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Selenium and type 2 diabetes risk - Coggle Diagram
Selenium and type 2 diabetes risk
When glucose rises, SELENOP rises. But this does not mean selenium causes T2DM
CONCLUSIONS OF SE AND T2DM
Se, selenoproteins and insulin signalling and CHO metabolism linked in numerous sways. Cross-sectional studies show association between high plasma se and T2DM/ fasting plasma glucose explained by: 1. SELENOP and gluconeogenic enzymes have same transcription factors requiring methylation 2. T2DM/ hyperglycaemia increases SELENOP biosynthesis 4. SELENOP increases glucose release and insulin resistance = DOES NOT MEAN Se causes T2DM
RCT do not support Se as cause of T2DM
dietary supplementation of se does not cause T2DM
History of se and risk of T2DM
B cells poorly protected by antioxidants and susceptible to injury so GPX1 protect against oxidative damage by cell death and H2O2
In vitro studies showed se (as selenate) has antidiabetic effect but epidemiological studies did not confirm this
NPC trial follow up-
se participants had higher incidents of diabetes compared to controls but all had non-melanoma skin cancer so not all health/ general population. risk only increased in those with highest selenium tertile at baseline
Observational studies
: found +ve association between se in plasma and T2DM. Some showed SELENOP involved so ? high SELENOP cuasing T2DM. BUT some studies showed invese with other markers e.g. toenail which found lower risk as se rose (Big cohort studies e.g. HPFS, Nurses health study).
One study showed se deficiency linearly associated with hypoglycaemia
in healthy adults.** Se of 88.9ug/L and below, worse the glucose is (wang y et al, 2010)
Meta-analyses of observational studies associating se with T2DM- most did find sig. association between Se an plasma serum/diet/urine levels with diabetes. BUT number found no association or complex non-linear or inverse with increasing Se(risk drops then rises again). With very low Se, low glucose.
Observational study- selenium in 3rd trimester, as selenium drops, GDM goes down. As GPX activity drops, LGA increases.= Se not concern in pregnancy
Meta-analyses of RCTs: SELECT study in men.no sig. effect on risk of T2DM and effect size reduced after 2008 as number of cases rose. Larger study and more important than NPC trial which showed +ve association.
SELECT - Trial stopped early and no sig. risk of T2DM in se group compared to placebo and 3 years later no effect of se on group risk T2DM =
se DOES NOT INCREASE T2DM (
all men had high se at baseline- already above threshold risk so that further treatment with Se made no or little difference?)
of 5 trials,
only SELECT carried out in healthy people, others were carried out in people with cancer or high risk (unhealthy population group confounding).
NPC people all worked on farms using arsenic as pesticide and had keratosis (indicating arsenic poisoning) which increases risk of T2DM shown in large study (NHANES)
Selenium toxicity
Selenosis- toxic selenium- causes dermatitis, increases skin cancer risk, increased mortality, risk of T2DM , garlic breath, skin lesions, brittle/thick nails , numbness and convulsions and paralysis
U.S. tolerable upper intake 400ug/day but this is too high. EFSA statement suggest 270ug/day?
SELECT: those in top 40% at baseline had higher risk of prostate cancer (toenail measruement)
NPC trial: se supplemented group has increase risk of squamous cell carcinoma, total non-melanoma skin cancer (started with history of non-melanoma skin cancer)
NHANES (National Health and Nutrition Examination Survey)- u-shaped risk of death =death greater at low and high selenium status
Long term se supplementation on mortality: RCT. Danish PRECISE Trial. Followed-up=all-cause mortality increased with 300ug/day compared to placebo. lower than placebo with 100-200ug/day for 5 years. Those with higher se at baseline worse off. current smokers died less often as smoking raises tollerance to selenium
200ug/day supplementation safe unless high se intake e.g. countries like venzuela, Japan and N America (alkaline soil)