A prospective study of dietary selenium intake and risk of type 2 diabetes
Saverio Stranges
0
Sabina Sieri
2
Marco Vinceti
1
Sara Grioni
2
Eliseo Guallar
5
6
Martin Laclaustra
5
6
Paola Muti
4
Franco Berrino
3
Vittorio Krogh
2
0
Health Sciences Research Institute, University of Warwick Medical School
,
Coventry
,
UK
1
Department of Public Health Sciences, University of Modena and Reggio Emilia
,
Modena
,
Italy
2
Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori
,
Milan
,
Italy
3
Etiological and Preventive Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori
,
Milan
,
Italy
4
Epidemiology and Prevention Unit, Regina Elena Italian National Cancer Institute
,
Rome
,
Italy
5
Department of Cardiovascular Epidemiology and Population Genetics, National Center for Cardiovascular Research (CNIC)
,
Madrid
,
Spain
6
Departments of Epidemiology and Medicine, and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Bloomberg School of Public Health
,
Baltimore, MD
,
USA
Background: Growing evidence raises concern about possible associations of high selenium exposure with diabetes in selenium-replete populations such as the US. In countries with lower selenium status, such as Italy, there is little epidemiological evidence on the association between selenium and diabetes. This study examined the prospective association between dietary selenium intake and risk of type 2 diabetes. Methods: The ORDET cohort study comprised a large sample of women from Northern Italy (n = 7,182). Incident type 2 diabetes was defined as a self-report of a physician diagnosis, use of antidiabetic medication, or a hospitalization discharge. Dietary selenium intake was measured by a semi-quantitative food-frequency questionnaire at the baseline examination (1987-1992). Participants were divided in quintiles based on their baseline dietary selenium intake. Results: Average selenium intake at baseline was 55.7 g/day. After a median follow-up of 16 years, 253 women developed diabetes. In multivariate logistic regression analyses, the odds ratio for diabetes comparing the highest to the lowest quintile of selenium intake was 2.39, (95% CI: 1.32, 4.32; P for linear trend = 0.005). The odds ratio for diabetes associated with a 10 g/d increase in selenium intake was 1.29 (95% CI: 1.10, 1.52). Conclusions: In this population, increased dietary selenium intake was associated with an increased risk of type 2 diabetes. These findings raise additional concerns about the association of selenium intake above the Recommended Dietary Allowance (55 g/day) with diabetes risk.
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Background
Selenium is a key component of a number of
selenoproteins involved in essential enzymatic functions, such as
redox homeostasis, thyroid hormone metabolism,
immunity and reproduction [1]. Because of antioxidant
properties of selenoproteins, and because selenate mimics
insulin activity in experimental models [2,3], selenium
was expected to prevent type 2 diabetes and
cardiovascular disease (CVD) [4]. However, recent findings from
observational studies and randomised clinical trials have
raised concerns with respect to possible adverse
cardiometabolic effects of high selenium exposure, at least in
well-nourished populations. Specifically, several unrelated
studies from the US indicate that high selenium status or
selenium supplementation is associated with an increased
diabetes risk [5-8]. Furthermore, recent evidence from
several populations indicates that high selenium exposure
may also be associated with an adverse lipid profile [9-12]
and hypertension [13], raising additional concerns about
metabolic toxicity of high selenium exposure and
prolonged use of selenium supplements [14].
Dietary intake of selenium varies considerably between
countries and regions largely due to the variability of
the selenium content of soil and hence of plant foods
and animal forage [15]. Current recommendations on
selenium intake are based on optimizing the activity of
plasma glutathione peroxidases, which are maximized at
intakes as high as 55 g/day [16]. In the US, selenium
intake ranges from 60-220 g/day [8,12,13,15] and it is
unclear if there are health benefits of increased selenium
intake above the Recommended Dietary Allowance
(RDA), or if metabolic toxicity might occur at these
levels. Selenium intakes in Europe are lower than in the
US, but with large between-country variability ranging
from adequate or marginally adequate (Western and
Central Europe: 30-90 g/day) to low or deficient intake
(Eastern European countries: 7-30 g/day) [15].
There is little epidemiological evidence on the
association of selenium with diabetes among European
populations [17,18]. The objective of the present study was
thus to examine the association of dietary selenium
intake with risk of incident type 2 diabetes in the
ORDET cohort study, a large sample of women from
Northern Italy [19].
Methods
Study population
The ORDET study (HORmones and Diet in the
ETiology of Breast Cancer) is an ongoing prospective
follow (...truncated)