R01AI153152

Immunometabolic Impact of Stress Hyperglycemia on Tuberculosis Treatment Outcomes and Risk of Diabetes Mellitus - Project Summary

The intersection of tuberculosis (TB) with non-communicable diseases, including diabetes mellitus, has emerged as a critical clinical and public health obstacle. Rapidly expanding diabetes epidemics threaten TB control in low- and middle-income countries, including the country of Georgia, where preventing and treating TB disease remains a great burden. However, to date, the notion that TB disease may increase the risk of metabolic diseases like diabetes has not been well explored.

This study will determine the extent to which TB-induced stress hyperglycemia impacts the risk of poor TB treatment outcomes. We will also assess whether stress hyperglycemia or adipose tissue inflammation during TB increase the risk of diabetes post-TB. This research will advance understanding of the dual burdens of TB-diabetes and inform treatment guidelines for the management of stress hyperglycemia during TB.

The long-term objective of this research is to develop an evidence base to help identify which patients with TB are likely to benefit most from adjunctive anti-inflammatory glucose-lowering agents. The specific aims of this proposal are to:

1. Determine the relationship between stress hyperglycemia and TB outcomes, including TB cure rate and time to sputum culture conversion.
2. Determine the extent that stress hyperglycemia during TB increases the risk of diabetes 1-year after TB treatment.
3. Explore the relationship between plasma and subcutaneous tissue biomarkers of adipose tissue inflammation with stress hyperglycemia and diabetes risk.

The aims of this project will be achieved by enrolling a cohort of patients at the time of TB diagnosis and following them prospectively during treatment and for 1-year post-TB treatment. At multiple time points during this study, we will measure glucose, insulin resistance, lipids, adipokines, and anthropometry among participants with diabetes, stress hyperglycemia, and euglycemia. In a subset of the cohort, we will perform adipose tissue biopsies and measure adipose tissue inflammation. The analyses will include multiple modeling strategies to assess the relationship between patient and host factors and the risk of post-TB metabolic disease.

This proposal will directly address clinical uncertainties related to the growing global concern of intersecting TB and diabetes epidemics. The study will help to characterize the extent to which TB contributes to diabetes incidence and will identify which patients with hyperglycemia are at the greatest risk of poor TB outcomes. In addition, this R01 will explore novel biomarkers of adipose tissue inflammation to determine whether TB alters immune activity or metabolic function within human adipose tissue. A long-term goal of the proposed work is to prepare for prospective interventional studies that will evaluate glucose-lowering agents during active TB as adjunctive therapy to improve TB outcomes and reduce the risk of diabetes after TB.

Emory University

TO ASSIST PUBLIC AND PRIVATE NONPROFIT INSTITUTIONS AND INDIVIDUALS TO ESTABLISH, EXPAND AND IMPROVE BIOMEDICAL RESEARCH AND RESEARCH TRAINING IN INFECTIOUS DISEASES AND RELATED AREAS, TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS. TO ASSIST PUBLIC, PRIVATE AND COMMERCIAL INSTITUTIONS TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS, TO PROVIDE RESEARCH SERVICES AS REQUIRED BY THE AGENCY FOR PROGRAMS IN INFECTIOUS DISEASES, AND CONTROLLING DISEASE CAUSED BY INFECTIOUS OR PARASITIC AGENTS, ALLERGIC AND IMMUNOLOGIC DISEASES AND RELATED AREAS. PROJECTS RANGE FROM STUDIES OF MICROBIAL PHYSIOLOGY AND ANTIGENIC STRUCTURE TO COLLABORATIVE TRIALS OF EXPERIMENTAL DRUGS AND VACCINES, MECHANISMS OF RESISTANCE TO ANTIBIOTICS AS WELL AS RESEARCH DEALING WITH EPIDEMIOLOGICAL OBSERVATIONS IN HOSPITALIZED PATIENTS OR COMMUNITY POPULATIONS AND PROGRESS IN ALLERGIC AND IMMUNOLOGIC DISEASES. BECAUSE OF THIS DUAL FOCUS, THE PROGRAM ENCOMPASSES BOTH BASIC RESEARCH AND CLINICAL RESEARCH. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM EXPANDS AND IMPROVES PRIVATE SECTOR PARTICIPATION IN BIOMEDICAL RESEARCH. THE SBIR PROGRAM INTENDS TO INCREASE AND FACILITATE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM STIMULATES AND FOSTERS SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. RESEARCH CAREER DEVELOPMENT AWARDS SUPPORT THE DEVELOPMENT OF SCIENTISTS DURING THE FORMATIVE STAGES OF THEIR CAREERS. INDIVIDUAL NATIONAL RESEARCH SERVICE AWARDS (NRSAS) ARE MADE DIRECTLY TO APPROVE APPLICANTS FOR RESEARCH TRAINING IN SPECIFIED BIOMEDICAL SHORTAGE AREAS. IN ADDITION, INSTITUTIONAL NATIONAL RESEARCH SERVICE AWARDS ARE MADE TO ENABLE INSTITUTIONS TO SELECT AND MAKE AWARDS TO INDIVIDUALS TO RECEIVE TRAINING UNDER THE AEGIS OF THEIR INSTITUTIONAL PROGRAM.

93.855 - Allergy and Infectious Diseases Research

National Institute of Allergy and Infectious Diseases (NIAID) [HHS - NIH]

Atlanta, Georgia 30322 United States

Single Zip Code

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the total obligations have increased 391% from $752,999 to $3,694,016.