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Guo SH, Xu J, Gong YQ, Hu WB, Li C, Lu K. Sex-specific association between triglyceride-glucose index and all-cause mortality in patients with osteoporotic fractures: a retrospective cohort study. Front Endocrinol (Lausanne) 2025; 16:1574238. [PMID: 40370776 PMCID: PMC12074978 DOI: 10.3389/fendo.2025.1574238] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2025] [Accepted: 04/03/2025] [Indexed: 05/16/2025] Open
Abstract
Background Osteoporotic fractures (OPFs) pose a considerable global health burden and are linked with an elevated mortality risk. The triglyceride-glucose index (TyG-I) is a recognized marker of insulin resistance across various populations. The association between all-cause mortality (ACM) and the TyG-I has been widely investigated in a variety of clinical settings. The potential sex-specific differences in this association among OPF patients remain uncertain. Methods In this retrospective cohort study, 2,307 patients ≥ 50 years old admitted to the hospital between January 2018 and August 2023 for surgical treatment of OPFs were included. The TyG-I was determined using fasting triglyceride and glucose levels measured at admission. The association between ACM and the TyG-I was evaluated by Cox proportional hazards regression, adjusting for possible confounding variables. Analyses were categorized by sex, and subgroup analyses evaluated possible interaction effects. The ACM rates among TyG-I tertiles were compared via Kaplan-Meier curves. Results This research study analyzed 2,307 patients, of whom 247 (10.71%) died from any cause during the follow-up period. In females, a linear association of the TyG-I with ACM was observed even after adjusting for confounders, with each unit increase in the TyG-I correlating with a 37% increased risk of death (HR: 1.37, 95% CI: 1.06-1.77, p = 0.02). However, in males, there was a non-linear correlation, where patients in the uppermost TyG-I tertile showed a substantially decreased mortality risk relative to those in the lowest tertile (HR: 0.53, 95% CI: 0.30-0.92, p = 0.02). TyG-I indicated a statistically significant relation with sex (P for interaction = 0.01). Conclusion In patients diagnosed with OPFs, distinct sex-specific variations were observed in the relationship between ACM and the TyG-I. Among female patients, each unit increase in the TyG-I was linked to a 37% greater risk of mortality. Conversely, male patients within the highest TyG-I tertile indicated a lower mortality risk than those in the lowest tertile. Further research is required to confirm these sex-specific associations.
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Affiliation(s)
- Shao-han Guo
- Department of Orthopedics, Affiliated Kunshan Hospital of Jiangsu University, Suzhou, Jiangsu, China
- Kunshan Biomedical Big Data Innovation Application Laboratory, Suzhou, Jiangsu, China
| | - Jian Xu
- Kunshan Biomedical Big Data Innovation Application Laboratory, Suzhou, Jiangsu, China
- Department of Orthopedics, The First People’s Hospital of Kunshan, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, China
| | - Ya-qin Gong
- Kunshan Biomedical Big Data Innovation Application Laboratory, Suzhou, Jiangsu, China
- Information Department, Affiliated Kunshan Hospital of Jiangsu University, Suzhou, Jiangsu, China
| | - Wen-bin Hu
- Chronic Disease Department, Kunshan Center for Disease Control and Prevention, Suzhou, Jiangsu, China
| | - Chong Li
- Department of Orthopedics, Affiliated Kunshan Hospital of Jiangsu University, Suzhou, Jiangsu, China
- Kunshan Biomedical Big Data Innovation Application Laboratory, Suzhou, Jiangsu, China
| | - Ke Lu
- Department of Orthopedics, Affiliated Kunshan Hospital of Jiangsu University, Suzhou, Jiangsu, China
- Kunshan Biomedical Big Data Innovation Application Laboratory, Suzhou, Jiangsu, China
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Zhu Q, Zong Q, Guo S, Ye H, Ma Z, Zhang R, Zou H, Ba Y. Mean amplitude of glycemic excursion and mortality in critically ill patients: A retrospective analysis using the MIMIC-IV database. Diabetes Obes Metab 2025. [PMID: 40259524 DOI: 10.1111/dom.16410] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2025] [Revised: 04/02/2025] [Accepted: 04/04/2025] [Indexed: 04/23/2025]
Abstract
BACKGROUND Glycemic variability (GV) is increasingly recognised as a critical determinant of outcomes in critically ill patients. However, standardised criteria for assessing GV remain undefined. OBJECTIVE This study aimed to evaluate the relationship between the Mean Amplitude of Glycemic Excursion (MAGE) and mortality in intensive care unit (ICU) patients, and to determine optimal MAGE thresholds for distinct patient populations. METHODS A retrospective cohort of 13 852 critically ill adults with ICU stays exceeding 24 h was analysed. Patients were stratified into MAGE quartiles, and various GV metrics were compared for their predictive performance on mortality. Multivariable-adjusted models were employed to examine associations between MAGE and mortality outcomes. RESULTS Patients in higher MAGE quartiles exhibited significantly elevated mortality risks, with the highest quartile associated with ICU mortality (HR 3.59 [95% CI: 2.99-4.31]), in-hospital mortality (HR: 3.43 [95% CI: 2.92-4.02]) and 28-day mortality (HR 2.04 [95% CI: 1.47-2.82]). The relationship between MAGE and mortality was notably stronger in non-diabetic patients (HR: 3.36 [95% CI: 2.90-3.89]) compared to diabetic patients (HR: 1.59 [95% CI: 1.33-1.91]). Restricted cubic spline analyses identified optimal MAGE thresholds of 44.28 mg/dL for the overall population, 58.97 mg/dL for diabetic patients and 17.11 and 37.72 mg/dL for non-diabetic patients. MAGE demonstrated effective predictive performance for all-cause mortality (AUC: 0.6286 [95% CI: 0.6171-0.6400]) compared to other GV metrics. Incorporating MAGE into prognostic models alongside SAPS II and SOFA scores improved performance for all-cause mortality, with net reclassification improvement (NRI) of 0.238 and integrated discrimination improvement (IDI) of 0.008. CONCLUSION MAGE exhibits effective predictive value for mortality in ICU patients, with distinct thresholds for diabetic and non-diabetic populations. These findings underscore the importance of tailored GV management strategies in critical care settings and support the adoption of MAGE as a standardised metric for GV assessment in ICU settings.
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Affiliation(s)
- Qiang Zhu
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Qinghai University, Xining, China
- Department of Endocrinology and Metabolism, Yibin Fifth People's Hospital, Yibin, China
| | - Qunchuan Zong
- Department of Traumatology and Orthopaedics, The Affiliated Hospital of Qinghai University, Xining, China
| | - Shiying Guo
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Qinghai University, Xining, China
| | - Huimin Ye
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Qinghai University, Xining, China
| | - Zilan Ma
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Qinghai University, Xining, China
| | - Ruixia Zhang
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Qinghai University, Xining, China
| | - Huajie Zou
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Qinghai University, Xining, China
| | - Yinggui Ba
- Department of Nephrology, The Affiliated Hospital of Qinghai University, Xining, China
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Xu H, Xia Y, Mo R, Liu Y. The association between the triglyceride‒glucose index and short-term mortality in ICU patients with sepsis-associated acute kidney injury. BMC Infect Dis 2025; 25:257. [PMID: 39994563 PMCID: PMC11849171 DOI: 10.1186/s12879-025-10649-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Accepted: 02/14/2025] [Indexed: 02/26/2025] Open
Abstract
BACKGROUND The triglyceride-glucose (TyG) index has emerged as a novel marker for insulin resistance and is commonly observed in patients suffering from sepsis-associated acute kidney injury (SA-AKI). This study explored the correlation between the TyG index and short-term all-cause mortality among SA-AKI patients. METHODS We performed a retrospective analysis of ICU patients with SA-AKI using data from the MIMIC-IV database. The primary outcomes were 28-day and 90-day all-cause mortality. Multivariate Cox proportional hazards regression, restricted cubic spline (RCS) models, and Kaplan‒Meier (K‒M) survival analyses were used to examine the associations between the TyG index and mortality. Subgroup and sensitivity analyses were conducted to ensure the robustness of the findings. RESULTS The study included 4971 SA-AKI patients, with 2873 males (57.8%), an average age of 65.4 years (± 15.8), and an average TyG index of 9.10 (± 0.70). RCS analysis revealed a U-shaped relationship between the TyG index and mortality. When the TyG index was below 9.04, the risk of mortality at both 28 days and 90 days was reduced (adjusted HRs of 0.695, 95% CI: 0.542-0.890 and 0.691, 95% CI: 0.557-0.858, respectively). In contrast, values above 9.04 were associated with increased mortality, though the relationship was not statistically significant (adjusted HRs of 1.026, 95% CI: 0.855-1.231 and 1.012, 95% CI: 0.863-1.188, respectively). K‒M analysis revealed higher mortality rates for patients with either high (T3) or low (T1) TyG indices than for those with moderate (T2) TyG indices. Sensitivity analyses confirmed these associations even after excluding patients with diabetes, cerebrovascular diseases, or ICU stays of less than 2 days. CONCLUSION The TyG index is significantly and nonlinearly associated with short-term all-cause mortality in SA-AKI patients; however, establishing a causal relationship between the two requires validation through larger prospective studies.
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Affiliation(s)
- Heping Xu
- Department of Emergency Medicine, Hainan General Hospital/Hainan Affiliated Hospital of Hainan Medical University, No. 19, Xiuhua Road, Xiuying District, Haikou City, Hainan Province, 570311, China.
| | - Yan Xia
- Department of General Practice, The First Affiliated Hospital of Hainan Medical University, Haikou City, Hainan Province, 570103, China
| | - Ruiyong Mo
- Department of Emergency Medicine, Hainan Affiliated Hospital of Hainan Medical University, Haikou City, Hainan Province, 570311, China
| | - Yiqiao Liu
- Department of Emergency Medicine, Hainan Affiliated Hospital of Hainan Medical University, Haikou City, Hainan Province, 570311, China
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Xu H, Xie J, Xia Y, Niu H, Wang H, Zhan F. Association of TyG index with mortality at 28 days in sepsis patients in intensive care from MIMIC IV database. Sci Rep 2025; 15:2344. [PMID: 39833386 PMCID: PMC11747252 DOI: 10.1038/s41598-025-86746-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Accepted: 01/13/2025] [Indexed: 01/22/2025] Open
Abstract
The relationship between the triglyceride‒glucose (TyG) index and the clinical prognosis of septic patients in intensive care units (ICUs) remains unclear. This study aimed to explore the correlation between the TyG index and 28-day all-cause mortality in septic patients. A retrospective observational cohort study was conducted, including 8955 septic patients from the MIMIC IV 2.2 database. The primary outcome was 28-day all-cause mortality. Multivariate logistic regression analysis and restricted cubic spline regression analysis were used to assess the relationship between the TyG index and 28-day all-cause mortality in septic patients. Subgroup analyses and sensitivity analyses were performed to further validate the robustness of the results. A total of 8955 septic patients were included, 5219 (58.3%) of whom were male, with a mean age of 66.3 (15.8) years and an average TyG index of 9.08 (0.70) and the number of deaths within 28 days was 1639 (18.3%). The RCS curve demonstrated a U-shaped relationship between the TyG index and 28-day all-cause mortality (nonlinear P value = 0.0003). The risk of 28-day all-cause mortality was negatively associated with the TyG index until it decreased to 9.03 (adjusted odds ratio [OR] 0.727, 95% confidence interval [CI] 0.577-0.915). However, when the TyG index exceeded 9.03, the odds ratio for 28-day all-cause mortality significantly increased (adjusted OR 1.185, 95% CI 1.001-1.404). These findings were consistent across subgroups and various sensitivity analyses. Our study revealed a nonlinear U-shaped relationship between the TyG index and 28-day all-cause mortality, with a critical point at a TyG index of 9.03. Our results suggest that the TyG index may be a novel and important factor for the short-term clinical prognosis of critically ill septic patients.
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Affiliation(s)
- Heping Xu
- Department of Emergency Medicine, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, No. 19, Xiuhua Road, Xiuying District, Haikou, Hainan, 570311, Hainan Province, China.
| | - Jinyuan Xie
- Department of Emergency Medicine, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, No. 19, Xiuhua Road, Xiuying District, Haikou, Hainan, 570311, Hainan Province, China
| | - Yan Xia
- Department of Cardiovascular Medicine, The First Affiliated Hospital of Hainan Medical University, Haikou, Hainan, 570102, China
| | - Huan Niu
- Department of Emergency Medicine, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, No. 19, Xiuhua Road, Xiuying District, Haikou, Hainan, 570311, Hainan Province, China
| | - Hong Wang
- Department of Emergency Medicine, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, No. 19, Xiuhua Road, Xiuying District, Haikou, Hainan, 570311, Hainan Province, China
| | - Feng Zhan
- Department of Emergency Medicine, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, No. 19, Xiuhua Road, Xiuying District, Haikou, Hainan, 570311, Hainan Province, China
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Deer TR, Hayek SM, Grider JS, Pope JE, Brogan SE, Gulati A, Hagedorn JM, Strand N, Hah J, Yaksh TL, Staats PS, Perruchoud C, Knezevic NN, Wallace MS, Pilitsis JG, Lamer TJ, Buchser E, Varshney V, Osborn J, Goel V, Simpson BA, Lopez JA, Dupoiron D, Saulino MF, McDowell GC, Piedimonte F, Levy RM. The Polyanalgesic Consensus Conference (PACC)®: Updates on Clinical Pharmacology and Comorbidity Management in Intrathecal Drug Delivery for Cancer Pain. Neuromodulation 2024:S1094-7159(24)00670-6. [PMID: 39297833 DOI: 10.1016/j.neurom.2024.08.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Revised: 07/23/2024] [Accepted: 08/13/2024] [Indexed: 09/29/2024]
Abstract
INTRODUCTION The International Neuromodulation Society convened a multispecialty group of physicians based on expertise with international representation to establish evidence-based guidance on using intrathecal drug delivery in chronic pain treatment. This Polyanalgesic Consensus Conference (PACC)® project's scope is to provide evidence-based guidance for clinical pharmacology and best practices for intrathecal drug delivery for cancer pain. MATERIALS AND METHODS Authors were chosen on the basis of their clinical expertise, familiarity with the peer-reviewed literature, research productivity, and contributions to the neuromodulation literature. Section leaders supervised literature searches using Medline, EMBASE, Cochrane CENTRAL, BioMed Central, Web of Science, Google Scholar, PubMed, Current Contents Connect, Meeting Abstracts, and Scopus from 2017 (when the PACC last published guidelines) to the present. Identified studies were graded using the United States Preventive Services Task Force criteria for evidence and certainty of net benefit. Recommendations were based on the strength of evidence, and when evidence was scant, recommendations were based on expert consensus. RESULTS The PACC evaluated the published literature and established evidence- and consensus-based expert opinion recommendations to guide best practices in treating cancer pain. Additional guidance will occur as new evidence is developed in future iterations of this process. CONCLUSIONS The PACC recommends best practices regarding the use of intrathecal drug delivery in cancer pain, with an emphasis on managing the unique disease and patient characteristics encountered in oncology. These evidence- and consensus-based expert opinion recommendations should be used as a guide to assist decision-making when clinically appropriate.
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Affiliation(s)
- Timothy R Deer
- The Spine and Nerve Center of the Virginias, Charleston, WV, USA.
| | - Salim M Hayek
- Case Western Reserve University, University Hospitals of Cleveland, Cleveland, OH, USA
| | - Jay S Grider
- UKHealthCare Pain Services, Department of Anesthesiology, University of Kentucky College of Medicine, Lexington, KY, USA
| | | | - Shane E Brogan
- Department of Anesthesiology, Division of Pain Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA
| | - Amitabh Gulati
- Department of Anesthesiology and Critical Care, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | | | - Natalie Strand
- Department of Anesthesiology, Division of Pain Medicine, Mayo Clinic, Phoenix, AZ, USA
| | - Jennifer Hah
- Department of Anesthesiology, Perioperative, and Pain Medicine, Stanford University, Palo Alto, CA, USA
| | - Tony L Yaksh
- Anesthesiology and Pharmacology, University of California San Diego, San Diego, CA, USA
| | - Peter S Staats
- ElectroCore, Rockaway, NJ, USA; National Spine and Pain Centers, Rockville, MD, USA
| | | | - Nebojsa Nick Knezevic
- Department of Anesthesiology and Surgery at University of Illinois, Department of Anesthesiology, Advocate Illinois Masonic Medical Center, Chicago, IL, USA
| | - Mark S Wallace
- Division of Pain Management, Department of Anesthesiology, University of California San Diego, San Diego, CA, USA
| | - Julie G Pilitsis
- Department of Neurosurgery, University of Arizona, Tucson, AZ, USA
| | - Tim J Lamer
- Department of Anesthesia and Perioperative Medicine, Mayo Clinic, Rochester, MN, USA
| | - Eric Buchser
- Department of Anaesthesia and Pain Management, Neuromodulation Centre, Morges, Switzerland
| | - Vishal Varshney
- Providence Health Care, University of British Columbia, British Columbia, Canada
| | - Jill Osborn
- Department of Anesthesiology, Providence Health Care, Vancouver, British Columbia, Canada
| | - Vasudha Goel
- Department of Anesthesiology, University of Minnesota, Minneapolis, MN, USA
| | - Brian A Simpson
- Department of Neurosurgery, Cardiff and Vale University Health Board, Cardiff, UK
| | - Jose A Lopez
- Service of Neurosurgery and Pain Clinic, University Hospital "Puerta del Mar," Cadiz, Spain
| | - Denis Dupoiron
- Department of Anesthesiology and Pain Medicine, Institut de Cancerologie de L'Ouset, Angers, France
| | | | | | - Fabian Piedimonte
- Fundaciόn CENIT, University of Buenos Aires, Buenos Aires, Argentina
| | - Robert M Levy
- International Neuromodulation Society and Director of Neurosurgical Services, Director of Clinical Research, Anesthesia Pain Care Consultants, Tamarac, FL, USA
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Bogart AM, Lopez CR, Obeidalla SN, Wang C, Willmore A, Jauregui A, Kangelaris KN, Hendrickson C, Gomez A, Liu KD, Matthay MA, Shaver CM, Bastarache JA, Calfee CS, Kerchberger VE, Ware LB. Elevated Hemoglobin A1c and the Risk of Developing ARDS in Two Cohort Studies. CHEST CRITICAL CARE 2024; 2:100082. [PMID: 39421542 PMCID: PMC11485198 DOI: 10.1016/j.chstcc.2024.100082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 10/19/2024]
Abstract
BACKGROUND Only a subset of patients at risk for ARDS go on to develop it, and the contribution of preexisting comorbidities (eg, diabetes) to ARDS risk is not well understood. Prior studies of the association between diabetes and ARDS have yielded conflicting results. RESEARCH QUESTION Does assessing ARDS risk based on hemoglobin A1c (HbA1c) as a marker of long-term blood glucose levels, rather than a charted diagnosis of diabetes, clarify the relationship between diabetes and ARDS? STUDY DESIGN AND METHODS Using data from two prospective observational cohorts of critically ill adults (Validating Acute Lung Injury Biomarkers for Diagnosis [VALID] and Early Assessment of Renal and Lung Injury [EARLI]), we analyzed the association between clinical HbA1c category and development of ARDS in patients with a risk factor for ARDS and at least one clinical HbA1c measurement within the 180 days prior through 14 days after enrollment. RESULTS A total of 599 patients in VALID and 276 in EARLI met inclusion criteria, of whom 164 and 58 developed ARDS, respectively. Patients with a charted diagnosis of diabetes were not shown to be more likely to develop ARDS (VALID: 24.6% ARDS in those categorized as nondiabetic vs 30.0% in those categorized as diabetic, P = .14; EARLI: 19.6% vs 22.8%, respectively; P = .55). However, in VALID, patients categorized as diabetic with inadequate glycemic control based on their HbA1c had an increased risk of developing ARDS compared with those with nondiabetic HbA1c (20.9% vs 34.0%, respectively; P = .0073), a finding that persisted in multivariable analysis (OR for those categorized as diabetic with inadequate glycemic control vs those categorized as nondiabetic range HbA1c, 1.25; 95% CI, 1.01-1.57). These findings were not reproduced in the smaller EARLI cohort, but were appreciated when the cohorts were combined for analysis. INTERPRETATION Elevated HbA1c may be associated with risk of developing ARDS, independent of clinical diagnosis of diabetes, but prospective validation is needed. If confirmed, these findings suggest that inadequate glycemic control could be an unrecognized risk factor for ARDS.
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Affiliation(s)
- Avery M Bogart
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN
- Vanderbilt University School of Medicine, Nashville, TN
| | - Christine R Lopez
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN
| | - Sarah N Obeidalla
- Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN
| | | | - Andrew Willmore
- Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, Department of Medicine, University of California, San Francisco, CA
| | - Alejandra Jauregui
- Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, Department of Medicine, University of California, San Francisco, CA
| | - Kirsten N Kangelaris
- Division of Hospital Medicine, Department of Medicine, University of California, San Francisco, CA
| | - Carolyn Hendrickson
- Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, Department of Medicine, University of California, San Francisco, CA
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Zuckerberg San Francisco General Hospital, San Francisco, CA
| | - Antonio Gomez
- Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, Department of Medicine, University of California, San Francisco, CA
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Zuckerberg San Francisco General Hospital, San Francisco, CA
| | - Kathleen D Liu
- Department of Medicine, Zuckerberg San Francisco General Hospital, San Francisco, CA
- Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA
- Division of Nephrology, Department of Medicine, University of California San Francisco, San Francisco, CA
| | - Michael A Matthay
- Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, Department of Medicine, University of California, San Francisco, CA
- Department of Anesthesia, University of California San Francisco, San Francisco, CA
| | - Ciara M Shaver
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN
- Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN
| | - Julie A Bastarache
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN
- Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN
| | - Carolyn S Calfee
- Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, Department of Medicine, University of California, San Francisco, CA
- Department of Anesthesia, University of California San Francisco, San Francisco, CA
| | - V Eric Kerchberger
- Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN
| | - Lorraine B Ware
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN
- Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN
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Peng M, Grootaert C, Vercauteren M, Boon N, Janssen C, Rajkovic A, Asselman J. Probing Long-Term Impacts: Low-Dose Polystyrene Nanoplastics Exacerbate Mitochondrial Health and Evoke Secondary Glycolysis via Repeated and Single Dosing. ENVIRONMENTAL SCIENCE & TECHNOLOGY 2024; 58:9967-9979. [PMID: 38814788 DOI: 10.1021/acs.est.3c10868] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/01/2024]
Abstract
Nanoplastics (NPs) are omnipresent in the environment and contribute to human exposure. However, little is known regarding the long-term effects of NPs on human health. In this study, human intestinal Caco-2 cells were exposed to polystyrene nanoplastics (nanoPS) in an environmentally relevant concentration range (102-109 particles/mL) under two realistic exposure scenarios. In the first scenario, cells were repeatedly exposed to nanoPS every 2 days for 12 days to study the long-term effects. In the second scenario, only nanoPS was added once and Caco-2 cells were cultured for 12 days to study the duration of the initial effects of NPs. Under repeated dosing, initial subtle effects on mitochondria induced by low concentrations would accrue over consistent exposure to nanoPS and finally lead to significant impairment of mitochondrial respiration, mitochondrial mass, and cell differentiation process at the end of prolonged exposure, accompanied by significantly increased glycolysis over the whole exposure period. Single dosing of nanoPS elicited transient effects on mitochondrial and glycolytic functions, as well as increased reactive oxygen species (ROS) production in the early phase of exposure, but the self-recovery capacity of cells mitigated these effects at intermediate culture times. Notably, secondary effects on glycolysis and ROS production were observed during the late culture period, while the cell differentiation process and mitochondrial mass were not affected at the end. These long-term effects are of crucial importance for comprehensively evaluating the health hazards arising from lifetime exposure to NPs, complementing the extensively observed acute effects associated with prevalent short-term exposure to high concentrations. Our study underlines the need to study the toxicity of NPs in realistic long-term exposure scenarios such as repeated dosing.
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Affiliation(s)
- Miao Peng
- Laboratory of Environmental Toxicology and Aquatic Ecology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent, Belgium
- Blue Growth Research Lab, Ghent University, Wetenschapspark 1, 8400 Oostende Belgium
| | - Charlotte Grootaert
- Department of Food Technology, Safety and Health, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent, Belgium
| | - Maaike Vercauteren
- Laboratory of Environmental Toxicology and Aquatic Ecology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent, Belgium
- Blue Growth Research Lab, Ghent University, Wetenschapspark 1, 8400 Oostende Belgium
| | - Nico Boon
- Center for Microbial Technology and Ecology (CMET), Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent, Belgium
| | - Colin Janssen
- Laboratory of Environmental Toxicology and Aquatic Ecology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent, Belgium
- Blue Growth Research Lab, Ghent University, Wetenschapspark 1, 8400 Oostende Belgium
| | - Andreja Rajkovic
- Department of Food Technology, Safety and Health, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent, Belgium
| | - Jana Asselman
- Laboratory of Environmental Toxicology and Aquatic Ecology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent, Belgium
- Blue Growth Research Lab, Ghent University, Wetenschapspark 1, 8400 Oostende Belgium
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Conte C, Cipponeri E, Roden M. Diabetes Mellitus, Energy Metabolism, and COVID-19. Endocr Rev 2024; 45:281-308. [PMID: 37934800 PMCID: PMC10911957 DOI: 10.1210/endrev/bnad032] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Revised: 08/30/2023] [Accepted: 11/01/2023] [Indexed: 11/09/2023]
Abstract
Obesity, diabetes mellitus (mostly type 2), and COVID-19 show mutual interactions because they are not only risk factors for both acute and chronic COVID-19 manifestations, but also because COVID-19 alters energy metabolism. Such metabolic alterations can lead to dysglycemia and long-lasting effects. Thus, the COVID-19 pandemic has the potential for a further rise of the diabetes pandemic. This review outlines how preexisting metabolic alterations spanning from excess visceral adipose tissue to hyperglycemia and overt diabetes may exacerbate COVID-19 severity. We also summarize the different effects of SARS-CoV-2 infection on the key organs and tissues orchestrating energy metabolism, including adipose tissue, liver, skeletal muscle, and pancreas. Last, we provide an integrative view of the metabolic derangements that occur during COVID-19. Altogether, this review allows for better understanding of the metabolic derangements occurring when a fire starts from a small flame, and thereby help reducing the impact of the COVID-19 pandemic.
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Affiliation(s)
- Caterina Conte
- Department of Human Sciences and Promotion of the Quality of Life, San Raffaele Roma Open University, Rome 00166, Italy
- Department of Endocrinology, Nutrition and Metabolic Diseases, IRCCS MultiMedica, Milan 20099, Italy
| | - Elisa Cipponeri
- Department of Endocrinology, Nutrition and Metabolic Diseases, IRCCS MultiMedica, Milan 20099, Italy
| | - Michael Roden
- Department of Endocrinology and Diabetology, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Düsseldorf 40225, Germany
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine-University Düsseldorf, Düsseldorf 40225, Germany
- German Center for Diabetes Research, Partner Düsseldorf, Neuherberg 85764, Germany
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Gunst J, Debaveye Y, Güiza F, Dubois J, De Bruyn A, Dauwe D, De Troy E, Casaer MP, De Vlieger G, Haghedooren R, Jacobs B, Meyfroidt G, Ingels C, Muller J, Vlasselaers D, Desmet L, Mebis L, Wouters PJ, Stessel B, Geebelen L, Vandenbrande J, Brands M, Gruyters I, Geerts E, De Pauw I, Vermassen J, Peperstraete H, Hoste E, De Waele JJ, Herck I, Depuydt P, Wilmer A, Hermans G, Benoit DD, Van den Berghe G. Tight Blood-Glucose Control without Early Parenteral Nutrition in the ICU. N Engl J Med 2023; 389:1180-1190. [PMID: 37754283 DOI: 10.1056/nejmoa2304855] [Citation(s) in RCA: 70] [Impact Index Per Article: 35.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/28/2023]
Abstract
BACKGROUND Randomized, controlled trials have shown both benefit and harm from tight blood-glucose control in patients in the intensive care unit (ICU). Variation in the use of early parenteral nutrition and in insulin-induced severe hypoglycemia might explain this inconsistency. METHODS We randomly assigned patients, on ICU admission, to liberal glucose control (insulin initiated only when the blood-glucose level was >215 mg per deciliter [>11.9 mmol per liter]) or to tight glucose control (blood-glucose level targeted with the use of the LOGIC-Insulin algorithm at 80 to 110 mg per deciliter [4.4 to 6.1 mmol per liter]); parenteral nutrition was withheld in both groups for 1 week. Protocol adherence was determined according to glucose metrics. The primary outcome was the length of time that ICU care was needed, calculated on the basis of time to discharge alive from the ICU, with death accounted for as a competing risk; 90-day mortality was the safety outcome. RESULTS Of 9230 patients who underwent randomization, 4622 were assigned to liberal glucose control and 4608 to tight glucose control. The median morning blood-glucose level was 140 mg per deciliter (interquartile range, 122 to 161) with liberal glucose control and 107 mg per deciliter (interquartile range, 98 to 117) with tight glucose control. Severe hypoglycemia occurred in 31 patients (0.7%) in the liberal-control group and 47 patients (1.0%) in the tight-control group. The length of time that ICU care was needed was similar in the two groups (hazard ratio for earlier discharge alive with tight glucose control, 1.00; 95% confidence interval, 0.96 to 1.04; P = 0.94). Mortality at 90 days was also similar (10.1% with liberal glucose control and 10.5% with tight glucose control, P = 0.51). Analyses of eight prespecified secondary outcomes suggested that the incidence of new infections, the duration of respiratory and hemodynamic support, the time to discharge alive from the hospital, and mortality in the ICU and hospital were similar in the two groups, whereas severe acute kidney injury and cholestatic liver dysfunction appeared less prevalent with tight glucose control. CONCLUSIONS In critically ill patients who were not receiving early parenteral nutrition, tight glucose control did not affect the length of time that ICU care was needed or mortality. (Funded by the Research Foundation-Flanders and others; TGC-Fast ClinicalTrials.gov number, NCT03665207.).
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Affiliation(s)
- Jan Gunst
- From the Clinical Department of Intensive Care Medicine (J.G., Y.D., F.G., A.D.B., D.D., E.D.T., M.P.C., G.D.V., R.H., B.J., G.M., C.I., J.M., D.V., L.D., L.M., P.J.W., G.V.B.) and the Medical Intensive Care Unit (A.W., G.H.), University Hospitals of KU Leuven, Leuven, the Department of Anesthesiology and Intensive Care Medicine, Jessa Hospital, Hasselt (J.D., B.S., L.G., J. Vandenbrande, M.B., I.G., E.G., I.D.P.), and the Department of Intensive Care Medicine, Ghent University Hospital, Ghent (J. Vermassen, H.P., E.H., J.J.D.W., I.H., P.D., D.D.B.) - all in Belgium
| | - Yves Debaveye
- From the Clinical Department of Intensive Care Medicine (J.G., Y.D., F.G., A.D.B., D.D., E.D.T., M.P.C., G.D.V., R.H., B.J., G.M., C.I., J.M., D.V., L.D., L.M., P.J.W., G.V.B.) and the Medical Intensive Care Unit (A.W., G.H.), University Hospitals of KU Leuven, Leuven, the Department of Anesthesiology and Intensive Care Medicine, Jessa Hospital, Hasselt (J.D., B.S., L.G., J. Vandenbrande, M.B., I.G., E.G., I.D.P.), and the Department of Intensive Care Medicine, Ghent University Hospital, Ghent (J. Vermassen, H.P., E.H., J.J.D.W., I.H., P.D., D.D.B.) - all in Belgium
| | - Fabian Güiza
- From the Clinical Department of Intensive Care Medicine (J.G., Y.D., F.G., A.D.B., D.D., E.D.T., M.P.C., G.D.V., R.H., B.J., G.M., C.I., J.M., D.V., L.D., L.M., P.J.W., G.V.B.) and the Medical Intensive Care Unit (A.W., G.H.), University Hospitals of KU Leuven, Leuven, the Department of Anesthesiology and Intensive Care Medicine, Jessa Hospital, Hasselt (J.D., B.S., L.G., J. Vandenbrande, M.B., I.G., E.G., I.D.P.), and the Department of Intensive Care Medicine, Ghent University Hospital, Ghent (J. Vermassen, H.P., E.H., J.J.D.W., I.H., P.D., D.D.B.) - all in Belgium
| | - Jasperina Dubois
- From the Clinical Department of Intensive Care Medicine (J.G., Y.D., F.G., A.D.B., D.D., E.D.T., M.P.C., G.D.V., R.H., B.J., G.M., C.I., J.M., D.V., L.D., L.M., P.J.W., G.V.B.) and the Medical Intensive Care Unit (A.W., G.H.), University Hospitals of KU Leuven, Leuven, the Department of Anesthesiology and Intensive Care Medicine, Jessa Hospital, Hasselt (J.D., B.S., L.G., J. Vandenbrande, M.B., I.G., E.G., I.D.P.), and the Department of Intensive Care Medicine, Ghent University Hospital, Ghent (J. Vermassen, H.P., E.H., J.J.D.W., I.H., P.D., D.D.B.) - all in Belgium
| | - Astrid De Bruyn
- From the Clinical Department of Intensive Care Medicine (J.G., Y.D., F.G., A.D.B., D.D., E.D.T., M.P.C., G.D.V., R.H., B.J., G.M., C.I., J.M., D.V., L.D., L.M., P.J.W., G.V.B.) and the Medical Intensive Care Unit (A.W., G.H.), University Hospitals of KU Leuven, Leuven, the Department of Anesthesiology and Intensive Care Medicine, Jessa Hospital, Hasselt (J.D., B.S., L.G., J. Vandenbrande, M.B., I.G., E.G., I.D.P.), and the Department of Intensive Care Medicine, Ghent University Hospital, Ghent (J. Vermassen, H.P., E.H., J.J.D.W., I.H., P.D., D.D.B.) - all in Belgium
| | - Dieter Dauwe
- From the Clinical Department of Intensive Care Medicine (J.G., Y.D., F.G., A.D.B., D.D., E.D.T., M.P.C., G.D.V., R.H., B.J., G.M., C.I., J.M., D.V., L.D., L.M., P.J.W., G.V.B.) and the Medical Intensive Care Unit (A.W., G.H.), University Hospitals of KU Leuven, Leuven, the Department of Anesthesiology and Intensive Care Medicine, Jessa Hospital, Hasselt (J.D., B.S., L.G., J. Vandenbrande, M.B., I.G., E.G., I.D.P.), and the Department of Intensive Care Medicine, Ghent University Hospital, Ghent (J. Vermassen, H.P., E.H., J.J.D.W., I.H., P.D., D.D.B.) - all in Belgium
| | - Erwin De Troy
- From the Clinical Department of Intensive Care Medicine (J.G., Y.D., F.G., A.D.B., D.D., E.D.T., M.P.C., G.D.V., R.H., B.J., G.M., C.I., J.M., D.V., L.D., L.M., P.J.W., G.V.B.) and the Medical Intensive Care Unit (A.W., G.H.), University Hospitals of KU Leuven, Leuven, the Department of Anesthesiology and Intensive Care Medicine, Jessa Hospital, Hasselt (J.D., B.S., L.G., J. Vandenbrande, M.B., I.G., E.G., I.D.P.), and the Department of Intensive Care Medicine, Ghent University Hospital, Ghent (J. Vermassen, H.P., E.H., J.J.D.W., I.H., P.D., D.D.B.) - all in Belgium
| | - Michael P Casaer
- From the Clinical Department of Intensive Care Medicine (J.G., Y.D., F.G., A.D.B., D.D., E.D.T., M.P.C., G.D.V., R.H., B.J., G.M., C.I., J.M., D.V., L.D., L.M., P.J.W., G.V.B.) and the Medical Intensive Care Unit (A.W., G.H.), University Hospitals of KU Leuven, Leuven, the Department of Anesthesiology and Intensive Care Medicine, Jessa Hospital, Hasselt (J.D., B.S., L.G., J. Vandenbrande, M.B., I.G., E.G., I.D.P.), and the Department of Intensive Care Medicine, Ghent University Hospital, Ghent (J. Vermassen, H.P., E.H., J.J.D.W., I.H., P.D., D.D.B.) - all in Belgium
| | - Greet De Vlieger
- From the Clinical Department of Intensive Care Medicine (J.G., Y.D., F.G., A.D.B., D.D., E.D.T., M.P.C., G.D.V., R.H., B.J., G.M., C.I., J.M., D.V., L.D., L.M., P.J.W., G.V.B.) and the Medical Intensive Care Unit (A.W., G.H.), University Hospitals of KU Leuven, Leuven, the Department of Anesthesiology and Intensive Care Medicine, Jessa Hospital, Hasselt (J.D., B.S., L.G., J. Vandenbrande, M.B., I.G., E.G., I.D.P.), and the Department of Intensive Care Medicine, Ghent University Hospital, Ghent (J. Vermassen, H.P., E.H., J.J.D.W., I.H., P.D., D.D.B.) - all in Belgium
| | - Renata Haghedooren
- From the Clinical Department of Intensive Care Medicine (J.G., Y.D., F.G., A.D.B., D.D., E.D.T., M.P.C., G.D.V., R.H., B.J., G.M., C.I., J.M., D.V., L.D., L.M., P.J.W., G.V.B.) and the Medical Intensive Care Unit (A.W., G.H.), University Hospitals of KU Leuven, Leuven, the Department of Anesthesiology and Intensive Care Medicine, Jessa Hospital, Hasselt (J.D., B.S., L.G., J. Vandenbrande, M.B., I.G., E.G., I.D.P.), and the Department of Intensive Care Medicine, Ghent University Hospital, Ghent (J. Vermassen, H.P., E.H., J.J.D.W., I.H., P.D., D.D.B.) - all in Belgium
| | - Bart Jacobs
- From the Clinical Department of Intensive Care Medicine (J.G., Y.D., F.G., A.D.B., D.D., E.D.T., M.P.C., G.D.V., R.H., B.J., G.M., C.I., J.M., D.V., L.D., L.M., P.J.W., G.V.B.) and the Medical Intensive Care Unit (A.W., G.H.), University Hospitals of KU Leuven, Leuven, the Department of Anesthesiology and Intensive Care Medicine, Jessa Hospital, Hasselt (J.D., B.S., L.G., J. Vandenbrande, M.B., I.G., E.G., I.D.P.), and the Department of Intensive Care Medicine, Ghent University Hospital, Ghent (J. Vermassen, H.P., E.H., J.J.D.W., I.H., P.D., D.D.B.) - all in Belgium
| | - Geert Meyfroidt
- From the Clinical Department of Intensive Care Medicine (J.G., Y.D., F.G., A.D.B., D.D., E.D.T., M.P.C., G.D.V., R.H., B.J., G.M., C.I., J.M., D.V., L.D., L.M., P.J.W., G.V.B.) and the Medical Intensive Care Unit (A.W., G.H.), University Hospitals of KU Leuven, Leuven, the Department of Anesthesiology and Intensive Care Medicine, Jessa Hospital, Hasselt (J.D., B.S., L.G., J. Vandenbrande, M.B., I.G., E.G., I.D.P.), and the Department of Intensive Care Medicine, Ghent University Hospital, Ghent (J. Vermassen, H.P., E.H., J.J.D.W., I.H., P.D., D.D.B.) - all in Belgium
| | - Catherine Ingels
- From the Clinical Department of Intensive Care Medicine (J.G., Y.D., F.G., A.D.B., D.D., E.D.T., M.P.C., G.D.V., R.H., B.J., G.M., C.I., J.M., D.V., L.D., L.M., P.J.W., G.V.B.) and the Medical Intensive Care Unit (A.W., G.H.), University Hospitals of KU Leuven, Leuven, the Department of Anesthesiology and Intensive Care Medicine, Jessa Hospital, Hasselt (J.D., B.S., L.G., J. Vandenbrande, M.B., I.G., E.G., I.D.P.), and the Department of Intensive Care Medicine, Ghent University Hospital, Ghent (J. Vermassen, H.P., E.H., J.J.D.W., I.H., P.D., D.D.B.) - all in Belgium
| | - Jan Muller
- From the Clinical Department of Intensive Care Medicine (J.G., Y.D., F.G., A.D.B., D.D., E.D.T., M.P.C., G.D.V., R.H., B.J., G.M., C.I., J.M., D.V., L.D., L.M., P.J.W., G.V.B.) and the Medical Intensive Care Unit (A.W., G.H.), University Hospitals of KU Leuven, Leuven, the Department of Anesthesiology and Intensive Care Medicine, Jessa Hospital, Hasselt (J.D., B.S., L.G., J. Vandenbrande, M.B., I.G., E.G., I.D.P.), and the Department of Intensive Care Medicine, Ghent University Hospital, Ghent (J. Vermassen, H.P., E.H., J.J.D.W., I.H., P.D., D.D.B.) - all in Belgium
| | - Dirk Vlasselaers
- From the Clinical Department of Intensive Care Medicine (J.G., Y.D., F.G., A.D.B., D.D., E.D.T., M.P.C., G.D.V., R.H., B.J., G.M., C.I., J.M., D.V., L.D., L.M., P.J.W., G.V.B.) and the Medical Intensive Care Unit (A.W., G.H.), University Hospitals of KU Leuven, Leuven, the Department of Anesthesiology and Intensive Care Medicine, Jessa Hospital, Hasselt (J.D., B.S., L.G., J. Vandenbrande, M.B., I.G., E.G., I.D.P.), and the Department of Intensive Care Medicine, Ghent University Hospital, Ghent (J. Vermassen, H.P., E.H., J.J.D.W., I.H., P.D., D.D.B.) - all in Belgium
| | - Lars Desmet
- From the Clinical Department of Intensive Care Medicine (J.G., Y.D., F.G., A.D.B., D.D., E.D.T., M.P.C., G.D.V., R.H., B.J., G.M., C.I., J.M., D.V., L.D., L.M., P.J.W., G.V.B.) and the Medical Intensive Care Unit (A.W., G.H.), University Hospitals of KU Leuven, Leuven, the Department of Anesthesiology and Intensive Care Medicine, Jessa Hospital, Hasselt (J.D., B.S., L.G., J. Vandenbrande, M.B., I.G., E.G., I.D.P.), and the Department of Intensive Care Medicine, Ghent University Hospital, Ghent (J. Vermassen, H.P., E.H., J.J.D.W., I.H., P.D., D.D.B.) - all in Belgium
| | - Liese Mebis
- From the Clinical Department of Intensive Care Medicine (J.G., Y.D., F.G., A.D.B., D.D., E.D.T., M.P.C., G.D.V., R.H., B.J., G.M., C.I., J.M., D.V., L.D., L.M., P.J.W., G.V.B.) and the Medical Intensive Care Unit (A.W., G.H.), University Hospitals of KU Leuven, Leuven, the Department of Anesthesiology and Intensive Care Medicine, Jessa Hospital, Hasselt (J.D., B.S., L.G., J. Vandenbrande, M.B., I.G., E.G., I.D.P.), and the Department of Intensive Care Medicine, Ghent University Hospital, Ghent (J. Vermassen, H.P., E.H., J.J.D.W., I.H., P.D., D.D.B.) - all in Belgium
| | - Pieter J Wouters
- From the Clinical Department of Intensive Care Medicine (J.G., Y.D., F.G., A.D.B., D.D., E.D.T., M.P.C., G.D.V., R.H., B.J., G.M., C.I., J.M., D.V., L.D., L.M., P.J.W., G.V.B.) and the Medical Intensive Care Unit (A.W., G.H.), University Hospitals of KU Leuven, Leuven, the Department of Anesthesiology and Intensive Care Medicine, Jessa Hospital, Hasselt (J.D., B.S., L.G., J. Vandenbrande, M.B., I.G., E.G., I.D.P.), and the Department of Intensive Care Medicine, Ghent University Hospital, Ghent (J. Vermassen, H.P., E.H., J.J.D.W., I.H., P.D., D.D.B.) - all in Belgium
| | - Björn Stessel
- From the Clinical Department of Intensive Care Medicine (J.G., Y.D., F.G., A.D.B., D.D., E.D.T., M.P.C., G.D.V., R.H., B.J., G.M., C.I., J.M., D.V., L.D., L.M., P.J.W., G.V.B.) and the Medical Intensive Care Unit (A.W., G.H.), University Hospitals of KU Leuven, Leuven, the Department of Anesthesiology and Intensive Care Medicine, Jessa Hospital, Hasselt (J.D., B.S., L.G., J. Vandenbrande, M.B., I.G., E.G., I.D.P.), and the Department of Intensive Care Medicine, Ghent University Hospital, Ghent (J. Vermassen, H.P., E.H., J.J.D.W., I.H., P.D., D.D.B.) - all in Belgium
| | - Laurien Geebelen
- From the Clinical Department of Intensive Care Medicine (J.G., Y.D., F.G., A.D.B., D.D., E.D.T., M.P.C., G.D.V., R.H., B.J., G.M., C.I., J.M., D.V., L.D., L.M., P.J.W., G.V.B.) and the Medical Intensive Care Unit (A.W., G.H.), University Hospitals of KU Leuven, Leuven, the Department of Anesthesiology and Intensive Care Medicine, Jessa Hospital, Hasselt (J.D., B.S., L.G., J. Vandenbrande, M.B., I.G., E.G., I.D.P.), and the Department of Intensive Care Medicine, Ghent University Hospital, Ghent (J. Vermassen, H.P., E.H., J.J.D.W., I.H., P.D., D.D.B.) - all in Belgium
| | - Jeroen Vandenbrande
- From the Clinical Department of Intensive Care Medicine (J.G., Y.D., F.G., A.D.B., D.D., E.D.T., M.P.C., G.D.V., R.H., B.J., G.M., C.I., J.M., D.V., L.D., L.M., P.J.W., G.V.B.) and the Medical Intensive Care Unit (A.W., G.H.), University Hospitals of KU Leuven, Leuven, the Department of Anesthesiology and Intensive Care Medicine, Jessa Hospital, Hasselt (J.D., B.S., L.G., J. Vandenbrande, M.B., I.G., E.G., I.D.P.), and the Department of Intensive Care Medicine, Ghent University Hospital, Ghent (J. Vermassen, H.P., E.H., J.J.D.W., I.H., P.D., D.D.B.) - all in Belgium
| | - Michiel Brands
- From the Clinical Department of Intensive Care Medicine (J.G., Y.D., F.G., A.D.B., D.D., E.D.T., M.P.C., G.D.V., R.H., B.J., G.M., C.I., J.M., D.V., L.D., L.M., P.J.W., G.V.B.) and the Medical Intensive Care Unit (A.W., G.H.), University Hospitals of KU Leuven, Leuven, the Department of Anesthesiology and Intensive Care Medicine, Jessa Hospital, Hasselt (J.D., B.S., L.G., J. Vandenbrande, M.B., I.G., E.G., I.D.P.), and the Department of Intensive Care Medicine, Ghent University Hospital, Ghent (J. Vermassen, H.P., E.H., J.J.D.W., I.H., P.D., D.D.B.) - all in Belgium
| | - Ine Gruyters
- From the Clinical Department of Intensive Care Medicine (J.G., Y.D., F.G., A.D.B., D.D., E.D.T., M.P.C., G.D.V., R.H., B.J., G.M., C.I., J.M., D.V., L.D., L.M., P.J.W., G.V.B.) and the Medical Intensive Care Unit (A.W., G.H.), University Hospitals of KU Leuven, Leuven, the Department of Anesthesiology and Intensive Care Medicine, Jessa Hospital, Hasselt (J.D., B.S., L.G., J. Vandenbrande, M.B., I.G., E.G., I.D.P.), and the Department of Intensive Care Medicine, Ghent University Hospital, Ghent (J. Vermassen, H.P., E.H., J.J.D.W., I.H., P.D., D.D.B.) - all in Belgium
| | - Ester Geerts
- From the Clinical Department of Intensive Care Medicine (J.G., Y.D., F.G., A.D.B., D.D., E.D.T., M.P.C., G.D.V., R.H., B.J., G.M., C.I., J.M., D.V., L.D., L.M., P.J.W., G.V.B.) and the Medical Intensive Care Unit (A.W., G.H.), University Hospitals of KU Leuven, Leuven, the Department of Anesthesiology and Intensive Care Medicine, Jessa Hospital, Hasselt (J.D., B.S., L.G., J. Vandenbrande, M.B., I.G., E.G., I.D.P.), and the Department of Intensive Care Medicine, Ghent University Hospital, Ghent (J. Vermassen, H.P., E.H., J.J.D.W., I.H., P.D., D.D.B.) - all in Belgium
| | - Ilse De Pauw
- From the Clinical Department of Intensive Care Medicine (J.G., Y.D., F.G., A.D.B., D.D., E.D.T., M.P.C., G.D.V., R.H., B.J., G.M., C.I., J.M., D.V., L.D., L.M., P.J.W., G.V.B.) and the Medical Intensive Care Unit (A.W., G.H.), University Hospitals of KU Leuven, Leuven, the Department of Anesthesiology and Intensive Care Medicine, Jessa Hospital, Hasselt (J.D., B.S., L.G., J. Vandenbrande, M.B., I.G., E.G., I.D.P.), and the Department of Intensive Care Medicine, Ghent University Hospital, Ghent (J. Vermassen, H.P., E.H., J.J.D.W., I.H., P.D., D.D.B.) - all in Belgium
| | - Joris Vermassen
- From the Clinical Department of Intensive Care Medicine (J.G., Y.D., F.G., A.D.B., D.D., E.D.T., M.P.C., G.D.V., R.H., B.J., G.M., C.I., J.M., D.V., L.D., L.M., P.J.W., G.V.B.) and the Medical Intensive Care Unit (A.W., G.H.), University Hospitals of KU Leuven, Leuven, the Department of Anesthesiology and Intensive Care Medicine, Jessa Hospital, Hasselt (J.D., B.S., L.G., J. Vandenbrande, M.B., I.G., E.G., I.D.P.), and the Department of Intensive Care Medicine, Ghent University Hospital, Ghent (J. Vermassen, H.P., E.H., J.J.D.W., I.H., P.D., D.D.B.) - all in Belgium
| | - Harlinde Peperstraete
- From the Clinical Department of Intensive Care Medicine (J.G., Y.D., F.G., A.D.B., D.D., E.D.T., M.P.C., G.D.V., R.H., B.J., G.M., C.I., J.M., D.V., L.D., L.M., P.J.W., G.V.B.) and the Medical Intensive Care Unit (A.W., G.H.), University Hospitals of KU Leuven, Leuven, the Department of Anesthesiology and Intensive Care Medicine, Jessa Hospital, Hasselt (J.D., B.S., L.G., J. Vandenbrande, M.B., I.G., E.G., I.D.P.), and the Department of Intensive Care Medicine, Ghent University Hospital, Ghent (J. Vermassen, H.P., E.H., J.J.D.W., I.H., P.D., D.D.B.) - all in Belgium
| | - Eric Hoste
- From the Clinical Department of Intensive Care Medicine (J.G., Y.D., F.G., A.D.B., D.D., E.D.T., M.P.C., G.D.V., R.H., B.J., G.M., C.I., J.M., D.V., L.D., L.M., P.J.W., G.V.B.) and the Medical Intensive Care Unit (A.W., G.H.), University Hospitals of KU Leuven, Leuven, the Department of Anesthesiology and Intensive Care Medicine, Jessa Hospital, Hasselt (J.D., B.S., L.G., J. Vandenbrande, M.B., I.G., E.G., I.D.P.), and the Department of Intensive Care Medicine, Ghent University Hospital, Ghent (J. Vermassen, H.P., E.H., J.J.D.W., I.H., P.D., D.D.B.) - all in Belgium
| | - Jan J De Waele
- From the Clinical Department of Intensive Care Medicine (J.G., Y.D., F.G., A.D.B., D.D., E.D.T., M.P.C., G.D.V., R.H., B.J., G.M., C.I., J.M., D.V., L.D., L.M., P.J.W., G.V.B.) and the Medical Intensive Care Unit (A.W., G.H.), University Hospitals of KU Leuven, Leuven, the Department of Anesthesiology and Intensive Care Medicine, Jessa Hospital, Hasselt (J.D., B.S., L.G., J. Vandenbrande, M.B., I.G., E.G., I.D.P.), and the Department of Intensive Care Medicine, Ghent University Hospital, Ghent (J. Vermassen, H.P., E.H., J.J.D.W., I.H., P.D., D.D.B.) - all in Belgium
| | - Ingrid Herck
- From the Clinical Department of Intensive Care Medicine (J.G., Y.D., F.G., A.D.B., D.D., E.D.T., M.P.C., G.D.V., R.H., B.J., G.M., C.I., J.M., D.V., L.D., L.M., P.J.W., G.V.B.) and the Medical Intensive Care Unit (A.W., G.H.), University Hospitals of KU Leuven, Leuven, the Department of Anesthesiology and Intensive Care Medicine, Jessa Hospital, Hasselt (J.D., B.S., L.G., J. Vandenbrande, M.B., I.G., E.G., I.D.P.), and the Department of Intensive Care Medicine, Ghent University Hospital, Ghent (J. Vermassen, H.P., E.H., J.J.D.W., I.H., P.D., D.D.B.) - all in Belgium
| | - Pieter Depuydt
- From the Clinical Department of Intensive Care Medicine (J.G., Y.D., F.G., A.D.B., D.D., E.D.T., M.P.C., G.D.V., R.H., B.J., G.M., C.I., J.M., D.V., L.D., L.M., P.J.W., G.V.B.) and the Medical Intensive Care Unit (A.W., G.H.), University Hospitals of KU Leuven, Leuven, the Department of Anesthesiology and Intensive Care Medicine, Jessa Hospital, Hasselt (J.D., B.S., L.G., J. Vandenbrande, M.B., I.G., E.G., I.D.P.), and the Department of Intensive Care Medicine, Ghent University Hospital, Ghent (J. Vermassen, H.P., E.H., J.J.D.W., I.H., P.D., D.D.B.) - all in Belgium
| | - Alexander Wilmer
- From the Clinical Department of Intensive Care Medicine (J.G., Y.D., F.G., A.D.B., D.D., E.D.T., M.P.C., G.D.V., R.H., B.J., G.M., C.I., J.M., D.V., L.D., L.M., P.J.W., G.V.B.) and the Medical Intensive Care Unit (A.W., G.H.), University Hospitals of KU Leuven, Leuven, the Department of Anesthesiology and Intensive Care Medicine, Jessa Hospital, Hasselt (J.D., B.S., L.G., J. Vandenbrande, M.B., I.G., E.G., I.D.P.), and the Department of Intensive Care Medicine, Ghent University Hospital, Ghent (J. Vermassen, H.P., E.H., J.J.D.W., I.H., P.D., D.D.B.) - all in Belgium
| | - Greet Hermans
- From the Clinical Department of Intensive Care Medicine (J.G., Y.D., F.G., A.D.B., D.D., E.D.T., M.P.C., G.D.V., R.H., B.J., G.M., C.I., J.M., D.V., L.D., L.M., P.J.W., G.V.B.) and the Medical Intensive Care Unit (A.W., G.H.), University Hospitals of KU Leuven, Leuven, the Department of Anesthesiology and Intensive Care Medicine, Jessa Hospital, Hasselt (J.D., B.S., L.G., J. Vandenbrande, M.B., I.G., E.G., I.D.P.), and the Department of Intensive Care Medicine, Ghent University Hospital, Ghent (J. Vermassen, H.P., E.H., J.J.D.W., I.H., P.D., D.D.B.) - all in Belgium
| | - Dominique D Benoit
- From the Clinical Department of Intensive Care Medicine (J.G., Y.D., F.G., A.D.B., D.D., E.D.T., M.P.C., G.D.V., R.H., B.J., G.M., C.I., J.M., D.V., L.D., L.M., P.J.W., G.V.B.) and the Medical Intensive Care Unit (A.W., G.H.), University Hospitals of KU Leuven, Leuven, the Department of Anesthesiology and Intensive Care Medicine, Jessa Hospital, Hasselt (J.D., B.S., L.G., J. Vandenbrande, M.B., I.G., E.G., I.D.P.), and the Department of Intensive Care Medicine, Ghent University Hospital, Ghent (J. Vermassen, H.P., E.H., J.J.D.W., I.H., P.D., D.D.B.) - all in Belgium
| | - Greet Van den Berghe
- From the Clinical Department of Intensive Care Medicine (J.G., Y.D., F.G., A.D.B., D.D., E.D.T., M.P.C., G.D.V., R.H., B.J., G.M., C.I., J.M., D.V., L.D., L.M., P.J.W., G.V.B.) and the Medical Intensive Care Unit (A.W., G.H.), University Hospitals of KU Leuven, Leuven, the Department of Anesthesiology and Intensive Care Medicine, Jessa Hospital, Hasselt (J.D., B.S., L.G., J. Vandenbrande, M.B., I.G., E.G., I.D.P.), and the Department of Intensive Care Medicine, Ghent University Hospital, Ghent (J. Vermassen, H.P., E.H., J.J.D.W., I.H., P.D., D.D.B.) - all in Belgium
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10
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Fitzgerald O, Perez-Concha O, Gallego-Luxan B, Rudd L, Jorm L. The relationship between hyperglycaemia on admission and patient outcome is modified by hyperlactatemia and diabetic status: a retrospective analysis of the eICU collaborative research database. Sci Rep 2023; 13:15692. [PMID: 37735615 PMCID: PMC10514185 DOI: 10.1038/s41598-023-43044-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Accepted: 09/18/2023] [Indexed: 09/23/2023] Open
Abstract
Both blood glucose and lactate are well-known predictors of organ dysfunction and mortality in critically ill patients. Previous research has shown that concurrent adjustment for glucose and lactate modifies the relationship between these variables and patient outcomes, including blunting of the association between blood glucose and patient outcome. We aim to investigate the relationship between ICU admission blood glucose and hospital mortality while accounting for lactate and diabetic status. Across 43,250 ICU admissions, weighted to account for missing data, we assessed the predictive ability of several logistic regression and generalised additive models that included blood glucose, blood lactate and diabetic status. We found that inclusion of blood glucose marginally improved predictive performance in all patients: AUC-ROC 0.665 versus 0.659 (p = 0.005), with a greater degree of improvement seen in non-diabetics: AUC-ROC 0.675 versus 0.663 (p < 0.001). Inspection of the estimated risk profiles revealed the standard U-shaped risk profile for blood glucose was only present in non-diabetic patients after controlling for blood lactate levels. Future research should aim to utilise observational data to estimate whether interventions such as insulin further modify this effect, with the goal of informing future RCTs of interventions targeting glycaemic control in the ICU.
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Affiliation(s)
- Oisin Fitzgerald
- Centre for Big Data Research in Health, Level 2, AGSM Building, UNSW Sydney, Kensington, NSW, 2052, Australia.
| | - Oscar Perez-Concha
- Centre for Big Data Research in Health, Level 2, AGSM Building, UNSW Sydney, Kensington, NSW, 2052, Australia
| | - Blanca Gallego-Luxan
- Centre for Big Data Research in Health, Level 2, AGSM Building, UNSW Sydney, Kensington, NSW, 2052, Australia
| | - Lachlan Rudd
- Data and Analytics, eHealth NSW, 1 Reserve Road, St Leonards, NSW, 2065, Australia
| | - Louisa Jorm
- Centre for Big Data Research in Health, Level 2, AGSM Building, UNSW Sydney, Kensington, NSW, 2052, Australia
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11
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Srinivasan V. Glucose Metabolism and Stress Hyperglycemia in Critically Ill Children. Indian J Pediatr 2023; 90:272-279. [PMID: 36645581 DOI: 10.1007/s12098-022-04439-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2022] [Accepted: 11/13/2022] [Indexed: 01/17/2023]
Abstract
Abnormalities in glucose metabolism and stress hyperglycemia (SH) are commonly seen in critically ill children. While SH may represent an adaptive stress response as a source of fuel for the body during the "fight or flight response" of critical illness, several studies have observed the association of SH with worse outcomes in different disease states. In addition to alterations in glucose metabolism and acquired insulin resistance from inflammation and organ dysfunction, specific intensive care unit (ICU) interventions can also affect glucose homeostasis and SH during critical illness. Common ICU interventions can mediate the development of SH in critical illness. The strategy of tight glucose control combined with intensive insulin therapy (TGC-IIT) has been well studied to improve outcomes in both adult and pediatric critical illness. Though early single-center studies of TGC-IIT observed benefits with better outcomes albeit with greater incidence of hypoglycemia, subsequent larger multicenter studies in both children and adults have not conclusively demonstrated benefits and have even observed harm. Several possible reasons for these contrasting results include differences in patient populations, glycemic control targets, and glucose control protocols including nutrition support, and variability in achieving these targets, measurement methods, and expertise in protocol implementation. Future studies may need to individualize management of SH in critically ill children with improved monitoring of indices of glycemia utilizing continuous sensors and closed-loop insulin administration.
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Affiliation(s)
- Vijay Srinivasan
- Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA, 19104, USA. .,Departments of Anesthesiology, Critical Care and Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
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12
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Li B, Li W, Liu T, Zha L. Extracellular vesicles regulate the transmission of insulin resistance and redefine noncommunicable diseases. Front Mol Biosci 2023; 9:1024786. [PMID: 36699697 PMCID: PMC9868246 DOI: 10.3389/fmolb.2022.1024786] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Accepted: 12/19/2022] [Indexed: 01/10/2023] Open
Abstract
Noncommunicable diseases (NCDs), such as diabetes and related neurological disorders, are considered to not be directly transmissible from one person to another. However, NCDs may be transmissible in vivo through extracellular vesicles (EVs). A long-term high-fat diet (HFD) can induce a series of health issues like hyperlipidemia, type 2 diabetes mellitus (T2DM), and diabetic peripheral neuropathy (DPN) due to insulin resistance. Multiple molecular signaling changes can stimulate insulin resistance, especially blocking insulin signaling by increased insulin resistance inducer (phosphorylation of negative regulatory sites of insulin receptor substrate (IRS) proteins) and decreased tyrosine phosphorylation of insulin receptor substrate (phosphorylation of positive regulatory sites of IRS), thus leading to reduced phosphorylation of AKT enzymes. Current efforts to treat T2DM and prevent its complications mainly focus on improving insulin sensitivity, enhancing insulin secretion, or supplementing exogenous insulin based on a common assumption that insulin resistance is noncommunicable. However, insulin resistance is transmissible within multiple tissues or organs throughout the body. Exploring the regulatory roles of EVs in developing insulin resistance may provide novel and effective preventive and therapeutic strategies.
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Affiliation(s)
- Biao Li
- Department of Nutrition and Food Hygiene, Guangdong Provincial Key Laboratory of Tropical Disease Research, National Medical Products Administration Key Laboratory of Cosmetic Safety Evaluation, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China
| | - Wan Li
- School of Physical Education, Hubei Minzu University, Enshi, China
| | - Tiancai Liu
- Key Laboratory of Antibody Engineering of Guangdong Higher Education Institutes, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong, China
| | - Longying Zha
- Department of Nutrition and Food Hygiene, Guangdong Provincial Key Laboratory of Tropical Disease Research, National Medical Products Administration Key Laboratory of Cosmetic Safety Evaluation, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China
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13
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Yang Q, Sun F, Wang X, Luo J, Wang S, Jia C, Pan Y, Zhang J, Zhou Y. Surface charge modulation enhanced high stability of gold oxidation intermediates for electrochemical glucose sensors. ANALYTICAL METHODS : ADVANCING METHODS AND APPLICATIONS 2022; 14:4474-4484. [PMID: 36317565 DOI: 10.1039/d2ay01375d] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
Rapid and accurate blood glucose detection is significant for diagnosing and treating diabetes. Herein, ultra-low-content gold nanoparticles were loaded on different metal foams and applied to electrochemical enzyme-free glucose sensors via simple displacement reactions. The structures and properties of the produced catalysts were determined by various characterization methods. The performance of the glucose sensor was examined in relation to the interactions between three different metal substrates and gold. The one with the best performance is the sample of gold nanoparticles grown on copper foam (Au300 Cu Foam). It has the advantage of a porous three-dimensional network, a large electroactive surface area, and the high catalytic activity of gold. The combination of Cu and Au increased the valence state of Au, thus favoring the catalytic activity for glucose oxidation. Cyclic voltammetry and chronoamperometry measurements revealed that Au is responsible for the electrocatalytic oxidation of glucose. The sensitivity of Au300 Cu Foam was found to be 10 839 μA mM-1 cm-2 in the linear range of 0.00596-0.0566 mM, with a detection limit (LOD) of 0.223 μM, and 2-3 s response time at 0.4 V vs. Ag/AgCl. The Au300 Cu Foam glucose sensor also offered outstanding stability and anti-interference performance. The prepared Au300 Cu Foam electrode was also successfully applied to detect different levels of glucose in human body fluids, such as saliva. These characteristics make Au300 Cu Foam promising for non-invasive glucose detection.
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Affiliation(s)
- Qingyi Yang
- School of Materials Science and Engineering, China University of Petroleum (East China), Qingdao 266580, China.
- School of Chemistry and Chemical Engineering, China University of Petroleum (East China), Qingdao 266580, China.
| | - Fengchao Sun
- School of Materials Science and Engineering, China University of Petroleum (East China), Qingdao 266580, China.
- School of Chemistry and Chemical Engineering, China University of Petroleum (East China), Qingdao 266580, China.
| | - Xingzhao Wang
- School of Materials Science and Engineering, China University of Petroleum (East China), Qingdao 266580, China.
- School of Chemistry and Chemical Engineering, China University of Petroleum (East China), Qingdao 266580, China.
| | - Jiabing Luo
- School of Materials Science and Engineering, China University of Petroleum (East China), Qingdao 266580, China.
| | - Shutao Wang
- School of Chemistry and Chemical Engineering, China University of Petroleum (East China), Qingdao 266580, China.
| | - Cuiping Jia
- College of Science, China University of Petroleum (East China), Qingdao 266580, China
| | - Yuan Pan
- School of Chemistry and Chemical Engineering, China University of Petroleum (East China), Qingdao 266580, China.
| | - Jun Zhang
- School of Materials Science and Engineering, China University of Petroleum (East China), Qingdao 266580, China.
| | - Yan Zhou
- School of Materials Science and Engineering, China University of Petroleum (East China), Qingdao 266580, China.
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14
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Krinsley JS, Rule P, Brownlee M, Roberts G, Preiser JC, Chaudry S, Dionne K, Heluey-Rodrigues C, Umpierrez GE, Hirsch IB. Acute and Chronic Glucose Control in Critically Ill Patients With Diabetes: The Impact of Prior Insulin Treatment. J Diabetes Sci Technol 2022; 16:1483-1495. [PMID: 34396800 PMCID: PMC9631540 DOI: 10.1177/19322968211032277] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND Emerging data highlight the interactions of preadmission glycemia, reflected by admission HbA1c levels, glycemic control during critical illness, and mortality. The association of preadmission insulin treatment with outcomes is unknown. METHODS This observational cohort study includes 5245 patients admitted to the medical-surgical intensive care unit of a university-affiliated teaching hospital. Three groups were analyzed: patients with diabetes with prior insulin treatment (DM-INS, n = 538); patients with diabetes with no prior insulin treatment (DM-No-INS, n = 986); no history of diabetes (NO-DM, n = 3721). Groups were stratified by HbA1c level: <6.5%; 6.5%-7.9% and >8.0%. RESULTS Among the three strata of HbA1c, mean blood glucose (BG), coefficient of variation (CV), and hypoglycemia increased with increasing HbA1c, and were higher for DM-INS than for DM-No-INS. Among patients with HbA1c < 6.5%, mean BG ≥ 180 mg/dL and CV > 30% were associated with lower severity-adjusted mortality in DM-INS compared to patients with mean BG 80-140 mg/dL and CV < 15%, (P = .0058 and < .0001, respectively), but higher severity-adjusted mortality among DM-No-INS (P = .0001 and < .0001, respectively) and NON-DM (P < .0001 and < .0001, respectively). Among patients with HbA1c ≥ 8.0%, mean BG ≥ 180 mg/dL was associated with lower severity-adjusted mortality for both DM-INS and DM-No-INS than was mean BG 80-140 mg/dL (p < 0.0001 for both comparisons). CONCLUSIONS Significant differences in mortality were found among patients with diabetes based on insulin treatment and HbA1c at home and post-admission glycemic control. Prospective studies need to confirm an individualized approach to glycemic control in the critically ill.
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Affiliation(s)
- James S. Krinsley
- Division of Critical Care, Department
of Medicine, Stamford Hospital, and the Columbia Vagelos College of Physicians and
Surgeons, Stamford, CT, USA
- James S Krinsley MD, FCCM, FCCP, Division
of Critical Care, Department of Medicine, Stamford Hospital, and the Columbia
Vagelos College of Physicians and Surgeons, 1 Hospital Plaza, Stamford, CT
06902, USA. Emails: ;
| | | | - Michael Brownlee
- Einstein Diabetes Research Center,
Professor of Medicine and Pathology Emeritus, Albert Einstein College of Medicine,
Bronx, NY, USA
| | | | | | - Sherose Chaudry
- Division of Critical Care, Department
of Medicine, Stamford Hospital, and the Columbia Vagelos College of Physicians and
Surgeons, Stamford, CT, USA
| | - Krista Dionne
- Division of Critical Care, Department
of Medicine, Stamford Hospital, and the Columbia Vagelos College of Physicians and
Surgeons, Stamford, CT, USA
| | - Camilla Heluey-Rodrigues
- Division of Critical Care, Department
of Medicine, Stamford Hospital, and the Columbia Vagelos College of Physicians and
Surgeons, Stamford, CT, USA
| | | | - Irl B. Hirsch
- University of Washington Medicine
Diabetes Institute, Seattle, WA, USA
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15
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Kılınç N. Resorcinol Derivatives as Novel Aldose Reductase Inhibitors: In Silico and
In Vitro Evaluation. LETT DRUG DES DISCOV 2022. [DOI: 10.2174/1570180819666220414103203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Background:
The polyol pathway, an alternative way of carbohydrate metabolism, is activated
by hyperglycemia. Aldose reductase (AR), the first and rate-limiting enzyme of the polyol pathway, is
responsible for the reduction of glucose to sorbitol. Inhibiting the aldose reductase enzyme and reducing
the polyol pathway is considered an effective method to prevent and postpone the onset of diabetic complications.
Objective:
Therefore, in this work, we investigate the inhibition effects of certain resorcinol derivatives
and the positive control compound quercetin on the AR enzyme in vitro and in silico. These phenolic
compounds, whose inhibitory effects on the AR enzyme were investigated, were also compared with
known drugs in terms of their drug-like characteristics.
Methods:
Three methods were used to determine the inhibitory effects of resorcinol derivatives on recombinant
human AR enzyme. After the in vitro inhibition effects were determined spectrophotometrically,
the binding energy and binding modes were determined by molecular docking method. Finally, the
MM-GBSA method was used to determine the free binding energies of the inhibitors for the AR enzyme.
Results:
5-pentylresorcinol compound showed the strongest inhibition effect on recombinant human AR
enzyme with an IC50 value of 9.90 μM. The IC50 values of resorcinol, 5-methylresorcinol, 4-
ethylresorcinol, 4-hexylresorcinol, 2-methylresorcinol, and 2,5-dimethylresorcinol compounds were determined
as 49.50 μM, 43.31 μM, 19.25 μM, 17.32 μM, 28.87 μM, 57.75 μM, respectively.
Conclusion:
The results of this research showed that resorcinol compounds are effective AR inhibitors.
These findings are supported by molecular docking, molecular mechanics, and ADME investigations
undertaken to corroborate the experimental in vitro results.
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Affiliation(s)
- Namık Kılınç
- Department of Medical Services and Techniques, Vocational School of Health Service, Igdir University, Igdir, Turkey
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16
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Expert consensus on the glycemic management of critically ill patients. JOURNAL OF INTENSIVE MEDICINE 2022; 2:131-145. [PMID: 36789019 PMCID: PMC9923981 DOI: 10.1016/j.jointm.2022.06.001] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Revised: 06/02/2022] [Accepted: 06/06/2022] [Indexed: 11/21/2022]
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17
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Rodríguez-González M, Estepa-Pedregosa L, Estalella-Mendoza A, Rodríguez-Campoy P, Romero-Castillo E, Castellano-Martínez A, Flores-González JC. Routine laboratory test to assess the need of respiratory support in acute bronchiolitis. Pediatr Pulmonol 2022; 57:1339-1347. [PMID: 35224889 DOI: 10.1002/ppul.25870] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Revised: 11/23/2021] [Accepted: 02/22/2022] [Indexed: 01/08/2023]
Abstract
BACKGROUND AND OBJECTIVES Accurate and readily available biomarkers to predict the clinical course of bronchiolitis would enable enhanced decision-making in this setting. We explored the relationship of several biochemical parameters available at the pediatric emergency care setting with the need of advanced respiratory support (ARS): continuous positive airway pressure (CPAP), biphasic positive airway pressure (BiPAP), or invasive mechanical ventilation (MV) in bronchiolitis. METHODS Single-center, prospective, observational, including infants aged less than 12 months diagnosed with acute bronchiolitis at the Pediatric Emergency Department. Determination of plasmatic values of several laboratory tests was performed at the time of hospital admission. Multivariate logistic analysis identified independent predictors for need of ARS. RESULTS From October 1, 2018 to May 1, 2020, we recruited 149 infants (58% males; median age of 1 [0.5-2.5] month). Thirty-seven (25%) cases required ARS. After adjusting by age, bacterial superinfection, and comorbidities in the multivariate analysis, only higher levels of glycemia (p = 0.001), C-reactive protein (CRP) (p = 0.028), CRP/albumin ratio (p = 0.032), and NT-proBNP (p = 0.001) remained independently associated with ARS. These biomarkers reached moderate prediction accuracy with area under the curve of receiver operator curve curves ranging from 0.701 to 0.830 (p = 0.001). All they presented relatively high specificity (0.75-0.84) and negative predictive values (0.77-0.89) with low sensitivity and positive predictive values. They also correlated significantly with length of stay hospitalization (p = 0.001). CONCLUSION Increased plasmatic levels of CRP, CRP/albumin ratio, glycemia, and NT-proBNP at hospital admission are associated with the need for ARS in infants with acute bronchiolitis.
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Affiliation(s)
- Moisés Rodríguez-González
- Pediatric Cardiology Unit, Puerta del Mar University Hospital, Cádiz, Spain
- Biomedical Research and Innovation Institute of Cádiz (INiBICA) Research Unit, Puerta del Mar University Hospital, University of Cádiz, Cádiz, Spain
| | - Lorena Estepa-Pedregosa
- Biomedical Research and Innovation Institute of Cádiz (INiBICA) Research Unit, Puerta del Mar University Hospital, University of Cádiz, Cádiz, Spain
- Pediatric Intensive Care Unit, Puerta del Mar University Hospital, Cádiz, Spain
| | - Ana Estalella-Mendoza
- Biomedical Research and Innovation Institute of Cádiz (INiBICA) Research Unit, Puerta del Mar University Hospital, University of Cádiz, Cádiz, Spain
- Pediatric Intensive Care Unit, Puerta del Mar University Hospital, Cádiz, Spain
| | - Patricia Rodríguez-Campoy
- Biomedical Research and Innovation Institute of Cádiz (INiBICA) Research Unit, Puerta del Mar University Hospital, University of Cádiz, Cádiz, Spain
- Pediatric Intensive Care Unit, Puerta del Mar University Hospital, Cádiz, Spain
| | | | - Ana Castellano-Martínez
- Biomedical Research and Innovation Institute of Cádiz (INiBICA) Research Unit, Puerta del Mar University Hospital, University of Cádiz, Cádiz, Spain
- Pediatric Nephrology Division, Puerta del Mar University Hospital, Cádiz, Spain
| | - Jose C Flores-González
- Biomedical Research and Innovation Institute of Cádiz (INiBICA) Research Unit, Puerta del Mar University Hospital, University of Cádiz, Cádiz, Spain
- Pediatric Intensive Care Unit, Puerta del Mar University Hospital, Cádiz, Spain
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18
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Naghipour B, Bagerpour M, Shadvar K, Golzari SE, Faridaalaee G. Effect of hyperglycemia treatment on complications rate after pediatric cardiac surgery. J Cardiovasc Thorac Res 2022; 14:18-22. [PMID: 35620747 PMCID: PMC9106938 DOI: 10.34172/jcvtr.2022.05] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2021] [Accepted: 02/25/2022] [Indexed: 11/09/2022] Open
Abstract
Introduction: The goal of this study was to elucidate harmful complications of intraoperative hyperglycemia following children cardiac surgery and benefits of insulin administration for accurate blood sugar controlling.
Methods: this study is a Randomized clinical trial. We conducted this study in the operating room of shahid madani hospital. Fifty patients who were children under 12 years old undergone cardiac surgery using cardiopulmonary bypass (CPB). Intraoperative insulin infusion was administered intravenously targeting blood sugar levels of 110-140 mg/dL. Blood sugar and arterial blood gas (ABG) were measured every 30 min during operation.
Results: Inotropes were used less in the study than the placebo group during surgery. The means of hospitalization and extubation time were more in the placebo group than the study group(P =0.03) and (P =0.005), respectively. However, the mean time of hospitalization in the ICU ward did not differ significantly between the two groups.
Conclusion: Hyperglycemia has a relation with long time of intubation and hospitalization in ICU. These findings suggest the positive effect of accurate blood sugar control on reducing complication and hospitalization time in children undergoing cardiac surgery.
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Affiliation(s)
- Bahman Naghipour
- Department of Anesthesiology and Intensive Care, Medical Faculty, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mahdieh Bagerpour
- Department of Gynecology and obestetric, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Kamran Shadvar
- Department of Anesthesiology and Intensive Care, Medical Faculty, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Samad E.J. Golzari
- Department of Anesthesiology and Intensive Care, Medical Faculty, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Gholamreza Faridaalaee
- Emergency Medicine Research Team, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Emergency Medicine, Maragheh University of Medical Sciences, Maragheh, Iran
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19
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Abramson TM, Bosson N, Whitfield D, Gausche-Hill M, Niemann JT. Elevated prehospital point-of-care glucose is associated with worse neurologic outcome after out-of-hospital cardiac arrest. Resusc Plus 2022; 9:100204. [PMID: 35141573 PMCID: PMC8814821 DOI: 10.1016/j.resplu.2022.100204] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Revised: 12/16/2021] [Accepted: 01/08/2022] [Indexed: 11/29/2022] Open
Abstract
OBJECTIVES Hyperglycemia is associated with poor outcomes in critically-ill patients. This has implications for prognostication of patients with out-of-hospital cardiac arrest (OHCA) and for post-resuscitation care. We assessed the association of hyperglycemia, on field point-of-care (POC) testing, with survival and neurologic outcome in patients with return of spontaneous circulation (ROSC) after OHCA. METHODS This was a retrospective analysis of data in a regional cardiac care system from April 2011 through December 2017 of adult patients with OHCA and ROSC who had a field POC glucose. Patients were excluded if they were hypoglycemic (glucose <60 mg/dl) or received empiric dextrose. We compared hyperglycemic (glucose >250 mg/dL) with euglycemic (glucose 60-250 mg/dL) patients. Primary outcome was survival to hospital discharge (SHD). Secondary outcome was survival with good neurologic outcome (cerebral performance category 1 or 2 at discharge). We determined the adjusted odds ratios (AORs) for SHD and survival with good neurologic outcome. RESULTS Of 9008 patients with OHCA and ROSC, 6995 patients were included; 1941 (28%) were hyperglycemic and 5054 (72%) were euglycemic. Hyperglycemic patients were more likely to be female, of non-White race, and have an initial non-shockable rhythm compared to euglycemic patients (p < 0.0001 for all). Hyperglycemic patients were less likely to have SHD compared to euglycemic survivors, 24.4% vs 32.9%, risk difference (RD) -8.5% (95 %CI -10.8%, -6.2%), p < 0.0001. Hyperglycemic survivors were also less likely to have good neurologic outcome compared to euglycemic survivors, 57.0% vs 64.6%, RD -7.6% (95 %CI -12.9%, -2.4%), p = 0.004. The AOR for SHD was 0.72 (95 %CI 0.62, 0.85), p < 0.0001 and for good neurologic outcome, 0.70 (95 %CI 0.57, 0.86), p = 0.0005. CONCLUSION In patients with OHCA, hyperglycemia on field POC glucose was associated with lower survival and worse neurologic outcome.
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Affiliation(s)
- Tiffany M. Abramson
- Keck School of Medicine of the University of Southern California, Department of Emergency Medicine, Division of Emergency Medical Services, United States
| | - Nichole Bosson
- Los Angeles County Emergency Medical Services Agency, United States
- Harbor-UCLA Medical Center and the Lundquist Research Institute at Harbor-UCLA, United States
- The David Geffen School of Medicine at UCLA, United States
| | - Denise Whitfield
- Los Angeles County Emergency Medical Services Agency, United States
- Harbor-UCLA Medical Center and the Lundquist Research Institute at Harbor-UCLA, United States
- The David Geffen School of Medicine at UCLA, United States
| | - Marianne Gausche-Hill
- Los Angeles County Emergency Medical Services Agency, United States
- Harbor-UCLA Medical Center and the Lundquist Research Institute at Harbor-UCLA, United States
- The David Geffen School of Medicine at UCLA, United States
| | - James T. Niemann
- Harbor-UCLA Medical Center and the Lundquist Research Institute at Harbor-UCLA, United States
- The David Geffen School of Medicine at UCLA, United States
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20
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Xia Z, Gu T, Zhao Z, Xing Q, Zhang Y, Zhang Z, Zhu B. The stress hyperglycemia ratio, a novel index of relative hyperglycemia, predicts short-term mortality in critically ill patients after esophagectomy. J Gastrointest Oncol 2022; 13:56-66. [PMID: 35284100 PMCID: PMC8899743 DOI: 10.21037/jgo-22-11] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Accepted: 02/16/2022] [Indexed: 03/19/2025] Open
Abstract
BACKGROUND Postoperative mortality and severe complications are associated with both long-term blood glucose management and the severity of stress hyperglycemia. The purpose of this study was to assess the predictive value of a novel index, the stress hyperglycemia ratio (SHR), for short-term mortality in critically ill patients following esophagectomy. METHODS A total of 356 patients who underwent esophagectomy for esophageal squamous cell carcinoma (ESCC) and were admitted to the intensive care unit (ICU) were included in this retrospective study. Based on the SHR values, patients were divided into low (SHR <1.14) or high (SHR ≥1.14) groups in the overall and diabetic populations. The major outcomes of this study were the 30- and 90-day all-cause mortalities. We used Cox proportional hazard regression, Kaplan-Meier survival analysis, and competing risk regression models to analyze the relationships between risk factors and outcomes. RESULTS The 30- and 90-day mortality in the high-SHR group were significantly higher compared to the low-SHR group in the total population (30-day: 1.3% vs. 10.5%, P<0.001; 90-day: 5.8% vs. 20.0%, P<0.001) and the diabetic population (30-day: 2.6% vs. 17.3%, P=0.026; 90-day: 5.1% vs. 36.5%, P<0.001). After adjusting for covariables, the risk of the 30-day mortality [1.770 (1.442, 3.170)] and 90-day mortality [1.869 (1.289, 3.409)] remained significant (P=0.035, P=0.045) in the total population. A similar result was observed in patients with diabetes [30-day: 1.642 (1.131, 2.710), P=0.015; 90-day: 2.136 (1.254, 3.946), P=0.005]. The Kaplan-Meier survival estimates for the 30-/90-day mortality also showed comparable results. The multivariable logistic regression analysis, including all glucose-related indices and the Acute Physiology and Chronic Health Evaluation (APACHE) II score, showed that SHR was independently correlated with the 30- and 90-day mortality; each 0.1-increase was related to a 3-4% elevation in the 30-/90-day mortality [odds ratio (OR), 1.044; 95% confidence interval (CI), 1.036-1.069; OR, 1.036; 95% CI, 1.021-1.051]. CONCLUSIONS In this study, we found that a relative increase in blood glucose, as quantified by the SHR ≥1.14, was independently related to the higher 30-/90-day mortality in patients admitted to the ICU with severe complications following esophagectomy, while absolute hyperglycemia was not.
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Affiliation(s)
- Zhili Xia
- Department of Critical Care, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Ting Gu
- Department of Critical Care, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Zhiyong Zhao
- Department of Critical Care, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Qian Xing
- Department of Critical Care, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Yaodong Zhang
- Department of Critical Care, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Zhongwei Zhang
- Department of Critical Care, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Biao Zhu
- Department of Critical Care, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
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21
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Vargas-Rodriguez JR, Garza-Veloz I, Flores-Morales V, Badillo-Almaraz JI, Rocha-Pizaña MR, Valdés-Aguayo JJ, Martinez-Fierro ML. Hyperglycemia and Angiotensin-Converting Enzyme 2 in Pulmonary Function in the Context of SARS-CoV-2 Infection. Front Med (Lausanne) 2022; 8:758414. [PMID: 35096863 PMCID: PMC8792738 DOI: 10.3389/fmed.2021.758414] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2021] [Accepted: 12/20/2021] [Indexed: 01/18/2023] Open
Abstract
Since the appearance of the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003 in China, diabetes mellitus (DM) and hyperglycemia in patients infected with SARS-CoV, represent independent predictors of mortality. Therefore, metabolic control has played a major role in the prognosis of these patients. In the current pandemic of coronavirus disease 19 (COVID-19), multiple studies have shown that DM is one of the main comorbidities associated with COVID-19 and higher risk of complications and death. The incidence and prevalence of COVID-19 complications and death related with hyperglycemia in patients with or without DM are high. There are many hypotheses related with worse prognosis and death related to COVID-19 and/or hyperglycemia. However, the information about the interplay between hyperglycemia and angiotensin-converting enzyme 2 (ACE2), the critical receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in the context of SARS-CoV-2 infection, is almost null, but there is enough information to consider the possible participation of hyperglycemia in the glycation of this protein, unleashing a pool of reactions leading to acute respiratory distress syndrome and death in patients with COVID-19. In this document we investigated the current evidence related with ACE2 as a key element within the pathophysiological mechanism related with hyperglycemia extrapolating it to context of SARS-CoV-2 infection and its relationship with worse prognosis and death for COVID-19.
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Affiliation(s)
- Jose R Vargas-Rodriguez
- Molecular Medicine Laboratory, Unidad Academica de Medicina Humana y C.S., Campus UAZ Siglo XXI, Universidad Autonoma de Zacatecas, Zacatecas, Mexico
| | - Idalia Garza-Veloz
- Molecular Medicine Laboratory, Unidad Academica de Medicina Humana y C.S., Campus UAZ Siglo XXI, Universidad Autonoma de Zacatecas, Zacatecas, Mexico
| | - Virginia Flores-Morales
- Laboratorio de Sintesis Asimetrica y Bioenergetica, Ingenieria Quimica, Unidad Academica de Ciencias Quimicas, Campus UAZ Siglo XXI, Universidad Autonoma de Zacatecas, Zacatecas, Mexico
| | - Jose I Badillo-Almaraz
- Molecular Medicine Laboratory, Unidad Academica de Medicina Humana y C.S., Campus UAZ Siglo XXI, Universidad Autonoma de Zacatecas, Zacatecas, Mexico
| | - Maria R Rocha-Pizaña
- Escuela de Ingenieria y Ciencias, Tecnologico de Monterrey Campus Puebla, Puebla, Mexico
| | - José J Valdés-Aguayo
- Molecular Medicine Laboratory, Unidad Academica de Medicina Humana y C.S., Campus UAZ Siglo XXI, Universidad Autonoma de Zacatecas, Zacatecas, Mexico
| | - Margarita L Martinez-Fierro
- Molecular Medicine Laboratory, Unidad Academica de Medicina Humana y C.S., Campus UAZ Siglo XXI, Universidad Autonoma de Zacatecas, Zacatecas, Mexico
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22
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Holgersen K, Rasmussen MB, Carey G, Burrin DG, Thymann T, Sangild PT. Clinical outcome and gut development after insulin-like growth factor-1 supplementation to preterm pigs. Front Pediatr 2022; 10:868911. [PMID: 35989990 PMCID: PMC9389362 DOI: 10.3389/fped.2022.868911] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Accepted: 07/08/2022] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND Elevation of circulating insulin-like growth factor-1 (IGF-1) within normal physiological levels may alleviate several morbidities in preterm infants but safety and efficacy remain unclear. We hypothesized that IGF-1 supplementation during the first 1-2 weeks after preterm birth improves clinical outcomes and gut development, using preterm pigs as a model for infants. METHODS Preterm pigs were given vehicle or recombinant human IGF-1/binding protein-3 (rhIGF-1, 2.25 mg/kg/d) by subcutaneous injections for 8 days (Experiment 1, n = 34), or by systemic infusion for 4 days (Experiment 2, n = 19), before collection of blood and organs for analyses. RESULTS In both experiments, rhIGF-1 treatment increased plasma IGF-1 levels 3-4 fold, reaching the values reported for term suckling piglets. In Experiment 1, rhIGF-1 treatment increased spleen and intestinal weights without affecting clinical outcomes like growth, blood biochemistry (except increased sodium and gamma-glutamyltransferase levels), hematology (e.g., red and white blood cell populations), glucose homeostasis (e.g., basal and glucose-stimulated insulin and glucose levels) or systemic immunity variables (e.g., T cell subsets, neutrophil phagocytosis, LPS stimulation, bacterial translocation to bone marrow). The rhIGF-1 treatment increased gut protein synthesis (+11%, p < 0.05) and reduced the combined incidence of all-cause mortality and severe necrotizing enterocolitis (NEC, p < 0.05), but had limited effects on intestinal morphology, cell proliferation, cell apoptosis, brush-border enzyme activities, permeability and levels of cytokines (IL-1β, IL-6, IL-8). In Experiment 2, rhIGF-1 treated pigs had reduced blood creatine kinase, creatinine, potassium and aspartate aminotransferase levels, with no effects on organ weights (except increased spleen weight), blood chemistry values, clinical variables or NEC. CONCLUSION Physiological elevation of systemic IGF-1 levels for 8 days after preterm birth increased intestinal weight and protein synthesis, spleen weight and potential overall viability of pigs, without any apparent negative effects on recorded clinical parameters. The results add further preclinical support for safety and efficacy of supplemental IGF-1 to hospitalized very preterm infants.
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Affiliation(s)
- Kristine Holgersen
- Comparative Pediatrics and Nutrition, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark
| | - Martin Bo Rasmussen
- Comparative Pediatrics and Nutrition, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark
| | | | - Douglas G Burrin
- Department of Pediatrics, United States Department of Agriculture/Agricultural Research Service, Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX, United States
| | - Thomas Thymann
- Comparative Pediatrics and Nutrition, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark
| | - Per Torp Sangild
- Comparative Pediatrics and Nutrition, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.,Department of Neonatology, Rigshospitalet, Copenhagen, Denmark.,Department of Pediatrics, Odense University Hospital, Odense, Denmark
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23
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Difficulties in managing hyperglycemia in extremely low birth weight infants – case report. GINECOLOGIA.RO 2022. [DOI: 10.26416/gine.38.4.2022.7392] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
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Mandani S, Rezaei B, Asghar Ensafi A. Developing a highly-sensitive aptasensor based on surface energy transfer between InP/ZnS quantum dots and Ag-nanoplates for the determination of insulin. J Photochem Photobiol A Chem 2022. [DOI: 10.1016/j.jphotochem.2021.113601] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
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25
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Santana MF, Frank CHM, Almeida TVR, Jeronimo CMP, de Araújo Pinto RA, Martins YF, de Farias MEL, Dutra BG, Brito-Sousa JD, Baía-da-Silva DC, Xavier MS, Lacerda MVG, Almeida Val FF, Monteiro GC, Sampaio VDS, Monteiro WM, Ferreira LCDL. Hemorrhagic and thrombotic manifestations in the central nervous system in COVID-19: A large observational study in the Brazilian Amazon with a complete autopsy series. PLoS One 2021; 16:e0255950. [PMID: 34506501 PMCID: PMC8432786 DOI: 10.1371/journal.pone.0255950] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2021] [Accepted: 07/27/2021] [Indexed: 12/25/2022] Open
Abstract
SARS-CoV-2 affects mainly the lungs, however, other manifestations, including neurological manifestations, have also been described during the disease. Some of the neurological findings have involved intracerebral or subarachnoid hemorrhage, strokes, and other thrombotic/hemorrhagic conditions. Nevertheless, the gross pathology of hemorrhagic lesions in the central nervous system has not been previously described in Brazilian autopsy cases. This study aimed to describe gross and microscopic central nervous system (CNS) pathology findings from the autopsies and correlate them with the clinical and laboratory characteristics of forty-five patients with COVID-19 from Manaus, Amazonas, Brazil. Forty-four patients were autopsied of which thirty-eight of these (86.36%) were positive by RT-PCR for COVID-19, and six (13.3%) were positive by the serological rapid test. Clinical and radiological findings were compatible with the infection. The patients were classified in two groups: presence (those who had hemorrhagic and/or thrombotic manifestations in the CNS) and absence (those who did not present hemorrhagic and/or thrombotic manifestations in the CNS). For risk assessment, relative risk and respective confidence intervals were estimated. Macroscopic or microscopic hemorrhages were found in twenty-three cases (52,27%). The postmortem gross examination of the brain revealed a broad spectrum of hemorrhages, from spots to large and confluent areas and, under microscopy, we observed mainly perivascular discharge. The association analyses showed that the use of corticosteroid, anticoagulant and antibiotic had no statistical significance with a risk of nervous system hemorrhagic manifestations. However, it is possible to infer a statistical tendency that indicates that individuals with diabetes had a higher risk for the same outcome (RR = 1.320, 95% CI = 0.7375 to 2.416, p = 0.3743), which was not observed in relation to other comorbidities. It is unknown whether the new variants of the virus can cause different clinical manifestations, such as those observed or indeed others. As a result, more studies are necessary to define clinical and radiologic monitoring protocols and strategic interventions for patients at risk of adverse and fatal events, such as the extensive hemorrhaging described here. It is imperative that clinicians must be aware of comorbidities and the drugs used to treat patients with COVID-19 to prevent CNS hemorrhagic and thrombotic events.
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Affiliation(s)
- Monique Freire Santana
- Departamento de Ensino e Pesquisa, Fundação Centro de Controle de Oncologia do Estado do Amazonas–FCECON, Manaus, AM, Brazil
- Universidade do Estado do Amazonas, Programa de Pós-Graduação em Medicina Tropical, Manaus, AM, Brazil
- Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, Manaus, AM, Brazil
| | | | - Taynná Vernalha Rocha Almeida
- Programa de Pós-graduação em Ciências da Saúde, Faculdade de Medicina, Universidade Federal do Amazonas, Manaus, AM, Brazil
| | | | - Rebecca Augusta de Araújo Pinto
- Departamento de Patologia e Medicina Legal, Hospital Universitário Getúlio Vargas, Universidade Federal do Amazonas, Manaus, AM, Brazil
| | - Yasmin Ferreira Martins
- Programa de Pós-graduação em Ciências da Saúde, Faculdade de Medicina, Universidade Federal do Amazonas, Manaus, AM, Brazil
| | | | | | | | | | - Mariana Simão Xavier
- Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, Manaus, AM, Brazil
- Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
| | - Marcus Vinicius Guimarães Lacerda
- Universidade do Estado do Amazonas, Programa de Pós-Graduação em Medicina Tropical, Manaus, AM, Brazil
- Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, Manaus, AM, Brazil
- Instituto de Pesquisas Leônidas & Maria Deane, Fundação Oswaldo Cruz, Manaus, AM, Brazil
| | - Fernando Fonseca Almeida Val
- Universidade do Estado do Amazonas, Programa de Pós-Graduação em Medicina Tropical, Manaus, AM, Brazil
- Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, Manaus, AM, Brazil
- Programa de Pós-graduação em Ciências da Saúde, Faculdade de Medicina, Universidade Federal do Amazonas, Manaus, AM, Brazil
| | - Gisely Cardoso Monteiro
- Universidade do Estado do Amazonas, Programa de Pós-Graduação em Medicina Tropical, Manaus, AM, Brazil
- Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, Manaus, AM, Brazil
| | - Vanderson de Souza Sampaio
- Universidade do Estado do Amazonas, Programa de Pós-Graduação em Medicina Tropical, Manaus, AM, Brazil
- Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, Manaus, AM, Brazil
- Fundação de Vigilância em Saúde do Amazonas, Manaus, AM, Brazil
| | - Wuelton Marcelo Monteiro
- Universidade do Estado do Amazonas, Programa de Pós-Graduação em Medicina Tropical, Manaus, AM, Brazil
- Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, Manaus, AM, Brazil
| | - Luiz Carlos de Lima Ferreira
- Universidade do Estado do Amazonas, Programa de Pós-Graduação em Medicina Tropical, Manaus, AM, Brazil
- Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, Manaus, AM, Brazil
- Programa de Pós-graduação em Ciências da Saúde, Faculdade de Medicina, Universidade Federal do Amazonas, Manaus, AM, Brazil
- Departamento de Patologia e Medicina Legal, Hospital Universitário Getúlio Vargas, Universidade Federal do Amazonas, Manaus, AM, Brazil
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Abstract
Background and Objectives Obesity is the accumulation of adipose tissue caused by excess energy in the body, accompanied by long-term chronic low-grade inflammation of adipose tissue. More than 50% of interstitial cells in adipose tissue are macrophages, which produce cytokines closely related to insulin resistance. Macrophage biology is driven by two polarization phenotypes, M1 (proinflammatory) and M2 (anti-inflammatory). This study aimed to investigate the effect of gastric hormone des-acyl ghrelin (DAG) on the polarization phenotype of macrophages and elucidate the role of macrophages in adipose tissue inflammation and insulin sensitivity and its molecular mechanism. Methods Mice were subcutaneously administrated with DAG in osmotic minipumps. The mice were fed a normal diet or a high-fat diet (HFD). Different macrophage markers were detected by real-time revere transcription polymerase chain reaction. Results Exogenous administration of DAG significantly inhibited the increase of adipocyte volume caused by HFD and reduced the number of rosette-like structures in adipose tissue. HFD in the control group significantly increased M1 macrophage markers, tumor necrosis factor α (TNFα), and inducible NO synthase (iNOS). However, these increases were reduced or even reversed after DAG administration in vitro. The M2 markers, macrophage galactose type C-type Lectin-1 (MGL1), arginase 1 (Arg1), and macrophage mannose receptor 1 (MRC1) were decreased by HFD, and the downward trend was inhibited or reversed after DAG administration. Although Arg1 was elevated after HFD, the fold increase after DAG administration in vitro was much greater than that in the control group. Conclusion DAG inhibits adipose tissue inflammation caused by HFD, reduces infiltration of macrophages in adipose tissue, and promotes polarization of macrophages to M2, thus alleviating obesity and improving insulin sensitivity.
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Soluble Epoxide Hydrolase Blockade after Stroke Onset Protects Normal but Not Diabetic Mice. Int J Mol Sci 2021; 22:ijms22115419. [PMID: 34063817 PMCID: PMC8196561 DOI: 10.3390/ijms22115419] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Revised: 05/11/2021] [Accepted: 05/20/2021] [Indexed: 01/04/2023] Open
Abstract
Soluble epoxide hydrolase (sEH) is abundant in the brain, is upregulated in type 2 diabetes mellitus (DM2), and is possible mediator of ischemic injury via the breakdown of neuroprotective epoxyeicosatrienoic acids (EETs). Prophylactic, pre-ischemic sEH blockade with 4-[[trans-4-[[(tricyclo[3.3.1.13,7]dec-1-ylamino)carbonyl]amino]cyclohexyl]oxy]-benzoic acid (tAUCB) reduces stroke-induced infarct in normal and diabetic mice, with larger neuroprotection in DM2. The present study tested whether benefit occurs in normal and DM2 mice if tAUCB is administered after stroke onset. We performed 60 min middle cerebral artery occlusion in young adult male C57BL mice divided into four groups: normal or DM2, with t-AUCB 2 mg/kg or vehicle 30 min before reperfusion. Endpoints were (1) cerebral blood flow (CBF) by laser Doppler, and (2) brain infarct at 24 h. In nondiabetic mice, t-AUCB reduced infarct size by 30% compared to vehicle-treated mice in the cortex (31.4 ± 4 vs. 43.8 ± 3 (SEM)%, respectively) and 26% in the whole hemisphere (26.3 ± 3 vs. 35.2 ± 2%, both p < 0.05). In contrast, in DM2 mice, tAUCB failed to ameliorate either cortical or hemispheric injury. No differences were seen in CBF. We conclude that tAUCB administered after ischemic stroke onset exerts brain protection in nondiabetic but not DM2 mice, that the neuroprotection appears independent of changes in gross CBF, and that DM2-induced hyperglycemia abolishes t-AUCB-mediated neuroprotection after stroke onset.
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Loss of FOXO transcription factors in the liver mitigates stress-induced hyperglycemia. Mol Metab 2021; 51:101246. [PMID: 33964506 PMCID: PMC8175408 DOI: 10.1016/j.molmet.2021.101246] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Revised: 04/21/2021] [Accepted: 04/29/2021] [Indexed: 12/16/2022] Open
Abstract
Objective Stress-induced hyperglycemia is associated with poor outcomes in nearly all critical illnesses. This acute elevation in glucose after injury or illness is associated with increased morbidity and mortality, including multiple organ failure. Stress-induced hyperglycemia is often attributed to insulin resistance as controlling glucose levels via exogenous insulin improves outcomes, but the mechanisms are unclear. Forkhead box O (FOXO) transcription factors are direct targets of insulin signaling in the liver that regulate glucose homeostasis via direct and indirect pathways. Loss of hepatic FOXO transcription factors reduces hyperglycemia in chronic insulin resistance; however, the role of FOXOs in stress-induced hyperglycemia is unknown. Methods We subjected mice lacking FOXO transcription factors in the liver to a model of injury known to cause stress-induced hyperglycemia. Glucose, insulin, glycerol, fatty acids, cytokines, and adipokines were assessed before and after injury. Liver and adipose tissue were analyzed for changes in glycogen, FOXO target gene expression, and insulin signaling. Results Stress-induced hyperglycemia was associated with reduced hepatic insulin signaling and increased hepatic FOXO target gene expression while loss of FOXO1, 3, and 4 in the liver attenuated hyperglycemia and prevented hyperinsulinemia. Mechanistically, the loss of FOXO transcription factors mitigated the stress-induced hyperglycemia response by directly altering gene expression and glycogenolysis in the liver and indirectly suppressing lipolysis in adipose tissue. Reductions were associated with decreased IL-6, TNF-α, and follistatin and increased FGF21, suggesting that cytokines and FOXO-regulated hepatokines contribute to the stress-induced hyperglycemia response. Conclusions This study implicates FOXO transcription factors as a predominant driver of stress-induced hyperglycemia through means that include cross-talk between the liver and adipose, highlighting a novel mechanism underlying acute hyperglycemia and insulin resistance in stress.
Liver forkhead box O (FOXO) target gene expression is increased in critical illness. Loss of FOXO1, 3, and 4 in the liver mitigates stress-induced hyperglycemia (SIH). Hepatic FOXO drives SIH via direct and indirect means in the liver and adipose.
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Cheung K, Rathbone A, Melanson M, Trier J, Ritsma BR, Allen MD. Pathophysiology and management of critical illness polyneuropathy and myopathy. J Appl Physiol (1985) 2021; 130:1479-1489. [PMID: 33734888 PMCID: PMC8143786 DOI: 10.1152/japplphysiol.00019.2021] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2021] [Revised: 03/10/2021] [Accepted: 03/12/2021] [Indexed: 12/19/2022] Open
Abstract
Critical illness-associated weakness (CIAW) is an umbrella term used to describe a group of neuromuscular disorders caused by severe illness. It can be subdivided into three major classifications based on the component of the neuromuscular system (i.e. peripheral nerves or skeletal muscle or both) that are affected. This includes critical illness polyneuropathy (CIP), critical illness myopathy (CIM), and an overlap syndrome, critical illness polyneuromyopathy (CIPNM). It is a common complication observed in people with critical illness requiring intensive care unit (ICU) admission. Given CIAW is found in individuals experiencing grave illness, it can be challenging to study from a practical standpoint. However, over the past 2 decades, many insights into the pathophysiology of this condition have been made. Results from studies in both humans and animal models have found that a profound systemic inflammatory response and factors related to bioenergetic failure as well as microvascular, metabolic, and electrophysiological alterations underlie the development of CIAW. Current management strategies focus on early mobilization, achieving euglycemia, and nutritional optimization. Other interventions lack sufficient evidence, mainly due to a dearth of large trials. The goal of this Physiology in Medicine article is to highlight important aspects of the pathophysiology of these enigmatic conditions. It is hoped that improved understanding of the mechanisms underlying these disorders will lead to further study and new investigations for novel pharmacologic, nutritional, and exercise-based interventions to optimize patient outcomes.
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Affiliation(s)
- Kevin Cheung
- School of Medicine, Faculty of Health Sciences, Queen's University, Kingston, Ontario, Canada
| | - Alasdair Rathbone
- Department of Physical Medicine and Rehabilitation, Queen's University, Kingston, Ontario, Canada
| | - Michel Melanson
- Division of Neurology, Department of Medicine, Queen's University, Kingston, Ontario, Canada
| | - Jessica Trier
- Department of Physical Medicine and Rehabilitation, Queen's University, Kingston, Ontario, Canada
| | - Benjamin R Ritsma
- Department of Physical Medicine and Rehabilitation, Queen's University, Kingston, Ontario, Canada
| | - Matti D Allen
- Department of Physical Medicine and Rehabilitation, Queen's University, Kingston, Ontario, Canada
- School of Kinesiology, Faculty of Arts and Sciences, Queen's University, Kingston, Ontario, Canada
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Liu R, Zuo R, Hudalla GA. Harnessing molecular recognition for localized drug delivery. Adv Drug Deliv Rev 2021; 170:238-260. [PMID: 33484737 PMCID: PMC8274479 DOI: 10.1016/j.addr.2021.01.008] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Revised: 01/06/2021] [Accepted: 01/08/2021] [Indexed: 12/18/2022]
Abstract
A grand challenge in drug delivery is providing the right dose, at the right anatomic location, for the right duration of time to maximize therapeutic efficacy while minimizing off-target toxicity and other deleterious side-effects. Two general modalities are receiving broad attention for localized drug delivery. In the first, referred to as "targeted accumulation", drugs or drug carriers are engineered to have targeting moieties that promote their accumulation at a specific tissue site from circulation. In the second, referred to as "local anchoring", drugs or drug carriers are inserted directly into the tissue site of interest where they persist for a specified duration of time. This review surveys recent advances in harnessing molecular recognition between proteins, peptides, nucleic acids, lipids, and carbohydrates to mediate targeted accumulation and local anchoring of drugs and drug carriers.
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Affiliation(s)
- Renjie Liu
- J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL 32611, USA
| | - Ran Zuo
- J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL 32611, USA
| | - Gregory A Hudalla
- J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL 32611, USA.
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31
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Beardsall K. Hyperglycaemia in the Newborn Infant. Physiology Verses Pathology. Front Pediatr 2021; 9:641306. [PMID: 34368024 PMCID: PMC8333866 DOI: 10.3389/fped.2021.641306] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Accepted: 06/18/2021] [Indexed: 12/25/2022] Open
Abstract
Hyperglycemia is common in newborns requiring intensive care, particularly in preterm infants, in sepsis and following perinatal hypoxia. The clinical significance, and optimal intervention strategy varies with context, but hyperglycaemia is associated with increased mortality and morbidity. The limited evidence for optimal clinical targets mean controversy remains regarding thresholds for intervention, and management strategies. The first consideration in the management of hyperglycaemia must be to ascertain potentially treatable causes. Calculation of the glucose infusion rate (GIR) to insure this is not excessive, is critical but the use of insulin is often helpful in the extremely preterm infant, but is associated with an increased risk of hypoglycaemia. The use of continuous glucose monitoring (CGM) has recently been demonstrated to be helpful in targeting glucose control, and reducing the risk from hypoglycaemia in the preterm infant. Its use in other at risk infants remains to be explored, and further studies are needed to provide a better understanding of the optimal glucose targets for different clinical conditions. In the future the combination of CGM and advances in computer algorithms, to provide intelligent closed loop systems, could allow a safer and more personalized approached to management.
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Affiliation(s)
- Kathryn Beardsall
- Department of Paediatrics, University of Cambridge, Cambridge University Hospitals National Health Service Foundation Trust, Cambridge, United Kingdom.,Neonatal Unit, Cambridge University Hospitals National Health Service Foundation Trust, Cambridge, United Kingdom
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32
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Lu PP, Chen MH, Dai GC, Li YJ, Shi L, Rui YF. Understanding cellular and molecular mechanisms of pathogenesis of diabetic tendinopathy. World J Stem Cells 2020; 12:1255-1275. [PMID: 33312397 PMCID: PMC7705468 DOI: 10.4252/wjsc.v12.i11.1255] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2020] [Revised: 08/19/2020] [Accepted: 09/10/2020] [Indexed: 02/06/2023] Open
Abstract
There is accumulating evidence of an increased incidence of tendon disorders in people with diabetes mellitus. Diabetic tendinopathy is an important cause of chronic pain, restricted activity, and even tendon rupture in individuals. Tenocytes and tendon stem/progenitor cells (TSPCs) are the dominant cellular components associated with tendon homeostasis, maintenance, remodeling, and repair. Some previous studies have shown alterations in tenocytes and TSPCs in high glucose or diabetic conditions that might cause structural and functional variations in diabetic tendons and even accelerate the development and progression of diabetic tendinopathy. In this review, the biomechanical properties and histopathological changes in diabetic tendons are described. Then, the cellular and molecular alterations in both tenocytes and TSPCs are summarized, and the underlying mechanisms involved are also analyzed. A better understanding of the underlying cellular and molecular pathogenesis of diabetic tendinopathy would provide new insight for the exploration and development of effective therapeutics.
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Affiliation(s)
- Pan-Pan Lu
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
- Orthopaedic Trauma Institute (OTI), Southeast University, Nanjing 210009, Jiangsu Province, China
- Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
- School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
| | - Min-Hao Chen
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
- Orthopaedic Trauma Institute (OTI), Southeast University, Nanjing 210009, Jiangsu Province, China
- Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
- School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
| | - Guang-Chun Dai
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
- Orthopaedic Trauma Institute (OTI), Southeast University, Nanjing 210009, Jiangsu Province, China
- Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
- School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
| | - Ying-Juan Li
- School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
- Department of Geriatrics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
- China Orthopedic Regenerative Medicine Group, Hangzhou 310000, Zhejiang Province, China
| | - Liu Shi
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
- Orthopaedic Trauma Institute (OTI), Southeast University, Nanjing 210009, Jiangsu Province, China
- Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
- China Orthopedic Regenerative Medicine Group, Hangzhou 310000, Zhejiang Province, China
| | - Yun-Feng Rui
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
- Orthopaedic Trauma Institute (OTI), Southeast University, Nanjing 210009, Jiangsu Province, China
- Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
- School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
- China Orthopedic Regenerative Medicine Group, Hangzhou 310000, Zhejiang Province, China.
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Yang P, Wang N, Wang J, Luo A, Gao F, Tu Y. Admission fasting plasma glucose is an independent risk factor for 28-day mortality in patients with COVID-19. J Med Virol 2020; 93:2168-2176. [PMID: 33073361 DOI: 10.1002/jmv.26608] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2020] [Revised: 09/26/2020] [Accepted: 10/14/2020] [Indexed: 01/08/2023]
Abstract
Hyperglycemia commonly occurs in severe cases with COVID-19. In this study, we explored the associations between admission fasting plasma glucose (FPG) and 28-day mortality in COVID-19 patients. In this single centre retrospective study, 263 adult patients with COVID-19 were included. Demographic and clinical information were collected and compared between patients with and without diabetes. Cox regression analyses were used to investigate the risk factors of 28-day mortality in hospitals. Of 263 patients, 161 (61.2%) were male, 62 (25.6%) had a known history of diabetes, and 135 (51.3%) experienced elevated FPG (>7.0 mmol/L) at hospital admission. The median FPG in patients with diabetes was much higher than in patients without diabetes (12.79 vs. 6.47 mmol/L). Patients with diabetes had higher neutrophil count and D-dimer, less lymphocyte count, lower albumin level, and more fatal complications. Multivariable Cox regression analyses showed that age (per 10-year increase) (hazard ratio [HR], 1.41; 95% confidence interval [CI], 1.13-1.74), admission FPG between 7.0 and 11.0 and ≥11.1 mmol/L (HR, 1.90; 95% CI, 1.11-3.25 and HR, 2.09; 95% CI, 1.21-3.64, respectively), chronic obstructive pulmonary disease (HR, 2.89; 95% CI, 1.31-6.39), and cardiac injury (HR, 2.14; 95% CI, 1.33-3.47) were independent predictors of 28-day mortality in COVID-19 patients. Hyperglycemia on admission predicted worse outcome in hospitalized patients with COVID-19. Intensive monitoring and optimal glycemic control may improve the prognosis of COVID-19 patients.
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Affiliation(s)
- Ping Yang
- Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Nan Wang
- Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jingjing Wang
- Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ailin Luo
- Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Feng Gao
- Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ye Tu
- Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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34
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Bondy SC, Wu M, Prasad KN. Alternatives to Insulin for the Regulation of Blood Sugar Levels in Type 2 Diabetes. Int J Mol Sci 2020; 21:E8302. [PMID: 33167495 PMCID: PMC7663956 DOI: 10.3390/ijms21218302] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Revised: 10/29/2020] [Accepted: 10/31/2020] [Indexed: 12/29/2022] Open
Abstract
This short overview focuses on the causation and treatment of type 2 diabetes (T2D). Emphasis is given to the historical basis of understanding this disease and the background leading to emergence of the central role of insulin. The strengths of insulin administration in the treatment of diabetes are profound, but these need to be balanced against several serious shortcomings of its extended use. Some alternative approaches to T2D management are considered. Insulin is no longer considered as the first choice for type 2 diabetes, and an expanding range of new therapeutic possibilities is emerging. While these may lack the potency of insulin, at a minimum, they allow a major reduction in the intensity of insulin use. In view of the rising worldwide incidence of this disease, it is imperative to develop safe and inexpensive means of limiting its potential for impairment of normal functioning.
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Affiliation(s)
- Stephen C. Bondy
- Center for Occupational and Environmental Health, Department of Medicine, University of California, Irvine, CA 92697, USA
| | - Meixia Wu
- Evergreen World Healthcare Center, Garden Grove, CA 92844, USA;
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35
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Liu H, Bian W, Yang D, Yang M, Luo H. Inhibiting the Piezo1 channel protects microglia from acute hyperglycaemia damage through the JNK1 and mTOR signalling pathways. Life Sci 2020; 264:118667. [PMID: 33127514 DOI: 10.1016/j.lfs.2020.118667] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2020] [Revised: 10/21/2020] [Accepted: 10/23/2020] [Indexed: 01/20/2023]
Abstract
AIM Diabetes is a high-risk factor for neurocognitive dysfunction. Diabetic acute hyperglycaemia accompanied by high osmotic pressure can induce immune cell dysfunction, but its mechanism of action in brain microglia remains unclear. This study aimed to evaluate the role of the mechanically sensitive ion channel Piezo1 in the dysfunction of microglia in acute hyperglycaemia. MATERIALS AND METHODS To construct an in vitro acute hyperglycaemia model using the BV2 microglial cell line, Piezo1 in microglia was inhibited by GsMTx4 and siRNA, and the changes in microglial function were further evaluated. KEY FINDINGS High concentrations of glucose upregulated the expression of Piezo1, led to weakened cell proliferation and migration, and reduced the immune response to inflammatory stimulating factors (Aβ and LPS). Additionally, LPS upregulated Piezo1 in BV2 microglial cultures in vitro. The activation of Piezo1 channels increased the intracellular Ca2+ concentration and reduced the phosphorylation of JNK1 and mTOR. Inhibiting Piezo1 did not affect cell viability at average glucose concentrations but improved acute HCG-induced cell damage and increased the phosphorylation of JNK1 and mTOR, suggesting that the latter modification may be a potential downstream mechanism of Piezo1. SIGNIFICANCE Piezo1 is necessary for microglial damage in acute hyperglycaemia and may become a promising target to treat hyperglycaemic brain injury.
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Affiliation(s)
- Hailin Liu
- Department of Anesthesiology, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330008, China; Jiangxi Key Laboratory of Cancer Metastasis and Precision Treatment, The Third Affiliated Hospital of Nanchang University, Nanchang, China; Graduate School of School of Medicine, Nanchang University, China
| | - Wengong Bian
- Department of Anesthesiology, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330008, China; Jiangxi Key Laboratory of Cancer Metastasis and Precision Treatment, The Third Affiliated Hospital of Nanchang University, Nanchang, China; Graduate School of School of Medicine, Nanchang University, China
| | - Dongxia Yang
- Department of Anesthesiology, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330008, China; Jiangxi Key Laboratory of Cancer Metastasis and Precision Treatment, The Third Affiliated Hospital of Nanchang University, Nanchang, China; Graduate School of School of Medicine, Nanchang University, China
| | - Mingmin Yang
- Department of Anesthesiology, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330008, China
| | - Heguo Luo
- Department of Anesthesiology, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330008, China.
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36
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Ranney DN, Williams JB, Albrecht ÁS, Li S, Kalil RAK, Peterson ED, Lopes RD. Insulin Use and Clinical Outcomes in Patients Undergoing Coronary Artery Bypass Graft Surgery. Braz J Cardiovasc Surg 2020; 35:666-674. [PMID: 33118731 PMCID: PMC7598983 DOI: 10.21470/1678-9741-2019-0347] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
Objective To describe insulin use and postoperative glucose control in patients undergoing coronary artery bypass graft (CABG) surgery. Methods We examined 2,390 patients with and without diabetes enrolled in the Contemporary Analysis of Perioperative Cardiovascular Surgical Care (CAPS-Care) Study who underwent CABG surgery (01/2004 - 06/2005) to describe postoperative insulin use, variation in insulin use across different hospitals, and associated in-hospital complications and clinical outcomes. Logistic regression was used to assess the adjusted relationship between insulin use and clinical outcomes. Results Overall, insulin was used in 82% (n=1,959) of patients, including 95% (n=1,203) with diabetes (n=1,258) and 67% (n=756) without diabetes (n=1,132). Continuous insulin was used in 35.5% of patients in the operating room and in 56% in the intensive care unit. Continuous insulin use varied significantly among centers from 8-100% in patients with diabetes. When compared with all patients not receiving insulin, insulin use in patients without diabetes was associated with a higher rate of death or major complication (adjusted odds ratio [OR]=1.54; 95% confidence interval [CI] 1.15-2.04; P=0.003). In patients with diabetes, insulin use was not associated with a higher risk of adverse outcomes (adjusted OR=1.01; 95% CI 0.52-1.98; P=0.98). Conclusion The postoperative use of insulin is high among CABG patients in the United States of America. Insulin use in patients without diabetes was associated with worse clinical outcomes compared to patients (both with and without diabetes) who did not receive insulin. Further investigation is needed to determine the optimal use of postoperative insulin after CABG.
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Affiliation(s)
- David N Ranney
- Duke Clinical Research Institute Durham North Carolina United States of America Duke Clinical Research Institute, Durham, North Carolina, United States of America.,Duke University School of Medicine North Carolina United States of America Duke University School of Medicine, North Carolina, United States of America
| | - Judson B Williams
- Duke Clinical Research Institute Durham North Carolina United States of America Duke Clinical Research Institute, Durham, North Carolina, United States of America.,Duke University School of Medicine North Carolina United States of America Duke University School of Medicine, North Carolina, United States of America
| | - Álvaro S Albrecht
- Fundação Universitária de Cardiologia Instituto de Cardiologia do Rio Grande do Sul Porto Alegre Rio Grande do Sul Brazil Instituto de Cardiologia do Rio Grande do Sul/Fundação Universitária de Cardiologia, Santana, Porto Alegre, Rio Grande do Sul, Brazil
| | - Shuang Li
- Duke Clinical Research Institute Durham North Carolina United States of America Duke Clinical Research Institute, Durham, North Carolina, United States of America
| | - Renato A K Kalil
- Fundação Universitária de Cardiologia Instituto de Cardiologia do Rio Grande do Sul Porto Alegre Rio Grande do Sul Brazil Instituto de Cardiologia do Rio Grande do Sul/Fundação Universitária de Cardiologia, Santana, Porto Alegre, Rio Grande do Sul, Brazil.,Universidade Federal de Ciências da Saúde de Porto Alegre Department of Cardiology Porto Alegre Rio Grande do Sul Brazil Department of Cardiology, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil
| | - Eric D Peterson
- Duke Clinical Research Institute Durham North Carolina United States of America Duke Clinical Research Institute, Durham, North Carolina, United States of America.,Duke University School of Medicine North Carolina United States of America Duke University School of Medicine, North Carolina, United States of America
| | - Renato D Lopes
- Duke Clinical Research Institute Durham North Carolina United States of America Duke Clinical Research Institute, Durham, North Carolina, United States of America.,Duke University School of Medicine North Carolina United States of America Duke University School of Medicine, North Carolina, United States of America.,Universidade Federal de São Paulo São Paulo São Paulo Brazil Universidade Federal de São Paulo, São Paulo, São Paulo, Brazil
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37
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Erdogmus S, Ates D, Nemli S, Yagmur B, Asciogul TK, Ozkuru E, Karaca N, Yilmaz H, Esiyok D, Tanyolac MB. Genome-wide association studies of Ca and Mn in the seeds of the common bean (Phaseolus vulgaris L.). Genomics 2020; 112:4536-4546. [PMID: 32763354 DOI: 10.1016/j.ygeno.2020.03.030] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2019] [Revised: 03/09/2020] [Accepted: 03/14/2020] [Indexed: 12/16/2022]
Abstract
SNP markers linked to genes controlling Ca and Mn uptake were identified in the common bean seeds using DArT-based association mapping (AM). The Ca concentration in the seeds varied between 475 and 3,100 mg kg-1 with an average of 1,280.9 mg kg-1 and the Mn concentration ranged from 4.87 to 27.54 mg kg-1 with a mean of 11.76 mg kg-1. A total of 19,204 SNP markers were distributed across 11 chromosomes that correspond to the haploid genome number of the common bean. The highest value of ΔK was determined as K = 2, and 173 common bean genotypes were split into two main subclusters as POP1 (Mesoamerican) and POP2 (Andean). The results of the UPGMA dendrogram and PCA confirmed those of STRUCTURE analysis. MLM based on the Q + K model identified a large number of markers-trait associations. Of the 19,204 SNPs, five (on Pv2, 3, 8, 10 and 11) and four (on Pv2, 3, 8 and 11) SNPs were detected to be significantly related to the Ca content of the beans grown in Bornova and Menemen, respectively in 2015. In 2016, six SNPs (on Pv1-4, 8 and 10) were identified to be significantly associated with the Ca content of the seeds obtained from Bornova and six SNPs (on Pv1-4, 8 and 10) from Menemen. Eight (on Pv3, 5 and 11) and four (on Pv2, 5 and 11) SNPs had a significant association with Mn content in Bornova in 2015 and 2016, respectively. In Menemen, eight (on Pv3, 5, 8 and 11) and 11 (on Pv1, 2, 5, 10 and 11) SNPs had a significant correlation with Mn content in 2015 and 2016, respectively.
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Affiliation(s)
- Semih Erdogmus
- Ege University, Department of Bioengineering, Bornova-Izmir 35100, Turkey
| | - Duygu Ates
- Ege University, Department of Bioengineering, Bornova-Izmir 35100, Turkey
| | - Seda Nemli
- Ege University, Faculty of Fisheries, Bornova-Izmir 35100, Turkey
| | - Bulent Yagmur
- Ege University, Department of Soil Science and Plant Nutrition, Bornova-Izmir 35100, Turkey
| | | | - Esin Ozkuru
- Ege University, Department of Bioengineering, Bornova-Izmir 35100, Turkey
| | - Nur Karaca
- Ege University, Department of Bioengineering, Bornova-Izmir 35100, Turkey
| | - Hasan Yilmaz
- Ege University, Department of Bioengineering, Bornova-Izmir 35100, Turkey
| | - Dursun Esiyok
- Ege University, Department of Horticulture, Bornova-Izmir, 35040, Turkey
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Koliaki C, Tentolouris A, Eleftheriadou I, Melidonis A, Dimitriadis G, Tentolouris N. Clinical Management of Diabetes Mellitus in the Era of COVID-19: Practical Issues, Peculiarities and Concerns. J Clin Med 2020; 9:2288. [PMID: 32708504 PMCID: PMC7408673 DOI: 10.3390/jcm9072288] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2020] [Revised: 07/11/2020] [Accepted: 07/15/2020] [Indexed: 02/07/2023] Open
Abstract
The management of patients with diabetes mellitus (DM) in the era of the COVID-19 pandemic can be challenging. Even if they are not infected, they are at risk of dysregulated glycemic control due to the restrictive measures which compromise and disrupt healthcare delivery. In the case of infection, people with DM have an increased risk of developing severe complications. The major principles of optimal care for mild outpatient cases include a patient-tailored therapeutic approach, regular glucose monitoring and adherence to medical recommendations regarding lifestyle measures and drug treatment. For critically ill hospitalized patients, tight monitoring of glucose, fluids, electrolytes, pH and blood ketones is of paramount importance to optimize outcomes. All patients with DM do not have an equally increased risk for severity and mortality due to COVID-19. Certain clinical and biological characteristics determine high-risk phenotypes within the DM population and such prognostic markers need to be characterized in future studies. Further research is needed to examine which subgroups of DM patients are expected to benefit the most from specific antiviral, immunomodulatory and other treatment strategies in the context of patient-tailored precision medicine, which emerges as an urgent priority in the era of COVID-19.
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Affiliation(s)
- Chrysi Koliaki
- First Department of Propaedeutic Internal Medicine and Diabetes Center, Medical School, National Kapodistrian University of Athens, Laiko General Hospital, 11527 Athens, Greece; (C.K.); (A.T.); (I.E.)
| | - Anastasios Tentolouris
- First Department of Propaedeutic Internal Medicine and Diabetes Center, Medical School, National Kapodistrian University of Athens, Laiko General Hospital, 11527 Athens, Greece; (C.K.); (A.T.); (I.E.)
| | - Ioanna Eleftheriadou
- First Department of Propaedeutic Internal Medicine and Diabetes Center, Medical School, National Kapodistrian University of Athens, Laiko General Hospital, 11527 Athens, Greece; (C.K.); (A.T.); (I.E.)
| | - Andreas Melidonis
- Hellenic Diabetes Association, 11528 Athens, Greece; (A.M.); (G.D.)
- Cardiometabolic Department, Metropolitan Hospital, 18547 Neo Faliro, Greece
| | - George Dimitriadis
- Hellenic Diabetes Association, 11528 Athens, Greece; (A.M.); (G.D.)
- Second Department of Internal Medicine and Research Institute, Medical School, National and Kapodistrian University of Athens, Attikon University General Hospital, 12462 Chaidari, Greece
| | - Nikolaos Tentolouris
- First Department of Propaedeutic Internal Medicine and Diabetes Center, Medical School, National Kapodistrian University of Athens, Laiko General Hospital, 11527 Athens, Greece; (C.K.); (A.T.); (I.E.)
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Pappada SM, Owais MH, Cameron BD, Jaume JC, Mavarez-Martinez A, Tripathi RS, Papadimos TJ. An Artificial Neural Network-based Predictive Model to Support Optimization of Inpatient Glycemic Control. Diabetes Technol Ther 2020; 22:383-394. [PMID: 31687844 DOI: 10.1089/dia.2019.0252] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
Background: Achieving glycemic control in critical care patients is of paramount importance, and has been linked to reductions in mortality, intensive care unit (ICU) length of stay, and morbidities such as infection. The myriad of illnesses and patient conditions render maintenance of glycemic control very challenging in this setting. Materials and Methods: This study involved collection of continuous glucose monitoring (CGM) data, and other associated measures, from the electronic medical records of 127 patients for the first 72 h of ICU care who upon admission to the ICU had a diagnosis of type 1 (n = 8) or type 2 diabetes (n = 97) or a glucose value >150 mg/dL (n = 22). A neural network-based model was developed to predict a complete trajectory of glucose values up to 135 min ahead of time. Model accuracy was validated using data from 15 of the 127 patients who were not included in the model training set to simulate model performance in real-world health care settings. Results: Predictive models achieved an improved accuracy and performance compared with previous models that were reported by our research team. Model error, expressed as mean absolute difference percent, was 10.6% with respect to interstitial glucose values (CGM) and 15.9% with respect to serum blood glucose values collected 135 min in the future. A Clarke Error Grid Analysis of model predictions with respect to the reference CGM and blood glucose measurements revealed that >99% of model predictions could be regarded as clinically acceptable and would not lead to inaccurate insulin therapy or treatment recommendations. Conclusion: The noted clinical acceptability of these models illustrates their potential utility within a clinical decision support system to assist health care providers in the optimization of glycemic management in critical care patients.
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Affiliation(s)
- Scott M Pappada
- Department of Anesthesiology, University of Toledo, College of Medicine and Life Sciences, Toledo, Ohio
- Department of Bioengineering, University of Toledo, College of Engineering, Toledo, Ohio
- Department of Anesthesiology, The Ohio State University, College of Medicine, Columbus, Ohio
| | - Mohammad Hamza Owais
- Department of Electrical Engineering and Computer Science, University of Toledo, College of Engineering, Toledo, Ohio
| | - Brent D Cameron
- Department of Bioengineering, University of Toledo, College of Engineering, Toledo, Ohio
| | - Juan C Jaume
- Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Toledo, College of Medicine and Life Sciences, Toledo, Ohio
| | - Ana Mavarez-Martinez
- Department of Anesthesiology, The Ohio State University, College of Medicine, Columbus, Ohio
| | - Ravi S Tripathi
- Department of Anesthesiology, The Ohio State University, College of Medicine, Columbus, Ohio
| | - Thomas J Papadimos
- Department of Anesthesiology, University of Toledo, College of Medicine and Life Sciences, Toledo, Ohio
- Department of Anesthesiology, The Ohio State University, College of Medicine, Columbus, Ohio
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Gentile S, Strollo F, Ceriello A. COVID-19 infection in Italian people with diabetes: Lessons learned for our future (an experience to be used). Diabetes Res Clin Pract 2020; 162:108137. [PMID: 32259611 PMCID: PMC7270733 DOI: 10.1016/j.diabres.2020.108137] [Citation(s) in RCA: 62] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Affiliation(s)
| | - Felice Strollo
- Elle-Di and San Raffaele Research Institute, Rome, Italy.
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Gus EI, Shahrokhi S, Jeschke MG. Anabolic and anticatabolic agents used in burn care: What is known and what is yet to be learned. Burns 2019; 46:19-32. [PMID: 31852612 DOI: 10.1016/j.burns.2018.03.009] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2017] [Revised: 01/17/2018] [Accepted: 03/18/2018] [Indexed: 12/15/2022]
Abstract
Major thermal injury induces profound metabolic derangements secondary to an inflammatory "stress-induced" hormonal environment. Several pharmacological interventions have been tested in an effort to halt the hypermetabolic response to severe burns. Insulin, insulin growth factor 1, insulin growth factor binding protein 3, metformin, human growth hormone, thyroid hormones, testosterone, oxandrolone, and propranolol, among others, have been proposed to have anabolic or anticatabolic effects. The aim of this broad analysis of pharmacological interventions was to raise awareness of treatment options and to help establishing directions for future clinical research efforts. A PubMed search was conducted on the anabolic and anticatabolic agents used in burn care. One hundred and thirty-five human studies published between 1999 and 2017 were included in this review. The pharmacological properties, rationale for the treatments, efficacy considerations and side effect profiles are summarized in the article. Many of the drugs tested for investigational purposes in the severely thermally injured are not yet gold-standard therapies in spite of their potential benefit. Propranolol and oxandrolone have shown great promise but further evidence is still needed to clarify their potential use for anabolic and anticatabolic purposes.
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Affiliation(s)
- Eduardo I Gus
- Ross Tilley Burn Centre, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Avenue, D704, Toronto, ON M4N 3M5, Canada
| | - Shahriar Shahrokhi
- Ross Tilley Burn Centre, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Avenue, D704, Toronto, ON M4N 3M5, Canada; Division of Plastic Surgery, Department of Surgery, University of Toronto, Toronto, ON, Canada
| | - Marc G Jeschke
- Ross Tilley Burn Centre, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Avenue, D704, Toronto, ON M4N 3M5, Canada; Division of Plastic Surgery, Department of Surgery, University of Toronto, Toronto, ON, Canada; Department of Immunology, University of Toronto, Toronto, ON, Canada; Sunnybrook Research Institute, Toronto, ON, Canada.
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van Niekerk G, Christowitz C, Conradie D, Engelbrecht AM. Insulin as an immunomodulatory hormone. Cytokine Growth Factor Rev 2019; 52:34-44. [PMID: 31831339 DOI: 10.1016/j.cytogfr.2019.11.006] [Citation(s) in RCA: 55] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2019] [Revised: 11/26/2019] [Accepted: 11/28/2019] [Indexed: 12/11/2022]
Abstract
Insulin plays an indispensable role in the management of hyperglycaemia that arises in a variety of settings, including Type I and II diabetes, gestational diabetes, as well as is in hyperglycaemia following a severe inflammatory insult. However, insulin receptors are also expressed on a range of cells that are not canonically implicated in glucose homeostasis. This includes immune cells, where the anti-inflammatory effects of insulin have been repeatedly reported. However, recent findings have also implicated a more involved role for insulin in shaping the immune response during an infection. This includes the ability of insulin to modulate immune cell differentiation and polarisation as well as the modulation of effector functions such as biocidal ROS production. Finally, inflammatory mediators can through both direct and indirect mechanisms also regulate serum insulin levels, suggesting that insulin may be co-opted by the immune system during an infection to direct immunological operations. Collectively, these observations implicate insulin as a bona fide immune-modulating hormone and suggest that a better understanding of insulin's immunological function may aid in optimising insulin therapy in a range of clinical settings.
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Affiliation(s)
- Gustav van Niekerk
- Department of Physiological Sciences, Stellenbosch University, Stellenbosch, South Africa.
| | - Claudia Christowitz
- Department of Physiological Sciences, Stellenbosch University, Stellenbosch, South Africa
| | - Daleen Conradie
- Department of Physiological Sciences, Stellenbosch University, Stellenbosch, South Africa
| | - Anna-Mart Engelbrecht
- Department of Physiological Sciences, Stellenbosch University, Stellenbosch, South Africa
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43
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Chaves MHM, Wolf ARDS, Nascimento KAL, Nawcki D, Feustel GM, Bettega PVC, Ignacio SA, Brancher JA, Tannous LA, Werneck RI, Souza PHC, de Barros MMT, Johann ACBR. Sialochemical analysis in polytraumatized patients in intensive care units. PLoS One 2019; 14:e0222974. [PMID: 31581248 PMCID: PMC6776458 DOI: 10.1371/journal.pone.0222974] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2019] [Accepted: 09/11/2019] [Indexed: 02/07/2023] Open
Abstract
The profiles of polytraumatized patients in intensive care units were characterized. Serum and salivary markers were compared with normality between Classes I and II of APACHE II and between periods of hospitalization; these results were correlated. This was a prospective study on saliva charts and collection (n = 70). Profile: male, 27 years old, blunt traumas and collisions. Serum parameters with normality: decrease in pH, creatinine at admission to Class I, and at 48 and 72 hours in both classes; K+ at 48 h in Class II; Ca+ on admission in both classes and at 72 h in Class I. Increase in urea at 72 h in Class II, glucose at all times and in all classes, and Ca+ at 48 h in both classes. Class II had high Na+ at 48 and 72 h compared to Class I. In Class I, creatinine reduction occurred in 48 h and 72 h compared to admission and an increase of Ca+ at 48 h with admission. In Class II, pH and Na+ increased at 48 h and 72 h compared to admission. K+ decreased from admission to 48 h and increased from 48 h to 72 h. Urea increased from 48 to 72 hours. Creatinine decreased from admission to 48 and 72 hours. Ca+ increased from admission to 48 hours and decreased from 48 to 72 hours. There was an increase in the saliva levels in both classes and times in relation to normality. There was an increase in urea at admission, glucose at 72 h, and Ca+ at 48 h in Class II compared with Class I. Class I urea increased from admission to 48 h and Ca+ decreased from admission to 48 h. Class II urea decreased from 48 h to 72 h. Strong or very strong positive correlation was identified between blood and creatinine saliva at all times and regular and negative Ca+ at 72 h. This study provides evidence that salivary and serum biomarkers can be used together to monitor the evolution of the clinical symptoms of ICU patients.
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Affiliation(s)
- Maria Heloisa Madruga Chaves
- School of Life Sciences, Department of Nursing, Pontifícia Universidade Católica do Paraná, Curitiba, Paraná, Brazil
| | | | - Kelly Aline Lima Nascimento
- School of Life Sciences, Department of Nursing, Pontifícia Universidade Católica do Paraná, Curitiba, Paraná, Brazil
| | - Danielle Nawcki
- School of Life Sciences, Department of Nursing, Pontifícia Universidade Católica do Paraná, Curitiba, Paraná, Brazil
| | - Gabriele Muller Feustel
- School of Life Sciences, Department of Nursing, Pontifícia Universidade Católica do Paraná, Curitiba, Paraná, Brazil
| | - Patricia Vida Cassi Bettega
- School of Life Sciences, Department of Dentistry, Pontifícia Universidade Católica do Paraná, Curitiba, Paraná, Brazil
| | - Sergio Aparecido Ignacio
- School of Life Sciences, Department of Dentistry, Pontifícia Universidade Católica do Paraná, Curitiba, Paraná, Brazil
| | - João Armando Brancher
- School of Life Sciences, Department of Dentistry, Pontifícia Universidade Católica do Paraná, Curitiba, Paraná, Brazil
| | - Luana Alves Tannous
- School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba, Paraná, Brazil
| | - Renata Iani Werneck
- School of Life Sciences, Department of Dentistry, Pontifícia Universidade Católica do Paraná, Curitiba, Paraná, Brazil
| | - Paulo Henrique Couto Souza
- School of Life Sciences, Department of Dentistry, Pontifícia Universidade Católica do Paraná, Curitiba, Paraná, Brazil
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Abstract
PURPOSE OF REVIEW Insulin has been the standard of care for the management of inpatient diabetes for achieving strict glycemic control. This review supports continuing insulin therapy for hyperglycemic management in the hospital compared with the use of non-insulin treatment regimens. RECENT FINDINGS Oral hypoglycemic agents and glucagon-like peptide 1 (GLP-1) receptor agonists have typically not been used in the inpatient setting. Recent studies regarding DPP-4 inhibitors have led to variable results with fairly high glycemic values during the hospitalization. Similarly, studies looking at GLP-1 receptor agonists are limited, but gastrointestinal side effects limit their inpatient use. Overall, there is a paucity of data to support the use of non-insulin-based therapy in the inpatient setting. Insulin has repeatedly demonstrated that its advantageous quality of being easily titratable leads to more consistently efficacious glycemic control that improves morbidity and mortality.
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Affiliation(s)
- Smita Kumar
- Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, 645 N. Michigan Ave., Suite 530, Chicago, IL, 60611, USA
| | - Mark E Molitch
- Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, 645 N. Michigan Ave., Suite 530, Chicago, IL, 60611, USA.
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Pinchefsky EF, Hahn CD, Kamino D, Chau V, Brant R, Moore AM, Tam EWY. Hyperglycemia and Glucose Variability Are Associated with Worse Brain Function and Seizures in Neonatal Encephalopathy: A Prospective Cohort Study. J Pediatr 2019; 209:23-32. [PMID: 30982528 DOI: 10.1016/j.jpeds.2019.02.027] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2018] [Revised: 01/17/2019] [Accepted: 02/15/2019] [Indexed: 02/07/2023]
Abstract
OBJECTIVES To investigate how glucose abnormalities correlate with brain function on amplitude-integrated electroencephalography (aEEG) in infants with neonatal encephalopathy. STUDY DESIGN Neonates born at full term with encephalopathy were enrolled within 6 hours of birth in a prospective cohort study at a pediatric academic referral hospital. Continuous interstitial glucose monitors and aEEG were placed soon after birth and continued for 3 days. Episodes of hypoglycemia (≤50 mg/dL; ≤2.8 mmol/L) and hyperglycemia (>144 mg/dL; >8.0 mmol/L) were identified. aEEG was classified in 6-hour epochs for 3 domains (background, sleep-wake cycling, electrographic seizures). Generalized estimating equations assessed the relationship of hypo- or hyperglycemia with aEEG findings, adjusting for clinical markers of hypoxia-ischemia (Apgar scores, umbilical artery pH, and base deficit). RESULTS Forty-five infants (gestational age 39.5 ± 1.4 weeks) were included (24 males). During aEEG monitoring, 16 episodes of hypoglycemia were detected (9 infants, median duration 77.5, maximum 220 minutes) and 18 episodes of hyperglycemia (13 infants, median duration 237.5, maximum 3125 minutes). Epochs of hypoglycemia were not associated with aEEG changes. Compared with epochs of normoglycemia, epochs of hyperglycemia were associated with worse aEEG background scores (B 1.120, 95% CI 0.501-1.738, P < .001), less sleep-wake cycling (B 0.587, 95% CI 0.417-0.757, P < .001) and more electrographic seizures (B 0.433, 95% CI 0.185-0.681, P = .001), after adjusting for hypoxia-ischemia severity. CONCLUSIONS In neonates with encephalopathy, epochs of hyperglycemia were temporally associated with worse global brain function and seizures, even after we adjusted for hypoxia-ischemia severity. Whether hyperglycemia causes neuronal injury or is simply a marker of severe brain injury requires further study.
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Affiliation(s)
- Elana F Pinchefsky
- Division of Neurology, Department of Paediatrics, The Hospital for Sick Children and the University of Toronto, Toronto, Ontario, Canada; Program in Neurosciences and Mental Health, SickKids Research Institute, Toronto, Ontario, Canada.
| | - Cecil D Hahn
- Division of Neurology, Department of Paediatrics, The Hospital for Sick Children and the University of Toronto, Toronto, Ontario, Canada; Program in Neurosciences and Mental Health, SickKids Research Institute, Toronto, Ontario, Canada
| | - Daphne Kamino
- Division of Neurology, Department of Paediatrics, The Hospital for Sick Children and the University of Toronto, Toronto, Ontario, Canada; Program in Neurosciences and Mental Health, SickKids Research Institute, Toronto, Ontario, Canada
| | - Vann Chau
- Division of Neurology, Department of Paediatrics, The Hospital for Sick Children and the University of Toronto, Toronto, Ontario, Canada; Program in Neurosciences and Mental Health, SickKids Research Institute, Toronto, Ontario, Canada; BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada
| | - Rollin Brant
- BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada; Department of Statistics, The University of British Columbia, Vancouver, British Columbia, Canada
| | - Aideen M Moore
- Department of Paediatrics, The Hospital for Sick Children and the University of Toronto, Toronto, Ontario, Canada
| | - Emily W Y Tam
- Division of Neurology, Department of Paediatrics, The Hospital for Sick Children and the University of Toronto, Toronto, Ontario, Canada; Program in Neurosciences and Mental Health, SickKids Research Institute, Toronto, Ontario, Canada
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46
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Sandström J, Kratschmar DV, Broyer A, Poirot O, Marbet P, Chantong B, Zufferey F, Dos Santos T, Boccard J, Chrast R, Odermatt A, Monnet-Tschudi F. In vitro models to study insulin and glucocorticoids modulation of trimethyltin (TMT)-induced neuroinflammation and neurodegeneration, and in vivo validation in db/db mice. Arch Toxicol 2019; 93:1649-1664. [PMID: 30993381 DOI: 10.1007/s00204-019-02455-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2019] [Accepted: 04/09/2019] [Indexed: 02/06/2023]
Abstract
Brain susceptibility to a neurotoxic insult may be increased in a compromised health status, such as metabolic syndrome. Both metabolic syndrome and exposure to trimethyltin (TMT) are known to promote neurodegeneration. In combination the two factors may elicit additive or compensatory/regulatory mechanisms. Combined effects of TMT exposure (0.5-1 μM) and mimicked metabolic syndrome-through modulation of insulin and glucocorticoid (GC) levels-were investigated in three models: tridimensional rat brain cell cultures for neuron-glia effects; murine microglial cell line BV-2 for a mechanistic analysis of microglial reactivity; and db/db mice as an in vivo model of metabolic syndrome. In 3D cultures, low insulin condition significantly exacerbated TMT's effect on GABAergic neurons and promoted TMT-induced neuroinflammation, with increased expression of cytokines and of the regulator of intracellular GC activity, 11β-hydroxysteroid dehydrogenase 1 (11β-Hsd1). Microglial reactivity increased upon TMT exposure in medium combining low insulin and high GC. These results were corroborated in BV-2 microglial cells where lack of insulin exacerbated the TMT-induced increase in 11β-Hsd1 expression. Furthermore, TMT-induced microglial reactivity seems to depend on mineralocorticoid receptor activation. In diabetic BKS db mice, a discrete exacerbation of TMT neurotoxic effects on GABAergic neurons was observed, together with an increase of interleukin-6 (IL-6) and of basal 11β-Hsd1 expression as compared to controls. These results suggest only minor additive effects of the two brain insults, neurotoxicant TMT exposure and metabolic syndrome conditions, where 11β-Hsd1 appears to play a key role in the regulation of neuroinflammation and of its protective or neurodegenerative consequences.
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Affiliation(s)
- Jenny Sandström
- Department of Physiology, Faculty of Biology and Medicine, University of Lausanne, Rue du Bugnon 7, 1005, Lausanne, Switzerland.,Swiss Centre for Applied Human Toxicology, Basel, Switzerland
| | - Denise V Kratschmar
- Division of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.,Swiss Centre for Applied Human Toxicology, Basel, Switzerland
| | - Alexandra Broyer
- Department of Physiology, Faculty of Biology and Medicine, University of Lausanne, Rue du Bugnon 7, 1005, Lausanne, Switzerland
| | - Olivier Poirot
- Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland
| | - Philippe Marbet
- Division of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland
| | - Boonrat Chantong
- Division of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland
| | - Fanny Zufferey
- Department of Physiology, Faculty of Biology and Medicine, University of Lausanne, Rue du Bugnon 7, 1005, Lausanne, Switzerland.,Swiss Centre for Applied Human Toxicology, Basel, Switzerland
| | - Tania Dos Santos
- Department of Physiology, Faculty of Biology and Medicine, University of Lausanne, Rue du Bugnon 7, 1005, Lausanne, Switzerland
| | - Julien Boccard
- Swiss Centre for Applied Human Toxicology, Basel, Switzerland.,School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland
| | - Roman Chrast
- Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland.,Department of Neuroscience and Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden
| | - Alex Odermatt
- Division of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.,Swiss Centre for Applied Human Toxicology, Basel, Switzerland
| | - Florianne Monnet-Tschudi
- Department of Physiology, Faculty of Biology and Medicine, University of Lausanne, Rue du Bugnon 7, 1005, Lausanne, Switzerland. .,Swiss Centre for Applied Human Toxicology, Basel, Switzerland.
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van Niekerk G, Davis T, Patterton HG, Engelbrecht AM. How Does Inflammation-Induced Hyperglycemia Cause Mitochondrial Dysfunction in Immune Cells? Bioessays 2019; 41:e1800260. [PMID: 30970156 DOI: 10.1002/bies.201800260] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2018] [Revised: 02/26/2019] [Indexed: 12/15/2022]
Abstract
Inflammatory mediators have an established role in inducing insulin resistance and promoting hyperglycemia. In turn, hyperglycemia has been argued to drive immune cell dysfunction as a result of mitochondrial dysfunction. Here, the authors review the evidence challenging this view. First, it is pointed out that inflammatory mediators are known to induce altered mitochondrial function. In this regard, critical care patients suffer both an elevated inflammatory tone as well as hyperglycemia, rendering it difficult to distinguish between the effects of inflammation and hyperglycemia. Second, emerging evidence indicates that a decrease in mitochondrial respiration and an increase in reactive oxygen species (ROS) production are not necessarily manifestations of pathology, but adaptations taking shape as the mitochondria is abdicating its adenosine triphosphate (ATP)-producing function (which is taken over by glycolysis) and instead becomes "retooled" for an immunological role. Collectively, these observations challenge the commonly held belief that acute hyperglycemia induces mitochondrial damage leading to immune cell dysfunction.
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Affiliation(s)
- Gustav van Niekerk
- Department of Physiological Sciences, Stellenbosch University, 7602, Stellenbosch, South Africa
| | - Tanja Davis
- Department of Physiological Sciences, Stellenbosch University, 7602, Stellenbosch, South Africa
| | - Hugh-George Patterton
- Centre for Bioinformatics and Computational Biology, Stellenbosch University, 7602, Stellenbosch, South Africa
| | - Anna-Mart Engelbrecht
- Department of Physiological Sciences, Stellenbosch University, 7602, Stellenbosch, South Africa
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Abstract
SIGNIFICANCE Hexokinases are key enzymes that are responsible for the first reaction of glycolysis, but they also moonlight other cellular processes, including mitochondrial redox signaling regulation. Modulation of hexokinase activity and spatiotemporal location by reactive oxygen and nitrogen species as well as other gasotransmitters serves as the basis for a unique, underexplored method of tight and flexible regulation of these fundamental enzymes. Recent Advances: Redox modifications of thiols serve as a molecular code that enables the precise and complex regulation of hexokinases. Redox regulation of hexokinases is also used by multiple parasites to cause widespread and severe diseases, including malaria, Chagas disease, and sleeping sickness. Redox-active molecules affect each other, and the moonlighting activity of hexokinases provides another feedback loop that affects the cellular redox status and is hijacked in malignantly transformed cells. CRITICAL ISSUES Several compounds affect the redox status of hexokinases in vivo. These include the dehydroascorbic acid (oxidized form of vitamin C), pyrrolidinium porrolidine-1-carbodithioate (contraceptive), peroxynitrite (product of ethanol metabolism), alloxan (a glucose analog), and isobenzothiazolinone ebselen. However, very limited information is available regarding which amino acid residues in hexokinases are affected by redox signaling. Except in cases of monogenic diabetes, direct evidence is absent for disease phenotypes that are associated with variations within motifs that are susceptible to redox signaling. FUTURE DIRECTIONS Further studies should address the propensity of hexokinases and their disease-associated variants to participate in redox regulation. Robust and straightforward proteomic methods are needed to understand the context and consequences of hexokinase-mediated redox regulation in health and disease.
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Affiliation(s)
- Petr Heneberg
- Third Faculty of Medicine, Charles University , Prague, Czech Republic
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49
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Mehta Y, Mithal A, Kulkarni A, Reddy BR, Sharma J, Dixit S, Zirpe K, Sivakumar MN, Bathina H, Chakravarti S, Joshi A, Rao S. Practice Guidelines for Enteral Nutrition Management in Dysglycemic Critically Ill Patients: A Relook for Indian Scenario. Indian J Crit Care Med 2019; 23:594-603. [PMID: 31988554 PMCID: PMC6970214 DOI: 10.5005/jp-journals-10071-23298] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Background and aim Intensive-care practices and settings differ for India in comparison to other countries. While guidelines are available to direct the use of enteral nutrition (EN), there are no recommendations specific to nutritional management of EN in dysglycemic patients, specific to patients in Indian critical care settings. Advisory board meetings were arranged to develop the practice guidelines specific to the Indian context, for the use of EN in dysglycemic critically ill patients and to overcome challenges in this field. Materials and methods Two advisory board meetings were organized to review various existing guidelines, meta-analyses, randomized controlled trials (RCTs), controlled trials and review articles, for their contextual relevance and strength. Three rounds of Delphi voting were done to arrive at consensus on certain recommendations. A systematic grading of practice guidelines by the advisory board was done based on strength of the consensus voting and reviewed supporting evidences. Results Based on the literature review, the recommendations for developing the practice guidelines were made as per the grading criteria agreed upon by the advisory board. The recommendations were to address challenges regarding prediction and assessment of dysglycemia (DG), acceptable glycemic targets in such settings, general nutritional aspects pertaining to DG nutrition, and nutrition in various superspecialty cases in critical care settings, where DG is commonly encountered. Conclusion This paper summarizes the optimum EN practices for managing DG in critically ill patients. The practical solutions to overcome the challenges in this field are presented as practice guidelines at the end of each section. These guidelines are expected to provide guidance for EN management in dysglycemic critically ill patients. These guidelines also outline the model glycemic control task force and its roles in nutrition care as well as an intensive care unit DG nutrition protocol. How to cite this article Mehta Y, Mithal A, Kulkarni A, Reddy BR, Sharma J, Dixit S, et al. Practice Guidelines for Enteral Nutrition Management in Dysglycemic Critically Ill Patients: A Relook for Indian Scenario. Indian J Crit Care Med 2019;23(12):594–603.
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Affiliation(s)
- Yatin Mehta
- Institute of Critical Care and Anesthesiology, Medanta: The Medicity, Gurugram, Haryana, India
| | - Ambrish Mithal
- Department of Endocrinology and Diabetology, Institute of Endocrinology and Diabetology, Medanta: The Medicity, Gurugram, Haryana, India
| | - Atul Kulkarni
- Department of Anesthesiology, Critical Care and Pain, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - B Ravinder Reddy
- Department of Gastrointestinal Surgery, The Institute of Medical Sciences, Care Hospitals, Hyderabad, Telangana, India
| | - Jeetendra Sharma
- Department of Critical Care Medicine, Artemis Hospital, Gurugram, Haryana, India
| | - Subhal Dixit
- Department of Critical Care Medicine, Sanjeevan and MJM Hospital, Pune, Maharashtra, India
| | - Kapil Zirpe
- Department of Intensive Care and Neurotrauma-Stroke Unit, Ruby Hall Clinic, Pune, Maharashtra, India
| | - M N Sivakumar
- Department of Critical Care Medicine, Royal Care Super Specialty Hospital, Coimbatore, Tamil Nadu, India
| | - Harita Bathina
- Department of Dietetics, Apollo Hospitals, Hyderabad, Telangana, India
| | - Sanghamitra Chakravarti
- Department of Nutrition and Dietetics, Medica Superspecialty Hospital, Kolkata, West Bengal, India
| | - Anshu Joshi
- Department of Scientific and Medical Affairs, Abbott Nutrition International, India
| | - Sameer Rao
- Department of Scientific and Medical Affairs, Abbott Nutrition International, India
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Krane EJ, Rhodes ET, Claure RE, Rowe E, Wolfsdorf JI. Essentials of Endocrinology. A PRACTICE OF ANESTHESIA FOR INFANTS AND CHILDREN 2019:629-654.e6. [DOI: 10.1016/b978-0-323-42974-0.00027-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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