POPs and Diabetes-Please Share Widely!
john
From: Joe
DiGangi [mailto:dig...@environmentalhealthfund.org]
Sent: August 11, 2006 8:26 AM
To: ipenn...@npogroups.org
Subject: [ipenlistserve]
US: POPs and
Diabetes
“Another striking finding in Lee and co-workers' study is that there was no association between obesity and diabetes in individuals with non-detectable levels of persistent organic pollutants. Obesity was a risk factor for diabetes only if people had blood concentrations of these pollutants above a certain level. This finding might imply that virtually all the risk of diabetes conferred by obesity is attributable to persistent organic pollutants, and that obesity is only a vehicle for such chemicals. This possibility is shocking.”
The Lancet
August 12, 2006
Persistent
organic pollutants and the burden of diabetes
Miquel Porta
a, b, mpo...@imim.es
Studies from the USA1,2 have drawn
attention to the possibility that persistent organic pollutants might contribute
to cause diabetes.3-6 Dioxins, polychlorinated biphenyls,
dichlorodiphenyldichloroethylene (DDE, the main degradation product of the
pesticide dichlorodiphenyltrichloroethane [DDT]), trans-nonachlor,
hexachlorobenzene, and the hexachlorociclohexanes (including lindane) are some
of the persistent organic pollutants most commonly found in human beings.7,8
Lipophilic and highly resistant to degradation, these pollutants are present in
many fatty foods, usually at low concentrations.9 Because they contaminate
virtually all people, even if they confer only a low individual risk of
diabetes, these pollutants might have a substantial overall population effect.10
Dae-Hee Lee and colleagues' recent study1 is the first to analyse serum
concentrations of persistent organic pollutants and fasting plasma-glucose
concentrations in a random sample of a general population. Previous studies have
focused on selected populations, often occupationally or accidentally exposed to
high levels of such pollutants. Not studying a less-exposed group might have led
to a blurring of risks. Widely prevalent exposures are particularly difficult to
isolate as causal agents.3 Concentrations of persistent organic pollutants in
the study are typical of levels in many societies globally, and the risk of
diabetes seems higher than ever. After adjustment for age, sex, race, income,
lipids, body-mass index, and waist circumference, Lee and colleagues showed that
the prevalence of diabetes was more than five times higher in groups with higher
concentrations of polychlorinated biphenyl 153, oxychlordane, or trans-nonachlor
than in those with lower concentrations. The prevalence of diabetes doubled and
tripled in those in the upper quintiles of DDE and other compounds.1
Lee
and co-workers adjusted their results by multiple factors.1 Such adjustment is
fine if we wish to isolate the "pure" effect of persistent organic pollutants on
diabetes separately from that of obesity, age, or income. However, adjustment by
body-mass index and waist circumference might be an overadjustment, because
dietary fats are the main source of persistent organic pollutants for human
beings, and the body burden of these lipophilic chemicals often increases with
increasing body-mass index. Crude or less adjusted prevalence odds ratios would
provide information about the actual prevalence of diabetes in people with
specific concentrations of these pollutants. Indeed, a priority should be to
assess the validity of the study's1 main finding: diabetes might be several
times more prevalent in people with higher concentrations of these pollutants
than in those with lower or no detectable levels. Causal inferences need to be
extremely cautious. The cross-sectional nature of Lee's study, in particular,
prompts assessment of the direction of the association: might diabetes cause a
higher accumulation of persistent organic pollutants? Unfortunately, data for
the toxicokinetics of these pollutants in patients with diabetes are scarce,
while many studies indicate that most persistent organic pollutants are
resistant to active metabolism.1,7,8 Even if diabetes is some day shown to be
the first major disease favouring accumulation of persistent organic pollutants,
patients and clinicians would need to cope with the consequences: individuals
with diabetes would be more likely to experience the adverse effects of these
pollutants.6
Another striking finding in Lee and co-workers' study is
that there was no association between obesity and diabetes in individuals with
non-detectable levels of persistent organic pollutants. Obesity was a risk
factor for diabetes only if people had blood concentrations of these pollutants
above a certain level. This finding might imply that virtually all the risk of
diabetes conferred by obesity is attributable to persistent organic pollutants,
and that obesity is only a vehicle for such chemicals. This possibility is
shocking. Standard measures were used for body-mass index, but weight changes
were not considered. Weight gains and weight losses in individuals with and
without diabetes will be difficult to measure in large studies. But cohort
studies with repeated measurements of individual weight and blood could help
solve the puzzle.
An association between diabetes and blood
concentrations of polychlorinated biphenyls has also been reported in a study
from Michigan.2 Although the study was prospective, diabetes was self-assessed
and participants had had accidental food contamination 30 years previously.
Women in groups with higher serum concentrations of polychlorinated biphenyls
had a twofold increased incidence of diabetes (again adjusted by several
factors, including age and body-mass index). The crude incidence also doubled in
men with the highest levels of polychlorinated biphenyls, but adjusted results
were non-significant.
Exposure to many persistent organic pollutants has
fluctuated in the past 60 years: birth cohort and period effects are plausible.
But time-series and age-period cohort analyses of the potential link between
persistent organic pollutants and diabetes are not available. Ecological and
individual-based studies would allow estimations to be made of the fraction of
diabetes that is influenced by persistent organic pollutants, other
environmental agents, genetic factors such as susceptibility haplotypes, and by
their interactions.3-6
The causal role of persistent organic pollutants
in diabetes is more likely to be contributory and indirect-eg, through
immunosuppressant, non-genotoxic, perhaps epigenetic mechanisms.3-7,11,12 A
proper understanding of how genes and persistent organic pollutants interact to
cause diabetes is important both for primary prevention and to advance basic
knowledge on diabetogenic mechanisms. When assessing the mechanisms linking
diet, fat intake, obesity, and diabetes, persistent organic pollutants should
also be considered. We need a better understanding of the burden of diabetes
that these pollutants might contribute to cause.
I declare that I have no
conflict of interest.
NOTES: AFFILIATION:
a Institut Municipal
d'Investigació Mèdica, Universitat Autònoma de Barcelona, E-08003 Barcelona,
Spain;
b University of North Carolina, Chapel Hill, North Carolina,
USA
References
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strong dose-response relation between serum concentrations of persistent organic
pollutants and diabetes: results from the national health and examination survey
1999-2002, Diabetes Care, Vol. 29, 2006, p. 1638-1644, .
2 O Vasiliu, L
Cameron, J Gardiner, P DeGuire, W Karmaus, Polybrominated biphenyls,
polychlorinated biphenyls, body weight, and incidence of adult-onset diabetes
mellitus, Epidemiology, Vol. 17, 2006, p. 352-359, .
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Zimmet, The rising tide of childhood type 1 diabetes: what is the elusive
environmental trigger?, Lancet, Vol. 364, 2004, p. 1645-1647, .
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Daneman, Type 1 diabetes, Lancet, Vol. 367, 2006, p. 847-858, .
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Remillard, NJ Bunce, Linking dioxins to diabetes: epidemiology and biologic
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8 Department of Health and Human Services, Centers for Disease Control
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Vol. 59, 2002, p. 651-652, .
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12 P
Alonso-Magdalena, S Morimoto, C Ripoll, The estrogenic effect of bisphenol A
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Environ Health Perspect, Vol. 114, 2006, p. 106-112,
.