Type 2 Diabetes in Asian Indians on Two Continents: Insights into the Epidemic and Pathophysiology Open Access

Abstract

Asian Indians are at high risk for type 2 diabetes despite having, on average, lower levels of traditional risk factors such as age and adiposity compared to other ethnic groups. As a result, it is possible that Asian Indians may experience unique biological susceptibilities to β-cell dysfunction which could be the driving factor behind diabetes risk in this population. These susceptibilities, coupled with recent nutritional transitions in India, may be resulting in a much higher prevalence of diabetes in Asian Indians living in India compared to those who have migrated to the United States as well as those from other ethnic populations. This dissertation sought to address these issues by utilizing data from four cross-sectional population based surveys representative of Asian Indians living in San Francisco or Chicago (The Mediators of Atherosclerosis in South Asians Living in America (MASALA) pilot study (n=150) and full cohort study (n=757)) Asian Indians living in Chennai, India (the Centre for cArdiometabolic Risk Reduction in South-Asia study (CARRS) (n=2,305)), and Caucasians, Blacks, and Hispanics living in the United States (the Nutrition Examination Survey (NHANES) (n=6,512)). Major findings indicated that: (1) Compared to poor insulin sensitivity, poor β-cell function was more strongly associated with diabetes and prediabetes and was also associated with glycemic progression in a cohort of migrant Asian Indians; (2) After adjusting for age, sex, and anthropometry, adjustment for β-cell function was associated with an increased odds of diabetes in Blacks and Hispanics compared to Asian Indians living in India; (3) There is a high prevalence of diabetes and a relatively low prevalence of prediabetes in Asian Indians living in India; (4) Migration to a high income country may no longer increase diabetes risk in some populations. The work provided in this dissertation adds evidence to the idea that biological susceptibilities for β-cell dysfunction may be a stronger contributing factor to diabetes risk in Asian Indians compared to obesity driven insulin resistance and provides a basis for future studies that seek to disentangle the longitudinal contributions of β-cell dysfunction and insulin resistance on diabetes development in various ethnic groups.

Table of Contents

Chapter 1: Introduction. 1

Research Aim 1. 2

Research Aim 2. 3

Research Aim 3. 4

Chapter 2: Background. 5

Diabetes: The global burden. 5

Diabetes in Asian Indians. 5

Pathophysiology. 6

Immigration and Diabets Risk. 7

Nutrition Transition in India. 8

Chapter 3: Methods. 10

The MASALA study. 10

The CARRS study. 12

Sample Size Estimation. 12

Sampling Method. 12

Sampling Weights. 13

Surveillance Indicators and Study Instruments. 15

NHANES. 16

Sampling Method. 16

Sampling Weight. 17

CHAPTER 4: The Relative associations of β-Cell function and insulin sensitivity with glycemic status and incident glycemic progression in migrant asian indians in the united states: The MASALA study. 20

Abstract. 21

Introduction. 23

Research Design and Methods. 24

Study Population. 24

Study Procedures. 24

Calculations. 26

Statistical Analysis. 27

Results. 29

Baseline Visit. 29

Follow-Up Visit. 31

Discussion. 32

Acknowledgements and Author Contributions. 37

References. 39

Chapter 4 Tables and Figures. 43

CHAPTER 5: Comparing type 2 diabetes, prediabetes and their associated risk factors in Asian Indians in India and the United States: The carrs and MASALA Studies. 47

Abstract. 48

Introduction. 49

Research Design and Methods. 49

Statistical Analysis. 52

Results. 52

Conclusions. 55

Acknowledgments and Author Contributions. 60

References. 62

Chapter 5 Tables and Figures. 67

CHAPTER 6: Comparing Type 2 diabetes, prediabets, and their associated risk factors in Asian Indians in India and Caucasians, Blacks, and Hispanics in the United States: The Carrs and NHANES studies. 72

Abstract. 73

Introduction. 74

Research Design and Methods. 75

Statistical Analysis. 77

Results. 78

Discussion. 82

Acknowledgements and Author Contributions. 87

References. 88

Chapter 6 Tables and Figures. 92

Chapter 7: Summary and Conclusions. 101

Summary of Main Findings. 101

Limitations. 104

Strengths and Innovations. 109

Public Health Implications. 110

Gaps in the Published Literature. 110

Prevention. 112

Future Directions. 113

Summary. 115

Literature Cited (Chapters 1-3, 7). 117

Appendices. 129

Appendix A: CARRS Study Methodology and Sampling Frame. 129

Appendix B: CARRS Study Sample Weights Calculation. 133

Appendix C: Article Attachment Pending Permission of Journal: The Relative Associations of β-Cell Function and Insulin Sensitivity on Glycemic Status and Glycemic Progression on

Migrant Asian Indians In The United States: The MASALA Study. 136

About this Dissertation

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School	Laney Graduate School
Department	Biological and Biomedical Sciences
Degree	PhD
Submission	Dissertation
Language	English
Research Field	Health Sciences, Public Health
Keyword	Pathophysiology Asian Indians Diabetes
Committee Chair / Thesis Advisor	Venkat Narayan, K.M., Emory University
Committee Members	Gregg, Edward, CDC Binongo, Jose N, Emory University Mehta, Neil K., Emory University Ramakrishnan, Usha, Emory University

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