Scholars@Duke
William Todd Cade

William Todd Cade

Professor of Orthopaedic Surgery
Orthopaedic Surgery, Physical Therapy
todd.cade@duke.edu
311 Trent Drive, Durham, NC 27710
311 Trent Drive, Durham, NC 27710

Selected Publications

Metabolic Health and Heterogenous Outcomes of Prenatal Interventions: A Secondary Analysis of a Randomized Clinical Trial.

Journal Article JAMA Netw Open · August 1, 2025 IMPORTANCE: Prenatal intensive behavioral therapy (IBT) interventions that promote adequate gestational weight gain (GWG) have had variable and mostly modest effects on clinically relevant maternal and infant outcomes. It is unknown whether different mater ... Full text Link to item Cite

Cardiac Transplantation Does Not Improve Exercise Tolerance, Muscle Mass, or Substrate Metabolism in Barth Syndrome.

Journal Article JIMD Rep · July 2025 Barth syndrome (BTHS) is a rare X-linked recessive disorder characterized by mutations in the TAFAZZIN gene, leading to mitochondrial dysfunction, cardioskeletal myopathy, neutropenia, exercise intolerance, and growth delay. While cardiac transplantation c ... Full text Link to item Cite

0309 Neighborhood Perceptions and Sleep Health in Pregnant African American Women of Low Socioeconomic Status

Conference SLEEP · May 19, 2025 AbstractIntroductionPoor sleep health is associated with pregnancy complications. Perceptions of neighborhood likely affect sleep in p ... Full text Cite

Rescue of mitochondrial dysfunction through alteration of extracellular matrix composition in barth syndrome cardiac fibroblasts.

Journal Article Biomaterials · April 2025 Fibroblast-ECM (dys)regulation is associated with a plethora of diseases. The ECM acts as a reservoir of inflammatory factors and cytokines that mediate molecular mechanisms within cardiac cell populations. The role of ECM-mitochondria crosstalk in the dev ... Full text Link to item Cite

Feasibility of a community-based structured exercise program for persons with spinal cord injury.

Journal Article J Spinal Cord Med · March 2025 OBJECTIVES: (1) Examine the feasibility of a community-based exercise intervention for persons with spinal cord injury and (2) compare the cardiorespiratory fitness, skeletal muscle strength, and psychosocial well-being of participants in the intervention ... Full text Link to item Cite

Metabolic and Pharmacokinetic Profiling of a Ketone Ester by Background SGLT2 Inhibitor Therapy in HFrEF.

Journal Article JACC Basic Transl Sci · March 2025 Growing evidence supports therapeutic ketosis in heart failure with reduced ejection fraction, though uncertainty exists regarding use with SGLT2i and dose-dependent effects. In a phase I trial of 2 ketone ester (KE) doses in 20 heart failure with reduced ... Full text Link to item Cite

Abstract 4116177: Metabolic and Pharmacokinetic Profiling of Ketone Ester by Background SGLT2 Inhibitor Therapy in Heart Failure with Reduced Ejection: A Phase I Clinical Trial

Conference Circulation · November 12, 2024 Background: Growing evidence supports a therapeutic role for ketones in HFrEF. However, no pharmacokinetic (PK) studies are available to guide further investigation, and uncertainty exists regarding u ... Full text Cite

Feasibility of a Community-Based Structured Exercise Program for Persons With Spinal Cord Injury

Conference The American Journal of Occupational Therapy · August 1, 2024 AbstractDate Presented 03/23/24This poster highlights the results of a randomized controlled trial of a community-based exercise program that improved health outcomes for per ... Full text Cite

Manual therapy and exercise effects on inflammatory cytokines: a narrative overview.

Journal Article Front Rehabil Sci · 2024 BACKGROUND: Matching disease and treatment mechanisms is a goal of the Precision Medicine Initiative. Pro- and anti-inflammatory cytokines (e.g., Tumor Necrosis Factor-alpha, Transforming Growth Factor-beta, and Interleukin-2, 10, and 12) have gained a sig ... Full text Link to item Cite

Insulin Sensitivity and β-Cell Function During Early and Late Pregnancy in Women With and Without Gestational Diabetes Mellitus.

Journal Article Diabetes Care · December 1, 2023 OBJECTIVE: To evaluate the metabolic alterations associated with gestational diabetes mellitus (GDM) in women with overweight or obesity. RESEARCH DESIGN AND METHODS: We compared fasting and postprandial plasma glucose and free fatty acid (FFA) concentrati ... Full text Link to item Cite

One episode of low intensity aerobic exercise prior to systemic AAV9 administration augments transgene delivery to the heart and skeletal muscle.

Journal Article J Transl Med · October 24, 2023 INTRODUCTION: The promising potential of adeno-associated virus (AAV) gene delivery strategies to treat genetic disorders continues to grow with an additional three AAV-based therapies recently approved by the Food and Drug Administration and dozens of oth ... Full text Link to item Cite

Exercise Training to Improve Brain Health in Older People Living With HIV: Study Protocol for a Randomized Controlled Trial.

Journal Article JMIR Res Protoc · March 21, 2023 BACKGROUND: With the advent of antiretrovirals, people living with HIV are living near-normal lifespans. However, people living with HIV are at greater risk of experiencing cognitive impairment and reduced brain integrity despite well-controlled viremia. A ... Full text Link to item Cite

Elevated liver glycogenolysis mediates higher blood glucose during acute exercise in Barth syndrome.

Journal Article PLoS One · 2023 UNLABELLED: Barth syndrome (BTHS) is an X-linked recessive genetic disorder due to mutations in the Tafazzin (TAFAZZIN) gene that lead to cardiac and skeletal muscle mitochondrial dysfunction. Previous studies in humans with BTHS demonstrate that the defec ... Full text Link to item Cite

Matrix produced by diseased cardiac fibroblasts affects early myotube formation and function.

Journal Article Acta Biomater · October 15, 2022 The extracellular matrix (ECM) provides both physical and chemical cues that dictate cell function and contribute to muscle maintenance. Muscle cells require efficient mitochondria to satisfy their high energy demand, however, the role the ECM plays in mod ... Full text Link to item Cite

Effect of excessive gestational weight gain on insulin sensitivity and insulin kinetics in women with overweight/obesity.

Journal Article Obesity (Silver Spring) · October 2022 OBJECTIVE: Obesity increases the risk for pregnancy complications and maternal hyperglycemia. The Institute of Medicine developed guidelines for gestational weight gain (GWG) targets for women with overweight/obesity, but it is unclear whether exceeding th ... Full text Link to item Cite

Longitudinal Observational Study of Cardiac Outcome Risk Factor Prediction in Children, Adolescents, and Adults with Barth Syndrome.

Journal Article Pediatr Cardiol · August 2022 Barth Syndrome (BTHS) is an X-linked mitochondrial cardioskeletal myopathy caused by defects in TAFAZZIN, a gene responsible for cardiolipin remodeling. Altered mitochondrial levels of cardiolipin lead to cardiomyopathy (CM), muscle weakness, exercise into ... Full text Link to item Cite

Socioeconomic status largely explains integrase inhibitors-related body composition differences in chronically infected men living with HIV.

Journal Article Antivir Ther · June 2022 BACKGROUND: Substantial body composition alterations have been reported after starting combined antiretroviral therapy (cART). We characterized a cohort of chronically infected and virologically suppressed (VL < 50 copies/ml) men (≥50 years old) living wit ... Full text Link to item Cite

High rates of undiagnosed and uncontrolled hypertension upon a screening campaign in rural Rwanda: a cross-sectional study.

Journal Article BMC Cardiovasc Disord · April 26, 2022 BACKGROUND: Hypertension remains the major risk factor for cardiovascular diseases (CVDs) worldwide with a prevalence and mortality in low- and middle-income countries (LMICs) among the highest. The early detection of hypertension risk factors is a crucial ... Full text Link to item Cite

Cardiorespiratory Fitness Is Associated With Better White Matter Integrity in Persons Living With HIV.

Journal Article J Acquir Immune Defic Syndr · April 15, 2022 BACKGROUND: Despite improved survival rates, neurocognitive impairment persists in persons living with HIV (PLWH). An active lifestyle is linked to improved cognition among PLWH, yet the neural substrates remain unclear. Diffusion tensor imaging and diffus ... Full text Link to item Cite

Resistance exercise training with protein supplementation improves skeletal muscle strength and improves quality of life in late adolescents and young adults with Barth syndrome: A pilot study.

Journal Article JIMD Rep · November 2021 BACKGROUND: Muscle weakness and exercise intolerance contribute to reduced quality of life (QOL) in Barth syndrome (BTHS). Our group previously found that 12 weeks of resistance exercise training (RET) improved muscle strength, however, did not increase mu ... Full text Link to item Cite

Validity of the 6-Minute Walk Test and YMCA Submaximal Cycle Test During Midpregnancy

Journal Article Journal of Strength & Conditioning Research · November 2021 AbstractTinius, RA, Blankenship, M, Maples, JM, Pitts, BC, Furgal, K, Norris, ES, Hoover, DL, Olenick, A, Lambert, J, and Cade, WT. Validity of the 6-minute walk test and Young Men’s Christian Association (YMCA) ... Full text Cite

Elevated lipid oxidation is associated with exceeding gestational weight gain recommendations and increased neonatal anthropometrics: a cross-sectional analysis.

Journal Article BMC Pregnancy Childbirth · August 21, 2021 BACKGROUND: Deviations from gestational weight gain (GWG) recommendations are associated with unfavorable maternal and neonatal outcomes. There is a need to understand how maternal substrate metabolism, independent of weight status, may contribute to GWG a ... Full text Link to item Cite

Association of Balance Function With All-Cause and Cause-Specific Mortality Among US Adults.

Journal Article JAMA Otolaryngol Head Neck Surg · May 1, 2021 IMPORTANCE: Difficulty maintaining balance is common among individuals aged 40 years or older and increases the risk of falls. However, little is known about the association of balance function with long-term mortality outcomes in adults. OBJECTIVE: To inv ... Full text Link to item Cite

A Single Bout of Premeal Resistance Exercise Improves Postprandial Glucose Metabolism in Obese Men with Prediabetes.

Journal Article Med Sci Sports Exerc · April 1, 2021 INTRODUCTION: Prediabetes is a major risk factor for type 2 diabetes and cardiovascular diseases. Although resistance exercise (RE) is recommended for individuals with prediabetes, the effects of RE on postprandial glucose metabolism in this population are ... Full text Link to item Cite

Metabolic flexibility during late pregnancy is associated with neonatal adiposity.

Journal Article Appl Physiol Nutr Metab · April 2021 The aim of this study was to determine the relationships between maternal metabolic flexibility during pregnancy and neonatal health outcomes. Percent change in lipid oxidation (before and after a high-fat meal) was calculated as the measure of "metabolic ... Full text Link to item Cite

The TDR MOOC training in implementation research: evaluation of feasibility and lessons learned in Rwanda

Journal Article Pilot and Feasibility Studies · December 2020 AbstractBackgroundHypertension (HTN) affects nearly 1 billion people globally and is a major cause of morbidity and mortality. In low- and middle-income countries (LMICs), HTN represents ... Full text Cite

Arginine kinetics are altered in a pilot sample of adolescents and young adults with Barth syndrome.

Journal Article Mol Genet Metab Rep · December 2020 Barth syndrome (BTHS) is a rare, X-linked cardiomyopathy that is characterized by abnormalities in glucose and lipid metabolism, with less known regarding amino acid metabolism. This pilot study characterized whole-body arginine kinetics and found lower ar ... Full text Link to item Cite

Association of Hot Tea Consumption with Regional Adiposity Measured by Dual‐Energy X‐Ray Absorptiometry in NHANES 2003‐2006

Journal Article Obesity · February 2020 ObjectiveThis study aimed to investigate the potential antiobesity benefits of hot tea consumption at the population level.MethodsUsing data from the ... Full text Cite

Increased mtDNA Abundance and Improved Function in Human Barth Syndrome Patient Fibroblasts Following AAV-TAZ Gene Delivery

Journal Article International Journal of Molecular Sciences · July 11, 2019 Barth syndrome (BTHS) is a rare, X-linked, mitochondrial disorder caused by mutations in the gene encoding tafazzin. BTHS results in cardiomyopathy, muscle fatigue, and neutropenia in patients. Tafazzin is responsible for remodeling cardiolipin, a ... Full text Cite

AAV9-TAZ Gene Replacement Ameliorates Cardiac TMT Proteomic Profiles in a Mouse Model of Barth Syndrome

Journal Article Molecular Therapy - Methods & Clinical Development · June 2019 Full text Cite

Blunted fat oxidation upon submaximal exercise is partially compensated by enhanced glucose metabolism in children, adolescents, and young adults with Barth syndrome.

Journal Article J Inherit Metab Dis · May 2019 Barth syndrome (BTHS) is a rare X-linked condition resulting in abnormal mitochondria, cardioskeletal myopathy, and growth delay; however, the effects of BTHS on substrate metabolism regulation and their relationships with tissue function in humans are unk ... Full text Link to item Cite

Randomized Controlled Trial of Home‐Based Lifestyle Therapy on Postpartum Weight in Underserved Women with Overweight or Obesity

Journal Article Obesity · April 2019 ObjectiveThis study aimed to assess the efficacy of a home‐based lifestyle intervention delivered through Parents as Teachers (PAT), a national home‐visiting organization, designed to minimize excessive weight gai ... Full text Cite

Low dose chloroquine decreases insulin resistance in human metabolic syndrome but does not reduce carotid intima-media thickness.

Journal Article Diabetol Metab Syndr · 2019 BACKGROUND: Metabolic syndrome, an obesity-related condition associated with insulin resistance and low-grade inflammation, leads to diabetes, cardiovascular diseases, cancer, osteoarthritis, and other disorders. Optimal therapy is unknown. The antimalaria ... Full text Link to item Cite

The manifold role of the mitochondria in skeletal muscle insulin resistance

Journal Article Current Opinion in Clinical Nutrition & Metabolic Care · July 2018 Full text Cite

Mitochondrial inefficiency in infants born to overweight African-American mothers

Journal Article International Journal of Obesity · July 2018 Full text Cite

Weight Control Program and Gestational Weight Gain in Disadvantaged Women with Overweight or Obesity: A Randomized Clinical Trial

Journal Article Obesity · March 2018 ObjectiveThis study aimed to evaluate the efficacy of a home‐based lifestyle intervention delivered through Parents as Teachers (PAT) to reduce excessive gestational weight gain (GWG). Full text Cite

Peak oxygen uptake (VO2peak) across childhood, adolescence and young adulthood in Barth syndrome: Data from cross-sectional and longitudinal studies.

Journal Article PLoS One · 2018 UNLABELLED: Barth syndrome (BTHS) is an ultra-rare, X-linked recessive disorder characterized by cardio-skeletal myopathy, exercise intolerance, and growth delay. Oxygen uptake during peak exercise (VO2peak) has been shown to be severely limited in individ ... Full text Link to item Cite

Relationships between consumption of ultra-processed foods, gestational weight gain and neonatal outcomes in a sample of US pregnant women

Journal Article PeerJ · December 7, 2017 BackgroundAn increasingly large share of diet comes from ultra-processed foods (UPFs), which are assemblages of food substances designed to create durable, convenient and ... Full text Cite

HIV infection does not prevent the metabolic benefits of diet‐induced weight loss in women with obesity

Journal Article Obesity · April 2017 ObjectiveTo test the hypothesis that HIV infection impairs the beneficial effects of weight loss on insulin sensitivity, adipose tissue inflammation, and endoplasmic reticulum (ER) stress. Full text Cite

Explanators of Sarcopenia in Individuals With Diabesity: A Cross-Sectional Analysis

Journal Article Journal of Geriatric Physical Therapy · April 2017 Background and Purpose:Excess lower extremity intermuscular adipose tissue (IMAT), reduced strength, and functional limitations are common in obese individuals with and without diabetes ( ... Full text Cite

Impaired cardiac and skeletal muscle bioenergetics in children, adolescents, and young adults with Barth syndrome

Journal Article Physiological Reports · February 2017 AbstractBarth syndrome (BTHS) is an X‐linked condition characterized by altered cardiolipin metabolism and cardioskeletal myopathy. We sought to compare cardiac ... Full text Cite

Origins in the Womb: Potential Role of the Physical Therapist in Modulating the Deleterious Effects of Obesity on Maternal and Offspring Health Through Movement Promotion and Prescription During Pregnancy

Journal Article Physical Therapy · January 1, 2017 AbstractMaternal obesity and associated metabolic disease contribute to adverse outcomes in women and their offspring, and many of these outcomes have significant acute and chronic implications for both moth ... Full text Cite

Maternal Glucose and Fatty Acid Kinetics and Infant Birth Weight in Obese Women With Type 2 Diabetes

Journal Article Diabetes · April 1, 2016 The objectives of this study were 1) to describe maternal glucose and lipid kinetics and 2) to examine the relationships with infant birth weight in obese women with pregestational type 2 diabetes during late pregnancy. Using stable isotope tracer ... Full text Cite

Maternal inflammation during late pregnancy is lower in physically active compared with inactive obese women

Journal Article Applied Physiology, Nutrition, and Metabolism · February 2016 The primary purpose of this study was to compare maternal plasma inflammation between physically active and inactive obese women during late pregnancy. The secondary purpose was to examine the relationships between maternal plasma inflammation and ... Full text Cite

A Diet Rich in Medium-Chain Fatty Acids Improves Systolic Function and Alters the Lipidomic Profile in Patients With Type 2 Diabetes: A Pilot Study

Journal Article The Journal of Clinical Endocrinology & Metabolism · February 1, 2016 AbstractContext:Excessive cardiac long-chain fatty acid (LCFA) metabolism/storage causes cardiomyopathy in animal models of type 2 diabetes. Medium-chain fatty acids (MCFAs) are absorbed a ... Full text Cite

Markers of Glycemic Control and Neonatal Morbidity in High-Risk Insulin-Resistant Pregnancies

Journal Article American Journal of Perinatology · September 2, 2015 Full text Cite

Effects of Moderate- Versus High-Intensity Exercise Training on Physical Fitness and Physical Function in People With Type 2 Diabetes: A Randomized Clinical Trial

Journal Article Physical Therapy · December 1, 2014 BackgroundExercise training is effective for improving physical fitness and physical function in people with type 2 diabetes. However, limited research has been conducted on t ... Full text Cite

Impact of Obesity on Maternal and Neonatal Outcomes in Insulin-Resistant Pregnancy

Journal Article American Journal of Perinatology · July 22, 2013 Full text Cite

Substrate metabolism during basal and hyperinsulinemic conditions in adolescents and young‐adults with Barth syndrome

Journal Article Journal of Inherited Metabolic Disease · January 2013 AbstractBackgroundBarth syndrome (BTHS) is a rare X‐linked disorder that is characterized by mitochondrial abnormalities, infantile or childhood onset of cardioskeletal myopathy, and high ... Full text Cite

Impaired cardiac reserve and severely diminished skeletal muscle O2 utilization mediate exercise intolerance in Barth syndrome

Journal Article American Journal of Physiology-Heart and Circulatory Physiology · November 2011 Barth syndrome (BTHS) is a mitochondrial myopathy characterized by reports of exercise intolerance. We sought to determine if 1) BTHS leads to abnormalities of skeletal muscle O2 extraction/utilization and 2) exercise intolera ... Full text Cite

Exercise training augments the peripheral insulin-sensitizing effects of pioglitazone in HIV-infected adults with insulin resistance and central adiposity

Journal Article American Journal of Physiology-Endocrinology and Metabolism · January 2011 The prevalence and incidence of insulin resistance and type 2 diabetes mellitus (DM) are higher in people treated for human immunodeficiency virus-1 (HIV) infection than in the general population. Identifying safe and effective interventions is a h ... Full text Cite

School-Based Physical Activity and Fitness Promotion

Journal Article Physical Therapy · September 1, 2010 Full text Cite

Yoga lifestyle intervention reduces blood pressure in HIV‐infected adults with cardiovascular disease risk factors*

Journal Article HIV Medicine · July 2010 ObjectivePeople living with HIV infection are at increased risk for developing cardiovascular disease (CVD). Safe and effective interventions for lowering CVD risk in HIV infection are high priorities. We conducte ... Full text Cite

Protease inhibitors used in the treatment of HIV+ induce β-cell apoptosis via the mitochondrial pathway and compromise insulin secretion

Journal Article American Journal of Physiology-Endocrinology and Metabolism · April 2009 Inclusion of HIV protease inhibitors (PIs) in the treatment of people living with HIV+ has markedly decreased mortality but also increased the incidence of metabolic abnormalities, causes of which are not well understood. Here ... Full text Cite

Diabetes-Related Microvascular and Macrovascular Diseases in the Physical Therapy Setting

Journal Article Physical Therapy · November 1, 2008 Physical therapists commonly treat people with diabetes for a wide variety of diabetes-associated impairments, including those from diabetes-related vascular disease. Diabetes is associated with both microvascular and macrovascular diseases affecti ... Full text Cite

The Human Immunodeficiency Virus and the Cardiometabolic Syndrome in the Developing World: An African Perspective

Journal Article Journal of the CardioMetabolic Syndrome · March 2008 The advent of highly active antiretroviral therapy (HAART) has transformed human immunodeficiency virus (HIV)/AIDS into a manageable chronic disorder. Clinical care, however, needs to address the metabolic, anthropometric, and cardiov ... Full text Cite

Left Ventricular Dysfunction in Human Immunodeficiency Virus Infection

Journal Article Journal of the CardioMetabolic Syndrome · March 2008 The relationship between human immunodeficiency virus (HIV) infection and cardiovascular disease is still under debate, but it appears that the risk of myocardial infarction in those with HIV infection who are receiving highly active ... Full text Cite

Cardiometabolic Disease in the Human Immunodeficiency Virus: The Tip of the Iceberg?

Journal Article Journal of the CardioMetabolic Syndrome · March 2008 Full text Cite

HIV-protease inhibitors induce expression of suppressor of cytokine signaling-1 in insulin-sensitive tissues and promote insulin resistance and type 2 diabetes mellitus

Journal Article American Journal of Physiology-Endocrinology and Metabolism · March 2008 Insulin resistance, hyperglycemia, and type 2 diabetes are among the sequelae of metabolic syndromes that occur in 60–80% of human immunodeficiency virus (HIV)-positive patients treated with HIV-protease inhibitors (PIs). Studies to elucidate the ... Full text Cite

Post‐exercise heart rate recovery in HIV‐positive individuals on highly active antiretroviral therapy. Early indicator of cardiovascular disease?

Journal Article HIV Medicine · February 2008 BackgroundHIV infection and its treatment, specifically protease inhibitor (PI) therapy, have been associated with an increased risk for cardiovascular disease. Heart rate recovery (HRR) following peak exercise is ... Full text Cite

Blunted lipolysis and fatty acid oxidation during moderate exercise in HIV-infected subjects taking HAART

Journal Article American Journal of Physiology-Endocrinology and Metabolism · March 2007 The protease inhibitor (PI) ritonavir (RTV) has been associated with elevated resting lipolytic rate, hyperlipidemia, and insulin resistance/glucose intolerance. The purpose of this study was to examine relationships between lipolysis and fatty aci ... Full text Cite

PPARα activation elevates blood pressure and does not correct glucocorticoid-induced insulin resistance in humans

Journal Article American Journal of Physiology-Endocrinology and Metabolism · December 2006 Fibrates, activators of the nuclear receptor PPARα, improve dyslipidemia, but their effects on insulin resistance and vascular disease are unresolved. To test the hypothesis that PPARα activation improves insulin resistance and vascular function, ... Full text Cite

Whole-Body Proteolysis Rate Is Elevated in HIV-Associated Insulin Resistance

Journal Article Diabetes · October 1, 2006 Type 2 diabetes is characterized by impaired glucose tolerance (IGT) and insulin resistance with respect to glucose metabolism but not amino acid metabolism. We examined whether whole-body leucine and protein metabolism are dysregulated in HIV-infe ... Full text Cite

Alterations in liver, muscle, and adipose tissue insulin sensitivity in men with HIV infection and dyslipidemia

Journal Article American Journal of Physiology-Endocrinology and Metabolism · January 2006 Dyslipidemia is common in patients with HIV infection. In this study, a two-stage euglycemic hyperinsulinemic clamp, with infusion of stable isotopically labeled tracers, was used to evaluate insulin action in skeletal muscle, liver, and adipose ti ... Full text Cite

A Comparison of &OV0422;t and a-vO2 in Individuals with HIV Taking and Not Taking HAART

Journal Article Medicine & Science in Sports & Exercise · July 2003 Full text Cite

Aerobic capacity in late adolescents infected with HIV and controls

Journal Article Pediatric Rehabilitation · January 2002 Full text Cite