RESUMEN
Although literature has been consistently showing an increased risk of type 2 diabetes (T2DM) in populations with high exposure to selenium, there is a lack of information quantifying the association between diabetes-related markers and the nutritional status of selenium. Therefore, we aimed to investigate the association between blood selenium concentration and glucose markers in a representative sample of the US population, which is known to have moderate to high exposure to selenium. This cross-sectional analysis included 4,339 participants ≥18 years from the 2013 to 2018 National Health and Nutrition Examination Survey (NHANES). All participants were assessed for whole blood selenium concentration, fasting plasma insulin and glucose, HbA1c, and HOMA-IR (Homeostatic Model Assessment for Insulin Resistance). In this cohort, all participants presented with adequate selenium status [196.2 (SD: 0.9) µg/L] and 867 (15%) had diabetes mellitus. Selenium was positively associated with insulin, glucose and HOMA-IR in models adjusted for age and sex. When the models were further adjusted for smoking status, physical activity, metabolic syndrome and BMI, the associations with insulin and HOMA-IR remained but the association with glucose was no longer significant. A 10 µg/L increase in selenium was associated with 1.5% (95% CI: 0.4-2.6%) increase in insulin and 1.7% (95% CI: 0.5-2.9%) increase in HOMA-IR in fully adjusted models. There was no evidence of an association between selenium and diabetes prevalence. Our findings corroborate the notion that selenium supplementation should not be encouraged in populations with high dietary intake of selenium.
RESUMEN
Severe disruption of brain iron homeostasis can cause fatal neurodegenerative disease, however debate surrounds the neurologic effects of milder, more common iron loading disorders such as hereditary hemochromatosis, which is usually caused by loss-of-function polymorphisms in the HFE gene. There is evidence from both human and animal studies that HFE gene variants may affect brain function and modify risks of brain disease. To investigate how disruption of HFE influences brain transcript levels, we used microarray and real-time reverse transcription polymerase chain reaction to assess the brain transcriptome in Hfe(-/-) mice relative to wildtype AKR controls (age 10 weeks, n≥4/group). The Hfe(-/-) mouse brain showed numerous significant changes in transcript levels (p<0.05) although few of these related to proteins directly involved in iron homeostasis. There were robust changes of at least 2-fold in levels of transcripts for prominent genes relating to transcriptional regulation (FBJ osteosarcoma oncogene Fos, early growth response genes), neurotransmission (glutamate NMDA receptor Grin1, GABA receptor Gabbr1) and synaptic plasticity and memory (calcium/calmodulin-dependent protein kinase IIα Camk2a). As previously reported for dietary iron-supplemented mice, there were altered levels of transcripts for genes linked to neuronal ceroid lipofuscinosis, a disease characterized by excessive lipofuscin deposition. Labile iron is known to enhance lipofuscin generation which may accelerate brain aging. The findings provide evidence that iron loading disorders can considerably perturb levels of transcripts for genes essential for normal brain function and may help explain some of the neurologic signs and symptoms reported in hemochromatosis patients.