persistent pesticide exposure, polycyclic aromatic hydrocarbons and cardiome

75 Pages·2014·0.53 MB·English

ASSOCIATIONS BETWEEN URINARY CONCENTRATIONS OF NON-
PERSISTENT PESTICIDE EXPOSURE, POLYCYCLIC AROMATIC
HYDROCARBONS AND CARDIOMETABOLIC HEALTH

MAHSA RANJBAR

A THESIS SUBMITTED TO THE FACULTY OF GRADUATE STUDIES IN
PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF
MASTER OF SCIENCE

GRADUATE PROGRAM IN KINESIOLOGY AND HEALTH SCIENCE
YORK UNIVERSITY
TORONTO, ONTARIO
AUGUST 2014

© MAHSA RANJBAR, 2014
ABSTRACT
Recent literature has established environmental pollutants to be associated
with health risk. However, it remains unclear whether the less studied
organophosphate (OP) pesticides and polycyclic aromatic hydrocarbons (PAH)
influence cardiometabolic health independent of BMI. The first study in this thesis
used 2,227 participants from the National Health and Nutrition Examination Survey
(NHANES). It was demonstrated that most OPs are associated with a detrimental
cardiometabolic health outcome with higher BMIs amplifying health risk. However
one metabolite (dimethylphosphate) was associated with advantageous health
outcomes. In the second study, 6,159 NHANES participants were used to demonstrate
that high levels of PAH are positively and negatively associated with obesity. PAH
was also associated with a greater risk of metabolic syndrome, dyslipidemia,
hypertension, and type 2 diabetes, independent of BMI. Thus, OP and PAH influence
obesity-related health risk, however, more research is needed to further elucidate the
mechanistic pathways associated with OP, PAH and health.

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ACKNOWLEDGEMENTS

Tell me and I forget, teach me and I may remember, involve me and I learn –
Benjamin Franklin. Thank you to my committee members, Dr. Michael Rotondi and
Dr. Chris Ardern for your insight, helpful suggestions, comments, and edits of both
studies. Thank you to my teacher and supervisor, Dr. Jennifer Kuk, for instilling in me
a sense of curiosity and passion for research. Thank you for being patient with me as
we went through draft after draft of work, and thank you for believing in me a heck of
a lot more than I believed in myself.

What is a friend? A single soul dwelling in two bodies. – Aristotle. Thank you
Karissa for showing me the ropes and giving me hope. Thank you Ruth for all of your
help and encouragement. Thank you Thiru for being a beacon of advice and for your
honesty. Thank you Mike and Dishay for lightening the mood and for always being
positive. Finally, thank you Sarah, for whom this experience would not have been
nearly as memorable. I cherish the late nights and weekends we spent together and all
the outrageous and silly situations we managed to find ourselves in. I can’t imagine
having gone through this experience without you.

In family life, love is the oil that eases friction, the cement that binds closer
together, and the music that brings harmony - Friedrich Nietzsche. Thank you to my
parents who never falter in their love for me, who have made sacrifices for me, and
whose aim is to see me happy. Thank you to my brother, Shervin, for pushing me to
take risks and make change, for inspiring me to be proactive, and for always being
supportive of me.

What lies behind us and what lies before us are tiny matters compared to what lies
within us – Ralph Waldo Emerson

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TABLE OF CONTENTS
ABSTRACT .............................................................................................................................. ii
TABLE OF CONTENTS......................................................................................................... iv
LIST OF TABLES ................................................................................................................... vi
LIST OF FIGURES ................................................................................................................ vii
LIST OF ABBREVIATIONS ................................................................................................ viii
CHAPTER 1.0 GENERAL INTRODUCTION ....................................................................... 1
CHAPTER 2.0 REVIEW OF RELATED LITERATURE ..................................................... 3
Introduction on Organophosphate Pesticide ............................................................................................... 3
Organophosphate Pesticide................................................................................................................................ 5
Organophosphate Pesticide and Glucose Markers ................................................................................... 5
Organophosphate Pesticide and Blood Lipids ........................................................................................... 6
Organophosphate Pesticide and Blood Pressure ....................................................................................... 7
Organophosphate Pesticide and Weight Gain ........................................................................................... 8
Summary of Organophosphate Pesticide ..................................................................................................... 9
Introduction to Polycyclic Aromatic Hydrocarbons ............................................................................ 10
Polycyclic Aromatic Hydrocarbons and Obesity .................................................................................. 11
Polycyclic Aromatic Hydrocarbons and Type 2 Diabetes ................................................................. 12
Polycyclic Aromatic Hydrocarbons and Blood Lipids ....................................................................... 12
Polycyclic Aromatic Hydrocarbons and Cardiac Health ................................................................... 13
Summary of Polycyclic Aromatic Hydrocarbon Literature .............................................................. 14
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CHAPTER 3.0 MANUSCRIPT 1........................................................................................... 15
RESEARCH DESIGN AND METHODS ........................................................................... 16
National Health and Nutrition Examination Survey (NHANES) ........................................... 16
Study Participants and Exclusion Criteria ....................................................................................... 16
Assessment of Organophosphate Pesticide Exposure .................................................................. 17
Cardiometabolic Risk Factors ................................................................................................................ 18
Statistical Analysis ....................................................................................................................................... 19
RESULTS ................................................................................................................................ 20
DISCUSSION .......................................................................................................................... 22
CONCLUSIONS ..................................................................................................................... 25
CHAPTER 4.0 MANUSCRIPT 2........................................................................................... 32
RESEARCH METHODS ...................................................................................................... 34
Participants .................................................................................................................................................... 34
Polycyclic Aromatic Hydrocarbons ...................................................................................................... 34
Metabolic Syndrome, Dyslipidemia, Type 2 Diabetes and Hypertension ........................... 35
Statistical Analysis ....................................................................................................................................... 36
RESULTS ................................................................................................................................ 38
DISCUSSION .......................................................................................................................... 40
CHAPTER 5.0 GENERAL DISCUSSION ............................................................................ 50
CHAPTER 6.0 REFERENCES .............................................................................................. 53

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LIST OF TABLES

CHAPTER 3- MANUSCRIPT 1
Table 1a: Participant characteristics for those above and below the detection limit for
DMP, DMTP and DMDTP metabolites ............................................................................. 26

Table 1b: Participant characteristics for those above and below the detection limit for
DEP, DETP and DEDTP metabolites ................................................................................. 27

Table 2: Adjusted Least Square Means of cardiometabolic risk factors with each
individual organophosphate (OP) pesticide metabolite ....................................................... 28

CHAPTER 4- MANUSCRIPT 2
Table 1: Participant characteristic and metabolic syndrome status .................................... 45

Table 2: The association between PAH and BMI .............................................................. 46

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LIST OF FIGURES

CHAPTER 3- MANUSCRIPT 1
Figure 1 A-F): Relationship between HDL and BMI by DMP A), DMTP B),
DMDTP C), DEP D), DETP E) and DEDTP F) detection limit status. .............................. 29

Figure 2 A-F): Relationship between triglyceride and BMI by DMP A), DMTP B),
DMDTP C), DEP D), DETP E) and DEDTP F) detection limit status. ............................... 30

Figure 3 A-F): Relationship between insulin and BMI by DMP A), DMTP B),
DMDTP C), DEP D), DETP E) and DEDTP F) detection limit status. ............................... 31

CHAPTER 4- MANUSCRIPT 2
Figure 1: Prevalent ratio of metabolic syndrome A) and type 2 diabetes B) for those
in the highest quintiles of PAH compared to lower levels .................................................. 47

Figure 2: Prevalent ratio of hypertension for those in the highest quintiles of PAH
compared to lower levels ................................................................................................... 48

Figure 3: Prevalent ratio of dyslipidemia for those in the highest quintiles of PAH
compared to lower levels ................................................................................................... 49
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LIST OF ABBREVIATIONS

BMI Body Mass Index
CDC Center for Disease Control and Prevention
CRP C-reactive protein
CHD Coronary heart disease
CVD Cardiovascular disease
DAP Dialkyl phosphate
DBP Diastolic blood pressure
DEDTP Diethydithiophosphate
DEP Diethylphosphate
DETP Diethylthiophosphate
DMDTP Dimethyldithiophosphate
DMP Dimethylphosphate
DMTP Dimethylthiophosphate
GLU Plasma glucose
HbA1c Glycohemoglobin
HDL High-density lipoprotein cholesterol
HOMA-IR Homeostatic assessment of insulin resistance
LDL Low-density lipoprotein cholesterol
LSM Least squares means
MEC Mobile examination center
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MetS Metabolic syndrome
NHANES National Health and Nutrition Examination Survey
NWMP National Waste Minimization Program
OP Organophosphate
PAH Polycyclic aromatic hydrocarbons
PIR Poverty income ratio
PR Prevalence risk
SBP Systolic blood pressure
T2D Type 2 diabetes
WC Waist circumference

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CHAPTER 1.0 GENERAL INTRODUCTION
Cardiovascular disease (CVD) is the leading cause of death in the United States
(1) and the world (2). The economic burden of CVD is astronomical, costing the U.S an
estimated 500 billion dollars in direct and indirect costs in 2010 (3). Health conditions
including type 2 diabetes (T2D), hypertension, dyslipidemia, metabolic syndrome
(MetS), inflammation, and obesity are major risk factors for CVD (4). Due to its high
economic burden and its relation to disease and mortality, researchers have attempted to
identify the risk factors associated with CVD. The overwhelming majority of studies have
focused on demonstrating the significant influence health behaviours such as diet and
physical activity has on CVD (5,6), however, other possible factors contributing to
cardiometabolic health has gone largely unnoticed.
The environment is one aspect of cardiovascular health that has received less
attention. With the increased frequency and quantity of pesticide use, the likelihood of
exposure to such pollutants by the general public is high. Of the few studies examining
the effects of pesticides and environmental pollutants on health, the majority report
detrimental health effects associated with high exposure. For example, Brook et al. report
on the negative impact of air pollution on CVD in a comprehensive literature review (7).
Persistent organic pesticides (pesticides that remain in the environment for long periods
of time) have also been found to increase health risk for T2D, obesity (8) and even CVD
(9).
However, non-persistent pesticides such as organophosphates (OPs) and certain
environmental pollutants such polycyclic aromatic hydrocarbons (PAH) have not been
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