Selenium and Selenoproteins at the Intersection of Type 2 Diabetes and Thyroid Pathophysiology

Abstract

Type 2 diabetes (T2D) is considered one of the largest global public-health concerns, affecting approximately more than 400 million individuals worldwide. The pathogenesis of T2D is very complex and, among the modifiable risk factors, selenium (Se) has recently emerged as a determinant of T2D pathogenesis and progression. Selenium is considered an essential element with antioxidant properties, and is incorporated into the selenoproteins involved in the antioxidant response. Furthermore, deiodinases, the enzymes responsible for homeostasis and for controlling the activity of thyroid hormones (THs), contain Se. Given the crucial action of oxidative stress in the onset of insulin resistance (IR) and T2D, and the close connection between THs and glucose metabolism, Se may be involved in these fundamental relationships; it may cover a dual role, both as a protective factor and as a risk factor of T2D, depending on its basal plasma concentration and the individual’s diet intake. In this review we discuss the current evidence (from experimental, observational and randomized clinical studies) on how Se is associated with the occurrence of T2D and its influence on the relationship between thyroid pathophysiology, IR and T2D.

Selenium in Bodily Homeostasis: Hypothalamus, Hormones, and Highways of Communication

“…Many reviews have been published in recent years summarizing the ways in which selenium is implicated in numerous pathologies related to thyroid endocrine abnormalities, including autoimmune thyroiditis [ 177 , 178 ], Hashimoto’s thyroiditis [ 179 , 180 ], Graves’ disease [ 181 , 182 ] and Graves orbitopathy [ 181 ], subclinical hypothyroidism [ 183 ], subclinical hyperthyroidism [ 184 ], goiter [ 185 ], postpartum thyroid dysfunction [ 186 ], post-COVID-19 thyroid dysfunction [ 187 ], as well as thyroid disorders in general [ 188 ]. Reviews have also been published highlighting the relevance of selenium to non-thyroidal conditions that remain metabolically pertinent, including metabolic syndrome [ 189 ], type 2 diabetes [ 190 ], gestational diabetes mellitus [ 191 ], and gestational disorders [ 192 ]. Despite numerous studies [ 178 ] reporting that selenium supplementation reduces thyroid autoantibody levels in patients with autoimmune thyroiditis, however, recent meta-analyses have found evidence of clinical efficacy to be lacking [ 193 , 194 , 195 ].…”

“…Produced by β-cells in the pancreas, insulin is secreted during food consumption and provides an anorexigenic signal to the hypothalamus to suppress feeding and promote lipogenesis and the uptake of glucose by muscle. There are strong associations between selenium status, selenoprotein action, and type 2 diabetes (T2D), which have been thoroughly described in several recent review articles [ 24 , 43 , 190 , 334 , 335 ]. The nature of these interactions is complicated, as both low and high levels of selenium have been correlated with heightened T2D risk, and some results have shown a strong sexual dimorphism.…”

Microbiota Alterations in Patients with Autoimmune Thyroid Diseases: A Systematic Review

“…Animal models have shown limited iodine uptake in individuals lacking the microbiome; however, no such association has been observed in parenterally fed humans with short bowel syndrome or after bariatric surgery [ 20 , 26 , 27 ]. In contrast, the competitive bacterial uptake of selenium has been observed, thereby reducing the bioavailability under reduced selenium conditions [ 26 , 28 , 29 ]. The diversity of reports on the interaction between the microbiota and the thyroid gland prompts an investigation into the involvement of the microbiome in thyroid disorders ( Figure 1 ).…”

Selenoprotein F Knockout Caused Glucose Metabolism Disorder in Young Mice by Disrupting Redox Homeostasis

“…Selenium (Se), as an essential trace element, is implicated in many facets of human health and diseases, including cardiovascular disease, cancer and diabetes. The role of Se in diabetes is still a matter of discussion with respect to both Se deficiency and Se supranutrition [ 5 , 6 , 7 ]. Se may have a dual role, both as a protective factor and as a risk factor of diabetes, depending on its basal plasma concentration and the individual’s diet intake [ 6 , 8 ].…”

“…The role of Se in diabetes is still a matter of discussion with respect to both Se deficiency and Se supranutrition [ 5 , 6 , 7 ]. Se may have a dual role, both as a protective factor and as a risk factor of diabetes, depending on its basal plasma concentration and the individual’s diet intake [ 6 , 8 ]. A number of epidemiological studies have shown that an inadequate intake of Se is associated with an increased incidence of diabetes [ 9 , 10 , 11 ].…”