Role of selenium in type 2 diabetes, insulin resistance and insulin secretion

Table 1 Summary of a wide variety of studies suggesting a beneficial or detrimental role of selenium in different diseases and physiological processes

Ref.	Type of study	Number of participants	Effects on Se intake
Hu et al[16], 2021	Longitudinal study (6 mo)	90 with HT; 36 healthy subjects	Reductions in thyroid autoantibodies and thyroid-stimulating hormone levels in HT patients
Karimi and Omrani[17], 2019	Longitudinal study (3 mo)	102 with AIT	Decreased antithyroid peroxidase antibody levels
Karunasinghe et al[18], 2016	Longitudinal study (6 mo)	572 males	Improved leukocyte DNA integrity through increased homeostatic apoptosis when folate intake levels were low and methionine intake levels were high
Kočan et al[19] 2014	Longitudinal study (6 d)	65 septic patients	Improvement of patients with acute lung injury and elevated oxidative stress
Guo et al[20], 2019	Longitudinal study (21 d)	76 severe septic patients	Neutral effect
Vinceti et al[21], 2018	Review	-	Se had no effect in preventing cancer overall, including in patients with low Se levels
Rocourt and Cheng[22], 2013	Review	-	Supplementing Se to people with Se deficiency improved cancer prevention due to elimination of such deficiency
Radomska et al[23], 2021	Review	-	Se species as coadjuvant agents in cancer treatment due to their lower toxicity, higher selectivity and efficacy in inducing cell apoptosis
Wu et al[14], 2018	Cross-sectional study	8011 participants	Higher incidence of hypertension in the group with higher serum Se concentration
Xie et al[24], 2021	Longitudinal study (20 yr)	10025 participants	Protective factor for blood pressure in low-Se regions
Rayman et al[25], 2011	Longitudinal study (6 mo)	501 people aged 60 yr to 74 yr	Se supplementation decreased total and non-HDL cholesterol
Chen et al[26], 2015	Longitudinal study (7 yr)	2000 aged 65 and older	Decrease in total cholesterol and an increase in HDL in relation with increasing Se
González-Estecha et al[27], 2017	Cross-sectional study	372 participants	Positive association of Se with total and LDL cholesterol
Fülöp et al[28], 2013	Study population	81 hyperlipidemic patients; 43 healthy volunteers	Higher Se levels in hyperlipidemic patients
Park and Seo[29], 2017	Cross-sectional study	501 participants	Decreased lipid dysregulation caused by elevated toenail levels of mercury
Berger et al[30], 2008	Longitudinal study (5 d)	2000 cardiac surgery or major trauma or subarachnoid hemorrhage patients	Correction of initial alterations and restoration of antioxidant defenses
Fink and Busch[31], 2018	Longitudinal study (24 h)	28 resuscitated patients	Improvement in neurological outcome and survival rate with early Se treatment in patients after cardiopulmonary resuscitation
Colangelo et al[32], 2014	Study population	5115 participants	High Se levels were associated with a greater probability of having depressive symptoms
Czernichow et al[33], 2009	Longitudinal study (7.5 yr)	5220 participants	No benefit or adverse effect of multiple antioxidant supplementation on the incidence of metabolic syndrome
Wang et al[34], 2021	Cross-sectional study	3827 participants	Only positive associations when serum Se level > 130 μg/L in patients with NAFLD

AIT: Autoimmune thyroiditis; HDL: High density lipoprotein; HT: Hashimoto’s thyroiditis; LDL: Low-density lipoprotein; NAFLD: Nonalcoholic fatty liver disease; Se: selenium.

Table 2 Summary of evidence showing an association between elevated selenium levels and increased risk of type 2 diabetes mellitus

Ref.	Type of study	Number of participants	Evidence for T2DM risk
Vinceti et al[35], 2021	Dose-response meta-analysis	-	Non-linear dose-response association. Dramatically increase from 80 μg of daily Se intake and above
Wang et al[36], 2016	Dose-response meta-analysis	-	Non-linear dose-response association with T2DM at low and high Se concentrations
Duntas and Benvenga[37], 2015; Rocourt and Cheng[22], 2013	Reviews	-	U-shaped risk response. An excess of Se promotes hyperinsulinemia, hyperglycemia and hyperlipidemia
Rayman and Stranges[38], 2013	Review	-	Increased selenoprotein levels in T2DM patients were reduced by the characteristic inflammatory response of T2DM
Wang et al[39], 2017	Cross-sectional study	2420 participants	Negative associations were found between Se dose and insulin resistance
Wongdokmai et al[40], 2021	Cross-sectional study	655 men	Abnormal metabolism in adipocytes by excessive release of fatty acids and/or hormones
Vinceti et al[41], 2021	Prospective study	24325 participants	High Se intake increased the risk of hospitalization for T2DM
Galan-Chilet et al[42], 2017	Cross-sectional study	1452 participants	Positive association between plasma Se with prevalent and incident diabetes
Hoque and Shi[43], 2022	Cross-sectional study	18932 participants	Positively associated with diabetes but inversely associated with all-cause mortality
Faghihi et al[44], 2014	3 mo	60 T2DM patients	Se supplementation in T2DM patients with deficient Se levels resulted in adverse effects on blood glucose homeostasis

Se: Selenium; T2DM: Type 2 diabetes mellitus.