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Mubanga M, Gong T, Smew AI, Wikström A, Caffrey Osvald E, Eeg-Olofsson K, Janson C, Lundholm C, Almqvist C. Association between asthma and type 2 diabetes in a Swedish adult population: a register-based cross-sectional study. Thorax 2025; 80:385-391. [PMID: 40122610 DOI: 10.1136/thorax-2024-222819] [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: 12/05/2024] [Accepted: 03/06/2025] [Indexed: 03/25/2025]
Abstract
OBJECTIVE Asthma and type 2 diabetes are two important causes of morbidity globally. We examined both the association of type 2 diabetes with asthma in Swedish adults and the familial co-aggregation of the diseases. METHODS We conducted a cross-sectional study of all adults aged 25-85 in Sweden between 2009 and 2013. Asthma and type 2 diabetes status were ascertained from the health registers. Models were adjusted for sex, age, education level, income and country of birth and in a subset, for body mass index (BMI). We further conducted a familial coaggregation analysis to determine if shared familial factors could explain any observed findings. RESULTS The study included 5 299 245 participants, 25 292 (0.5%) had both asthma and type 2 diabetes. In the total population, the OR for the association between type 2 diabetes and asthma was 1.47 (95% CI 1.45 to 1.49); in the population of men (1.30 (95% CI 1.27 to 1.32)) and women (1.63 (95% CI 1.60 to 1.66)). The ORs were slightly higher among men (1.51 (95% CI 1.45 to 1.56)) and women (2.04 (95% CI 1.96 to 2.11)) for whom BMI measurements were available but attenuated with adjustment for BMI (1.45 (95% CI 1.40 to 1.51)) and (1.76 (95% CI 1.68 to 1.84)). Diabetes was more likely if a full sibling had asthma than if the sibling did not (1.13 (95% CI 1.10 to 1.15)). CONCLUSIONS We found an association between asthma and type 2 diabetes that was sustained after adjusting for BMI, indicating that BMI alone does not explain this relationship. We also found that the two conditions coaggregate in siblings, indicating that the association is partly due to shared familial genetic and environmental risk factors.
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Affiliation(s)
- Mwenya Mubanga
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
- HIV Surveillance Unit, Center for Infectious Disease Research, Lusaka, Zambia
| | - Tong Gong
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Awad I Smew
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Amanda Wikström
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Emma Caffrey Osvald
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
- Pediatric Allergy and Pulmonology Unit, Astrid Lindgren Children's Hospital, Stockholm, Sweden
| | - Katarina Eeg-Olofsson
- Västra Götalandsregionen, Vanersborg, Sweden
- Department of Molecular and Clinical Medicine, University of Gothenburg, Goteborg, Sweden
| | - Christer Janson
- Department of Medical Sciences, Respiratory Medicine, Uppsala University, Uppsala, Sweden
| | - Cecilia Lundholm
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Catarina Almqvist
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
- Pediatric Allergy and Pulmonology Unit, Astrid Lindgren Children's Hospital, Stockholm, Sweden
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Chen C, Huang Z, Liu L, Su B, Feng Y, Huang Y. Lung Function Impairment and Risks of Incident Cardiovascular Diseases and Mortality Among People With Type 2 Diabetes: A Prospective Cohort Study. Diabetes Care 2025; 48:728-736. [PMID: 39932813 PMCID: PMC12034904 DOI: 10.2337/dc24-2188] [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: 10/06/2024] [Accepted: 01/17/2025] [Indexed: 02/13/2025]
Abstract
OBJECTIVE Individuals with type 2 diabetes (T2D) frequently exhibit impaired lung function, potentially accelerating the onset of cardiovascular disease (CVD), although prospective studies remain limited. We aimed to explore the relationship between lung function impairment and risk of CVD and mortality within this high-risk population. RESEARCH DESIGN AND METHODS This prospective study included 16,242 participants with T2D and free of CVD from the UK Biobank. Obstructive physiology (OP), restrictive physiology (RP), and preserved ratio impaired spirometry (PRISm) were defined using spirometry, including forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC). Fine-Gray subdistribution hazards models and Cox proportional hazards models were used to estimate risks of CVD and all-cause mortality, respectively. RESULTS During a median follow-up of 13.9 years, 2,825 incident cases of CVD and 2,811 deaths were documented. Lower FEV1, FVC, FEV1/FVC ratio, FEV1 percent predicted, and FVC percent predicted were related to higher risks of CVD and all-cause mortality. Compared with preserved lung function, the adjusted subdistribution hazard ratios (HRs) for CVD were 1.19 (95% CI 1.05-1.35) for OP and 1.47 (95% CI 1.33-1.65) for RP. Compared with the control group, the subdistribution HRs for CVD were 1.20 (95% CI 1.06-1.36) for OP and 1.43 (95% CI 1.29-1.59) for PRISm. These associations were consistent across subgroups and sensitivity analyses. Adding lung function measurements significantly enhanced the performance of CVD prediction beyond the SCORE2-Diabetes model. CONCLUSIONS Lung function impairment was associated with increased risks of CVD and all-cause mortality among individuals with T2D.
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Affiliation(s)
- Chaolei Chen
- Hypertension Research Laboratory, Cardiovascular Center of Guangdong Province, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Zehan Huang
- Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Lin Liu
- Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Bingbing Su
- Department of Cardiac Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Yingqing Feng
- Hypertension Research Laboratory, Cardiovascular Center of Guangdong Province, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
- Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Yuqing Huang
- Hypertension Research Laboratory, Cardiovascular Center of Guangdong Province, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
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Fan Q, Meng Y, Nie Z, Yi Z, Chen L, Xie S. The role of inflammatory factors in mediating the causal effects of type 1 diabetes mellitus on idiopathic pulmonary fibrosis: A two-step Mendelian randomization study. Medicine (Baltimore) 2025; 104:e41320. [PMID: 39854757 PMCID: PMC11771656 DOI: 10.1097/md.0000000000041320] [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: 06/19/2024] [Revised: 12/15/2024] [Accepted: 01/03/2025] [Indexed: 01/26/2025] Open
Abstract
While recent studies suggested a potential causal link between type 1 diabetes mellitus (T1DM) but not type 2 diabetes mellitus (T2DM) and idiopathic pulmonary fibrosis (IPF), the involved mechanism remains unclear. Here, using a Mendelian randomization (MR) approach, we verified the causal relationship between the two types of diabetes mellitus and IPF and investigated the possible role of inflammation in the association between diabetes mellitus and IPF. Based on genome-wide association study (GWAS) summary data of T1DM, T2DM, and IPF, the univariable MR, multivariable MR (MVMR), and mediation MR were successively used to analyze the causal relationship. Inverse variance weighted was used as the main method to infer the causal effect, together with a series of sensitivity analyses. The univariable MR showed that only T1DM increased the risk of IPF, and there was no significant causal relationship between T2DM and IPF. The MVMR further verified that there was an independent direct causal effect of T1DM on IPF. Further mediation analysis showed that this effect was partly mediated by increasing C-X-C motif chemokine ligand 10 (CXCL10) and interleukin-12 subunit beta (IL-12B). In conclusion, T1DM is related to an increased risk of IPF. Notably, the causal effect was partially mediated by CXCL10 and IL-12B. Hence, monitoring T1DM patients may help in the early detection and prevention of IPF.
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Affiliation(s)
- Qinglu Fan
- Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, China
| | - Yang Meng
- Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Zhihao Nie
- Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, China
| | - Zuohuizi Yi
- Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Liao Chen
- Department of Ultrasound Imaging, Renmin Hospital of Wuhan University, Wuhan, China
| | - Songping Xie
- Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, China
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Hu WS, Lin CL. Effect of anti-diabetic agent on interstitial lung disease in patients with diabetes mellitus. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025; 398:581-589. [PMID: 39031184 DOI: 10.1007/s00210-024-03296-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Accepted: 07/10/2024] [Indexed: 07/22/2024]
Abstract
The objective was to assess the protective role of anti-diabetic agent (ADA) in predicting interstitial lung disease (ILD) among patients with diabetes mellitus (DM). We formed a cohort of DM patients between 2009 and 2016 using data from Taiwan. Univariable and multivariable Cox proportion hazards regression models were used to examine the effect of risk factor on the risk of developing ILD, presented as a hazard ratio (HR) with a 95% confidence interval (CI). Cox proportional hazard regression analysis for the risk of DM-associated ILD with joint effect of dipeptidyl peptidase-4 inhibitor (DPP4I), glucagon-like peptide-1 receptor agonist (GLP-1 RA), and sodium-glucose cotransporter 2 inhibitors (SGLT2I) showed that SGLT2I, GLP-1 RA, and DPP-4I had a decreased risk of ILD with adjusted HR of 0.14 (0.11, 0.18), 0.29 (0.24, 0.35), and 0.64 (0.62, 0.67), respectively. DPP4I, GLP-1 RA, and SGLT2I could be considered to be introduced to this DM population for ILD risk reduction in DM, especially with SGLT2I usage.
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Affiliation(s)
- Wei-Syun Hu
- School of Medicine, College of Medicine, China Medical University, Taichung, 40402, Taiwan.
- Division of Cardiovascular Medicine, Department of Medicine, China Medical University Hospital, 2, Yuh-Der Road, Taichung, 40447, Taiwan.
| | - Cheng-Li Lin
- Management Office for Health Data, China Medical University Hospital, Taichung, 40447, Taiwan
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Wang L, Zhou Y, Jiao X, Zhang Q, Feng K, Shen Y. The discrepant effect of blood glucose on the risk of early and late lung injury: a national cohort study. BMC Pulm Med 2024; 24:628. [PMID: 39709361 DOI: 10.1186/s12890-024-03376-0] [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: 02/18/2024] [Accepted: 10/31/2024] [Indexed: 12/23/2024] Open
Abstract
BACKGROUND The association between glycemic control and short-, and long-term lung health remains controversial. This study aimed to investigate the relationship between glucose control and overall lung health in a national cohort. METHODS The analysis included 5610 subjects from NHANES 2007-2012. We assessed the correlation of glycemic status with respiratory symptoms (cough, sputum, wheeze, and exertional dyspnea), lung function (forced expiratory volume in 1-s (FEV1), forced vital capacity (FVC)), and obstructive or restrictive lung disease (RLD). Furthermore, we determined all-cause mortality in patients with restrictive lung disease by linking data to the National Mortality Index records up to December 31, 2019. RESULTS The study involved the examination of respiratory symptoms, pulmonary function tests, and mortality analyses encompassing 3714, 3916, and 173 subjects, respectively. Multifactorial regression analyses revealed that a 1% increase in blood glucose was associated with a reduction in effect sizes (β) for FVC and FEV1 by -1.66% (-2.47%, -0.86%) and -1.94% (-2.65%, -1.23%), respectively. This increase also exhibited correlations with an elevated risk of exertional dyspnoea, restrictive ventilation dysfunction, and all-cause mortality, presenting odds ratios (ORs) of 1.19 (1.06, 1.33), 1.22 (1.10, 1.36), and 1.61 (1.29, 2.01), respectively. Regarding glycemic control, patients with improved control demonstrated stronger associations with early lung damage, significantly correlating with reduced FVC (β -10.90%, [-14.45%, -7.36%]) and FEV1 (β -9.38%, [-12.90%, -5.87%]). Moreover, they experienced a notably higher risk of exertional dyspnoea (adjusted OR 2.09, [1.35- 3.24]), while the diabetic group with poorer glycemic control showed more significant connections with advanced lung damage. This group exhibited significant associations with an increased risk of restrictive ventilatory dysfunction (adjusted OR, 2.56, [1.70-3.86]) and all-cause mortality (hazard ratios [HRs] 2.65, [1.05-6.67]), all compared to the reference group with normal glycemic metabolism. CONCLUSIONS Elevated blood glucose exhibited an inverse correlation with both long-term and short-term lung health. A negative L-shaped relationship was observed between glycemic control and early lung injury, along with a linearly negative association concerning late-stage lung damage. Given the cross-sectional nature of this study, a longitudinal investigation is needed to validate our findings.
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Affiliation(s)
- Lu Wang
- Department of Endocrinology and Metabolism, Nanchang University Second Affiliated Hospital, Nanchang, 330006, China
- Pingshan District People's Hospital of Shenzhen, Shenzhen, Guangdong, 518118, China
| | - Yicheng Zhou
- Department of Endocrinology and Metabolism, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, 518033, China
- Department of Endocrinology and Metabolism, Nanchang University Second Affiliated Hospital, Nanchang, 330006, China
| | - Xiaojuan Jiao
- Department of Endocrinology and Metabolism, Nanchang University Second Affiliated Hospital, Nanchang, 330006, China
| | - Qin Zhang
- Department of Endocrinology and Metabolism, Nanchang University Second Affiliated Hospital, Nanchang, 330006, China
| | - Kun Feng
- Pingshan District People's Hospital of Shenzhen, Shenzhen, Guangdong, 518118, China.
| | - Yunfeng Shen
- Department of Endocrinology and Metabolism, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, 518033, China.
- Department of Endocrinology and Metabolism, Nanchang University Second Affiliated Hospital, Nanchang, 330006, China.
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Breuil-Marsal Z, Godek C, Lotti A, Feiereisen P, Marçal IR, Rehder-Santos P, Milan-Mattos JC, de Abreu RM. Acute and chronic effects of inspiratory muscle training in patients with type 2 diabetes mellitus: a systematic review of randomized controlled trials. Front Sports Act Living 2024; 6:1423308. [PMID: 39722739 PMCID: PMC11668605 DOI: 10.3389/fspor.2024.1423308] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Accepted: 11/15/2024] [Indexed: 12/28/2024] Open
Abstract
Objectives To conduct a systematic review to determine the acute and chronic effects of inspiratory muscle training (IMT) in type 2 diabetes mellitus (T2DM) patients on cardiac autonomic function, glucose variability, inspiratory muscle strength and endurance, hemodynamic variables, and exercise capacity. Methods A search was carried out according to a specific search strategy, following the PRISMA statement, and three independent reviewers have undertaken the article selection process. Searches were carried out in June 2023, on the following electronic databases: EMBASE, MEDLINE (PubMed), SCOPUS (Elsevier), and Web of Science. The methodological quality of the studies was assessed using the PEDro scale. The search was limited to English-language, randomized controlled trials (RCTs), involving T2DM patients (>18 years old, with or without autonomic neuropathy, and/or inspiratory muscle weakness) following an acute or chronic intervention protocol based on IMT. Exclusion criteria were reviews, clinical trials, case studies, theses, dissertations, scientific conference abstracts, subjects with other chronic respiratory/neurological/cardiovascular diseases, and studies addressing other breathing exercises. Results The search strategy identified 1,352 studies, of which eight (two involving acute and six involving chronic IMT effects) were included. A total of 214 adults aged 52-63 years (51/49 male/female ratio), with BMI ranging from 27 to 36.8 kg/m², were included. The results demonstrated that after IMT, acute effects were reported, such as reduced glucose levels and an increase in the parasympathetic pathway, but also chronic effects including improved inspiratory muscle strength, endurance, and exercise capacity. Conclusion Although some methodological differences among the studies were found, IMT may have beneficial effects on cardiac autonomic function, glucose level control, inspiratory muscle strength/endurance as well as exercise capacity. However, further studies are necessary to confirm these benefits.
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Affiliation(s)
- Zoé Breuil-Marsal
- Department of Health, LUNEX University of Applied Sciences, Differdange, Luxembourg
| | - Clémence Godek
- Department of Health, LUNEX University of Applied Sciences, Differdange, Luxembourg
| | - Amandine Lotti
- Department of Health, LUNEX University of Applied Sciences, Differdange, Luxembourg
| | - Patrick Feiereisen
- Department of Cardiology, Centre Hospitalier de Luxembourg, Luxembourg, Luxembourg
| | - Isabela Roque Marçal
- Exercise Physiology and Cardiovascular Health Lab, Division of Cardiac Prevention and Rehabilitation, University of Ottawa Heart Institute, Ottawa, ON, Canada
| | - Patricia Rehder-Santos
- Dr. Washington Antônio de Barros Teaching Hospital (HU UNIVASF), Brazilian Hospital Services Company (EBSERH), Petrolina, Brazil
| | | | - Raphael Martins de Abreu
- Department of Health, LUNEX University of Applied Sciences, Differdange, Luxembourg
- Department of Health, LUNEX ASBL Luxembourg Health & Sport Sciences Research Institute, Differdange, Luxembourg
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Lin CC, Li CI, Yang CW, Liu CS, Lin CH, Yang SY, Li TC. Effect modification of glycemic control on association of lung function with all-cause and cardiovascular mortality in persons with type 2 diabetes - A retrospective cohort study. Respir Med 2024; 234:107804. [PMID: 39251096 DOI: 10.1016/j.rmed.2024.107804] [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: 04/12/2024] [Revised: 08/14/2024] [Accepted: 09/07/2024] [Indexed: 09/11/2024]
Abstract
BACKGROUND Poor glucose control might deteriorate the impaired pulmonary function, which can ultimately lead to mortality. However, few studies have examined the effect modification of glucose control on the association between pulmonary function and mortality. This study aimed to examine the association of pulmonary function with mortality and determine the effect modification of glycemic level on the association of pulmonary function with mortality in persons with type 2 diabetes (T2DM). METHODS A retrospective cohort study included 3846 persons with T2DM with pulmonary function testing in Taiwan during 2002-2020. Expiratory volume in 1 s (FEV1) was measured as pulmonary function. Cox proportional hazards models were used and the effect modification of pulmonary function parameters and glucose control was assessed by their product terms. RESULTS There were 733 deaths during an average follow-up of 7.83 years. Significant associations of FEV1 and mortality were found (hazards ratio [HR] for FEV1 Z-scores of <0 to -1, <-1 to -2 and <-2: 1.47 [1.20, 1.80], 2.48 [1.95, 3.14] and 3.07 [1.74, 5.44] compared with participants with Z-score ≥0, respectively. All p for trend<0.001). Significant effect modifications were found and the association between FEV1 and mortality was stronger in persons with good glycemic control compared with poor glycemic control (FEV1-FPG effect modification, P = 0.01; FEV1-HbA1c effect modification, P = 0.03). CONCLUSION Pulmonary function, measured by FEV1, is significantly associated with mortality in persons with T2DM. Significant effect modification of glucose control on the association between pulmonary function parameters and mortality was found.
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Affiliation(s)
- Cheng-Chieh Lin
- School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan; Department of Medical Research, China Medical University Hospital, Taichung, Taiwan; Department of Family Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Chia-Ing Li
- School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan; Department of Medical Research, China Medical University Hospital, Taichung, Taiwan
| | - Chuan-Wei Yang
- School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan; Department of Medical Research, China Medical University Hospital, Taichung, Taiwan
| | - Chiu-Shong Liu
- School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan; Department of Medical Research, China Medical University Hospital, Taichung, Taiwan; Department of Family Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Chih-Hsueh Lin
- School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan; Department of Family Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Shing-Yu Yang
- Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan
| | - Tsai-Chung Li
- Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan; Department of Audiology and Speech-Language Pathology, College of Medical and Health Science, Asia University, Taichung, Taiwan.
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Mohammadzadeh M, Athari SZ, Ghiasi F, Keyhanmanesh R, Ghaffari-Nasab A, Roshangar L, Korjan ES, Delkhosh A, Bavil FM. Bone Marrow-Derived C-Kit + Cells Improved Inflammatory IL-33/ST-2/ILC2 Axis in the Lung Tissue of Type 2 Diabetic Rats. Appl Biochem Biotechnol 2024; 196:7074-7088. [PMID: 38478319 DOI: 10.1007/s12010-024-04870-1] [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] [Accepted: 02/12/2024] [Indexed: 11/21/2024]
Abstract
Inflammation is an essential factor in pulmonary complications of diabetes. Bone marrow (BM)-derived C-kit+ cells have immunomodulatory properties and their transplantation is suggested as a promising strategy for ameliorating diabetes complications. This study evaluated the effect of BM-derived C-kit+ cells on the inflammation signaling pathway in lung tissue of type 2 diabetic male rats. Ten rats were used to extract C-kit cells, and 48 male Wistar rats weighing 180 ± 20 g were randomly divided into four equal groups: (1) Control (Cont), (2) Diabetic (D), (3) Diabetic + C-kit+ cells (D + C-kit pos) intravenously injected 50-µl phosphate buffer saline (PBS) containing 300,000 C-kit+ cells, and (4) Diabetic + C-kit- cells (D + C-kit neg), intravenously injected C-kit- cells. Diabetes induction increased IL-33, ST-2, CD127, and IL-2 levels and decreased IL-10. C-kit+ cell therapy significantly decreased IL-33 and CD127 and increased IL-10. In addition, lung histopathological changes significantly improved in the C-kit+ group compared to the diabetic group. These findings suggest that C-kit+ cells may have a potential therapeutic role in mitigating diabetes-induced respiratory complications via ameliorating the inflammation and histopathological changes in lung tissue.
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Affiliation(s)
- Milad Mohammadzadeh
- Stem Cell Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Golgasht Street, Tabriz, 51666-14766, Iran
- Department of Basic Sciences, Maragheh University of Medical Sciences, Maragheh, Iran
| | - Seyed Zanyar Athari
- Stem Cell Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Golgasht Street, Tabriz, 51666-14766, Iran
- Department of Physiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Fariba Ghiasi
- Stem Cell Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Golgasht Street, Tabriz, 51666-14766, Iran
| | - Rana Keyhanmanesh
- Stem Cell Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Golgasht Street, Tabriz, 51666-14766, Iran
| | - Arshad Ghaffari-Nasab
- Stem Cell Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Golgasht Street, Tabriz, 51666-14766, Iran
| | - Leila Roshangar
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Physiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Elnaz Salmani Korjan
- Department of Physiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Aref Delkhosh
- Stem Cell Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Golgasht Street, Tabriz, 51666-14766, Iran
| | - Fariba Mirzaei Bavil
- Department of Basic Sciences, Maragheh University of Medical Sciences, Maragheh, Iran.
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Kaur R, Uppal N, Uppal V, Sharma A. Impaired glycemic control as a risk factor for reduced lung function in the Indian diabetic population. Monaldi Arch Chest Dis 2024. [PMID: 40129369 DOI: 10.4081/monaldi.2024.2912] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2024] [Accepted: 06/03/2024] [Indexed: 03/26/2025] Open
Abstract
Diabetes mellitus (DM) is a metabolic syndrome associated with chronic hyperglycemia, which results in various acute and chronic complications. DM leads to a state of chronic low-grade inflammation, which can have adverse effects on pulmonary functions. There have been contradictory studies related to the relationship between defects in lung functions in diabetic individuals and their correlation with glycemic control and systemic inflammatory markers. The present study aims to compare pulmonary function in controlled and uncontrolled diabetes in the Indian population while exploring the link between inflammatory markers and lung functions in diabetic patients. This observational, case-control study was conducted in the Department of Biochemistry at Sri Guru Ram Das Institute of Medical Sciences and Research in Amritsar, Punjab, on 116 subjects suffering from DM in the age group of 30-65 years. 58 diabetic patients with poor glycemic control [glycated hemoglobin (HbA1c)>7%] and 58 diabetic patients with good glycemic control served as controls (HbA1c≤7%). The duration of the study was two years. Blood samples of each patient were investigated for glycemic control, high-sensitivity C-reactive protein (hsCRP), and serum fibrinogen. Spirometry as a pulmonary function test was undertaken for all participants. The statistical analysis of good and poor glycemic control diabetics showed that the average duration of disease (in years) was 8±5 and 10.2±5.4, respectively. A significant positive correlation was found between inflammatory markers (hsCRP and fibrinogen) and HbA1c and fasting blood glucose. A substantial decline in forced vital capacity and normal values of forced expiratory volume in the first second was observed in poor glycemic control diabetics, depicting a restrictive pattern of lung disease. Lung damage is seen to be more prevalent in patients with a longer duration of disease and increased levels of inflammatory markers. Chronic inflammation due to DM can lead to fibrosis and destruction of lung tissue, resulting in the development of diabetic lung disease, which includes a decline in lung function, an increased risk of infection, and an increased risk of respiratory failure. Therefore, it is essential for individuals with DM to have regular pulmonary function tests and to manage their diabetes to minimize the impact on their lung health.
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Affiliation(s)
- Rozandeep Kaur
- Department of Biochemistry, Sri Guru Ram Das Institute of Medical Sciences and Research, Amritsar, Punjab
| | - Neha Uppal
- Department of Biochemistry, Sri Guru Ram Das Institute of Medical Sciences and Research, Amritsar, Punjab
| | - Vibha Uppal
- Department of Biochemistry, Vardhman Mahavir Medical College and Safdarjung Hospital, Delhi
| | - Anju Sharma
- Department of Biochemistry, Sri Guru Ram Das Institute of Medical Sciences and Research, Amritsar, Punjab
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Shashikadze B, Flenkenthaler F, Kemter E, Franzmeier S, Stöckl JB, Haid M, Riols F, Rothe M, Pichl L, Renner S, Blutke A, Wolf E, Fröhlich T. Multi-omics analysis of diabetic pig lungs reveals molecular derangements underlying pulmonary complications of diabetes mellitus. Dis Model Mech 2024; 17:dmm050650. [PMID: 38900131 PMCID: PMC11583917 DOI: 10.1242/dmm.050650] [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: 12/07/2023] [Accepted: 06/14/2024] [Indexed: 06/21/2024] Open
Abstract
Growing evidence shows that the lung is an organ prone to injury by diabetes mellitus. However, the molecular mechanisms of these pulmonary complications have not yet been characterized comprehensively. To systematically study the effects of insulin deficiency and hyperglycaemia on the lung, we combined proteomics and lipidomics with quantitative histomorphological analyses to compare lung tissue samples from a clinically relevant pig model for mutant INS gene-induced diabetes of youth (MIDY) with samples from wild-type littermate controls. Among others, the level of pulmonary surfactant-associated protein A (SFTPA1), a biomarker of lung injury, was moderately elevated. Furthermore, key proteins related to humoral immune response and extracellular matrix organization were significantly altered in abundance. Importantly, a lipoxygenase pathway was dysregulated as indicated by 2.5-fold reduction of polyunsaturated fatty acid lipoxygenase ALOX15 levels, associated with corresponding changes in the levels of lipids influenced by this enzyme. Our multi-omics study points to an involvement of reduced ALOX15 levels and an associated lack of eicosanoid switching as mechanisms contributing to a proinflammatory milieu in the lungs of subjects with diabetes mellitus.
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Affiliation(s)
- Bachuki Shashikadze
- Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, LMU Munich, 81377 Munich, Germany
| | - Florian Flenkenthaler
- Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, LMU Munich, 81377 Munich, Germany
- German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany
| | - Elisabeth Kemter
- German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany
- Chair for Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, 81377 Munich, Germany
- Center for Innovative Medical Models (CiMM), LMU Munich, 85764 Oberschleißheim, Germany
| | - Sophie Franzmeier
- Institute for Veterinary Pathology, Center for Clinical Veterinary Medicine, LMU Munich, 80539, Germany
| | - Jan B. Stöckl
- Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, LMU Munich, 81377 Munich, Germany
| | - Mark Haid
- Metabolomics and Proteomics Core (MPC), Helmholtz Munich, 85764 Neuherberg, Germany
| | - Fabien Riols
- Metabolomics and Proteomics Core (MPC), Helmholtz Munich, 85764 Neuherberg, Germany
| | | | - Lisa Pichl
- Institute for Veterinary Pathology, Center for Clinical Veterinary Medicine, LMU Munich, 80539, Germany
| | - Simone Renner
- German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany
- Chair for Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, 81377 Munich, Germany
- Center for Innovative Medical Models (CiMM), LMU Munich, 85764 Oberschleißheim, Germany
| | - Andreas Blutke
- Institute for Veterinary Pathology, Center for Clinical Veterinary Medicine, LMU Munich, 80539, Germany
| | - Eckhard Wolf
- Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, LMU Munich, 81377 Munich, Germany
- German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany
- Chair for Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, 81377 Munich, Germany
- Center for Innovative Medical Models (CiMM), LMU Munich, 85764 Oberschleißheim, Germany
| | - Thomas Fröhlich
- Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, LMU Munich, 81377 Munich, Germany
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11
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Guo J, Zhang Y, Zhou R, Hao Y, Wu X, Li G, Du Q. Deciphering the molecular mechanism of Bu Yang Huan Wu Decoction in interference with diabetic pulmonary fibrosis via regulating oxidative stress and lipid metabolism disorder. J Pharm Biomed Anal 2024; 243:116061. [PMID: 38430615 DOI: 10.1016/j.jpba.2024.116061] [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: 12/12/2023] [Revised: 01/27/2024] [Accepted: 02/17/2024] [Indexed: 03/05/2024]
Abstract
BACKGROUND Diabetes mellitus type 2 and pulmonary fibrosis have been found to be closely related in clinical practice. Diabetic pulmonary fibrosis (DPF) is a complication of diabetes mellitus, but its treatment has yet to be thoroughly investigated. Bu Yang Huan Wu Decoction (BYHWD) is a well-known traditional Chinese prescription that has shown great efficacy in treating pulmonary fibrosis with hypoglycemic and hypolipidemic effects. METHODS The active ingredients of BYHWD and the corresponding targets were retrieved from the Traditional Chinese Medicine Systematic Pharmacology Database (TCMSP) and SymMap2. Disease-related targets were obtained from the GeneCard, OMIM and CTD databases. GO enrichment and KEGG pathway enrichment were carried out using the DAVID database. AutoDock Vina software was employed to perform molecular docking. Molecular dynamics simulations of proteinligand complexes were conducted by Gromacs. Animal experiments were further performed to validate the effects of BYHWD on the selected core targets, markers of oxidative stress, serum lipids, blood glucose and pulmonary fibrosis. RESULTS A total of 84 active ingredients and 830 target genes were screened in BYHWD, among which 56 target genes intersected with DPF-related targets. Network pharmacological analysis revealed that the active ingredients can regulate target genes such as IL-6, TNF-α, VEGFA and CASP3, mainly through AGE-RAGE signaling pathway, HIF-1 signaling pathway and TNF signaling pathway. Molecular docking and molecular dynamics simulations suggested that IL6-astragaloside IV, IL6-baicalein, TNFα-astragaloside IV, and TNFα-baicalein docking complexes could bind stably. Animal experiments showed that BYHWD could reduce the expression of core targets such as VEGFA, CASP3, IL-6 and TNF-α. In addition, BYHWD could reduce blood glucose, lipid, and MDA levels in DPF while increasing the activities of SOD, CAT and GSH-Px. BYHWD attenuated the expression of HYP and collagen I, mitigating pathological damage and collagen deposition within lung tissue. CONCLUSIONS BYHWD modulates lipid metabolism disorders and oxidative stress by targeting the core targets of IL6, TNF-α, VEGFA and CASP3 through the AGE-RAGE signaling pathway, making it a potential therapy for DPF.
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Affiliation(s)
- Junfeng Guo
- Endocrinology Department, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610072, China
| | - Yuwei Zhang
- Geriatric Department, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610072, China
| | - Rui Zhou
- Geriatric Department, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610072, China
| | - Yanwei Hao
- Geriatric Department, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610072, China
| | - Xuanyu Wu
- Geriatric Department, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610072, China
| | - Ganggang Li
- Geriatric Department, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610072, China
| | - Quanyu Du
- Endocrinology Department, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610072, China; TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Chengdu, Sichuan 610072, China.
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12
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Ha KS. Transglutaminase 2 in diabetes mellitus: Unraveling its multifaceted role and therapeutic implications for vascular complications. Theranostics 2024; 14:2329-2344. [PMID: 38646650 PMCID: PMC11024853 DOI: 10.7150/thno.95742] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Accepted: 03/17/2024] [Indexed: 04/23/2024] Open
Abstract
Diabetes, a severe metabolic disease characterized by chronic hypoglycemia, poses debilitating and life-threatening risks of microvascular and macrovascular complications, including blindness, kidney failure, heart attacks, and limb amputation. Addressing these complications is paramount, urging the development of interventions targeting diabetes-associated vascular dysfunctions. To effectively combat diabetes, a comprehensive understanding of the pathological mechanisms underlying complications and identification of precise therapeutic targets are imperative. Transglutaminase 2 (TGase2) is a multifunctional enzyme implicated in the pathogenesis of diverse diseases such as neurodegenerative disorders, fibrosis, and inflammatory conditions. TGase2 has recently emerged as a key player in both the pathogenesis and therapeutic intervention of diabetic complications. This review highlights TGase2 as a therapeutic target for diabetic complications and explores TGase2 inhibition as a promising therapeutic approach in their treatment.
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Affiliation(s)
- Kwon-Soo Ha
- Department of Molecular and Cellular Biochemistry, Kangwon National University School of Medicine, Chuncheon, Kangwon-do 24341, Korea
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13
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Goel V, Raizada A, Aggarwal A, Madhu SV, Kar R, Agrawal A, Mahla V, Goel A. Long-Term Persistence of COVID-Induced Hyperglycemia: A Cohort Study. Am J Trop Med Hyg 2024; 110:512-517. [PMID: 38350147 PMCID: PMC10919180 DOI: 10.4269/ajtmh.22-0695] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2022] [Accepted: 11/16/2023] [Indexed: 02/15/2024] Open
Abstract
Although the short-term mortality of patients with COVID-19 infection and hyperglycemia has been well documented, there is little available data regarding longer-term prognosis. The presence of diabetes has not only influenced disease severity but has also impacted its transmission dynamics. In this study, we followed a historical cohort of patients without previous history of diabetes who presented with moderate to severe COVID-19 and were found to have hyperglycemia (random blood glucose > 140 mg/dL) at the time of admission. We evaluated the need for antidiabetic therapy in these patients at the end of 6 months and the risk factors associated with persistent hyperglycemia determined by monthly values of self-monitored blood glucose. Of the seventy participants who were followed telephonically, 54 (77%) continued to receive antidiabetic therapy or have persistent hyperglycemia (> 140 mg/dL) at the end of 6 months. Persistent hyperglycemia at the end of follow-up, was found to be associated with a higher blood glucose at presentation.
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Affiliation(s)
- Vrinda Goel
- Department of Medicine, University College of Medical Sciences, Delhi, India
| | - Alpana Raizada
- Department of Medicine, University College of Medical Sciences, Delhi, India
| | - Amitesh Aggarwal
- Department of Medicine, University College of Medical Sciences, Delhi, India
| | - SV Madhu
- Department of Endocrinology, University College of Medical Sciences, Delhi, India
| | - Rajarshi Kar
- Department of Biochemistry, University College of Medical Sciences, Delhi, India
| | - Ananya Agrawal
- Hamdard Institute of Medical Sciences and Research, Delhi, India
| | - Vikash Mahla
- Department of Medicine, University College of Medical Sciences, Delhi, India
| | - Ashish Goel
- Department of Medicine, Ambedkar State Institute of Medical Sciences, Sahibzada Ajit Singh Nagar, Punjab, India
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14
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Rajizadeh MA, Khoramipour K, Joukar S, Darvishzadeh-Mahani F, Iranpour M, Bejeshk MA, Zaboli MD. Lung molecular and histological changes in type 2 diabetic rats and its improvement by high-intensity interval training. BMC Pulm Med 2024; 24:37. [PMID: 38233819 PMCID: PMC10792831 DOI: 10.1186/s12890-024-02840-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Accepted: 01/02/2024] [Indexed: 01/19/2024] Open
Abstract
BACKGROUND Type 2 diabetes (T2D) leads to serious respiratory problems. This study investigated the effectiveness of high-intensity interval training (HIIT) on T2D-induced lung injuries at histopathological and molecular levels. METHODS Forty-eight male Wistar rats were randomly allocated into control (CTL), Diabetes (Db), exercise (Ex), and Diabetes + exercise (Db + Ex) groups. T2D was induced by a high-fat diet plus (35 mg/kg) of streptozotocin (STZ) administration. Rats in Ex and Db + Ex performed HIIT for eight weeks. Tumor necrosis factor-alpha (TNFα), Interleukin 10 (IL-10), BAX, Bcl2, Lecithin, Sphingomyelin (SPM) and Surfactant protein D (SPD) levels were measured in the bronchoalveolar lavage fluid (BALF) and malondialdehyde (MDA) and total antioxidant capacity (TAC) levels were measured in lung tissue. Lung histopathological alterations were assessed by using H&E and trichrome mason staining. RESULTS Diabetes was significantly associated with imbalance in pro/anti-inflammatory, pro/anti-apoptosis and redox systems, and reduced the SPD, lecithin sphingomyelin and alveolar number. Performing HIIT by diabetic animals increased Bcl2 (P < 0.05) and IL10 (P < 0.01) levels as well as surfactants components and TAC (P < 0.05) but decreased fasting blood glucose (P < 0.001), TNFα (P < 0.05), BAX (P < 0.05) and BAX/Bcl2 (P < 0.001) levels as well as MDA (P < 0.01) and MDA/TAC (P < 0.01) compared to the diabetic group. Furthermore, lung injury and fibrosis scores were increased by T2D and recovered in presence of HIIT. CONCLUSION These findings suggested that the attenuating effect of HIIT on diabetic lung injury mediated by reducing blood sugar, inflammation, oxidative stress, and apoptosis as well as improving pulmonary surfactants components.
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Affiliation(s)
- Mohammad Amin Rajizadeh
- Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
- Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
- Department of Physiology and Pharmacology, Afzalipour Medical Faculty, Kerman University of Medical Sciences, Kerman, Iran
| | - Kayvan Khoramipour
- Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
| | - Siyavash Joukar
- Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
- Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran.
- Department of Physiology and Pharmacology, Afzalipour Medical Faculty, Kerman University of Medical Sciences, Kerman, Iran.
| | - Fatemeh Darvishzadeh-Mahani
- Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
| | - Maryam Iranpour
- Pathology and Stem Cell Research Center, Department of Pathology, Afzalipour Medical Faculty, Kerman University of Medical Sciences, Kerman, Iran
| | - Mohammad Abbas Bejeshk
- Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
- Department of Physiology and Pharmacology, Afzalipour Medical Faculty, Kerman University of Medical Sciences, Kerman, Iran
| | - Maryam Doustaki Zaboli
- Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
- Department of Physiology and Pharmacology, Afzalipour Medical Faculty, Kerman University of Medical Sciences, Kerman, Iran
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15
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Cao GZ, Tian LL, Hou JY, Zhang Y, Xu H, Yang HJ, Zhang JJ. Integrating RNA-sequencing and network analysis to explore the mechanism of topical Pien Tze Huang treatment on diabetic wounds. Front Pharmacol 2024; 14:1288406. [PMID: 38293673 PMCID: PMC10826880 DOI: 10.3389/fphar.2023.1288406] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Accepted: 12/28/2023] [Indexed: 02/01/2024] Open
Abstract
Introduction: Diabetic ulcers have become one of the major complications of diabetes mellitus (DM) and are a leading cause of death and disabling disease. However, current therapies are not effective enough to meet clinical needs. A traditional Chinese medicine (TCM) formula, Pien Tze Huang (PZH), is known as a medicine that is used to treat diabetic ulcers. Methods: In this study, PZH (0.05 g/cm2 and 0.15 g/cm2) and the positive drug-rhEGF were topically administered in a high-fat diet (HFD) and streptozotocin (STZ)-induced diabetic full-thickness incisional wounds, respectively. Wound healing was assessed by wound closure rate, two-photon microscope (SHG), staining with Hematoxylin and eosin (H&E), and Masson's trichrome (MTC). Then, RNA sequencing (RNA-seq) analysis, Enzyme-linked immunosorbent assay (ELISA), western blotting, and immunofluorescence (IF), network analysis, were performed. Results and discussion: The results showed that PZH significantly accelerated wound healing, as well as enhanced the expression of collagen. RNA-seq analysis showed that PZH has functions on various biological processes, one of the key biological processes is inflammatory response. Tlr9, Klrk1, Nod2, Tlr2, and Ifng were identified as vital targets and the NF-κB signaling pathway was identified as the vital pathway. Additionally, PZH profoundly reduced the levels of Cleaved caspase-3 and promoted the expression of CD31 and TGF-β1. Mechanically, PZH significantly decreased expression of NKG2-D, NOD2, and TLR2, and further inhibited the activation of downstream NF-κB signaling pathway and inhibited expression of inflammatory factors (IFN-γ and IL-1β). Importantly, we found that several active ingredients may play a significant role in diabetic wound healing, including Notoginsenoside R1, Deoxycorticosterone, Ursolic acid, and 4-Methoxyphenol. In summary, our study sheds light on the complicated mechanisms underlying the promising anti-diabetic wounds of PZH and provides the discovery of agents treating diabetic ulcers.
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Affiliation(s)
- Guang-Zhao Cao
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
- Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing, China
| | - Liang-Liang Tian
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
| | - Jing-Yi Hou
- Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yi Zhang
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
| | - He Xu
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
| | - Hong-Jun Yang
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
- Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing, China
| | - Jing-Jing Zhang
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
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16
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Martínez-Sánchez JE, Cárdenas Y, Trujillo X, Ríos-Silva M, Díaz-Reval MI, Bricio-Barrios JA, Muñiz J, Alcaraz-Siqueiros J, Huerta M. Increased Frequency of Giant Miniature End-Plate Potentials at the Neuromuscular Junction in Diabetic Rats. Biomedicines 2023; 12:68. [PMID: 38255175 PMCID: PMC10813272 DOI: 10.3390/biomedicines12010068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Revised: 12/20/2023] [Accepted: 12/23/2023] [Indexed: 01/24/2024] Open
Abstract
There is a need for research addressing the functional characteristics of the motor end-plate in diabetes to identify mechanisms contributing to neuromuscular dysfunction. Here, we investigated the effect of diabetes on spontaneous acetylcholine release in the rat neuromuscular junction. We studied two randomized groups of male Wistar rats (n = 7 per group, 350 ± 50 g, 12-16 weeks of age): one with streptozotocin-induced experimental diabetes, and a healthy control group without diabetes. After 8 weeks of monitoring after diabetes induction, rats in both groups were anesthetized with pentobarbital. Then, the diaphragm muscle was dissected for electrophysiological recordings of miniature end-plate potentials (MEPPs) using a single electrode located at the region of the muscle end-plate. All experiments were conducted at environmental temperature (20-22 °C) in rat Ringer solution with constant bubbling carbogen (95% O2, 5% CO2). Compared to healthy controls, in the diaphragm neuromuscular end-plate derived from diabetic rats, the MEPPs were higher in amplitude and frequency, and the proportion of giant MEPPs was elevated (7.09% vs. 1.4% in controls). Our results showed that diabetes affected the acetylcholine MEPP pattern and increased the number of giant potentials compared to healthy controls.
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Affiliation(s)
- Julián Elías Martínez-Sánchez
- Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Av. 25 de julio # 965, Col. Villas San Sebastián, Colima 28045, Colima, Mexico; (J.E.M.-S.); (X.T.)
| | - Yolitzy Cárdenas
- Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Av. 25 de julio # 965, Col. Villas San Sebastián, Colima 28045, Colima, Mexico; (J.E.M.-S.); (X.T.)
| | - Xóchitl Trujillo
- Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Av. 25 de julio # 965, Col. Villas San Sebastián, Colima 28045, Colima, Mexico; (J.E.M.-S.); (X.T.)
| | - Mónica Ríos-Silva
- Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Av. 25 de julio # 965, Col. Villas San Sebastián, Colima 28045, Colima, Mexico; (J.E.M.-S.); (X.T.)
- Centro Universitario de Investigaciones Biomédicas, Universidad de Colima—CONAHCyT, Av. 25 de Julio 965, Col. Villas San Sebastián, Colima 28045, Colima, Mexico
| | - M. Irene Díaz-Reval
- Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Av. 25 de julio # 965, Col. Villas San Sebastián, Colima 28045, Colima, Mexico; (J.E.M.-S.); (X.T.)
| | - Jaime Alberto Bricio-Barrios
- Facultad de Medicina, Universidad de Colima, Av. Universidad #333, Col. Las Víboras, Colima 28040, Colima, Mexico;
| | - Jesús Muñiz
- Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Av. 25 de julio # 965, Col. Villas San Sebastián, Colima 28045, Colima, Mexico; (J.E.M.-S.); (X.T.)
| | - Julio Alcaraz-Siqueiros
- Facultad de Ciencias Biológicas y Agropecuarias, Universidad de Colima, Km 40 Autopista Colima-Manzanillo, Crucero de Tecomán, Tecomán 28930, Colima, Mexico
| | - Miguel Huerta
- Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Av. 25 de julio # 965, Col. Villas San Sebastián, Colima 28045, Colima, Mexico; (J.E.M.-S.); (X.T.)
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17
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Sababathy M, Ramanathan G, Abd Rahaman NY, Ramasamy R, Biau FJ, Qi Hao DL, Hamid NFS. A 'one stone, two birds' approach with mesenchymal stem cells for acute respiratory distress syndrome and Type II diabetes mellitus. Regen Med 2023; 18:913-934. [PMID: 38111999 DOI: 10.2217/rme-2023-0193] [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] [Indexed: 12/20/2023] Open
Abstract
This review explores the intricate relationship between acute respiratory distress syndrome (ARDS) and Type II diabetes mellitus (T2DM). It covers ARDS epidemiology, etiology and pathophysiology, along with current treatment trends and challenges. The lipopolysaccharides (LPS) role in ARDS and its association between non-communicable diseases and COVID-19 are discussed. The review highlights the therapeutic potential of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) for ARDS and T2DM, emphasizing their immunomodulatory effects. This review also underlines how T2DM exacerbates ARDS pathophysiology and discusses the potential of hUC-MSCs in modulating immune responses. In conclusion, the review highlights the multidisciplinary approach to managing ARDS and T2DM, focusing on inflammation, oxidative stress and potential therapy of hUC-MSCs in the future.
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Affiliation(s)
- Mogesh Sababathy
- Department of Veterinary Pathology & Microbiology, Faculty of Veterinary Medicine, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia
| | - Ghayathri Ramanathan
- Faculty of Computer Science & Information Technology, Universiti Malaya, 50603, Kuala Lumpur, Malaysia
| | - Nor Yasmin Abd Rahaman
- Department of Veterinary Laboratory Diagnostics, Faculty of Veterinary Medicine, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia
- Laboratory of Vaccines & Biomolecules, Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia
| | - Rajesh Ramasamy
- Department of Pathology, Faculty of Medicine & Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia
| | - Foo Jhi Biau
- Centre for Drug Discovery & Molecular Pharmacology (CDDMP), Faculty of Health & Medical Sciences, Taylor's University, Selangor, Subang Jaya, 47500, Malaysia
- School of Pharmacy, Faculty of Health & Medical Sciences, Taylor's University, Selangor, Subang Jaya, 47500, Malaysia
| | - Daniel Looi Qi Hao
- My Cytohealth Sdn. Bhd., 18-2, Jalan Radin Bagus 1, Bandar Seri Petaling, Kuala Lumpur, 57000, Malaysia
| | - Nur-Fazila Saulol Hamid
- Department of Veterinary Pathology & Microbiology, Faculty of Veterinary Medicine, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia
- Laboratory of Vaccines & Biomolecules, Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia
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18
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Wang AJ, Ren J, Wang A, Hascall VC. Monocyte adhesive hyaluronan matrix induced by hyperglycemia in diabetic lung injuries. J Biol Chem 2023; 299:104995. [PMID: 37394007 PMCID: PMC10413281 DOI: 10.1016/j.jbc.2023.104995] [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: 04/26/2023] [Revised: 06/19/2023] [Accepted: 06/26/2023] [Indexed: 07/04/2023] Open
Abstract
Infiltrated pre-inflammatory monocytes and macrophages have important roles in the induction of diabetic lung injuries, but the mechanism mediating their infiltration is still unclear. Here, we showed that airway smooth muscle cells (SMCs) activated monocyte adhesion in response to hyperglycemic glucose (25.6 mM) by significantly increasing hyaluronan (HA) in the cell matrix, with concurrent 2- to 4-fold increases in adhesion of U937 monocytic-leukemic cells. The HA-based structures were attributed directly to the high-glucose and not to increased extracellular osmolality, and they required growth stimulation of SMCs by serum. Treatment of SMCs with heparin in high-glucose induces synthesis of a much larger HA matrix, consistent with our observations in the glomerular SMCs. Further, we observed increases in tumor necrosis factor-stimulated gene-6 (TSG-6) expression in high-glucose and high-glucose plus heparin cultures, and the heavy chain (HC)-modified HA structures existed on the monocyte-adhesive cable structures in high-glucose and in high-glucose plus heparin-treated SMC cultures. Interestingly, these HC-modified HA structures were unevenly distributed along the HA cables. Further, the in vitro assay with recombinant human TSG-6 and the HA14 oligo showed that heparin has no inhibitory activity on the TSG-6-induced HC-transfer to HA, consistent with the results from SMC cultures. These results support the hypothesis that hyperglycemia in airway smooth muscle induces the synthesis of a HA matrix that recruits inflammatory cells and establishes a chronic inflammatory process and fibrosis that lead to diabetic lung injuries.
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Affiliation(s)
- Andrew Jun Wang
- Department of Biomedical Engineering, Cleveland Clinic, Cleveland, Ohio, USA
| | - Juan Ren
- Department of Biomedical Engineering, Cleveland Clinic, Cleveland, Ohio, USA
| | - Aimin Wang
- Department of Biomedical Engineering, Cleveland Clinic, Cleveland, Ohio, USA
| | - Vincent C Hascall
- Department of Biomedical Engineering, Cleveland Clinic, Cleveland, Ohio, USA.
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Bejeshk MA, Bagheri F, Salimi F, Rajizadeh MA. The Diabetic Lung Can Be Ameliorated by Citrullus colocynthis by Reducing Inflammation and Oxidative Stress in Rats with Type 1 Diabetes. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2023; 2023:5176645. [PMID: 37520024 PMCID: PMC10382246 DOI: 10.1155/2023/5176645] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Revised: 04/29/2023] [Accepted: 07/09/2023] [Indexed: 08/01/2023]
Abstract
Background Diabetes impacts various organs in the body and some reports showed that the lung is also affected by diabetes, and an imbalance of inflammation and oxidative stress may participate to diabetic lung impairments. The present study is conducted to assess the impacts of Citrullus colocynthis (CC) on some aspects of these impairments. Methods Frothy two male Wistar rats (3-4 months old and weighing 200-250 g) were used in the present research. Animals were divided into 3 groups of control, Diabetes, and Diabetes + Drug. CC was administered to diabetic rats orally. The lung tissue and BALF oxidative stress and inflammatory indices including the MDA, TAC, SOD, Gpx, TNFα, IL-6, IL-17, and IL-10 were evaluated by the ELISA method. Results Our observations disclosed the ameliorative impacts of CC administration against oxidative stress and inflammation imbalance. Also, it was found that CC improved body weight and fasting blood sugar in rats with diabetes. Conclusion We can conclude that the administration of CC can be effective in improving diabetic lungs in rats.
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Affiliation(s)
- Mohammad Abbas Bejeshk
- Department of Physiology, Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Fatemeh Bagheri
- Pathology and Stem Cell Research Center, Department of Pathology, Afzalipour Medical Faculty, Kerman University of Medical Sciences, Kerman, Iran
- Legal Medicine Research Center, Legal Medicine Organization, Kerman, Iran
| | - Fouzieh Salimi
- Department of Clinical Biochemistry, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Mohammad Amin Rajizadeh
- Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
- Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
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Rizk FH, El-Saka MH, Ibrahim RR, El-Deeb OS, Ibrahim HA, El Saadany AA, Mashal SS, Ammar L, Abdelsattar AM, Barhoma RA. Possible mitigating effect of adropin on lung injury in diabetic rats: Targeting the role of Rho A/Rho-associated kinase pathway. Biofactors 2023; 49:928-939. [PMID: 37103121 DOI: 10.1002/biof.1955] [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: 02/05/2023] [Accepted: 03/31/2023] [Indexed: 04/28/2023]
Abstract
This study evaluated possible mitigating effect of adropin on lung injury in diabetic rats, targeting role of Rho A/Rho-associated kinase pathway. Rats were allocated into four groups: control, adropin, diabetic, and diabetic+adropin groups. At the termination of the experiment, serum fasting glucose, insulin and adropin levels and insulin resistance were calculated. Wet/dry ratio, histopathological, immunohistochemical analyses, and relative real time gene expression of lung tissue was determined. Interleukin-6, tumor necrosis factor alpha, malondialdehyde, 8-Oxo-2'-deoxyguanosine, reduced glutathione, superoxide dismutase, Bcl-2, BAX, myeloperoxidase, intracellular adhesion molecule-1, vascular cell adhesion molecule-1, and transforming growth factor-β were determined in lung tissue. Adropin treatment in diabetic rats notably attenuated hyperglycemia and insulin resistance. Also, it mitigated diabetic lung injury via suppressing effect on Rho A/ROCK pathway, apoptosis, inflammatory reactions, oxidative stress, and fibrosis of lung tissue. Adropin can be considered as a promising therapeutic agent for treating diabetic lung injury.
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Affiliation(s)
- Fatma H Rizk
- Department of Physiology, Faculty of Medicine, Tanta University, Egypt
| | - Mervat H El-Saka
- Department of Physiology, Faculty of Medicine, Tanta University, Egypt
| | - Rowida Raafat Ibrahim
- Department of Medical Biochemistry & Molecular Biology, Faculty of Medicine, Tanta University, Egypt
| | - Omnia Safwat El-Deeb
- Department of Medical Biochemistry & Molecular Biology, Faculty of Medicine, Tanta University, Egypt
| | - Hoda A Ibrahim
- Department of Medical Biochemistry & Molecular Biology, Faculty of Medicine, Tanta University, Egypt
| | - Amira A El Saadany
- Department of Pharmacology, Faculty of Medicine, Tanta University, Egypt
| | - Shaimaa S Mashal
- Department of Internal Medicine, Faculty of Medicine, Tanta University, Egypt
| | - Leila Ammar
- Department of Histology, Faculty of Medicine, Tanta University, Egypt
| | | | - Ramez A Barhoma
- Department of Physiology, Faculty of Medicine, Tanta University, Egypt
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Liu XY, Wei DG, Li RS. Ghrelin attenuates inflammation in diabetic lung disease by TLR4 pathway in vivo and in vitro. BMJ Open Diabetes Res Care 2023; 11:11/2/e003027. [PMID: 37085277 PMCID: PMC10123865 DOI: 10.1136/bmjdrc-2022-003027] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Accepted: 03/11/2023] [Indexed: 04/23/2023] Open
Abstract
INTRODUCTION Diabetic lung disease is already known as one of the diabetes complications, but report on its therapeutic strategy is rare. The present study aimed to add novel therapeutic strategy for diabetic lung disease, to reveal the protective effect of ghrelin on diabetic lung disease both in vivo and in vitro, and to discuss its probable molecular mechanism. RESEARCH DESIGN AND METHODS Diabetic mice and 16HBE cells were our research objects. We surveyed the effect of ghrelin on streptozotocin-induced lung tissue morphology changes by H&E staining. Furthermore, the changes of proinflammatory cytokines (interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)) were detected by ELISA. To expound the molecular mechanism, we detected critical proteins of TLR4 pathway and observed their changes by immunohistochemistry (IHC), real-time PCR and western blot analysis in vivo and in vitro, respectively. RESULTS The results of H&E staining showed that pathological alterations of the lung induced by hyperglycemia were ameliorated by ghrelin. The results of ELISA demonstrated that the elevated levels of IL-1β and TNF-α induced by hyperglycemia turned to decrease in the lung after ghrelin treatment. In the results of IHC, real-time PCR and western blot analysis, we found that the TLR4 pathway was elevated by hyperglycemia or high glucose and is remarkably inhibited by the treatment of ghrelin both in vivo and in vitro. CONCLUSIONS Ghrelin could inhibit inflammation of diabetic lung disease by regulating the TLR4 pathway. This study might affect research on diabetic lung disease, and the therapeutic potential of ghrelin for diabetic lung disease is worth considering.
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Affiliation(s)
- Xiao-Yan Liu
- Department of Pulmonary and Critical Care Medicine, Shanxi Provincial People's Hospital, Taiyuan, Shanxi, China
| | - Dong-Guang Wei
- Department of Pulmonary and Critical Care Medicine, Shanxi Provincial People's Hospital, Taiyuan, Shanxi, China
| | - Rong-Shan Li
- Department of Nephrology, Shanxi Provincial People's Hospital, Taiyuan, Shanxi, China
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22
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Promsrisuk T, Kongsui R, Sriraksa N, Boonla O, Srithawong A. Elastic band resistance combined with modified Thai yoga exercise to alleviate oxidative stress and airway inflammation in type 2 diabetes mellitus. J Exerc Rehabil 2023; 19:114-125. [PMID: 37163180 PMCID: PMC10164522 DOI: 10.12965/jer.2346040.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Accepted: 02/26/2023] [Indexed: 05/11/2023] Open
Abstract
The objective of this study was to investigate the effects of the combination of elastic band resistance exercise (EBRE) with modified Thai yoga on the alleviation of blood glucose and oxidative stress in type 2 diabetes mellitus (T2DM). Forty-two patients with T2DM were enrolled and allocated to an exercise or control group (n=21/group). The exercise group participated in EBRE combination with modified Thai yoga for 40 min, 5 days/wk, for 12 consecutive weeks. Blood glucose, oxidative stress markers, antioxidants, pulmonary function, respiratory muscle strength, and airway inflammation were measured before and after the 12 weeks. The results showed that the exercise group had a significant reduction in fasting blood glucose and glycated hemoglobin. Moreover, T2DM patients in the exercise group showed a significant reduction in plasma malondialdehyde, while superoxide dismutase and catalase were significantly increased. The exercise group also observed a significant improvement in pulmonary function; forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), FEV1/FVC, peak expiratory flow, and forced midexpiratory flow as well as respiratory muscle strength. Interestingly, the combination of EBRE with modified Thai yoga markedly improved airway inflammation through the reduction in fractional exhaled nitric oxide. In conclusion, these findings suggest that the combination of EBRE with modified Thai yoga improves blood glucose, oxidative stress, antioxidants, pulmonary function, respiratory muscle strength, and airway inflammation in T2DM patients. Hence, it could be considered as a possible exercise program for T2DM patients.
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Affiliation(s)
- Tichanon Promsrisuk
- Division of Physiology, School of Medical Sciences, University of Phayao, Phayao,
Thailand
- Unit of Excellence in the Pulmonary and Cardiovascular Health Care, University of Phayao, Phayao,
Thailand
| | - Ratchaniporn Kongsui
- Division of Physiology, School of Medical Sciences, University of Phayao, Phayao,
Thailand
| | - Napatr Sriraksa
- Division of Physiology, School of Medical Sciences, University of Phayao, Phayao,
Thailand
- Unit of Excellence in the Pulmonary and Cardiovascular Health Care, University of Phayao, Phayao,
Thailand
| | - Orachorn Boonla
- Faculty of Allied Health Sciences, Burapha University, Chonburi,
Thailand
- Exercise and Nutrition Innovation and Sciences Research Unit, Burapha University, Chonburi,
Thailand
| | - Arunrat Srithawong
- Department of Physical Therapy, School of Allied Health Sciences, University of Phayao, Phayao,
Thailand
- Corresponding author: Arunrat Srithawong, Department of Physical Therapy, School of Allied Health Sciences, University of Phayao, Phayao 56000, Thailand,
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Bu F, Deng XH, Zhan NN, Cheng H, Wang ZL, Tang L, Zhao Y, Lyu QY. Development and validation of a risk prediction model for frailty in patients with diabetes. BMC Geriatr 2023; 23:172. [PMID: 36973658 PMCID: PMC10045211 DOI: 10.1186/s12877-023-03823-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Accepted: 02/14/2023] [Indexed: 03/29/2023] Open
Abstract
BACKGROUND Frailty is the third most common complication of diabetes after macrovascular and microvascular complications. The aim of this study was to develop a validated risk prediction model for frailty in patients with diabetes. METHODS The research used data from the China Health and Retirement Longitudinal Study (CHARLS), a dataset representative of the Chinese population. Twenty-five indicators, including socio-demographic variables, behavioral factors, health status, and mental health parameters, were analyzed in this study. The study cohort was randomly divided into a training set and a validation set at a ratio of 70 to 30%. LASSO regression analysis was used to screen the variables for the best predictors of the model based on a 10-fold cross-validation. The logistic regression model was applied to explore the associated factors of frailty in patients with diabetes. A nomogram was constructed to develop the prediction model. Calibration curves were applied to evaluate the accuracy of the nomogram model. The area under the receiver operating characteristic curve and decision curve analysis were conducted to assess predictive performance. RESULTS One thousand four hundred thirty-six patients with diabetes from the CHARLS database collected in 2013 (n = 793) and 2015 (n = 643) were included in the final analysis. A total of 145 (10.9%) had frailty symptoms. Multivariate logistic regression analysis showed that marital status, activities of daily living, waist circumference, cognitive function, grip strength, social activity, and depression as predictors of frailty in people with diabetes. These factors were used to construct the nomogram model, which showed good concordance and accuracy. The AUC values of the predictive model and the internal validation set were 0.912 (95%CI 0.887-0.937) and 0.881 (95% CI 0.829-0.934). Hosmer-Lemeshow test values were P = 0.824 and P = 0.608 (both > 0.05). Calibration curves showed significant agreement between the nomogram model and actual observations. ROC and DCA indicated that the nomogram had a good predictive performance. CONCLUSIONS Comprehensive nomogram constructed in this study was a promising and convenient tool to evaluate the risk of frailty in patients with diabetes, and contributed clinicians to screening the high-risk population.
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Affiliation(s)
- Fan Bu
- School of Nursing, Jinan University, No. 601, West Huangpu Avenue, Guangzhou, People's Republic of China
| | - Xiao-Hui Deng
- School of Nursing, Jinan University, No. 601, West Huangpu Avenue, Guangzhou, People's Republic of China
| | - Na-Ni Zhan
- School of Nursing, Jinan University, No. 601, West Huangpu Avenue, Guangzhou, People's Republic of China
| | - Hongtao Cheng
- School of Nursing, Jinan University, No. 601, West Huangpu Avenue, Guangzhou, People's Republic of China
| | - Zi-Lin Wang
- School of Nursing, Jinan University, No. 601, West Huangpu Avenue, Guangzhou, People's Republic of China
| | - Li Tang
- School of Nursing, Jinan University, No. 601, West Huangpu Avenue, Guangzhou, People's Republic of China
| | - Yu Zhao
- School of Nursing, Jinan University, No. 601, West Huangpu Avenue, Guangzhou, People's Republic of China
| | - Qi-Yuan Lyu
- School of Nursing, Jinan University, No. 601, West Huangpu Avenue, Guangzhou, People's Republic of China.
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Cheng TY, Chang CC, Luo CS, Chen KY, Yeh YK, Zheng JQ, Wu SM. Targeting Lung-Gut Axis for Regulating Pollution Particle-Mediated Inflammation and Metabolic Disorders. Cells 2023; 12:901. [PMID: 36980242 PMCID: PMC10047528 DOI: 10.3390/cells12060901] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Revised: 03/09/2023] [Accepted: 03/13/2023] [Indexed: 03/17/2023] Open
Abstract
Cigarette smoking (CS) or ambient particulate matter (PM) exposure is a risk factor for metabolic disorders, such as insulin resistance (IR), increased plasma triglycerides, hyperglycemia, and diabetes mellitus (DM); it can also cause gut microbiota dysbiosis. In smokers with metabolic disorders, CS cessation decreases the risks of serious pulmonary events, inflammation, and metabolic disorder. This review included recent studies examining the mechanisms underlying the effects of CS and PM on gut microbiota dysbiosis and metabolic disorder development; one of the potential mechanisms is the disruption of the lung-gut axis, leading to gut microbiota dysbiosis, intestinal dysfunction, systemic inflammation, and metabolic disease. Short-chain fatty acids (SCFAs) are the primary metabolites of gut bacteria, which are derived from the fermentation of dietary fibers. They activate G-protein-coupled receptor (GPCR) signaling, suppress histone deacetylase (HDAC) activity, and inhibit inflammation, facilitating the maintenance of gut health and biofunction. The aforementioned gut microbiota dysbiosis reduces SCFA levels. Treatment targeting SCFA/GPCR signaling may alleviate air pollution-associated inflammation and metabolic disorders, which involve lung-gut axis disruption.
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Affiliation(s)
- Tzu-Yu Cheng
- Division of Cardiovascular Surgery, Department of Surgery, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan;
- Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
| | - Chih-Cheng Chang
- Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan; (C.-C.C.); (C.-S.L.); (K.-Y.C.); (Y.-K.Y.); (J.-Q.Z.)
- Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
- TMU Research Center for Thoracic Medicine, Taipei Medical University, Taipei 11031, Taiwan
| | - Ching-Shan Luo
- Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan; (C.-C.C.); (C.-S.L.); (K.-Y.C.); (Y.-K.Y.); (J.-Q.Z.)
- Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
- TMU Research Center for Thoracic Medicine, Taipei Medical University, Taipei 11031, Taiwan
- International Ph.D. Program in Cell Therapy and Regenerative Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
| | - Kuan-Yuan Chen
- Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan; (C.-C.C.); (C.-S.L.); (K.-Y.C.); (Y.-K.Y.); (J.-Q.Z.)
- Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
- TMU Research Center for Thoracic Medicine, Taipei Medical University, Taipei 11031, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
| | - Yun-Kai Yeh
- Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan; (C.-C.C.); (C.-S.L.); (K.-Y.C.); (Y.-K.Y.); (J.-Q.Z.)
- TMU Research Center for Thoracic Medicine, Taipei Medical University, Taipei 11031, Taiwan
| | - Jing-Quan Zheng
- Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan; (C.-C.C.); (C.-S.L.); (K.-Y.C.); (Y.-K.Y.); (J.-Q.Z.)
- Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
- TMU Research Center for Thoracic Medicine, Taipei Medical University, Taipei 11031, Taiwan
| | - Sheng-Ming Wu
- Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan; (C.-C.C.); (C.-S.L.); (K.-Y.C.); (Y.-K.Y.); (J.-Q.Z.)
- Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
- TMU Research Center for Thoracic Medicine, Taipei Medical University, Taipei 11031, Taiwan
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Ordaz-Vázquez A, Torres-González P, Ferreyra-Reyes L, Canizales-Quintero S, Delgado-Sánchez G, García-García L, Ponce-De-León A, Sifuentes-Osornio J, Bobadilla-Del-Valle M. Mycobacterium tuberculosis lineage 4 associated with cavitations and treatment failure. BMC Infect Dis 2023; 23:154. [PMID: 36918814 PMCID: PMC10012486 DOI: 10.1186/s12879-023-08055-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Accepted: 02/06/2023] [Indexed: 03/16/2023] Open
Abstract
BACKGROUND Mycobacterium tuberculosis genotyping has been crucial to determining the distribution and impact of different families on disease clinical presentation. The aim of the study was to evaluate the associations among sociodemographic and clinical characteristics and M. tuberculosis lineages from patients with pulmonary tuberculosis in Orizaba, Veracruz, Mexico. METHODS We analyzed data from 755 patients whose isolates were typified by 24-loci mycobacterial interspersed repetitive unit-variable number of tandem repeats (MIRU-VNTR). The associations among patient characteristics and sublineages found were evaluated using logistic regression analysis. RESULTS Among M. tuberculosis isolates, 730/755 (96.6%) were assigned to eight sublineages of lineage 4 (Euro-American). Alcohol consumption (adjusted odds ratio [aOR] 1.528, 95% confidence interval (CI) 1.041-2.243; p = 0.030), diabetes mellitus type 2 (aOR 1.625, 95% CI 1.130-2.337; p = 0.009), sputum smear positivity grade (3+) (aOR 2.198, 95% CI 1.524-3.168; p < 0.001) and LAM sublineage isolates (aOR 1.023, 95% CI 1.023-2.333; p = 0.039) were associated with the presence of cavitations. Resistance to at least one drug (aOR 25.763, 95% CI 7.096-93.543; p < 0.001) and having isolates other than Haarlem and LAM sublineages (aOR 6.740, 95% CI 1.704-26.661; p = 0.007) were associated with treatment failure. In a second model, multidrug resistance was associated with treatment failure (aOR 31.497, 95% CI 5.119-193.815; p < 0.001). Having more than 6 years of formal education was not associated with treatment failure. CONCLUSIONS Knowing M. tuberculosis genetic diversity plays an essential role in disease development and outcomes, and could have important implications for guiding treatment and improving tuberculosis control.
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Affiliation(s)
- Anabel Ordaz-Vázquez
- Departamento de Infectología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Belisario Domínguez Sección XVI, Tlalpan, 14080, Mexico City, Mexico
| | - Pedro Torres-González
- Departamento de Infectología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Belisario Domínguez Sección XVI, Tlalpan, 14080, Mexico City, Mexico
| | - Leticia Ferreyra-Reyes
- Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca, Mexico
| | - Sergio Canizales-Quintero
- Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca, Mexico
| | - Guadalupe Delgado-Sánchez
- Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca, Mexico
| | - Lourdes García-García
- Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca, Mexico
| | - Alfredo Ponce-De-León
- Departamento de Infectología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Belisario Domínguez Sección XVI, Tlalpan, 14080, Mexico City, Mexico
| | - José Sifuentes-Osornio
- Departamento de Infectología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Belisario Domínguez Sección XVI, Tlalpan, 14080, Mexico City, Mexico
| | - Miriam Bobadilla-Del-Valle
- Departamento de Infectología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Belisario Domínguez Sección XVI, Tlalpan, 14080, Mexico City, Mexico.
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Wang W, Mei A, Qian H, Li D, Xu H, Chen J, Yang H, Min X, Li C, Cheng L, Chen J. The Role of Glucagon-Like Peptide-1 Receptor Agonists in Chronic Obstructive Pulmonary Disease. Int J Chron Obstruct Pulmon Dis 2023; 18:129-137. [PMID: 36815056 PMCID: PMC9939668 DOI: 10.2147/copd.s393323] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Accepted: 02/02/2023] [Indexed: 02/17/2023] Open
Abstract
Chronic obstructive pulmonary disease (COPD) is one of the common diseases of the respiratory system. As the disease recurs, damage to the airways and lung tissue gradually worsens, leading to a progressive decline in lung function, affecting the patient's workforce and quality of life, and causing a huge social and economic burden. Diabetes is a common comorbidity of COPD and patients with COPD are at increased risk of developing diabetes, while hyperglycemia can also reduce lung function and contribute to the progression and poor prognosis of COPD. Glucagon-like peptide-1 receptor agonist (GLP-1RA) is a new type of hypoglycemic agent that has been shown to regulate blood glucose levels, reduce inflammatory responses and oxidative stress, and regulate lipid metabolism, among other effects. GLP-1RAs may benefit COPD patients by acting directly on the lung from mechanisms such as reducing the inflammatory response, improving oxidative stress, regulating protease/anti-protease imbalance, improving airway mucus homeostasis, and reducing airway remodeling. This study provides a review of the potential role of GLP-1RAs in COPD and offers new ideas for the prevention and treatment of COPD.
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Affiliation(s)
- Wenwen Wang
- Sinopharm Dongfeng General Hospital, Hubei University of Medicine, Hubei Key Laboratory of Wudang Local Chinese Medicine Research (Hubei University of Medicine), Shiyan, People’s Republic of China
| | - Aihua Mei
- Sinopharm Dongfeng General Hospital, Hubei University of Medicine, Hubei Key Laboratory of Wudang Local Chinese Medicine Research (Hubei University of Medicine), Shiyan, People’s Republic of China
| | - Hang Qian
- Sinopharm Dongfeng General Hospital, Hubei University of Medicine, Hubei Key Laboratory of Wudang Local Chinese Medicine Research (Hubei University of Medicine), Shiyan, People’s Republic of China
| | - Dongfeng Li
- Sinopharm Dongfeng General Hospital, Hubei University of Medicine, Hubei Key Laboratory of Wudang Local Chinese Medicine Research (Hubei University of Medicine), Shiyan, People’s Republic of China
| | - Hao Xu
- Sinopharm Dongfeng General Hospital, Hubei University of Medicine, Hubei Key Laboratory of Wudang Local Chinese Medicine Research (Hubei University of Medicine), Shiyan, People’s Republic of China
| | - Jishun Chen
- Sinopharm Dongfeng General Hospital, Hubei University of Medicine, Hubei Key Laboratory of Wudang Local Chinese Medicine Research (Hubei University of Medicine), Shiyan, People’s Republic of China
| | - Handong Yang
- Sinopharm Dongfeng General Hospital, Hubei University of Medicine, Hubei Key Laboratory of Wudang Local Chinese Medicine Research (Hubei University of Medicine), Shiyan, People’s Republic of China
| | - Xinwen Min
- Sinopharm Dongfeng General Hospital, Hubei University of Medicine, Hubei Key Laboratory of Wudang Local Chinese Medicine Research (Hubei University of Medicine), Shiyan, People’s Republic of China
| | - Chunlei Li
- Sinopharm Dongfeng General Hospital, Hubei University of Medicine, Hubei Key Laboratory of Wudang Local Chinese Medicine Research (Hubei University of Medicine), Shiyan, People’s Republic of China
| | - Li Cheng
- Sinopharm Dongfeng General Hospital, Hubei University of Medicine, Hubei Key Laboratory of Wudang Local Chinese Medicine Research (Hubei University of Medicine), Shiyan, People’s Republic of China
| | - Jun Chen
- Sinopharm Dongfeng General Hospital, Hubei University of Medicine, Hubei Key Laboratory of Wudang Local Chinese Medicine Research (Hubei University of Medicine), Shiyan, People’s Republic of China
- Institute of Virology, Hubei University of Medicine, Shiyan, Hubei, 442000, People’s Republic of China
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Jeong HE, Park S, Noh Y, Bea S, Filion KB, Yu OHY, Jang SH, Cho YM, Yon DK, Shin JY. Association of adverse respiratory events with sodium-glucose cotransporter 2 inhibitors versus dipeptidyl peptidase 4 inhibitors among patients with type 2 diabetes in South Korea: a nationwide cohort study. BMC Med 2023; 21:47. [PMID: 36765407 PMCID: PMC9913005 DOI: 10.1186/s12916-023-02765-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Accepted: 02/01/2023] [Indexed: 02/12/2023] Open
Abstract
BACKGROUND Impaired respiratory function remains underrecognized in patients with type 2 diabetes (T2D), despite common pulmonary impairment. Meanwhile, there is little data available on the respiratory effects of sodium glucose cotransporter 2 inhibitors (SGLT2i). Hence, we examined the association between SGLT2i use and the risk of adverse respiratory events in a real-world setting. METHODS We conducted a population-based, nationwide cohort study using an active-comparator new-user design and nationwide claims data of South Korea from January 2015 to December 2020. Among individuals aged 18 years or older, propensity score matching was done to match each new user of SGLT2is with dipeptidyl peptidase 4 inhibitors (DPP4is), with patients followed up according to an as-treated definition. The primary outcome was respiratory events, a composite endpoint of acute pulmonary edema, acute respiratory distress syndrome (ARDS), pneumonia, and respiratory failure. Secondary outcomes were the individual components of the primary outcome and in-hospital death. Cox models were used to estimate hazard ratios (HRs) and 95% CIs. RESULTS Of 205,534 patient pairs in the propensity score matched cohort, the mean age of the entire cohort was 53.8 years and 59% were men, with a median follow-up of 0.66 years; all baseline covariates achieved balance between the two groups. Incidence rates for overall respiratory events were 4.54 and 7.54 per 1000 person-years among SGLT2i and DPP4i users, respectively, corresponding to a rate difference of 3 less events per 1000 person-years (95% CI - 3.44 to - 2.55). HRs (95% CIs) were 0.60 (0.55 to 0.64) for the composite respiratory endpoint, 0.35 (0.23 to 0.55) for acute pulmonary edema, 0.44 (0.18 to 1.05) for ARDS, 0.61 (0.56 to 0.66) for pneumonia, 0.49 (0.31 to 0.76) for respiratory failure, and 0.46 (0.41 to 0.51) for in-hospital death. Similar trends were found across individual SGLT2is, subgroup analyses of age, sex, history of comorbidities, and a range of sensitivity analyses. CONCLUSIONS These findings suggest a lower risk of adverse respiratory events associated with patients with T2D initiating SGLT2is versus DPP4is. This real-world evidence helps inform patients, clinicians, and guideline writers regarding the respiratory effects of SGLT2i in routine practice.
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Affiliation(s)
- Han Eol Jeong
- School of Pharmacy, Sungkyunkwan University, Suwon, South Korea.,Department of Biohealth Regulatory Science, Sungkyunkwan University, Suwon, South Korea
| | - Sohee Park
- School of Pharmacy, Sungkyunkwan University, Suwon, South Korea
| | - Yunha Noh
- School of Pharmacy, Sungkyunkwan University, Suwon, South Korea.,Department of Biohealth Regulatory Science, Sungkyunkwan University, Suwon, South Korea
| | - Sungho Bea
- School of Pharmacy, Sungkyunkwan University, Suwon, South Korea
| | - Kristian B Filion
- Departments of Medicine and of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC, Canada.,Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada
| | - Oriana H Y Yu
- Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada.,Division of Endocrinology and Metabolism, Jewish General Hospital, McGill University, Montreal, QC, Canada
| | - Seung Hun Jang
- Division of Pulmonary, Allergy, and Critical Care Medicine, College of Medicine, Hallym University Sacred Heart Hospital, Hallym University, Anyang, South Korea
| | - Young Min Cho
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea.,Department of Translational Medicine, Seoul National University College of Medicine, Seoul, South Korea.,Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea.,Institute On Aging, Seoul National University, Seoul, South Korea
| | - Dong Keon Yon
- Medical Science Research Institute, Kyung Hee University College of Medicine, Seoul, South Korea.,Department of Pediatrics, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, South Korea
| | - Ju-Young Shin
- School of Pharmacy, Sungkyunkwan University, Suwon, South Korea. .,Department of Biohealth Regulatory Science, Sungkyunkwan University, Suwon, South Korea. .,Department of Clinical Research Design & Evaluation, Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Sungkyunkwan University, Seoul, South Korea.
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28
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Allinson JP, Patel PH, Donaldson GC. Obesity, Insulin Resistance, and Asthma. Am J Respir Crit Care Med 2022; 206:1057-1058. [PMID: 35819866 PMCID: PMC9704836 DOI: 10.1164/rccm.202207-1271ed] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Affiliation(s)
- James P Allinson
- National Heart and Lung Institute Imperial College London London, United Kingdom
- Royal Brompton Hospital London, United Kingdom
| | | | - Gavin C Donaldson
- National Heart and Lung Institute Imperial College London London, United Kingdom
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29
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Zhu Y, Liu Y, Jiang H. Geriatric Health Care During the COVID-19 Pandemic: Managing the Health Crisis. Clin Interv Aging 2022; 17:1365-1378. [PMID: 36158515 PMCID: PMC9491878 DOI: 10.2147/cia.s376519] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2022] [Accepted: 08/20/2022] [Indexed: 01/08/2023] Open
Abstract
COVID-19 pandemic significantly threatens the health and well-being of older adults. Aging-related changes, including multimorbidity, weakened immunity and frailty, may make older people more susceptible to severe infection and place them at higher risk of morbidity and mortality from COVID-19. Various quarantine measures have been implemented to control the spread of COVID-19. Nevertheless, such social distancing has disrupted routine health care practices, such as accessibility of medical services and long-term continuous care services. The medical management of older adults with multimorbidity is significantly afflicted by COVID-19. Older persons with frailty or multiple chronic disease may poorly adapt to the altered health care system, having detrimental consequences on their physical and mental health. COVID-19 pandemic has posed great challenges to the health of older adults. We highlighted the difficulties and obstacles of older adults during this unprecedented time. Also, we provided potential strategies and recommendations for actions to mitigate the COVID-19 pandemic threats. Certain strategies like community primary health care, medication delivery and home care support are adopted by many health facilities and caregivers, whereas other services such as internet hospital and virtual medical care are promoted to be accessible in many regions. However, guidelines and policies based on high-quality data are still needed for better health promotion of older groups with increasing resilience during the COVID-19 pandemic.
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Affiliation(s)
- Yingqian Zhu
- Department of Geriatrics, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200123, People's Republic of China.,Department of General Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200123, People's Republic of China
| | - Yue Liu
- Department of Geriatrics, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200123, People's Republic of China.,Department of General Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200123, People's Republic of China
| | - Hua Jiang
- Department of Geriatrics, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200123, People's Republic of China.,Department of General Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200123, People's Republic of China
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30
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Tao ZS, Wang HS, Li TL, Wei S. Silibinin-modified Hydroxyapatite coating promotes the osseointegration of titanium rods by activation SIRT1/SOD2 signaling pathway in diabetic rats. JOURNAL OF MATERIALS SCIENCE. MATERIALS IN MEDICINE 2022; 33:62. [PMID: 36057883 PMCID: PMC9441422 DOI: 10.1007/s10856-022-06684-1] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Accepted: 08/01/2022] [Indexed: 05/06/2023]
Abstract
The purpose of this study is to investigate the role of Silibinin (SIL)-modified Hydroxyapatite coating on osseointegration in diabetes in vivo and in vitro and explore the mechanism of osteogenic differentiation of MC3T3-E1. RT-qPCR, Immunofluorescence, and Western blot were used to measure the expression level of oxidative Stress Indicators and osteogenic markers proteins. Moreover, CCK-8 assay was conducted to detect cell viability in hyperglycemia. Alizarin red staining and alkaline phosphatase staining were used to examine osteogenic function and calcium deposits. The diabetic rat model receive titanium rod implantation was set up successfully and Von-Gieson staining was used to examine femoral bone tissue around titanium rod. Our results showed that intracellular oxidative stress in hyperglycemia was overexpressed, while FoxO1, SIRT1, GPX1, and SOD2 were downregulated. SIL suppressed oxidative stress to promote osteogenic differentiation. Additionally, it was confirmed that SIL promoted osteogenic differentiation of MC3T3-E1 and obviously restored the osseointegration ability of diabetic rats. Further study indicated that SIL exerted its beneficial function through activation SIRT1/SOD2 signaling pathway to restore osteoblast function, and improved the osseointegration and stability of titanium rods in vivo. Our research suggested that the SIL-modulated oxidative Stress inhibition is responsible for the activation of the process of osteogenic differentiation through activation SIRT1/SOD2 signaling pathway in hyperglycemia, providing a novel insight into improving prosthetic osseointegration in diabetic patients. Hyperglycemia impaired the activity and function of MC3T3-E1 and inhibits bone formation by up-regulating intracellular ROS levels through inhibition of SIRT1/SOD2 signaling pathway. Local administrator SIL can improve the activity and function of osteoblasts and enhance osseointegration by reducing intracellular ROS through activation of SIRT1/SOD2 signaling pathway in DM rat models.
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Affiliation(s)
- Zhou-Shan Tao
- Department of Orthopedics, The First Affiliated Hospital of Wannan Medical College, Yijishan Hospital, No. 2, Zhe Shan Xi Road, Wuhu, 241001, Anhui, P.R. China.
- Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution (Wannan Medical College), No. 2, Zhe Shan Xi Road, Wuhu, China.
| | - Hai-Sheng Wang
- Department of Orthopedics, The First Affiliated Hospital of Wannan Medical College, Yijishan Hospital, No. 2, Zhe Shan Xi Road, Wuhu, 241001, Anhui, P.R. China
| | - Tian-Lin Li
- Department of Orthopedics, The First Affiliated Hospital of Wannan Medical College, Yijishan Hospital, No. 2, Zhe Shan Xi Road, Wuhu, 241001, Anhui, P.R. China
| | - Shan Wei
- School of Mechanical Engineering, Anhui Polytechnic University, Wuhu, 241000, P.R. China
- Additive Manufacturing Institute of Anhui Polytechnic University, Anhui Polytechnic University, Wuhu, 241000, P.R. China
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31
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Dash RR, Panda B, Panigrahi M, Nayak B. A Step Toward the Exploration of Better Spirometric Parameters for Early Diagnosis of Pulmonary Dysfunction in Persons With Type 2 Diabetes Mellitus. Cureus 2022; 14:e26622. [PMID: 35949805 PMCID: PMC9356661 DOI: 10.7759/cureus.26622] [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] [Accepted: 07/06/2022] [Indexed: 11/21/2022] Open
Abstract
Objectives: This study aims to determine the forced vital capacity (FVC) and slow vital capacity (SVC) along with other pulmonary functions in Indian diabetic patients for early diagnosis of pulmonary function reduction and to compare the ratios of forced expiratory volume in one second (FEV1) with FVC and SVC (FEV1/FVC and FEV1/SVC) in diabetic patients. Materials and methods: A prospective observational study was carried out in the physiology department for two years after the approval of the institutional ethics committee. The study included 90 type 2 diabetes mellitus patients previously diagnosed by the physician and 90 age and sex-matched controls for spirometric tests. Medspiror having Helios 401 software (Recorders & Medicare Systems Pvt. Ltd., Panchkula, India) was used to assess the pulmonary function in all subjects. A comparison of dynamic pulmonary function parameters among non-diabetic and diabetic groups and non-obese vs. overweight/obese individuals of the diabetic group has been done. FEV1/FVC ratio vs. FEV1/SVC ratio comparison was conducted between the non-obese vs. the overweight/obese group in diabetic patients. Results: A significant variation in FEV1 and FVC was observed in the type 2 diabetic group as compared to the non-diabetic group. However, in the case of type 2 diabetic subjects, FEV1/FVC ratio was almost constant in both BMI groups, whereas the FEV1/SVC ratio increased in the overweight/obese group. Conclusion: Type 2 diabetes mellitus accounts for a predictive factor for worsening pulmonary function. SVC, particularly the FEV1/SVC ratio, can be an earlier diagnostic marker for pulmonary dysfunction in diabetic subjects as this ratio changes even with a constant FEV1/FVC ratio.
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32
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Yamada Y, Sato T, Harada N, Kayawake H, Tanaka S, Yutaka Y, Hamaji M, Nakajima D, Ohsumi A, Date H. Perioperative diabetes mellitus affects the outcomes of lung transplant recipients. Eur J Cardiothorac Surg 2022; 62:6604741. [PMID: 35678573 DOI: 10.1093/ejcts/ezac344] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Revised: 05/05/2022] [Accepted: 06/03/2022] [Indexed: 11/13/2022] Open
Abstract
OBJECTIVE Identifying the risks for chronic lung allograft dysfunction (CLAD) after lung transplantation (LTx) is beneficial to the patient. We hypothesized that diabetes mellitus (DM) is relevant to CLAD development. Our study aimed to clarify if DM is a risk for poor post-LTx outcomes. METHODS The records of patients first undergoing LTx in our institution between 2010 and 2018 were reviewed retrospectively. Patient characteristics and postoperative outcomes were analyzed. We established 6 months post-LTx as the landmark point for predicting overall survival (OS) and CLAD development. To identify perioperative DM, we evaluated the patient for DM at 6 months post-LTx. RESULTS A total of 172 patients were investigated. DM and CLAD occurred in 76 and 39 patients, respectively, and 40 died. At 6 months post-LTx, the unadjusted and adjusted hazard ratios (HRs) of DM for OS were 3.36 (95% confidence interval [CI95%] = [1.67-6.73]) and 2.78 (CI95% = [1.35-5.75]), respectively. The unadjusted and adjusted HRs of DM for CLAD-free survival were 2.20 (CI95% = [1.27-3.80]) and 2.15 (CI95% = [1.24-3.74]). The patients with DM were older and had a higher body mass index and more incidents of post-LTx malignant disease than the non-DM patients. The five-year OS and CLAD-free survival rates of the patients with or without DM were 57.2% vs 86.5% and 50.1% vs 72.9%, respectively. CONCLUSIONS Perioperative DM was identified as an independent adverse factor for OS and CLAD-free survival. Perioperative management of DM should be emphasized in the clinical setting of lung transplantation.
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Affiliation(s)
- Yoshito Yamada
- Department of Thoracic Surgery, Kyoto University Hospital, Kyoto, Japan
| | - Tosiya Sato
- Department of Biostatistics, Kyoto University School of Public Health, Kyoto, Japan
| | - Norio Harada
- Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Hidenao Kayawake
- Department of Thoracic Surgery, Kyoto University Hospital, Kyoto, Japan
| | - Satona Tanaka
- Department of Thoracic Surgery, Kyoto University Hospital, Kyoto, Japan
| | - Yojiro Yutaka
- Department of Thoracic Surgery, Kyoto University Hospital, Kyoto, Japan
| | - Masatsugu Hamaji
- Department of Thoracic Surgery, Kyoto University Hospital, Kyoto, Japan
| | - Daisuke Nakajima
- Department of Thoracic Surgery, Kyoto University Hospital, Kyoto, Japan
| | - Akihiro Ohsumi
- Department of Thoracic Surgery, Kyoto University Hospital, Kyoto, Japan
| | - Hiroshi Date
- Department of Thoracic Surgery, Kyoto University Hospital, Kyoto, Japan
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33
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Luo L, Luo J, Jiang Y. A retrospective analysis of risk factors for massive hemoptysis in patients with bronchiectasis. BMC Pulm Med 2022; 22:214. [PMID: 35650568 PMCID: PMC9161452 DOI: 10.1186/s12890-022-02006-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2022] [Accepted: 05/25/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Massive hemoptysis is a common and fatal complication of bronchiectasis. However, the risk factors for massive hemoptysis in patients with bronchiectasis have not yet been reported. This study investigated the potential risk factors for massive hemoptysis in patients with bronchiectasis. METHODS This retrospective study included patients with bronchiectasis and their data were obtained from medical records. The risk factors for massive hemoptysis were evaluated by multivariate analysis of patient characteristics, medical history, and computed tomography imaging data, including the number of lesions, lesion location, and laboratory findings. RESULTS Among 379 patients, 61 (16.09%) experienced severe hemoptysis. Multivariate analysis revealed that diabetes (odds ratio (OR) 2.885; 95% confidence interval (CI) 1.009-8.247), lesions involving two lobes (OR 4.347; 95% CI 1.960-9.638) and three lobes (OR 2.787; 95% CI 1.055-7.363) were significant predictors of severe hemoptysis. However, a disease course between 1 and 5 years (OR 0.300; 95% CI 0.112-0.801) and involvement of the left lower lobe (OR 0.394; 95% CI 0.196-0.793) were protective factors for the prevention of massive hemoptysis. Lesions in the right upper lobe were more likely to cause massive hemoptysis (OR 1.458) than involvement of other lobes. CONCLUSIONS Diabetes and lesions involving two and three lobes, were risk factors for massive hemoptysis in patients with bronchiectasis. Disease duration between 1 and 5 years and involvement of the left lower lobe were protective factors, while lesions in the right upper lobe had a stronger relationship with massive hemoptysis in patients with bronchiectasis.
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Affiliation(s)
- Ling Luo
- Department of Respiratory and Critical Medicine, University-Town Hospital of Chongqing Medical University, Chongqing, 401331, China
| | - Jing Luo
- Department of Respiratory and Critical Medicine, University-Town Hospital of Chongqing Medical University, Chongqing, 401331, China
| | - Yu Jiang
- Department of Respiratory and Critical Medicine, University-Town Hospital of Chongqing Medical University, Chongqing, 401331, China.
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34
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BALIK AÖ, YAĞCI B. Quantitative computerized tomography evaluation of the effects of COVID-19 pneumonia on lung volume. CUKUROVA MEDICAL JOURNAL 2022. [DOI: 10.17826/cumj.1030243] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022] Open
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35
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Wonnacott A, Denby L, Coward RJM, Fraser DJ, Bowen T. MicroRNAs and their delivery in diabetic fibrosis. Adv Drug Deliv Rev 2022; 182:114045. [PMID: 34767865 DOI: 10.1016/j.addr.2021.114045] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Revised: 09/21/2021] [Accepted: 11/04/2021] [Indexed: 12/11/2022]
Abstract
The global prevalence of diabetes mellitus was estimated to be 463 million people in 2019 and is predicted to rise to 700 million by 2045. The associated financial and societal costs of this burgeoning epidemic demand an understanding of the pathology of this disease, and its complications, that will inform treatment to enable improved patient outcomes. Nearly two decades after the sequencing of the human genome, the significance of noncoding RNA expression is still being assessed. The family of functional noncoding RNAs known as microRNAs regulates the expression of most genes encoded by the human genome. Altered microRNA expression profiles have been observed both in diabetes and in diabetic complications. These transcripts therefore have significant potential and novelty as targets for therapy, therapeutic agents and biomarkers.
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Affiliation(s)
- Alexa Wonnacott
- Wales Kidney Research Unit, Division of Infection & Immunity, School of Medicine, College of Biomedical and Life Sciences, Cardiff University, Heath Park, Cardiff CF14 4XN, UK
| | - Laura Denby
- Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Little France Crescent, Edinburgh EH16 4TJ, UK
| | - Richard J M Coward
- Bristol Renal, Dorothy Hodgkin Building, Bristol Medical School, University of Bristol, Bristol BS1 3NY, UK
| | - Donald J Fraser
- Wales Kidney Research Unit, Division of Infection & Immunity, School of Medicine, College of Biomedical and Life Sciences, Cardiff University, Heath Park, Cardiff CF14 4XN, UK
| | - Timothy Bowen
- Wales Kidney Research Unit, Division of Infection & Immunity, School of Medicine, College of Biomedical and Life Sciences, Cardiff University, Heath Park, Cardiff CF14 4XN, UK.
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36
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Hyrylä VV, Rissanen APE, Peltonen JE, Koponen AS, Tikkanen HO, Tarvainen MP. Altered Expiratory Flow Dynamics at Peak Exercise in Adult Men With Well-Controlled Type 1 Diabetes. Front Physiol 2022; 13:836814. [PMID: 35250637 PMCID: PMC8894884 DOI: 10.3389/fphys.2022.836814] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Accepted: 01/26/2022] [Indexed: 11/13/2022] Open
Abstract
Type 1 diabetes may, in time, cause lung dysfunction including airflow limitation. We hypothesized that ventilatory flow morphology during a cardiopulmonary exercise test (CPET) would be altered in adult men with well-controlled type 1 diabetes. Thirteen men with type 1 diabetes [glycated hemoglobin A1c 59 (9) mmol/mol or 7.5 (0.8)%, duration of diabetes 12 (9) years, and age 33.9 (6.6) years] without diagnosed diabetes-related complications and 13 healthy male controls [age 37.2 (8.6) years] underwent CPET on a cycle ergometer (40 W increments every 3 min until volitional fatigue). We used a principal component analysis based method to quantify ventilatory flow dynamics throughout the CPET protocol. Last minute of each increment, peak exercise, and recovery were examined using linear mixed models, which accounted for relative peak oxygen uptake and minute ventilation. The type 1 diabetes participants had lower expiratory peak flow (P = 0.008) and attenuated slope from expiration onset to expiratory peak flow (P = 0.012) at peak exercise when compared with the healthy controls. Instead, during submaximal exercise and recovery, the type 1 diabetes participants possessed similar ventilatory flow dynamics to that of the healthy controls. In conclusion, men with relatively well-controlled type 1 diabetes and without clinical evidence of diabetes-related complications exhibited attenuated expiratory flow at peak exercise independently of peak oxygen uptake and minute ventilation. This study demonstrates that acute exercise reveals alterations in ventilatory function in men with type 1 diabetes but not until peak exercise.
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Affiliation(s)
- Vesa V. Hyrylä
- Department of Applied Physics, University of Eastern Finland, Kuopio, Finland
- *Correspondence: Vesa V. Hyrylä,
| | - Antti-Pekka E. Rissanen
- Department of Sports and Exercise Medicine, Clinicum, University of Helsinki, Helsinki, Finland
- HULA—Helsinki Sports and Exercise Medicine Clinic, Foundation for Sports and Exercise Medicine, Helsinki, Finland
| | - Juha E. Peltonen
- Department of Sports and Exercise Medicine, Clinicum, University of Helsinki, Helsinki, Finland
- HULA—Helsinki Sports and Exercise Medicine Clinic, Foundation for Sports and Exercise Medicine, Helsinki, Finland
| | - Anne S. Koponen
- Department of Sports and Exercise Medicine, Clinicum, University of Helsinki, Helsinki, Finland
| | - Heikki O. Tikkanen
- Department of Sports and Exercise Medicine, Clinicum, University of Helsinki, Helsinki, Finland
- School of Medicine, Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland
| | - Mika P. Tarvainen
- Department of Applied Physics, University of Eastern Finland, Kuopio, Finland
- Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland
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Hentsch L, Cocetta S, Allali G, Santana I, Eason R, Adam E, Janssens JP. Dificultad respiratoria y COVID-19: Un llamado a la investigación. KOMPASS NEUMOLOGÍA 2022. [PMCID: PMC9059027 DOI: 10.1159/000521663] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
La dificultad respiratoria, también conocida como disnea, es un síntoma frecuente que causa debilidad. Varios reportes han destacado la ausencia de disnea en un subgrupo de pacientes que padecen COVID-19, en la llamada hipoxemia «silenciosa» o «feliz». Los reportes también han mencionado la falta de una relación clara entre la gravedad clínica de la enfermedad y los niveles de disnea referidos por los pacientes. Se ha demostrado en gran medida que entre las complicaciones cerebrales del COVID-19 hay alta prevalencia de encefalopatía aguda, que podría afectar el procesamiento de las señales aferentes o bien la modulación descendente de las señales de disnea. En esta revisión pretendemos destacar los mecanismos implicados en la disnea y resumir la fisiopatología del COVID-19 y sus efectos en la interacción cerebro-pulmón. Posteriormente, presentamos hipótesis sobre la alteración de la percepción de la disnea en pacientes con COVID-19 y sugerimos formas de investigar más a fondo este fenómeno.
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Affiliation(s)
- Lisa Hentsch
- División de Medicina Paliativa, Hospitales de la Universidad de Ginebra, Ginebra, Suiza
- *Lisa Hentsch,
| | | | - Gilles Allali
- División de Neurología, Hospitales de la Universidad de Ginebra y Facultad de Medicina, Universidad de Ginebra, Ginebra, Suiza
- Departamento de Neurología, División de Envejecimiento Cognitivo y Motor, Albert Einstein College of Medicine, Yeshiva University, Bronx, New York, Estados Unidos
| | | | - Rowena Eason
- Phyllis Tuckwell Hospice Care, Surrey, Reino Unido
| | - Emily Adam
- Investigador independiente, Londres, Reino Unido
| | - Jean-Paul Janssens
- División de Enfermedades Pulmonares, Hospital de la Universidad de Ginebra, Ginebra, Suiza
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Pelle MC, Zaffina I, Provenzano M, Moirano G, Arturi F. COVID-19 and diabetes-Two giants colliding: From pathophysiology to management. Front Endocrinol (Lausanne) 2022; 13:974540. [PMID: 36060943 PMCID: PMC9437522 DOI: 10.3389/fendo.2022.974540] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Accepted: 08/01/2022] [Indexed: 01/08/2023] Open
Abstract
Since December 2019, a new coronavirus, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread around the world, causing the coronavirus 2019 (COVID-19) pandemic. From the beginning, SARS-CoV-2 has put a strain on the health system. In fact, many patients have had severe forms of the disease with the need for hospitalization due to respiratory failure. To contain the pandemic, the most widely used approach has been lockdowns. Social restrictions have been reduced thanks to the development of vaccines and targeted therapies. However, fatal events still occur among people at high risk of serious infection, such as patients with concomitant diabetes. Different mechanisms have been proposed to explain the poor prognosis of patients with diabetes and COVID-19, but the specific cause is unclear. It is now known that insulin resistance, inflammation, and cytokine storm are involved. Moreover, SARS-CoV-2 uses the angiotensin-converting enzyme 2 receptors to enter cells. This receptor is expressed on pancreatic beta cells and, during infection, it appears that receptor involvement may induce hyperglycemia in patients with or without diabetes. In this study, we discuss the mechanisms underlying the poor prognosis in people with COVID-19 and diabetes and what may improve the outcome in these patients.
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Affiliation(s)
- Maria Chiara Pelle
- Department of Medical and Surgical Sciences, University ‘Magna Graecia’ of Catanzaro, Catanzaro, Italy
| | - Isabella Zaffina
- Department of Medical and Surgical Sciences, University ‘Magna Graecia’ of Catanzaro, Catanzaro, Italy
| | - Michele Provenzano
- Nephrology, Dialysis and Transplantation Unit, Department of Experimental, Diagnostic and Specialty Medicine (DIMES) Alma Mater Studiorum, University of Bologna, Bologna, Italy
| | - Giovenale Moirano
- Department of Medical Sciences, University of Turin, CPO-Piemonte, Turin, Italy
| | - Franco Arturi
- Department of Medical and Surgical Sciences, University ‘Magna Graecia’ of Catanzaro, Catanzaro, Italy
- Research Center for the Prevention and Treatment of Metabolic Diseases (CR METDIS), University ‘Magna Graecia’ of Catanzaro, Catanzaro, Italy
- *Correspondence: Franco Arturi,
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Hentsch L, Cocetta S, Allali G, Santana I, Eason R, Adam E, Janssens JP. Atemnot und COVID-19: Ein Aufruf zu mehr Forschung. KOMPASS PNEUMOLOGIE 2022. [PMCID: PMC8805046 DOI: 10.1159/000521460] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Atemnot, auch als Dyspnoe bezeichnet, ist ein häufiges und lähmendes Symptom. In mehreren Berichten wurde die Abwesenheit von Atemnot bei einer Untergruppe von Patienten mit COVID-19 hervorgehoben, die manchmal als «stille» oder «glückliche Hypoxie» bezeichnet wird. Ebenfalls wurde in Berichten erwähnt, dass es an einem klaren Zusammenhang zwischen dem klinischen Schweregrad der Erkrankung und der von den Patienten berichteten Schwere der Atemnot fehlt. Die zerebralen Komplikationen von COVID-19 sind weitgehend nachgewiesen, mit einer hohen Prävalenz akuter Enzephalopathien, die möglicherweise die Verarbeitung afferenter Signale oder die absteigende Modulation von Atemnotsignalen beeinträchtigen könnte. In dieser Übersichtsarbeit möchten wir die an der Atemnot beteiligten Mechanismen hervorheben und die Pathophysiologie von COVID-19 und den bekannten Auswirkungen der Erkrankung auf die Interaktion von Gehirn und Lunge zusammenfassen. Anschließend stellen wir Hypothesen für die Veränderung der Wahrnehmung von Atemnot bei COVID-19-Patienten auf und schlagen Möglichkeiten vor, mit denen dieses Phänomen weiter erforscht werden könnte.
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Affiliation(s)
- Lisa Hentsch
- Abteilung für Pallativmedizin an den Hôpitaux universitaires de Genève, Genf, Schweiz
- *Lisa Hentsch,
| | | | - Gilles Allali
- Abteilung für Neurologie, Hôpitaux universitaires de Genève und Medizinische Fakultät der Universität Genf, Genf, Schweiz
- Division of Cognitive and Motor Aging, Department of Neurology, Albert Einstein College of Medicine, Yeshiva University, Bronx, New York, USA
| | | | - Rowena Eason
- Phyllis Tuckwell Hospice Care, Surrey, Vereinigtes Königreich
| | - Emily Adam
- Unabhängige Forscherin, London, Vereinigtes Königreich
| | - Jean-Paul Janssens
- Abteilung für Lungenkrankheiten, Hôpitaux universitaires de Genève, Genf, Schweiz
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Liu Y, Zhang H, Dai X, Zhu R, Chen B, Xia B, Ye Z, Zhao D, Gao S, Orekhov AN, Zhang D, Wang L, Guo S. A comprehensive review on the phytochemistry, pharmacokinetics, and antidiabetic effect of Ginseng. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2021; 92:153717. [PMID: 34583224 DOI: 10.1016/j.phymed.2021.153717] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Revised: 08/08/2021] [Accepted: 08/15/2021] [Indexed: 06/13/2023]
Abstract
BACKGROUND Radix Ginseng, one of the well-known medicinal herbs, has been used in the management of diabetes and its complications for more than 1000 years. PURPOSE The aim of this review is devoted to summarize the phytochemistry and pharmacokinetics of Ginseng, and provide evidence for the antidiabetic effects of Ginseng and its ingredients as well as the underlying mechanisms involved. METHODS For the purpose of this review, the following databases were consulted: the PubMed Database (https://pubmed.ncbi.nlm.nih.gov), Chinese National Knowledge Infrastructure (http://www.cnki.net), National Science and Technology Library (http://www.nstl.gov.cn/), Wanfang Data (http://www.wanfangdata.com.cn/) and the Web of Science Database (http://apps.webofknowledge.com/). RESULTS Ginseng exhibits glucose-lowering effects in different diabetic animal models. In addition, Ginseng may prevent the development of diabetic complications, including liver, pancreas, adipose tissue, skeletal muscle, nephropathy, cardiomyopathy, retinopathy, atherosclerosis and others. The main ingredients of Ginseng include ginsenosides and polysaccharides. The underlying mechanisms whereby this herb exerts antidiabetic activities may be attributed to the regulation of multiple signaling pathways, including IRS1/PI3K/AKT, LKB1/AMPK/FoxO1, AGEs/RAGE, MAPK/ERK, NF-κB, PPARδ/STAT3, cAMP/PKA/CERB and HIF-1α/VEGF, etc. The pharmacokinetic profiles of ginsenosides provide valuable information on therapeutic efficacy of Ginseng in diabetes. Although Ginseng is well-tolerated, dietary consumption of this herb should follow the doctors' advice. CONCLUSION Ginseng may offer an alternative strategy in protection against diabetes and its complications through the regulations of the multi-targets via various signaling pathways. Efforts to understand the underlying mechanisms with strictly-controlled animal models, combined with well-designed clinical trials and pharmacokinetic evaluation, will be important subjects of the further investigations and weigh in translational value of this herb in diabetes management.
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Affiliation(s)
- Yage Liu
- Diabetes Research Center, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Hao Zhang
- Diabetes Research Center, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Xuan Dai
- Diabetes Research Center, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Ruyuan Zhu
- Diabetes Research Center, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Beibei Chen
- Diabetes Research Center, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Bingke Xia
- Diabetes Research Center, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Zimengwei Ye
- Diabetes Research Center, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Dandan Zhao
- Diabetes Research Center, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Sihua Gao
- Diabetes Research Center, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Alexander N Orekhov
- Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Moscow 125315, Russia
| | - Dongwei Zhang
- Diabetes Research Center, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.
| | - Lili Wang
- Department of TCM Pharmacology, School of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing 100029, China.
| | - Shuzhen Guo
- Department of Scientific Research Center, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.
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Sen S, Chakraborty R, Kalita P, Pathak MP. Diabetes mellitus and COVID-19: Understanding the association in light of current evidence. World J Clin Cases 2021; 9:8327-8339. [PMID: 34754842 PMCID: PMC8554438 DOI: 10.12998/wjcc.v9.i28.8327] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2021] [Revised: 04/12/2021] [Accepted: 07/29/2021] [Indexed: 02/06/2023] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have posed a problematic healthcare situation worldwide since December 2019. Diabetes mellitus is associated with an increased risk and severity of coronavirus disease 2019 (COVID-19). While interacting with various other risk factors, high blood sugar was found to reduce immunity and increase the replication of SARS-CoV-2. Oxidative stress and the release of pro-inflammatory cytokines are greater in diabetic individuals than in healthy people, worsening the outcome of SARS-CoV-2 infection in diabetics. Increased expression of furin and angiotensin converting enzyme 2 (ACE-2) receptor in the hyperglycemic environment may promote the entry of SARS-CoV-2 in the host cell. COVID-19 infection primarily modulates immune and inflammatory responses, and may cause a cytokine storm, resulting in possible lethal outcomes in diabetics. An experimental report suggests that ACE expressed in the pancreas and the SARS-CoV-2 virus invariably destroy β-cells which contain ACE-2 receptors and results in acute diabetes. Moreover, COVID-19 also causes hyperglycemia in an individual with diabetes which may be related to insulin resistance and destruction of β-cells during SARS-CoV-2 infection. Early observations also suggest a correlation between oral hypoglycemic agents and the risk of COVID-19. This review focused on the possible cause and mechanism involved in SARS-CoV-2 infection in diabetics and the role of antidiabetic drugs in COVID-19.
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Affiliation(s)
- Saikat Sen
- Faculty of Pharmaceutical Science, Assam down town University, Guwahati 781026, Assam, India
| | - Raja Chakraborty
- Department of Pharmaceutical Technology, School of Medical Sciences, ADAMAS University, Kolkata 700 126, West Bengal, India
| | - Pratap Kalita
- Department of Pharmacy, Pratiksha Institute of Pharmaceutical Sciences, Guwahati 781026, Assam, India
| | - Manash Pratim Pathak
- Faculty of Pharmaceutical Science, Assam down town University, Guwahati 781026, Assam, India
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Fiorentino G, Coppola A, Izzo R, Annunziata A, Bernardo M, Lombardi A, Trimarco V, Santulli G, Trimarco B. Effects of adding L-arginine orally to standard therapy in patients with COVID-19: A randomized, double-blind, placebo-controlled, parallel-group trial. Results of the first interim analysis. EClinicalMedicine 2021; 40:101125. [PMID: 34522871 PMCID: PMC8428476 DOI: 10.1016/j.eclinm.2021.101125] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Revised: 08/11/2021] [Accepted: 08/20/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND We and others have previously demonstrated that the endothelium is a primary target of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and L-arginine has been shown to improve endothelial dysfunction. However, the effects of L-arginine have never been evaluated in coronavirus disease 2019 (COVID-19). METHODS This is a parallel-group, double-blind, randomized, placebo-controlled trial conducted on patients hospitalized for severe COVID-19. Patients received 1.66 g L-arginine twice a day or placebo, administered orally. The primary efficacy endpoint was a reduction in respiratory support assessed 10 and 20 days after randomization. Secondary outcomes were the length of in-hospital stay, the time to normalization of lymphocyte number, and the time to obtain a negative real-time reverse transcription polymerase chain reaction (RT-PCR) for SARS-CoV-2 on nasopharyngeal swab. This clinical trial had been registered at ClinicalTrials.gov, identifier: NCT04637906. FINDINGS We present here the results of the initial interim analysis on the first 101 patients. No treatment-emergent serious adverse events were attributable to L-arginine. At 10-day evaluation, 71.1% of patients in the L-arginine arm and 44.4% in the placebo arm (p < 0.01) had the respiratory support reduced; however, a significant difference was not detected 20 days after randomization. Strikingly, patients treated with L-arginine exhibited a significantly reduced in-hospital stay vs placebo, with a median (interquartile range 25th,75th percentile) of 46 days (45,46) in the placebo group vs 25 days (21,26) in the L-arginine group (p < 0.0001); these findings were also confirmed after adjusting for potential confounders including age, duration of symptoms, comorbidities, D-dimer, as well as antiviral and anticoagulant treatments. The other secondary outcomes were not significantly different between groups. INTERPRETATION In this interim analysis, adding oral L-arginine to standard therapy in patients with severe COVID-19 significantly decreases the length of hospitalization and reduces the respiratory support at 10 but not at 20 days after starting the treatment. FUNDING Both placebo and L-arginine were kindly provided by Farmaceutici Damor S.p.A., Naples.
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Affiliation(s)
| | | | - Raffaele Izzo
- Department of Advanced Biomedical Sciences, “Federico II” University, Naples, Italy
| | - Anna Annunziata
- COVID-19 Division, A.O.R.N. Ospedali dei Colli, Naples, Italy
| | | | - Angela Lombardi
- Department of Medicine, Fleischer Institute for Diabetes and Metabolsim (FIDAM), Einstein - Mount Sinai Diabetes Research Center (ES-DRC), Albert Einstein College of Medicine, New York, NY, USA
- Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY, USA
| | - Valentina Trimarco
- Department of Neuroscience, Reproductive Sciences, and Dentistry, "Federico II" University, Naples, Italy
| | - Gaetano Santulli
- Department of Advanced Biomedical Sciences, “Federico II” University, Naples, Italy
- Department of Medicine, Fleischer Institute for Diabetes and Metabolsim (FIDAM), Einstein - Mount Sinai Diabetes Research Center (ES-DRC), Albert Einstein College of Medicine, New York, NY, USA
- Department of Molecular Pharmacology, Wilf Family Cardiovascular Research Institute, Einstein Institute for Aging Research, Albert Einstein College of Medicine, New York, NY, USA
- International Translational Research and Medical Education (ITME) Consortium, Naples, Italy
| | - Bruno Trimarco
- Department of Advanced Biomedical Sciences, “Federico II” University, Naples, Italy
- International Translational Research and Medical Education (ITME) Consortium, Naples, Italy
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Lee WH, Wu DW, Chen YC, Liu YH, Liao WS, Chen SC, Hung CH, Kuo CH, Su HM. Association of Pulmonary Function Decline over Time with Longitudinal Change of Glycated Hemoglobin in Participants without Diabetes Mellitus. J Pers Med 2021; 11:jpm11100994. [PMID: 34683134 PMCID: PMC8537814 DOI: 10.3390/jpm11100994] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2021] [Revised: 09/20/2021] [Accepted: 09/29/2021] [Indexed: 01/13/2023] Open
Abstract
Pulmonary damage and function impairment were frequently noted in patients with diabetes mellitus (DM). However, the relationship between lung function and glycemic status in non-DM subjects was not well-known. Here, we evaluated the association of longitudinal changes of lung function parameters with longitudinal changes of glycated hemoglobin (HbA1c) in non-DM participants. The study enrolled participants without prior type 2 DM, hypertension, and chronic obstructive pulmonary disease (COPD) from the Taiwan Biobank database. Laboratory profiles and pulmonary function parameters, including forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1), were examined at baseline and follow-up. Finally, 7055 participants were selected in this study. During a mean 3.9-year follow-up, FVC and FEV1 were significantly decreased over time (both p < 0.001). In the multivariable analysis, the baseline (unstandardized coefficient β = −0.032, p < 0.001) and longitudinal change (unstandardized coefficient β = −0.025, p = 0.026) of FVC were negatively associated with the baseline and longitudinal change of HbA1c, respectively. Additionally, the longitudinal change of FVC was negatively associated with the risk of newly diagnosed type 2 DM (p = 0.018). During a mean 3.9-year follow-up, our present study, including participants without type 2 DM, hypertension, and COPD, demonstrated that the baseline and longitudinal change of FVC were negatively and respectively correlated with the baseline and longitudinal change of HbA1c. Furthermore, compared to those without new-onset DM, participants with new-onset DM had a more pronounced decline of FVC over time.
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Affiliation(s)
- Wen-Hsien Lee
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, 482 Shan-Ming Rd., Hsiao-Kang Dist., Kaohsiung 812, Taiwan; (W.-H.L.); (D.-W.W.); (Y.-C.C.); (Y.-H.L.); (W.-S.L.); (S.-C.C.); (C.-H.H.); (C.-H.K.)
- Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, 482 Shan-Ming Rd., Hsiao-Kang Dist., Kaohsiung 812, Taiwan
- Faculty of Medicine, College of Medicine, Kaohsiung Medical University, 482 Shan-Ming Rd., Hsiao-Kang Dist., Kaohsiung 812, Taiwan
- Research Center for Environmental Medicine, Kaohsiung Medical University, 482 Shan-Ming Rd., Hsiao-Kang Dist., Kaohsiung 812, Taiwan
| | - Da-Wei Wu
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, 482 Shan-Ming Rd., Hsiao-Kang Dist., Kaohsiung 812, Taiwan; (W.-H.L.); (D.-W.W.); (Y.-C.C.); (Y.-H.L.); (W.-S.L.); (S.-C.C.); (C.-H.H.); (C.-H.K.)
- Research Center for Environmental Medicine, Kaohsiung Medical University, 482 Shan-Ming Rd., Hsiao-Kang Dist., Kaohsiung 812, Taiwan
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, 482 Shan-Ming Rd., Hsiao-Kang Dist., Kaohsiung 812, Taiwan
| | - Ying-Chih Chen
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, 482 Shan-Ming Rd., Hsiao-Kang Dist., Kaohsiung 812, Taiwan; (W.-H.L.); (D.-W.W.); (Y.-C.C.); (Y.-H.L.); (W.-S.L.); (S.-C.C.); (C.-H.H.); (C.-H.K.)
- Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, 482 Shan-Ming Rd., Hsiao-Kang Dist., Kaohsiung 812, Taiwan
| | - Yi-Hsueh Liu
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, 482 Shan-Ming Rd., Hsiao-Kang Dist., Kaohsiung 812, Taiwan; (W.-H.L.); (D.-W.W.); (Y.-C.C.); (Y.-H.L.); (W.-S.L.); (S.-C.C.); (C.-H.H.); (C.-H.K.)
- Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, 482 Shan-Ming Rd., Hsiao-Kang Dist., Kaohsiung 812, Taiwan
| | - Wei-Sheng Liao
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, 482 Shan-Ming Rd., Hsiao-Kang Dist., Kaohsiung 812, Taiwan; (W.-H.L.); (D.-W.W.); (Y.-C.C.); (Y.-H.L.); (W.-S.L.); (S.-C.C.); (C.-H.H.); (C.-H.K.)
- Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, 482 Shan-Ming Rd., Hsiao-Kang Dist., Kaohsiung 812, Taiwan
| | - Szu-Chia Chen
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, 482 Shan-Ming Rd., Hsiao-Kang Dist., Kaohsiung 812, Taiwan; (W.-H.L.); (D.-W.W.); (Y.-C.C.); (Y.-H.L.); (W.-S.L.); (S.-C.C.); (C.-H.H.); (C.-H.K.)
- Faculty of Medicine, College of Medicine, Kaohsiung Medical University, 482 Shan-Ming Rd., Hsiao-Kang Dist., Kaohsiung 812, Taiwan
- Research Center for Environmental Medicine, Kaohsiung Medical University, 482 Shan-Ming Rd., Hsiao-Kang Dist., Kaohsiung 812, Taiwan
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, 482 Shan-Ming Rd., Hsiao-Kang Dist., Kaohsiung 812, Taiwan
| | - Chih-Hsing Hung
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, 482 Shan-Ming Rd., Hsiao-Kang Dist., Kaohsiung 812, Taiwan; (W.-H.L.); (D.-W.W.); (Y.-C.C.); (Y.-H.L.); (W.-S.L.); (S.-C.C.); (C.-H.H.); (C.-H.K.)
- Faculty of Medicine, College of Medicine, Kaohsiung Medical University, 482 Shan-Ming Rd., Hsiao-Kang Dist., Kaohsiung 812, Taiwan
- Research Center for Environmental Medicine, Kaohsiung Medical University, 482 Shan-Ming Rd., Hsiao-Kang Dist., Kaohsiung 812, Taiwan
| | - Chao-Hung Kuo
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, 482 Shan-Ming Rd., Hsiao-Kang Dist., Kaohsiung 812, Taiwan; (W.-H.L.); (D.-W.W.); (Y.-C.C.); (Y.-H.L.); (W.-S.L.); (S.-C.C.); (C.-H.H.); (C.-H.K.)
- Faculty of Medicine, College of Medicine, Kaohsiung Medical University, 482 Shan-Ming Rd., Hsiao-Kang Dist., Kaohsiung 812, Taiwan
- Research Center for Environmental Medicine, Kaohsiung Medical University, 482 Shan-Ming Rd., Hsiao-Kang Dist., Kaohsiung 812, Taiwan
| | - Ho-Ming Su
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, 482 Shan-Ming Rd., Hsiao-Kang Dist., Kaohsiung 812, Taiwan; (W.-H.L.); (D.-W.W.); (Y.-C.C.); (Y.-H.L.); (W.-S.L.); (S.-C.C.); (C.-H.H.); (C.-H.K.)
- Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, 482 Shan-Ming Rd., Hsiao-Kang Dist., Kaohsiung 812, Taiwan
- Faculty of Medicine, College of Medicine, Kaohsiung Medical University, 482 Shan-Ming Rd., Hsiao-Kang Dist., Kaohsiung 812, Taiwan
- Research Center for Environmental Medicine, Kaohsiung Medical University, 482 Shan-Ming Rd., Hsiao-Kang Dist., Kaohsiung 812, Taiwan
- Correspondence: ; Tel.: +886-7-8036783-3441; Fax: +886-7-8063346
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Leutner M, Kaleta M, Bellach L, Kautzky A, Thurner S, Klimek P, Kautzky-Willer A. Insulin as Monotherapy and in Combination with Other Glucose-Lowering Drugs Is Related to Increased Risk of Diagnosis of Pneumonia: A Longitudinal Assessment over Two Years. J Pers Med 2021; 11:jpm11100984. [PMID: 34683125 PMCID: PMC8537451 DOI: 10.3390/jpm11100984] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Revised: 09/21/2021] [Accepted: 09/24/2021] [Indexed: 01/22/2023] Open
Abstract
Objective: Patients with type 2 diabetes mellitus (T2DM) are at an increased risk of developing infectious diseases such as pneumonia. Hitherto, there has been uncertainty as to whether there is a relationship between different antidiabetic drug combinations and development of pneumonia in this specific cohort. Research Design and Methods: In this longitudinal retrospective study we used multiple logistic regression analysis to assess the odds ratios (ORs) of pneumonia during an observational period of 2 years in 31,397 patients with T2DM under previously prescribed stable antidiabetic drug combinations over a duration of 4 years in comparison to 6568 T2DM patients without drug therapy over 4 years adjusted for age, sex and hospitalization duration. Results: Of the 37,965 patients with T2DM, 3720 patients underwent stable monotherapy treatment with insulin (mean age: 66.57 ± 9.72 years), 2939 individuals (mean age: 70.62 ± 8.95 y) received stable statin and insulin therapy, and 1596 patients were treated with a stable combination therapy of metformin, insulin and statins (mean age: 68.27 ± 8.86 y). In comparison to the control group without antidiabetic drugs (mean age: 72.83 ± 9.96 y), individuals undergoing insulin monotherapy (OR: 2.07, CI: 1.54–2.79, p < 0.001); insulin and statin combination therapy (OR: 2.24, CI: 1.68–3.00, p < 0.001); metformin, insulin and statin combination therapy (OR: 2.27, CI: 1.55–3.31, p < 0.001); statin, insulin and dipeptidyl peptidase-4 inhibitor (DPP-IV inhibitor) combination therapy (OR: 4.31, CI: 1.80–10.33, p = 0.001); as well as individuals treated with metformin and sulfonylureas (OR: 1.70, CI: 1.08–2.69, p = 0.02) were at increased risk of receiving a diagnosis of pneumonia. Conclusions: Stable monotherapy with insulin, but also in combination with other antidiabetic drugs, is related to an increased risk of being diagnosed with pneumonia during hospital stays in patients with type 2 diabetes mellitus compared to untreated controls.
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Affiliation(s)
- Michael Leutner
- Department of Internal Medicine III, Clinical Division of Endocrinology and Metabolism, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria; (M.L.); (L.B.)
| | - Michaela Kaleta
- Section for Science of Complex Systems, CeMSIIS, Medical University of Vienna, Spitalgasse 23, A-1090 Vienna, Austria; (M.K.); (S.T.); (P.K.)
- Complexity Science Hub Vienna, Josefstaedter Strasse 39, A-1080 Vienna, Austria
| | - Luise Bellach
- Department of Internal Medicine III, Clinical Division of Endocrinology and Metabolism, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria; (M.L.); (L.B.)
| | - Alexander Kautzky
- Department of Psychiatry and Psychotherapy, Medical University of Vienna, A-1090 Vienna, Austria;
| | - Stefan Thurner
- Section for Science of Complex Systems, CeMSIIS, Medical University of Vienna, Spitalgasse 23, A-1090 Vienna, Austria; (M.K.); (S.T.); (P.K.)
- Complexity Science Hub Vienna, Josefstaedter Strasse 39, A-1080 Vienna, Austria
- Santa Fe Institute, 1399 Hyde Park Road, Santa Fe, NM 85701, USA
| | - Peter Klimek
- Section for Science of Complex Systems, CeMSIIS, Medical University of Vienna, Spitalgasse 23, A-1090 Vienna, Austria; (M.K.); (S.T.); (P.K.)
- Complexity Science Hub Vienna, Josefstaedter Strasse 39, A-1080 Vienna, Austria
| | - Alexandra Kautzky-Willer
- Department of Internal Medicine III, Clinical Division of Endocrinology and Metabolism, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria; (M.L.); (L.B.)
- Gender Institute, A-3571 Gars am Kamp, Austria
- Correspondence:
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Hentsch L, Cocetta S, Allali G, Santana I, Eason R, Adam E, Janssens JP. Breathlessness and COVID-19: A Call for Research. Respiration 2021; 100:1016-1026. [PMID: 34333497 PMCID: PMC8450822 DOI: 10.1159/000517400] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Accepted: 05/19/2021] [Indexed: 01/08/2023] Open
Abstract
Breathlessness, also known as dyspnoea, is a debilitating and frequent symptom. Several reports have highlighted the lack of dyspnoea in a subgroup of patients suffering from COVID-19, sometimes referred to as "silent" or "happy hyp-oxaemia." Reports have also mentioned the absence of a clear relationship between the clinical severity of the disease and levels of breathlessness reported by patients. The cerebral complications of COVID-19 have been largely demonstrated with a high prevalence of an acute encephalopathy that could possibly affect the processing of afferent signals or top-down modulation of breathlessness signals. In this review, we aim to highlight the mechanisms involved in breathlessness and summarize the pathophysiology of COVID-19 and its known effects on the brain-lung interaction. We then offer hypotheses for the alteration of breathlessness perception in COVID-19 patients and suggest ways of further researching this phenomenon.
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Affiliation(s)
- Lisa Hentsch
- Division of Palliative Medicine, Geneva University Hospitals, Geneva, Switzerland
| | | | - Gilles Allali
- Division of Neurology, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland
- Division of Cognitive and Motor Aging, Department of Neurology, Albert Einstein College of Medicine, Yeshiva University, Bronx, New York, USA
| | | | - Rowena Eason
- Phyllis Tuckwell Hospice Care, Surrey, United Kingdom
| | - Emily Adam
- Independent Researcher, London, United Kingdom
| | - Jean-Paul Janssens
- Division of Pulmonary Diseases, Geneva University Hospital, Geneva, Switzerland
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46
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Logette E, Lorin C, Favreau C, Oshurko E, Coggan JS, Casalegno F, Sy MF, Monney C, Bertschy M, Delattre E, Fonta PA, Krepl J, Schmidt S, Keller D, Kerrien S, Scantamburlo E, Kaufmann AK, Markram H. A Machine-Generated View of the Role of Blood Glucose Levels in the Severity of COVID-19. Front Public Health 2021; 9:695139. [PMID: 34395368 PMCID: PMC8356061 DOI: 10.3389/fpubh.2021.695139] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Accepted: 06/30/2021] [Indexed: 01/08/2023] Open
Abstract
SARS-CoV-2 started spreading toward the end of 2019 causing COVID-19, a disease that reached pandemic proportions among the human population within months. The reasons for the spectrum of differences in the severity of the disease across the population, and in particular why the disease affects more severely the aging population and those with specific preconditions are unclear. We developed machine learning models to mine 240,000 scientific articles openly accessible in the CORD-19 database, and constructed knowledge graphs to synthesize the extracted information and navigate the collective knowledge in an attempt to search for a potential common underlying reason for disease severity. The machine-driven framework we developed repeatedly pointed to elevated blood glucose as a key facilitator in the progression of COVID-19. Indeed, when we systematically retraced the steps of the SARS-CoV-2 infection, we found evidence linking elevated glucose to each major step of the life-cycle of the virus, progression of the disease, and presentation of symptoms. Specifically, elevations of glucose provide ideal conditions for the virus to evade and weaken the first level of the immune defense system in the lungs, gain access to deep alveolar cells, bind to the ACE2 receptor and enter the pulmonary cells, accelerate replication of the virus within cells increasing cell death and inducing an pulmonary inflammatory response, which overwhelms an already weakened innate immune system to trigger an avalanche of systemic infections, inflammation and cell damage, a cytokine storm and thrombotic events. We tested the feasibility of the hypothesis by manually reviewing the literature referenced by the machine-generated synthesis, reconstructing atomistically the virus at the surface of the pulmonary airways, and performing quantitative computational modeling of the effects of glucose levels on the infection process. We conclude that elevation in glucose levels can facilitate the progression of the disease through multiple mechanisms and can explain much of the differences in disease severity seen across the population. The study provides diagnostic considerations, new areas of research and potential treatments, and cautions on treatment strategies and critical care conditions that induce elevations in blood glucose levels.
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Affiliation(s)
- Emmanuelle Logette
- Blue Brain Project, École polytechnique fédérale de Lausanne (EPFL), Geneva, Switzerland
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | - Henry Markram
- Blue Brain Project, École polytechnique fédérale de Lausanne (EPFL), Geneva, Switzerland
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47
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Nouri-Keshtkar M, Taghizadeh S, Farhadi A, Ezaddoustdar A, Vesali S, Hosseini R, Totonchi M, Kouhkan A, Chen C, Zhang JS, Bellusci S, Tahamtani Y. Potential Impact of Diabetes and Obesity on Alveolar Type 2 (AT2)-Lipofibroblast (LIF) Interactions After COVID-19 Infection. Front Cell Dev Biol 2021; 9:676150. [PMID: 34307358 PMCID: PMC8295688 DOI: 10.3389/fcell.2021.676150] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Accepted: 06/11/2021] [Indexed: 01/14/2023] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a new emerging respiratory virus, caused evolving pneumonia outbreak around the world. In SARS-Cov-2 infected patients, diabetes mellitus (DM) and obesity are two metabolic diseases associated with higher severity of SARS-CoV-2 related complications, characterized by acute lung injury requiring assisted ventilation as well as fibrosis development in surviving patients. Different factors are potentially responsible for this exacerbated response to SARS-CoV-2 infection. In patients with DM, base-line increase in inflammation and oxidative stress represent preexisting risk factors for virus-induced damages. Such factors are also likely to be found in obese patients. In addition, it has been proposed that massive injury to the alveolar epithelial type 2 (AT2) cells, which express the SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2), leads to the activation of their stromal niches represented by the Lipofibroblasts (LIF). LIF are instrumental in maintaining the self-renewal of AT2 stem cells. LIF have been proposed to transdifferentiate into Myofibroblast (MYF) following injury to AT2 cells, thereby contributing to fibrosis. We hypothesized that LIF's activity could be impacted by DM or obesity in an age- and gender-dependent manner, rendering them more prone to transition toward the profibrotic MYF status in the context of severe COVID-19 pneumonia. Understanding the cumulative effects of DM and/or obesity in the context of SARS-CoV-2 infection at the cellular level will be crucial for efficient therapeutic solutions.
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Affiliation(s)
- Marjan Nouri-Keshtkar
- Faculty of Sciences and Advanced Technologies in Biology, University of Science and Culture, Tehran, Iran
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
| | - Sara Taghizadeh
- Key Laboratory of Interventional Pulmonology of Zhejiang Province, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Excellence Cluster Cardio-Pulmonary System, Justus Liebig University Giessen, Giessen, Germany
| | - Aisan Farhadi
- Faculty of Sciences and Advanced Technologies in Biology, University of Science and Culture, Tehran, Iran
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
| | | | - Samira Vesali
- Reproductive Epidemiology Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
| | - Roya Hosseini
- Reproductive Epidemiology Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
| | - Mehdi Totonchi
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
- Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
| | - Azam Kouhkan
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
- Reproductive Epidemiology Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
| | - Chengshui Chen
- Key Laboratory of Interventional Pulmonology of Zhejiang Province, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Jin-San Zhang
- Key Laboratory of Interventional Pulmonology of Zhejiang Province, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Saverio Bellusci
- Key Laboratory of Interventional Pulmonology of Zhejiang Province, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Excellence Cluster Cardio-Pulmonary System, Justus Liebig University Giessen, Giessen, Germany
| | - Yaser Tahamtani
- Faculty of Sciences and Advanced Technologies in Biology, University of Science and Culture, Tehran, Iran
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
- Reproductive Epidemiology Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
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48
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Maan HB, Meo SA, Al Rouq F, Meo IMU, Gacuan ME, Alkhalifah JM. Effect of Glycated Hemoglobin (HbA1c) and Duration of Disease on Lung Functions in Type 2 Diabetic Patients. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph18136970. [PMID: 34209922 PMCID: PMC8297156 DOI: 10.3390/ijerph18136970] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Revised: 06/23/2021] [Accepted: 06/24/2021] [Indexed: 11/16/2022]
Abstract
Diabetes mellitus is a highly challenging global health care problem. This study aimed to assess the effect of glycated hemoglobin (HbA1c) and duration of diabetes on lung function in type 2 diabetic patients and assess whether duration or high HbA1c is more noxious to damage the lung functions. A total of 202 participants, 101 patients with type 2 diabetes mellitus (T2DM), and 101 age-, gender-, height-, and weight-matched controlled subjects were recruited. The HbA1c was measured through a clover analyzer, and lung function test parameters were recorded by spirometry. The results revealed a significant inverse correlation between HbA1c and Vital Capacity (VC) (r = -0.221, p = 0.026), Forced Vital Capacity (FVC) (r = -0.261, p = 0.008), Forced Expiratory Volume in First Second (FEV1) (r = -0.272, p = 0.006), Forced Expiratory Flow 25% (FEF-25%) (r = -0.196, p = 0.050), Forced Expiratory Flow 50% (FEF-50%) (r = -0.223, p = 0.025), and Forced Expiratory Flow 75% (FEF-75%) (r = -0.169, p = 0.016). Moreover, FEV1 (p = 0.029), FEV1/FVC% (p = 0.006), FEF-50% (p = 0.001), and FEF-75% (p = 0.003) were significantly lower in the diabetic group with duration of disease 5-10 and >10 years compared to the control group. The overall results concluded that high HbA1c or uncontrolled diabetes mellitus has a more damaging effect on lung function impairment compared to the duration of diabetes mellitus. Physicians must regularly monitor the HbA1c level while treating diabetic patients, as good glycemic control is essential to minimize the complications of DM, including lung function impairment in patients with T2DM.
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49
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Sgrazzutti L, Sansone F, Attanasi M, Di Pillo S, Chiarelli F. Coaggregation of Asthma and Type 1 Diabetes in Children: A Narrative Review. Int J Mol Sci 2021; 22:ijms22115757. [PMID: 34071190 PMCID: PMC8198343 DOI: 10.3390/ijms22115757] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2021] [Revised: 05/20/2021] [Accepted: 05/25/2021] [Indexed: 02/06/2023] Open
Abstract
Asthma and type 1 diabetes mellitus (T1DM) are two of the most frequent chronic diseases in children, representing a model of the atopic and autoimmune diseases respectively. These two groups of disorders are mediated by different immunological pathways, T helper (Th)1 for diabetes and Th2 for asthma. For many years, these two groups were thought to be mutually exclusive according to the Th1/Th2 paradigm. In children, the incidence of both diseases is steadily increasing worldwide. In this narrative review, we report the evidence of the potential link between asthma and T1DM in childhood. We discuss which molecular mechanisms could be involved in the link between asthma and T1DM, such as genetic predisposition, cytokine patterns, and environmental influences. Cytokine profile of children with asthma and T1DM shows an activation of both Th1 and Th2 pathways, suggesting a complex genetic-epigenetic interaction. In conclusion, in children, the potential link between asthma and T1DM needs further investigation to improve the diagnostic and therapeutic approach to these patients. The aim of this review is to invite the pediatricians to consider the potential copresence of these two disorders in clinical practice.
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50
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Huang J, Covic M, Huth C, Rommel M, Adam J, Zukunft S, Prehn C, Wang L, Nano J, Scheerer MF, Neschen S, Kastenmüller G, Gieger C, Laxy M, Schliess F, Adamski J, Suhre K, de Angelis MH, Peters A, Wang-Sattler R. Validation of Candidate Phospholipid Biomarkers of Chronic Kidney Disease in Hyperglycemic Individuals and Their Organ-Specific Exploration in Leptin Receptor-Deficient db/db Mouse. Metabolites 2021; 11:metabo11020089. [PMID: 33546276 PMCID: PMC7913334 DOI: 10.3390/metabo11020089] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Revised: 01/27/2021] [Accepted: 01/29/2021] [Indexed: 12/03/2022] Open
Abstract
Biological exploration of early biomarkers for chronic kidney disease (CKD) in (pre)diabetic individuals is crucial for personalized management of diabetes. Here, we evaluated two candidate biomarkers of incident CKD (sphingomyelin (SM) C18:1 and phosphatidylcholine diacyl (PC aa) C38:0) concerning kidney function in hyperglycemic participants of the Cooperative Health Research in the Region of Augsburg (KORA) cohort, and in two biofluids and six organs of leptin receptor-deficient (db/db) mice and wild type controls. Higher serum concentrations of SM C18:1 and PC aa C38:0 in hyperglycemic individuals were found to be associated with lower estimated glomerular filtration rate (eGFR) and higher odds of CKD. In db/db mice, both metabolites had a significantly lower concentration in urine and adipose tissue, but higher in the lungs. Additionally, db/db mice had significantly higher SM C18:1 levels in plasma and liver, and PC aa C38:0 in adrenal glands. This cross-sectional human study confirms that SM C18:1 and PC aa C38:0 associate with kidney dysfunction in pre(diabetic) individuals, and the animal study suggests a potential implication of liver, lungs, adrenal glands, and visceral fat in their systemic regulation. Our results support further validation of the two phospholipids as early biomarkers of renal disease in patients with (pre)diabetes.
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Affiliation(s)
- Jialing Huang
- Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, 85764 Neuherberg, Germany; (J.H.); (M.C.); (M.R.); (J.A.); (L.W.); (C.G.)
- Institute of Epidemiology, Helmholtz Zentrum München, 85764 Neuherberg, Germany; (C.H.); (J.N.); (A.P.)
- German Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany;
| | - Marcela Covic
- Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, 85764 Neuherberg, Germany; (J.H.); (M.C.); (M.R.); (J.A.); (L.W.); (C.G.)
- Institute of Epidemiology, Helmholtz Zentrum München, 85764 Neuherberg, Germany; (C.H.); (J.N.); (A.P.)
- German Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany;
| | - Cornelia Huth
- Institute of Epidemiology, Helmholtz Zentrum München, 85764 Neuherberg, Germany; (C.H.); (J.N.); (A.P.)
| | - Martina Rommel
- Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, 85764 Neuherberg, Germany; (J.H.); (M.C.); (M.R.); (J.A.); (L.W.); (C.G.)
- Institute of Epidemiology, Helmholtz Zentrum München, 85764 Neuherberg, Germany; (C.H.); (J.N.); (A.P.)
| | - Jonathan Adam
- Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, 85764 Neuherberg, Germany; (J.H.); (M.C.); (M.R.); (J.A.); (L.W.); (C.G.)
- Institute of Epidemiology, Helmholtz Zentrum München, 85764 Neuherberg, Germany; (C.H.); (J.N.); (A.P.)
| | - Sven Zukunft
- Research Unit of Molecular Endocrinology and Metabolism, Helmholtz Zentrum München, 85764 Neuherberg, Germany; (S.Z.); (J.A.)
- Centre for Molecular Medicine, Institute for Vascular Signaling, Goethe University, 60323 Frankfurt am Main, Germany
| | - Cornelia Prehn
- Metabolomics and Proteomics Core Facility, Helmholtz Zentrum München, 85764 Neuherberg, Germany;
| | - Li Wang
- Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, 85764 Neuherberg, Germany; (J.H.); (M.C.); (M.R.); (J.A.); (L.W.); (C.G.)
- Institute of Epidemiology, Helmholtz Zentrum München, 85764 Neuherberg, Germany; (C.H.); (J.N.); (A.P.)
- Liaocheng People’s Hospital—Department of Scientific Research, Shandong University Postdoctoral Work Station, Liaocheng 252000, China
| | - Jana Nano
- Institute of Epidemiology, Helmholtz Zentrum München, 85764 Neuherberg, Germany; (C.H.); (J.N.); (A.P.)
- German Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany;
| | - Markus F. Scheerer
- Institute of Experimental Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany; (M.F.S.); (S.N.)
- Bayer AG, Medical Affairs & Pharmacovigilance, 13353 Berlin, Germany
| | - Susanne Neschen
- Institute of Experimental Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany; (M.F.S.); (S.N.)
- Sanofi Aventis Deutschland GmbH, Industriepark Hoechst, 65929 Frankfurt am Main, Germany
| | - Gabi Kastenmüller
- Institute of Computational Biology, Helmholtz Zentrum München, 85764 Neuherberg, Germany;
| | - Christian Gieger
- Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, 85764 Neuherberg, Germany; (J.H.); (M.C.); (M.R.); (J.A.); (L.W.); (C.G.)
- Institute of Epidemiology, Helmholtz Zentrum München, 85764 Neuherberg, Germany; (C.H.); (J.N.); (A.P.)
- German Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany;
| | - Michael Laxy
- Institute of Health Economics and Health Care Management, Helmholtz Zentrum München, 85764 Neuherberg, Germany;
| | | | - Jerzy Adamski
- Research Unit of Molecular Endocrinology and Metabolism, Helmholtz Zentrum München, 85764 Neuherberg, Germany; (S.Z.); (J.A.)
- Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
- Chair of Experimental Genetics, Center of Life and Food Sciences Weihenstephan, Technische Universität München, 85353 Freising, Germany
| | - Karsten Suhre
- Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar (WCMC-Q), Education City, Qatar Foundation, Doha P.O. Box 24144, Qatar;
| | - Martin Hrabe de Angelis
- German Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany;
- Institute of Experimental Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany; (M.F.S.); (S.N.)
- Chair of Experimental Genetics, Center of Life and Food Sciences Weihenstephan, Technische Universität München, 85353 Freising, Germany
| | - Annette Peters
- Institute of Epidemiology, Helmholtz Zentrum München, 85764 Neuherberg, Germany; (C.H.); (J.N.); (A.P.)
- German Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany;
| | - Rui Wang-Sattler
- Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, 85764 Neuherberg, Germany; (J.H.); (M.C.); (M.R.); (J.A.); (L.W.); (C.G.)
- Institute of Epidemiology, Helmholtz Zentrum München, 85764 Neuherberg, Germany; (C.H.); (J.N.); (A.P.)
- German Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany;
- Correspondence: ; Tel.: +49-89-3187-3978; Fax: + 49-89-3187-2428
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