Effects of selenium supplementation on glucose homeostasis, inflammation, and oxidative stress in gestational diabetes: Randomized, double-blind, placebo-controlled trial

Highlights

• We evaluated the effects of selenium supplementation on metabolic profiles in pregnant women with gestational diabetes mellitus.

• Selenium-supplemented patients showed beneficial effects on markers of insulin metabolism.

• Significant decreases were observed in serum high-sensitivity C-reactive protein levels and biomarkers of oxidative stress after intake of selenium supplements.

Abstract

Objective

To our knowledge, no reports are available indicating the effects of selenium supplementation on metabolic parameters, inflammatory factors, and oxidative stress in gestational diabetes mellitus (GDM). The aim of this study was to assess the effects of selenium supplementation on metabolic status in pregnant women with GDM who were not on oral hypoglycemic agents.

Methods

This randomized, double-blind, placebo-controlled clinical trial was performed with 70 women with GDM. Patients were randomly assigned to receive either 200 μg selenium supplements as tablet (n = 35) or placebo (n = 35) for 6 wk from weeks 24 to 28 of gestation. Fasting plasma samples were taken at study baseline and after 6 wk of intervention to quantify related variables.

Results

Selenium supplementation, compared with placebo, resulted in a significant reduction in fasting plasma glucose (−10.5 ± 11.9 versus +4.5 ± 12.9 mg/dL; P < 0.001), serum insulin levels (−1.98 ± 11.25 versus +5.26 ± 9.33 μIU/mL; P = 0.005), homeostasis model of assessment (HOMA)-insulin resistance (−0.84 ± 2.76 versus +1.47 ± 2.46; P < 0.001) and a significant increase in quantitative insulin sensitivity check index (+0.008 ± 0.03 versus −0.01 ± 0.01; P = 0.009). Additionally, a significant decrease in serum high-sensitivity C-reactive protein (hs-CRP) levels (−791.8 ± 2271.8 versus +500.5 ± 2563.3 ng/mL; P = 0.02) was seen after the administration of selenium supplements compared with placebo. Additionally, we observed a significant elevation in plasma glutathione (+52.14 ± 58.31 versus −39.93 ± 153.52 μmol/L; P = 0.002) and a significant reduction in plasma malondialdehyde levels (−0.01 ± 0.36 versus +0.67 ± 1.90 μmol/L; P = 0.04) after consumption of selenium supplements compared with placebo. We did not find any significant effect of taking selenium supplements on HOMA β-cell function, lipid profiles, plasma nitric oxide, or total antioxidant capacity concentrations.

Conclusion

Selenium supplementation in pregnant women with GDM demonstrated beneficial effects on glucose metabolism, hs-CRP levels, and biomarkers of oxidative stress.

Introduction

Gestational diabetes mellitus (GDM) is a common complication of pregnancy that has been defined as impaired insulin metabolism and carbohydrate intolerance of varying degrees of severity with onset or first recognition during pregnancy [1]. Requirement for selenium is increased during pregnancy [2]. Selenium is involved in inhibiting the expression of cyclooxygenase (COX)-2 and P-selectin [3], therefore, its nutritional inadequacy during pregnancy might increase the risk for GDM. Mean serum levels of selenium are less than normal in healthy Iranian women [4]. On the other hand, the prevalence of GDM in Iranian pregnant women is 4.7% [5]. It is associated with short- and long-term health complications for the mother, fetus, and the neonate [6]. Additionally, previous studies have reported that hyperglycemia in patients with diabetes could result in increased oxidative stress and nitrosative stress [7]. Poor glycemic control in these patients has been associated with the depletion of serum antioxidant activity [8].

Several dietary [9], [10] and nondietary [11], [12] strategies have been proposed for management of GDM. Some studies have reported a significant inverse association between body selenium status and plasma glucose levels in patients with GDM [13], [14]. Others have shown that selenium supplementation in pregnant women might result in decreased oxidative stress and improved pregnancy outcomes [15], [16]. Dietary sources of selenium are nuts, cereals, meat, mushrooms, fish, and eggs [17]. Selenium is an important component of the enzymes that protect cells from the adverse effects of free radicals [18]. Selenium is also involved in the production of thyroid hormones and has been shown to contain anti-inflammatory effects [19]. Current data supports the beneficial effect of selenium on hypertension [20], coronary artery disease [21], certain cancers [22], and inflammatory diseases [23]. Others have examined the efficacy of selenium supplementation in cancers [24]. Some studies have indicated [25] a significant decrease in serum insulin levels and insulin resistance in centrally obese women after supplementation with 200 μg/d selenium added to a hypocaloric diet enriched with legumes; however, no significant effect on lipid profiles, inflammatory factors, and biomarkers of oxidative stress have been reported. Additionally, selenium supplementation has resulted in increased erythrocyte and plasma total antioxidant status (TAS), erythrocyte-reduced glutathione (GSH) and glutathione peroxidase (GPx) in patients with epilepsy and refractory epilepsy [26].

Selenium supplementation might affect glucose homeostasis, inflammation, and oxidative stress by inhibiting the production of advanced glycation end products [3] and decreased free radical production and lipid hydroperoxides [27]. Therefore, we hypothesized that selenium supplementation might affect the metabolic status of pregnant women with GDM. We are not aware of any studies that examined the effect of selenium supplementation on glucose homeostasis, lipid profiles, inflammatory factors, and biomarkers of oxidative stress in women with GDM. This study aimed to investigate the effect of selenium supplementation on the metabolic profile of women with GDM who were not on oral hypoglycemic agents (OHAs).