R01DK141366

HIV, DEPRESSION, AND INSULIN RESISTANCE - PROJECT ABSTRACT DIABETES IS A KEY DRIVER OF SERIOUS NON-AIDS EVENTS IN PEOPLE WITH HIV (PWH). DEPRESSION POTENTIALLY CONTRIBUTES TO NEW-ONSET DIABETES IN PWH. COLLECTIVELY, OUR PRELIMINARY DATA INDICATE THAT SUCCESSFUL DEPRESSION TREATMENT WITH INTERNET COGNITIVE BEHAVIORAL THERAPY FOR DEPRESSION (ICBT-D) COULD REDUCE DIABETES RISK IN PWH BY IMPROVING GUT INTEGRITY, REDUCING MONOCYTE ACTIVATION, AND PREVENTING WORSENING INSULIN RESISTANCE. IN ADDITION, OUR DATA SUGGEST THAT EXAMINING THE METABOLOME MAY ELUCIDATE NEW MECHANISTIC AND POTENTIALLY THERAPEUTIC PATHWAYS LINKING SUCCESSFUL DEPRESSION TREATMENT TO IMPROVED INSULIN RESISTANCE. HOWEVER, THESE PROMISING FINDINGS ARE PRELIMINARY AND REQUIRE CONFIRMATION IN A SUFFICIENTLY POWERED RCT. OUR MULTIDISCIPLINARY GROUP OF INVESTIGATORS PROPOSE THE FOLLOWING SPECIFIC AIMS: AIM 1: TO DETERMINE THE EFFECTS OF ICBT-D ON INSULIN RESISTANCE IN DEPRESSED PWH ON ART. WE HYPOTHESIZE THAT ICBT-D, COMPARED TO ACTIVE CONTROL, WILL PREVENT WORSENING INSULIN RESISTANCE AS MEASURED BY HOMA-IR AT 24 WEEKS. IN SECONDARY ANALYSES, WE WILL ALSO COMPARE CHANGES IN HBA1C AND GLYCATED ALBUMIN AS ENDPOINTS MORE PROXIMAL TO DIABETES DIAGNOSIS. AIM 2: TO DETERMINE THE EFFECTS OF ICBT-D ON MONOCYTE ACTIVATION IN DEPRESSED PWH ON ART. WE HYPOTHESIZE THAT ICBT-D, COMPARED TO ACTIVE CONTROL, WILL LEAD TO REDUCED CIRCULATING SCD14, SCD163, AND CD14+CD16+ INTERMEDIATE MONOCYTE LEVELS AT 24 WEEKS. IN SECONDARY ANALYSES, WE WILL EXAMINE THE EFFECTS OF ICBT-D ON MARKERS OF GUT BARRIER INTEGRITY (REG3Α) AND MICROBIAL TRANSLOCATION (16S RDNA AND Β-D-GLUCAN). AIM 3: TO DETERMINE THE EFFECTS OF ICBT-D ON METABOLOMIC PROFILES IN DEPRESSED PWH ON ART. WE HYPOTHESIZE THAT ICBT-D, COMPARED TO ACTIVE CONTROL, WILL RESULT IN CHANGES IN THE CIRCULATING METABOLOME AT 24 WEEKS. WE WILL THEN PERFORM FORMAL PATHWAY ANALYSIS BASED ON DIFFERENTIAL METABOLITE PROFILES TO IDENTIFY NOVEL MECHANISTIC BIOLOGIC MECHANISMS TO EXPLAIN THE TREATMENT GROUP - HOMA-IR RELATIONSHIP. WE WILL TEST THESE HYPOTHESES BY CONDUCTING A 48-WEEK RCT COMPARING ICBT-D WITH AN ACTIVE CONTROL COMPARATOR GROUP (DEPRESSION EDUCATION, DEPRESSIVE SYMPTOM MONITORING, AND CURRENT CARE FOR DEPRESSION IN THE HIV CLINICS) IN 150 DEPRESSED PWH ON ART. THE PRIMARY ANALYSES WILL BE PERFORMED AT THE 24-WEEK TIMEPOINT WITH SIMILAR SECONDARY ANALYSES PERFORMED AT THE 48-WEEK TIMEPOINT TO ASSESS DURATION OF RESPONSE. GIVEN THE HIGH PREVALENCE OF DEPRESSION IN PWH OF UP TO 40%, DEPRESSION TREATMENT COULD HAVE SIGNIFICANT AND WIDESPREAD BENEFITS BY PREVENTING DIABETES IN ADDITION TO ITS MENTAL HEALTH IMPORTANCE. THUS, THIS APPLICATION MEETS THE STATED OBJECTIVES OF PAS-24-163, “PRIORITY HIV/AIDS RESEARCH WITHIN THE MISSION OF NIDDK.”

Trustees Of Indiana University

(1) TO PROMOTE EXTRAMURAL BASIC AND CLINICAL BIOMEDICAL RESEARCH THAT IMPROVES THE UNDERSTANDING OF THE MECHANISMS UNDERLYING DISEASE AND LEADS TO IMPROVED PREVENTIONS, DIAGNOSIS, AND TREATMENT OF DIABETES, DIGESTIVE, AND KIDNEY DISEASES. PROGRAMMATIC AREAS WITHIN THE NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES INCLUDE DIABETES, DIGESTIVE, ENDOCRINE, HEMATOLOGIC, LIVER, METABOLIC, NEPHROLOGIC, NUTRITION, OBESITY, AND UROLOGIC DISEASES. SPECIFIC PROGRAMS AREAS OF INTEREST INCLUDE THE FOLLOWING: (A) FOR DIABETES, ENDOCRINE, AND METABOLIC DISEASES AREAS: FUNDAMENTAL AND CLINICAL STUDIES INCLUDING THE ETIOLOGY, PATHOGENESIS, PREVENTION, DIAGNOSIS, TREATMENT AND CURE OF DIABETES MELLITUS AND ITS COMPLICATIONS, NORMAL AND ABNORMAL FUNCTION OF THE PITUITARY, THYROID, PARATHYROID, ADRENAL, AND OTHER HORMONE SECRETING GLANDS, HORMONAL REGULATION OF BONE, ADIPOSE TISSUE, AND LIVER, ON FUNDAMENTAL ASPECTS OF SIGNAL TRANSDUCTION, INCLUDING THE ACTION OF HORMONES, COREGULATORS, AND CHROMATIN REMODELING PROTEINS, HORMONE BIOSYNTHESIS, SECRETION, METABOLISM, AND BINDING, AND ON HORMONAL REGULATION OF GENE EXPRESSION AND THE ROLE(S) OF SELECTIVE RECEPTOR MODULATORS AS PARTIAL AGONISTS OR ANTAGONISTS OF HORMONE ACTION, AND FUNDAMENTAL STUDIES RELEVANT TO METABOLIC DISORDERS INCLUDING MEMBRANE STRUCTURE, FUNCTION, AND TRANSPORT PHENOMENA AND ENZYME BIOSYNTHESIS, AND BASIC AND CLINICAL STUDIES ON THE ETIOLOGY, PATHOGENESIS, PREVENTION, AND TREATMENT OF INHERITED METABOLIC DISORDERS (SUCH AS CYSTIC FIBROSIS). (B) FOR DIGESTIVE DISEASE AND NUTRITION AREAS: GENETICS AND GENOMICS OF THE GI TRACT AND ITS DISEASES, GENETICS AND GENOMICS OF LIVER/PANCREAS AND DISEASES, GENETICS AND GENOMICS OF NUTRITION, GENETICS AND GENOMICS OF OBESITY, BARIATRIC SURGERY, CLINICAL NUTRITION RESEARCH, CLINICAL OBESITY RESEARCH, COMPLICATIONS OF CHRONIC LIVER DISEASE, FATTY LIVER DISEASE, GENETIC LIVER DISEASE, HIV AND LIVER, CELL INJURY, REPAIR, FIBROSIS AND INFLAMMATION IN THE LIVER, LIVER CANCER, LIVER TRANSPLANTATION, PEDIATRIC LIVER DISEASE, VIRAL HEPATITIS AND INFECTIOUS DISEASES, GASTROINTESTINAL AND NUTRITION EFFECTS OF AIDS, GASTROINTESTINAL MUCOSAL AND IMMUNOLOGY, GASTROINTESTINAL MOTILITY, BASIC NEUROGASTROENTEROLOGY, GASTROINTESTINAL DEVELOPMENT, GASTROINTESTINAL EPITHELIAL BIOLOGY, GASTROINTESTINAL INFLAMMATION, DIGESTIVE DISEASES EPIDEMIOLOGY AND DATA SYSTEMS, NUTRITIONAL EPIDEMIOLOGY AND DATA SYSTEMS, AUTOIMMUNE LIVER DISEASE, BILE, BILIRUBIN AND CHOLESTASIS, BIOENGINEERING AND BIOTECHNOLOGY RELATED TO DIGESTIVE DISEASES, LIVER, NUTRITION AND OBESITY, CELL AND MOLECULAR BIOLOGY OF THE LIVER, DEVELOPMENTAL BIOLOGY AND REGENERATION, DRUG-INDUCED LIVER DISEASE, GALLBLADDER DISEASE AND BILIARY DISEASES, EXOCRINE PANCREAS BIOLOGY AND DISEASES, GASTROINTESTINAL NEUROENDOCRINOLOGY, GASTROINTESTINAL TRANSPORT AND ABSORPTION, NUTRIENT METABOLISM, PEDIATRIC CLINICAL OBESITY, CLINICAL TRIALS IN DIGESTIVE DISEASES, LIVER CLINICAL TRIALS, OBESITY PREVENTION AND TREATMENT, AND OBESITY AND EATING DISORDERS. (C) FOR KIDNEY, UROLOGIC AND HEMATOLOGIC DISEASES AREAS: STUDIES OF THE DEVELOPMENT, PHYSIOLOGY, AND CELL BIOLOGY OF THE KIDNEY, PATHOPHYSIOLOGY OF THE KIDNEY, GENETICS OF KIDNEY DISORDERS, IMMUNE MECHANISMS OF KIDNEY DISEASE, KIDNEY DISEASE AS A COMPLICATION OF DIABETES, EFFECTS OF DRUGS, NEPHROTOXINS AND ENVIRONMENTAL TOXINS ON THE KIDNEY, MECHANISMS OF KIDNEY INJURY REPAIR, IMPROVED DIAGNOSIS, PREVENTION AND TREATMENT OF CHRONIC KIDNEY DISEASE AND END-STAGE RENAL DISEASE, IMPROVED APPROACHES TO MAINTENANCE DIALYSIS THERAPIES, BASIC STUDIES OF LOWER URINARY TRACT CELL BIOLOGY, DEVELOPMENT, PHYSIOLOGY, AND PATHOPHYSIOLOGY, CLINICAL STUDIES OF BLADDER DYSFUNCTION, INCONTINENCE, PYELONEPHRITIS, INTERSTITIAL CYSTITIS, BENIGN PROSTATIC HYPERPLASIA, UROLITHIASIS, AND VESICOURETERAL REFLUX, DEVELOPMENT OF NOVEL DIAGNOSTIC TOOLS AND IMPROVED THERAPIES, INCLUDING TISSUE ENGINEERING STRATEGIES, FOR UROLOGIC DISORDERS,RESEARCH ON HEMATOPOIETIC CELL DIFFERENTIATION, METABOLISM OF IRON OVERLOAD AND DEFICIENCY, STRUCTURE, BIOSYNTHESIS AND GENETIC REGULATION OF HEMOGLOBIN, AS WELL AS RESEARCH ON THE ETIOLOGY, PATHOGENESIS, AND THERAPEUTIC MODALITIES FOR THE ANEMIA OF INFLAMMATION AND CHRONIC DISEASES. (2) TO ENCOURAGE BASIC AND CLINICAL RESEARCH TRAINING AND CAREER DEVELOPMENT OF SCIENTISTS DURING THE EARLY STAGES OF THEIR CAREERS. THE RUTH L. KIRSCHSTEIN NATIONAL RESEARCH SERVICE AWARD (NRSA) FUNDS BASIC AND CLINICAL RESEARCH TRAINING, SUPPORT FOR CAREER DEVELOPMENT, AND THE TRANSITION FROM POSTDOCTORAL BIOMEDICAL RESEARCH TRAINING TO INDEPENDENT RESEARCH RELATED TO DIABETES, DIGESTIVE, ENDOCRINE, HEMATOLOGIC, LIVER, METABOLIC, NEPHROLOGIC, NUTRITION, OBESITY, AND UROLOGIC DISEASES. (3) TO EXPAND AND IMPROVE THE SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM. THE SBIR PROGRAM AIMS TO INCREASE AND FACILITATE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO ENHANCE 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. (4) TO UTILIZE THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM. THE STTR PROGRAM INTENDS TO STIMULATE AND FOSTER 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.

93.847 - Diabetes, Digestive, and Kidney Diseases Extramural Research

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [HHS - NIH]

Indiana United States

State-Wide

Priority HIV/AIDS Research within the Mission of NIDDK (R01 Clinical Trial Optional) (PAS-24-163)