Urinary organophosphate esters metabolites, glucose homeostasis and prediabetes in adolescents

Emerging experimental evidence indicates that organophosphate esters (OPEs) can trigger glucose metabolic disorders. However, human evidence, especially in adolescents, is unavailable.

We utilized data from the National Health and Nutrition Examination Survey 2011-2014 to evaluate whether urinary OPEs metabolites were associated with prediabetes and glucose homeostasis.

A total of 349 adolescents (12-19-year old) who provided at least 8 h fasting blood samples, had urinary OPEs metabolites detected were included. Prediabetes was defined according to the levels of fasting plasma glucose (FPG), 2-h post oral plasma glucose (2 h-OGTT) and glycated hemoglobin A1c (HbA1c). The homeostatic model assessment (HOMA-IR) and the Single Point Insulin Sensitivity Estimator (SPISE) were used to assess insulin resistance and sensitivity, respectively. Multiple binary logistic and linear regressions were used to evaluate the associations with prediabetes and indices of glucose homeostasis. The least absolute shrinkage and selection operator (LASSO) regression was used to assess the associations in a multi-pollutant context.

After adjusting for covariates, certain urinary OPEs metabolites were associated with prediabetes and indices of glucose homeostasis in all adolescents. Stratified analyses by sex revealed that such associations were largely sex-dependent. In females, the multiple pollutant models showed that bis(1,3-32 dichloro-2-propyl) phosphate (BDCIPP) was positively associated with prediabetes [odds ratio (OR) = 2.51, 95%CI:1.29, 4.89, for one scaled unit increase in exposure] and 2 h-OGTT (β = 0.07, 95%CI:0.01,0.12); bis(2-chloroethyl) phosphate (BCEP) was negatively associated with fasting insulin (β = -0.10, 95%CI: 0.19,-0.01) and HOMA-IR (β = -0.10, 95%CI: 0.19,-0.003); and detectable bis(1-choloro-2-propyl) phosphate (BCIPP) (>LOD vs < LOD) was inversely associated with 2 h-OGTT (β = -0.11, 95%CI: 0.21,-0.02). In males, consistent inverse associations were found for detectable di-n-butyl phosphate (DNBP) with prediabetes, FPG, 2 h-OGTT, fasting insulin and HOMA-IR.

Urinary OPEs metabolites were associated with prediabetes and indices of glucose homeostasis in adolescents. But such associations varied by sex. Future studies with multiple measurements of OPEs exposure are needed to confirm our findings.