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

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