**1. Introduction**

Cardiometabolic diseases (CMDs) begin with clinically high-risk states ranging from insulin resistance (IR) to prediabetes states (e.g., obesity) and metabolic syndrome (MS), which then progress to type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) [1]. Most individuals diagnosed with CMDs also experience additional cardiometabolic risks, including obesity, dyslipidemia, hyperinsulinemia, and thrombosis [2]. Unhealthy diets and accelerated population aging have resulted in an annual increase in the prevalence and mortality of CMDs, which places a significant economic burden on the healthcare systems of various countries [3,4]. Studies have shown that these metabolic disorders may be influenced by nutrition. Individual nutrient and dietary supplements composed of sufficient nutrients may be associated with reduced cardiometabolic risks, suggesting that nutritional intervention measures are effective in managing these diseases [5–8].

**Citation:** Ouyang, J.; Cai, Y.; Song, Y.; Gao, Z.; Bai, R.; Wang, A. Potential Benefits of Selenium Supplementation in Reducing Insulin Resistance in Patients with Cardiometabolic Diseases: A Systematic Review and Meta-Analysis. *Nutrients* **2022**, *14*, 4933. https://doi.org/10.3390/ nu14224933

Academic Editor: Silvia V. Conde

Received: 15 October 2022 Accepted: 18 November 2022 Published: 21 November 2022

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Selenium is a micronutrient that is vital for human health, and its content in soil varies across different regions. In many countries, including China, selenium-containing soil is poor, and people are prone to selenium deficiency [9,10]. Selenium can exist in nature as inorganic forms (e.g., selenate and selenite) and organic forms (e.g., selenocysteine [Sec]) [11]. Selenium is highly absorbed and distributed throughout the body; in particular, organic selenium is more stable and bioavailable than inorganic selenium [11]. Sec is the main form of selenium in cells, and Sec-containing protein, namely selenoprotein (e.g., selenoprotein P, glutathione peroxidases [GPxs], and thioredoxin reductase [TrxRs]), is mainly responsible for the biological role of selenium in the human body [11–14]. Selenium is incorporated into selenoproteins, which have broad pleiotropic functions, such as antioxidant and anti-inflammatory properties [15]. Oxidative stress, which is an imbalance between antioxidant defense and prooxidant substances (e.g., reactive oxygen species [ROS] and reactive nitrogen species [RNS]), causes oxidative damage through various mechanisms, including lipid peroxidative damage, DNA damage, and protein oxidation [16,17]. Lately, increasing evidence has shown that the progression of insulin resistance, the pathogenesis of T2DM, and its microvascular ailments and macrovascular complications are significantly regulated by oxidative stress [18,19]. Higher oxidative stress is directly related to the emergence of CMDs [20,21]. Selenium is a well-known antioxidant; in particular, the selenoproteins GPxs and TrxRs are involved in antioxidant defenses and protection against oxidative damage [22]. Supplementing selenium could significantly reduce ROS, increase superoxide dismutase and GPxs activity, and reduce inflammatory cytokine content [23]. A meta-analysis of 13 trials found that selenium supplementation alleviated oxidative stress by raising the total antioxidant capacity and GPxs levels and lowering serum malonaldehyde [17]. It has been proposed that selenium is a hormetic chemical, a substance with a biphasic dose-response that is poisonous at high levels but beneficial at low concentrations [22]. Supra-nutritional levels of selenium produce ROS, which then disturb the redox states of cells [24], increase oxidative stress, and damage tissues and organs [25]. Therefore, maintaining an optimal selenium status is crucial to maintaining redox equilibrium.

Numerous studies have highlighted the significance of selenium and selenoproteins in the prevention and treatment of chronic metabolic diseases such as MS, T2DM, and CVD [26–28]. Huang et al. [29] reported that low selenium levels were related to an elevated risk of metabolic disorders, poor prognosis, and mortality. Interestingly, Kamali et al. [30] observed that selenium supplementation significantly improved glucose metabolism by decreasing fasting plasma glucose (FPG), insulin, and homeostatic model assessment of insulin resistance (HOMA-IR), and also increased high-density lipoprotein-cholesterol (HDL-C) levels, but did not affect other lipid profiles. However, selenium status has been reported to be positively associated with markers of insulin resistance and lipid profiles by Cardoso et al. [31] and Ju et al. [32]. On the other hand, a previous meta-analysis reported that selenium supplementation significantly alleviated oxidative stress and inflammation, but did not improve the blood lipid status [33]. To the best of our knowledge, the exact role of selenium in glycolipid metabolism in patients with CMDs remains undetermined. Therefore, to address these issues, we analyzed the impacts of selenium supplementation on glucose and lipid metabolism in CMDs, with the aim of verifying whether selenium supplementation could be a complementary treatment strategy for CMDs.
