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Molecular epidemiologic evidence for diabetogenic effects of dioxin exposure in U.S. Air force veterans of the Vietnam war.

ABSTRACT: One of the outcomes positively associated with dioxin exposure in humans is type 2 diabetes.This study was conducted in order to find the molecular biological evidence for the diabetogenic action of dioxin in adipose samples from Vietnam veterans.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.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.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.

SUBMITTER: Fujiyoshi PT

PROVIDER: S-EPMC1665440 | biostudies-literature | 2006 Nov

REPOSITORIES: biostudies-literature

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Molecular epidemiologic evidence for diabetogenic effects of dioxin exposure in U.S. Air force veterans of the Vietnam war.

Fujiyoshi Phillip Thomas PT Michalek Joel Edmund JE Matsumura Fumio F

Environmental health perspectives 20061101 11

<h4>Background</h4>One of the outcomes positively associated with dioxin exposure in humans is type 2 diabetes.<h4>Objectives</h4>This study was conducted in order to find the molecular biological evidence for the diabetogenic action of dioxin in adipose samples from Vietnam veterans.<h4>Methods</h4>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 ...[more]

PMID: 17107852

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Project description:ObjectivesThe aim was to observe the patterns of mortality and cancer incidence in New Zealand Vietnam veterans. The objectives were to assess whether the patterns of disease observed were consistent with those associated with military service in Vietnam, and similar to the patterns identified in other groups of Vietnam veterans.DesignA historical cohort study.SettingVeterans, identified from service records, with Vietnam service between 1964 and 1972.ParticipantsOf the 3322 survivors of Vietnam service, we followed up 2783 (84%).Outcome measuresStandardised mortality and incidence ratios (SMRs and SIRs, respectively) were calculated based on the number of deaths and cancer registrations observed, those expected being based on New Zealand national rates.ResultsAll cause mortality was significantly reduced (SMR 0.85, 95% CI 0.77 to 0.94) and cancer incidence non-significantly increased (SIR 1.06, 95% CI 0.97 to 1.16). The risk of mortality from cancers of the head and neck (SMR 2.20, 95% CI 1.09 to 3.93); oral cavity pharynx and larynx (SMR 2.13, 95% CI 1.06 to 3.81) and the incidence of chronic lymphatic leukaemia (CLL) (SIR 1.91, 95% CI 1.04 to 3.20) were, however, significantly increased. Other lymphohaematopoietic disorders, specifically multiple myeloma and Hodgkin disease, showed non-significant mortality excesses, reflected by a similar increase in incidence.ConclusionsService in the Vietnam war was associated with defoliant herbicide exposure, including 2,4,5-trichlorophenoxyacetic acid, 2,4-dichlorophenoxyacetic acid, picloram and cacodylic acid. Subsequent reviews of mechanistic, animal and epidemiological evidence led to certain conditions being deemed compensable. The pattern of mortality and cancer incidence is not at odds with the list of compensable conditions and consistent with that found in Australian veterans serving in the same area of Vietnam, but also consistent with smoking and the healthy soldier effect. In common with the Australian experience, this is the only veterans group to show a significant excess of CLL.

Project description:IntroductionThe Air Force uses dental caries risk assessments (CRA) to determine which active duty Air Force (ADAF) members are at high caries risk (HCR) and will benefit from additional preventive and restorative dental care. The purpose of this study is to describe the caries risk of ADAF from 2009 to 2017 and determine how demographic, military, and tobacco-use characteristics affect caries risk.Materials and methodsData from ~300,000 ADAF annual dental examinations from 2009 to 2017 were used. The outcome variable investigated was dental caries risk (high, moderate, or low). Independent variables analyzed were: age, sex, race, education, marital status, military rank, service years, flying status, and tobacco use. Descriptive and multivariable analyses were performed to explore associations between potential risk indicators and caries risk outcomes.ResultsFrom 2009 to 2013, there was a steady decline in ADAF that were diagnosed as low caries risk (LCR), from 80.3% to 67.7%. Since 2013, the prevalence of ADAF that are LCR has remained unchanged at about two-thirds of the force. The proportion of the ADAF that are moderate caries risk (MCR) increased from 15.7% in 2009 to 25.3% in 2013 and remained unchanged affecting about a quarter of the force since then. The proportion that was diagnosed as HCR increased from 3.9% in 2009 to 7.1% in 2013 and declined slightly in 2017 (6.0%). After controlling for other covariates, younger age (<20 years old: odds ratio [OR], 4.4; 95% confidence interval [CI], 3.3-5.8), less time in service (≤4 years: OR, 2.1; 95% CI, 1.7-2.6), junior rank (E-1-E-4: OR, 1.6; 95% CI, 1.3-1.8), less education (high-school graduate: OR, 2.3; 95% CI, 2.0-2.6), using tobacco (Smoker: OR, 1.6; 95% CI, 1.5-1.7), being a nonflyer (OR, 1.2; 95% CI, 1.1-1.3), being male (OR, 1.1; 95% CI, 1.1-1.2), or being black (OR, 1.2; 95% CI, 1.1-1.2) were each associated with being HCR. Among the cohort of Airmen who were LCR at baseline, the majority (75.9%) remained at low risk, but for nearly a quarter (24.1%), their risk of caries increased over 9 years. Among those who were originally MCR in 2009, 61.5% improved to LCR, whereas 4.6% progressed to HCR; among those identified as high risk for caries in 2009, a substantial majority (89.1%) improved over 9 years, but 10.9% remained unchanged.ConclusionsThe prevalence of HCR and MCR service members increased from 2009 to 2013 but has remained consistent since 2013. Overall caries risk in the Air Force is lower compared to previously published findings from 2001 to 2004. This suggests that CRA and prevention programs have been effective at helping to reduce caries prevalence among Airmen. Smoking prevalence among ADAF has also declined substantially over the past 16 years which may contribute to overall caries risk reductions. Using a CRA approach may be an effective tool for helping to identify and develop strategies to manage dental caries risk in patients.

Project description:BackgroundEnvironmental epidemiology, when focused on the life course of exposure to a specific pollutant, requires historical exposure estimates that are difficult to obtain for the full time period due to gaps in the historical record, especially in earlier years. We show that these gaps can be filled by applying multiple imputation methods to a formal risk equation that incorporates lifetime exposure. We also address challenges that arise, including choice of imputation method, potential bias in regression coefficients, and uncertainty in age-at-exposure sensitivities.MethodsDuring time periods when parameters needed in the risk equation are missing for an individual, the parameters are filled by an imputation model using group level information or interpolation. A random component is added to match the variance found in the estimates for study subjects not needing imputation. The process is repeated to obtain multiple data sets, whose regressions against health data can be combined statistically to develop confidence limits using Rubin's rules to account for the uncertainty introduced by the imputations. To test for possible recall bias between cases and controls, which can occur when historical residence location is obtained by interview, and which can lead to misclassification of imputed exposure by disease status, we introduce an "incompleteness index," equal to the percentage of dose imputed (PDI) for a subject. "Effective doses" can be computed using different functional dependencies of relative risk on age of exposure, allowing intercomparison of different risk models. To illustrate our approach, we quantify lifetime exposure (dose) from traffic air pollution in an established case-control study on Long Island, New York, where considerable in-migration occurred over a period of many decades.ResultsThe major result is the described approach to imputation. The illustrative example revealed potential recall bias, suggesting that regressions against health data should be done as a function of PDI to check for consistency of results. The 1% of study subjects who lived for long durations near heavily trafficked intersections, had very high cumulative exposures. Thus, imputation methods must be designed to reproduce non-standard distributions.ConclusionsOur approach meets a number of methodological challenges to extending historical exposure reconstruction over a lifetime and shows promise for environmental epidemiology. Application to assessment of breast cancer risks will be reported in a subsequent manuscript.

Dataset Information

Molecular epidemiologic evidence for diabetogenic effects of dioxin exposure in U.S. Air force veterans of the Vietnam war.

Publications

Molecular epidemiologic evidence for diabetogenic effects of dioxin exposure in U.S. Air force veterans of the Vietnam war.

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