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Experimental evidence from animal models suggests that supplementation with low doses of the antioxidant selenium may exert beneficial effects on glucose metabolism, possibly through many insulin-like actions, and may delay complications of diabetes.

The effects of high-dose selenium supplements, however, are less clear (7–10). MAX (Supplementation with Antioxidant Vitamins and Minerals) study (13) showed no effect of supplementation with a combination of antioxidants, including selenium (100 μg/d), on fasting plasma glucose levels after 7.5 years of follow-up.

Self-reported adherence indicated that 79.3% of participants (80.3% in the placebo group and 78.4% in the selenium group) adhered to the intervention (16).

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As a result, almost all participants in the NPC trial were non-Hispanic white persons; about 1.4% ( = 18) of persons who were randomly allocated were identified as Hispanic, and some persons were from other ethnic groups.

Although recruitment was sex-neutral, about three quarters of the participants were male.

We analyzed only participants with a valid baseline selenium value obtained within 4 days from the date of randomization (1250 of 1312 participants), a decision that is consistent with previously published studies from the NPC trial (15–17).

Baseline characteristics of the total NPC cohort of 1312 participants and the subsample of 1250 participants with valid baseline selenium levels did not statistically significantly differ (17), and our findings did not change substantially when analyses were expanded to include all 1312 participants (data not reported).

Of the 1316 persons recruited, random assignment was successful for 1312.

At the end of the blinded treatment period on 1 February 1996, no participant was lost to vital follow-up, generating a total of 9301 person-years of follow-up.

An exposure–response gradient was found across tertiles of baseline plasma selenium level, with a statistically significantly increased risk for type 2 diabetes in the highest tertile of baseline plasma selenium level (hazard ratio, 2.70 [CI, 1.30 to 5.61]).

Insulin resistance, impaired glucose tolerance, and type 2 diabetes are all linked to oxidative stress, which may be the pathogenic mechanism that links these conditions to cardiovascular disease (1).

The placebo group received a tablet containing yeast only.

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