Comparative Analysis of Type 2 Diabetes Pathophysiology Across Multiple Ethnicities Público

Abstract

Purpose: Type 2 diabetes is a complex chronic disease that develops under different conditions

of risk globally. Heterogeneity in diabetes pathophysiology will be examined by comparing

several high-risk populations across a wide spectrum of BMI and by examining the relative

contributions of insulin resistance and β-cell function on diabetes pathophysiology across these

populations, with particular emphasis on African and Asian Indian populations.

Methods: Participants were from four different cohorts without known diabetes: Asian Indian

(n=1750), African-born blacks living in America (African immigrants, n=523), Mixed ancestry

South African (n=1112), and African Americans (n=185). All participants had a 75g oral glucose

tolerance test, with glucose and insulin measured at 0 and 120 minutes, and glucose and insulin

at 30 minutes was additionally measured in Asian Indians, African immigrants, and African

Americans. Participants were classified on glycemic status based on the American Diabetes

Association criteria cutpoints. Key measures of insulin resistance (HOMA-IR: ([insulint0 x

glucoset0]/ 22.5)) and β-cell function (insulinogenic index: ([(insulint30 - insulint0) / (glucoset30 -

glucoset0)]) were calculated and compared between ethnicities by ANOVA and logistic

regression.

Results: SA-Mixed ancestry were the oldest (mean 45.6 ± SD 13.8, Asian Indians: 38.9 ± 10.8

years; African immigrants 38.5 ± 10.3 years; African Americans 34.5 ± 7.8 years). African

Americans had the highest BMI (mean 34.5 ± SD 7.8 kg/m2; SA-Mixed ancestry 28.6 ± 8.2;

African immigrants 27.7 ± 4.5; Asian Indians 25.8 ± 4.9). Fasting glucose adjusted for age, sex,

and BMI was highest in Asian Indians (mean 101.2 mg/dL ± SE 0.6; African immigrants 92.3 ±

1.1; SA-Mixed ancestry 89.9 ± 0.7; African Americans 86.6 ± 1.8). Adjusting for age, sex, and

BMI, Asian Indians were the most insulin resistant (HOMA-IR 2.3 ± SE 0.1; SA-Mixed ancestry

2.1 ± 0.1; African immigrants 1.6 ± 0.1; African Americans 1.6 ± 0.2) and had the poorest

insulin secretion (Insulinogenic Index 0.8 pmol/mmol ± SE 1.0; African immigrants: 1.4 ± 1.0;

African Americans: 1.4 ± 1.1). Among prediabetes subtypes Asian Indians had predominately

impaired fasting glucose (iIFG: Asian Indians 17.3%; SA-Mixed ancestry 6.2%; African

immigrants 4.8%; African Americans 2.7%), whereas African subgroups had predominately

impaired glucose tolerance (iIGT: African immigrants 20.7%; African Americans 20.5%; SAMixed

ancestry 9.8%; Asian Indians 3.2%) .The odds of prediabetes versus normoglycemia after

adjusting for age, sex, and BMI was lowest in African immigrants (OR insulinogenic index:

0.36, 95% CI: 0.26, 0.49; Asian Indians 0.49, 95% CI: 0.42, 0.57; African Americans 0.45, 95%

CI: 0.27, 0.74).

Conclusion: In the early natural history of disease, heterogenous pathways of disease

development seem to be present among the four populations. Asian Indians have poor insulin

secretion, as do African immigrants, but the pathways leading to impairments in insulin secretion

may vary across mechanisms related to glucose tolerance rather than maintenance of basal

glucose. The compensation for hyperglycemia may be greater in SA-Mixed ancestry who had

varying levels of insulin resistance compared to the other populations. African Americans appear

to have improved β-cell function even in the presence of insulin resistance.

Table of Contents

INTRODUCTION……………………………………………………………………………… 1

LITERATURE REVIEW……………………………………………………………………… 6

OBJECTIVE OF STUDY…………………………………………………………………….. 16

METHODS…………………………………………………………………………………….. 16

RESULTS……………………………………………………………………………………… 22

DISCUSSION………………………………………………………………………………….. 37

CONCLUSION………………………………………………………………………………... 40

PUBLIC HEALTH IMPLICATIONS……………………………………………………….. 41

REFERENCES………………………………………………………………………………… 44

APPENDIX…………………………………………………………………………………….. 58

About this Master's Thesis

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School	Rollins School of Public Health
Department	Hubert Department of Global Health
Degree	M.P.H.
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Public Health
Palabra Clave	Diabetes
Committee Chair / Thesis Advisor	Staimez, Lisa, Emory University

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