Persistent organic pollutants (POPs), such as dichlorodiphenyltrichloroethane (DDT)
and other organochlorine compounds, are abundant in the environment and in foodstuffs
from the Indian subcontinent. These environmental contaminants have been associated
with a higher risk of diabetes in numerous studies. Asian Indians are well known to
have a high risk of diabetes compared with other populations, and this risk is also
found in migrant populations of Asian Indians in the United States, Europe, and elsewhere.
We hypothesized that high plasma concentrations of POPs in Asian Indian migrants are
linked to a variety of diabetes-related pathologies and explored the mechanism for
the induction of these effects. We measured 30 environmental pollutants in plasma
samples obtained from 147 participants in the metabolic syndrome and atherosclerosis
in South Asians living in America pilot study using a gas chromatography–tandem mass
spectrometry analytical method that uses less than 0.5 mL of plasma. We found that
plasma levels of o , p ′-DDT and p , p ′-DDT were independently associated with
both body mass index (BMI) and waist circumference. Doubling the levels of the sums
of these DDTs was associated with insulin insensitivity (−0.54 Matsuda index, p
= 0.0009), increased adiposity (1.38 kg/m 2 BMI and 4.44 cm waist circumference increase,
p < 0.0001), circulating insulin (14.3 mIU/L, p = 0.001), hepatic fat (−0.07 HU,
p < 0.0001), as well as increased odds of obesity (OR = 2.17, p < 0.001, BMI-based;
OR = 2.37, p = 0.001, waist-based), prediabetes (OR = 1.73, p = 0.01), diabetes
(OR = 2.02, p = 0.003), and fatty liver (OR = 2.40, p = 0.002) in multivariable
models accounting for confounding by age, sex, years in the US, education, fish protein,
and a lindane isomer α -hexachlorocyclohexane. Furthermore, p , p ′-DDT levels were
associated with increased hepatic fat and circulating insulin, as well as decreased
insulin sensitivity, independent of obesity and confounders. These findings suggest
that p , p ′-DDT exposure may contribute to the risk of metabolic disease among Asian
Indians by affecting hepatic fat levels independent of obesity.