Family Forum / Parenting / Children's Health / November 2008

diabetes and POPS (persistent organic pollutants: dioxins, PCBs, BPA),
DH Lee, DR Jacobs, YL Guo, ED Rosen, and other recent studies -- is
formaldehyde from the 11% methanol part of aspartame a co-factor?
Murray 2008.09.22
http://rmforall.blogspot.com/2008_09_01_archive.htm
Monday, September 22, 2008
http://groups.yahoo.com/group/aspartameNM/message/1560

"...in people with the highest combined levels of all six POPs
the rate of diabetes was a massive 38 times greater than
in those with the lowest levels..."

From: <peter@rachel.org>
Date: Thu, Sep 18, 2008 at 6:28 PM
Subject: Rachel's #977: Chemicals and Diabetes
^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^

Rachel's Democracy & Health News #977
"Environment, health, jobs and justice -- Who gets to decide?"
Thursday, September 18, 2008
www.rachel.org
^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^

From: New Scientist (pg. 36), Sept. 10, 2008

COULD THE DIABETES EPIDEMIC BE DOWN TO POLLUTION?

By Phyllida Brown

On July 10, 1976, a reactor at a chemical plant near the small town of
Seveso in northern Italy exploded, sending a toxic cloud drifting into
the summer sky. Around 18 square kilometres of land was contaminated
with TCDD, a member of the notorious class of industrial chemicals
known as dioxins.

The immediate after-effects were relatively mild: 15 children landed
in hospital with skin inflammation and around 3300 small animals were
killed. Today, however, the accident casts a long shadow over the
people of Seveso, who are suffering increased numbers of premature
deaths from cancer, cardiovascular disease and, perhaps surprisingly,
diabetes (American Journal of Epidemiology, vol 167, p 847).

To some diabetes researchers, Seveso serves as a warning to us all.
Ask why diabetes is epidemic in the 21st century and most people will
point the finger at bad diet, laziness and obesity. According to a
small but growing group of scientists, though, the real culprit is a
family of toxic chemicals known as persistent organic pollutants, or
POPs. If these researchers are right, POPs -- which include some of
the most reviled chemicals ever created, including dioxins, DDT and
PCBs -- may be key players in the web of events that lead people to
develop the disease.

The claim has yet to attract widespread attention from mainstream
diabetes research. Even its champions were initially surprised by it.
"I had never even heard of POPs until 2005," says Duk-Hee Lee, an
epidemiologist at Kyungpook National University in Daegu, Korea, who
led the work. Lee and her co-workers are now convinced, albeit
reluctantly, that they are onto something. "The hypothesis is one that
I wish were not true," says her colleague David  R. Jacobs of the
University of Minnesota, Minneapolis.

[ http://news.bbc.co.uk/2/hi/health/6544709.stm ]

Diabetes, and particularly its commonest form, type 2 (see "Sidebar:
Diabetes basics"), is practically everyone's business. The World
Health Organization estimates that it already affects 180 million
people worldwide, with the number predicted to more than double by
2030. Last year the epidemic cost $174 billion in the US alone,
according to the American Diabetes Association.
========================================================

Sidebar: Diabetes basics

Diabetes has two main forms: type 1 and type 2. About 90 per cent of
diabetics have type 2.

Type 1 diabetes is an autoimmune disease in which insulin-producing
cells in the pancreas are progressively destroyed.

Type 2 diabetes usually develops in adulthood, although it is now
increasingly common in children. In this form, the pancreas either
produces too little insulin, or cells in the liver, muscles and fat
tissues fail to use it properly. Type 2 is most common in inactive,
overweight people who carry their fat on their midriff.
========================================================

The standard explanation for type 2 diabetes is that it is a
"lifestyle disease" caused by laziness and gluttony. For at least a
decade, however, epidemiologists have known that people briefly
exposed to high concentrations of POPs face a modest increase in their
risk of developing diabetes later in life. Those affected include the
people of Seveso and US veterans who were exposed to dioxin-
contaminated Agent Orange during the Vietnam war.

Two years ago, Lee, Jacobs and others decided to see whether everyday
exposure to POPs is also linked to diabetes. To their surprise and
horror, they found that it is.

For most people, POPs are inescapable: meat, fish and dairy products
all contain them. They enter the food chain from sources such as
pesticides, chemical manufacturing and incinerated waste, and
accumulate in animals higher up in the chain. Once in the body they
take up residence in fat.

POPs have long been recognised as nasty substances: their effects
include birth defects, cancer, immune dysfunction and endocrine
disruption. Since the 1970s, various measures have been put in place
to phase them out -- 12 of the worst POPs, known as the "dirty dozen",
were banned in 2004 -- but despite these efforts, POPs remain a
significant presence in the environment and food chain, partly because
many are still in use in the developing world, and partly because
these chemicals can take decades to break down.

Role of fat

Prior to her 2005 introduction to POPs, Lee was working on a humble
enzyme called gamma-glutamyltransferase (GGT), which is essential for
maintaining antioxidant levels in the liver. She was puzzled to find
that obesity combined with an elevated level of GGT is a strong
predictor of diabetes, but obesity alone isn't. "I searched the
literature and finally got an idea," she says.

As it turns out, GGT has an essential role to play in removing some
pollutants, including POPs, from inside cells (Diabetologia, vol 51, p
402). Could increased GGT activity simply be a marker of exposure to
POPs?

To find out, Lee and her colleagues analysed data from more than 2000
people in the US National Health and Nutrition Examination Survey
(NHANES), which measured both diabetes status and bloodstream levels
of POPs, among other things. They discovered that people with high
levels of six different POPs in their bloodstream were much more
likely to have diabetes, regardless of obesity (see diagram). The six
POPs were chosen because they were detectable in at least 80 per cent
of the participants.

Taking into account factors such as weight, age, waist circumference
and ethnic group, Lee calculated that in people with the highest
combined levels of all six POPs the rate of diabetes was a massive 38
times greater than in those with the lowest levels (Diabetes Care, vol
29, p 1638). "The people who disagree with us will say it's all
noise," says Jacobs, "but it's pretty hard to get odds ratios of 38
with noise."

To her even greater surprise, Lee found that in people with
undetectable levels of POPs the expected link between diabetes and
body weight melted away -- those who were obese were no more likely to
have diabetes than their lean counterparts. "This suggests that POPs
may be a more fundamental factor in the risk of diabetes than
obesity," says Lee. "The absolute risk of diabetes was extremely low
among subjects with very low concentrations of POPs."

"The expected link between diabetes and body weight melted away" But
fat is not off the hook just yet. While obesity alone appears not to
be linked with diabetes, the study suggests that POPs plus obesity is
bad news, and the fatter you are the worse it gets. When the
researchers examined the link with body mass index, they found that in
people with high levels of POPs the odds of being diabetic were much
higher for the obese than the lean. This suggests that something about
excess fat may be enhancing the toxicity of POPs. "It appears that
obesity can increase the harmful effects," says Lee.

Of course, the findings do not prove that POPs cause diabetes. "This
is an association between two things, not direct evidence of a causal
link," warns Oliver Jones, an environmental biochemist at the
University of Cambridge. The idea deserves further investigation,
though, he says.

Lee and her colleagues acknowledge that their interpretation could be
stood on its head. If diabetes causes the body to become less
efficient at dealing with POPs, then higher levels of POPs in people
with diabetes could be an effect of the disease, rather than its
cause. Lee does not rule out this possibility, but thinks it unlikely.
She points to a 2003 study by other researchers that found no
relationship between diabetes and the rate at which POPs are
eliminated from the body (Journal of Toxicology and Environmental
Health, vol 66, p 211).

The team also examined the link between POPs and a metabolic disorder
called insulin resistance, in which muscle, fat and liver cells fail
to use insulin properly and which often progresses to full-blown
diabetes. Once again, they found that people whose blood contained the
highest levels of POPs were most likely to have insulin resistance
(Diabetes Care, vol 30, p 622). The results add weight to the idea
that POPs may be playing a vital role in the disease pathway from
insulin resistance to diabetes, says Lee. "I am really excited about
this."

Even so, she acknowledges two obvious objections to her work. First,
while levels of POPs in the blood of Americans have been falling for a
couple of decades, the diabetes epidemic is just taking off. Lee
suggests that as obesity seems to make POPs more dangerous, its rising
prevalence may have cancelled out any health improvements that should
have followed the decline in POPs.

A second question is why, if POPs are central to diabetes, the
incidence of the disease is soaring not only in the meat-addicted west
but also in countries such as India, where many millions are
vegetarian. Lee's answer is that, while many POPs are banned in the
west, some are still used as pesticides in developing countries. "The
highest rate of increasing risk of type 2 diabetes is observed in Asia
and Africa, not North America with the highest obesity rate," she
says.

To try to slot POPs into the complex diabetes jigsaw, it is worth
taking a brief step into the mainstream to look at the role of fats,
or lipids, in the disease. Type 2 diabetes was once seen mainly as a
disorder of glucose metabolism. Now, says diabetes researcher Evan
Rosen of Beth Israel Deaconess Medical Center in Boston, the focus has
shifted, with many scientists considering that the primary problem
lies with the metabolism of fats.

For years, physiologists largely ignored fat cells, or adipocytes,
seeing them as little more than passive energy silos. Recently,
though, they have been revealed for what they are: highly active in
producing both hormones that regulate energy, and inflammatory
messenger chemicals that are important to the immune system (New
Scientist, 16 September 2000, p 36). If adipocytes malfunction, the
consequences can be widespread.

When we eat energy-rich foods, our bodies have to store any excess
energy not burned up by physical activity. Most is stored as fat in
adipocytes, but when these eventually fill up, excess lipid spills
over into other tissues, particularly the liver, muscles and the area
around the heart. The presence of this "ectopic fat" has been linked
to all sorts of health problems, including insulin resistance and
diabetes.

Just how might ectopic fat help to trigger diabetes, though? There is
no simple answer and researchers still disagree about the possible
mechanism. However, there are some clues.

In animals ectopic fat is known to attract the attention of the immune
system, which produces inflammatory messenger chemicals around it as
though it were an infection. Interestingly, people with diabetes have
chronically raised levels of these inflammatory chemicals, raising the
question of whether inflammation caused by ectopic fat could be a
factor in the disease.

Ectopic fat also causes problems when muscle cells try to burn it to
generate energy. In obese people this is a highly inefficient process,
probably because their mitochondria -- the cell's power plants -
function at a reduced capacity, says Rosen. Mitochondria in muscle
cells are already known to work less efficiently in people with
diabetes, and this year a team at Helsinki University Central Hospital
in Finland found similar changes in obese people with no symptoms of
diabetes (American Journal of Physiology -- Endocrinology and
Metabolism, vol 295, p E148)."You end up with a half-burned lipid,"
says Rosen.

He speculates that this half-burned lipid acts like a magnet for
reactive oxygen species (ROS), including free radicals and peroxides,
which then inflict damage to the muscle cells themselves. There is now
clear evidence that chronic damage from ROS -- known as oxidative
stress -- helps to drive cells into insulin resistance. "If you block
ROS, you can block insulin resistance," says Rosen.

If Lee is right, however, and POPs are at the root of diabetes, these
ideas tell only half the story. So how might POPs be involved? Again,
there are tantalising hints. Jones points out that POPs are known to
bind to a family of receptors on cell nuclei known as PPARs. These are
involved in lipid metabolism and are known not to work properly in
people with diabetes; the diabetes drug troglitazone works by
activating one member of the family, PPAR-gamma. People with an
inherited disorder of this receptor are unusually prone to insulin
resistance. Another intriguing link is that POPs are known to cause
mitochondrial dysfunction, which some researchers think is the root
cause of diabetes (Science, vol 307, p 384).

But none of this explains how POPs interact with obesity. It may be
that obese people simply have a higher load of POPs in their bodies.
Another possibility is that POPs in ectopic fat are particularly
dangerous. Perhaps, speculates Lee, adipocytes are a relatively safe
storage site for POPs. "Our body has to find some place to store
them," she says, "and in this sense, adipose tissue is a relatively
safe organ." The trouble might start when POP-contaminated ectopic fat
starts to build up in the muscles and liver, exposing the organs to a
direct toxic assault. "That way, the harmful effects of POPs could
become more serious," Lee suggests.

Clearly more work is needed to establish the precise link between POPs
and diabetes. For Jones, it is surprising that Lee's research has
remained relatively neglected, especially given its public health
implications. He does note, though, that other teams are starting to
investigate the hypothesis. Julian Griffin and others at Cambridge
have found that low-level mixtures of POPs can cause metabolic
disturbances similar to those seen in type 2 diabetes.

Rosen stresses that the lack of attention given to this research
should not be seen as an indictment of the work, but instead reflects
how deeply scientists specialise in their own areas. "We generally
stay inside our silos," he says. "It's incredibly difficult to move
outside of them." Another problem, says Jacobs, is that testing the
hypothesis to destruction would require complex and long-term studies
of the type that funding bodies are often reluctant to commit money
to.

If Lee is right, it is not good news for the diabetes epidemic. Even
though many POPs are being phased out, they will take decades to clear
from the food chain. Meanwhile, newer POPs such as brominated flame
retardants continue to be manufactured in large quantities.

There is perhaps one silver lining. If you need an extra incentive to
stay lean, eat less meat and keep active, then knowing that toxic
chemicals lurking in your body fat could be a sure route to diabetes
might just be the motivation you're looking for.
==============

Phyllida Brown is a writer based in Exeter, UK
pbrown@brixworks.freeserve.co.uk;
Copyright Reed Business Information Ltd.

From: Reuters health, Aug. 15, 2008
[Printer-friendly version]

HIGH PCB EXPOSURE TIED TO DIABETES RISK

NEW YORK (Reuters Health) -- People who have been exposed to high
levels of toxic polychlorinated biphenyls (PCBs) may face an elevated
risk of type 2 diabetes, a new study shows.

The findings, reported in the journal Diabetes Care, come from a
long-term study of Taiwanese adults who, in the 1970s, had been
poisoned by cooking oil contaminated with PCB pollutants.

Once used in products ranging from fluorescent lights and appliances
to insulation and insecticide, PCBs were banned in the late 1970s as
carcinogens and general health hazards. They linger in the
environment, however.

In the new study, Dr. Yueliang Leon Guo, from the National Taiwan
University in Taipei, and colleagues examined the incidence of type 2
diabetes among 378 Taiwanese "oil disease" victims and 370 of their
neighbors who had not been poisoned.

They found that women who had been exposed to the PCB-laced oil were
twice as likely as other women to develop type 2 diabetes over 24
years. And women who had been most severely affected by the PCB
exposure had a more than five-times higher diabetes risk.

There were no similar risks seen in men, however.

Other studies have found that people with diabetes tend to have
relatively higher levels of organic pollutants, such as PCBs, in their
blood. In comments to Reuters Health, Guo said that since "everyone"
has detectable PCB levels in his or her body, it's possible that
exposure to such pollutants has helped feed the widespread rise in
diabetes in recent decades.

"The public health implication of these findings can be huge," Guo
added, "considering the burden of diabetes and its multiple long-term
complications."

SOURCE: Diabetes Care 2008, August 2008.

Copyright 2008 Reuters Limited

From: The Telegraph (London, U.K.), Sept. 9, 2008
[Printer-friendly version]

POLLUTION LINKED TO OBESITY, NEW STUDY FINDS

By Chris Irvine

Pollution could determine whether a child is fat or not before they
have even been born, a new study has found.

Exposure to a range of common chemicals before birth increases the
chance of a baby to growing up overweight or obese, the research
indicates.

The study by scientists at Barcelona's Municipal Institute of Medical
Research is the first to link obesity with chemical contamination in
the womb, where humans are most vulnerable.

A quarter of all British adults and a fifth of children suffer from
obesity, with at least 300 million obese worldwide.

Published in the current issue of the journal Acta Paediatrica, the
research measured levels of hexachlorobenzene (HCB) in the umbilical
cords of 403 children born on the Spanish island of Menorca.

HCB is a pesticide banned internationally but which continues to
remain in the environment and can be found in food.

Those with the highest levels of HCB were twice as likely to be obese
when they reached the age of six and a half.

The report's authors are now calling for exposure to similar
pesticides to be minimised, including bisphenol A (BPA), used in baby
bottles and cans of food, and phthalates, found in cosmetics and
shampoos.

Tests have shown BPA is found in 95 per cent of Americans, while 90
per cent have been found to be exposed to phthalates in the womb.

Dr Pete Myers, chief scientist at the US-based Environmental Health
Sciences, said: "This is very important. It is the first good study of
the effects on the foetus. Its conclusions are not surprising, given
what we know from the animal experiments, but it firmly links such
chemicals to the biggest challenge facing public health today."

The research comes after Conservative leader David Cameron said that
obesity is purely a matter of "personal responsibility".

Copyright of Telegraph Media Group Limited 2008

From: Reuters, Sept. 16, 2008

COMMON PLASTICS CHEMICAL LINKED TO HUMAN DISEASES

London, Sept 16 -- A study has for the first time linked a common
chemical used in everyday products such as plastic drink containers
and baby bottles to health problems, specifically heart disease and
diabetes.

Until now, environmental and consumer activists who have questioned
the safety of bisphenol A, or BPA, have relied on studies showing harm
from exposure in laboratory animals.

But British researchers, who published their findings on Tuesday in
the Journal of the American Medical Association, analyzed urine and
blood samples from 1,455 U.S. adults aged 18 to 74 who were
representative of the general population.

Using government health data, they found that the 25 percent of people
with the highest levels of bisphenol A in their bodies were more than
twice as likely to have heart disease and, or diabetes compared to the
25 percent of with the lowest levels.

"Most of these findings are in keeping with what has been found in
animal models," Iain Lang, a researcher at the University of Exeter in
Britain who worked on the study, told a news conference.

"This is the first ever study (of this kind) that has been in the
general population," Lang said.

Steven Hentges of the American Chemistry Council, a chemical industry
group, said the design of the study did not allow for anyone to
conclude BPA causes heart disease and diabetes.

"At least from this study, we cannot draw any conclusion that
bisphenol A causes any health effect. As noted by the authors, further
research will be needed to understand whether these statistical
associations have any relevance at all for human health," Hentges said
in a telephone interview.

A U.S. Food and Drug Administration panel of outside experts on
Tuesday will hear testimony on health effects from BPA as it reviews a
draft report it issued last month calling BPA safe.

"The study, while preliminary with regard to these diseases in humans,
should spur U.S. regulatory agencies to follow recent action taken by
Canadian regulatory agencies, which have declared BPA a 'toxic
chemical' requiring aggressive action to limit human and environmental
exposures," Frederick vom Saal of the University of Missouri and John
Peterson Myers of the nonprofit U.S.-based Environmental Health
Sciences, wrote in a commentary accompanying the study.

BOTTLES TO UTENSILS

BPA is used to make polycarbonate plastic, a clear shatter-resistant
material in products ranging from baby and water bottles to plastic
eating utensils to sports safety equipment and medical devices.

It also is used to make durable epoxy resins used as the coating in
most food and beverage cans and in dental fillings.

People can consume BPA when it leaches out of plastic into liquid such
as baby formula, water or food inside a container.

In the study, the team said the chemical is present in more than 90
percent of people, suggesting there is not much that can be done to
avoid the chemical of which over 2.2 million tonnes is produced each
year.

The researchers, who will also present their findings at the U.S. FDA
session on Tuesday, added it was too early to identify a mechanism
through which the chemical may be doing harm.

Animal studies have suggested the chemical may disrupt hormones,
especially estrogen.

The researchers also cautioned that these findings are just the first
step and more work is needed to determine if the chemical actually is
a direct cause of disease.

"Bisphenol A is one of the world's most widely produced and used
chemicals, and one of the problems until now is we don't know what has
been happening in the general population," said Tamara Galloway, a
University of Exeter researcher who worked on the study.

Canada's government in April decided BPA was harmful to infants and
toddlers and announced plans to ban some products.

The European Union's top food safety body said in July the amount of
BPA found in baby bottles cannot harm human health.

Rachel's Democracy & Health News (formerly Rachel's Environment &
Health News) highlights the connections between issues that are
often considered separately or not at all.

The natural world is deteriorating and human health is declining
because those who make the important decisions aren't the ones who
bear the brunt. Our purpose is to connect the dots between human
health, the destruction of nature, the decline of community, the
rise of economic insecurity and inequalities, growing stress among
workers and families, and the crippling legacies of patriarchy,
intolerance, and racial injustice that allow us to be divided and
therefore ruled by the few.

In a democracy, there are no more fundamental questions than, "Who
gets to decide?" And, "How do the few control the many, and what
might be done about it?"

As you come across stories that might help people connect the dots,
please Email them to us at dhn@rachel.org .

Rachel's Democracy & Health News is published as often as
necessary to provide readers with up-to-date coverage of the
subject.

Editor:   Peter Montague - peter@rachel.org
____________________________________________________

http://care.diabetesjournals.org/cgi/content/abstract/31/8/1574
full text $ 45

Published online May 16, 2008
Diabetes Care 31:1574-1579, 2008
DOI: 10.2337/dc07-2449
© 2008 by the American Diabetes Association

Epidemiology/Health Services Research
Original Research
Increased Risk of Diabetes and Polychlorinated Biphenyls and Dioxins
A 24-year follow-up study of the Yucheng cohort
Shu-Li Wang, PHD 1,2,
Pei-Chien Tsai, PHD 3,
Chiu-Yueh Yang, PHD 3,4
and Yueliang Leon Guo, MD PHD 5   leonguo@ntu.edu.tw;

1 Division of Environmental Health and Occupational Medicine, National
Health Research Institutes, Miaoli, Taiwan
2 Institute of Environmental Medicine, College of Public Health, China
Medical University Hospital, Taichung, Taiwan
3 Department of Basic Medical Sciences, National Cheng-Kung University
Medical College, Tainan, Taiwan
4 Department of Health Business Administration, Hung-Kuang University,
Taichung, Taiwan
5 Department of Environmental and Occupational Medicine, National
Taiwan University College of Medicine, and National Taiwan University
Hospital, Taipei, Taiwan

Corresponding author: Yueliang Leon Guo, leonguo@ntu.edu.tw;

OBJECTIVE
Polychlorinated biphenyls (PCBs) and polychlorinated dibenzofurans
(PCDFs) are important and persistent organic pollutants (POPs) in
humans.
Recent cross-sectional studies have detected increased concentrations
of serum POPs in diabetic patients.
We aimed to examine the association between previous high exposures to
PCBs and PCDFs and the cumulative incidence of type 2 diabetes and
hypertension.

RESEARCH DESIGN AND METHODS
During the late 1970s, the consumption of rice-bran oil laced with
PCBs poisoned thousands of Taiwanese.
Between 1993 and 2003, we examined 1,054 Yucheng ("oil disease")
victims against neighborhood reference subjects using a protocol
blinded for POP exposure. Here, we report the results derived from 378
Yucheng subjects and 370 matched references.

RESULTS
The diabetes risk to members of the Yucheng cohort relative to their
reference subjects was significantly increased for women (odds ratio
[OR] 2.1 [95% CI 1.1–4.5]) but not for men after considering age, BMI,
cigarette smoking, and alcohol intake.
Yucheng women diagnosed with chloracne had adjusted ORs of 5.5 (95% CI
2.3–13.4) for diabetes and 3.5 (1.7–7.2) for hypertension compared
with those who were chloracne free.

CONCLUSIONS
Yucheng women, who had endured previous exposure to PCBs and PCDFs,
suffered from increased incidences of diabetes, particularly those who
had retained significant levels of pollutant as evident from
chloracne.
When planning treatments against diabetes, the body burden of PCBs and
dioxins should be carefully considered, especially for women.  PMID:
18487481
____________________________________________________

http://care.diabetesjournals.org/cgi/content/abstract/30/3/622?maxtoshow=&HITS=1
0&hits=10&RESULTFORMAT=&author1=Lee%2C+Duk-Hee+&fulltext=Duk-Hee+Lee+&searchid=1
&FIRSTINDEX=0&sortspec=relevance&resourcetype=HWCIT

Diabetes Care 30:622-628, 2007
DOI: 10.2337/dc06-2190
© 2007 by the American Diabetes Association
Pathophysiology/Complications
Original Article
Association Between Serum Concentrations of Persistent Organic
Pollutants and Insulin Resistance Among Nondiabetic Adults
Results from the National Health and Nutrition Examination Survey 1999–
2002
Duk-Hee Lee, MD, PHD 1,  lee_dh@knu.ac.kr;
In-Kyu Lee, MD, PHD 2,
Soo-Hee Jin, PHD 1,
Michael W. Steffes, MD, PHD 3  steff001@umn.edu;
and David R. Jacobs, Jr., PHD 4,5      jacob004@umn.edu;

1 Department of Preventive Medicine and Health Promotion Research
Center, School of Medicine, Kyungpook National University, Daegu,
Korea
2 Department of Endocrinology, School of Medicine, Kyungpook National
University, Daegu, Korea
3 Department of Laboratory Medicine and Pathology, University of
Minnesota, Minneapolis, Minnesota
4 Division of Epidemiology, School of Public Health, University of
Minnesota, Minneapolis, Minnesota
5 Department of Nutrition, University of Oslo, Oslo, Norway

Address correspondence and reprint requests to Duk-Hee Lee, MD, PhD,
Department of Preventive Medicine, School of Medicine, Kyungpook
University, 101 Dongin-dong, Jung-gu, Daegu, Korea 700-422. E-mail:
lee_dh@knu.ac.kr;

OBJECTIVE
We reported strong relations between serum concentrations of
persistent organic pollutants (POPs), especially organochlorine (OC)
pesticides or nondioxin-like polychlorinated biphenyls (PCBs), and
prevalence of diabetes in a U.S population with background exposure to
POPs.
Here, we investigated POPs and insulin resistance, a frequent
pathogenic precursor of type 2 diabetes.

RESEARCH DESIGN AND METHODS
Serum POPs and homeostasis model assessment of insulin resistance
(HOMA-IR) were investigated cross-sectionally in 749 nondiabetic
participants aged over 20 years.
Nineteen POPs in five subclasses were selected, detectable in over 60%
of participants.

RESULTS
Among subclasses, OC pesticides were most strongly associated with
HOMA-IR.
Adjusted geometric means of HOMA were 3.27, 3.36, 3.48, and 3.85 (P
for trend <0.01) across quartiles of OC pesticides.
The relationship strengthened with increasing HOMA-IR percentile:
adjusted odds ratios comparing the highest versus lowest POPs quartile
were 1.8 for being over 50th percentile of HOMA-IR, 4.4 for being over
75th percentile, and 7.5 for being over 90th percentile.
Associations with elevated HOMA-IR appeared to be specific to
oxychlordane and trans-nonachlor but also were found for two nondioxin-
like PCBs.
No HOMA-IR associations were seen in the other three POP subclasses.
The association between OC pesticides and HOMA-IR tended to strengthen
as waist circumference increased, with no apparent association in the
lowest quartile of OC pesticide concentrations.

CONCLUSIONS
These findings, coupled with those concerning diabetes prevalence,
suggest that OC pesticides and nondioxin-like PCBs may be associated
with type 2 diabetes risk by increasing insulin resistance, and POPs
may interact with obesity to increase the risk of type 2 diabetes.

Abbreviations:
HOMA-IR, homeostasis model assessment of insulin resistance
LOD, limit of detection
NHANES, National Health and Nutrition Examination Survey
OC, organochlorine
PCB, polychlorinated biphenyl
PCDD, polychlorinated dibenzo-p-dioxin
PCDF, polychlorinated dibenzofurans
POP, persistant organic pollutant
____________________________________________________

Diabetes
published online ahead of print July 22, 2008
DOI: 10.2337/db08-0668
Original Research
Association of Organochlorine Pesticides with Peripheral Neuropathy
among Patients with Diabetes or Impaired Fasting Glucose
Duk-Hee Lee, M.D., Ph.D. 1,
David R Jacobs, Jr, Ph.D. 2,3,
and Michael Steffes, M.D., Ph.D. 4

1 Department of Preventive Medicine and Health Promotion Research
Center, School of Medicine, Kyungpook National University, Daegu,
Korea
2 Division of Epidemiology, School of Public Health, University of
Minnesota, Minneapolis, Minnesota, USA
3 Department of Nutrition, University of Oslo, Oslo, Norway
4 Department of Laboratory Medicine and Pathology. University of
Minnesota, Minneapolis, MN

Objective:
Recent epidemiological studies have shown that background exposure to
persistent organic pollutants (POPs), xenobiotics accumulated in
adipose tissue, were strongly associated type 2 diabetes.
Hyperglycemia is the cause of long-term complications of diabetes as
well as diabetes itself and POPs themselves are well-known
neurotoxicants.
This study was performed to explore if POPs were associated with
peripheral neuropathy, a common long-term complication of diabetes,
among people with glucose abnormalities.

Research Design and Methods:
We studied cross-sectional associations of peripheral neuropathy with
25 POPs each detectable in at least 60% of study subjects among 246
patients aged over  40 years with diabetes or impaired fasting glucose
using National Health and Nutrition Examination Surveys 1999-2002
datasets.

Results:
Among 5 subclasses of POPs, organochlorine (OC) pesticides showed a
strong dose-response relation with prevalence of peripheral
neuropathy; adjusted ORs were 1.0, 3.6, and 7.3 (P for trend<0.01)
across 3 categories of serum concentrations of OC pesticides.
Furthermore, when we restricted the analyses to 187 participants with
HbA1C<7%, the adjusted ORs were still 1.0, 3.9, and 6.7 (P for
trend<0.01).
OC pesticides were also strongly associated with the prevalence of
HbA1C over 7%; adjusted ORs were 1.0, 2,5, and 5.0 (P for trend<0.01).
Specific POPs belonging to OC pesticides showed similar positive
associations.

Conclusions:
This study suggested that the background exposure to OC pesticides may
be associated with higher risk of peripheral neuropathic complications
among those with glucose abnormalities, even beyond the influence of
diabetes itself.

Correspondence: lee_dh@knu.ac.kr

Key Words: Persistent Organic Pollutants • Organochlorine Pesticides •
HbA1C • diabetes • neuropathy
____________________________________________________

M. P. Montgomery, F. Kamel, T. M. Saldana, M. C. R. Alavanja, and D.
P. Sandler
Incident Diabetes and Pesticide Exposure among Licensed Pesticide
Applicators: Agricultural Health Study, 1993-2003
Am. J. Epidemiol., May 15, 2008; 167(10): 1235 - 1246.

D.-H. Lee, I.-K. Lee, M. Steffes, and D. R. Jacobs Jr.
Extended Analyses of the Association Between Serum Concentrations of
Persistent Organic Pollutants and Diabetes
Diabetes Care, June 1, 2007; 30(6): 1596 - 1598.
____________________________________________________

http://www.bidmc-endocrine.org/faculty/erosen.asp

Evan D. Rosen, MD, PhD  erosen@bidmc.harvard.edu;

Nature. 2006 Dec 14; 444(7121): 847-53.
Adipocytes as regulators of energy balance and glucose homeostasis.
Rosen ED, Spiegelman BM. bruce_speigelman@dfci.harvard.edu;
Division of Endocrinology and Metabolism, Beth Israel Deaconess
Medical Centre, 330 Brookline Avenue, Boston, Massachusetts 02215,
USA.

Adipocytes have been studied with increasing intensity as a result of
the emergence of obesity as a serious public health problem and the
realization that adipose tissue serves as an integrator of various
physiological pathways.
In particular, their role in calorie storage makes adipocytes well
suited to the regulation of energy balance.
Adipose tissue also serves as a crucial integrator of glucose
homeostasis.
Knowledge of adipocyte biology is therefore crucial for understanding
the pathophysiological basis of obesity and metabolic diseases such as
type 2 diabetes. Furthermore, the rational manipulation of adipose
physiology is a promising avenue for therapy of these conditions.
PMID: 17167472
____________________________________________________

ALS, amyotrophic lateral sclerosis, 1156 deaths in a million
person study 1982-2004, correlates with years of formaldehyde
exposure [ aspartame diet soda sold after fall 1983 ],
MG Weisskopf et al, Harvard SPH 2008.04.16:
Rich Murray 2008.09.20
http://rmforall.blogspot.com/2008_09_01_archive.htm
Saturday, September 20, 2008
http://groups.yahoo.com/group/aspartameNM/message/1558

formaldehyde, aspartame, and migraines, the first case series,
Sharon E Jacob-Soo, Sarah A. Stechschulte, UCSD,
Dermatitis 2008 May: Rich Murray 2008.07.18
http://rmforall.blogspot.com/2008_07_01_archive.htm
Friday, July 18, 2008
http://groups.yahoo.com/group/aspartameNM/message/1553

Overlooked aspartame-induced hypertension, HJ Roberts,
Southern Medical J, 2008 Sept.: Murray 2008.09.16
http://rmforall.blogspot.com/2008_09_01_archive.htm
Tuesday, September 16, 2008
http://groups.yahoo.com/group/aspartameNM/message/1556

methanol impurity in alcohol drinks [ and aspartame ] is turned
into neurotoxic formic acid, prevented by folic acid,
re Fetal Alcohol Syndrome, BM Kapur, DC Lehotay,
PL Carlen at U. Toronto, Alc Clin Exp Res 2007 Dec.
plain text: detailed biochemistry, CL Nie et al. 2007.07.18:
Murray 2008.02.24
http://rmforall.blogspot.com/2008_02_01_archive.htm
Sunday, February 24, 2008
http://groups.yahoo.com/group/aspartameNM/message/1524

details on 6 epidemiological studies since 2004 on diet soda
(mainly aspartame) correlations, as well as 13 other
mainstream studies on aspartame toxicity since summer 2005:
Murray 2007.11.14
http://rmforall.blogspot.com/2007_11_01_archive.htm
Wednesday, November 14, 2007
http://groups.yahoo.com/group/aspartameNM/message/1490
____________________________________________________

"Of course, everyone chooses, as a natural priority, to enjoy
peace, joy, and love by helping to find, quickly share, and
positively act upon evidence about healthy and safe
food, drink, and environment."

Rich Murray, MA Room For All rmforall@comcast.net
505-501-2298 1943 Otowi Road, Santa Fe, New Mexico 87505

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