[Pharmwaste] A Strong Dose-Response Relation Between Serum Concentrations of Persistent Organic Pollutants and Diabetes

DeBiasi,Deborah dldebiasi at deq.virginia.gov
Mon Dec 4 11:33:10 EST 2006


http://www.ourstolenfuture.org/NewScience/obesity/2006/2006-0715leeetal.
html

Posted 20 November 2006. Research published July 2006. 

Lee, D-H, I-K Lee, K Song, M Steffes, W Toscano, BA Baker, and DR
Jacobs. 2006. A 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
29:1638-1644. 

According to the US Centers for Disease Control, from 1980 through 2004,
the number of Americans with diabetes more than doubled (from 5.8
million to 14.7 million). The chances that an American child will become
diabetic are now 1 in 3. The odds for a Latinos in the US and indigenous
peoples around the Pacific are even worse, 1 in 2. 

Prevailing wisdom blames Western lifestyles and diet. An alternative
explanation-- contaminants interfering with glucose and insulin
metabolism-- has begun to gain traction, based on studies in the lab
with cells and mice, and on epidemiological research with people. These
explanations are not mutually exclusive: both could be at work at the
same time. 

New research by Lee et al., summarized here, adds substantial weight to
the hypothesis that contaminants are involved. They find a strong dose
response relationship between type II diabetes risk and body burden of 6
persistent organic pollutants (POPs). Five of the 6 have highly
significant associations when examined singly. The association is
especially strong between diabetes risk and an estimate of the summed
exposure to all 6 POPs studied simultaneously. 
 
What did they do? Lee et al. analyzed data obtained by the Centers for
Disease Control in the National Health and Examination Survey (NHANES;
1999-2002). This periodic survey assesses the health of the American
public. The sampling protocol is carefully designed to obtain
representative data. In this analysis, Lee et al. assessed the
statistical relationship between risk of type II diabetes and 6
persistent organic pollutants: One PCB (hexachlorobiphenyl), two 
dioxins (heptadioxin and OCDdioxin) two pesticides (oxychlordane and
trans-nonachlor) and a pesticide metabolite (DDE, a metabolite of DDT).

They selected these contaminants because they were detectable in over
80% of participants. Total sample size in the study was 2,016. The
diagnosis of diabetes was confirmed by medical interview. 

Each organochlorine was assessed individually: Individuals with
contamination level beneath the limit of detection for a given
contaminant were used as the reference group ('control') for calculating
an odds-ratio. The remaining individuals, all with detectable levels,
were divided into 5 groups based on percentile exposure: up to 25th; up
to 50th, up to 75th, up to 90th, and above 90th percentile. 

To examine the association for the combination of POPs, each person
studied was assigned a score of 0 to 5 for each contaminant based on
which category of exposure they were in (reference, 25th, 50th...).. The
sum of the scores (minimum 0, maximum 30) was then used as an index of
total POPs exposure. People were separated into groups based on the sum
of the scores (from reference to 25th, 50th, etc.) and then an odds
ratio estimating the relative risk of type II diabetes was calculated
for each group. 

What did they find?

In general, older people had higher levels of individual contaminants
than younger. Men tended to have lower concentrations. For all but one
contaminant (PCB153), Hispanics tended to have higher levels as did
poorer people. 

Among the 2,016 people in the study, 217 had type II diabetes. 

Five of the 6 POPs demonstrated a strong trend of increasing risk of
diabetes with increasing body burden of POPs.

Because all people had detectable amounds of DDE, Lee et al. used the
2nd exposure category as reference group for this contaminant. Red line
is an odds-ratio of 1. 

Levels of trans-Nonachlor showed the most striking individual
relationship with diabetes risk, with the odds ratio for the highest
exposure group rising to 11.8 (95% confidence limits ran from 4.4 to
31.3). 

Overall, the lower boundary of thirteen of 30 calculated confidence
limits for all contaminants was greater than 1. For people in the two
highest exposure groups, 9 of 13 of the lower estimate of the 95%
confidence intervals were greater than 1. 

When they analyzed the index of simultaneous exposure to all 6 POPs,
they first observed that no one in the survey had undetectable levels of
every contaminant. This lead them to use the 2nd lowest exposure group,
(up to the 25th percentile), as the reference for calculating the odds
ratio for higher exposure groups. 

   Compared to people in the lowest exposure category (1), people in the
highest were almost 38 times more likely to have diabetes (graph to
left). All odds ratios calculated for categories 2 through 5 were
significant. 

The trend of increasing risk with increasing exposure was also highly
significant (p < 0.001) 

Red line is set at OR=1.0. Vertical black lines show 95% confidence
limits. Upper limit shown numerically. 
 
Because only 2 people in the lowest exposure group had diabetes, the
estimates of the confidence limits were quite broad. For example, for
group 5 the limits ranged from 7.8 to 182. In part this was due to the
fact that only 2 out of 463 people in the the lowest group had diabetes
(compared to 63 out of 246 in group 5). Lee et al. therefore provided a
separate estimate of the odds ratios using group 2 as the reference
group. This led to estimates of 1.1, 2.7 and 2.7 for groups 3, 4 and 5,
respectively. Confidence limits for groups 4 and 5 did not include OR=1.

Lee et al. report that there was "no association between obesity and
diabetes among subjects with nondetectable levels of POPs."

What does it mean? Numerous experimental studies have proven links in
animals and cells between contaminants, including persistent organic
pollutants, and changes in insulin and glucose metabolism associated
with diabetes. Some prior epidemiological research has found
associations, for example, between diabetes and dioxin. 

The odds ratios found by Lee et al. are nonetheless strikingly high.
They caution that epidemiological studies like theirs can't be used to
prove causation, but "we think that the relation between POPs and
diabetes observed in this study may be causal for several reasons." They
point out that there are high correlations among the levels of exposure
to POPs in this study and that the actual causal factor may be another
POP that was not measured. They also highlight the unexpected finding
that in people in the study with nondetectable levels of POPs there was
no relationship between obesity and diabetes. 

The good news is that POPs levels in people have begun to decline, at
least for some contaminants. Indeed, Swedish epidemiologists have
suggested that a recent decline in POPs in that country may be the cause
of recent drop there in cases of non-Hodgkin's lymphoma. 

Data on trends in POPs use and contamination would suggest that people
with the heaviest burdens will have been born during the decade that
followed steps taken, beginning in the mid-1970s, to reduce
environmental exposures to POPs. This is the cohort that is now in their
reproductive years, raising questions about how their own exposures may
be affecting insulin metabolism in their offspring. Steps taken in under
the auspices of the United Nations Stockholm Convention on Persistent
Organic Pollutants should lead to lower levels in the future. 
 


Deborah L. DeBiasi
Email:   dldebiasi at deq.virginia.gov
WEB site address:  www.deq.virginia.gov
Virginia Department of Environmental Quality
Office of Water Permit Programs
Industrial Pretreatment/Toxics Management Program
Mail:          P.O. Box 1105, Richmond, VA  23218 (NEW!)
Location:  629 E. Main Street, Richmond, VA  23219
PH:         804-698-4028
FAX:      804-698-4032



More information about the Pharmwaste mailing list