Endocrinology, Diabetes, and Metabolism Commons^™

Stat1 Dissociates Adipose Tissue Inflammation From Insulin Sensitivity In Obesity, Aaron R Cox, Natasha Chernis, David A Bader, Pradip K Saha, Peter M Masschelin, Jessica B Felix, Robert Sharp, Zeqin Lian, Vasanta Putluri, Kimal Rajapakshe, Kang Ho Kim, Dennis T Villareal, Reina Armamento-Villareal, Huaizhu Wu, Cristian Coarfa, Nagireddy Putluri, Sean M Hartig

Faculty, Staff and Students Publications

Obesity fosters low-grade inflammation in white adipose tissue (WAT) that may contribute to the insulin resistance that characterizes type 2 diabetes. However, the causal relationship of these events remains unclear. The established dominance of STAT1 function in the immune response suggests an obligate link between inflammation and the comorbidities of obesity. To this end, we sought to determine how STAT1 activity in white adipocytes affects insulin sensitivity. STAT1 expression in WAT inversely correlated with fasting plasma glucose in both obese mice and humans. Metabolomic and gene expression profiling established STAT1 deletion in adipocytes (STAT1a-KO) enhanced mitochondrial function …

Lifetime Risk Of Diabetes In Metropolitan Cities In India, Shammi Luhar, Dimple Kondal, Rebecca Jones, Ranjit M. Anjana, Shivani A. Patel, Sanjay Kinra, Lynda Clarke, Mohammed K. Ali, Dorairaj Prabhakaran, Muhammad Masood Kadir

Community Health Sciences

Aims/hypothesis: We aimed to estimate the lifetime risk of diabetes and diabetes-free life expectancy in metropolitan cities in India among the population aged 20 years or more, and their variation by sex, age and BMI.
Methods: A Markov simulation model was adopted to estimate age-, sex- and BMI-specific lifetime risk of developing diabetes and diabetes-free life expectancy. The main data inputs used were as follows: age-, sex- and BMI-specific incidence rates of diabetes in urban India taken from the Centre for Cardiometabolic Risk Reduction in South Asia (2010-2018); age-, sex- and urban-specific rates of mortality from period lifetables reported by …

Chronic Inflammatory Demyelinating Polyneuropathy (Cidp) In A Patient With Diabetes: A Primary Care Perspective, Jordan Dever, Adam M. Franks, Laura M. Given, William Rollyson, Adrienne Mays-Kingston

Marshall Journal of Medicine

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a recurrent and progressive disease that causes proximal, symmetrical extremity weakness. The disease is diagnosed using clinical features, electrophysiologic testing, albumino-cytological disassociation in the cerebrospinal fluid, and sural nerve plexus biopsy. However, because of the low sensitivity of diagnostic criteria and other similar neuropathies, including diabetic polyneuropathy (DPN), accurate diagnosis is difficult. Differentiating between these diseases is especially important as CIDP’s changes are reversible and DPN’s are not. Making this differentiation allows for symptomatic improvement in a patient’s quality of life that would not be achieved otherwise. Early recognition and treatment, with modalities including …

Diabetes Mellitus Does Not Predict Discharge In Hospitalized Patients With Acute Pyelonephritis: A Study From Karachi, Pakistan, Syed Furrukh Omair, Fazal Ur Rehman, Imrana Amin, Syed Ahsan Ali, Bakhtawar J. Rind, Bilal Ahmed

Section of Nephrology

Introduction: The incidence of acute pyelonephritis (APN) in the diabetic population is comparatively higher and tends to be more complicated, with serious outcomes. Although complicated pyelonephritis (PN) needs hospital admission and intravenous antibiotics, the magnitude of hospital stay due to comorbidities is limited. This study's aim was to assess the impact of diabetes mellitus on length of hospital stay among patients with PN.
Methods: We did a retrospective data review of 520 randomly selected hospitalized patients of PN from March 2015 to December 2019 from a tertiary care center. Electronic medical records were used for identifying medical conditions through ICD-10 …

A Body Shape Index Significantly Predicts Mri-Defined Abdominal Adipose Tissue Depots In Non-Obese Asian Indians With Type 2 Diabetes Mellitus, Shajith Anoop, Jesse Krakauer, Nir Krakauer, Anoop Misra

Publications and Research

Introduction: We aimed to determine the correlations of volumes of subcutaneous abdominal adipose tissue (SCAT) (anterior, posterior, superficial and deep), total SCAT, intraperitoneal adipose tissue, retroperitoneal abdominal adipose tissue (RPAT), total intra-abdominal adipose tissue (IAAT), pancreatic volume, liver span, total body fat (TBF) and truncal fat mass (TFM) with anthropometric indices, viz., A Body Shape Index (ABSI), Hip Index, their Z scores and Anthropometric Risk Index in non-obese (body mass index (BMI) /m²) Asian Indians with type 2 diabetes mellitus (T2DM).

Research design and methods: Non-obese patients with T2DM (cases; n, 85) and BMI-matched, healthy subjects …

Mir-30a Targets Gene Networks That Promote Browning Of Human And Mouse Adipocytes, Pradip K Saha, Mark P Hamilton, Kimal Rajapakshe, Vasanta Putluri, Jessica B Felix, Peter Masschelin, Aaron R Cox, Mandeep Bajaj, Nagireddy Putluri, Cristian Coarfa, Sean M Hartig

Faculty, Staff and Students Publications

MicroRNA-30a (miR-30a) impacts adipocyte function, and its expression in white adipose tissue (WAT) correlates with insulin sensitivity in obesity. Bioinformatic analysis demonstrates that miR-30a expression contributes to 2% of all miRNA expression in human tissues. However, molecular mechanisms of miR-30a function in fat cells remain unclear. Here, we expanded our understanding of how miR-30a expression contributes to antidiabetic peroxisome proliferator-activated receptor-γ (PPARγ) agonist activity and metabolic functions in adipocytes. We found that WAT isolated from diabetic patients shows reduced miR-30a levels and diminished expression of the canonical PPARγ target genes ADIPOQ and FABP4 relative to lean counterparts. In human adipocytes, …

Frequency Of Silent Carotid Artery Stenosis In Diabetics And Its Associated Factors: An Analysis In Tertiary Care Hospital, Faiza Sadaqat Ali, Nimrah Bader, Bader Faiyaz Zuberi, Sabiha Banu

Section of Diabetes, Endocrinology and Metabolism

Objective: To estimate frequency of silent carotid artery stenosis and its associated factors in diabetic patients attending a tertiary care hospital.
Methods: This cross-sectional study was conducted in tertiary care Civil Hospital, Karachi from March 2019 to September 2019,. A total of 166 patients with Diabetes Mellitus were included in this study. Brief history was taken for the duration of DM, treatment, and smoking habits. Carotid artery stenosis (CAS) wafrs measured by Doppler ultrasound of right and left common, internal, and external carotid arteries.
Results: Frequency of silent carotid artery stenosis (CAS) in diabetic patients was observed in 28.92% (48/166) …

Localizing An Occult Insulinoma By Selective Calcium Arterial Stimulation Test: First Ever Experience And A New Dimension To Diagnosis In Pakistan, Muhammad Owais Rashid, Sumerah Jabeen, Zareen Kiran,, Khurram Minhas, Muhammad Azeemuddin, Najmul Islam

Section of Diabetes, Endocrinology and Metabolism

Insulinomas are rare, usually benign, solitary tumours accounting for 60% of islet cell tumours. These tumours can be difficult to localize preoperatively due to their small size. We present a challenging case of a 40 year old male with frequent hypoglycaemic spells and endogenous hypoglycaemia who presented as a diagnostic dilemma. Patient had an occult insulinoma with inconclusive CT Abdomen, MRI Abdomen and Octreotide scan. The final localization of the tumour was made by selective arterial calcium stimulation testing (SCAT), done for the first time in Pakistan at Aga Khan University Hospital. This was followed by successful distal pancreatectomy as …

Vitamin D Usage Among Pakistani Population - Too Much Of A Good Thing, Bhagwan Das, Sarah Nadeem

Section of Diabetes, Endocrinology and Metabolism

No abstract provided.

Mtor-Initiated Metabolic Switch And Degeneration In The Retinal Pigment Epithelium, Young-Mi Go, Jing Zhang, Jolyn Fernandes, Christopher Litwin, Rui Chen, Theodore G Wensel, Dean P Jones, Jiyang Cai, Yan Chen

Faculty, Staff and Students Publications

The retinal pigment epithelium (RPE) is a particularly vulnerable tissue to age-dependent degeneration. Over the life span, the RPE develops an expanded endo-lysosomal compartment to maintain the high efficiency of phagocytosis and degradation of photoreceptor outer segments (POS) necessary for photoreceptor survival. As the assembly and activation of the mechanistic target of rapamycin complex 1 (mTORC1) occur on the lysosome surface, increased lysosome mass with aging leads to higher mTORC1 activity. The functional consequences of hyperactive mTORC1 in the RPE are unclear. In the current study, we used integrated high-resolution metabolomic and genomic approaches to examine mice with RPE-specific deletion …

The Utility Of Ultrasound In The Preoperative Localization Of Primary Hyperparathyroidism: Insights From Pakistan, Tehseen Fatima, Bhagwan Das, Saadia Sattar, Sumerah Jabeen, Abid Abbas Khan, Najmul Islam

Section of Diabetes, Endocrinology and Metabolism

Objective: We aimed to evaluate and compare the diagnostic performance of ultrasound (US) and 99m-Tc sestamibi scintigraphy for the preoperative localization of primary hyperparathyroidism (PHPT).
Methods: This retrospective study was conducted at the Aga Khan University Hospital in Karachi, Pakistan, and comprised the data of patients with PHPT who underwent parathyroidectomy from 2008 to 2017. Preoperative US and 99m-Tc sestamibi scintigraphy findings were recorded and compared to surgical and histological findings, which were taken as a reference standard.
Results: The sensitivity of US in the preoperative localization of PHPT was 88.3%, positive predictive value (PPV) was 94.6%, and accuracy …

Changing Prevalence Of Gestational Diabetes Mellitus During Pregnancy Over More Than A Decade, Aisha Sheikh, Lumaan Sheikh

Section of Diabetes, Endocrinology and Metabolism

No abstract provided.

A 2-Hour Diabetes Self-Management Education Program For Patients With Low Socioeconomic Status Improves Short-Term Glycemic Control, Michael G. Jakoby Iv, Melissa Schleder, Vickie Luff, Cynthia Yergler, Albert Botchway, Cheryl Burns

Journal of Patient-Centered Research and Reviews

Diabetes self-management education (DSME) improves glycemic control, but patients with low socioeconomic status face institutional and personal barriers to receiving DSME. A retrospective single cohort study of a 2-hour group DSME program prioritizing accessibility and completion of a tightly focused curriculum was performed to determine if glycemic control improved and whether a longer, more comprehensive, prospective evaluation of the program is indicated. All patients who participated in the program from September 2017 to December 2018 were included in the analysis. The primary study endpoint was change in hemoglobin A1c (HbA1c) from baseline. A total of 58 out of 94 patients …

Endocrine Significance Of Sars-Cov-2'S Reliance On Ace2, Eric Lazartigues, Mirza Muhammad Fahd Qadir, Franck Mauvais-Jarvis

School of Medicine Faculty Publications

The current COVID-19 pandemic is the most disruptive event in the past 50 years, with a global impact on health care and world economies. It is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a coronavirus that uses angiotensin-converting enzyme 2 (ACE2) as an entry point to the cells. ACE2 is a transmembrane carboxypeptidase and member of the renin-angiotensin system. This mini-review summarizes the main findings regarding ACE2 expression and function in endocrine tissues. We discuss rapidly evolving knowledge on the potential role of ACE2 and SARS coronaviruses in endocrinology and the development of diabetes mellitus, hypogonadism, and pituitary and …

Metformin Enhances Autophagy And Normalizes Mitochondrial Function To Alleviate Aging-Associated Inflammation, Leena P Bharath, Madhur Agrawal, Grace Mccambridge, Dequina A Nicholas, Hatice Hasturk, Jing Liu, Kai Jiang, Rui Liu, Zhenheng Guo, Jude Deeney, Caroline M Apovian, Jennifer Snyder-Cappione, Gregory S Hawk, Rebecca M Fleeman, Riley M F Pihl, Katherine Thompson, Anna C Belkina, Licong Cui, Elizabeth A Proctor, Philip A Kern, Barbara S Nikolajczyk

Faculty, Staff and Student Publications

Age is a non-modifiable risk factor for the inflammation that underlies age-associated diseases; thus, anti-inflammaging drugs hold promise for increasing health span. Cytokine profiling and bioinformatic analyses showed that Th17 cytokine production differentiates CD4+ T cells from lean, normoglycemic older and younger subjects, and mimics a diabetes-associated Th17 profile. T cells from older compared to younger subjects also had defects in autophagy and mitochondrial bioenergetics that associate with redox imbalance. Metformin ameliorated the Th17 inflammaging profile by increasing autophagy and improving mitochondrial bioenergetics. By contrast, autophagy-targeting siRNA disrupted redox balance in T cells from young subjects and activated the Th17 …

Trichosporon Species And Fusarium Species As A Cause Of Empyema Thoracis In A Diabetic Patient, Nousheen Iqbal, Muhammad Ammar, Muhammad Irfan, Kauser Jabeen

Section of Pulmonary & Critical Care

Of late, fungal infections are increasingly being recognized in diabetic patients. Here we present a case of polymicrobial fungal empyema due to Trichosporon species and Fusarium species developed after community-acquired pneumonia in a diabetic patient. Trichosporon species are basidiomycetous yeast and Fusarium species are soil saprophytes with a worldwide distribution. Fungal empyema cases are rare and are mostly caused by Aspergillus and Candida species. Polymicrobial fungal empyema with Trichosporon species and Fusarium species has not been reported previously. Our patient was successfully treated with antifungal therapy. This case highlights that fungal empyema should be considered in diabetic patients especially if …

Glycemic Control And Infections Among Us Hemodialysis Patients With Diabetes Mellitus, Jinnie J Rhee, Yuanchao Zheng, Sai Liu, Maria E Montez-Rath, Richard J Hamill, Julie H Ishida, Wolfgang C Winkelmayer

Faculty, Staff and Students Publications

INTRODUCTION: Patients with diabetes mellitus (DM) on hemodialysis (HD) may be particularly vulnerable to infections.

METHODS: We used merged data from the United States Renal Data System and electronic health records data from a large US dialysis provider to retrospectively examine the association between glycemic control and infections in these patients. Adult patients with DM aged ≥18 years who initiated in-center maintenance HD treatment from 2006 to 2011 and survived >90 days were included. Quarterly mean time-averaged hemoglobin A1c (HbA1c) values were categorized into

RESULTS: In a cohort of 33,753 eligible patients, those with higher HbA1c levels had higher rates …

Myeloma Cells Shift Osteoblastogenesis To Adipogenesis By Inhibiting The Ubiquitin Ligase Murf1 In Mesenchymal Stem Cells, Zhiqiang Liu, Huan Liu, Jin He, Pei Lin, Qiang Tong, Jing Yang

Faculty, Staff and Students Publications

The suppression of bone formation is a hallmark of multiple myeloma. Myeloma cells inhibit osteoblastogenesis from mesenchymal stem cells (MSCs), which can also differentiate into adipocytes. We investigated myeloma-MSC interactions and the effects of such interactions on the differentiation of MSCs into adipocytes or osteoblasts using single-cell RNA sequencing, in vitro co-culture, and subcutaneous injection of MSCs and myeloma cells into mice. Our results revealed that the α4 subunit of integrin on myeloma cells stimulated vascular cell adhesion molecule 1 (VCAM1) on MSCs, leading to the activation of protein kinase C β1 (PKCβ1) signaling and repression of the muscle ring-finger …

Developing A Clinical Practice Guideline For Surgical Diabetic Patients, Barbie Denise Harbaugh, Diane Whitehead

Walden Faculty and Staff Publications

Diabetes is a recognized risk factor for postoperative infection, acute renal failure, ileus, and lengthy hospital stay. Optimal screening, management, and scheduling of elective surgery for diabetic patients has been shown to improve quality care, decrease complications, and increase the efficiency and lower the costs of preoperative patient care. However, surgery cancellations are common due to inadequate preoperative glycemic control and poor intraoperative glycemic control, which is a recognized risk factor for perioperative or postoperative complications. There were no clinical practice guidelines or optimization protocols for elective surgery patients at a small rural hospital in the Northeast United States. The …

Teriparatide And Its Bone Healing Power, Aneeta J. Joseph, Jesus L. Penabad, Antonio Pinero-Pilona

West Florida Division GME Research Day 2020

Teriparatide, a parathyroid hormone analog, is an important anabolic agent approved by the U.S. Food and Drug Administration to increase bone mineral density in osteoporotic patients. Parathyroid hormone (PTH) regulates calcium, phosphate, and active vitamin-D metabolites. The amino terminal peptide fragments of PTH has been known to increase bone mass and are being used in clinical practice for osteoporosis management.3 Teriparatide increases bone density of lumbar spine and femoral neck, and decreases the risk of vertebral and non-vertebral fractures both in postmenopausal women and men. It is also known to prevent fractures in patients with osteoporosis and promote healing of …

Dietary Fat And Sugar Differentially Affect Β-Adrenergic Stimulation Of Cardiac Erk And Akt Pathways In C57bl/6 Male Mice Subjected To High-Calorie Feeding, Sadia Ashraf, Gizem Yilmaz, Xu Chen, Romain Harmancey

Faculty, Staff and Student Publications

BACKGROUND: High dietary fat and sugar promote cardiac hypertrophy independently from an increase in blood pressure. The respective contribution that each macronutrient exerts on cardiac growth signaling pathways remains unclear.

OBJECTIVE: The goal of this study was to investigate the mechanisms by which high amounts of dietary fat and sugar affect cardiac growth regulatory pathways.

METHODS: Male C57BL/6 mice (9 wk old; n = 20/group) were fed a standard rodent diet (STD; kcal% protein-fat-carbohydrate, 29-17-54), a high-fat diet (HFD; 20-60-20), a high-fat and high-sugar Western diet (WD; 20-45-35), a high-sugar diet with mixed carbohydrates (HCD; 20-10-70), or a high-sucrose diet …

Metabolic-Sensing Of The Skeletal Muscle Clock Coordinates Fuel Oxidation, Hongshan Yin, Weini Li, Somik Chatterjee, Xuekai Xiong, Pradip Saha, Vijay Yechoor, Ke Ma

Faculty, Staff and Students Publications

Circadian clock confers temporal control in metabolism, with its disruption leading to the development of insulin resistance. Metabolic substrate utilization in skeletal muscle is coordinated with diurnal nutrient cycles. However, whether the molecular clock is involved in this coordination is largely unknown. Using a myocyte-selective genetic ablation mouse model of the essential clock activator Bmal1, here we identify muscle-intrinsic clock as a sensor of feeding cues to orchestrate skeletal muscle oxidation required for global nutrient flux. Bmal1 in skeletal muscle responds robustly to feeding in vivo and insulin induces its expression. Muscle Bmal1 deficiency impaired the transcriptional control of glucose …

Effects Of Alternative Chemotherapeutic Agents On Thyroid Cancer Cell Line Ml-1, Husref Rizvanovic

Graduate Theses/Dissertations

Though differentiated thyroid carcinomas have decent prognosis when detected early, radioactive iodine (RAI) resistant and advanced thyroid cancers are still difficult to treat with existing therapies. Better therapeutic agents are needed. Studies have shown that aggressive thyroid cancers (ML-1) express the extracellular matrix protein, matrix metalloproteinase (MMP-2). MMP-2 has been linked to metastasis and aggressiveness of several cancers and has been shown to play a crucial role in tumor invasion. Chlorotoxin is a selective MMP-2 receptor agonist, and Saporin is a well-known ribosome-inactivating protein used for anti-cancer treatment; however, these two agents have never been studied when conjugated together. I …

Association Of Intensive Lifestyle Intervention, Fitness, And Body Mass Index With Risk Of Heart Failure In Overweight Or Obese Adults With Type 2 Diabetes Mellitus: An Analysis From The Look Ahead Trial, Ambarish Pandey, Kershaw V Patel, Judy L Bahnson, Sarah A Gaussoin, Corby K Martin, Ashok Balasubramanyam, Karen C Johnson, Darren K Mcguire, Alain G Bertoni, Dalane Kitzman, Jarett D Berry, Look Ahead Research Group

Faculty, Staff and Students Publications

BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with a higher risk for heart failure (HF). The impact of a lifestyle intervention and changes in cardiorespiratory fitness (CRF) and body mass index on risk for HF is not well established.

METHODS: Participants from the Look AHEAD trial (Action for Health in Diabetes) without prevalent HF were included. Time-to-event analyses were used to compare the risk of incident HF between the intensive lifestyle intervention and diabetes support and education groups. The associations of baseline measures of CRF estimated from a maximal treadmill test, body mass index, and longitudinal changes in these …

Levosulpiride-Induced Hyperprolactinemia, Sarah Nadeem, Bhagwan Das

Section of Diabetes, Endocrinology and Metabolism

No abstract provided.

Delivering Non-Communicable Disease Interventions To Women And Children In Conflict Settings: A Systematic Review, Shailja Shah, Mariella Munyuzangabo, Michelle F. Gaffey, Mahdis Kamali, Reena P. Jain, Daina Als, Sarah Meteke, Amruta Radhakrishnan, Fahad J. Siddiqui, Anushka Ataullahjan, Zulfiqar Ahmed Bhutta

Woman and Child Health

Background: Non-communicable diseases (NCDs) are the leading cause of death worldwide. In the context of conflict settings, population displacement, disrupted treatment, infrastructure damage and other factors impose serious NCD intervention delivery challenges, but relatively little attention has been paid to addressing these challenges. Here we synthesise the available indexed and grey literature reporting on the delivery of NCD interventions to conflict-affected women and children in low- and middle-income countries (LMICs).
Methods: A systematic search in MEDLINE, Embase, CINAHL and PsycINFO databases for indexed articles published between 1 January 1990 and 31 March 2018 was conducted, and publications reporting on NCD …

Association Of Dairy Consumption With Metabolic Syndrome, Hypertension And Diabetes In 147 812 Individuals From 21 Countries, Balaji Bhavadharini, Mahshid Dehghan, Andrew Mente, Sumathy Rangarajan, Patrick Sheridan, Viswanathan Mohan, Romaina Iqbal, Rajeev Gupta, Scott Lear, Edelweiss Wentzel-Viljoen

Community Health Sciences

Objective: Our aims were to assess the association of dairy intake with prevalence of metabolic syndrome (MetS) (cross-sectionally) and with incident hypertension and incident diabetes (prospectively) in a large multinational cohort study.
Methods: The Prospective Urban Rural Epidemiology (PURE) study is a prospective epidemiological study of individuals aged 35 and 70 years from 21 countries on five continents, with a median follow-up of 9.1 years. In the cross-sectional analyses, we assessed the association of dairy intake with prevalent MetS and its components among individuals with information on the five MetS components (n=112 922). For the prospective analyses, we …

Neurochemical Characterization Of Brainstem Pro-Opiomelanocortin Cells, Teodora Georgescu, David Lyons, Barbora Doslikova, Ana Paula Garcia, Oliver Marston, Luke K Burke, Raffaella Chianese, Brian Y H Lam, Giles S H Yeo, Justin J Rochford, Alastair S Garfield, Lora K Heisler

Faculty, Staff and Student Publications

Genetic research has revealed pro-opiomelanocortin (POMC) to be a fundamental regulator of energy balance and body weight in mammals. Within the brain, POMC is primarily expressed in the arcuate nucleus of the hypothalamus (ARC), while a smaller population exists in the brainstem nucleus of the solitary tract (POMCNTS). We performed a neurochemical characterization of this understudied population of POMC cells using transgenic mice expressing green fluorescent protein (eGFP) under the control of a POMC promoter/enhancer (PomceGFP). Expression of endogenous Pomc mRNA in the nucleus of the solitary tract (NTS) PomceGFP cells was confirmed using fluorescence-activating cell sorting (FACS) followed by …

A Case Series Of Hyponatremia And Management In Hospitalized Patients, Jake N. Cho, Rebecca Ong, Izuchukwu Nwakoby

Nephrology

No abstract provided.

The Impact Of Diabetic Foot Ulcers And Unilateral Offloading Footwear On Gait In People With Diabetes, Erica Ling, Brian Lepow, He Zhou, Ana Enriquez, Ashley Mullen, Bijan Najafi

Faculty, Staff and Students Publications

BACKGROUND: Unilateral offloading footwear prescribed to patients with diabetic foot ulcers elevates one limb relative to the other, which may lead to limp and abnormal gait. This study investigated whether the unilateral foot ulcer and offloading combination negatively impacts gait function beyond diabetic peripheral neuropathy.

METHODS: Eighty-six participants were recruited in 3 groups: 12 with diabetic peripheral neuropathy and unilateral foot ulcers wearing offloading footwear (offloading group, age = 55.6 ± 9.5 years, BMI = 30.9 ± 4.5 kg/m

FINDINGS: The offloading group exhibited deteriorated gait function compared to the non-diabetic group (p < 0.005, Cohen's effect size d = 0.90-2.61). They also had decreased gait speed (p < 0.001, d = 1.79) and stride length (p < 0.001, d = 1.76), as well as increased gait cycle time (p < 0.001, d = 1.67) and limp (p < 0.050, d = 0.72-1.49) compared to the neuropathy group. The offloading group showed increased gait unsteadiness compared to the neuropathy group, but the difference did not reach statistical significance in our samples.

INTERPRETATION: This study demonstrated that while diabetic …