Browsing by Author "Phatak, Sanat"

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    Corrigendum: Quantification of joint mobility limitation in adult type 1 diabetes.
    (Frontiers in endocrinology, 2023-01) Phatak, Sanat; Mahadevkar, Pranav; Chaudhari, Kaustubh Suresh; Chakladar, Shreya; Jain, Swasti; Dhadge, Smita; Jadhav, Sarita; Shah, Rohan; Bhalerao, Aboli; Patil, Anupama; Ingram, Jennifer L; Goel, Pranay; Yajnik, Chittaranjan S
    [This corrects the article DOI: 10.3389/fendo.2023.1238825.].
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    Does hand stiffness reflect internal organ fibrosis in diabetes mellitus?
    (Frontiers in clinical diabetes and healthcare, 2023-01) Phatak, Sanat; Ingram, Jennifer L; Goel, Pranay; Rath, Satyajit; Yajnik, Chittaranjan
    Fibrosis leads to irreversible stiffening of tissue and loss of function, and is a common pathway leading to morbidity and mortality in chronic disease. Diabetes mellitus (both type 1 and type 2 diabetes) are associated with significant fibrosis in internal organs, chiefly the kidney and heart, but also lung, liver and adipose tissue. Diabetes is also associated with the diabetic cheirarthropathies, a collection of clinical manifestations affecting the hand that include limited joint mobility (LJM), flexor tenosynovitis, Duypuytren disease and carpal tunnel syndrome. Histo-morphologically these are profibrotic conditions affecting various soft tissue components in the hand. We hypothesize that these hand manifestations reflect a systemic profibrotic state, and are potential clinical biomarkers of current or future internal organ fibrosis. Epidemiologically, there is evidence that fibrosis in one organ associates with fibrosis with another; the putative exposures that lead to fibrosis in diabetes (advanced glycation end product deposition, microvascular disease and hypoxia, persistent innate inflammation) are 'systemic'; a common genetic susceptibility to fibrosis has also been hinted at. These data suggest that a subset of the diabetic population is susceptible to multi-organ fibrosis. The hand is an attractive biomarker to clinically detect this susceptibility, owing to its accessibility to physical examination and exposure to repeated mechanical stresses. Testing the hypothesis has a few pre-requisites: being able to measure hand fibrosis in the hand, using clinical scores or imaging based scores, which will facilitate looking for associations with internal organ fibrosis using validated methodologies for each. Longitudinal studies would be essential in delineating fibrosis trajectories in those with hand manifestations. Since therapies reversing fibrosis are few, the onus lies on identification of a susceptible subset for preventative measures. If systematically validated, clinical hand examination could provide a low-cost, universally accessible and easily reproducible screening step in selecting patients for clinical trials for fibrosis in diabetes.
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    Quantification of joint mobility limitation in adult type 1 diabetes.
    (Frontiers in endocrinology, 2023-01) Phatak, Sanat; Mahadevkar, Pranav; Chaudhari, Kaustubh Suresh; Chakladar, Shreya; Jain, Swasti; Dhadge, Smita; Jadhav, Sarita; Shah, Rohan; Bhalerao, Aboli; Patil, Anupama; Ingram, Jennifer L; Goel, Pranay; Yajnik, Chittaranjan S

    Aims

    Diabetic cheiroarthropathies limit hand mobility due to fibrosis and could be markers of a global profibrotic trajectory. Heterogeneity in definitions and lack of a method to measure it complicate studying associations with organ involvement and treatment outcomes. We measured metacarpophalangeal (MCP) joint extension as a metric and describe magnetic resonance (MR) imaging determinants of MCP restriction.

    Methods

    Adults with type 1 diabetes were screened for hand manifestations using a symptom questionnaire, clinical examination, and function [Duruoz hand index (DHI) and grip strength]. Patients were segregated by mean MCP extension (<20°, 20°-40°, 40°-60°, and >60°) for MR imaging (MRI) scanning. Patients in the four groups were compared using ANOVA for clinical features and MRI tissue measurements (tenosynovial, skin, and fascia thickness). We performed multiple linear regression for determinants of MCP extension.

    Results

    Of the 237 patients (90 men), 79 (33.8%) with cheiroarthropathy had MCP extension limitation (39° versus 61°, p < 0.01). Groups with limited MCP extension had higher DHI (1.9 vs. 0.2) but few (7%) had pain. Height, systolic blood pressure, and nephropathy were associated with mean MCP extension. Hand MRI (n = 61) showed flexor tenosynovitis in four patients and median neuritis in one patient. Groups with MCP mobility restriction had the thickest palmar skin; tendon thickness or median nerve area did not differ. Only mean palmar skin thickness was associated with MCP extension angle on multiple linear regression.

    Conclusion

    Joint mobility limitation was quantified by restricted mean MCP extension and had structural correlates on MRI. These can serve as quantitative measures for future associative and interventional studies.
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    Vertical sleeve gastrectomy associates with airway hyperresponsiveness in a murine model of allergic airway disease and obesity.
    (Frontiers in endocrinology, 2023-01) Womble, Jack T; Ihrie, Mark D; McQuade, Victoria L; Hegde, Akhil; McCravy, Matthew S; Phatak, Sanat; Tighe, Robert M; Que, Loretta G; D'Alessio, David; Walker, Julia KL; Ingram, Jennifer L

    Introduction

    Asthma is a chronic airway inflammatory disease marked by airway inflammation, remodeling and hyperresponsiveness to allergens. Allergic asthma is normally well controlled through the use of beta-2-adrenergic agonists and inhaled corticosteroids; however, a subset of patients with comorbid obesity experience resistance to currently available therapeutics. Patients with asthma and comorbid obesity are also at a greater risk for severe disease, contributing to increased risk of hospitalization. Bariatric surgery improves asthma control and airway hyperresponsiveness in patients with asthma and comorbid obesity, however, the underlying mechanisms for these improvements remain to be elucidated. We hypothesized that vertical sleeve gastrectomy (VSG), a model of metabolic surgery in mice, would improve glucose tolerance and airway inflammation, resistance, and fibrosis induced by chronic allergen challenge and obesity.

    Methods

    Male C57BL/6J mice were fed a high fat diet (HFD) for 13 weeks with intermittent house dust mite (HDM) allergen administration to induce allergic asthma, or saline as control. At week 11, a subset of mice underwent VSG or Sham surgery with one week recovery. A separate group of mice did not undergo surgery. Mice were then challenged with HDM or saline along with concurrent HFD feeding for 1-1.5 weeks before measurement of lung mechanics and harvesting of tissues, both of which occurred 24 hours after the final HDM challenge. Systemic and pulmonary cytokine profiles, lung histology and gene expression were analyzed.

    Results

    High fat diet contributed to increased body weight, serum leptin levels and development of glucose intolerance for both HDM and saline treatment groups. When compared to saline-treated mice, HDM-challenged mice exhibited greater weight gain. VSG improved glucose tolerance in both saline and HDM-challenged mice. HDM-challenged VSG mice exhibited an increase in airway hyperresponsiveness to methacholine when compared to the non-surgery group.

    Discussion

    The data presented here indicate increased airway hyperresponsiveness in allergic mice undergoing bariatric surgery.