www.thelancet.com Vol 371 January 26, 2008 287
Environmental pollution and diabetes: a neglected association
Using cross-sectional data from the 1999–2002 US
National Health and Examination Survey, Duk-Hee Lee
and colleagues1,2 reported a strong correlation between
insulin resistance and serum concen trations of persis-
tent organic pollutants, especially for organochlorine
com pounds. This result was a surprise for many people
working in diabetes research, because most studies
to date have focused on the eff ects of genetics and
the westernisation of dietary habits and lifestyle,
while ignoring the potential eff ect of xenobiotics.
Nevertheless, as discussed by Porta,3 an increasing
number of reports suggest that chronic dietary expo-
sure to, and accumulation of, low concentrations
of environmental pollutants within the body might
also be associated with diabetogenesis. Ignoring the
potential eff ects of xenobiotics therefore risks ignoring
a potentially crucial component in the study of type 2
diabetes, obesity, and the metabolic syndrome.
Lee and co-workers note two important fi ndings
related to obesity. The fi rst was that the expected
association between obesity and diabetes was absent
in people with low concentrations of persistent organic
pollutants in their blood. The second was that the
association between obesity and diabetes became
stronger as the concentrations of such pollutants in
the blood increased. Interestingly, this report is not
the fi rst time that the presence of persistent organic
pollutants and other organochlorine compounds in
blood have been associated with diabetes. Rylander
and colleagues4 analysed the concentrations of
2,2’,4,4’,5,5’-hexachlorobiphenyl (CB-153) and 1,1-
dichloro-2,2-bis (p-chlorophenyl) -ethylene (p,p’-DDE,
a breakdown product of DDT) in the serum of 196 men
and 184 women in a fi shing community in Sweden.
Both compounds showed a strong association with the
occurrence of diabetes. Much the same results were seen
in a population-based study in Belgium.5 Studies of US
Air Force veterans of the Vietnam War exposed to Agent
Orange also suggest an adverse relation between dioxin
exposure and symptoms of diabetes.6–8
The potential of xenobiotics to disrupt glucose and lipid
metabolism in mammals is a well-developed theory in
toxicology. Indeed, many of the early toxicity responses
in animal studies with a range of pollutants note
glucosuria, dyslipidaemia, increased gluconeogenesis,
and fatty liver.9 The versatility of high-throughput
screening in metabolomics and metabonomics is an
especially useful way of monitoring metabolic changes
caused by disease or exposure to toxicants (eg, heavy
metals) in animal models.10 Although most studies have
tested acute exposure (ie, less than 2 weeks), in the few
chronic exposure studies (ie, more than 3 months),
glucosuria was recorded as long-term eff ect.11 This result
suggests that diabetes could be exacerbated by chronic
exposure to xenobiotics that disrupt normal metabolism
of glucose and lipids.
Although correlation does not necessarily prove the
existence of a causal relation, biologically plausible
ex plan ations exist for this association.12 For instance,
dioxin-like compounds exert their eff ects through
binding to the aryl-hydrocarbon receptor. This receptor is
thought to antagonise peroxisome proliferator-activated
receptors.12 One plausible hypothesis, there fore, is that
the aryl-hydrocarbon receptor promotes dia beto gen-
esis by antagonism of peroxisome proliferator-activated
receptors. However, no data are avail able to support this
See Correspondence page 302
US Air Force planes spray the defoliant chemical Agent Orange over
South Vietnam, 1966
The printed journal
includes an image merely
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www.thelancet.com Vol 371 January 26, 2008
argument. Some chemicals disrupt the ability of the body
to metabolise fats directly, thereby inducing symptoms,
such as weight gain, that can lead to diabetes. For
instance, the poly aromatic hydrocarbon benzo[a]pyrene
impairs lipolysis in adipose tissue, causes weight gain in
mice, and pro foundly impairs catecholamine-induced
lipolysis in murine and human adipocytes.13
Although little direct experimental evidence links
exposure to persistent organic pollutants and the
onset of diabetes, their epidemiological association is
increasingly well defi ned. The public-health implications
of such an association could be substantial. Thus, further
investigation of the possible relation between diabetes
and environmentally relevant levels of exposure to
persistent organic pollutants in the general population
is merited, but this subject is much neglected. Clinical,
toxicological, and epidemiological studies are all
needed, in particular those that integrate several levels
of evidence over a long period. However, at present,
few laboratories seem willing to commit resources to
the long-term longitudinal studies needed for such
*Oliver A H Jones, Mahon L Maguire, Julian L Griffi n
Department of Biochemistry, Hopkins Building, University of
Cambridge, Cambridge CB2 1QW, UK (OAHJ, JLG); and British
Heart Foundation Magnetic Resonance Unit, Department of
Cardiovascular Medicine, Wellcome Trust Centre for Human
Genetics, University of Oxford, Oxford OX3 7BN, UK (MLM)
Retraction—A growing, bleeding, violet mole
On Oct 13, 2007, The Lancet published a Case Report
by Michael Sand and Falk Bechara on cutaneous
endometriosis.1 We accepted the paper after having
been informed in writing, by the authors, that it had
not been submitted for publication elsewhere. In fact,
however, the same case had already been reported by the
same authors in Muenchener Medizinische Wochenschrift
Fortschritte der Medizin, a German medical journal.2 We
were alerted to this fact by Prof Benno Mann, who was a
coauthor of the paper published in German but who was
not named as an author of the paper we published and
was unaware of the decision to submit the paper to us.
Because the Case Report in The Lancet is a duplicate
publication, we retract it in full.
The Lancet, London NW1 7BY, UK
1 Sand M, Bechara FG. A growing, bleeding, violet mole. Lancet 2007;
2 Sand M, Bechara FG, Mann B. Nodules in the navel: from time to time
comes bloody secretion. MMW Fortschr Med 2007; 149: 5 (in German).
Our research is fi nancially supported by the European Union. JLG is supported by
the Royal Society (UK) and MLM is funded by the Medical Research Council (UK).
We declare that we have no confl ict of interest.
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