Effects of environmental polycyclic aromatic hydrocarbon exposure and pro-Inflammatory activity on Type 2 Diabetes Mellitus

Abstract

ABSTRACTBackgroundPolycyclic aromatic hydrocarbons (PAHs) are formed due to incomplete combustion and known for their potential impact and persistence in the environment. PAHs exposure have been linked to cause adverse health effect including cancer and genetic mutations. The understanding of metabolic effects of PAH exposure are still less clear especially in the presence of pro-inflammatory stress like alcoholism or diabetes.ObjectiveThe aim of this article is to understand the metabolic effects of PAH exposure by analyzing the clinical biomarkers. This study has also accessed the interactive impact of PAH and other proinflammatory factors, like alcohol intake on the metabolic syndrome, especially Type 2 Diabetes Mellitus (T2DM).MethodsAll the data in this study are retrieved from CDC NHANES (2015-16). We investigated urinary levels of hydroxylated PAH metabolites (OH-PAHs) along with demographic, clinical and laboratory data. Questionnaire data for alcohol use and diabetes status were also included along with laboratory data. Laboratory measures included in the study were levels of PAHs, glycohemoglobin, glucose, cholesterol, lipids, triglyceride, complete blood count, lymphocytes, and monocytes. Generalize linear model Univariate factorial ANOVA was used to evaluate the group differences (both between the groups; as well as across all the groups) in the demographics, PAH exposure, drinking patterns, clinical data, and biomarker levels. Linear regression model was used to analyze the association of biomarkers, PAH exposure and drinking data. Multivariable regression model was used for multi-independent model to assess comorbidity association and their effect sizes on the clinical outcomes.ResultsBMI (p=0.002), and age (≤0.001) are independent demographic risk factors for T2DM in high PAH exposure. Acute proinflammatory activity characterized by CRP, is augmented by elevated monocyte levels (p≤0.001) and stepwise addition of 1-HN (p=0.005), and 2-HN (p=0.001) independently. Prevalence of highest average drinks over time is observed in the high PAH exposure; with males drinking almost twice compared to females in Gr.3. Pathway response of T2DM shows sexual dimorphism; with males showing association with triglycerides (p≤0.001), and females with CRP (p=0.015) independently with HbA1C. The arrangement of CRP, absolute monocyte levels, serum triglycerides and average drinks over time predict the HbA1C levels (adjusted R2=0.226, p≤0.001) in individuals with high PAH exposure.DiscussionIn this large dataset investigation on humans, the adverse effects of high exposure of PAHs identified candidate demographic risk factors. Preclinical experimental studies on mice have suggested that PAHs exposure induces lipid metabolic disorders in a time-dependent manner, which we found in humans too. Sexual dimorphism is observed in alcohol drinking with males drinking more in the high PAH exposure group. Alcohol drinking as an independent factor associated with the DMT2 indicator, HbA1C in individuals with high PAH exposure.HighlightsBMI and Age are demographic risk factors for Diabetes Mellitus Type 2 (DMT2) in high PAH exposureAcute proinflammatory activity characterized by CRP, is augmented by elevated monocyte levels and 1-HN and 2-HN independentlyPrevalence of higher average drinks over time is observed with high PAH exposurePathway of DMT2 shows sexual dimorphism, with males showing association with triglycerides, and females with CRP independently with HbA1CThe arrangement of CRP, absolute monocyte levels, serum triglycerides and average drinks over time predict the HbA1C levels in individuals with high PAH exposure.