Diabetes mellitus and active tuberculosis disease: Clinical presentation and treatment outcomes in adult tuberculosis patients Restricted; Files Only

Magee, Matthew James (2013)

Permanent URL: https://etd.library.emory.edu/concern/etds/ms35t9316?locale=en
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Abstract

Objectives: Tuberculosis (TB) and diabetes mellitus (DM) contribute to extensive global morbidity and mortality. Although DM is an accepted risk factor for developing active TB disease, less is known about the relation between DM and TB clinical characteristics, including TB disease presentation and TB treatment outcomes. The overall goal of this dissertation was to estimate the association between DM and 1) TB disease severity at the time of TB diagnosis and 2) poor TB clinical outcomes. Methods: This dissertation included three studies, each examined a subset of specific aims comparing TB disease in patients with and without DM. Study 1 was a cohort of new adult TB patients from Tbilisi, Georgia, screened for DM and impaired glucose tolerance (pre-DM) using a point-of-care hemoglobin A1c (HbA1c) test. We compared measures of TB severity at clinical presentation (including lung cavitary disease, sputum smear grade, and hemoptysis) in patients with and without DM. In study 2, we estimated the association between DM and time to sputum culture conversion in a cohort of multidrug-resistant (MDR) TB patients from the country of Georgia. Study 3 estimated the association between DM and time to all-cause mortality during TB treatment in a cohort of adult TB patients from the state of Georgia, United States. Results: Study 1 demonstrated that patients with TB and DM were more likely to present with higher sputum smear grade (adjusted odds ratio 2.63, 95% confidence interval [CI] 1.14--6.06) compared to TB patients without DM. In study 2, the estimated hazard of sputum culture conversion was modestly, but non-significantly, lower in MDR TB patients with DM compared to those without DM (adjusted hazard ratio [aHR] 0.93, 95% CI 0.71--1.23). Compared to TB patients without DM, Study 3 reported TB-DM patients did not have significantly greater hazard of all-cause mortality during TB treatment (aHR 1.22, 95% CI 0.70--2.12). Conclusion: Adult TB patients with DM may have more severe TB disease at clinical presentation. However, our findings did not suggest that DM has a clinically meaningful impact on time to TB culture conversion or all-cause mortality during TB treatment.

Table of Contents

Table of Contents

CHAPTER 1: INTRODUCTION TO TUBERCULOSIS AND

DIABETES MELLITUS EPIDEMIOLOGY 1

Background 5

Biologic plausibility 23

Summary 27

Chapter 1 references 37

CHAPTER 2: DIABETES MELLITUS AND TUBERCULOSIS SEVERITY

IN THE COUNTRY OF GEORGIA 52

Introduction 53

Methods 54

Results 57

Discussion 59

Chapter 2 references 74

CHAPTER 3: CULTURE CONVERSION AMONG MULITDRUG-

RESISTANT TUBERCULOSIS PATIENTS WITH DIABETES

MELLITUS 79

Introduction 80

Methods 81

Results 85

Discussion 87

Chapter 3 references 102

CHAPTER 4: MORTALITY DURING TUBERCULOSIS TREATMENT

AMONG PATIENTS WITH DIABETES MELLITUS IN THE STATE OF

GEORGIA 107

Introduction 108

Methods 109

Results 112

Discussion 113

Chapter 4 references 124

CHAPTER 5: SUMMARY AND CONCLUSIONS 128

Strengths and limitations 129

Remaining gaps in knowledge and future research recommendations 132

Public health and clinical implications 135

Chapter 5 references 138

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