|
1
|
Cacace J, Luna-Marco C, Hermo-Argibay A, Pesantes-Somogyi C, Hernández-López OA, Pelechá-Salvador M, Bañuls C, Apostolova N, de Miguel-Rodríguez L, Morillas C, Rocha M, Rovira-Llopis S, Víctor VM. Poor glycaemic control in type 2 diabetes compromises leukocyte oxygen consumption rate, OXPHOS complex content and neutrophil-endothelial interactions. Redox Biol 2025; 81:103516. [PMID: 39986115 PMCID: PMC11893319 DOI: 10.1016/j.redox.2025.103516] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2024] [Revised: 01/23/2025] [Accepted: 01/24/2025] [Indexed: 02/24/2025] Open
Abstract
The mitochondrial electron transport chain becomes overloaded in type 2 diabetes (T2D), which increases ROS (Reactive Oxygen Species) production and impairs mitochondrial function. Peripheral blood mononuclear cells (PBMCs) are critical players in the inflammatory process that underlies T2D. Poor glycaemic control in T2D is closely linked to the development of comorbidities. Our aim was to evaluate if glycaemic control in T2D has an impact on the oxygen consumption rates (OCR) of PBMC, OXPHOS complexes and inflammation. We recruited 181 subjects, consisting of 79 healthy controls, 64 patients with T2D and good glycaemic control (HbA1c<7 %), and 38 T2D patients with poor glycaemic control (HbA1c>7 %). We found a decrease in the basal OCR of PBMCs from patients with HbA1c>7 % with respect to controls (p < 0.05). Maximal OCR and spare respiratory capacity were lower in patients with HbA1c>7 % than in controls and patients with HbA1c<7 % (p < 0.05 for all). Mitochondrial ROS levels were higher in T2D patients, and particularly in the HbA1c > 7 group (p < 0.05 HbA1c<7 % vs control, p < 0.001 HbA1c>7 % vs control; p < 0.001 HbA1c > 7 vs HbA1c < 7). With respect to controls, poor glycaemic control in T2D patients was associated with a decrease in mitochondrial complex III and V (p < 0.05 and p < 0.01, respectively) and enhanced neutrophil-endothelial interactions (p < 0.001 vs controls). MPO levels were enhanced in T2D patients in general (p < 0.05 vs controls), and ICAM-1 and VCAM-1 were specifically increased in HbA1c > 7 patients vs controls (p < 0.01 and p < 0.001, respectively). Negative low-to-moderate correlations were found between HbA1c and basal respiration (r = -0.319, p < 0.05), maximal respiration (r = -0.350, p < 0.01) and spare respiratory capacity (r = -0.295, p < 0.05). Our findings suggest that poor glycaemic control during the progression of T2D compromises mitochondrial respiration and OXPHOS complex content in PBMCs. These alterations occur in parallel to enhanced neutrophil-endothelial interactions and adhesion molecule levels, leaving T2D patients with poor glycaemic control at a higher risk of developing vascular diseases.
Collapse
Affiliation(s)
- Julia Cacace
- Service of Endocrinology and Nutrition, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), University Hospital Doctor Peset, Valencia, Spain
| | - Clara Luna-Marco
- Service of Endocrinology and Nutrition, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), University Hospital Doctor Peset, Valencia, Spain; Department of Physiology, University of Valencia, INCLIVA (Biomedical Research Institute Valencia), Valencia, Spain
| | - Alberto Hermo-Argibay
- Service of Endocrinology and Nutrition, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), University Hospital Doctor Peset, Valencia, Spain
| | - Catherine Pesantes-Somogyi
- Service of Endocrinology and Nutrition, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), University Hospital Doctor Peset, Valencia, Spain
| | - Omar A Hernández-López
- Service of Endocrinology and Nutrition, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), University Hospital Doctor Peset, Valencia, Spain
| | - María Pelechá-Salvador
- Service of Endocrinology and Nutrition, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), University Hospital Doctor Peset, Valencia, Spain
| | - Celia Bañuls
- Service of Endocrinology and Nutrition, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), University Hospital Doctor Peset, Valencia, Spain
| | - Nadezda Apostolova
- National Network of Biomedical Research on Hepatic and Digestive Diseases (CIBERehd), Valencia, Spain; Department of Pharmacology, University of Valencia, Valencia, Spain
| | - Luis de Miguel-Rodríguez
- Service of Endocrinology and Nutrition, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), University Hospital Doctor Peset, Valencia, Spain
| | - Carlos Morillas
- Service of Endocrinology and Nutrition, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), University Hospital Doctor Peset, Valencia, Spain
| | - Milagros Rocha
- Service of Endocrinology and Nutrition, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), University Hospital Doctor Peset, Valencia, Spain; National Network of Biomedical Research on Hepatic and Digestive Diseases (CIBERehd), Valencia, Spain.
| | - Susana Rovira-Llopis
- Service of Endocrinology and Nutrition, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), University Hospital Doctor Peset, Valencia, Spain.
| | - Víctor M Víctor
- Service of Endocrinology and Nutrition, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), University Hospital Doctor Peset, Valencia, Spain; Department of Physiology, University of Valencia, INCLIVA (Biomedical Research Institute Valencia), Valencia, Spain; National Network of Biomedical Research on Hepatic and Digestive Diseases (CIBERehd), Valencia, Spain.
| |
Collapse
|
|
2
|
Pappas G, Gow A, Punjabi NM, Aurora RN. Sex-specific differences in overnight nitrate levels in persons with obstructive sleep apnea and type 2 diabetes. Sleep Med 2025; 128:159-164. [PMID: 39952069 DOI: 10.1016/j.sleep.2025.02.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2024] [Revised: 01/27/2025] [Accepted: 02/05/2025] [Indexed: 02/17/2025]
Abstract
STUDY OBJECTIVES Sex-specific differences in OSA-associated symptoms and polysomnographic findings are well recognized. However, sex differences in intermediate pathways potentially linking OSA and cardiometabolic outcomes are limited. OSA is known to be associated with decreased nitric oxide (NO)-related vasodilation and endothelial dysfunction. The current study sought to characterize the independent association between OSA severity and overnight NO metabolites (i.e. markers of oxidative stress) and determine if there were differences by sex in persons with type 2 diabetes mellitus (T2DM). METHODS Adults with T2DM and undiagnosed OSA were recruited from the community. Demographic information, an overnight polysomnogram, and pre- and post-sleep plasma samples were collected. The association between OSA and nitrite and nitrate levels were examined using multivariable linear regression. Analyses were done for the entire sample and stratified by sex. RESULTS The sample included 83 participants with 52 % men. Stratified, fully adjusted models showed that compared to women with mild OSA, women with moderate or severe OSA did not exhibit the expected decline in overnight nitrate levels: 4.84 μM (-12.3, 2.7: p = 0.09) and 5.82 μM (-4.7, 16.3: p < 0.01) for moderate and severe OSA, respectively. Overnight nitrate levels decreased in males regardless of OSA severity, without significant differences across severity categories. An interaction between OSA severity and sex was seen for post-sleep nitrates in women with severe OSA. CONCLUSION The association between OSA and overnight nitrates varies by sex and OSA severity. Women with severe OSA did not have a decline in overnight nitrate levels whereas men did, suggesting they have higher overnight oxidative stress.
Collapse
Affiliation(s)
- Gregory Pappas
- Ernest Mario School of Pharmacy, Picastaway, NJ, USA; War Related Illness and Injury Study Center, VA New Jersey Healthcare System, East Orange, NJ, USA.
| | - Andrew Gow
- Ernest Mario School of Pharmacy, Picastaway, NJ, USA.
| | - Naresh M Punjabi
- Divsion of Pulmonary, Critical Care, and Sleep Medicine, University of Miami, Miller School of Medicine, Miami, FL, USA; Division of Pulmonary, Critical Care, and Sleep Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
| | - R Nisha Aurora
- Division of Pulmonary, Critical Care, and Sleep Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Division of Pulmonary, Critical Care, and Sleep Medicine, NYU Grossman School of Medicine, New York, NY, USA.
| |
Collapse
|
|
3
|
Feng LX, Gao H, Zhang J, Gu J, Wang Y, Li T, Gao B. Endovascular recanalization of subacute or chronic symptomatic occlusion of the internal carotid artery ophthalmic segment. Eur J Radiol 2025; 183:111885. [PMID: 39689634 DOI: 10.1016/j.ejrad.2024.111885] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Revised: 11/21/2024] [Accepted: 12/09/2024] [Indexed: 12/19/2024]
Abstract
OBJECTIVE To investigate the safety and effect of endovascular recanalization for subacute or chronic occlusion of the internal carotid artery (ICA) ophthalmic segment and risk factors for the prognosis. MATERIALS AND METHODS 135 patients with subacute or chronic occlusion of the ICA ophthalmic segment were retrospectively enrolled to undergo endovascular recanalization, with the clinical, imaging and follow-up data being analyzed. RESULTS Among 135 patients with ICA ophthalmic segment occlusion, hypertension was presented in 72 (53.3 %) patients, diabetes mellitus in 44 (32.6 %), coronary heart disease in 12 (8.9 %), smoking in 51 (37.8 %), and alcohol abuse in 38 (28.1 %). Endovascular recanalization was performed in all patients, and recanalization was successful in 130 (96.3 %). Five patients (3.7 %) were not recanalized because of intraprocedural complications. Periprocedural complications occurred in 16 patients, resulting in a total complication rate of 11.9 %. The mRS (modified Rankin Scale score) was 1.45 ± 0.03 after recanalization, significantly (P < 0.001) better than that (2.25 ± 0.12) before recanalization. The NIHSS (National Institute of Health Stroke Scale) was 11.91 ± 0.67, significantly (P < 0.0001) better than that (18.45 ± 1.33) before recanalization. Eighty-nine (65.9 %) patients underwent angiography at follow-up 6-86 (mean 48) months after recanalization, which demonstrated good prognosis in 72 (80.9 %) patients and poor prognosis in the other 17 (19.1 %) with instent restenosis > 50 %. Telephone follow-up was conducted in 46 (34.1 %) patients 6-38 (mean 27) months after recanalization, which revealed good prognosis in 38 (82.6 %) patients and poor prognosis in 8 (17.4 %). In total, good prognosis was present in 110 (81.5 %) patients while poor prognosis in 25 (18.5 %). In angiographic follow-up, instent restenosis > 50 % was present in nine (10.1 %) patients. Univariate analysis showed age (OR = 1.82), hypertension (OR = 2.38), diabetes mellitus (OR = 1.84), and alcohol abuse (OR = 1.49) were significant (P < 0.05) risk factors, whereas multivariate analysis demonstrated that only hypertension (OR = 1.54) and diabetes mellitus (OR = 2.67) were significant (P < 0.05) independent risk factors to affect the prognosis of recanalization. CONCLUSION Subacute or chronic occlusion of the internal carotid artery ophthalmic segment can be safely and efficiently recanalized using endovascular skills, and hypertension and diabetes mellitus are the independent risk factors for the prognosis of endovascular recanalization.
Collapse
Affiliation(s)
- Ling-Xiao Feng
- Henan Provincial People's Hospital, Zhengzhou University, China
| | - Huili Gao
- Henan Provincial People's Hospital, Zhengzhou University, China
| | - Jinlong Zhang
- Henan Provincial People's Hospital, Zhengzhou University, China
| | - Jianjun Gu
- Henan Provincial People's Hospital, Zhengzhou University, China
| | - Yongfeng Wang
- Henan Provincial People's Hospital, Zhengzhou University, China
| | - Tianxiao Li
- Henan Provincial People's Hospital, Zhengzhou University, China
| | - Bulang Gao
- Henan Provincial People's Hospital, Zhengzhou University, China
| |
Collapse
|
|
4
|
Nwokocha C, Palacios J, Ojukwu VE, Nna VU, Owu DU, Nwokocha M, McGrowder D, Orie NN. Oxidant-induced disruption of vascular K + channel function: implications for diabetic vasculopathy. Arch Physiol Biochem 2024; 130:361-372. [PMID: 35757993 DOI: 10.1080/13813455.2022.2090578] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Accepted: 06/07/2022] [Indexed: 11/02/2022]
Abstract
Diabetes in humans a chronic metabolic disorder characterised by hyperglycaemia, it is associated with an increased risk of cardiovascular disease, disruptions to metabolism and vascular functions. It is also linked to oxidative stress and its complications. Its role in vascular dysfunctions is generally reported without detailed impact on the molecular mechanisms. Potassium ion channel (K+ channels) are key regulators of vascular tone, and as membrane proteins, are modifiable by oxidant stress associated with diabetes. This review manuscript examined the impact of oxidant stress on vascular K+ channel functions in diabetes, its implication in vascular complications and metabolic and cardiovascular diseases.
Collapse
Affiliation(s)
| | - Javier Palacios
- Department of Pharmacy, Faculty of Health Sciences, Arturo Prat University, Iquique, Chile
| | - Victoria E Ojukwu
- Basic Medical Sciences, University of the West Indies, Mona, Kingston, Jamaica
| | - Victor Udo Nna
- Department of Physiology, College of Medical Sciences, University of Calabar, Calabar, Nigeria
| | - Daniel Udofia Owu
- Department of Physiology, College of Medical Sciences, University of Calabar, Calabar, Nigeria
| | - Magdalene Nwokocha
- Department of Pathology, Faculty of Medical Sciences, University of the West Indies, Mona, Kingston, Jamaica
| | - Donovan McGrowder
- Department of Pathology, Faculty of Medical Sciences, University of the West Indies, Mona, Kingston, Jamaica
| | - Nelson N Orie
- Centre of Metabolism and Inflammation, University College London, London, UK
| |
Collapse
|
|
5
|
Alves-Costa S, Nascimento GG, Peres MA, Li H, Costa SA, Ribeiro CCC, Leite FRM. Sugar-sweetened beverage consumption and periodontitis among adults: A population-based cross-sectional study. J Clin Periodontol 2024; 51:712-721. [PMID: 38454156 DOI: 10.1111/jcpe.13961] [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: 05/22/2023] [Revised: 01/22/2024] [Accepted: 01/26/2024] [Indexed: 03/09/2024]
Abstract
AIM Investigating the association between sugar-sweetened beverages (SSBs) and periodontitis and whether the awareness of diabetes modifies this relationship. MATERIALS AND METHODS Cross-sectional analysis was conducted using the National Health and Nutrition Examination Survey (NHANES III) data involving US adults aged 30-50. Periodontitis was classified according to the Centers for Disease Control and Prevention and American Academy of Periodontology (CDC-AAP), and SSB consumption as dichotomous (<5 or ≥5, <7 or ≥7 and <14 or ≥14 times/week), ordinal and continuous variables. Confounders included family income poverty ratio, education, race/ethnicity, sex, age, food energy intake, smoking and alcohol. Odds ratios (ORs) were obtained by logistic regressions using inverse probability weighting. Effect modification analysis was performed considering self-reported diabetes. RESULTS Among 4473 cases analysed, 198 self-reported diabetes. SSBs were associated with periodontitis when individuals consumed ≥5 (OR 1.64; 95% confidence interval [CI] = 1.30-2.06), ≥7 (OR 1.92; 95% CI = 1.50-2.46) and ≥14 (OR 2.19; 95% CI = 1.50-3.18) times/week. The combined effect of consuming SSBs (≥5 and ≥14 times/week) and self-reported diabetes had less impact than the cumulative effect. CONCLUSIONS SSB consumption was associated with higher odds of periodontitis, and the estimates were reduced among those with awareness of diabetes.
Collapse
Affiliation(s)
- Silas Alves-Costa
- Graduate Program in Dentistry, Federal University of Maranhão, São Luís, Maranhão, Brazil
- National Dental Research Institute Singapore, National Dental Centre Singapore, Singapore, Singapore
| | - Gustavo G Nascimento
- National Dental Research Institute Singapore, National Dental Centre Singapore, Singapore, Singapore
- Oral Health Academic Clinical Programme, Duke-NUS Medical School, Singapore, Singapore
| | - Marco A Peres
- National Dental Research Institute Singapore, National Dental Centre Singapore, Singapore, Singapore
- Oral Health Academic Clinical Programme, Duke-NUS Medical School, Singapore, Singapore
| | - Huihua Li
- National Dental Research Institute Singapore, National Dental Centre Singapore, Singapore, Singapore
- Oral Health Academic Clinical Programme, Duke-NUS Medical School, Singapore, Singapore
| | - Susilena Arouche Costa
- Graduate Program in Dentistry, Federal University of Maranhão, São Luís, Maranhão, Brazil
| | | | - Fábio Renato Manzolli Leite
- National Dental Research Institute Singapore, National Dental Centre Singapore, Singapore, Singapore
- Oral Health Academic Clinical Programme, Duke-NUS Medical School, Singapore, Singapore
| |
Collapse
|
|
6
|
Rugg C, Schmid S, Zipperle J, Kreutziger J. Stress hyperglycaemia following trauma - a survival benefit or an outcome detriment? Curr Opin Anaesthesiol 2024; 37:131-138. [PMID: 38390910 DOI: 10.1097/aco.0000000000001350] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/24/2024]
Abstract
PURPOSE OF REVIEW Stress hyperglycaemia occur often in critically injured patients. To gain new consideration about it, this review compile current as well as known immunological and biochemical findings about causes and emergence. RECENT FINDINGS Glucose is the preferred energy substrate for fending immune cells, reparative tissue and the cardiovascular system following trauma. To fulfil these energy needs, the liver is metabolically reprogrammed to rebuild glucose from lactate and glucogenic amino acids (hepatic insulin resistance) at the expenses of muscles mass and - to a less extent - fat tissue (proteolysis, lipolysis, peripheral insulin resistance). This inevitably leads to stress hyperglycaemia, which is evolutionary preserved and seems to be an essential and beneficial survival response. It is initiated by damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs), intensified by immune cells itself and mainly ruled by tumour necrosis factor (TNF)α and catecholamines with lactate and hypoxia inducible factor (HIF)-1α as intracellular signals and lactate as an energy shuttle. Important biochemical mechanisms involved in this response are the Warburg effect as an efficient metabolic shortcut and the extended Cori cycle. SUMMARY Stress hyperglycaemia is beneficial in an acute life-threatening situation, but further research is necessary, to prevent trauma patients from the detrimental effects of persisting hyperglycaemia.
Collapse
Affiliation(s)
- Christopher Rugg
- Department of Anaesthesia and Intensive Care Medicine, Medical University of Innsbruck, Innsbruck, Austria
| | - Stefan Schmid
- Department of Anaesthesia and Intensive Care Medicine, Medical University of Innsbruck, Innsbruck, Austria
| | - Johannes Zipperle
- Johannes Zipperle, Ludwig Boltzmann Institute for Traumatology, The Research Center in Cooperation with AUVA, Vienna, Austria
| | - Janett Kreutziger
- Department of Anaesthesia and Intensive Care Medicine, Medical University of Innsbruck, Innsbruck, Austria
| |
Collapse
|
|
7
|
Weng J, Ross C, Baker J, Alfuraih S, Shamloo K, Sharma A. Diabetes-Associated Hyperglycemia Causes Rapid-Onset Ocular Surface Damage. Invest Ophthalmol Vis Sci 2023; 64:11. [PMID: 37938936 PMCID: PMC10637200 DOI: 10.1167/iovs.64.14.11] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Accepted: 10/16/2023] [Indexed: 11/10/2023] Open
Abstract
Purpose The metabolic alterations due to chronic hyperglycemia are well-known to cause diabetes-associated complications. Short-term hyperglycemia has also been shown to cause many acute changes, including hemodynamic alterations and osmotic, oxidative, and inflammatory stress. The present study was designed to investigate whether diabetes-associated hyperglycemia can cause rapid-onset detrimental effects on the tear film, goblet cells, and glycocalyx and can lead to activation of an inflammatory cascade or cellular stress response in the cornea. Methods Mouse models of type 1 and type 2 diabetes were used. Tear film volume, goblet cell number, and corneal glycocalyx area were measured on days 7, 14, and 28 after the onset of hyperglycemia. Transcriptome analysis was performed to quantify changes in 248 transcripts of genes involved in inflammatory, apoptotic, and stress response pathways. Results Our data demonstrate that type 1 and type 2 diabetes-associated hyperglycemia caused a significant decrease in the tear film volume, goblet cell number, and corneal glycocalyx area. The decrease in tear film and goblet cell number was noted as early as 7 days after onset of hyperglycemia. The severity of ocular surface injury was significantly more in type 1 compared to type 2 diabetes. Diabetes mellitus also caused an increase in transcripts of genes involved in the inflammatory, apoptotic, and cellular stress response pathways. Conclusions The results of the present study demonstrate that diabetes-associated hyperglycemia causes rapid-onset damage to the ocular surface. Thus, short-term hyperglycemia in patients with diabetes mellitus may also play an important role in causing ocular surface injury and dry eye.
Collapse
Affiliation(s)
- Judy Weng
- Chapman University School of Pharmacy, Chapman University, Irvine, California, United States
| | - Christopher Ross
- Chapman University School of Pharmacy, Chapman University, Irvine, California, United States
| | - Jacob Baker
- Chapman University School of Pharmacy, Chapman University, Irvine, California, United States
| | - Saleh Alfuraih
- Chapman University School of Pharmacy, Chapman University, Irvine, California, United States
| | - Kiumars Shamloo
- Chapman University School of Pharmacy, Chapman University, Irvine, California, United States
| | - Ajay Sharma
- Chapman University School of Pharmacy, Chapman University, Irvine, California, United States
| |
Collapse
|
|
8
|
Ahn J, Baik JW, Kim D, Choi K, Lee S, Park SM, Kim JY, Nam SH, Kim C. In vivo photoacoustic monitoring of vasoconstriction induced by acute hyperglycemia. PHOTOACOUSTICS 2023; 30:100485. [PMID: 37082618 PMCID: PMC10112177 DOI: 10.1016/j.pacs.2023.100485] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Revised: 03/19/2023] [Accepted: 03/29/2023] [Indexed: 05/03/2023]
Abstract
Postprandial hyperglycemia, blood glucose spikes, induces endothelial dysfunction, increasing cardiovascular risks. Endothelial dysfunction leads to vasoconstriction, and observation of this phenomenon is important for understanding acute hyperglycemia. However, high-resolution imaging of microvessels during acute hyperglycemia has not been fully developed. Here, we demonstrate that photoacoustic microscopy can noninvasively monitor morphological changes in blood vessels of live animals' extremities when blood glucose rises rapidly. As blood glucose level rose from 100 to 400 mg/dL following intraperitoneal glucose injection, heart/breath rate, and body temperature remained constant, but arterioles constricted by approximately -5.7 ± 1.1% within 20 min, and gradually recovered for another 40 min. In contrast, venular diameters remained within about 0.6 ± 1.5% during arteriolar constriction. Our results experimentally and statistically demonstrate that acute hyperglycemia produces transitory vasoconstriction in arterioles, with an opposite trend of change in blood glucose. These findings could help understanding vascular glucose homeostasis and the relationship between diabetes and cardiovascular diseases.
Collapse
Affiliation(s)
- Joongho Ahn
- Departments of Electrical Engineering, Convergence IT Engineering, Mechanical Engineering, and Medical Science and Engineering, and Medical Device Innovation Center, Pohang University of Science and Technology, Pohang 37673, Republic of Korea
| | - Jin Woo Baik
- Departments of Electrical Engineering, Convergence IT Engineering, Mechanical Engineering, and Medical Science and Engineering, and Medical Device Innovation Center, Pohang University of Science and Technology, Pohang 37673, Republic of Korea
| | - Donggyu Kim
- Departments of Electrical Engineering, Convergence IT Engineering, Mechanical Engineering, and Medical Science and Engineering, and Medical Device Innovation Center, Pohang University of Science and Technology, Pohang 37673, Republic of Korea
| | - Karam Choi
- Samsung Advanced Institute of Technology, Samsung Electronics Co. Ltd., Suwon 16678, Republic of Korea
| | - Seunghyun Lee
- Departments of Electrical Engineering, Convergence IT Engineering, Mechanical Engineering, and Medical Science and Engineering, and Medical Device Innovation Center, Pohang University of Science and Technology, Pohang 37673, Republic of Korea
| | - Sung-Min Park
- Departments of Electrical Engineering, Convergence IT Engineering, Mechanical Engineering, and Medical Science and Engineering, and Medical Device Innovation Center, Pohang University of Science and Technology, Pohang 37673, Republic of Korea
| | - Jin Young Kim
- Departments of Electrical Engineering, Convergence IT Engineering, Mechanical Engineering, and Medical Science and Engineering, and Medical Device Innovation Center, Pohang University of Science and Technology, Pohang 37673, Republic of Korea
| | - Sung Hyun Nam
- Samsung Advanced Institute of Technology, Samsung Electronics Co. Ltd., Suwon 16678, Republic of Korea
- Corresponding authors.
| | - Chulhong Kim
- Departments of Electrical Engineering, Convergence IT Engineering, Mechanical Engineering, and Medical Science and Engineering, and Medical Device Innovation Center, Pohang University of Science and Technology, Pohang 37673, Republic of Korea
- Corresponding authors.
| |
Collapse
|
|
9
|
Eligini S, Porro B, Werba JP, Capra N, Genovese S, Greco A, Cavalca V, Banfi C. Oxidative Stress and Arginine/Nitric Oxide Pathway in Red Blood Cells Derived from Patients with Prediabetes. Biomedicines 2022; 10:biomedicines10061407. [PMID: 35740426 PMCID: PMC9219800 DOI: 10.3390/biomedicines10061407] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Revised: 06/09/2022] [Accepted: 06/11/2022] [Indexed: 11/25/2022] Open
Abstract
The effects of the oral glucose tolerance test (OGTT) on red blood cells (RBCs) have not been thoroughly investigated, although it is known that the ingestion of 75 g of glucose during OGTT results in a systemic state of inflammation and oxidative stress. Therefore, we evaluated the effect of OGTT on oxidative stress and L-arginine/Nitric Oxide (L-Arg/NO) metabolic pathway in RBCs obtained from patients with prediabetes. Blood samples were collected from all participants before (T0) and at 10 (T1), 20 (T2), 30 (T3), 60 (T4), 90 (T5), 120 (T6), 150 (T7), and 180 (T8) minutes after glucose loading. Results showed a significant increase in oxidative stress status characterized by a rise in the GSSG/GSH ratio at T4 and T6 that increased in parallel with a reduction of NO production in RBCs. In addition, in this time frame, increased exposure of phosphatidylserine on RBCs membrane was observed. These metabolic modifications were rescued at T8, together with an increase in activated RBC NO synthase expression. These findings provide a possible explanation of the phenomena occurring after glucose loading and suggest that, even in the early stages of diabetes, it may be important to avoid acute variations in glycemia in order to prevent diabetic complications.
Collapse
Affiliation(s)
- Sonia Eligini
- Centro Cardiologico Monzino, IRCCS, 20138 Milano, Italy; (S.E.); (B.P.); (N.C.); (S.G.); (A.G.); (C.B.)
| | - Benedetta Porro
- Centro Cardiologico Monzino, IRCCS, 20138 Milano, Italy; (S.E.); (B.P.); (N.C.); (S.G.); (A.G.); (C.B.)
| | - José Pablo Werba
- Centro Cardiologico Monzino, IRCCS, 20138 Milano, Italy; (S.E.); (B.P.); (N.C.); (S.G.); (A.G.); (C.B.)
- Correspondence:
| | - Nicolò Capra
- Centro Cardiologico Monzino, IRCCS, 20138 Milano, Italy; (S.E.); (B.P.); (N.C.); (S.G.); (A.G.); (C.B.)
| | - Stefano Genovese
- Centro Cardiologico Monzino, IRCCS, 20138 Milano, Italy; (S.E.); (B.P.); (N.C.); (S.G.); (A.G.); (C.B.)
| | - Arianna Greco
- Centro Cardiologico Monzino, IRCCS, 20138 Milano, Italy; (S.E.); (B.P.); (N.C.); (S.G.); (A.G.); (C.B.)
| | - Viviana Cavalca
- Dipartimento di Scienze Cliniche e di Comunità, Università Degli Studi di Milano, 20122 Milano, Italy;
| | - Cristina Banfi
- Centro Cardiologico Monzino, IRCCS, 20138 Milano, Italy; (S.E.); (B.P.); (N.C.); (S.G.); (A.G.); (C.B.)
| |
Collapse
|
|
10
|
Roberts-Thomson KM, Parker L, Betik AC, Wadley GD, Gatta PAD, Marwick TH, Keske MA. Oral and intravenous glucose administration elicit opposing microvascular blood flow responses in skeletal muscle of healthy people: role of incretins. J Physiol 2022; 600:1667-1681. [PMID: 35045191 PMCID: PMC9303176 DOI: 10.1113/jp282428] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Accepted: 01/11/2022] [Indexed: 11/30/2022] Open
Abstract
Abstract Insulin infusion increases skeletal muscle microvascular blood flow (MBF) in healthy people but is impaired during insulin resistance. However, we have shown that eliciting insulin secretion via oral glucose loading in healthy people impairs muscle MBF, whilst others have demonstrated intravenous glucose infusion stimulates MBF. We aimed to show that the route of glucose administration (oral versus intravenous) influences muscle MBF, and explore potential gut‐derived hormones that may explain these divergent responses. Ten healthy individuals underwent a 120 min oral glucose tolerance test (OGTT; 75 g glucose) and on a subsequent occasion an intravenous glucose tolerance test (IVGTT, bypassing the gut) matched for similar blood glucose excursions. Femoral artery and thigh muscle microvascular (contrast‐enhanced ultrasound) haemodynamics were measured at baseline and during the OGTT/IVGTT. Plasma insulin, C‐peptide, glucagon, non‐esterified fatty acids and a range of gut‐derived hormones and incretins (gastric inhibitory polypeptide (GIP) and glucagon‐like peptide‐1(GLP‐1)) were measured at baseline and throughout the OGTT/IVGTT. The IVGTT increased whereas the OGTT impaired MBF (1.3‐fold versus 0.5‐fold from baseline, respectively, P = 0.0006). The impairment in MBF during the OGTT occurred despite producing 2.8‐fold higher plasma insulin concentrations (P = 0.0001). The change in MBF from baseline (ΔMBF) negatively correlated with ΔGIP concentrations (r = −0.665, P < 0.0001). The natural log ratio of incretins GLP‐1:GIP was positively associated with ΔMBF (r = 0.658, P < 0.0001), suggesting they have opposing actions on the microvasculature. Postprandial hyperglycaemia per se does not acutely determine opposing microvascular responses between OGTT and IVGTT. Incretins may play a role in modulating skeletal muscle MBF in humans. Key points
Insulin or mixed nutrient meals stimulate skeletal muscle microvascular blood flow (MBF) to aid in the delivery of nutrients; however, this vascular effect is lost during insulin resistance. Food/drinks containing large glucose loads impair MBF in healthy people; however, this impairment is not observed when glucose is infused intravenously (bypassing the gut). We investigated skeletal muscle MBF responses to a 75 g oral glucose tolerance test and intravenous glucose infusion and aimed to identify potential gut hormones responsible for glucose‐mediated changes in MBF. Despite similar blood glucose concentrations, orally ingested glucose impaired, whereas intravenously infused glucose augmented, skeletal muscle MBF. The incretin gastric inhibitory polypeptide was negatively associated with MBF, suggestive of an incretin‐mediated MBF response to oral glucose ingestion. This work provides new insight into why diets high in glucose may be detrimental to vascular health and provides new avenues for novel treatment strategies targeting microvascular dysfunction.
Collapse
Affiliation(s)
- Katherine M Roberts-Thomson
- Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Geelong, Victoria, Australia
| | - Lewan Parker
- Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Geelong, Victoria, Australia.,Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia
| | - Andrew C Betik
- Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Geelong, Victoria, Australia.,Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia
| | - Glenn D Wadley
- Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Geelong, Victoria, Australia
| | - Paul A Della Gatta
- Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Geelong, Victoria, Australia
| | - Thomas H Marwick
- Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia
| | - Michelle A Keske
- Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Geelong, Victoria, Australia.,Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia
| |
Collapse
|
|
11
|
Roberts AM, Moulana NZ, Jagadapillai R, Cai L, Gozal E. Intravital assessment of precapillary pulmonary arterioles of type 1 diabetic mice shows oxidative damage and increased tone in response to NOS inhibition. J Appl Physiol (1985) 2021; 131:1552-1564. [PMID: 34590907 PMCID: PMC11961051 DOI: 10.1152/japplphysiol.00395.2021] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Revised: 09/07/2021] [Accepted: 09/28/2021] [Indexed: 11/22/2022] Open
Abstract
Microvascular dilation, important for peripheral tissue glucose distribution, also modulates alveolar perfusion and is inhibited by loss of bioavailable nitric oxide (NO) in diabetes mellitus (DM). We hypothesized that DM-induced oxidative stress decreases bioavailable NO and pulmonary precapillary arteriolar diameter, causing endothelial injury. We examined subpleural pulmonary arterioles after acute NO synthase (NOS) inhibition with NG-nitro-l-arginine methyl ester (l-NAME) in streptozotocin (STZ)- and saline (CTRL)-treated C57BL/6J mice. Microvascular changes were assessed by intravital microscopy in the right lung of anesthetized mice with open chest and ventilated lungs. Arteriolar tone in pulmonary arterioles (27.2-48.7 µm diameter) increased in CTRL mice (18.0 ± 11% constriction, P = 0.034, n = 5) but decreased in STZ mice (13.6 ± 7.5% dilation, P = 0.009, n = 5) after l-NAME. Lung tissue dihydroethidium (DHE) fluorescence (superoxide), inducible NOS expression, and protein nitrosylation (3-nitrotyrosine) increased in STZ mice and correlated with increased glucose levels (103.8 ± 8.8 mg/dL). Fluorescently labeled fibrinogen administration and fibrinogen immunostaining showed fibrinogen adhesion, indicating endothelial injury in STZ mice. In CTRL mice, vasoconstriction to l-NAME was likely due to the loss of bioavailable NO. Vasodilation in STZ mice may be due to decreased formation of a vasoconstrictor or emergence of a vasodilator. These findings provide novel evidence that DM targets the pulmonary microcirculation and that decreased NO bioavailability and increased precapillary arteriolar tone could potentially lead to ventilation-perfusion abnormalities, exacerbating systemic DM complications.NEW & NOTEWORTHY Diabetes pulmonary and microvascular consequences are well recognized but have not been characterized. We assessed lung microvascular changes in a live anesthetized mouse model of type 1 diabetes, using a novel intravital microscopy technique. Our results show new evidence that a diabetes-induced decrease in lung nitric oxide bioavailability underlies oxidative damage, enhanced platelet activation, and endothelial injury causing pulmonary microvascular dysfunction and altered vasoreactivity. These findings could provide novel strategies to prevent or reverse diabetes systemic consequences.
Collapse
Affiliation(s)
- Andrew M Roberts
- Department of Physiology, University of Louisville School of Medicine, Louisville, Kentucky
- Department of Pediatrics, Pediatric Research Institute, University of Louisville School of Medicine, Louisville, Kentucky
| | - Nayeem Z Moulana
- Department of Physiology, University of Louisville School of Medicine, Louisville, Kentucky
| | - Rekha Jagadapillai
- Department of Pediatrics, Pediatric Research Institute, University of Louisville School of Medicine, Louisville, Kentucky
| | - Lu Cai
- Department of Pediatrics, Pediatric Research Institute, University of Louisville School of Medicine, Louisville, Kentucky
| | - Evelyne Gozal
- Department of Physiology, University of Louisville School of Medicine, Louisville, Kentucky
- Department of Pediatrics, Pediatric Research Institute, University of Louisville School of Medicine, Louisville, Kentucky
| |
Collapse
|
|
12
|
Reduced Endothelial Leptin Signaling Increases Vascular Adrenergic Reactivity in a Mouse Model of Congenital Generalized Lipodystrophy. Int J Mol Sci 2021; 22:ijms221910596. [PMID: 34638939 PMCID: PMC8508873 DOI: 10.3390/ijms221910596] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Revised: 09/20/2021] [Accepted: 09/27/2021] [Indexed: 01/19/2023] Open
Abstract
The adipokine leptin, which is best-known for its role in the control of metabolic function, is also a master regulator of cardiovascular function. While leptin has been approved for the treatment of metabolic disorders in patients with congenital generalized lipodystrophy (CGL), the effects of chronic leptin deficiency and the treatment on vascular contractility remain unknown. Herein, we investigated the effects of leptin deficiency and treatment (0.3 mg/day/7 days) on aortic contractility in male Berardinelli-Seip 2 gene deficient mice (gBscl2-/-, model of CGL) and their wild-type control (gBscl2+/+), as well as in mice with selective deficiency in endothelial leptin receptor (LepREC-/-). Lipodystrophy selectively increased vascular adrenergic contractility via NO-independent mechanisms and induced hypertrophic vascular remodeling. Leptin treatment and Nox1 inhibition blunted adrenergic hypercontractility in gBscl2-/- mice, however, leptin failed to rescue vascular media thickness. Selective deficiency in endothelial leptin receptor did not alter baseline adrenergic contractility but abolished leptin-mediated reduction in adrenergic contractility, supporting the contribution of endothelium-dependent mechanisms. These data reveal a new direct role for endothelial leptin receptors in the control of vascular contractility and homeostasis, and present leptin as a safe therapy for the treatment of vascular disease in CGL.
Collapse
|
|
13
|
Rayyan-Assi H, Feldman B, Leventer-Roberts M, Akriv A, Raz I. The relationship between inpatient hyperglycaemia and mortality is modified by baseline glycaemic status. Diabetes Metab Res Rev 2021; 37:e3420. [PMID: 33137237 DOI: 10.1002/dmrr.3420] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2019] [Revised: 10/14/2020] [Accepted: 10/20/2020] [Indexed: 01/09/2023]
Abstract
AIMS There is a well-established association between inpatient hyperglycaemia and mortality. However, evidence is inconsistent regarding whether this association is differential among those with and without type 2 diabetes mellitus (T2DM). Most studies are based on convenience samples or are unable to adjust for comorbidities. We examined whether the association between hyperglycaemia and 30-day mortality was modified by baseline glycaemic status. MATERIALS AND METHODS This was a retrospective cohort study of 174,671 eligible hospitalized individuals between 2012 and 2015. Thirty-day mortality was assessed during the first inpatient stay up to 30 days post discharge. The adjusted association between hyperglycaemia and mortality was assessed with logistic regression models. Then, four interaction terms were entered into the model to assess if the association between hyperglycaemia and mortality differed by baseline glycaemic status. RESULTS The multivariate model demonstrated a 2.18-fold risk of mortality associated with hyperglycaemia (odds ratio [OR] [95%CI]: 2.19 [2.08-2.31]). Adding the interaction terms between hyperglycaemia and baseline glycaemic status the ORs of 30-day mortality were 1.41 (1.25-1.60) in non-T2DM status, 1.32 (1.16-1.51) in pre-diabetes status and 1.30 (1.04-1.62) in unscreened status, as compared to T2DM status with hyperglycaemia. CONCLUSIONS Hyperglycaemia is positively associated with mortality and both those without and with controlled T2DM are at highest risk. These findings may help medical staff identify potential increased risk of mortality upon hospital entry and discharge, and direct further research to assess how hyperglycaemia control and proactive deterioration prevention throughout the entire inpatient stay may prevent adverse outcomes.
Collapse
Affiliation(s)
- Hana'a Rayyan-Assi
- Clalit Research Institute, Chief Physician's Office, Clalit Health Services, Tel Aviv, Israel
| | - Becca Feldman
- Clalit Research Institute, Chief Physician's Office, Clalit Health Services, Tel Aviv, Israel
| | - Maya Leventer-Roberts
- Clalit Research Institute, Chief Physician's Office, Clalit Health Services, Tel Aviv, Israel
- Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Amichay Akriv
- Clalit Research Institute, Chief Physician's Office, Clalit Health Services, Tel Aviv, Israel
| | - Itamar Raz
- The Internal Medicine Unit, Hadassah Hebrew University Hospital, Jerusalem, Israel
| |
Collapse
|
|
14
|
McCarthy O, Pitt J, Wellman B, Eckstein ML, Moser O, Bain SC, Bracken RM. Blood Glucose Responses during Cardiopulmonary Incremental Exercise Testing in Type 1 Diabetes: A Pooled Analysis. Med Sci Sports Exerc 2021; 53:1142-1150. [PMID: 33315813 DOI: 10.1249/mss.0000000000002584] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
PURPOSE This study aimed to determine the glycemic responses to cardiopulmonary exercise testing (CPET) in individuals with type 1 diabetes (T1D) and to explore the influence of starting blood glucose (BG) concentrations on subsequent CPET outcomes. METHODS This study was a retrospective, secondary analysis of pooled data from three randomized crossover trials using identical CPET protocols. During cycling, cardiopulmonary variables were measured continuously, with BG and lactate values obtained minutely via capillary earlobe sampling. Anaerobic threshold was determined using ventilatory parameters. Participants were split into (i) euglycemic ([Eu] >3.9 to ≤10.0 mmol·L-1, n = 26) and (ii) hyperglycemic ([Hyper] >10.0 mmol·L-1, n = 10) groups based on preexercise BG concentrations. Data were assessed via general linear modeling techniques and regression analyses. P values of ≤0.05 were accepted as significant. RESULTS Data from 36 individuals with T1D (HbA1c, 7.3% ± 1.1% [56.0 ± 11.5 mmol·mol-1]) were included. BG remained equivalent to preexercise concentrations throughout CPET, with an overall change in BG of -0.32 ± 1.43 mmol·L-1. Hyper had higher HR at peak (+10 ± 2 bpm, P = 0.04) and during recovery (+9 ± 2 bpm, P = 0.038) as well as lower O2 pulse during the cool down period (-1.6 ± 0.04 mL per beat, P = 0.021). BG responses were comparable between glycemic groups. Higher preexercise BG led to greater lactate formation during exercise. HbA1c was inversely related to time to exhaustion (r = -0.388, P = 0.04) as well as peak power output (r = -0.355, P = 0.006) and O2 pulse (r = -0.308, P = 0.015). CONCLUSIONS This study demonstrated 1) stable BG responses to CPET in patients with T1D; 2) although preexercise hyperglycemia did not influence subsequent glycemic dynamics, it did potentiate alterations in various cardiac and metabolic responses to CPET; and 3) HbA1c was a significant factor in the determination of peak performance outcomes during CPET.
Collapse
Affiliation(s)
- Olivia McCarthy
- Applied Sport, Technology, Exercise and Medicine Research Centre (A-STEM), College of Engineering, Swansea University, Swansea, UNITED KINGDOM
| | - Jason Pitt
- Applied Sport, Technology, Exercise and Medicine Research Centre (A-STEM), College of Engineering, Swansea University, Swansea, UNITED KINGDOM
| | - Ben Wellman
- Applied Sport, Technology, Exercise and Medicine Research Centre (A-STEM), College of Engineering, Swansea University, Swansea, UNITED KINGDOM
| | | | | | - Stephen C Bain
- Diabetes Research Group, Medical School, Swansea University, Swansea, UNITED KINGDOM
| | | |
Collapse
|
|
15
|
Chen YC, Tsai SJ. Bilateral cerebral infarction in diabetic ketoacidosis and bilateral internal carotid artery occlusion: A case report and review of literature. World J Clin Cases 2021; 9:3787-3795. [PMID: 34046484 PMCID: PMC8130090 DOI: 10.12998/wjcc.v9.i15.3787] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Revised: 03/02/2021] [Accepted: 03/29/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Diabetic ketoacidosis (DKA) is a serious complication of type 1 diabetes mellitus (T1DM). Very rarely does DKA lead to cerebral edema, and it is even rarer for it to result in cerebral infarction. Bilateral internal carotid artery occlusion (BICAO) is also rare and can cause fatal stroke. Moreover, case reports about acute cerebral infarction throughout both internal carotid arteries with simultaneous BICAO are very scarce. In this study, we present a patient with BICAO, T1DM, hypertension, and hyperlipidemia, who had a catastrophic bilateral cerebral infarction after a DKA episode. We briefly introduce BICAO and the mechanisms by which DKA results in cerebral infarction. CASE SUMMARY A 41-year-old woman presented with ischemic stroke that took place 3 mo prior over the left corona radiata, bilateral frontal lobe, and parietal lobe with right hemiplegia and Broca's aphasia. She had a history of hypertension for 5 years, hyperlipidemia for 4 years, hyperthyroidism for 3 years, and T1DM for 31 years. The first brain magnetic resonance imaging not only revealed the aforementioned ischemic lesions but also bilateral internal carotid artery occlusion. She was admitted to our ward for rehabilitation due to prior stroke sequalae. DKA took place on hospital day 2. On hospital day 6, she had a new massive infarction over the bilateral anterior cerebral artery and middle cerebral artery territory. After weeks of aggressive treatment, she remained in a coma and on mechanical ventilation due to respiratory failure. After discussion with her family, compassionate extubation was performed on hospital day 29 and she died. CONCLUSION DKA can lead to cerebral infarction due to several mechanisms. In people with existing BICAO and several stroke risk factors such as hypertension, T1DM, hyperlipidemia, DKA has the potential to cause more serious ischemic strokes.
Collapse
Affiliation(s)
- Yi-Chung Chen
- Department of Physical Medicine and Rehabilitation, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
| | - Su-Ju Tsai
- Department of Physical Medicine and Rehabilitation, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
| |
Collapse
|
|
16
|
Yang T, Li Z, Jiang L, Xi X. Hyperlactacidemia as a risk factor for intensive care unit-acquired weakness in critically ill adult patients. Muscle Nerve 2021; 64:77-82. [PMID: 33831220 DOI: 10.1002/mus.27248] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Revised: 04/03/2021] [Accepted: 04/06/2021] [Indexed: 01/03/2023]
Abstract
INTRODUCTION/AIMS Intensive care unit-acquired weakness (ICUAW) is a severe neuromuscular complication of critical illness. Serum lactate is a useful biomarker in critically ill patients. The relationship between serum lactate level and ICUAW remains controversial. This study evaluated whether hyperlactacidemia (lactate level >2 mmol/L) was an independent risk factor for ICUAW in critically ill adult patients. METHODS An observational cohort study was performed in a general multidisciplinary intensive care unit (ICU). Sixty-eight consecutive adult critically ill patients without preexisting neuromuscular disease or a poor pre-ICU functional status whose length of ICU stay was 7 or more days were evaluated. Patients were screened daily for signs of awakening. Muscle strength assessment using the Medical Research Council score was performed on the first day a patient was considered awake. Patients with clinical muscle weakness were considered to have ICUAW. RESULTS Among the 68 patients who achieved a satisfactory state of consciousness, the diagnosis of ICUAW was made in 30 patients (44.1%). After multivariate analysis, hyperlactacidemia (P = .02), Acute Physiology and Chronic Health Evaluation II score (P = .04), duration of mechanical ventilation (P = .02), and the use of norepinephrine (P = .04) were found to be significantly associated with the development of ICUAW in critically ill patients. DISCUSSION This study shows a number of risk factors to be significantly associated with the development of ICUAW in critically ill adults. These factors should be considered when building early prediction models or designing prevention strategies for ICUAW in future studies.
Collapse
Affiliation(s)
- Tao Yang
- Department of Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,Department of Critical Care Medicine, Fu Xing Hospital, Capital Medical University, Beijing, China
| | - Zhiqiang Li
- Department of Critical Care Medicine, North China University of Science and Technology Affiliated Hospital, Tangshan, China
| | - Li Jiang
- Department of Critical Care Medicine, Fu Xing Hospital, Capital Medical University, Beijing, China
| | - Xiuming Xi
- Department of Critical Care Medicine, Fu Xing Hospital, Capital Medical University, Beijing, China
| |
Collapse
|
|
17
|
Song F, Zhou Y, Zhang K, Liang YF, He X, Li L. The role of the plasma glycosylated hemoglobin A1c/Apolipoprotein A-l ratio in predicting cardiovascular outcomes in acute coronary syndrome. Nutr Metab Cardiovasc Dis 2021; 31:570-578. [PMID: 33358616 DOI: 10.1016/j.numecd.2020.10.008] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Revised: 09/30/2020] [Accepted: 10/12/2020] [Indexed: 01/25/2023]
Abstract
BACKGROUND AND AIMS Glucose and lipid metabolism are major prognostic indicators of coronary heart disease. The ratio of plasma glycosylated hemoglobin A1c (HbA1c) to apolipoprotein A-l (ApoA-l) is an indirect measure of insulin resistance. The study aimed to evaluate whether the HbA1c/ApoA-1 ratio can predict the prognosis in patients with the acute coronary syndrome (ACS). METHODS AND RESULTS A total of 476 ACS patients diagnosed by coronary angiography were enrolled in this longitudinal, observational, retrospective study. Plasma HbA1c, fasting blood glucose and lipid profile were measured. Patients were stratified according to the tertiles of HbA1c/ApoA-l levels. Cox proportional hazard model was used to examine the predictive value of HbA1c/ApoA-l for study endpoints. The association between the Log HbA1c/ApoA-l ratio and major adverse cardiovascular events (MACEs) was estimated using multiple logistic regression. Baseline characteristics showed a mean age of 66 ± 8 years, and 52.5% were hypertensive, 26.8% diabetic, and 54.5% current or prior smokers. During a mean follow-up period of 22.3 ± 1.7 months, 59 deaths occurred. After adjusting for age, gender, smoking, hypertension, diabetes, and coronary artery disease severity, patients in the highest HbA1c/ApoA-l ratio tertile had a 4.36-fold increased risk of mortality compared with those in the lowest tertile. The multivariate logistic regression showed that the Log HbA1c/ApoA-l ratio was associated with MACEs (Odds ratio 2.95, p = 0.013). CONCLUSION After adjusting for traditional cardiovascular risk factors and ACS severity scores, the HbA1c/ApoA-1 ratio remained an independent predictor of all-cause mortality and MACEs in the ACS patients undergoing angiography.
Collapse
Affiliation(s)
- Feier Song
- Department of Emergency and Critical Care Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.
| | - Yu Zhou
- Division of Vascular Surgery, National-Local Joint Engineering Laboratory of Vascular Disease Treatment, Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangdong Engineering Laboratory of Diagnosis and Treatment of Vascular Disease, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.
| | - Kunyi Zhang
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, 510060, China; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, 510060, China.
| | - Yuan-Feng Liang
- General Division, Guangdong Geriatric Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.
| | - Xuyu He
- Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.
| | - Liwen Li
- Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.
| |
Collapse
|
|
18
|
Role of Fluid Milk in Attenuating Postprandial Hyperglycemia and Hypertriglyceridemia. Nutrients 2020; 12:nu12123806. [PMID: 33322540 PMCID: PMC7763034 DOI: 10.3390/nu12123806] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2020] [Revised: 12/07/2020] [Accepted: 12/08/2020] [Indexed: 12/18/2022] Open
Abstract
Postprandial plasma glucose and triglyceride concentrations are predictive of relative cardiovascular disease (CVD) risk, and the pathogenesis of both insulin resistance and atherosclerosis has been attributed to acute states of hyperglycemia and hypertriglyceridemia. Postprandial lipemia and hyperglycemia suppress vascular reactivity and induce endothelial dysfunction. Epidemiological studies suggest that chronically-high consumption of milk and milk products is associated with a reduced risk of type 2 diabetes, metabolic syndrome, and CVD. The addition of dairy products to meals high in carbohydrates and fat may lessen these risks through reductions in postprandial glucose and triglyceride responses. Purported mechanisms include dairy proteins and bioactive compounds, which may explain the inverse relationship between dairy consumption and cardiometabolic diseases. The current review evaluates the available literature describing the relationships between metabolic dysfunction, postprandial metabolism, and vascular dysfunction and discusses the potential role of milk and dairy products in attenuating these impairments.
Collapse
|
|
19
|
Au JS, Beaudry KM, Pancevski K, Hughson RL, Devries MC. The impact of preconditioning exercise on the vascular response to an oral glucose challenge. Appl Physiol Nutr Metab 2020; 46:443-451. [PMID: 33113337 DOI: 10.1139/apnm-2020-0559] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Exercise elicits direct benefits to insulin sensitivity but may also indirectly improve glucose uptake by hemodynamic conditioning of the vasculature. The purpose of this study was to examine the modifying effect of 3 different types of exercise on the vascular response to an oral glucose challenge. Twenty healthy adults (9 women, 11 men; aged 23 ± 3 years) completed a standard oral glucose tolerance test (OGTT) at rest, as well as 1.5 hours after moderate continuous cycling exercise (30 min; 65% peak oxygen consumption), high-intensity interval cycling exercise (10 × 1 min at 90% peak heart rate), and lower-load higher-repetition resistance exercise (25-35 repetitions/set, 3 sets). Brachial and superficial femoral artery blood flow, conductance, and oscillatory shear index were measured throughout the OGTT. Regardless of rested state or exercise preconditioning, the OGTT induced reductions in brachial artery blood flow and conductance (p < 0.001), and transient increases in brachial and superficial femoral artery oscillatory shear index and retrograde blood flow (p < 0.01). Continuous cycling and resistance exercise were followed with a small degree of protection against prolonged periods of oscillatory flow. Our findings imply transient peripheral vasoconstriction and decreased limb blood flow during a standard OGTT, for which prior exercise was unable to prevent in healthy adults. Novelty: We investigated the impact of continuous, interval, and resistance exercise on the hemodynamic response to an OGTT. Our findings suggest decreased upper-limb blood flow during an OGTT is not prevented by prior exercise in healthy adults.
Collapse
Affiliation(s)
- Jason S Au
- Department of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada
| | - Kayleigh M Beaudry
- Department of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada
| | - Kristian Pancevski
- Department of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada
| | - Richard L Hughson
- Department of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada.,Schlegel-University of Waterloo Research Institute for Aging, Waterloo, Ontario, Canada
| | - Michaela C Devries
- Department of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada
| |
Collapse
|
|
20
|
Gische C, West SG, Voelkle MC. Forecasting Causal Effects of Interventions versus Predicting Future Outcomes. STRUCTURAL EQUATION MODELING : A MULTIDISCIPLINARY JOURNAL 2020; 28:475-492. [PMID: 35464622 PMCID: PMC9030387 DOI: 10.1080/10705511.2020.1780598] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/24/2023]
Abstract
The present article provides a didactic presentation and extension of selected features of Pearl's DAG-based approach to causal inference for researchers familiar with structural equation modeling. We illustrate key concepts using a cross-lagged panel design. We distinguish between (a) forecasts of the value of an outcome variable after an intervention and (b) predictions of future values of an outcome variable. We consider the mean level and variance of the outcome variable as well as the probability that the outcome will fall within an acceptable range. We extend this basic approach to include additive random effects, allowing us to distinguish between average effects of interventions and person-specific effects of interventions. We derive optimal person-specific treatment levels and show that optimal treatment levels may differ across individuals. We present worked examples using simulated data based on the results of a prior empirical study of the relationship between blood insulin and glucose levels.
Collapse
Affiliation(s)
| | | | - Manuel C. Voelkle
- Humboldt-Universität zu Berlin, Germany
- Max Planck Institute for Human Development, Germany
| |
Collapse
|
|
21
|
de Marañón AM, Iannantuoni F, Abad-Jiménez Z, Canet F, Díaz-Pozo P, López-Domènech S, Roldán-Torres I, Morillas C, Rocha M, Víctor VM. Association between Proinflammatory Markers, Leukocyte-Endothelium Interactions, and Carotid Intima-Media Thickness in Type 2 Diabetes: Role of Glycemic Control. J Clin Med 2020; 9:E2522. [PMID: 32764458 PMCID: PMC7465892 DOI: 10.3390/jcm9082522] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Revised: 07/23/2020] [Accepted: 07/29/2020] [Indexed: 12/12/2022] Open
Abstract
Glycated hemoglobin monitorization could be a tool for maintaining type 2 diabetes (T2D) under control and delaying the appearance of cardiovascular events. This cross-sectional study was designed to assess the role of glycemic control in modulating early-stage markers of cardiovascular complications. One hundred and eight healthy controls and 161 type 2 diabetic patients were recruited and distributed according to their glycemic control, setting the threshold at 6.5% (good control). Biochemical and anthropometrical parameters were registered during the initial visit, and peripheral blood was extracted to obtain polymorphonuclear cells and analyze inflammatory markers, adhesion molecules, leukocyte-endothelium interactions, and carotid intima-media thickness. Correlations between these parameters were explored. We found that inflammatory markers and adhesion molecules were augmented in type 2 diabetic subjects with poor glycemic control. Polymorphonuclear leukocytes interacted more with the endothelium in the diabetic population, and even more significantly in the poorly controlled subjects. In parallel, carotid intima-media thickness was also increased in the diabetic population, and the difference was greater among poorly controlled subjects. Finally, correlation measurement revealed that carotid intima-media thickness was related to glycemic control and lipid metabolism in diabetic patients. Our results suggest that glycemic control delays the onset of cardiovascular comorbidities in diabetic subjects.
Collapse
Affiliation(s)
- Aranzazu Martinez de Marañón
- Service of Endocrinology and Nutrition, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), 46017 Valencia, Spain; (A.M.d.M.); (F.I.); (Z.A.-J.); (F.C.); (P.D.-P.); (S.L.-D.); (C.M.)
| | - Francesca Iannantuoni
- Service of Endocrinology and Nutrition, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), 46017 Valencia, Spain; (A.M.d.M.); (F.I.); (Z.A.-J.); (F.C.); (P.D.-P.); (S.L.-D.); (C.M.)
| | - Zaida Abad-Jiménez
- Service of Endocrinology and Nutrition, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), 46017 Valencia, Spain; (A.M.d.M.); (F.I.); (Z.A.-J.); (F.C.); (P.D.-P.); (S.L.-D.); (C.M.)
| | - Francisco Canet
- Service of Endocrinology and Nutrition, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), 46017 Valencia, Spain; (A.M.d.M.); (F.I.); (Z.A.-J.); (F.C.); (P.D.-P.); (S.L.-D.); (C.M.)
| | - Pedro Díaz-Pozo
- Service of Endocrinology and Nutrition, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), 46017 Valencia, Spain; (A.M.d.M.); (F.I.); (Z.A.-J.); (F.C.); (P.D.-P.); (S.L.-D.); (C.M.)
| | - Sandra López-Domènech
- Service of Endocrinology and Nutrition, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), 46017 Valencia, Spain; (A.M.d.M.); (F.I.); (Z.A.-J.); (F.C.); (P.D.-P.); (S.L.-D.); (C.M.)
| | - Ildefonso Roldán-Torres
- Service of Cardiology, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), 46017 Valencia, Spain;
| | - Carlos Morillas
- Service of Endocrinology and Nutrition, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), 46017 Valencia, Spain; (A.M.d.M.); (F.I.); (Z.A.-J.); (F.C.); (P.D.-P.); (S.L.-D.); (C.M.)
| | - Milagros Rocha
- Service of Endocrinology and Nutrition, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), 46017 Valencia, Spain; (A.M.d.M.); (F.I.); (Z.A.-J.); (F.C.); (P.D.-P.); (S.L.-D.); (C.M.)
- Centro de Investigación Biomédica en Red (CIBERehd)—Department of Pharmacology, University of Valencia, 46010 Valencia, Spain
| | - Víctor M. Víctor
- Service of Endocrinology and Nutrition, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), 46017 Valencia, Spain; (A.M.d.M.); (F.I.); (Z.A.-J.); (F.C.); (P.D.-P.); (S.L.-D.); (C.M.)
- Centro de Investigación Biomédica en Red (CIBERehd)—Department of Pharmacology, University of Valencia, 46010 Valencia, Spain
- Department of Physiology, University of Valencia, 46010 Valencia, Spain
| |
Collapse
|
|
22
|
Feng L, Yang J, Zhang S, Zhang L, Chen X, Li P, Gao Y, Xie S, Zhang Y, Wang H. A capillary-based fluorimetric platform for the evaluation of glucose in blood using gold nanoclusters and glucose oxidase in the ZIF-8 matrix. Analyst 2020; 145:5273-5279. [PMID: 32658223 DOI: 10.1039/d0an01090a] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
A capillary-based fluorimetric analysis method was developed for probing glucose (Glu) in blood using Glu oxidase-anchored gold nanoclusters (GOD-AuNCs) and the ZIF-8 matrix. AuNCs were attached with GOD to be further encapsulated into the ZIF-8 matrix through the protein-mediated formation route. The resulting GOD-AuNCs@ZIF-8 nanocomposites could present the AuNC-improved catalysis of GOD and ZIF-8-improved environmental stability. The ZIF-8-enhanced fluorescence intensity of AuNCs could also be expected. Moreover, a capillary-based fluorometric platform was constructed for sensing Glu by coating the capillaries first with GOD-AuNCs and then the ZIF-8 matrix. Herein, Glu was introduced through the self-driven sampling to trigger the GOD-catalyzed production of hydrogen peroxide, which could induce the fluorescence quenching rationally depending on the Glu concentrations. The developed fluorimetric method could allow for the rapid and simple detection of Glu with the concentrations linearly ranging from 5.0 μM to 2.5 mM. Besides, the feasibility of practical applications was demonstrated by the evaluation of Glu in blood showing the recoveries of 96.2%-103.4%. Importantly, the proposed design of the capillary-based fluorimetric platform by the synergetic combination of catalysis-specific recognition and fluorescence signaling may open a new door toward extensive applications in the biological sensing, catalysis, and imaging fields.
Collapse
Affiliation(s)
- Luping Feng
- Institute of Medicine and Materials Applied Technologies, College of Chemistry and Chemical Engineering, Qufu Normal University, Qufu, Shandong 273165, P. R. China.
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
23
|
Parker L, Morrison DJ, Betik AC, Roberts-Thomson K, Kaur G, Wadley GD, Shaw CS, Keske MA. High-glucose mixed-nutrient meal ingestion impairs skeletal muscle microvascular blood flow in healthy young men. Am J Physiol Endocrinol Metab 2020; 318:E1014-E1021. [PMID: 32286881 DOI: 10.1152/ajpendo.00540.2019] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
Oral glucose ingestion leads to impaired muscle microvascular blood flow (MBF), which may contribute to acute hyperglycemia-induced insulin resistance. We investigated whether incorporating lipids and protein into a high-glucose load would prevent postprandial MBF dysfunction. Ten healthy young men (age, 27 yr [24, 30], mean with lower and upper bounds of the 95% confidence interval; height, 180 cm [174, 185]; weight, 77 kg [70, 84]) ingested a high-glucose (1.1 g/kg glucose) mixed-nutrient meal (10 kcal/kg; 45% carbohydrate, 20% protein, and 35% fat) in the morning after an overnight fast. Femoral arterial blood flow was measured via Doppler ultrasound, and thigh MBF was measured via contrast-enhanced ultrasound, before meal ingestion and 1 h and 2 h postprandially. Blood glucose and plasma insulin were measured at baseline and every 15 min throughout the 2-h postprandial period. Compared with baseline, thigh muscle microvascular blood volume, velocity, and flow were significantly impaired at 60 min postprandial (-25%, -27%, and -46%, respectively; all P < 0.05) and to a greater extent at 120 min postprandial (-37%, -46%, and -64%; all P < 0.01). Heart rate and femoral arterial diameter, blood velocity, and blood flow were significantly increased at 60 min and 120 min postprandial (all P < 0.05). Higher blood glucose area under the curve was correlated with greater MBF dysfunction (R2 = 0.742; P < 0.001). Ingestion of a high-glucose mixed-nutrient meal impairs MBF in healthy individuals for up to 2 h postprandial.
Collapse
Affiliation(s)
- Lewan Parker
- Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Geelong, Victoria, Australia
| | - Dale J Morrison
- Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Geelong, Victoria, Australia
| | - Andrew C Betik
- Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Geelong, Victoria, Australia
| | - Katherine Roberts-Thomson
- Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Geelong, Victoria, Australia
| | - Gunveen Kaur
- Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Geelong, Victoria, Australia
| | - Glenn D Wadley
- Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Geelong, Victoria, Australia
| | - Christopher S Shaw
- Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Geelong, Victoria, Australia
| | - Michelle A Keske
- Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Geelong, Victoria, Australia
| |
Collapse
|
|
24
|
Bock JM, Iwamoto E, Horak JG, Feider AJ, Hanada S, Casey DP. Aerobic exercise offsets endothelial dysfunction induced by repetitive consumption of sugar-sweetened beverages in young healthy men. Am J Physiol Regul Integr Comp Physiol 2020; 319:R11-R18. [PMID: 32401628 DOI: 10.1152/ajpregu.00055.2020] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Consumption of a single, sugar-sweetened beverage (SSB) impairs vascular endothelial function. Regular aerobic exercise improves endothelium-dependent vasodilation; however, it is unknown whether these beneficial effects persist with frequent SSB consumption. Therefore, the purpose of this study was twofold; we studied the effects of repetitive SSB consumption (75 g d-glucose, 3 times/day) for 1 wk (Glu, n = 13, 23 ± 4 yr, 23.5 ± 3.4 kg/m2) on endothelium-dependent vasodilation (FMD). Then, in a separate cohort, we investigated whether 45 min of moderate-intensity aerobic exercise on five separate days offset the hypothesized decrease in FMD during the Glu protocol (Glu+Ex, n = 11, 21 ± 3 yr, 23.8 ± 2.4 kg/m2). Baseline, fasting [glucose] (P = 0.15), [insulin] (P = 0.25), %FMD (P = 0.48), absolute FMD (P = 0.66), and shear rate area under the curve (SRAUC; P = 0.82) were similar between groups. Following the interventions, fasting [glucose] (Glu: 94 ± 6 to 92 ± 6 mg/dL, Glu+Ex: 89 ± 8 to 87 ± 6 mg/dL, P = 0.74) and [insulin] (Glu: 11.3 ± 6.2 to 11.8 ± 8.9 μU/mL, Glu+Ex: 8.7 ± 2.9 to 9.4 ± 3.2 μU/mL, P = 0.89) were unchanged. %FMD was reduced in Glu (6.1 ± 2.2 to 5.1 ± 1.3%) and increased in Glu+Ex (6.6 ± 2.2 to 7.8 ± 2.4%, P < 0.05 for both). SRAUC increased similarly in both Glu [17,715 ± 8,275 to 22,922 ± 4,808 arbitrary units (A.U.)] and Glu+Ex (18,216 ± 4,516 to 21,666 ± 5,392 A.U., main effect of time P < 0.05). When %FMD was adjusted for SRAUC, attenuation was observed in Glu (0.41 ± 0.18 to 0.23 ± 0.08%/s × 103, P < 0.05) but not Glu+Ex (0.38 ± 0.14 to 0.38 ± 0.13%/s × 103, P = 0.88). Despite unchanged fasting [glucose] and [insulin], repeated consumption of SSBs impaired conduit artery vascular endothelial function. Additionally, subjects who engaged in regular moderate-intensity aerobic exercise did not demonstrate the same SSB-induced endothelial dysfunction. Collectively, these data suggest aerobic exercise may offset the deleterious effects of repetitive SSB consumption.
Collapse
Affiliation(s)
- Joshua M Bock
- Department of Physical Therapy and Rehabilitation Science, University of Iowa, Iowa City, Iowa
| | - Erika Iwamoto
- Department of Physical Therapy and Rehabilitation Science, University of Iowa, Iowa City, Iowa.,School of Health Sciences, Sapporo Medical University, Sapporo, Japan
| | - Jeffrey G Horak
- Department of Physical Therapy and Rehabilitation Science, University of Iowa, Iowa City, Iowa
| | - Andrew J Feider
- Department of Anesthesia, University of Iowa, Iowa City, Iowa
| | - Satoshi Hanada
- Department of Anesthesia, University of Iowa, Iowa City, Iowa
| | - Darren P Casey
- Department of Physical Therapy and Rehabilitation Science, University of Iowa, Iowa City, Iowa.,Abboud Cardiovascular University of Iowa, Iowa City, Iowa.,Fraternal Order of Eagles Diabetes Research Center, Carver College of Medicine, University of Iowa, Iowa City, Iowa
| |
Collapse
|
|
25
|
Libert C, Ayala A, Bauer M, Cavaillon JM, Deutschman C, Frostell C, Knapp S, Kozlov AV, Wang P, Osuchowski MF, Remick DG. Part II: Minimum Quality Threshold in Preclinical Sepsis Studies (MQTiPSS) for Types of Infections and Organ Dysfunction Endpoints. Shock 2020; 51:23-32. [PMID: 30106873 DOI: 10.1097/shk.0000000000001242] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Although the clinical definitions of sepsis and recommended treatments are regularly updated, a systematic review has not been done for preclinical models. To address this deficit, a Wiggers-Bernard Conference on preclinical sepsis modeling reviewed the 260 most highly cited papers between 2003 and 2012 using sepsis models to create a series of recommendations. This Part II report provides recommendations for the types of infections and documentation of organ injury in preclinical sepsis models. Concerning the types of infections, the review showed that the cecal ligation and puncture model was used for 44% of the studies while 40% injected endotoxin. Recommendation #8 (numbered sequentially from Part I): endotoxin injection should not be considered as a model of sepsis; live bacteria or fungal strains derived from clinical isolates are more appropriate. Recommendation #9: microorganisms should replicate those typically found in human sepsis. Sepsis-3 states that sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection, but the review of the papers showed limited attempts to document organ dysfunction. Recommendation #10: organ dysfunction definitions should be used in preclinical models. Recommendation #11: not all activities in an organ/system need to be abnormal to verify organ dysfunction. Recommendation #12: organ dysfunction should be measured in an objective manner using reproducible scoring systems. Recommendation #13: not all experiments must measure all parameters of organ dysfunction, but investigators should attempt to fully capture as much information as possible. These recommendations are proposed as "best practices" for animal models of sepsis.
Collapse
Affiliation(s)
- Claude Libert
- Center for Inflammation Research, VIB, Ghent, Belgium.,Ghent University, Ghent, Belgium
| | - Alfred Ayala
- Rhode Island Hospital & Alpert School of Medicine at Brown University, Providence, Rhode Island
| | | | | | - Clifford Deutschman
- Feinstein Institute for Medical Research, Northwell Health, Manhasset, New York
| | - Claes Frostell
- Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden
| | | | - Andrey V Kozlov
- Ludwig Boltzmann Institute for Experimental and Clinical Traumatology in the AUVA Research Center, Vienna, Austria
| | - Ping Wang
- Feinstein Institute for Medical Research, Manhasset, New York
| | - Marcin F Osuchowski
- Ludwig Boltzmann Institute for Experimental and Clinical Traumatology in the AUVA Research Center, Vienna, Austria
| | | |
Collapse
|
|
26
|
Roberts-Thomson KM, Betik AC, Premilovac D, Rattigan S, Richards SM, Ross RM, Russell RD, Kaur G, Parker L, Keske MA. Postprandial microvascular blood flow in skeletal muscle: Similarities and disparities to the hyperinsulinaemic-euglycaemic clamp. Clin Exp Pharmacol Physiol 2019; 47:725-737. [PMID: 31868941 DOI: 10.1111/1440-1681.13237] [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: 07/27/2019] [Revised: 12/12/2019] [Accepted: 12/18/2019] [Indexed: 12/22/2022]
Abstract
Skeletal muscle contributes to ~40% of total body mass and has numerous important mechanical and metabolic roles in the body. Skeletal muscle is a major site for glucose disposal following a meal. Consequently, skeletal muscle plays an important role in postprandial blood glucose homeostasis. Over the past number of decades, research has demonstrated that insulin has an important role in vasodilating the vasculature in skeletal muscle in response to an insulin infusion (hyperinsulinaemic-euglycaemic clamp) or following the ingestion of a meal. This vascular action of insulin is pivotal for glucose disposal in skeletal muscle, as insulin-stimulated vasodilation increases the delivery of both glucose and insulin to the myocyte. Notably, in insulin-resistant states such as obesity and type 2 diabetes, this vascular response of insulin in skeletal muscle is significantly impaired. Whereas the majority of work in this field has focussed on the action of insulin alone on skeletal muscle microvascular blood flow and myocyte glucose metabolism, there is less understanding of how the consumption of a meal may affect skeletal muscle blood flow. This is in part due to complex variations in glucose and insulin dynamics that occurs postprandially-with changes in humoral concentrations of glucose, insulin, amino acids, gut and pancreatic peptides-compared to the hyperinsulinaemic-euglycaemic clamp. This review will address the emerging body of evidence to suggest that postprandial blood flow responses in skeletal muscle may be a function of the nutritional composition of a meal.
Collapse
Affiliation(s)
- Katherine M Roberts-Thomson
- Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Geelong, VIC, Australia
| | - Andrew C Betik
- Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Geelong, VIC, Australia
| | - Dino Premilovac
- School of Medicine, University of Tasmania, Hobart, TAS, Australia
| | - Stephen Rattigan
- Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia
| | | | - Renee M Ross
- School of Medicine, University of Tasmania, Hobart, TAS, Australia
| | - Ryan D Russell
- Department of Health and Human Performance, College of Health Professions, University of Texas Rio Grande Valley, Brownsville, TX, USA
| | - Gunveen Kaur
- Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Geelong, VIC, Australia
| | - Lewan Parker
- Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Geelong, VIC, Australia
| | - Michelle A Keske
- Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Geelong, VIC, Australia.,Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia
| |
Collapse
|
|
27
|
Liu H, Liu J, Zhao H, Wang H. Relationship between glycated hemoglobin and low Ankle-Brachial Index: a cross-sectional observational study from the Beijing Vascular Disease Evaluation Study (BEST Study). INT ANGIOL 2019; 38:502-507. [PMID: 31782279 DOI: 10.23736/s0392-9590.19.04210-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
BACKGROUND Studies have confirmed that the low Ankle Brachial Index (ABI) and high glycated hemoglobin (HbA1c) level were both risk factors of cardiovascular disease (CVD). However, the association has rarely been explored between ABI and HbA1c. This study was to evaluate the independent relationship between HbA1c and low ABI. METHODS A total of 3102 subjects (male 1539, female 1563, aged 67.72±10.69 years) were enrolled into the study from 2010 to 2018. The odds ratio (OR) and linear regression coefficient of low ABI group (defined as ABI≤0.9) and ABI value in associations with the HbA1c were modelled using multivariable logistic and linear regression analyses by adjusting for possible confounders. RESULTS Compared with participants with normal ABI, those presenting the low ABI showed a significantly older age, smoking rate, higher level of heart rate (HR), systolic blood pressure (SBP), pulse pressure (PP), fasting plasma glucose (FPG), triglyceride (TG), highly sensitive C-reactive protein (hs-CRP), HbA1c and carotid femoral pulse wave velocity (CF-PWV); and higher prevalence rate of hypertension, diabetes, coronary artery disease (CAD); and higher rate on medication of statins, diabetes drug and cardiovascular drug (all P<0.001). After multiple adjustment for age, sex, smoke, FPG, blood lipids, hs-CRP, SBP, diastolic blood pressure (DBP), PP, CF-PWV, hypertension, diabetes, CAD and medications, the OR of HbA1c for low ABI was of statistical significance (95% CI: 1.204-1.410, P<0.001). After further multivariate adjustment analysis by linear regression, with left and right ABI as dependent variables, the results showed that HbA1c was independently linearly correlated to left and right ABI (all P<0.001). CONCLUSIONS HbA1c was an independent associated factor of lower ABI and linearly correlated to ABI level independent of fasting plasma glucose and other cardiovascular factors. We should not only focus on the HbA1c in diabetes mellitus patients, but also people with lower ABI.
Collapse
Affiliation(s)
- Huan Liu
- Department of Vascular Medicine, Peking University Shougang Hospital, Beijing, China
| | - Jinbo Liu
- Department of Vascular Medicine, Peking University Shougang Hospital, Beijing, China
| | - Hongwei Zhao
- Department of Vascular Medicine, Peking University Shougang Hospital, Beijing, China
| | - Hongyu Wang
- Department of Vascular Medicine, Peking University Shougang Hospital, Beijing, China -
| | | |
Collapse
|
|
28
|
The Postprandial Appearance of Features of Cardiometabolic Risk: Acute Induction and Prevention by Nutrients and Other Dietary Substances. Nutrients 2019; 11:nu11091963. [PMID: 31438565 PMCID: PMC6770341 DOI: 10.3390/nu11091963] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2019] [Revised: 08/18/2019] [Accepted: 08/19/2019] [Indexed: 12/11/2022] Open
Abstract
The purpose of this review is to provide an overview of diets, food, and food components that affect postprandial inflammation, endothelial function, and oxidative stress, which are related to cardiometabolic risk. A high-energy meal, rich in saturated fat and sugars, induces the transient appearance of a series of metabolic, signaling and physiological dysregulations or dysfunctions, including oxidative stress, low-grade inflammation, and endothelial dysfunction, which are directly related to the amplitude of postprandial plasma triglycerides and glucose. Low-grade inflammation and endothelial dysfunction are also known to cluster together with insulin resistance, a third risk factor for cardiovascular diseases (CVD) and type-II diabetes, thus making a considerable contribution to cardiometabolic risk. Because of the marked relevance of the postprandial model to nutritional pathophysiology, many studies have investigated whether adding various nutrients and other substances to such a challenge meal might mitigate the onset of these adverse effects. Some foods (e.g., nuts, berries, and citrus), nutrients (e.g., l-arginine), and other substances (various polyphenols) have been widely studied. Reports of favorable effects in the postprandial state have concerned plasma markers for systemic or vascular pro-inflammatory conditions, the activation of inflammatory pathways in plasma monocytes, vascular endothelial function (mostly assessed using physiological criteria), and postprandial oxidative stress. Although the literature is fragmented, this topic warrants further study using multiple endpoints and markers to investigate whether the interesting candidates identified might prevent or limit the postprandial appearance of critical features of cardiometabolic risk.
Collapse
|
|
29
|
Henriksson P, Lind L, Qing L, Freyschuss A. Microvascular capillary assessment in relation to forearm blood flow. Clin Physiol Funct Imaging 2019; 39:322-326. [PMID: 31074581 DOI: 10.1111/cpf.12575] [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: 11/05/2018] [Accepted: 04/25/2019] [Indexed: 12/01/2022]
Abstract
OBJECTIVE To study whether vascular reactivity as assessed by the methods forearm blood flow (FBF) and postocclusive reactive hyperaemia (PRH) in the nail fold was related as a measure of endothelium-dependent vasodilation in the microcirculation. METHODS Microvascular reactivity was assessed in forearm blood flow and in the nail fold by vital capillaroscopy of individual microvessels as postocclusive reactive hyperaemia. Vascular reactivity was assessed at baseline (n = 25) as well as after infusion of acetylcholine and of sodium nitroprusside (n = 13). We also performed a multivariate regression analysis to assess whether forearm blood flow or flow-mediated dilatation related to postocclusive reactive hyperaemia. RESULTS This study showed a distinct microvascular response to both acetylcholine (endothelium-dependent vasodilation) and sodium nitroprusside (endothelium-independent vasodilation) during forearm blood flow assessment and postocclusive reactive hyperaemia assessment in the nail fold (n = 13). These changes were inversely related (r- = -0·57; P<0·05). CONCLUSIONS Forearm blood flow was inversely correlated to postocclusive reactive hyperaemia. Postocclusive reactive hyperaemia was shortened after infusion with both acetylcholine and sodium nitroprusside. This occurred in parallel with the expected increase in forearm blood flow, conceivably reflecting that both methods can be used to assess endothelium-dependent vasodilation in the microcirculation.
Collapse
Affiliation(s)
- Peter Henriksson
- Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden
| | - Lars Lind
- Department of Medical Sciences, Uppsala University, Stockholm, Sweden
| | - Lu Qing
- Division of Clinical Chemistry, Department of Medicine, Karolinska University Hospital, Stockholm, Sweden
| | - Anna Freyschuss
- Department of Medicine, Karolinska University Hospital, Stockholm, Sweden
| |
Collapse
|
|
30
|
Mahdi A, Kövamees O, Checa A, Wheelock CE, von Heijne M, Alvarsson M, Pernow J. Arginase inhibition improves endothelial function in patients with type 2 diabetes mellitus despite intensive glucose-lowering therapy. J Intern Med 2018; 284:388-398. [PMID: 30151846 DOI: 10.1111/joim.12785] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Arginase is implicated in the pathogenesis behind endothelial dysfunction in type 2 diabetes mellitus (T2DM) by its inhibition of nitric oxide formation. Strict glycaemic control is not sufficient to improve endothelial function or cardiovascular outcomes in patients with T2DM, thus other treatment strategies are needed. We hypothesized that arginase inhibition improves endothelial function beyond glucose-lowering therapy following glucose optimization in patients with poorly controlled T2DM. METHODS AND RESULTS Endothelial function was evaluated in 16 patients with poorly controlled T2DM (visit 1) and 16 age-matched controls using venous occlusion plethysmography. T2DM patients were re-evaluated (visit 2) after intensive glucose-lowering regimen. Endothelium-dependent (EDV) and -independent (EIDV) vasodilatations were evaluated before and after 120 min intra-arterial infusion of the arginase inhibitor N(ω)-hydroxy-nor-L-arginine (nor-NOHA). HbA1c was reduced from 87 ± 17 (visit 1) to 65 ± 11 mmol mol-1 (visit 2, P < 0.001). Basal EDV, but not EIDV, was significantly lower in patients with T2DM than in healthy subjects (P < 0.05). EDV and EIDV were unaffected by glucose-lowering regimen in patients with T2DM. Arginase inhibition enhanced EDV in T2DM patients both at visit 1 and visit 2 (P < 0.01). There was no difference in improvement in EDV between the two occasions. EIDV was unaltered by nor-NOHA in T2DM at visit 1, but was slightly improved at visit 2. CONCLUSIONS Arginase inhibition improves endothelial function in patients with poorly controlled T2DM, which is maintained following glucose optimization. Thus, arginase inhibition is a promising therapeutic target beyond glucose lowering for improving endothelial function in T2DM patients.
Collapse
Affiliation(s)
- A Mahdi
- Division of Cardiology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - O Kövamees
- Division of Cardiology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - A Checa
- Division of Physiological Chemistry 2, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - C E Wheelock
- Division of Physiological Chemistry 2, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - M von Heijne
- Division of Endocrinology, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - M Alvarsson
- Division of Endocrinology and Diabetology, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - J Pernow
- Division of Cardiology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| |
Collapse
|
|
31
|
Russell RD, Hu D, Greenaway T, Sharman JE, Rattigan S, Richards SM, Keske MA. Oral glucose challenge impairs skeletal muscle microvascular blood flow in healthy people. Am J Physiol Endocrinol Metab 2018; 315:E307-E315. [PMID: 29763373 DOI: 10.1152/ajpendo.00448.2017] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Skeletal muscle microvascular (capillary) blood flow increases in the postprandial state or during insulin infusion due to dilation of precapillary arterioles to augment glucose disposal. This effect occurs independently of changes in large artery function. However, acute hyperglycemia impairs vascular function, causes insulin to vasoconstrict precapillary arterioles, and causes muscle insulin resistance in vivo. We hypothesized that acute hyperglycemia impairs postprandial muscle microvascular perfusion, without disrupting normal large artery hemodynamics, in healthy humans. Fifteen healthy people (5 F/10 M) underwent an oral glucose challenge (OGC, 50 g glucose) and a mixed-meal challenge (MMC) on two separate occasions (randomized, crossover design). At 1 h, both challenges produced a comparable increase (6-fold) in plasma insulin levels. However, the OGC produced a 1.5-fold higher increase in blood glucose compared with the MMC 1 h postingestion. Forearm muscle microvascular blood volume and flow (contrast-enhanced ultrasound) were increased during the MMC (1.3- and 1.9-fold from baseline, respectively, P < 0.05 for both) but decreased during the OGC (0.7- and 0.6-fold from baseline, respectively, P < 0.05 for both) despite a similar hyperinsulinemia. Both challenges stimulated brachial artery flow (ultrasound) and heart rate to a similar extent, as well as yielding comparable decreases in diastolic blood pressure and total vascular resistance. Systolic blood pressure and aortic stiffness remained unaltered by either challenge. Independently of large artery hemodynamics, hyperglycemia impairs muscle microvascular blood flow, potentially limiting glucose disposal into skeletal muscle. The OGC reduced microvascular blood flow in muscle peripherally and therefore may underestimate the importance of skeletal muscle in postprandial glucose disposal.
Collapse
Affiliation(s)
- Ryan D Russell
- Menzies Institute for Medical Research, University of Tasmania , Hobart, Tasmania , Australia
- Department of Health and Human Performance, College of Health Affairs, University of Texas Rio Grande Valley , Brownsville, Texas
| | - Donghua Hu
- Menzies Institute for Medical Research, University of Tasmania , Hobart, Tasmania , Australia
| | - Timothy Greenaway
- Royal Hobart Hospital , Hobart, Tasmania , Australia
- School of Medicine, University of Tasmania , Hobart, Tasmania , Australia
| | - James E Sharman
- Menzies Institute for Medical Research, University of Tasmania , Hobart, Tasmania , Australia
| | - Stephen Rattigan
- Menzies Institute for Medical Research, University of Tasmania , Hobart, Tasmania , Australia
| | - Stephen M Richards
- Menzies Institute for Medical Research, University of Tasmania , Hobart, Tasmania , Australia
- School of Medicine, University of Tasmania , Hobart, Tasmania , Australia
| | - Michelle A Keske
- Menzies Institute for Medical Research, University of Tasmania , Hobart, Tasmania , Australia
- Institute for Physical Activity and Nutrition, School of Exercise and Nutrition. Deakin University , Geelong, Victoria , Australia
| |
Collapse
|
|
32
|
Mitchell WK, Phillips BE, Wilkinson DJ, Williams JP, Rankin D, Lund JN, Smith K, Atherton PJ. Supplementing essential amino acids with the nitric oxide precursor, l-arginine, enhances skeletal muscle perfusion without impacting anabolism in older men. Clin Nutr 2017; 36:1573-1579. [PMID: 27746000 DOI: 10.1016/j.clnu.2016.09.031] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2015] [Revised: 05/22/2016] [Accepted: 09/30/2016] [Indexed: 01/01/2023]
Abstract
Postprandial limb blood flow and skeletal muscle microvascular perfusion reduce with aging. Here we tested the impact of providing bolus essential amino acids (EAA) in the presence and absence of the nitric oxide precursor, l-Arginine (ARG), upon skeletal muscle blood flow and anabolism in older men. Healthy young (YOUNG: 19.7 ± 0.5 y, N = 8) and older men (OLD, 70 ± 0.8 y, N = 8) received 15 g EAA or (older only) 15 g EAA +3 g ARG (OLD-ARG, 69.2 ± 1.2 y, N = 8). We quantified responses in muscle protein synthesis (MPS; incorporation of 13C phenylalanine into myofibrillar proteins), leg and muscle microvascular blood flow (Doppler/contrast enhanced ultrasound (CEUS)) and insulin/EAA in response to EEA ± ARG. Plasma EAA increased similarly across groups but argininemia was evident solely in OLD-ARG (∼320 mmol, 65 min post feed); increases in plasma insulin (to ∼13 IU ml-1) were similar across groups. Increases in femoral flow were evident in YOUNG >2 h after feeding; these effects were blunted in OLD and OLD-ARG. Increases in microvascular blood volume (MBV) occurred only in YOUNG and these effects were isolated to the early postprandial phase (+45% at ∼45 min after feeding) coinciding with detectable arterio-venous differences in EAA reflecting net uptake by muscle. Increases in microvascular flow velocity (MFV) and tissue perfusion (MBV × MFV) occurred (∼2 h) in YOUNG and OLD-ARG, but not OLD. Postprandial protein accretion was greater in YOUNG than OLD or OLD-ARG; the latter two groups being indistinguishable. Therefore, ARG rescues aspects of muscle perfusion in OLD without impacting anabolic blunting, perhaps due to the "rescue" being beyond the period of active EAA-uptake.
Collapse
Affiliation(s)
- W Kyle Mitchell
- MRC-ARUK Centre of Excellence for Musculoskeletal Ageing Research, School of Medicine, University of Nottingham, Derby, DE22 3DT, UK
| | - Bethan E Phillips
- MRC-ARUK Centre of Excellence for Musculoskeletal Ageing Research, School of Medicine, University of Nottingham, Derby, DE22 3DT, UK
| | - Daniel J Wilkinson
- MRC-ARUK Centre of Excellence for Musculoskeletal Ageing Research, School of Medicine, University of Nottingham, Derby, DE22 3DT, UK
| | - John P Williams
- MRC-ARUK Centre of Excellence for Musculoskeletal Ageing Research, School of Medicine, University of Nottingham, Derby, DE22 3DT, UK
| | - Debbie Rankin
- MRC-ARUK Centre of Excellence for Musculoskeletal Ageing Research, School of Medicine, University of Nottingham, Derby, DE22 3DT, UK
| | - Jonathan N Lund
- MRC-ARUK Centre of Excellence for Musculoskeletal Ageing Research, School of Medicine, University of Nottingham, Derby, DE22 3DT, UK
| | - Kenneth Smith
- MRC-ARUK Centre of Excellence for Musculoskeletal Ageing Research, School of Medicine, University of Nottingham, Derby, DE22 3DT, UK
| | - Philip J Atherton
- MRC-ARUK Centre of Excellence for Musculoskeletal Ageing Research, School of Medicine, University of Nottingham, Derby, DE22 3DT, UK.
| |
Collapse
|
|
33
|
Goyal A, Agrawal N. Ischemic preconditioning: Interruption of various disorders. J Saudi Heart Assoc 2017; 29:116-127. [PMID: 28373786 PMCID: PMC5366670 DOI: 10.1016/j.jsha.2016.09.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2016] [Revised: 08/05/2016] [Accepted: 09/04/2016] [Indexed: 02/05/2023] Open
Abstract
Ischemic heart diseases are the leading cause of morbidity and mortality worldwide. Reperfusion of an ischemic heart is necessary to regain the normal functioning of the heart. However, abrupt reperfusion of an ischemic heart elicits a cascade of adverse events that leads to injury of the myocardium, i.e., ischemia-reperfusion injury. An endogenous powerful strategy to protect the ischemic heart is ischemic preconditioning, in which the myocardium is subjected to short periods of sublethal ischemia and reperfusion before the prolonged ischemic insult. However, it should be noted that the cardioprotective effect of preconditioning is attenuated in some pathological conditions. The aim of this article is to review present knowledge on how menopause and some metabolic disorders such as diabetes and hyperlipidemia affect myocardial ischemic preconditioning and the mechanisms involved.
Collapse
Affiliation(s)
- Ahsas Goyal
- Institute of Pharmaceutical Research, GLA University, Mathura 281406, U.P., India
| | - Neetu Agrawal
- Institute of Pharmaceutical Research, GLA University, Mathura 281406, U.P., India
| |
Collapse
|
|
34
|
Schneditz D, Niemczyk S, Sauseng N, Bachler I, Zierler E, Lackner HK, Hafner-Giessauf H. Osmotic and Hemodynamic Effects of Hypertonic Glucose During Hemodialysis. ASAIO J 2017; 63:824-831. [PMID: 28338477 DOI: 10.1097/mat.0000000000000574] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
It was the purpose to quantify the hemodynamic effects of a bolus of hypertonic glucose injected into the extracorporeal system in a group of stable and nondiabetic patients during hemodialysis (HD). Glucose and electrolytes were measured in frequent intervals. Arterial blood pressures and heart rates were continuously recorded by noninvasive vascular unloading technique. Beat-to-beat stroke volume, cardiac output, and total peripheral resistance were determined by Modelflow method. Relative blood volumes were continuously measured by ultrasonic and optical means. Eight patients were studied in two treatments. Although arterial pressures and heart rates remained stable, stroke volume and cardiac output transiently increased above (19.2 ± 12.3%) and total peripheral resistance dropped below baseline (18.2 ± 8.6%) by a comparable magnitude. Relative blood volume transiently increased above baseline at 100% (104.9 ± 1.0%). Glucose concentrations were significantly related to relative blood volumes (r = 0.86, p < 0.001). In spite of a substantial increase in blood volume, a bolus of hypertonic glucose does not increase arterial pressures in nondiabetic patients because of concomitant vasodilatation. The relative increase in blood volume quantified by noninvasive HD technology follows the course of glucose and could be used as a surrogate to characterize patients with regard to their glucose metabolism during HD.
Collapse
Affiliation(s)
- Daniel Schneditz
- From the *Institute of Physiology, Medical University of Graz, Graz, Austria; †Department of Internal Diseases, Military Institute of Medicine, Warsaw, Poland; and ‡Division of Nephrology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
| | | | | | | | | | | | | |
Collapse
|
|
35
|
Oridupa OA, Folasire OF, Owolabi AJ. Evaluation of the sub-chronic toxicity profile of the corm of Xanthosoma sagittifolium on hematology and biochemistry of alloxan-induced diabetic Wistar rats. JOURNAL OF COMPLEMENTARY & INTEGRATIVE MEDICINE 2017; 14:/j/jcim.ahead-of-print/jcim-2016-0072/jcim-2016-0072.xml. [PMID: 28306532 DOI: 10.1515/jcim-2016-0072] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/19/2016] [Accepted: 01/12/2017] [Indexed: 01/04/2023]
Abstract
Background Hematological and biochemical changes associated with diabetes mellitus and probable reversal were assessed in alloxan-induced diabetic Wistar rats fed with varied percentages of Xanthosoma sagittifolium corm feed (Xs). The changes were compared to normoglycemic rats and diabetic rats treated with glibenclamide. Methods The study had eight groups in all with group 8 (control) consisting of five normoglycemic rats fed with normal rat pellets (Nrp). Diabetes was experimentally induced by intraperitoneal injection of alloxan to normoglycemic rats. Diabetic rats (serum glucose >200 mg/dL) at 48 h postinjection were randomly divided into the seven groups, each diabetic group consisting of five rats. One group was untreated and fed with Nrp, four groups were fed with 25 %, 50 %, 75 % or 100 % Xs, one group was fed with 100 % Xs and administered with glibenclamide, while a 7th group was fed with Nrp and administered with glibenclamide. Results This study shows that treatment of diabetes with corm of X. sagittifolium increases cellular response to inflammation which is required for body defense against assaulting agents. Decreased serum protein levels observed in untreated diabetic rats were restored in diabetic rats fed with X. sagittifolium corm with particular increase in serum albumin levels but depression of globulin fraction, except in rats fed with X. sagittifolium feed and administered with glibenclamide. X. sagittifolium showed a potent antihyperglycemic effect and corrected the dyslipidemia in a manner comparable to that observed for glibenclamide. Although HDL levels were still low, significant (p<0.05) decrease of LDL levels was a positive indicator of reduced risk for development of cardiovascular and/or coronary heart disease. Conclusions X. sagittifolium corm can be recommended for inclusion in diets of diabetics without causing further deterioration of health of the diabetic patients.
Collapse
|
|
36
|
Lyons J, Foster B, Castillo L, Lyons BE. Insulin therapy for glycaemic control in critically ill children. Hippokratia 2017. [DOI: 10.1002/14651858.cd009983.pub2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Affiliation(s)
- Jeremy Lyons
- Royal Belfast Hospital for Sick Children; Paediatric Intensive Care Unit; Belfast Hospital Trust Grosvenor Road Belfast Northern Ireland UK BT12 6BA
| | - Brian Foster
- Royal Belfast Hospital for Sick Children; Belfast Hospital Trust Grosvenor Road Belfast Northern Ireland UK BT12 6BA
| | - Leticia Castillo
- Cleveland Clinic; Pediatric Critical Care Medicine; Cleveland Clinic Main Campus 9500 Euclid Avenue Cleveland OH USA 44195
| | | |
Collapse
|
|
37
|
Yu L, Fan C, Li Z, Zhang J, Xue X, Xu Y, Zhao G, Yang Y, Wang H. Melatonin rescues cardiac thioredoxin system during ischemia-reperfusion injury in acute hyperglycemic state by restoring Notch1/Hes1/Akt signaling in a membrane receptor-dependent manner. J Pineal Res 2017; 62. [PMID: 27753144 DOI: 10.1111/jpi.12375] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2016] [Accepted: 10/14/2016] [Indexed: 01/08/2023]
Abstract
Stress hyperglycemia is commonly observed in patients suffering from ischemic heart disease. It not only worsens cardiovascular prognosis but also attenuates the efficacies of various cardioprotective agents. This study aimed to investigate the protective effect of melatonin against myocardial ischemia-reperfusion (MI/R) injury in acute hyperglycemic state with a focus on Notch1/Hes1/Akt signaling and intracellular thioredoxin (Trx) system. Sprague Dawley rats were subjected to MI/R surgery and high-glucose (HG, 500 g/L) infusion (4 mL/kg/h) to induce temporary hyperglycemia. Rats were treated with or without melatonin (10 mg/kg/d) during the operation. Furthermore, HG (33 mmol/L)-incubated H9c2 cardiomyoblasts were treated in the presence or absence of luzindole (a competitive melatonin receptor antagonist), DAPT (a γ-secretase inhibitor), LY294002 (a PI3-kinase/Akt inhibitor), or thioredoxin-interacting protein (Txnip) adenoviral vectors. We found that acute hyperglycemia aggravated MI/R injury by suppressing Notch1/Hes1/Akt signaling and intracellular Trx activity. Melatonin treatment effectively ameliorated MI/R injury by reducing infarct size, myocardial apoptosis, and oxidative stress. Moreover, melatonin also markedly enhanced Notch1/Hes1/Akt signaling and rescued intracellular Trx system by upregulating Notch1, N1ICD, Hes1, and p-Akt expressions, increasing Trx activity, and downregulating Txnip expression. However, these effects were blunted by luzindole, DAPT, or LY294002. Additionally, Txnip overexpression not only decreased Trx activity, but also attenuated the cytoprotective effect of melatonin. We conclude that impaired Notch1 signaling aggravates MI/R injury in acute hyperglycemic state. Melatonin rescues Trx system by reducing Txnip expression via Notch1/Hes1/Akt signaling in a membrane receptor-dependent manner. Its role as a prophylactic/therapeutic drug deserves further clinical study.
Collapse
Affiliation(s)
- Liming Yu
- Department of Cardiovascular Surgery, General Hospital of Shenyang Military Area Command, Shenyang, Liaoning, China
| | - Chongxi Fan
- Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Zhi Li
- Department of Cardiovascular Surgery, General Hospital of Shenyang Military Area Command, Shenyang, Liaoning, China
| | - Jian Zhang
- Department of Cardiovascular Surgery, General Hospital of Shenyang Military Area Command, Shenyang, Liaoning, China
| | - Xiaodong Xue
- Department of Cardiovascular Surgery, General Hospital of Shenyang Military Area Command, Shenyang, Liaoning, China
| | - Yinli Xu
- Department of Cardiovascular Surgery, General Hospital of Shenyang Military Area Command, Shenyang, Liaoning, China
| | - Guolong Zhao
- Department of Cardiovascular Surgery, Northwest Women's and Children's Hospital, Xi'an, Shaanxi, China
| | - Yang Yang
- Department of Biomedical Engineering, The Fourth Military Medical University, Xi'an, China
- Department of Thoracic and Cardiovascular Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Huishan Wang
- Department of Cardiovascular Surgery, General Hospital of Shenyang Military Area Command, Shenyang, Liaoning, China
| |
Collapse
|
|
38
|
Hiesmayr MJ. Hyperglycemia and Outcome After Myocardial Infarction and Cardiac Surgery: So What? Semin Cardiothorac Vasc Anesth 2016; 10:220-3. [PMID: 16959754 DOI: 10.1177/1089253206291139] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Hyperglycemia is a frequent observation during acute illness such as myocardial infarction and after major surgery. The proportion of patients with hyperglycemia may be as high as 95% to 100% after cardiac surgery. This stress-induced hyperglycemia has a detrimental effect on outcome after myocardial infarction and cardiac surgery. Mortality may increase by a factor of 4, especially in non-diabetic patients. Control of hyperglycemia to normalize blood glucose is associated with a clear clinical benefit. This effect is most beneficial in nondiabetic patients with hyperglycemia. The exact target level of glycemia is still a matter of investigation, but normalization to values between 80 and 125 mg/dL is probably optimal.
Collapse
Affiliation(s)
- Michael J Hiesmayr
- Department of Cardiac-Thoracic-Vascular Anaesthesia & Intensive Care Medicine, Medical University Vienna, Vienna, Austria.
| |
Collapse
|
|
39
|
Han S, Jin SM, Ko JS, Kim YR, Gwak MS, Son HJ, Joh JW, Kim GS. Association between Serum Bilirubin and Acute Intraoperative Hyperglycemia Induced by Prolonged Intermittent Hepatic Inflow Occlusion in Living Liver Donors. PLoS One 2016; 11:e0156957. [PMID: 27367602 PMCID: PMC4930162 DOI: 10.1371/journal.pone.0156957] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2016] [Accepted: 05/02/2016] [Indexed: 11/19/2022] Open
Abstract
Background Intermittent hepatic inflow occlusion (IHIO) is associated with acute hyperglycemia during living donor hepatectomy when the ischemia is prolonged. Bilirubin is a potent antioxidant to play an important role for maintaining insulin sensitivity and preventing hyperglycemia. Thus, we aimed to test whether serum bilirubin level is associated with prolonged IHIO-induced intraoperative hyperglycemia. Methods Seventy-five living liver donors who underwent a prolonged IHIO with a >30 minute cumulative ischemia were included. The association between preoperative serum bilirubin concentrations and the risk of intraoperative hyperglycemia (blood glucose concentration >180 mg/dl) was analyzed using binary logistic regression with adjusting for potential confounders including age and steatosis. Results The number of donors who underwent 3, 4, 5, and 6 rounds of IHIO was 41, 22, 7, and 5, respectively. Twenty-nine (35%) donors developed intraoperative hyperglycemia. Total bilirubin concentration was inversely associated with hyperglycemia risk (odds ratio [OR] 0.033, 95% confidence interval [CI] 0.004–0.313, P = 0.003). There was an interaction between age and total bilirubin concentration: the effect of lower serum total bilirubin (≤0.7 mg/dl) on the development of hyperglycemia was greater in older donors (>40 years) than in younger donors (P = 0.0.028 versus P = 0.212). Both conjugated bilirubin (OR 0.001 95% CI 0.001–0.684) and unconjugated bilirubin (OR 0.011 95% CI 0.001–0.246) showed an independent association with hyperglycemia risk. Conclusions Lower preoperative serum bilirubin was associated with greater risk of prolonged IHIO-induced hyperglycemia during living donor hepatectomy particularly in older donors. Thus, more meticulous glycemic management is recommended when prolonged IHIO is necessary for surgical purposes in old living donors with lower serum bilirubin levels.
Collapse
Affiliation(s)
- Sangbin Han
- Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
- Department of Anesthesiology and Pain Medicine, Kangwon National University School of Medicine, Chuncheon, Korea
| | - Sang-Man Jin
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Justin Sangwook Ko
- Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Young Ri Kim
- Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Mi Sook Gwak
- Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hee Jeong Son
- Department of Anesthesiology and Pain Medicine, Kangwon National University School of Medicine, Chuncheon, Korea
| | - Jae-Won Joh
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Gaab Soo Kim
- Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
- * E-mail:
| |
Collapse
|
|
40
|
Mahmoud AM, Brown MD, Phillips SA, Haus JM. Skeletal Muscle Vascular Function: A Counterbalance of Insulin Action. Microcirculation 2016; 22:327-47. [PMID: 25904196 DOI: 10.1111/micc.12205] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2015] [Accepted: 04/20/2015] [Indexed: 12/11/2022]
Abstract
Insulin is a vasoactive hormone that regulates vascular homeostasis by maintaining balance of endothelial-derived NO and ET-1. Although there is general agreement that insulin resistance and the associated hyperinsulinemia disturb this balance, the vascular consequences for hyperinsulinemia in isolation from insulin resistance are still unclear. Presently, there is no simple answer for this question, especially in a background of mixed reports examining the effects of experimental hyperinsulinemia on endothelial-mediated vasodilation. Understanding the mechanisms by which hyperinsulinemia induces vascular dysfunction is essential in advancing treatment and prevention of insulin resistance-related vascular complications. Thus, we review literature addressing the effects of hyperinsulinemia on vascular function. Furthermore, we give special attention to the vasoregulatory effects of hyperinsulinemia on skeletal muscle, the largest insulin-dependent organ in the body. This review also characterizes the differential vascular effects of hyperinsulinemia on large conduit vessels versus small resistance microvessels and the effects of metabolic variables in an effort to unravel potential sources of discrepancies in the literature. At the cellular level, we provide an overview of insulin signaling events governing vascular tone. Finally, we hypothesize a role for hyperinsulinemia and insulin resistance in the development of CVD.
Collapse
Affiliation(s)
- Abeer M Mahmoud
- Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, Illinois, USA.,Integrative Physiology Laboratory, College of Applied Health Sciences, University of Illinois at Chicago, Chicago, Illinois, USA
| | - Michael D Brown
- Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, Illinois, USA.,Integrative Physiology Laboratory, College of Applied Health Sciences, University of Illinois at Chicago, Chicago, Illinois, USA
| | - Shane A Phillips
- Integrative Physiology Laboratory, College of Applied Health Sciences, University of Illinois at Chicago, Chicago, Illinois, USA.,Department of Physical Therapy, University of Illinois at Chicago, Chicago, Illinois, USA
| | - Jacob M Haus
- Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, Illinois, USA.,Integrative Physiology Laboratory, College of Applied Health Sciences, University of Illinois at Chicago, Chicago, Illinois, USA
| |
Collapse
|
|
41
|
Abstract
Sepsis predisposes to disordered metabolism and dysglycemia; the latter is a broad term that includes hyperglycemia, hypoglycemia, and glycemic variability. Dysglycemia is a marker of illness severity. Large randomized controlled trials have provided considerable insight into the optimal blood glucose targets for critically ill patients with sepsis. However, it may be that the pathophysiologic consequences of dysglycemia are dynamic throughout the course of a septic insult and also altered by premorbid glycemia. This review highlights the relevance of hyperglycemia, hypoglycemia, and glycemic variability in patients with sepsis with an emphasis on a rational approach to management.
Collapse
Affiliation(s)
- Mark P Plummer
- Discipline of Acute Care Medicine, University of Adelaide, North Terrace, Adelaide 5000, Australia; Department of Critical Care Services, Royal Adelaide Hospital, North Terrace, Adelaide 5000, Australia.
| | - Adam M Deane
- Discipline of Acute Care Medicine, University of Adelaide, North Terrace, Adelaide 5000, Australia; Department of Critical Care Services, Royal Adelaide Hospital, North Terrace, Adelaide 5000, Australia
| |
Collapse
|
|
42
|
Jackson R, Brennan S, Fielding P, Sims MW, Challiss RAJ, Adlam D, Squire IB, Rainbow RD. Distinct and complementary roles for α and β isoenzymes of PKC in mediating vasoconstrictor responses to acutely elevated glucose. Br J Pharmacol 2016; 173:870-87. [PMID: 26660275 DOI: 10.1111/bph.13399] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2015] [Revised: 11/23/2015] [Accepted: 11/30/2015] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND AND PURPOSE We investigated the hypothesis that elevated glucose increases contractile responses in vascular smooth muscle and that this enhanced constriction occurs due to the glucose-induced PKC-dependent inhibition of voltage-gated potassium channels. EXPERIMENTAL APPROACH Patch-clamp electrophysiology in rat isolated mesenteric arterial myocytes was performed to investigate the glucose-induced inhibition of voltage-gated potassium (Kv ) current. To determine the effects of glucose in whole vessel, wire myography was performed in rat mesenteric, porcine coronary and human internal mammary arteries. KEY RESULTS Glucose-induced inhibition of Kv was PKC-dependent and could be pharmacologically dissected using PKC isoenzyme-specific inhibitors to reveal a PKCβ-dependent component of Kv inhibition dominating between 0 and 10 mM glucose with an additional PKCα-dependent component becoming evident at concentrations greater than 10 mM. These findings were supported using wire myography in all artery types used, where contractile responses to vessel depolarization and vasoconstrictors were enhanced by increasing bathing glucose concentration, again with evidence for distinct and complementary PKCα/PKCβ-mediated components. CONCLUSIONS AND IMPLICATIONS Our results provide compelling evidence that glucose-induced PKCα/PKCβ-mediated inhibition of Kv current in vascular smooth muscle causes an enhanced constrictor response. Inhibition of Kv current causes a significant depolarization of vascular myocytes leading to marked vasoconstriction. The PKC dependence of this enhanced constrictor response may present a potential therapeutic target for improving microvascular perfusion following percutaneous coronary intervention after myocardial infarction in hyperglycaemic patients.
Collapse
Affiliation(s)
- Robert Jackson
- Department of Cardiovascular Sciences, University of Leicester, Glenfield General Hospital, Leicester, UK
| | - Sean Brennan
- Department of Cardiovascular Sciences, University of Leicester, Glenfield General Hospital, Leicester, UK
| | - Peter Fielding
- Department of Cardiovascular Sciences, University of Leicester, Glenfield General Hospital, Leicester, UK
| | - Mark W Sims
- Department of Cardiovascular Sciences, University of Leicester, Glenfield General Hospital, Leicester, UK
| | - R A John Challiss
- Department of Molecular and Cell Biology, University of Leicester, Leicester, UK
| | - David Adlam
- Department of Cardiovascular Sciences, University of Leicester, Glenfield General Hospital, Leicester, UK
| | - Iain B Squire
- Department of Cardiovascular Sciences, University of Leicester, Glenfield General Hospital, Leicester, UK
| | - Richard D Rainbow
- Department of Cardiovascular Sciences, University of Leicester, Glenfield General Hospital, Leicester, UK
| |
Collapse
|
|
43
|
Rezende PC, Rahmi RM, Hueb W. The Influence of Diabetes Mellitus in Myocardial Ischemic Preconditioning. J Diabetes Res 2016; 2016:8963403. [PMID: 27656659 PMCID: PMC5021496 DOI: 10.1155/2016/8963403] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2016] [Accepted: 08/14/2016] [Indexed: 11/24/2022] Open
Abstract
Ischemic preconditioning (IP) is a powerful mechanism of protection discovered in the heart in which ischemia paradoxically protects the myocardium against other ischemic insults. Many factors such as diseases and medications may influence IP expression. Although diabetes poses higher cardiovascular risk, the physiopathology underlying this condition is uncertain. Moreover, although diabetes is believed to alter intracellular pathways related to myocardial protective mechanisms, it is still controversial whether diabetes may interfere with ischemic preconditioning and whether this might influence clinical outcomes. This review article looks at published reports with animal models and humans that tried to evaluate the possible influence of diabetes in myocardial ischemic preconditioning.
Collapse
Affiliation(s)
- Paulo Cury Rezende
- Department of Atherosclerosis, Heart Institute of the University of São Paulo Medical School, São Paulo, SP, Brazil
| | - Rosa Maria Rahmi
- Department of Atherosclerosis, Heart Institute of the University of São Paulo Medical School, São Paulo, SP, Brazil
| | - Whady Hueb
- Department of Atherosclerosis, Heart Institute of the University of São Paulo Medical School, São Paulo, SP, Brazil
- *Whady Hueb:
| |
Collapse
|
|
44
|
Grisé KN, Olver TD, McDonald MW, Dey A, Jiang M, Lacefield JC, Shoemaker JK, Noble EG, Melling CWJ. High Intensity Aerobic Exercise Training Improves Deficits of Cardiovascular Autonomic Function in a Rat Model of Type 1 Diabetes Mellitus with Moderate Hyperglycemia. J Diabetes Res 2016; 2016:8164518. [PMID: 26885531 PMCID: PMC4739461 DOI: 10.1155/2016/8164518] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2015] [Revised: 12/11/2015] [Accepted: 12/15/2015] [Indexed: 02/07/2023] Open
Abstract
Indices of cardiovascular autonomic neuropathy (CAN) in experimental models of Type 1 diabetes mellitus (T1DM) are often contrary to clinical data. Here, we investigated whether a relatable insulin-treated model of T1DM would induce deficits in cardiovascular (CV) autonomic function more reflective of clinical results and if exercise training could prevent those deficits. Sixty-four rats were divided into four groups: sedentary control (C), sedentary T1DM (D), control exercise (CX), or T1DM exercise (DX). Diabetes was induced via multiple low-dose injections of streptozotocin and blood glucose was maintained at moderate hyperglycemia (9-17 mM) through insulin supplementation. Exercise training consisted of daily treadmill running for 10 weeks. Compared to C, D had blunted baroreflex sensitivity, increased vascular sympathetic tone, increased serum neuropeptide Y (NPY), and decreased intrinsic heart rate. In contrast, DX differed from D in all measures of CAN (except NPY), including heart rate variability. These findings demonstrate that this T1DM model elicits deficits and exercise-mediated improvements to CV autonomic function which are reflective of clinical T1DM.
Collapse
Affiliation(s)
- Kenneth N. Grisé
- Exercise Biochemistry Laboratory, School of Kinesiology, Faculty of Health Sciences, Western University, London, ON, Canada N6A 3K7
| | - T. Dylan Olver
- Neurovascular Research Laboratory, School of Kinesiology, Faculty of Health Sciences, Western University, London, ON, Canada N6A 3K7
| | - Matthew W. McDonald
- Exercise Biochemistry Laboratory, School of Kinesiology, Faculty of Health Sciences, Western University, London, ON, Canada N6A 3K7
| | - Adwitia Dey
- Exercise Biochemistry Laboratory, School of Kinesiology, Faculty of Health Sciences, Western University, London, ON, Canada N6A 3K7
| | - Mao Jiang
- Exercise Biochemistry Laboratory, School of Kinesiology, Faculty of Health Sciences, Western University, London, ON, Canada N6A 3K7
| | - James C. Lacefield
- Department of Electrical and Computer Engineering, Department of Medical Biophysics and Robarts Research Institute, Western University, London, ON, Canada N6A 3K7
| | - J. Kevin Shoemaker
- Neurovascular Research Laboratory, School of Kinesiology, Faculty of Health Sciences, Western University, London, ON, Canada N6A 3K7
- Department of Physiology and Pharmacology, Western University, London, ON, Canada N6A 3K7
- Lawson Health Research Institute, London, ON, Canada N6C 2R5
| | - Earl G. Noble
- Exercise Biochemistry Laboratory, School of Kinesiology, Faculty of Health Sciences, Western University, London, ON, Canada N6A 3K7
- Lawson Health Research Institute, London, ON, Canada N6C 2R5
| | - C. W. James Melling
- Exercise Biochemistry Laboratory, School of Kinesiology, Faculty of Health Sciences, Western University, London, ON, Canada N6A 3K7
- *C. W. James Melling:
| |
Collapse
|
|
45
|
Yorek MA. Vascular Impairment of Epineurial Arterioles of the Sciatic Nerve: Implications for Diabetic Peripheral Neuropathy. Rev Diabet Stud 2015; 12:13-28. [PMID: 26676659 PMCID: PMC5397981 DOI: 10.1900/rds.2015.12.13] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2015] [Accepted: 04/30/2015] [Indexed: 12/11/2022] Open
Abstract
This article reviews the impact of diabetes and its treatment on vascular function with a focus on the reactivity of epineurial arterioles, blood vessels that provide circulation to the sciatic nerve. Another focus is the relationship between the dysregulation of neurovascular function and diabetic peripheral neuropathy. Diabetic peripheral neuropathy is a debilitating disorder that occurs in more than 50 percent of patients with diabetes. The etiology involves metabolic, vascular, and immunologic pathways besides neurohormonal growth factor deficiency and extracellular matrix remodeling. In the light of this complex etiology, an effective treatment for diabetic peripheral neuropathy has not yet been identified. Current opinion postulates that any effective treatment for diabetic peripheral neuropathy will require a combination of life style and therapeutic interventions. However, a more comprehensive understanding of the factors contributing to neurovascular and neural dysfunction in diabetes is needed before such a treatment strategy can be developed. After reading this review, the reader should have gained insight into the complex regulation of vascular function and blood flow to the sciatic nerve, and the impact of diabetes on numerous elements of vascular reactivity of epineurial arterioles of the sciatic nerve.
Collapse
Affiliation(s)
- Mark A Yorek
- Department of Veterans Affairs Iowa City Health Care System, Iowa City, IA 52246, USA
| |
Collapse
|
|
46
|
Activation of Adenosine Triphosphate-regulated Potassium Channels during Reperfusion Restores Isoflurane Postconditioning-induced Cardiac Protection in Acutely Hyperglycemic Rabbits. Anesthesiology 2015; 122:1299-311. [PMID: 25812079 DOI: 10.1097/aln.0000000000000648] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
BACKGROUND Hyperglycemia is known to inhibit myocardial anesthetic postconditioning. The authors tested whether activation of adenosine triphosphate-regulated potassium (KATP) channels would restore anesthetic postconditioning during acute hyperglycemia. METHODS Rabbits subjected to 40-min myocardial ischemia and 3-h reperfusion (ischemia-reperfusion [I/R]) were assigned to groups (n = 10 in each group) with or without isoflurane postconditioning (2.1% for 5 min) in the presence or absence of hyperglycemia and/or the KATP channel agonist diazoxide. Creatine kinase MB fraction and infarct size were measured. Phosphorylated protein kinase B (Akt) and endothelial nitric oxide synthase (eNOS) were assessed. Oxidative stress was evaluated by measuring malondialdehyde, and apoptosis was assessed by dUTP nick-end labeling and activated caspase-3. RESULTS Postconditioning significantly reduced myocardial infarct size (26 ± 4% in the isoflurane [ISO] group vs. 53 ± 2% in the I/R group; P = 0.007); whereas, hyperglycemia inhibited this effect (infarct size: 47 ± 2%, P = 0.02 vs. the ISO group). Phosphorylated and eNOS levels increased, whereas malondialdehyde and myocardial apoptosis were significantly lower after isoflurane postconditioning compared with I/R. These effects were inhibited by acute hyperglycemia. Diazoxide restored the protective effect of isoflurane in the hyperglycemic animals (infarct size: 29 ± 2%; P = 0.01 vs. the I/R group), reduced malondialdehyde levels and myocardial apoptosis, but did not affect the expression of phosphorylated Akt or eNOS. CONCLUSIONS KATP channel activation restored anesthetic postconditioning-induced myocardial protection under acute hyperglycemia. This effect occurred without increasing Akt or eNOS phosphorylation, suggesting that KATP channels are located downstream to Akt and eNOS in the pathway of isoflurane-induced myocardial postconditioning.
Collapse
|
|
47
|
Han S, Sangwook Ko J, Jin SM, Man Kim J, Choi SJ, Joh JW, Hoon Chung Y, Lee SK, Gwak MS, Kim G. Glycemic responses to intermittent hepatic inflow occlusion in living liver donors. Liver Transpl 2015; 21:180-6. [PMID: 25330942 DOI: 10.1002/lt.24029] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2014] [Revised: 10/07/2014] [Accepted: 10/12/2014] [Indexed: 02/07/2023]
Abstract
The occurrence of glycemic disturbances has been described for patients undergoing intermittent hepatic inflow occlusion (IHIO) for tumor removal. However, the glycemic responses to IHIO in living liver donors are unknown. This study investigated the glycemic response to IHIO in these patients and examined the association between this procedure and the occurrence of hyperglycemia (blood glucose > 180 mg/dL). The data from 154 living donors were retrospectively reviewed. The decision to perform IHIO was made on the basis of the extent of bleeding that occurred during parenchymal dissection. One round of IHIO consisted of 15 minutes of clamping and 5 minutes of unclamping the hepatic artery and portal vein. Blood glucose concentrations were measured at predetermined time points, including the start and end of IHIO. Repeated hyperglycemic episodes occurred after unclamping. The mean maximum intraoperative blood glucose concentration was greater in donors who underwent ≥3 rounds of IHIO versus those who underwent 1 or 2 rounds (169 ± 30 versus 149 ± 31 mg/dL, P = 0.005). The incidence of intraoperative hyperglycemia was also greater in donors who underwent ≥3 rounds of IHIO versus those who underwent 1 or 2 rounds (38.7% versus 7.7%, odds ratio = 7.1, 95% confidence interval = 2.5-20.4, P < 0.001). Donors who did not undergo IHIO and those who underwent 1 or 2 rounds of IHIO exhibited similar maximum glucose concentrations and similar incidence rates of hyperglycemia. In conclusion, IHIO induced repeated hyperglycemic responses in living donors, and donors who underwent ≥3 rounds of IHIO were more likely to experience intraoperative hyperglycemia. These results provide additional information on the risks and benefits of IHIO in living donors.
Collapse
Affiliation(s)
- Sangbin Han
- Department of Anesthesiology and Pain Medicine, Sungkyunkwan University School of Medicine, Seoul, Korea
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
48
|
Shen Y, Zhang X, Huang X, Zhang Y, Zhang C, Jin J, Liu X, Li H, Yao S. A new fluorescence and colorimetric sensor for highly selective and sensitive detection of glucose in 100% water. RSC Adv 2015. [DOI: 10.1039/c5ra11116a] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
A new naphthalimide derivative containing hexanoic acid and boronate groups was designed and synthesized.
Collapse
Affiliation(s)
- Youming Shen
- College of Chemistry and Chemical Engineering
- Hunan University of Arts and Science
- Changde
- PR China
- Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education)
| | - Xiangyang Zhang
- College of Chemistry and Chemical Engineering
- Hunan University of Arts and Science
- Changde
- PR China
| | - Xi Huang
- Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education)
- College of Chemistry and Chemical Engineering
- Hunan Normal University
- Changsha 410081
- PR China
| | - Youyu Zhang
- Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education)
- College of Chemistry and Chemical Engineering
- Hunan Normal University
- Changsha 410081
- PR China
| | - Chunxiang Zhang
- College of Chemistry and Chemical Engineering
- Hunan University of Arts and Science
- Changde
- PR China
| | - Junling Jin
- College of Chemistry and Chemical Engineering
- Hunan University of Arts and Science
- Changde
- PR China
| | - Xuewen Liu
- College of Chemistry and Chemical Engineering
- Hunan University of Arts and Science
- Changde
- PR China
| | - Haitao Li
- Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education)
- College of Chemistry and Chemical Engineering
- Hunan Normal University
- Changsha 410081
- PR China
| | - Shouzhuo Yao
- Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education)
- College of Chemistry and Chemical Engineering
- Hunan Normal University
- Changsha 410081
- PR China
| |
Collapse
|
|
49
|
Jensen MK, Bertoia ML, Cahill LE, Agarwal I, Rimm EB, Mukamal KJ. Novel metabolic biomarkers of cardiovascular disease. Nat Rev Endocrinol 2014; 10:659-72. [PMID: 25178732 DOI: 10.1038/nrendo.2014.155] [Citation(s) in RCA: 71] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Coronary heart disease (CHD) accounts for one in every six deaths in US individuals. Great advances have been made in identifying important risk factors for CHD, such as hypertension, diabetes mellitus, smoking and hypercholesterolaemia, which have led to major developments in therapy. In particular, statins represent one of the greatest successes in the prevention of CHD. While these standard risk factors are important, an obvious opportunity exists to take advantage of ongoing scientific research to better risk-stratify individuals and to identify new treatment targets. In this Review, we summarize ongoing scientific research in a number of metabolic molecules or features, including lipoproteins, homocysteine, calcium metabolism and glycaemic markers. We evaluate the current state of the research and the strength of evidence supporting each emerging biomarker. We also discuss whether the associations with CHD are strong and consistent enough to improve current risk stratification metrics, and whether these markers enhance our understanding of the underlying biology of CHD and thus point towards new treatment options.
Collapse
Affiliation(s)
- Majken K Jensen
- Department of Nutrition, Harvard School of Public Health, 665 Huntington Avenue, 02115 Boston, MA, USA
| | - Monica L Bertoia
- Department of Nutrition, Harvard School of Public Health, 665 Huntington Avenue, 02115 Boston, MA, USA
| | - Leah E Cahill
- Department of Nutrition, Harvard School of Public Health, 665 Huntington Avenue, 02115 Boston, MA, USA
| | - Isha Agarwal
- Department of Nutrition, Harvard School of Public Health, 665 Huntington Avenue, 02115 Boston, MA, USA
| | - Eric B Rimm
- Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, 181 Longwood Avenue, 02115 Boston, MA, USA
| | - Kenneth J Mukamal
- Department of Medicine, Beth Israel Deaconess Medical Centre, 1309 Beacon Street, 02446 Brookline, MA, USA
| |
Collapse
|
|
50
|
Jun JH, Jun NH, Shim JK, Shin EJ, Kwak YL. Erythropoietin protects myocardium against ischemia-reperfusion injury under moderate hyperglycemia. Eur J Pharmacol 2014; 745:1-9. [PMID: 25446919 DOI: 10.1016/j.ejphar.2014.09.038] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2014] [Revised: 09/23/2014] [Accepted: 09/23/2014] [Indexed: 01/26/2023]
Abstract
Erythropoietin (EPO), an essential hormone for erythropoiesis, provides protection against myocardial ischemia/reperfusion (I/R) injury. Hyperglycemia during acute myocardial infarction aggravates organ damage and attenuates the efficacies of various protective measures. This study aimed to investigate the protective role of EPO against myocardial I/R injury under a clinically relevant moderate hyperglycemic condition and its associated mechanisms. Eighty-two Sprague-Dawley rats were randomly assigned to six groups: normoglycemia-Sham, normoglycemia-I/R-control-saline (IRC), normoglycemia-I/R-EPO (IRE), hyperglycemia-Sham, hyperglycemia-IRC, and hyperglycemia-IRE. The rats received 1.2 g/kg dextrose or same volume of normal saline depending on the group. I/R was induced by a 30 min period of ischemia followed by reperfusion for 4 h. For 1 h before I/R injury, intravenous 4000 IU/kg of EPO was administered. EPO pretreatment significantly reduced the number of apoptotic cells and the infarct size compared with those of the control groups. EPO increased GATA-4 phosphorylation and acetylation against I/R in hyperglycemic myocardium. It also enhanced ERK induced GATA-4 post-translational modifications such as increased GATA-4 phosphorylation and acetylation, and decreased GATA-4 ubiquitination following hypoxia-reoxygenation in H9c2 cells in hyperglycemic medium. Increased GATA-4 stability by EPO diminished I/R-related down-regulation of Bcl-2 and reduction of caspase-3 activities in hyperglycemic myocardium. In conclusion, EPO pretreatment before I/R injury conveyed significant myocardial protection under moderate hyperglycemic condition through mechanisms involved in reduction of caspase-3 activity and up-regulation of Bcl-2 in association with enhanced ERK-induced GATA-4 stability.
Collapse
Affiliation(s)
- Ji Hae Jun
- Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Na-Hyung Jun
- Department of Anesthesiology and Pain Medicine, National Health Insurance Corporation Ilsan Hospital, Goyang, Republic of Korea
| | - Jae-Kwang Shim
- Department of Anesthesiology and Pain Medicine, Yonsei Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Eun Jung Shin
- Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Young-Lan Kwak
- Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea; Department of Anesthesiology and Pain Medicine, Yonsei Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
| |
Collapse
|