diabetes & 6 Persistent Organic Pollutants (dioxins, pesticides)
correlate strongly, D-H Lee, DR Jacobs et al,  Diabetes Care 2006 July:
Murray 2006.12.05
http://groups.yahoo.com/group/aspartameNM/message/1387

[ This could well be relevant to studies on the chronic toxicity of
methanol, an 11 % part of aspartame, and its products in human bodies,
formaldehyde and formic acid:

http://groups.yahoo.com/group/aspartameNM/message/1366
toxicity in rat brains from aspartame, Vences-Mejia A, Espinosa-Aguirre
JJ et al 2006 Aug: Murray 2006.09.06

http://groups.yahoo.com/group/aspartameNM/message/1373
aspartame rat brain toxicity re cytochrome P450 enzymes, expecially
CYP2E1, Vences-Mejia A, Espinosa-Aguirre JJ et al, 2006 Aug,
Hum Exp Toxicol: relevant abstracts re formaldehyde from methanol in
alcohol drinks: Murray 2006.09.29 ]

http://care.diabetesjournals.org/cgi/content/full/29/7/1638
free full text

Diabetes Care. 2006 Jul; 29(7): 1638-44.
A strong dose-response relation between serum concentrations of
persistent organic pollutants and diabetes:
results from the National Health and Examination Survey 1999-2002.
Lee DH,  lee_dh@knu.ac.kr
Lee IK,   inkyulee@dsmc.or.kr,
Song K,
Steffes MW,  steff001@umn.edu,
Toscano WA,  tosca001@umn.edu,
Baker BA,  beth.a.baker@healthpartners.com,
Jacobs DR Jr.  jacobs@epi.umn.edu,
Department of Preventive Medicine, School of Medicine,
Kyungpook University, 101 Dongin-dong, Jung-gu, Daegu, Korea 700-422.
lee_dh@knu.ac.kr

Duk-Hee Lee, MD, PHD 1,
In-Kyu Lee, MD, PHD 2,
Kyungeun Song, MD, PHD 3,
Michael W. Steffes, MD, PHD 4,
William A. Toscano, PHD 5,
Beth A. Baker, MD, PHD5, 6 and
David R. Jacobs, Jr, PHD 7,8

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 Clinical Pathology, School of Medicine, Kyungpook
National University, Daegu, Korea

4 Department of Laboratory Medicine and Pathology, University of
Minnesota, Minneapolis, Minnesota

5 Division of Environmental Health Sciences, School of Public Health,
University of Minnesota, Minneapolis, Minnesota

6 Regions Hospital, Occupational and Environmental Medicine, St. Paul,
Minnesota

7 Division of Epidemiology, School of Public Health, University of
Minnesota, Minneapolis, Minnesota

8 Department of Nutrition, University of Oslo, Oslo, Norway

OBJECTIVE:
Low-level exposure to some persistent organic pollutants (POPs) has
recently become a focus because of their possible link with the risk of
diabetes.

RESEARCH DESIGN AND METHODS:
Cross-sectional associations of the serum concentrations of POPs with
diabetes prevalence were investigated in 2,016 adult participants in
the National Health and Nutrition Examination Survey 1999-2002.
Six POPs
( 2,2',4,4',5,5'-hexachlorobiphenyl,
1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin,
1,2,3,4,6,7,8,9-octachlorodibenzo-p-dioxin,
oxychlordane,
p,p'-dichlorodiphenyltrichloroethane,
and trans-nonachlor ) were selected,
because they were detectable in >or=80% of participants.

RESULTS:
Compared with subjects with serum concentrations below the limit of
detection, after adjustment for age, sex, race and ethnicity, poverty
income ratio, BMI, and waist circumference,
diabetes prevalence was strongly positively associated with
lipid-adjusted serum concentrations of all six POPs.

When the participants were classified according to the sum of category
numbers of the six POPs,
adjusted odds ratios were 1.0, 14.0, 14.7, 38.3, and 37.7
(P for trend < 0.001).

The association was consistent in stratified analyses and stronger in
younger participants, Mexican Americans, and obese individuals.

CONCLUSIONS:
There were striking dose-response relations between serum
concentrations of six selected POPs and the prevalence of diabetes.
The strong graded association could offer a compelling challenge to
future epidemiologic and toxicological research.
PMID: 16801591

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.

© EnvironmentalHealthNews 2003-2004

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.

Table of probabilities

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.

POPs and diabetes risk

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.

Summed POPs and diabetes risk

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.

[ selections from full text ]

CONCLUSIONS

An inference that observed associations are causal should be made
carefully in a cross-sectional study such as this one.
It may be that metabolic changes caused by diabetes slow metabolism
and/or excretion of POPs, leading to a greater accumulation.
The fact that diabetes was associated with all six POPs investigated,
despite different toxicological profiles, could lend credence to such
an alternative possibility.

However, we think that the relation between POPs and diabetes observed
in this study may be causal for several reasons.

First, our finding is basically consistent with prospective cohort
studies whose study subjects were exposed to high doses of POPs in
occupational or accidental settings, despite a difference in strength
of association (4-10).
As we discuss later, the strength of association in the current study
subjects with large chronic lifetime exposure to low doses of POPs
could be stronger than in those with short-term exposure to high doses
of POPs.

Second, the idea that dioxin exposure may cause diabetes is in line
with the known biology of these pollutants.

Third, reverse causality is unlikely because the metabolism of POPs in
mammalian systems is intractable;
the half-life of the compounds ranges from 7 to 10 years in humans
(29,30).
Supporting our assertion, one human study reported that the rate of
elimination of POPs from blood was not associated with the duration of
diabetes (31).

Fourth, the associations of diabetes with all the POPs investigated may
be reasonably explained by the high correlations among serum
concentrations of various POPs in the human body.
Yet it is entirely possible that the six POPs studied here are not
themselves causally related to diabetes.
Rather, they could be surrogates of exposure to a mixture of POPs.

Finally, >90% of POPs comes from animal foods in the general population
without occupational or accidental exposures (1),
but diabetic patients tend to alter their diet toward consuming more
plant foods than animal foods.

Thus, dietary changes after diagnosis of diabetes would seem to be a
negative confounder, not a positive one.

Another scientifically interesting finding was that obesity did not
increase the prevalence of diabetes among subjects with nondetectable
levels of POPs even though there were sufficient numbers of study
subjects at risk in each BMI category.

In the U.S., the serum concentrations of POPs in the general population
have been decreasing over several decades (32).

Thus, the current dramatic increase in type 2 diabetes incidence may be
puzzling if the striking association between serum concentration of
POPs and diabetes shown in this study is causal.

This puzzle may be explained by the epidemic of obesity in the U.S.;
our study showed that the association between POPs and diabetes was
much stronger among obese subjects compared with that of lean subjects.

As people get fatter, the retention and toxicity of POPs related to the
risk of diabetes may increase.

The concept of toxic equivalency factors (TEFs),
a measure of ability to bind to the AhR,
has been developed to facilitate risk assessment and regulatory control
of exposure to complex PCDD, PCDF, and PCB mixtures (33,34).
However, we did not use TEFs to calculate the cumulative effect of POPs
because the strength of association of each POP observed in this study
did not appear to be correlated with the TEF of each POP,
leading us to hypothesize that binding to the AhR may not be the
critical pathway.
In fact, the AhR hypothesis does not explain all aspects of toxicity,
notably the extreme variation of toxicity between different animal
species (35).

In most previous epidemiological studies (4-10),
only TCDD was evaluated as a risk factor for diabetes because TCDD is
the most potent congener of these POPs.
We did not examine TCDD here because so few individuals had detectable
levels.
In women and non-Hispanic blacks in the NHANES 1999-2002,
only the 95th TCDD percentiles could be characterized,
which were 6.4 and 7.4 pg/g lipid, respectively (23).
The remainder of the U.S. population is likely to have even lower
levels of this hallmark dioxin.

Dose-response relations shown in this study were surprisingly strong
compared with the weak to modest associations shown in the previous
epidemiological studies (4,5,6,7,8,9,10).

Our study had two important design features lacking in other studies:

first, we selected those POPs for which we were sure those with
nondetectable levels would have very low levels and could serve as the
reference group; and second, we evaluated a composite of POP levels.
In our study, the risk of prevalent diabetes increased consistently
across the range of SUMPOPs.
In this situation, the selection of the reference group is
statistically critical to the estimated strength of ORs.

For example, if we pooled the lower four categories of POPs as the
referent group and compared it with the highest category,
the OR would be substantially underestimated.

In fact, most previous epidemiological studies on POPs were performed
with subjects who had exposure to higher concentrations of POPs in
occupational or accidental settings, taking the general population as
the reference group.

However, our current result suggests that this kind of approach may not
be valid because there may be a much clearer dose-response relation in
the lower concentrations of background concentrations of POPs in the
general population.

Interestingly, this observation appeared to be in good agreement with
the dose-response relation of TCDD observed in experimental studies.

According to experimental studies, the administered dose of TCDD
linearly increased the hepatic TCDD concentrations;
however, the induction of cytochrome P-450 enzymes (CYP1A1 and CYP1A2),
one of the most sensitive responses to TCDD and its structural analogs,
increased nonlinearly as a function of the hepatic concentration of
TCDD, reaching the maximum effect (36).

Similar findings were observed with some PCBs (37).
Humans are currently regarded as a less-susceptible species with
respect to TCDD or other congeners based on findings of previous
epidemiological studies with subjects having high exposure to POPs
(38).

However, the chronic exposure to low concentrations of POPs in the
general population may be more detrimental in developing adverse health
effects than previously thought.
Along these lines, it is worthwhile to note that the most consistent
dose-response associations between POPs and diabetes appeared to occur
in epidemiological studies with subjects having lower serum
concentrations of TCDD than in occupational settings (4,8),
conceivably because of the statistical artifact of not identifying a
true low-risk subgroup.

Unlike prior studies, in this study, we analyzed several POPs
simultaneously so that we could estimate the cumulative effect of
exposure mixtures.
In most previous studies, only serum concentrations of TCDD were
measured.
Although TCDD is well known to be the most potent POP because of a
strong affinity to AhR, other mechanisms might also be involved in the
toxicity of POPs for diabetes (39).
Thus, other POPs, as well as TCDD, might be relevant in the
pathogenesis of diabetes.

This study has several limitations.

The current findings should be interpreted with caution because of the
cross-sectional nature of this study, despite both strength and
consistency of associations.

The NHANES dataset did not allow us to differentiate type 1 from type 2
diabetes,
and the association of POP levels with diabetes prevalence might differ
by diabetes type.

Only 11 subjects were aged <40, so most subjects probably had type 2
diabetes.

Experimental studies have shown that TCDD could cause hypoinsulinemia
through an alteration of pancreatic membrane tyrosine phosphorylation,
suggesting that POPs may be involved in the pathogenesis of type 1
diabetes as well as type 2 diabetes (40).

Also, misclassification bias is possible because some subjects with a
higher POP value but a lower sample volume could be classified in the
reference group or vice versa.

Such misclassification would be nondifferential if (as is likely)
sample volume is unrelated to prevalence of diabetes.

Finally, because diabetes was extremely rare in those with the least
exposure to POPs, the reference category may not be stable and ORs
could be overestimated.

In summary, there were striking monotonic and additive dose-response
relations between serum concentrations of six selected POPs and the
prevalence of diabetes.

These cross-sectional findings,
although not definitive,
are sufficiently provocative that further study should be done.

A prospective study of the relation between dioxin exposure and
diabetes is needed because both the exposure and the disease have
substantial prevalence and the public health significance could be
marked.

Acknowledgments

This research was funded by the Korea Health 21 R&D Project, Ministry
of Health & Welfare, Republic of Korea (A050349),
by grant RTI04-01-01 from the Regional Technology Innovation Program of
the Ministry of Commerce, Industry and Energy (MOCIE), Republic of
Korea, and
by grant R01 HL 53560 from the U.S. National Institutes of Health (to
M.S. and D.R.J.).

Footnotes

Received for publication March 10, 2006.
Accepted for publication April 5, 2006.

References

1. Fisher BE:
Most unwanted.
Environ Health Perspect 107: A18-A23, 1999 [Medline]

2. Abelsohn A, Gibson BL, Sanborn MD, Weir E:
Identifying and managing adverse environmental health effects.
5. Persistent organic pollutants.
CMAJ 166: 1549-1554, 2002 [Abstract/Free Full Text]

3. Remillard RB, Bunce NJ:
Linking dioxins to diabetes: epidemiology and biologic plausibility.
Environ Health Perspect 110: 853-858, 2002 [Medline]

4. Henriksen GL, Ketchum NS, Michalek JE, Swaby JA:
Serum dioxin and diabetes mellitus in veterans of Operation Ranch Hand.
Epidemiology 8: 252-258, 1997 [Medline]

5. Bertazzi PA, Bernucci I, Brambilla G, Consonni D, Pesatori AC:
The Seveso studies on early and long-term effects of dioxin exposure:
a review.
Environ Health Perspect 106(Suppl. 2): 625-633, 1998

6. Vena J, Boffetta P, Becher H, Benn T, Bueno-de-Mesquita HB, Coggon
D, Colin D, Flesch-Janys D, Green L, Kauppinen T, Littorin M, Lynge E,
Mathews JD, Neuberger M, Pearce N, Pesatori AC, Saracci R, Steenland K,
Kogevinas M:
Exposure to dioxin and nonneoplastic mortality in the expanded IARC
international cohort study of phenoxy herbicide and chlorophenol
production workers and sprayers.
Environ Health Perspect 106(Suppl. 2): 645-653, 1998

7. Steenland K, Piacitelli L, Deddens J, Fingerhut M, Chang LI:
Cancer, heart disease, and diabetes in workers exposed to
2,3,7,8-tetrachlorodibenzo-p-dioxin.
J Natl Cancer Inst 91: 779-786, 1999 [Abstract/Free Full Text]

8. Longnecker MP, Michalek JE:
Serum dioxin level in relation to diabetes mellitus among Air Force
veterans with background levels of exposure.
Epidemiology 11: 44-48, 2000 [Medline]

9. Sweeney MH, Calvert GM, Egeland GA, Fingerhut MA, Halperin WE,
Piacitelli LA:
Review and update of the results of the NIOSH medical study of workers
exposed to chemicals contaminated with
2,3,7,8-tetrachlorodibenzodioxin. Teratog Carcinog Mutagen 17:
241-247, 1997-1998 [Medline]

10. Zober A, Ott MG, Messerer P:
Morbidity follow up study of BASF employees exposed to
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
after a 1953 chemical reactor incident.
Occup Environ Med 51: 479-486, 1994 [Abstract]

11. Testimony of Ronald Ziegler before the Joint Session of the
Committees on Veterans Affairs, United States House of Representatives
and United States Senate on Veterans Legislative Agenda for 2001.
Available from
http://veterans.house.gov/hearings/schedule107/mar01/3-8-01/
rziegler.htm. Accessed 28 February 2006.

12. Hankinson O:
The aryl hydrocarbon receptor complex.
Annu Rev Pharmacol Toxicol 35: 307-340, 1995 [Medline]

13. Enan E, Lasley B, Stewart D, Overstreet J, Vandevoort CA:
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) modulates function of human
luteinizing granulosa cells via cAMP signaling and early reduction of
glucose transporting activity.
Reprod Toxicol 10: 191-198, 1996 [Medline]

14. Olsen H, Enan E, Matsumura F:
Regulation of glucose transport in the NIH 3T3 L1 preadipocyte cell
line by TCDD.
Environ Health Perspect 102: 454-458, 1994 [Medline]

15. Enan E, Matsumura F:
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-induced changes in glucose
transporting activity in guinea pigs, mice, and rats in vivo and in
vitro.
J Biochem Toxicol 9: 97-106, 1994 [Medline]

16. Liu PC, Matsumura F:
Differential effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the
"adipose-type" and "brain-type" glucose transporters in mice.
Mol Pharmacol 47: 65-73, 1995 [Abstract]

17. Dohr O, Vogel C, Abel J:
Modulation of growth factor expression by
2,3,7,8-tetrachlorodibenzo-p-dioxin.
Exp Clin Immunogenet 11: 142-148, 1994 [Medline]

18. Vogel C, Abel J:
Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on growth factor
expression in the human breast cancer cell line MCF-7. Arch Toxicol 69:
259-265, 1995 [Medline]

19. Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM:
Increased adipose tissue expression of tumor necrosis factor-{alpha} in
human obesity and insulin resistance.
J Clin Invest 95: 2409-2415, 1995 [Medline]

20. Hotamisligil GS, Shargill NS, Spiegelman BM:
Adipose expression of tumor necrosis factor-{alpha}:
direct role in obesity-linked insulin resistance.
Science 259:87-91, 1993 [Abstract/Free Full Text]

21. Uysal KT, Wiesbrock SM, Marino MW, Hotamisligil GS:
Protection from obesity-induced insulin resistance in mice lacking
TNF-alpha function.
Nature 389: 610-614, 1997 [Medline]

22. Gunton JE, Kulkarni RN, Yim S, Okada T, Hawthorne WJ, Tseng YH,
Roberson RS, Ricordi C, O'Connell PJ, Gonzalez FJ, Kahn CR:
Loss of ARNT/HIF1beta mediates altered gene expression and
pancreatic-islet dysfunction in human type 2 diabetes.
Cell 122: 337-349, 2005 [Medline]

23. Third national report on human expoure to environmental chemicals
[article online], 2005. Available from
http://www.cdc.gov/exposurereport/3rd/pdf/thirdreport.pdf.
Accessed 28 February 2006

24. NHANES 1999-2000 public data release file documentation
[article online], 2005. Available from
http://www.cdc.gov/nchs/about/major/nhanes/nhanes99-00.htm.
Accessed 28 February 2006

25. NHANES 2000-2001 public data release file documentation [article
online], 2005. Available from
http://www.cdc.gov/nchs/about/major/nhanes/nhanes01-02.htm.
Accessed 28 February 2006

26. Turner W, DiPietro E, Lapeza C, Green V, Gill J, Patterson DG Jr:
A fast universal automated cleanup system for the isotope-dilution HRMS
analysis of PCDDs, PCDFs, coplanar PCBs, PCB congeners, and persistent
pesticides from the same serum sample.
Organohalogen Comp 31: 26-31, 1997

27. Korn EL, Graubard BI:
Epidemiologic studies utilizing surveys: accounting for the sampling
design.
Am J Public Health 81: 1166-1173, 1991 [Abstract]

28. Graubard BI, Korn EL:
Analyzing health surveys for cancer-related objectives.
J Natl Cancer Inst 91: 1005-1016, 1999 [Abstract/Free Full Text]

29. DeVito MJ, Birnbaum LS, Farland WH, Gasiewicz TA:
Comparisons of estimated human body burdens of dioxin-like chemicals
and TCDD body burdens in experimentally exposed animals.
Environ Health Perspect 103: 820-831, 1995 [Medline]

30. Olson JR:
Pharmacokinetics of dioxins and related chemicals.
In Dioxins and Health. Schecter A, Ed. New York,
Plenum Press, 1994, p. 163-197

31. Michalek JE, Ketchum NS, Tripathi RC:
Diabetes mellitus and 2,3,7,8-tetrachlorodibenzo-p-dioxin elimination
in veterans of Operation Ranch Hand.
J Toxicol Environ Health 66: 211-221, 2003

32. Needham LL, Barr DB, Caudill SP, Pirkle JL, Turner WE, Osterloh J,
Jones RL, Sampson J:
Concentrations of environmental chemicals associated with
neurodevelopmental effects in U.S. population.
Neurotoxicology 26: 531-545, 2005 [Medline]

33. Masuda Y:
Fate of PCDF/PCB congeners and change of clinical symptoms in patients
with Yusho PCB poisoning for 30 years.
Chemosphere 43: 925-930, 2001 [Medline]

34. Masuda Y, Schecter A, Papke O:
Concentrations of PCBs, PCDFs and PCDDs in the blood of Yusho patients
and their toxic equivalent contribution.
Chemosphere 37: 1773-1780, 1998 [Medline]

35. van den Berg M, Peterson RE, Schrenk D:
Human risk assessment and TEFs.
Food Addit Contam 17: 347-358, 2000 [Medline]

36. Tritscher AM, Goldstein JA, Portier CJ, McCoy Z, Clark GC,
Lucier GW:
Dose-response relationships for chronic exposure to
2,3,7,8-tetrachlorodibenzo-p'-dioxin in a rat tumor promotion model:
quantification and immunolocalization of CYP1A1 and CYP1A2 in the
liver. Cancer Res 52: 3436-3442, 1992 [Abstract]

37. Hennig B, Meerarani P, Slim R, Toborek M, Daugherty A, Silverstone
AE, Robertson LW:
Proinflammatory properties of coplanar PCBs:
in vitro and in vivo evidence.
Toxicol Appl Pharmacol 181: 174-183, 2002 [Medline]

38. Neubert D:
Reflections on the assessment of the toxicity of "dioxins" for humans,
using data from experimental and epidemiological studies.
Teratog Carcinog Mutagen 17: 157-215, 1997-1998 [Medline]

39. Kern PA, Fishman RB, Song W, Brown AD, Fonseca V:
The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on oxidative
enzymes in adipocytes and liver.
Toxicology 171: 117-125, 2002 [Medline]

40. Ebner K, Matsumura F, Enan E, Olsen H:
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) alters pancreatic membrane
tyrosine phosphorylation following acute treatment.
J Biochem Toxicol 8: 71-81, 1993 [Medline]

Diabetes Care 29:  Nov 1, 2006; 29(11): 2567 - 2567.
DOI: 10.2337/dc06-1531
© 2006 by the American Diabetes Association

Letters: Comments and Responses

A Strong Dose-Response Relation Between Serum Concentrations of
Persistent Organic Pollutants and Diabetes:
Results From the National Health and Nutrition Examination Survey
1999-2002
Response to Lee et al.
Miquel Porta, MD, MPH, PHD

Institut Municipal d'Investigació Mèdica, Barcelona, Catalonia,
Spain

Address correspondence to Prof. Miquel Porta, School of Medicine,
Universitat Autònoma de Barcelona
and Institut Municipal d'Investigació Mèdica, Carrer del Dr
Aiguader 80, E-08003 Barcelona, Catalonia, Spain. E-mail:
mporta@imim.es

The first 20% of the full text of this article appears below.

Lee et al. (1) and Diabetes Care deserve praise for publishing what may
be the first study worldwide to analyze, in a sample of a general
population, serum concentrations of persistent organic pollutants
(POPs) and plasma fasting glucose.
The main implication of the study is that POPs stored in the adipose
tissue may be a key player in the etiopathogenesis of type 2 diabetes.
It is even rational to speculate that POPs might be, if not "the single
factor" (2), then one factor linking some core components of the
metabolic syndrome.

In the study by Lee et al. and other studies (3,4), it . . .
[ $ 12 for Full Text of this Article ]
*******************************************************

short aspartame (methanol, formaldehyde) toxicity research summary:
Murray 2006.12.09
http://groups.yahoo.com/group/aspartameNM/message/1379

"Of course, everyone chooses, as a natural priority,
to actively find, quickly share, and positively act upon the facts
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

http://groups.yahoo.com/group/aspartameNM/messages
group with 78 members, 1,387 posts in a public, searchable archive
http://RMForAll.blogspot.com

http://groups.yahoo.com/group/aspartameNM/message/1340
aspartame groups and books: updated research review of 2004.07.16:
Murray 2006.05.11

http://groups.yahoo.com/group/aspartameNM/message/1378
11 members of New Mexico legislature sign letter to ban aspartame as a
source of toxic methanol and formaldehyde, Stephen Fox, NM Senator
Gerald Ortiz y Pino: Murray 2006.10.22

http://groups.yahoo.com/group/aspartameNM/message/1374
47 UK Members of Parliament now support aspartame ban initiative of
Roger Williams, MP: Murray 2006.10.16

http://groups.yahoo.com/group/aspartameNM/message/1271
combining aspartame and quinoline yellow, or MSG and brilliant blue,
harms nerve cells, eminent C. Vyvyan Howard et al, 2005
education.guardian.co.uk, Felicity Lawrence: Murray 2005.12.21

http://groups.yahoo.com/group/aspartameNM/message/1277
50% UK baby food is now organic -- aspartame or MSG
with food dyes harm nerve cells, CV Howard 3 year study
funded by Lizzy Vann, CEO, Organix Brands,
Children's Food Advisory Service: Murray 2006.01.13

http://groups.yahoo.com/group/aspartameNM/message/1279
all three aspartame metabolites harm human erythrocyte [red blood cell]
membrane enzyme activity, KH Schulpis et al, two studies in 2005,
Athens, Greece, 2005.12.14: 2004 research review, RL Blaylock:
Murray 2006.01.14

http://groups.yahoo.com/group/aspartameNM/message/1366
toxicity in rat brains from aspartame, Vences-Mejia A, Espinosa-Aguirre
JJ et al 2006 Aug: Murray 2006.09.06

http://groups.yahoo.com/group/aspartameNM/message/1373
aspartame rat brain toxicity re cytochrome P450 enzymes, expecially
CYP2E1, Vences-Mejia A, Espinosa-Aguirre JJ et al, 2006 Aug,
Hum Exp Toxicol: relevant abstracts re formaldehyde from methanol
in alcohol drinks: Murray 2006.09.29

http://groups.yahoo.com/group/aspartameNM/message/1369
Bristol, Connecticut, schools join state program to limit artificial
sweeteners, sugar, fats for 8800 students, Johnny J Burnham, The
Bristol Press: Murray 2006.09.22

http://groups.yahoo.com/group/aspartameNM/message/1341
Connecticut bans artificial sweeteners in schools, Nancy Barnes,
New Milford Times: Murray 2006.05.25

http://groups.yahoo.com/group/aspartameNM/message/1353
carcinogenic effect of inhaled formaldehyde, Federal Institute of Risk
Assessment, Germany -- same safe level as for Canada:
Murray 2006.06.02

http://groups.yahoo.com/group/aspartameNM/message/1352
Home sickness -- indoor air often worse, as our homes seal in
pollutants
[one is formaldehyde, also from the 11% methanol part of aspartame],
Megan Gillis, WinnipegSun.com: Murray 2006.06.01

http://groups.yahoo.com/group/aspartameNM/message/1143
methanol (formaldehyde, formic acid) disposition: Bouchard M
et al, full plain text, 2001: substantial sources are
degradation of fruit pectins, liquors, aspartame, smoke:
Murray 2005.04.02

http://groups.yahoo.com/group/aspartameNM/message/1349
NIH NLM ToxNet HSDB Hazardous Substances Data Bank
inadequate re aspartame (methanol, formaldehyde, formic acid):
Murray 2006.08.19

http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~HwoSfJ:1
HSDB  Hazardous Substances Data Bank: Aspartame

ASPARTAME   CASRN: 22839-47-0
METHANOL  CASRN: 67-56-1
FORMALDEHYDE   CASRN: 50-00-0
FORMIC ACID  CASRN: 64-18-6

http://groups.yahoo.com/group/aspartameNM/message/1307
formaldehyde from 11% methanol part of aspartame or from red wine
causes same toxicity (hangover) harm: Murray 2006.05.24

Dark wines and liquors, as well as aspartame, provide
similar levels of methanol, above 120 mg daily, for
long-term heavy users, 2 L daily, about 6 cans.

Within hours, methanol is inevitably largely turned into formaldehyde,
and thence largely into formic acid --  the major causes of the dreaded
symptoms of "next morning" hangover.

Fully 11% of aspartame is methanol -- 1,120 mg aspartame
in 2 L diet soda, almost six 12-oz cans, gives 123 mg
methanol (wood alcohol). If 30% of the methanol is turned
into formaldehyde, the amount of formaldehyde, 37 mg,
is 18.5 times the USA EPA limit for daily formaldehyde in
drinking water, 2.0 mg in 2 L average daily drinking water.

Any unsuspected source of methanol, which the body always quickly
and largely turns into formaldehyde and then formic acid, must be
monitored, especially for high responsibility occupations, often with
night shifts, such as pilots and nuclear reactor operators.

http://groups.yahoo.com/group/aspartameNM/message/1052
DMDC: Dimethyl dicarbonate 200mg/L in drinks adds methanol 98 mg/L
( becomes formaldehyde in body ):  EU Scientific Committee on Foods
2001.07.12:  Murray 2004.01.22

http://www.HolisticMed.com/aspartame    mgold@holisticmed.com
Aspartame Toxicity Information Center    Mark D. Gold
12 East Side Drive #2-18 Concord, NH 03301     603-225-2100

http://www.holisticmed.com/aspartame/abuse/methanol.html
"Scientific Abuse in Aspartame Research"

http://groups.yahoo.com/group/aspartameNM/message/957
safety of aspartame Part 1/2 12.4.2: EC HCPD-G SCF:
Murray 2003.01.12 rmforall  EU Scientific Committee on Food,
a whitewash

http://groups.yahoo.com/group/aspartameNM/message/1045
http://www.holisticmed.com/aspartame/scf2002-response.htm
Mark Gold exhaustively critiques European Commission Scientific
Committee on Food re aspartame ( 2002.12.04 ):
59 pages, 230 references

http://groups.yahoo.com/group/aspartameNM/message/1371
Russell L. Blaylock, MD discusses MSG, aspartame, excitotoxins
with Mike Adams: Murray 2006.09.27

http://groups.yahoo.com/group/aspartameNM/message/1372
Mike Adams interviews Randall Fitzgerald on "The Hundred Year Lie:
How Food and Medicine are Destroying Your Health" 2006.06.21:
Murray 2006.09.28
*******************************************************