi-square tests or Fisher exact tests, as appropriate. Within-group changes in glycaemic parameters were assessed using paired t tests. Between-group effects on fasting plasma glucose, postprandial plasma glucose and glycated haemoglobin were evaluated using analysis of covariance adjusted for the corresponding baseline value. Adjusted mean differences with 95% confidence intervals were reported. Other continuous outcomes were compared using Welch t tests, while categorical outcomes were expressed as risk ratios with 95% confidence intervals. Mode of delivery was compared using a chi-square test. All tests were two-sided, with p < 0.05 considered statistically significant. Statistical analyses were performed using SPSS version 24.

Participant disposition and baseline characteristics

All 200 enrolled women were included in the analysis, with n=100 (50.0%) in the control group and n=100 (50.0%) in the selenium intervention group. Follow-up through delivery was available for n=190 (95.0%), comprising n=95 (95.0%) in each group. Complete data for all three primary glycaemic outcomes were available for n=182 (91.0%): n=89 (89.0%) in the control group and n=93 (93.0%) in the intervention group. Baseline demographic, obstetric, anthropometric, blood pressure and glycaemic characteristics were comparable between groups (Table 1).

Glycaemic outcomes

Fasting plasma glucose, postprandial plasma glucose and HbA1c decreased significantly from baseline in both groups. The reductions were consistently greater in the intervention group. After adjustment for the corresponding baseline value, the intervention group had lower follow-up fasting plasma glucose (adjusted mean difference -4.4 mg/dL), postprandial plasma glucose (-4.7 mg/dL) and HbA1c (-0.09 percentage points); all comparisons were statistically significant (Table 2). The relative magnitude of change across the three glycaemic parameters is shown in Figure 1.

Requirement for glucose-lowering treatment

Recommended glycaemic targets were achieved in n=34 (34.0%) women in the intervention group and n=14 (14.0%) women in the control group. Among women not receiving insulin at enrolment (intervention n=92; control n=89), insulin was initiated in n=22 (23.9%) and n=35 (39.3%), respectively. Any insulin use during the study occurred in n=30 (30.0%) women in the intervention group and n=46 (46.0%) women in the control group. Among women who required insulin, insulin dose escalation and the final daily insulin dose did not differ significantly between groups (Table 3 and Figure 2).

Maternal outcomes

Maternal outcomes were similar between groups. No statistically significant differences were observed in gestational hypertension, pre-eclampsia, gestational age at delivery, induction of labour or the distribution of mode of delivery (Table 4).

Neonatal outcomes

Birth weight and the frequencies of preterm birth, large-for-gestational-age birth, macrosomia, neonatal hypoglycaemia and respiratory distress did not differ significantly between groups. Neonatal intensive care unit admission occurred in n=6 (6.3%) neonates in the intervention group and n=14 (14.7%) in the control group, although the difference did not reach statistical significance. One stillbirth occurred in the intervention group, and one neonatal death occurred in the control group (Table 5 and Figure 2).

Adherence and safety

In the intervention group, mean supplementation adherence was 89.9 ± 7.8%, and n=87 (87.0%) women consumed at least 80% of prescribed tablets. At least one potentially selenium-related adverse event was recorded in n=20 (20.0%) women. The most frequently recorded events were nausea in n=6 (6.0%), metallic taste in n=5 (5.0%) and vomiting in n=4 (4.0%). No suspected selenium toxicity, serious adverse event or discontinuation for safety was recorded (Table 3).

Table 1. Baseline characteristics of the study groups

Values are mean ± SD, median [IQR], or n (%). Welch independent-samples t tests were used for continuous variables, Mann-Whitney U tests for gravidity and parity, Pearson chi-square tests for categorical variables, and Fisher exact test for baseline hypertension. GDM, gestational diabetes mellitus; HbA1c, glycated haemoglobin; IQR, interquartile range; SD, standard deviation.

Table 2. Changes in glycaemic parameters from baseline to follow-up

Values are mean ± SD and mean change (95% CI). Change was calculated as follow-up minus baseline; negative values indicate improvement. Within-group comparisons used paired t tests. Adjusted differences represent intervention minus control at follow-up from analysis of covariance adjusted for the baseline value. n denotes participants with paired measurements. ANCOVA, analysis of covariance; CI, confidence interval; HbA1c, glycated haemoglobin; SD, standard deviation.

Table 3. Glycaemic target attainment, insulin requirements, supplementation adherence and safety

Values are n (%) or mean ± SD. Risk ratios compare intervention with control. The insulin initiation denominator excluded women using insulin at enrolment. Insulin dose escalation and final dose were evaluated among women who used insulin during the study. Supplementation adherence and safety rows are descriptive for the intervention group. CI, confidence interval; MD, mean difference; RR, risk ratio; SD, standard deviation.

Table 4. Maternal outcomes

Values are n (%) or mean ± SD. Hypertensive outcome denominators were n=100 per group; delivery outcome denominators were n=95 per group. Risk ratios compare intervention with control, and mean differences represent intervention minus control. CI, confidence interval; MD, mean difference; RR, risk ratio; SD, standard deviation.

Table 5. Neonatal outcomes

Values are n (%) or mean ± SD. Denominators were n=95 births per group, except neonatal death, which was evaluated among live births (control n=95; intervention n=94). Risk ratios compare intervention with control, and mean differences represent intervention minus control. Fisher exact tests were used for stillbirth and neonatal death; risk ratios were not estimable when one group had no events. CI, confidence interval; MD, mean difference; NICU, neonatal intensive care unit; RR, risk ratio; SD, standard deviation.

Figure 1. Mean percentage change from baseline in fasting plasma glucose, postprandial plasma glucose and HbA1c by study group. Points represent group means and error bars represent 95% confidence intervals. Negative values indicate improvement. HbA1c, glycated haemoglobin.

Figure 2. Risk ratios for key treatment, maternal and neonatal outcomes. For glycaemic target attainment, a risk ratio greater than 1 favours the intervention; for all other outcomes, a risk ratio less than 1 favours the intervention. Insulin initiation was evaluated among women not using insulin at enrolment, insulin dose escalation among insulin users, and delivery and neonatal outcomes among n=95 births per group. CI, confidence interval; NICU, neonatal intensive care unit; RR, risk ratio.

In this prospective comparative study, adjunctive selenium supplementation was associated with modest but statistically significant improvements in glycaemic control among women with gestational diabetes mellitus (GDM). Compared with standard treatment alone, selenium reduced follow-up fasting plasma glucose by an adjusted 4.4 mg/dL, postprandial glucose by 4.7 mg/dL and HbA1c by 0.09 percentage points. It also increased achievement of recommended glycaemic targets and reduced both insulin initiation and overall insulin use. However, insulin-dose escalation among users and maternal and neonatal outcomes did not differ significantly between groups. These findings are consistent with previous evidence suggesting that selenium may improve glucose regulation through antioxidant and insulin-sensitizing mechanisms. Saifi et al. reported that 12 weeks of selenium supplementation in women with GDM reduced fasting glucose while increasing erythrocyte glutathione peroxidase activity and other antioxidant enzymes and decreasing malondialdehyde concentrations [10]. Although the intervention duration and metabolic assessments differed from the present study, both studies support a potential relationship between enhanced antioxidant defence and improved glycaemic control. The present study extends this evidence by demonstrating concurrent improvements in fasting glucose, postprandial glucose and HbA1c, together with reduced need for insulin therapy. Observational studies also support an association between lower selenium status and gestational dysglycaemia. Tan et al. found lower serum selenium concentrations in women with GDM and impaired glucose tolerance than in normoglycaemic pregnant women, with selenium concentrations declining as pregnancy advanced [11]. Similarly, Kilinc et al. reported lower selenium levels in women with GDM or glucose intolerance and an inverse relationship between selenium and blood glucose [12]. Moshfeghy et al. further observed substantially lower first- and second-trimester selenium concentrations in women who later developed GDM and reported strong predictive performance for a low selenium threshold [13]. These studies provide biological plausibility for supplementation but cannot establish causality, because reduced selenium may be a consequence rather than a cause of altered glucose metabolism. Not all prospective evidence is consistent. Liu et al. found that selenium insufficiency was common in early pregnancy, but serum selenium was not independently associated with GDM after adjustment for confounding variables [14]. In contrast, a nested case-control study using urinary selenium showed progressively higher GDM risk among women in the lower selenium tertiles, with stronger associations in older women and in pregnancies involving female fetuses [15]. Differences in population nutrition, biological specimen, gestational timing and selenium distribution may explain these discrepancies. They also indicate that the metabolic response to supplementation may depend on baseline selenium status, which was not measured in the present study. Functional selenium biomarkers may be more informative than serum selenium alone. In the Odense Child Cohort, higher glutathione peroxidase-3 activity was associated with lower fasting glucose, insulin resistance, 2-hour glucose and GDM risk, while lower late-pregnancy activity was associated with large-for-gestational-age birth [16]. These findings support a selenoprotein-mediated mechanism involving oxidative stress and glucose metabolism. However, because the present study did not assess serum selenium, selenoprotein P or glutathione peroxidase activity, the biological pathway underlying the observed glycaemic improvement remains uncertain. The reduction in insulin initiation is clinically relevant despite the small mean differences in glucose values. Selenium supplementation increased glycaemic-target attainment from 14% to 34% and reduced insulin initiation from 39.3% to 23.9%. However, the absence of a difference in final insulin dose among insulin users suggests that supplementation may help some women remain below the threshold for pharmacological treatment but may have limited effect once insulin becomes necessary. As insulin initiation may also be influenced by clinician judgement, monitoring intensity and treatment adherence, this outcome should be confirmed in blinded randomized trials. No significant benefit was observed for hypertensive disorders, mode of delivery, gestational age at delivery or neonatal outcomes. Tara et al., in a randomized placebo-controlled trial of selenium during pregnancy, similarly reported no significant reduction in pre-eclampsia despite improved maternal selenium status [17]. In the present study, the lower frequency of neonatal intensive care admission in the selenium group did not reach statistical significance and should be considered exploratory. The study was not powered to detect differences in relatively uncommon outcomes such as pre-eclampsia, stillbirth or neonatal death. The strengths of this study include prospective follow-up, comparable baseline characteristics, adjustment of primary outcomes for baseline values, high supplementation adherence and assessment of treatment, maternal, neonatal and safety outcomes. Important limitations include its single-centre design, absence of placebo control and blinding, lack of baseline selenium and dietary assessments, variable supplementation duration and limited power for obstetric and neonatal complications. Adverse events were also recorded only in the intervention group, preventing direct comparison with background pregnancy-related symptoms.

Adjunctive selenium supplementation at 200 µg/day was associated with modest improvements in fasting glucose, postprandial glucose and HbA1c and with reduced insulin initiation in women with GDM. It did not significantly affect maternal or neonatal outcomes. These findings support further multicentre, randomized, placebo-controlled trials incorporating baseline selenium status and functional selenoprotein biomarkers before routine supplementation can be recommended.

1. Zhu Y, Zhang C. Prevalence of gestational diabetes and risk of progression to type 2 diabetes: a global perspective. Curr Diab Rep. 2016;16(1):7. doi:10.1007/s11892-015-0699-x.
2. HAPO Study Cooperative Research Group. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med. 2008;358(19):1991–2002. doi:10.1056/NEJMoa0707943.
3. Plows JF, Stanley JL, Baker PN, Reynolds CM, Vickers MH. The pathophysiology of gestational diabetes mellitus. Int J Mol Sci. 2018;19(11):3342. doi:10.3390/ijms19113342.
4. Lappas M, Hiden U, Desoye G, Froehlich J, Hauguel-de Mouzon S, Jawerbaum A. The role of oxidative stress in the pathophysiology of gestational diabetes mellitus. Antioxid Redox Signal. 2011;15(12):3061–3100. doi:10.1089/ars.2010.3765.
5. Rayman MP. Selenium and human health. 2012;379(9822):1256–1268. doi:10.1016/S0140-6736(11)61452-9.
6. Askari G, Iraj B, Salehi-Abargouei A, Fallah AA, Jafari T. The association between serum selenium and gestational diabetes mellitus: a systematic review and meta-analysis. J Trace Elem Med Biol. 2015;29:195–201. doi:10.1016/j.jtemb.2014.09.006.
7. Asemi Z, Jamilian M, Mesdaghinia E, Esmaillzadeh A. Effects of selenium supplementation on glucose homeostasis, inflammation, and oxidative stress in gestational diabetes: randomized, double-blind, placebo-controlled trial. 2015;31(10):1235–1242. doi:10.1016/j.nut.2015.04.014.
8. Najib FS, Poordast T, Rezvan Nia M, Dabbaghmanesh MH. Effects of selenium supplementation on glucose homeostasis in women with gestational diabetes mellitus: a randomized, controlled trial. Int J Reprod Biomed. 2020;18(1):57–64. doi:10.18502/ijrm.v18i1.6201.
9. Yigit E, Sayar I. Selenium supplementation and gestational diabetes: a randomised controlled trial. J Coll Physicians Surg Pak. 2024;34(5):561–567. doi:10.29271/jcpsp.2024.05.561.

10. Saifi H, Mabrouk Y, Saifi R, Benabdelkader M, Saidi M. Influence of selenium supplementation on carbohydrate metabolism and oxidative stress in pregnant women with gestational diabetes mellitus. J Med Biochem. 2020;39(2):191–198. doi:10.2478/jomb-2019-0034.
11. Tan M, Sheng L, Qian Y, Ge Y, Wang Y, Zhang H, et al. Changes of serum selenium in pregnant women with gestational diabetes mellitus. Biol Trace Elem Res. 2001;83(3):231–237. doi:10.1385/BTER:83:3:231.
12. Kilinc M, Guven MA, Ezer M, Ertas IE, Coskun A. Evaluation of serum selenium levels in Turkish women with gestational diabetes mellitus, glucose intolerants, and normal controls. Biol Trace Elem Res. 2008;123:35–40. doi:10.1007/s12011-007-8087-2.
13. Moshfeghy Z, Bashiri K, Dabbaghmanesh MH, Akbarzadeh M, Asadi N, Sayadi M. The predictive value of selenium in diagnosis of gestational diabetes: a nested case-control study. Int J Gen Med. 2020;13:53–60. doi:10.2147/IJGM.S233950.
14. Liu PJ, Yao A, Ma L, Chen XY, Yu SL, Liu Y, et al. Associations of serum selenium levels in the first trimester of pregnancy with the risk of gestational diabetes mellitus and preterm birth: a preliminary cohort study. Biol Trace Elem Res. 2021;199(2):527–534. doi:10.1007/s12011-020-02191-y.
15. Liu Y, Chen H, Zhang M, Zhu G, Yang Y, Li Y, et al. The relationship between urinary selenium levels and risk of gestational diabetes mellitus: a nested case-control study. Front Public Health. 2023;11:1145113. doi:10.3389/fpubh.2023.1145113.
16. Demircan K, Jensen RC, Chillon TS, Jensen TK, Sun Q, Bonnema SJ, et al. Serum selenium, selenoprotein P, and glutathione peroxidase 3 during early and late pregnancy in association with gestational diabetes mellitus: prospective Odense Child Cohort. Am J Clin Nutr. 2023;118(6):1224–1234. doi:10.1016/j.ajcnut.2023.09.025.
17. Tara F, Maamouri G, Rayman MP, Ghayour-Mobarhan M, Sahebkar A, Yazarlu O, et al. Selenium supplementation and the incidence of preeclampsia in pregnant Iranian women: a randomized, double-blind, placebo-controlled pilot trial. Taiwan J Obstet Gynecol. 2010;49(2):181–187. doi:10.1016/S1028-4559(10)60038-1.