Veterans and Agent Orange Herbicide/Dioxin Exposure and Type 2 Diabetes (2000) / Chapter Skim
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Appendix B: Excerpts from the Discussion of Type 2 Diabetes in Veterans and Agent Orange: Update 1998
Appendix B: Excerpts from the Discussion of Type 2 Diabetes in Veterans and Agent Orange: Update 1998
Pages 47-60
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From page 47... ...
The usual autoi~une form results in complete p-cell destruction and complete insulinopenia, hence the "insulin dependency" of earlier classifications. The genetic basis of the autoimmune form is linked to the human lymphocyte antigen (HLA)
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From page 48... ...
The insulin receptor itself, insulin receptor tyrosine kinase activity, insulin receptor substrate proteins, insulin-regulated glucose transporters, enhanced protein kinase C (PKC) activity, tumor necrosis factor-a, red (ras associated with diabetes)
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Pathogenetic diversity and diagnostic uncertainty are two of the more significant problems. Pathogenetic Diversity Given the multiple likely pathogenetic mechanisms leading to diabetes, which include diverse genetic susceptibilities (ranging from autoimmunity to obesity)
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of 117 2,4,5-T production workers with chloracne compared to 109 without, 10-20+ years after mixed accidental and chronic TCDD exposure (Moses et al., 1984~. Two mortality studies provide further negative data.
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The major impact of obesity in determining both diabetes risk and serum dioxin level has to be fully controlled for before firm conclusions can be drawn. In view of the potential importance of the most recent report from this ongoing Ranch Hand study, it is reviewed here in more detail.
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May, 1982 TCP production workers 2 Pazderova-Vejlupkova et 2,4,5-T and TCP production al., 1981 workers lion workers BASE production workers 10 0.5 (0.2-1.0) ENVIRONMENTAL Studies reviewed in VAO Bertazzi et al., 1989b Seveso residents Males Females VIETNAM VETERANS New Studies Henriksen et al., 1997c Ranch Hands o.o6c 1.6 (0.9-3 0)
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From page 53... ...
Two somewhat conflicting definitions are given of a case of diabetes: one implies that all cases were clinically verified in medical records; the other is a combination of history and glucose testing after a standard meal or 100-g oral glucose tolerance test (OGTT)
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From page 54... ...
and appears to eliminate the significance of the negative coefficient of "time to onset of diabetes." A further matched analysis is described, including matching within 3 percent body fat, but relative risks (without confidence intervals) are given only for glucose and insulin values and not for diabetes risk or diabetes severity.
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From page 55... ...
However, in a multiple logistic regression analysis, significant associations between sermon TCDD level and diabetic status or (in those without diabetes) fasting blood sugar, were apparently noted that were independent of major confounders (age, body mass index, race, and family history of diabetes)
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From page 56... ...
Finally, since TCDD has been shown to affect hormone (including insulins signaling, the likelihood that TCDD may be diabetogenic is further increased (Liu and Safe, 1996~. Thus, in su~runa~, many animal studies provide potential biological mechanisms for an association between herbicide exposure and diabetes risk, and although the majority of earlier reports on humans suggest little association, the potentially more definitive 1997 report from the Ranch Hand study (Henriksen et al., 1997)
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1993. 2,3,7,8-Tetrachlorodibenzo-p-dioxin induced alterations in protein phosphorylation in guinea pig adipose tissue.
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Subject: Answers to Questions Regarding Dioxin and Diabetes Mellitus posed by the Committee to Review the Health Effects of Exposure to Herbicides in Vietnam Veterans. Population Research Branch, Epidemiologic Research Division, Armstrong Laboratory, Brooks Air Force Base, Texas.
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1997. Review and update of the results of the NIOSH medical study of workers exposed to chemicals contaminated with 2,3,7,8-tetrachlorodibenzodioxin.
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APPENDIX C Committee and Staff Biographies COMMITTEE BIOGRAPHIES DAVID TOLLERUD, M.D., M.P.H. (Chair)
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