THE EFFECTS OF ACUTE PSYCHOSOCIAL STRESS ON HPA-AXIS AND SAM-AXIS FUNCTION ...

308 Pages·2014·12.18 MB·English

by  Kimberly Walter

The Pennsylvania State University

The Graduate School

Department of Biobehavioral Health

THE EFFECTS OF ACUTE PSYCHOSOCIAL STRESS ON HPA-AXIS AND
SAM-AXIS FUNCTION IN MEN WITH TYPE 2 DIABETES MELLITUS

A Dissertation in

Biobehavioral Health

by

Kimberly N. Walter

© 2014 Kimberly N. Walter

Submitted in Partial Fulfillment
of the Requirements for the Degree of
Doctor of Philosophy

May 2014
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The dissertation of Kimberly N. Walter was reviewed and approved* by the following:

Laura Cousino Klein
Associate Professor of Biobehavioral Health
Dissertation Adviser
Chair of Committee

David M. Almeida
Professor of Human Development and Family Studies

Elizabeth J. Susman
Professor of Biobehavioral Health

Sheila G. West
Associate Professor of Biobehavioral Health

John W. Graham
Professor of Biobehavioral Health
Professor-in-Charge of the Biobehavioral Health Graduate Program

*Signatures on file in the Graduate School
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Abstract
Type 2 diabetes mellitus is one of the most common and costly chronic diseases
in the United States and the world (Whiting et al., 2011). Scientists estimate that by 2050
one in three Americans will have type 2 DM (Boyle et al., 2010). Although type 2 DM
related mortality has declined in recent years, it remains a major public health concern
(Whiting et al., 2011). The exact etiology of type 2 DM is not known, but scientists have
identified multiple genetic and environmental factors (e.g., obesity, diet, socioeconomic
status, physical inactivity) that likely contribute to the pathogenesis and pathophysiology
of the disease (Codario, 2011). In recent years, scientists have started to investigate the
role of psychological factors, such as psychosocial stress, in the pathophysiology of type
2 DM (Nathan et al., 2009). Data from observational studies provide suggestive evidence
that psychosocial stress is a factor affecting type 2 DM onset and progression (e.g.,
Mommersteeg et al., 2012; Pouwer et al., 2010; Toshihiro et al., 2008). However, the
stress physiological mechanisms involved in the relationship are unclear, and there is a
paucity of research examining stress physiological processes in individuals with type 2
DM.
The primary aim of this dissertation was to determine if men with type 2 DM who
do not have major disease-related complications have dysregulated stress systems by
examining the effects of acute psychosocial stress exposure on HPA-axis and SAM-axis
function. A secondary aim of this dissertation was to investigate if allostatic load, a
measure of chronic stress exposure, influences stress physiological processes in men with
type 2 DM. This dissertation study used a mixed between- and within subjects-design to
examine the effects of type 2 DM and acute psychosocial stress (Trier Social Stress Test)
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on stress physiology in a sample of 34 men (20 healthy, 14 type 2 DM) between the ages
of 25 and 65. Primary dependent measures included biomarkers of the HPA-axis
(salivary cortisol, salivary DHEA-S) and SAM-axis (salivary alpha-amylase), as well as
allostatic load parameters (cardiovascular, metabolic, neuroendocrine, anthropometric,
immune measures). Results revealed that men with type 2 DM displayed significantly
higher total allostatic load levels and significantly lower DHEA-S levels compared to
healthy men. Furthermore, men with type 2 DM were able to mount both HPA- and
SAM-axis responses to the acute stressor that was comparable to the healthy participants.
Overall, the findings suggest that men with type 2 DM without major disease-related
complications are able to physiologically respond to acute psychosocial stressors, in spite
of having increased total allostatic load and decreased DHEA-S levels.
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Table of Contents

LIST OF TABLES…………………………………………………………………….............xi
LIST OF FIGURES …..…………………...………………….…………………...………....xii
ABBREVIATIONS………………………………………………………………………….xiii
ACKNOWLEDGEMENTS……………………………………………..…………………...xvi
CHAPTER 1: INTRODUCTION .............................................................................................. 1
SCOPE OF PROBLEM ............................................................................................................. 1
TYPE 2 DIABETES MELLITUS ............................................................................................... 4
Pathophysiology of Type 2 Diabetes Mellitus ............................................................... 4
Diagnosis and Treatment................................................................................................ 7
ACUTE STRESS PHYSIOLOGY ............................................................................................... 9
HPA-Axis ..................................................................................................................... 10
Sympathetic Nervous System ...................................................................................... 15
Immune System ............................................................................................................ 18
CHRONIC STRESS AND ALLOSTATIC LOAD......................................................................... 19
TYPE 2 DIABETES MELLITUS AND STRESS ......................................................................... 24
Psychosocial Stress and Type 2 DM ............................................................................ 25
Type 2 DM and Stress Physiology ............................................................................... 26
Type 2 DM and Allostatic Load................................................................................... 30
TYPE 2 DIABETES MELLITUS, ALLOSTATIC LOAD, AND STRESS PHYSIOLOGY ................... 31
CHAPTER 2: METHODS ....................................................................................................... 33
OVERVIEW ......................................................................................................................... 33
HYPOTHESES ...................................................................................................................... 33
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Hypothesis 1: Salivary Free Cortisol ........................................................................... 33
Hypothesis 2: Salivary DHEA-S .................................................................................. 34
Hypothesis 3: Salivary Alpha-Amylase (sAA) ............................................................ 35
Hypothesis 4: Allostatic Load ...................................................................................... 35
Hypothesis 5: Effect of Allostatic Load on Stress Reactivity and Stress Recovery .... 36
PARTICIPANTS .................................................................................................................... 37
Participant Characteristics ............................................................................................ 37
Recruitment .................................................................................................................. 39
Exclusionary Criteria ................................................................................................... 42
Type 2 Diabetes Mellitus Status .................................................................................. 43
PROTOCOL ......................................................................................................................... 43
Health Screening Session ............................................................................................. 43
Test Session .................................................................................................................. 45
Biological Sample Collection and Storage .................................................................. 51
Biomarker Assay Procedures ....................................................................................... 52
Self-Report Measures ................................................................................................... 55
DATA ANALYTIC STRATEGY .............................................................................................. 57
Data Preparation ........................................................................................................... 57
Statistical Analysis Plan ............................................................................................... 63
CHAPTER 3: RESULTS ......................................................................................................... 68
STRESSOR CONFIRMATION ................................................................................................. 68
Self-Reported Stress ..................................................................................................... 68
Systolic Blood Pressure ............................................................................................... 68
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Diastolic Blood Pressure .............................................................................................. 69
Heart Rate..................................................................................................................... 70
HPA-AXIS STRESS PHYSIOLOGY ......................................................................................... 70
Salivary Cortisol .......................................................................................................... 70
Salivary DHEA-S ......................................................................................................... 72
SAM-AXIS STRESS PHYSIOLOGY....................................................................................... 75
Salivary α-amylase ....................................................................................................... 75
ALLOSTATIC LOAD ............................................................................................................ 77
Group Differences in Allostatic Load .......................................................................... 77
Allostatic Load and Stress System Physiology ............................................................ 79
SUMMARY OF HYPOTHESES ............................................................................................... 82
Hypothesis 1: Salivary free cortisol ............................................................................. 82
Hypothesis 2: Salivary DHEA-S .................................................................................. 82
Hypothesis 3: Salivary alpha-amylase (sAA) .............................................................. 84
Hypothesis 4: Allostatic Load ...................................................................................... 84
Hypothesis 5: Effect of Allostatic Load on Stress Reactivity and Stress Recovery .... 85
CHAPTER FOUR: DISCUSSION .......................................................................................... 87
OVERVIEW ......................................................................................................................... 87
STRESS PHYSIOLOGY AND TYPE 2 DM FINDINGS .............................................................. 88
Stressor Confirmation .................................................................................................. 88
HPA-Axis Findings ...................................................................................................... 89
SAM-Axis .................................................................................................................... 96
ALLOSTATIC LOAD FINDINGS ............................................................................................ 98
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LIMITATIONS .................................................................................................................... 100
OVERALL CONCLUSIONS .................................................................................................. 103
REFERENCES ....................................................................................................................... 123
APPENDICES ....................................................................................................................... 146
APPENDIX A. INSTITUTIONAL REVIEW BOARD APPROVAL LETTER ................................. 147
1. Pennsylvania State University IRB ....................................................................... 148
2. Mount Nittany Hospital......................................................................................... 150
APPENDIX B. RECRUITMENT MATERIALS ........................................................................ 152
1. Advertisements ....................................................................................................... 153
2. Letter to Medical Offices ....................................................................................... 162
3. Penn State Listserv Text ........................................................................................ 164
4. Diabetes Registry Letter ......................................................................................... 166
5. Penn State Hershey Medical Group Recruitment Script ........................................ 168
APPENDIX C. TELEPHONE SCREENING INTERVIEW........................................................... 170
APPENDIX D. TELEPHONE SCREENING INELIGIBILITY LETTER ......................................... 177
APPENDIX E. REMINDER LETTERS................................................................................... 179
1. Health Screening Session ....................................................................................... 180
2. Test Session ............................................................................................................ 182
APPENDIX F. INFORMED CONSENT FORM ........................................................................ 184
APPENDIX G. HEALTH SCREENING SESSION PROCEDURES............................................... 191
APPENDIX H. HEALTH SCREENING SESSION QUESTIONNAIRES ........................................ 193
1. Demographic Form ................................................................................................ 194
2. Tobacco Use Form ................................................................................................. 197
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3. Medication Use Form ............................................................................................. 200
4. Brief COPE Scale ................................................................................................... 202
5. Interpersonal Social Support Evaluation ................................................................ 205
6. Cognitive Failures Questionnaire ........................................................................... 208
7. Problem Areas in Diabetes scale (Type 2 DM Only) ............................................ 211
APPENDIX I. TEST SESSION PROCEDURES ........................................................................ 213
APPENDIX J. TEST SESSION QUESTIONNAIRE SET #1 ....................................................... 215
1. Positive and Negative Affect Scale ........................................................................ 216
2. Mood Assessment Scale ......................................................................................... 218
3. Mindfulness Attention Awareness Scale .............................................................. 220
APPENDIX K. TRIER SOCIAL STRESS TEST PROCEDURES ................................................. 223
APPENDIX L. TEST SESSION QUESTIONNAIRE SET # 2 ...................................................... 225
1. Post-Task Appraisal Questionnaire ........................................................................ 226
2. Positive and Negative Affect Scale ........................................................................ 228
3. Mood Assessment Scale ......................................................................................... 230
APPENDIX M. TEST SESSION QUESTIONNAIRE SET #3 ..................................................... 232
1. Positive and Negative Affect Scale ........................................................................ 233
2. Mood Assessment Scale ......................................................................................... 235
3. Perceived Stress Scale ............................................................................................ 237
4. Diabetes Quality of Life Scale Brief Clinical Inventory (Type 2 DM Only) ........ 239
5. Medical Outcomes Study SF-12V2 ....................................................................... 241
6. Spielberger Trait Anxiety Scale ............................................................................. 243
7. Five Facet Mindfulness Questionnaire................................................................... 245
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APPENDIX N. DEBRIEFING STATEMENT ........................................................................... 248
APPENDIX O. BLOOD PROCESSING PROTOCOL ................................................................. 250
APPENDIX P. BIOMARKER ASSAY INFORMATION ............................................................ 256
1. Salivary Free Cortisol ............................................................................................ 257
2. Salivary DHEA-S ................................................................................................... 265
3. Salivary Alpha-Amylase ........................................................................................ 276
4. Serum C-Reactive Protein ...................................................................................... 281
5. Quest Diagnostics Procedures ................................................................................ 286