Selenium status and type 2 diabetes risk.

Optimal selenium (Se) status is necessary for overall health. That status can be affected by food intake pattern, age, sex, and health status. At nutritional levels of intake, Se functions metabolically as an essential constituent of some two dozen selenoproteins, most, if not all, of which have redox functions. Insufficient dietary intake of Se reduces, to varying degrees, the expression of these selenoproteins. Recent clinical and animal studies have indicated that both insufficient and excessive Se intakes may increase risk of type 2 diabetes mellitus (T2D), perhaps by way of selenoprotein actions. In this review, we discuss the current evidence linking Se status and T2D risk, and the roles of 14 selenoproteins and other proteins involved in selenoprotein biosynthesis. Understanding such results can inform the setting of safe and adequate Se intakes.

Dietary Selenium Requirement for the Prevention of Glucose Intolerance and Insulin Resistance in Middle-Aged Mice.

BACKGROUND: Although dietary selenium (Se) deficiency or excess induces type 2 diabetes-like symptoms in mice, suboptimal body Se status usually causes no symptoms but may promote age-related decline in overall health. OBJECTIVES: We sought to determine the dietary Se requirement for protection against type 2 diabetes-like symptoms in mice. METHODS: Thirty mature (aged 4 mo) male C57BL/6J mice were fed a Se-deficient torula yeast AIN-93M diet supplemented with Na2SeO4 in graded concentrations totaling 0.01 (basal), 0.04, 0.07, 0.10, and 0.13 (control) mg Se/kg for 4 mo (n = 6) until they were middle-aged (8 mo). Droplets of whole blood were used to determine glucose tolerance and insulin sensitivity in the mice from ages 5 to 8 mo. Postmortem serum, liver, and skeletal muscle were collected to assay for selenoprotein expression and markers of glucose metabolism. Data were analyzed by 1-way ANCOVA with or without random effects for time-repeated measurements using live mice or postmortem samples, respectively. RESULTS: Compared with control, the consumption of basal diet increased (P < 0.05) fasting serum insulin (95% CI: 52%, 182%) and leptin (95% CI: 103%, 118%) concentrations in middle-aged mice. Dietary Se insufficiency decreased (P < 0.05) 1) glucose tolerance (13-79%) and insulin sensitivity (15-65%) at ≤0.10 mg Se/kg; 2) baseline thymoma viral proto-oncogene phosphorylation on S473 (27-54%) and T308 (22-46%) at ≤0.10 and ≤0.07 mg Se/kg, respectively, in the muscle but not the liver; and 3) serum glutathione peroxidase 3 (51-83%), liver and muscle glutathione peroxidase 1 (32-84%), serum and liver selenoprotein P (28-42%), and liver and muscle selenoprotein H (39-48%) and selenoprotein W (16-73%) protein concentrations at ≤0.04, ≤0.10, ≤0.07, and ≤0.10 mg Se/kg, respectively. CONCLUSIONS: Mice fed diets containing ≤0.10 mg Se/kg display impaired glucose tolerance and insulin sensitivity, suggesting increased susceptibility to type 2 diabetes by suboptimal Se status at levels ≤23% of nutritional needs.

Analyses of Selenotranscriptomes and Selenium Concentrations in Response to Dietary Selenium Deficiency and Age Reveal Common and Distinct Patterns by Tissue and Sex in Telomere-Dysfunctional Mice.

Background: The hierarchies of tissue selenium distribution and selenotranscriptomes are thought to critically affect healthspan and longevity.Objective: We determined selenium status and selenotranscriptomes in response to long-term dietary selenium deficiency and age in tissues of male and female mice.Methods: Weanling telomerase RNA component knockout C57BL/6 mice were fed a selenium-deficient (0.03 mg Se/kg) Torula yeast-based AIN-93G diet or a diet supplemented with sodium selenate (0.15 mg Se/kg) until age 18 or 24 mo. Plasma, hearts, kidneys, livers, and testes were collected to assay for selenotranscriptomes, selected selenoproteins, and tissue selenium concentrations. Data were analyzed with the use of 2-factor ANOVA (diet × age) in both sexes.Results: Dietary selenium deficiency decreased (P ≤ 0.05) selenium concentrations (65-72%) and glutathione peroxidase (GPX) 3 (82-94%) and selenoprotein P (SELENOP) (17-41%) levels in the plasma of both sexes of mice and mRNA levels (9-68%) of 4, 4, and 12 selenoproteins in the heart, kidney, and liver of males, respectively, and 5, 16, and 14 selenoproteins, respectively, in females. Age increased selenium concentrations and SELENOP levels (27% and 30%, respectively; P ≤ 0.05) in the plasma of males only but decreased (12-46%; P < 0.05) mRNA levels of 1, 5, and 13 selenoproteins in the heart, kidney, and liver of males, respectively, and 6, 5, and 0 selenoproteins, respectively, in females. Among these mRNAs, selenoprotein H (Selenoh), selenoprotein M (Selenom), selenoprotein W (Selenow), methionine-R-sulfoxide reductase 1 (MsrB1), Gpx1, Gpx3, thioredoxin reductase 1 (Txnrd1), Txnrd2, selenoprotein S (Selenos), selenoprotein F (Selenof), and selenoprotein O (Selenoo) responded in parallel to dietary selenium deficiency and age in ≥1 tissue or sex, or both. Dietary selenium deficiency upregulated (40-160%; P ≤ 0.05) iodothyronine deiodinase 2 (Dio2) and selenoprotein N (Selenon) in the kidneys of males. Age upregulated (11-44%; P < 0.05) Selenon in the kidneys of males, selenoprotein K (Selenok) and selenoprotein I (Selenoi) in the kidneys of females, and Selenof and Selenok in the testes.Conclusions: These results illustrate tissue-specific sexual dimorphisms of selenium status and selenotranscriptomes because of dietary selenium deficiency and age.

Forrest Classification for Bleeding Peptic Ulcer: A New Look at the Old Endoscopic Classification.

The management of peptic ulcer bleeding is clinically challenging. For decades, the Forrest classification has been used for risk stratification for nonvariceal ulcer bleeding. The perception and interpretation of the Forrest classification vary among different endoscopists. The relationship between the bleeder and ulcer images and the different stages of the Forrest classification has not been studied yet. Endoscopic still images of 276 patients with peptic ulcer bleeding for the past 3 years were retrieved and reviewed. The intra-rater agreement and inter-rater agreement were compared. The obtained endoscopic images were manually drawn to delineate the extent of the ulcer and bleeding area. The areas of the region of interest were compared between the different stages of the Forrest classification. A total of 276 images were first classified by two experienced tutor endoscopists. The images were reviewed by six other endoscopists. A good intra-rater correlation was observed (0.92-0.98). A good inter-rater correlation was observed among the different levels of experience (0.639-0.859). The correlation was higher among tutor and junior endoscopists than among experienced endoscopists. Low-risk Forrest IIC and III lesions show distinct patterns compared to high-risk Forrest I, IIA, or IIB lesions. We found good agreement of the Forrest classification among different endoscopists in a single institution. This is the first study to quantitively analyze the obtained and explain the distinct patterns of bleeding ulcers from endoscopy images.