Women with high levels of iron in their bodies may have three times the risk of developing type 2 diabetes, says a study in the Journal of the American Medical Association.
Someday this could mean doctors can use a simple iron test to help find out your risk for diabetes.
However, these findings are preliminary, says JoAnn Manson, M.D., a co- author of the study, professor of medicine at Harvard Medical School and chief of preventive medicine at Brigham and Women's Hospital in Boston.
"We're not recommending doctors begin routinely screening for high levels of iron in order to detect those at high risk," she says. "But this study adds to mounting evidence that this test can be a very strong predictor for diabetes."
Researchers took blood samples of 32,800 women at the start of the study. Ten years later they were asked about their health outcomes, including whether they had been diagnosed with diabetes. About 700 women had developed type 2 diabetes. When blood was drawn at the beginning of the study, these women generally had higher levels of iron.
Women otherwise healthy
"This is a completely independent risk factor for type 2 diabetes," Manson says. That means these women did not have the typical factors that increase chances for the disease. Typically, people who are obese, have a family history of diabetes, are older than 45, and don't exercise have higher chances.
Higher levels of iron might increase the number of free radicals, which are produced as your cells work in your body. Too many free radicals can damage organs, including the pancreas, which makes insulin. (Insulin is a hormone that helps the body turn sugar into energy.) In type 2 diabetes, the body cannot use insulin effectively and eventually the pancreas is unable to make enough insulin.
Or the higher levels of iron might cause cells to become resistant to insulin.
"There is no doubt that the results show a strong association between higher iron stores and later development of diabetes," says Simeon Margolis, M.D., Ph.D., professor of medicine, endocrinology and biological chemistry at The Johns Hopkins University School of Medicine in Baltimore. "But this cannot show or prove that higher iron stores are the cause of diabetes."
Other iron risks possible
Margolis points out researchers are still learning about iron's role in cardiovascular health. Some researchers think high levels can damage arteries, contributing to the risk of heart attacks, atherosclerosis (hardening of the arteries) and strokes. Iron may interfere with nitric acid, which causes blood vessels to relax. In a Finnish study, men with the highest amounts of iron in their bodies had almost three times more heart attacks than men with less.
Iron is an essential mineral. It is a part of oxygen-carrying hemoglobin in red blood cells and in energy-producing proteins in all body cells. About 30 percent of iron in the body is in storage, readily available to replace any that is lost. Too much iron in the body causes hemosiderosis, which can happen when taking too many iron supplements. In extreme cases, too much can cause problems with the heart or immune system. Another condition known as hemochromatosis is an inherited disorder that causes the body to store too much iron. There is abundant evidence that damage to the pancreas by hemochromatosis can cause diabetes.
The iron in red meat is the most easily absorbed by the body.
"People might lower intakes of red meat to less than one serving a week," Manson says, as an easy way of decreasing the amount of iron in their diet.
> Women with high levels of iron in their bodies may have three times > the risk of developing type 2 diabetes, says a study in the Journal of > the American Medical Association.
Molecular epidemiologic evidence for diabetogenic effects of dioxin exposure in U.S. Air force veterans of the Vietnam war. BACKGROUND: One of the outcomes positively associated with dioxin exposure in humans is type 2 diabetes. OBJECTIVES: This study was conducted in order to find the molecular biological evidence for the diabetogenic action of dioxin in adipose samples from Vietnam veterans. METHODS: We obtained 313 adipose tissue samples both from Vietnam veterans who were exposed to dioxin (Operation Ranch Hand) and from comparison veterans who served in Southeast Asia with no record of dioxin exposure. We conducted quantitative reverse-transcribed polymerase chain reaction studies on selected marker mRNAs from these samples. RESULTS: We found the most sensitive and reliable molecular indicator of dioxin-induced diabetes to be the ratio of mRNA of glucose transporter 4 (GLUT4) and nuclear transcription factor kappa B (NFkappaB), a marker of inflammation. This ratio showed significant correlations to serum dioxin residues and to fasting glucose among those in the Ranch Hand group and, surprisingly, even in the comparison group, who have low levels of dioxin comparable to the general public. Such a correlation in the comparison group was particularly significant among those with known risk factors such as obesity and family history of diabetes. CONCLUSIONS: These results show that the GLUT4:NFkappaB ratio is a reliable marker for the diabetogenic action of dioxin, particularly at very low exposure levels that are not much higher than those found in the general public, implying a need to address current exposure levels. PMID: 17107852
>>> three times the risk of developing type 2 diabetes
>> CONCLUSIONS: GLUT4:NFkappaB ratio is a reliable marker >> for the diabetogenic action of dioxin, particularly at very low >> exposure levels that are not much higher than those found >> in the general public, implying a need to address >> current exposure levels.
> No mention of iron in the article you provided ..
Stimulation of iron absorption by polychlorinated aromatic hydrocarbons. Oral and intraperitoneal treatment of rats with a single dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 33 microgram/kg, causes a 41--67% increase in iron adsorption in vivo. The major effect is on the transfer of iron from the mucosa into the bloodstream rather than on the uptake of iron from the lumen of the gut. These results are confirmed in studies with everted gut sacs. The effect is maximal at 1--2 days with a dose of 22-42 microgram/kg. Calcium transport is inhibited by TCDD treatment, whereas galactose and proline transport are unaffected. Treatment of rats with 1,1,1-trichloro-2,2-bis(p- chlorophenyl)ethane also stimulates iron transport. Concomitant with iron transport stimulation, aryl hydrocarbon hydroxylase activity in the intestine and liver is increased by TCDD treatment. These studies suggest that polychlorinated aromatic hydrocarbons, which are environmental health hazards, may effect the intestinal absorption of essential mineral nutrients. PMID: 443429
Oxidative stress induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is one of the most potent toxins and tumor promoters known to man. It is prototypical of many halogenated polycyclic hydrocarbons that occur as environmental contaminants. Pathologic lesions produced by these compounds are mediated by an intracellular receptor protein called the TCDD (Ah) receptor which functions as a trans-acting effector of gene expression...Evidence demonstrating the involvement of iron in TCDD- induced formation of reactive oxygen species and DNA damage is reviewed. Oxidative damage may contribute to many of the toxic responses produced by TCDD and its bioisosteres, and may be common to most of the tissue-damaging effects. PMID: 2210442
Polychlorinated biphenyl-77 induces adipocyte differentiation and proinflammatory adipokines and promotes obesity and atherosclerosis. BACKGROUND: Obesity, an inflammatory condition linked to cardiovascular disease, is associated with expansion of adipose tissue. Highly prevalent coplanar polychlorinated biphenyls (PCBs) such as 3,3',4,4'-tetrachlorobiphenyl (PCB-77) accumulate in adipose tissue because of their lipophilicity and increase with obesity. However, the effects of PCBs on adipocytes, obesity, and obesity- associated cardiovascular disease are unknown.... mice injected with PCB-77 exhibited greater body weight, adipocyte hypertrophy, serum dyslipidemia, and augmented atherosclerosis. CONCLUSIONS: Our findings suggest that PCB-77 may contribute to the development of obesity and obesity-associated atherosclerosis. PMID: 18560532
http://en.wikipedia.org/wiki/Cytochrome_P450 Cytochrome P450 (abbreviated CYP, P450, infrequently CYP450) is a very large and diverse superfamily of hemoproteins found in all domains of life. Cytochromes P450 use a plethora of both exogenous and endogenous compounds as substrates in enzymatic reactions.
On July 6, 2005, the Department of Defense released the latest report of the Air Force Health Study on the health effects of exposure to herbicides in Vietnam, which includes the strongest evidence to date that Agent Orange is associated with adult-onset diabetes. This supports the findings from earlier reports in 1992 and 1997. Herbicide Orange [a mixture of 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5- trichlorophenoxy-acetic acid (2,4,5-T)] was used as a defoliant during the Vietnam War. Other herbicides containing 2,4,5-T were also used extensively; and as commonly used by the news media, the term “Herbicide Orange” refers to all of these 2,4,5-T products. These herbicides were contaminated with 2,3,7,8-tetrachlorodibenzo-p dioxin (TCDD), and the presence of this toxin is the basis for much of the concern over exposure to these defoliants. More than 3,000 veterans have filed claims for compensation against the Veterans Administration. In response to Congress, the General Accounting Office investigated the issue and subsequently recommended that the Department of Defense conduct a long-term epidemiologic study of the problem. The Department of the Air Force has made a formal commitment to the Congress and the White House to conduct such a study. On September 16, 1980, the White House directed the Department of Defense to initiate the Ranch Hand study with reasonable speed and high quality. This decision was subsequently reaffirmed by the new administration. The Air Force Health Study summarizes the results of the 2002 physical examination of 1,951 veterans, which is the final examination of the 20-year epidemiological study. The Ranch Hand Study was named after the operation responsible for spraying herbicides in Vietnam between 1962 and 1971 to deny cover and destroy crops of the North Vietnamese Army. ince the first examination in 1982, the Air Force has tried to determine hether long-term health effects exist in the Ranch Hand pilots and ground crews, and if these effects can be attributed to the herbicides used in Vietnam, mainly Agent Orange and its contaminant, dioxin. The report, along with many other studies on herbicide and dioxin exposure, will be reviewed by the National Academy of Sciences. Based upon this review, the Secretary of Veterans Affairs can ask Congress for legislation on disability compensation and health care. Results from the 2002 physical examination support adult-onset diabetes as the most important health problem seen in the Air Force Health Study. They suggest that as dioxin levels increase, not only are the presence and severity of adult-onset diabetes increased, but the time to onset of the disease is decreased. A 166 percent increase in diabetes requiring insulin control was seen in those with the highest levels of dioxin, consistent with the strong evidence found in animal studies.
> There seems to be a no studies > which have proven dioxin to actually causing diabetes.
http://en.wikipedia.org/wiki/GLUT4 GLUT4 is the insulin-regulated glucose transporter found in adipose tissues and striated muscle (skeletal and cardiac) that is responsible for insulin-regulated glucose disposal.
TCDD suppresses insulin-responsive glucose transporter (GLUT-4) gene expression through C/EBP nuclear transcription factors in 3T3-L1 adipocytes. TCDD is known to reduce significantly the level of the functionally active form of glucose transporter type 4 (GLUT4) in vivo in adipose tissue and muscles ... These results implicate the C/EBP proteins to be the main mediator of suppressive action of TCDD on GLUT4 gene expression in 3T3-L1 cells. PMID: 16615095
Differential effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the "adipose- type" and "brain-type" glucose transporters in mice. ... We conclude that regulation by TCDD of glucose transport activity in mice is an aryl, hydrocarbon receptor-dependent process and that the adipose-type GLUT4 appears to be regulated at the mRNA level, whereas the brain-type GLUT1 is affected mainly at the protein level. PMID: 7530807
Associations of environmental exposure to dioxins with prevalent diabetes among general inhabitants in Japan. The aim of this study was to evaluate the associations of environmental exposure to dioxins with diabetes among general inhabitants in Japan. A cross-sectional study was performed on 1374 participants, who were not occupationally exposed to dioxins, aged 15-73 years, living widely in 75 different residential areas of 25 prefectures in Japan through 2002-2006. ...This recent representative data from general inhabitants in Japan showed associations of environmental exposure to dioxins, especially dioxin-like PCBs, with diabetes. PMID: 18649880
Environmental contaminants as risk factors for developing diabetes. The contribution of exposure to persistent organic pollutants (POPs) to the incidence of diabetes has received little attention until recently. A number of reports have emerged, however, concerning elevated diabetes in persons occupationally exposed to dioxin. United States (US) Air Force personnel in Vietnam who sprayed Agent Orange containing dioxin as a contaminant had elevated rates of diabetes, leading to US government compensation for diabetes in these veterans. Recent studies in populations exposed to polychlorinated biphenyls (PCBs) and chlorinated pesticides found a dose-dependent elevated risk of diabetes. An elevation in risk of diabetes in relation to levels of several POPs has been demonstrated by two different groups using the National Health and Nutrition Examination Survey (NHANES), a random sampling of US citizens. The strong associations seen in quite different studies suggest the possibility that exposure to POPs could cause diabetes. One striking observation is that obese persons that do not have elevated POPs are not at elevated risk of diabetes, suggesting that the POPs rather than the obesity per se is responsible for the association. Although a specific mechanism is not known, most POPs induce a great number and variety of genes, including several that alter insulin action. Because diabetes is a dangerous disease that is increasing in frequency throughout the world, further study of the possibility that exposure to POPs contributes to the etiology of diabetes is critical. PMID: 18557598
Increased risk of diabetes and polychlorinated biphenyls and dioxins: a 24-year follow-up study of the Yucheng cohort. 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... 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
Bisphenol-A disruption of the endocrine pancreas and blood glucose homeostasis. The link between endocrine disruptors and altered blood glucose homeostasis has been recently suggested. Epidemiological studies have correlated levels of phthalates, dioxins and persistent organic pollutants with alterations of blood glucose homeostasis in humans. Environmentally relevant doses of the ubiquitous endocrine disruptor bisphenol-A (BPA) have profound effects on mice endocrine pancreas--an essential tissue involved in glucose metabolism. BPA exerts rapid non- genomic effects on insulin releasing beta-cells and glucagon releasing alpha-cells within freshly isolated islets of Langerhans. In vivo, a single BPA injection of 10 microg/kg rapidly increases plasma insulin and concomitantly decreases glycaemia. When mice were treated with BPA 100 microg/kg/day for 4 days, the environmental oestrogen produced an increase in beta-cell insulin content along with a post-prandial hyperinsulinaemia and insulin resistance. The results reviewed here demonstrate that doses well below the current lowest observed adverse effect level considered by the US-EPA, disrupt pancreatic beta-cell function producing insulin resistance in male mice. Therefore, this altered blood glucose homeostasis by BPA exposure may enhance the risk of developing type II diabetes. PMID: 17971160
Exposure to persistent organochlorine pollutants and type 2 diabetes mellitus. Persistent organochlorine pollutants (POPs), such as polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs), dichloro diphenyl trichloroethane (DDT) and its major metabolite 1,1- dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p' -DDE) have been associated with type 2 diabetes mellitus (T2DM) in recent epidemiological studies...The study shows an association between POP serum concentrations and an increased prevalence of T2DM. PMID: 17623770
Association of a polychlorinated dibenzo-p-dioxin, a polychlorinated biphenyl, and DDT with diabetes in the 1999-2002 National Health and Nutrition Examination Survey. The association of a polychlorinated dibenzo-p-dioxin, a polychlorinated biphenyl, and p,p'-DDT with diabetes was evaluated using the 1999-2002 National Health and Nutrition Examination Survey. ... PCB 126 and p,p'-DDT were significantly associated with undiagnosed diabetes. 1,2,3,6,7,8-hexachlorodibenzo-p-dioxin (HxCDD) was not associated with undiagnosed diabetes. ... These findings add to the list of chemicals found to be associated with diabetes in the 1999-2002 National Health and Nutrition Examination Survey. PMID: 17187776
White adipose tissue: storage and effector site for environmental pollutants. White adipose tissue (WAT) represents a reservoir of lipophilic environmental pollutants, especially of those which are resistant to biological and chemical degradation - so-called persistent organic pollutants (POPs). Large amounts of different congeners and isomers of these compounds exhibit a variety of adverse biological effects. Interactions among different classes of compounds, frequently with opposing effects, complicate hazard evaluation and risk assessment. WAT is the key organ for energy homeostasis and it also releases metabolites into the circulation and adipokines with systemic effects on insulin sensitivity and fuel partitioning in muscles and other tissues. Its beneficial role is lost in obesity when excessive accumulation of WAT contributes to severe diseases, such as diabetes. POPs may crossroad or modulate the effect of endogenous ligands of nuclear transcription factors, participating in differentiation, metabolism and the secretory function of adipocytes. These mechanisms include, most importantly: i) endocrine disrupting potency of POPs mixtures on androgen, estrogen or thyroid hormone metabolism/functions in WAT, ii) interference of dioxin-like chemicals with retinoic acid homeostasis, where impact on retinoid receptors is expected, and iii) interaction with transcriptional activity of peroxisome proliferator- activated receptors is likely. Thus, the accumulation and action of POPs in WAT represents a unitary mechanism explaining, at least in part, the effects of POPs in the whole organism. By modulating WAT differentiation, metabolism and function, the POPs could affect not only the physiological role of WAT, but they may also influence the development of obesity-associated diseases. PMID: 16925464
> There seems to be a no studies which have proven dioxin to actually > causing diabetes.
Transcriptional regulation of cyclooxygenase-2 gene in pancreatic beta- cells. Prostaglandin E(2) (PGE(2)) has been shown to negatively affect pancreatic beta-cell function, and its inducible synthesis is mediated in part by cycloxygenase-2 (COX-2)...COX-2 promoter activity was also increased by 2,3,7,8-tetrachlorodibenzo-p-dioxin, an AhR activator, ... 2,3,7,8-tetrachlorodibenzo-p-dioxin increased COX-2 mRNA in a dose-dependent manner... PMID: 15213229
The stimulation of tumor necrosis factor and inhibition of glucose transport and lipoprotein lipase in adipose cells by 2,3,7,8- tetrachlorodibenzo-p-dioxin. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is found throughout the environment in industrialized countries, and most people have had some exposure. TCDD has very high lipid solubility and is concentrated in adipose tissue. Because an epidemiologic association between TCDD exposure and diabetes has been described, we examined the effects of TCDD in adipocytes. The addition of TCDD to 3T3-F442a cells, both at the initiation of differentiation and after cells were fully differentiated, resulted in a 2-fold increase in the secretion of tumor necrosis factor (TNF). When added during differentiation, there was also a 25% decrease in lipid accumulation. In addition to the stimulation of TNF, TCDD affected glucose transport and lipoprotein lipase (LPL) activity. When added to cultures of cells that were undergoing differentiation, TCDD inhibited total 2-deoxyglucose transport in a dose-dependent fashion, with 50% inhibition of glucose transport when added to cultures for 48 hours at 5 nmol/L TCDD. In addition, when cells were exposed to 50 nmol/L TCDD for 48 hours, there was a 40% reduction in LPL activity. Thus, the addition of TCDD to adipocyte cultures resulted in an increase in TNF secretion and a decrease in glucose transport and LPL activity. Because TCDD is concentrated in adipose tissue, these studies provide a possible physiologic mechanism for epidemiologic studies that link dioxin to diabetes. PMID: 11782874
Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is associated with hyperinsulinemia and insulin resistance. High exposures of Vietnam veterans to 2,3,7, 8-Tetrachlorodibenzo-p- dioxin, a dioxin contained in the herbicide mixture Agent Orange, have previously been demonstrated to be associated with an increased prevalence of diabetes and hyperinsulinemia in non-diabetic subjects. Sixty-nine persons were identified who were in good health and had normal glucose levels during glucose tolerance testing. These subjects lived within 25 miles of the Vertac/Hercules Superfund site located in Jacksonville, Arkansas. The blood sera lipid concentrations of TCDD for the 69 subjects ranged between 2 and 94 ppt. When subjects with blood sera lipid TCDD levels in the top 10% (TCDD > 15 ppt, n = 7) were compared to subjects with lower levels (2-15 ppt, n = 62), there were no group differences in age, obesity, gender distribution, total lipids, or glucose levels. However, plasma insulin concentrations, at fasting and 30, 60, and 120 min following a 75 g glucose load, were significantly higher in the group with high blood TCDD levels. These finding could not be explained by other known risk factors for hyperinsulinemia. The finding of the TCDD-hyperinsulinemia relationship is consistent with studies of Vietnam veterans and suggests that high blood TCDD levels may cause insulin resistance. PMID: 10911003
Evaluation of diabetes mellitus, serum glucose, and thyroid function among United States workers exposed to 2,3,7,8-tetrachlorodibenzo-p- dioxin. OBJECTIVE: Some studies suggest that exposure to 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD) may affect glucose metabolism and thyroid function. To further assess the relation between exposure to TCDD and endocrine function, data from the largest morbidity study of industrial workers exposed to TCDD were examined.... CONCLUSIONS: These findings provide modest evidence that exposure to TCDD may affect thyroid function and glucose metabolism. PMID: 10450245
