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Jena PP, Nanda R, Ghosh A, Patel S, Shah S, Mohapatra E. Endocan expression and correlation with other endothelial determinants in developing a score for early identification of diabetic peripheral neuropathy. Sci Rep 2025; 15:850. [PMID: 39757242 PMCID: PMC11701089 DOI: 10.1038/s41598-024-68790-0] [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: 03/31/2024] [Accepted: 07/29/2024] [Indexed: 01/07/2025] Open
Abstract
Diabetic peripheral neuropathy is a common complication of diabetes mellitus that has dire outcomes, affecting the economic profile of a country. Despite the multifactorial background of the pathogenesis of this disease, the mechanism underlying peripheral neuropathy is still unclear. Endothelial damage is a new determinant of pathogenesis, with endocan as a potential biomarker for endothelial dysfunction in diabetic peripheral neuropathy patients. In this cross-sectional study, with 49 patients with diabetes with peripheral neuropathy and 48 patients with diabetes without neuropathy, endothelial biomarkers such as endocan, hs-CRP, vitamin D, and lipid profiles were measured and analyzed in both groups. The standardized scores for dyslipidemia, inflammation, vitamin D and endocan were calculated. All of these biomarkers were significantly altered in peripheral neuropathy patients. A strong correlation between endocan levels and lipid profiles and between hs-CRP and vitamin D levels was detected. The inflammatory score and a combined score including all the above biomarkers might help in the early stratification of diabetic patients who are at greater risk of developing peripheral neuropathy.
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Affiliation(s)
- Prajna Parimita Jena
- Department of Biochemistry, All India Institute of Medical Sciences Raipur, GE Road, Tatibandh. Raipur, Raipur, Chhattisgarh, 492099, India
| | - Rachita Nanda
- Department of Biochemistry, All India Institute of Medical Sciences Raipur, GE Road, Tatibandh. Raipur, Raipur, Chhattisgarh, 492099, India.
| | - Amritava Ghosh
- Department of Endocrinology and Metabolism, All India Institute of Medical Sciences Raipur, Raipur, Chhattisgarh, 492099, India
| | - Suprava Patel
- Department of Biochemistry, All India Institute of Medical Sciences Raipur, GE Road, Tatibandh. Raipur, Raipur, Chhattisgarh, 492099, India
| | - Seema Shah
- Department of Biochemistry, All India Institute of Medical Sciences Raipur, GE Road, Tatibandh. Raipur, Raipur, Chhattisgarh, 492099, India
| | - Eli Mohapatra
- Department of Biochemistry, All India Institute of Medical Sciences Raipur, GE Road, Tatibandh. Raipur, Raipur, Chhattisgarh, 492099, India
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Liu Y, He W, Ji Y, Wang Q, Li X. A linear positive association between high-sensitivity C-reactive protein and the prevalence of cardiovascular disease among individuals with diabetes. BMC Cardiovasc Disord 2024; 24:411. [PMID: 39118024 PMCID: PMC11308650 DOI: 10.1186/s12872-024-04091-8] [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: 12/19/2023] [Accepted: 08/01/2024] [Indexed: 08/10/2024] Open
Abstract
AIMS To assess the correlation between high-sensitivity C-reactive protein (Hs-CRP) and the prevalence of cardiovascular disease (CVD) among individuals with diabetes. METHODS A total of 1,555 participants from the National Health and Nutrition Examination Survey were enrolled in this cross-sectional study after excluding individuals without diabetes and those who lacked data on Hs-CRP, diabetes and CVD. All participants were divided into four groups based on quartiles of Hs-CRP: Q1 (≤ 1.20 mg/L), Q2 (1.20-2.86 mg/L), Q3 (2.86-6.40 mg/L), and Q4 (> 6.40 mg/L). Logistic regression analysis, subgroup analysis and restricted cubic spline (RCS) analysis were used to evaluate the correlation between Hs-CRP and the prevalence of CVD in individuals with diabetes. RESULTS In univariate logistic regression analysis, a higher level of Hs-CRP was associated with a higher prevalence of CVD (P < 0.05). In the multivariate logistic regression analysis adjusting for confounders, the correlation between Hs-CRP and the prevalence of CVD remained significant (Q3 vs. Q1, OR: 1.505, 95% CI: 1.056-2.147, P = 0.024; Q4 vs. Q1, OR: 1.711, 95% CI: 1.171-2.499, P = 0.006; log10(Hs-CRP), OR: 1.504, 95% CI: 1.168-1.935, P = 0.002). Further subgroup analysis showed that a higher Hs-CRP was independently associated with a higher prevalence of CVD in the < 60 years, male, non-hypertension and non-hypercholesterolemia subgroups (P < 0.05). Additionally, RCS analysis revealed a linear positive correlation between Hs-CRP and CVD prevalence (P for nonlinearity = 0.244). CONCLUSION A higher level of Hs-CRP was closely related to a higher prevalence of CVD in people with diabetes.
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Affiliation(s)
- Yu Liu
- Department of Cardiology, The Affiliated Changzhou, No.2 People's Hospital of Nanjing Medical University, Changzhou, 213003, Jiangsu, China
| | - Wei He
- Department of Medical Imaging, The Affiliated Hospital of Jiangsu University, Zhenjiang, 212000, China
| | - Yuan Ji
- Department of Cardiology, The Affiliated Changzhou, No.2 People's Hospital of Nanjing Medical University, Changzhou, 213003, Jiangsu, China
| | - Qingjie Wang
- Department of Cardiology, The Affiliated Changzhou, No.2 People's Hospital of Nanjing Medical University, Changzhou, 213003, Jiangsu, China
| | - Xun Li
- Department of Cardiology, The First Affiliated Hospital of Soochow University, No.188, Shizi Street, Suzhou, 215006, China.
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Liu B, Liu R, Gu Y, Shen X, Zhou J, Luo C. Polyunsaturated fatty acids and diabetic microvascular complications: a Mendelian randomization study. Front Endocrinol (Lausanne) 2024; 15:1406382. [PMID: 39170741 PMCID: PMC11335686 DOI: 10.3389/fendo.2024.1406382] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Accepted: 07/25/2024] [Indexed: 08/23/2024] Open
Abstract
Background Observational studies and clinical trials have implicated polyunsaturated fatty acids (PUFAs) in potentially safeguarding against diabetic microvascular complication. Nonetheless, the causal nature of these relationships remains ambiguous due to conflicting findings across studies. This research employs Mendelian randomization (MR) to assess the causal impact of PUFAs on diabetic microvascular complications. Methods We identified instrumental variables for PUFAs, specifically omega-3 and omega-6 fatty acids, using the UK Biobank data. Outcome data regarding diabetic microvascular complications were sourced from the FinnGen Study. Our analysis covered microvascular outcomes in both type 1 and type 2 diabetes, namely diabetic neuropathy (DN), diabetic retinopathy (DR), and diabetic kidney disease (DKD). An inverse MR analysis was conducted to examine the effect of diabetic microvascular complications on PUFAs. Sensitivity analyses were performed to validate the robustness of the results. Finally, a multivariable MR (MVMR) analysis was conducted to determine whether PUFAs have a direct influence on diabetic microvascular complications. Results The study indicates that elevated levels of genetically predicted omega-6 fatty acids substantially reduce the risk of DN in type 2 diabetes (odds ratio (OR): 0.62, 95% confidence interval (CI): 0.47-0.82, p = 0.001). A protective effect against DR in type 2 diabetes is also suggested (OR: 0.75, 95% CI: 0.62-0.92, p = 0.005). MVMR analysis confirmed the stability of these results after adjusting for potential confounding factors. No significant effects of omega-6 fatty acids were observed on DKD in type 2 diabetes or on any complications in type 1 diabetes. By contrast, omega-3 fatty acids showed no significant causal links with any of the diabetic microvascular complications assessed. Conclusions Our MR analysis reveals a causal link between omega-6 fatty acids and certain diabetic microvascular complications in type 2 diabetes, potentially providing novel insights for further mechanistic and clinical investigations into diabetic microvascular complications.
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Affiliation(s)
- Bingyang Liu
- Department of Critical Care Medicine, Ningbo Medical Center Lihuili Hospital, Ningbo University, Ningbo, China
| | - Ruiyan Liu
- Wenzhou Medical University Renji College, Wenzhou, China
| | - Yi Gu
- Ningbo Institute of Innovation for Combined Medicine and Engineering, Ningbo Medical Center Lihuili Hospital, Ningbo University, Ningbo, China
| | - Xiaoying Shen
- Department of Endocrinology, Ningbo Medical Center Lihuili Hospital, Ningbo University, Ningbo, China
| | - Jianqing Zhou
- Department of Cardiovascular, Ningbo Medical Center Lihuili Hospital, Ningbo University, Ningbo, China
| | - Chun Luo
- Department of Endocrinology, Ningbo Medical Center Lihuili Hospital, Ningbo University, Ningbo, China
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Kim CK, Karslioglu MZ, Zhao SH, Lee OL. Infectious Keratitis in Patients Over 65: A Review on Treatment and Preserving Eyesight. Clin Interv Aging 2024; 19:1393-1405. [PMID: 39099749 PMCID: PMC11298191 DOI: 10.2147/cia.s467262] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Accepted: 07/25/2024] [Indexed: 08/06/2024] Open
Abstract
Infectious keratitis (IK) represents a significant global health concern, ranking as the fifth leading cause of blindness worldwide despite being largely preventable and treatable. Elderly populations are particularly susceptible due to age-related changes in immune response and corneal structure. However, research on IK in this demographic remains scarce. Age-related alterations such as increased permeability and reduced endothelial cell density further compound susceptibility to infection and hinder healing mechanisms. Additionally, inflammaging, characterized by chronic inflammation that develops with advanced age, disrupts the ocular immune balance, potentially exacerbating IK and other age-related eye diseases. Understanding these mechanisms is paramount for enhancing IK management, especially in elderly patients. This review comprehensively assesses risk factors, clinical characteristics, and management strategies for bacterial, viral, fungal, and acanthamoeba keratitis in the elderly population, offering crucial insights for effective intervention.
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Affiliation(s)
- Christine K Kim
- Gavin Herbert Eye Institute, University of California, Irvine School of Medicine, Irvine, CA, USA
| | - Melisa Z Karslioglu
- Gavin Herbert Eye Institute, University of California, Irvine School of Medicine, Irvine, CA, USA
| | - Sharon H Zhao
- Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Olivia L Lee
- Gavin Herbert Eye Institute, University of California, Irvine School of Medicine, Irvine, CA, USA
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Laskow T, Langdon J, Sepehri S, Davalos-Bichara M, Varadhan R, Walston J. Soluble TNFR1 has greater reproducibility than IL-6 for the assessment of chronic inflammation in older adults: the case for a new inflammatory marker in aging. GeroScience 2024; 46:2521-2530. [PMID: 37993568 PMCID: PMC10828298 DOI: 10.1007/s11357-023-01006-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Accepted: 11/01/2023] [Indexed: 11/24/2023] Open
Abstract
Chronic inflammatory pathway activation, commonly referred to as "Inflammaging" or chronic inflammation (CI), is associated with frailty, cognitive and functional decline, and other causes of health span decline in older adults. We investigated the variability of candidate serum measures of CI among community-dwelling older adults selected for mild low-grade inflammation. We focused on serum cytokines known to be highly predictive of adverse health outcomes in older adults (sTNFR1, IL-6) during a short-term (weeks) and medium-term (months) follow-up, as well as immune markers that are less studied in aging but reflect other potentially relevant domains such as adaptive immune activation (sCD25), innate immune activation (sCD14 and sCD163), and the inflammation-metabolism interface (adiponectin/Acrp30) during short-term (weeks) follow up. We found that sTNFR1 was more reproducible than IL-6 over a period of weeks and months short-term and medium-term. The intra-class correlation coefficient (ICC) for sTNFR1 was 0.95 on repeated measures over 6 weeks, and 0.79 on repeated measures with mean interval of 14 weeks, while the ICC for IL-6 was 0.52 over corresponding short-term and 0.67 over corresponding medium-term follow-up. This suggests that sTNFR1 is a more reliable marker of CI than IL-6. This study provides new insights into the reproducibility of serum markers of CI in older adults. The findings suggest that sTNFR1 may be a better marker of CI than IL-6 in this population. Further studies are needed to confirm these findings and to investigate the clinical utility of sTNFR1 in older adults.
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Affiliation(s)
- Thomas Laskow
- Johns Hopkins University School of Medicine, 5505 Hopkins Bayview Circle, Baltimore, MD, 21224-6821, USA
| | - Jacqueline Langdon
- Johns Hopkins University School of Medicine, 5505 Hopkins Bayview Circle, Baltimore, MD, 21224-6821, USA
| | - Sam Sepehri
- Johns Hopkins University School of Medicine, 5505 Hopkins Bayview Circle, Baltimore, MD, 21224-6821, USA
| | - Marcela Davalos-Bichara
- Johns Hopkins University School of Medicine, 5505 Hopkins Bayview Circle, Baltimore, MD, 21224-6821, USA
| | - Ravi Varadhan
- Johns Hopkins University School of Medicine, 5505 Hopkins Bayview Circle, Baltimore, MD, 21224-6821, USA
| | - Jeremy Walston
- Johns Hopkins University School of Medicine, 5505 Hopkins Bayview Circle, Baltimore, MD, 21224-6821, USA.
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Catanese L, Rupprecht H, Huber TB, Lindenmeyer MT, Hengel FE, Amann K, Wendt R, Siwy J, Mischak H, Beige J. Non-Invasive Biomarkers for Diagnosis, Risk Prediction, and Therapy Guidance of Glomerular Kidney Diseases: A Comprehensive Review. Int J Mol Sci 2024; 25:3519. [PMID: 38542491 PMCID: PMC10970781 DOI: 10.3390/ijms25063519] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Revised: 03/13/2024] [Accepted: 03/18/2024] [Indexed: 04/09/2025] Open
Abstract
Effective management of glomerular kidney disease, one of the main categories of chronic kidney disease (CKD), requires accurate diagnosis, prognosis of progression, assessment of therapeutic efficacy, and, ideally, prediction of drug response. Multiple biomarkers and algorithms for the assessment of specific aspects of glomerular diseases have been reported in the literature. Though, the vast majority of these have not been implemented in clinical practice or are not available on a global scale due to limited access, missing medical infrastructure, or economical as well as political reasons. The aim of this review is to compile all currently available information on the diagnostic, prognostic, and predictive biomarkers currently available for the management of glomerular diseases, and provide guidance on the application of these biomarkers. As a result of the compiled evidence for the different biomarkers available, we present a decision tree for a non-invasive, biomarker-guided diagnostic path. The data currently available demonstrate that for the large majority of patients with glomerular diseases, valid biomarkers are available. However, despite the obvious disadvantages of kidney biopsy, being invasive and not applicable for monitoring, especially in the context of rare CKD etiologies, kidney biopsy still cannot be replaced by non-invasive strategies.
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Affiliation(s)
- Lorenzo Catanese
- Department of Nephrology, Angiology and Rheumatology, Klinikum Bayreuth GmbH, 95445 Bayreuth, Germany; (L.C.); (H.R.)
- Kuratorium for Dialysis and Transplantation (KfH) Bayreuth, 95445 Bayreuth, Germany
- Department of Nephrology, Medizincampus Oberfranken, Friedrich-Alexander-University Erlangen-Nürnberg, 91054 Erlangen, Germany
| | - Harald Rupprecht
- Department of Nephrology, Angiology and Rheumatology, Klinikum Bayreuth GmbH, 95445 Bayreuth, Germany; (L.C.); (H.R.)
- Kuratorium for Dialysis and Transplantation (KfH) Bayreuth, 95445 Bayreuth, Germany
- Department of Nephrology, Medizincampus Oberfranken, Friedrich-Alexander-University Erlangen-Nürnberg, 91054 Erlangen, Germany
| | - Tobias B. Huber
- III Department of Medicine, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany; (T.B.H.); (M.T.L.); (F.E.H.)
| | - Maja T. Lindenmeyer
- III Department of Medicine, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany; (T.B.H.); (M.T.L.); (F.E.H.)
| | - Felicitas E. Hengel
- III Department of Medicine, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany; (T.B.H.); (M.T.L.); (F.E.H.)
| | - Kerstin Amann
- Department of Nephropathology, Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany;
| | - Ralph Wendt
- Division of Nephrology, St. Georg Hospital, 04129 Leipzig, Germany;
| | - Justyna Siwy
- Mosaiques Diagnostics GmbH, 30659 Hannover, Germany; (J.S.); (H.M.)
| | - Harald Mischak
- Mosaiques Diagnostics GmbH, 30659 Hannover, Germany; (J.S.); (H.M.)
| | - Joachim Beige
- Division of Nephrology, St. Georg Hospital, 04129 Leipzig, Germany;
- Department of Internal Medicine II, Martin-Luther-University Halle-Wittenberg, 06108 Halle, Germany
- Kuratorium for Dialysis and Transplantation (KfH) Leipzig, 04129 Leipzig, Germany
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Fang Y, Wang B, Pang B, Zhou Z, Xing Y, Pang P, Zheng D, Zhang G, Yang B. Exploring the relations of NLR, hsCRP and MCP-1 with type 2 diabetic kidney disease: a cross-sectional study. Sci Rep 2024; 14:3211. [PMID: 38332001 PMCID: PMC10853504 DOI: 10.1038/s41598-024-53567-2] [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: 09/14/2023] [Accepted: 02/02/2024] [Indexed: 02/10/2024] Open
Abstract
Type 2 diabetic kidney disease (T2DKD) is a common microvascular complication of type 2 diabetes mellitus (T2DM), and its incidence is significantly increasing. Microinflammation plays an important role in the development of T2DKD. Based on this, this study investigated the value of inflammatory markers including neutrophil-lymphocyte ratio (NLR), high-sensitivity C-reactive protein (hs-CRP), monocyte chemoattractant protein-1 (MCP-1) in the prediction of T2DKD. This was a cross-sectional survey study. A total of 90 patients with T2DM, who were hospitalized in the nephrology and endocrinology departments of the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine from June 2021 to January 2022, were included and divided into three groups (A1, A2, A3) according to the urinary albumin-to-creatinine ratio (UACR). Observe and compare the basic information, clinical and laboratory data, and the inflammatory markers NLR, hs-CRP, MCP-1. Results revealed that high levels of NLR (OR = 6.562, 95% CI 2.060-20.902, P = 0.001) and MCP-1 (OR = 1.060, 95% CI 1.026-1.095, P < 0.001) were risk factors in the development of T2DKD. Receiver operating characteristic curve analysis showed that the area under curve of NLR and MCP-1 in diagnosing T2DKD were 0.760 (95% CI 0.6577-0.863, P < 0.001) and 0.862 (95% CI 0.7787-0.937, P < 0.001). Therefore, the inflammatory markers NLR and MCP-1 are risk factors affecting the development of T2DKD, which of clinical value may be used as novel markers of T2DKD.
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Affiliation(s)
- Yaxuan Fang
- Department of Nephrology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Liqizhuang Street, Xiqing District, Tianjin, 300380, China
- Department of Nephrology, National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China
| | - Bin Wang
- Department of Endocrinology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
- Department of Endocrinology, National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China
| | - Bo Pang
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Zijun Zhou
- Department of Nephrology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Liqizhuang Street, Xiqing District, Tianjin, 300380, China
- Department of Nephrology, National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China
| | - Yunze Xing
- Department of Nephrology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Liqizhuang Street, Xiqing District, Tianjin, 300380, China
- Department of Nephrology, National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China
| | - Pai Pang
- Department of Endocrinology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
- Department of Endocrinology, National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China
| | - Dingyuan Zheng
- Department of Nephrology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Liqizhuang Street, Xiqing District, Tianjin, 300380, China
- Department of Nephrology, National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China
| | - Gang Zhang
- The Community Health Service Center of Hangzhou Road Street in Tianjin Binhai New Area, Tianjin, China
| | - Bo Yang
- Department of Nephrology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Liqizhuang Street, Xiqing District, Tianjin, 300380, China.
- Department of Nephrology, National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China.
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Jin Y, Xu Z, Zhang Y, Zhang Y, Wang D, Cheng Y, Zhou Y, Fawad M, Xu X. Serum/plasma biomarkers and the progression of cardiometabolic multimorbidity: a systematic review and meta-analysis. Front Public Health 2023; 11:1280185. [PMID: 38074721 PMCID: PMC10701686 DOI: 10.3389/fpubh.2023.1280185] [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: 08/19/2023] [Accepted: 10/27/2023] [Indexed: 12/18/2023] Open
Abstract
Background The role of certain biomarkers in the development of single cardiometabolic disease (CMD) has been intensively investigated. Less is known about the association of biomarkers with multiple CMDs (cardiometabolic multimorbidity, CMM), which is essential for the exploration of molecular targets for the prevention and treatment of CMM. We aimed to systematically synthesize the current evidence on CMM-related biomarkers. Methods We searched PubMed, Embase, Web of Science, and Ebsco for relevant studies from inception until August 31st, 2022. Studies reported the association of serum/plasma biomarkers with CMM, and relevant effect sizes were included. The outcomes were five progression patterns of CMM: (1) no CMD to CMM; (2) type 2 diabetes mellitus (T2DM) followed by stroke; (3) T2DM followed by coronary heart disease (CHD); (4) T2DM followed by stroke or CHD; and (5) CHD followed by T2DM. Newcastle-Ottawa Quality Assessment Scale (NOS) was used to assess the quality of the included studies. A meta-analysis was conducted to quantify the association of biomarkers and CMM. Results A total of 68 biomarkers were identified from 42 studies, which could be categorized into five groups: lipid metabolism, glycometabolism, liver function, immunity, and others. Lipid metabolism biomarkers were most reported to associate with CMM, including TC, TGs, HDL-C, LDL-C, and Lp(a). Fasting plasma glucose was also reported by several studies, and it was particularly associated with coexisting T2DM with vascular diseases. According to the quantitative meta-analysis, HDL-C was negatively associated with CHD risk among patients with T2DM (pooled OR for per 1 mmol/L increase = 0.79, 95% CI = 0.77-0.82), whereas a higher TGs level (pooled OR for higher than 150 mg/dL = 1.39, 95% CI = 1.10-1.75) was positively associated with CHD risk among female patients with T2DM. Conclusion Certain serum/plasma biomarkers were associated with the progression of CMM, in particular for those related to lipid metabolism, but heterogeneity and inconsistent findings still existed among included studies. There is a need for future research to explore more relevant biomarkers associated with the occurrence and progression of CMM, targeted at which is important for the early identification and prevention of CMM.
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Affiliation(s)
- Yichen Jin
- School of Public Health, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- The Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province, Hangzhou, Zhejiang, China
| | - Ziyuan Xu
- School of Public Health, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- The Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province, Hangzhou, Zhejiang, China
| | - Yuting Zhang
- School of Public Health, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- The Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province, Hangzhou, Zhejiang, China
| | - Yue Zhang
- School of Public Health, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- The Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province, Hangzhou, Zhejiang, China
| | - Danyang Wang
- School of Public Health, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- The Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province, Hangzhou, Zhejiang, China
| | - Yangyang Cheng
- School of Public Health, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- The Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province, Hangzhou, Zhejiang, China
| | - Yaguan Zhou
- School of Public Health, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- The Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province, Hangzhou, Zhejiang, China
| | - Muhammad Fawad
- School of Public Health, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- The Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province, Hangzhou, Zhejiang, China
| | - Xiaolin Xu
- School of Public Health, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- The Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province, Hangzhou, Zhejiang, China
- School of Public Health, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
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Cheng MK, Guo YY, Kang XN, Zhang L, Wang D, Ren HH, Yuan G. Advances in cardiovascular-related biomarkers to predict diabetic peripheral neuropathy. World J Diabetes 2023; 14:1226-1233. [PMID: 37664477 PMCID: PMC10473952 DOI: 10.4239/wjd.v14.i8.1226] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Revised: 06/24/2023] [Accepted: 07/07/2023] [Indexed: 08/11/2023] Open
Abstract
Diabetic peripheral neuropathy (DPN) is a common chronic complication of diabetes mellitus. One of the most common types is distal symmetric poly-neuropathy, which begins as bilateral symmetry pain and hyperesthesia and gradually progresses into hypoesthesia with nerve fibre disorder and is frequently accompanied by depression and anxiety. Notably, more than half of patients with DPN can be asymptomatic, which tends to delay early detection. Furthermore, the study of adverse outcomes showed that DPN is a prominent risk factor for foot ulceration, gangrene and nontraumatic amputation, which decreases quality of life. Thus, it is essential to develop convenient diagnostic biomarkers with high sensitivity for screening and early intervention. It has been reported that there may be common pathways for microvascular and macrovascular complications of diabetes. The pathogenesis of both disorders involves vascular endothelial dys-function. Emerging evidence indicates that traditional and novel cardiovascular-related biomarkers have the potential to characterize patients by subclinical disease status and improve risk prediction. Additionally, beyond traditional cardiovascular-related biomarkers, novel cardiovascular-related biomarkers have been linked to diabetes and its complications. In this review, we evaluate the association between major traditional and nontraditional car-diovascular-related biomarkers of DPN, such as cardiac troponin T, B-type natriuretic peptide, C-reactive protein, myeloperoxidase, and homocysteine, and assess the evidence for early risk factor-based management strategies to reduce the incidence and slow the progression of DPN.
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Affiliation(s)
- Meng-Ke Cheng
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430030, Hubei Province, China
| | - Yao-Yao Guo
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430030, Hubei Province, China
| | - Xiao-Nan Kang
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430030, Hubei Province, China
| | - Lu Zhang
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430030, Hubei Province, China
| | - Dan Wang
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430030, Hubei Province, China
| | - Hui-Hui Ren
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430030, Hubei Province, China
| | - Gang Yuan
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430030, Hubei Province, China
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10
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Liu X, Chen D, Fu H, Liu X, Zhang Q, Zhang J, Ding M, Wen J, Chang B. Development and validation of a risk prediction model for early diabetic peripheral neuropathy based on a systematic review and meta-analysis. Front Public Health 2023; 11:1128069. [PMID: 36908480 PMCID: PMC9992641 DOI: 10.3389/fpubh.2023.1128069] [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: 12/20/2022] [Accepted: 02/06/2023] [Indexed: 02/24/2023] Open
Abstract
Background Early identification and intervention of diabetic peripheral neuropathy is beneficial to improve clinical outcome. Objective To establish a risk prediction model for diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes mellitus (T2DM). Methods The derivation cohort was from a meta-analysis. Risk factors and the corresponding risk ratio (RR) were extracted. Only risk factors with statistical significance were included in the model and were scored by their weightings. An external cohort were used to validate this model. The outcome was the occurrence of DPN. Results A total of 95,604 patients with T2DM from 18 cohorts were included. Age, smoking, body mass index, duration of diabetes, hemoglobin A1c, low HDL-c, high triglyceride, hypertension, diabetic retinopathy, diabetic kidney disease, and cardiovascular disease were enrolled in the final model. The highest score was 52.0. The median follow-up of validation cohort was 4.29 years. The optimal cut-off point was 17.0, with a sensitivity of 0.846 and a specificity of 0.668, respectively. According to the total scores, patients from the validation cohort were divided into low-, moderate-, high- and very high-risk groups. The risk of developing DPN was significantly increased in moderate- (RR 3.3, 95% CI 1.5-7.2, P = 0.020), high- (RR 15.5, 95% CI 7.6-31.6, P < 0.001), and very high-risk groups (RR 45.0, 95% CI 20.5-98.8, P < 0.001) compared with the low-risk group. Conclusion A risk prediction model for DPN including 11 common clinical indicators were established. It is a simple and reliable tool for early prevention and intervention of DPN in patients with T2DM.
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Affiliation(s)
- Xixi Liu
- NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China
| | - Dong Chen
- Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China
| | - Hongmin Fu
- NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China
| | - Xinbang Liu
- NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China
| | - Qiumei Zhang
- NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China
| | - Jingyun Zhang
- NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China
| | - Min Ding
- NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China
| | - Juanjuan Wen
- NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China
| | - Bai Chang
- Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China
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11
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Okdahl T, Wegeberg AM, Pociot F, Brock B, Størling J, Brock C. Low-grade inflammation in type 2 diabetes: a cross-sectional study from a Danish diabetes outpatient clinic. BMJ Open 2022; 12:e062188. [PMID: 36517105 PMCID: PMC9756179 DOI: 10.1136/bmjopen-2022-062188] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
OBJECTIVES To investigate low-grade inflammation in type 2 diabetes and explore associations to clinical aspects as well as microvascular and macrovascular complications. DESIGN Cross-sectional analysis. SETTING The outpatient diabetes clinic at the Department of Endocrinology at Aalborg University Hospital, Denmark. PARTICIPANTS 100 participants with type 2 diabetes confirmed by a haemoglobin A1c (HbA1c)≥6.5% for a minimum of 1 year and 21 healthy controls. OUTCOME MEASURES Serum levels of 27 inflammation-related biomarkers measured by immunoassay. Associations with microvascular and macrovascular complications, body weight, glycaemic control, medication and sex were investigated in the diabetes cohort. RESULTS Serum levels of tumour necrosis factor (TNF)-α and eotaxin were elevated in type 2 diabetes (p<0.05), while interleukin (IL)-7 was decreased (p<0.001). IL-12/IL-23p40, IL-15, macrophage-derived chemokine (MDC) and C reactive protein (CRP) levels were increased with body weight (p<0.05), while eotaxin and TNF-α were increased with elevated HbA1c levels (p<0.04). Dipeptidyl peptidase-4 inhibitor therapy was associated with lower levels of induced protein-10, MDC and thymus and activation regulated chemokine (p<0.02), while females had higher levels of MDC (p=0.027). Individuals with ≥3 diabetic complications had elevated levels of IL-6, IL-10, IL-12/IL-23p40, IL-15 and CRP compared with those with ≤3 (p<0.05). CONCLUSION The level of low-grade inflammation in type 2 diabetes is associated with obesity, glycaemic regulation, therapeutical management, sex and complications. Our results underline the importance of addressing inflammatory issues in type 2 diabetes, as these may predispose for crippling comorbidities.
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Affiliation(s)
- Tina Okdahl
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
| | - Anne-Marie Wegeberg
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
- Thisted Research Unit, Aalborg University Hospital Thisted, Thisted, Denmark
| | - Flemming Pociot
- Steno Diabetes Center Copenhagen, Capital Region of Denmark, Herlev, Denmark
- Faculty of Health and Medical Sciences, University of Copenhagen, Kobenhavn, Denmark
| | - Birgitte Brock
- Steno Diabetes Center Copenhagen, Capital Region of Denmark, Herlev, Denmark
| | - Joachim Størling
- Steno Diabetes Center Copenhagen, Capital Region of Denmark, Herlev, Denmark
- Department of Biomedical Sciences, University of Copenhagen, Kobenhavn, Denmark
| | - Christina Brock
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
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12
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Khanijou V, Zafari N, Coughlan MT, MacIsaac RJ, Ekinci EI. Review of potential biomarkers of inflammation and kidney injury in diabetic kidney disease. Diabetes Metab Res Rev 2022; 38:e3556. [PMID: 35708187 PMCID: PMC9541229 DOI: 10.1002/dmrr.3556] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2021] [Revised: 02/18/2022] [Accepted: 04/02/2022] [Indexed: 11/17/2022]
Abstract
Diabetic kidney disease is expected to increase rapidly over the coming decades with rising prevalence of diabetes worldwide. Current measures of kidney function based on albuminuria and estimated glomerular filtration rate do not accurately stratify and predict individuals at risk of declining kidney function in diabetes. As a result, recent attention has turned towards identifying and assessing the utility of biomarkers in diabetic kidney disease. This review explores the current literature on biomarkers of inflammation and kidney injury focussing on studies of single or multiple biomarkers between January 2014 and February 2020. Multiple serum and urine biomarkers of inflammation and kidney injury have demonstrated significant association with the development and progression of diabetic kidney disease. Of the inflammatory biomarkers, tumour necrosis factor receptor-1 and -2 were frequently studied and appear to hold most promise as markers of diabetic kidney disease. With regards to kidney injury biomarkers, studies have largely targeted markers of tubular injury of which kidney injury molecule-1, beta-2-microglobulin and neutrophil gelatinase-associated lipocalin emerged as potential candidates. Finally, the use of a small panel of selective biomarkers appears to perform just as well as a panel of multiple biomarkers for predicting kidney function decline.
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Affiliation(s)
- Vuthi Khanijou
- Melbourne Medical SchoolUniversity of MelbourneAustin HealthMelbourneVictoriaAustralia
| | - Neda Zafari
- Department of MedicineUniversity of MelbourneAustin HealthMelbourneVictoriaAustralia
| | - Melinda T. Coughlan
- Department of DiabetesCentral Clinical SchoolMonash UniversityAlfred Medical Research AllianceMelbourneVictoriaAustralia
- Baker Heart & Diabetes InstituteMelbourneVictoriaAustralia
| | - Richard J. MacIsaac
- Department of Endocrinology & DiabetesSt. Vincent's Hospital Melbourne and University of MelbourneMelbourneVictoriaAustralia
| | - Elif I. Ekinci
- Melbourne Medical SchoolUniversity of MelbourneAustin HealthMelbourneVictoriaAustralia
- Department of EndocrinologyAustin HealthMelbourneVictoriaAustralia
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13
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Role of C-Reactive Protein in Diabetic Inflammation. Mediators Inflamm 2022; 2022:3706508. [PMID: 35620114 PMCID: PMC9129992 DOI: 10.1155/2022/3706508] [Citation(s) in RCA: 50] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 04/20/2022] [Accepted: 04/29/2022] [Indexed: 01/08/2023] Open
Abstract
Even though type 2 diabetes mellitus (T2DM) represents a worldwide chronic health issue that affects about 462 million people, specific underlying determinants of insulin resistance (IR) and impaired insulin secretion are still unknown. There is growing evidence that chronic subclinical inflammation is a triggering factor in the origin of T2DM. Increased C-reactive protein (CRP) levels have been linked to excess body weight since adipocytes produce tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6), which are pivotal factors for CRP stimulation. Furthermore, it is known that hepatocytes produce relatively low rates of CRP in physiological conditions compared to T2DM patients, in which elevated levels of inflammatory markers are reported, including CRP. CRP also participates in endothelial dysfunction, the production of vasodilators, and vascular remodeling, and increased CRP level is closely associated with vascular system pathology and metabolic syndrome. In addition, insulin-based therapies may alter CRP levels in T2DM. Therefore, determining and clarifying the underlying CRP mechanism of T2DM is imperative for novel preventive and diagnostic procedures. Overall, CRP is one of the possible targets for T2DM progression and understanding the connection between insulin and inflammation may be helpful in clinical treatment and prevention approaches.
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14
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Ryan E, Ahn J, Wukich DK, Fontaine JL, Crisologo PA, Malone M, Oz OK, Lavery LA. Effect of Sensory Neuropathy on the Predictive Value of Inflammatory Biomarkers for Osteomyelitis in Diabetic and Nondiabetic Patients with Foot Infections. J Am Podiatr Med Assoc 2022; 112:20-168. [PMID: 33142316 DOI: 10.7547/20-168] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE To investigate the predictive value of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in persons with and without diabetes with osteomyelitis (OM). METHODS We evaluated 455 patients in a retrospective cohort study of patients admitted to the hospital with diabetic foot OM (n = 177), diabetic foot soft-tissue infections (STIs) (n = 176), nondiabetic OM (n = 51), and nondiabetic STIs (n = 51). Infection diagnosis was determined through bone culture, histopathologic examination for OM, and/or imaging (magnetic resonance imaging/single-photon emission computed tomography) for STI. The optimal cutoff values of ESR and CRP in predicting OM were determined by receiver operating characteristic curve analysis. Sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios were determined through contingency tables. RESULTS In persons without diabetes with STI or OM, the mean ESR and CRP differences were 10.0 mm/h and 2.6 mg/dL, respectively. In contrast, persons with diabetes had higher levels of each: 24.8 mm/h and 6.8 mg/dL, respectively. As a result, ESR and CRP predicted OM better in patients with diabetes. However, when patients were stratified by neuropathy status, ESR remained predictive of OM in diabetic patients with neuropathy (75% sensitivity, 58% specificity) but not in diabetic patients without neuropathy (50% sensitivity, 44% specificity). Also, CRP remained predictive irrespective of neuropathy status. A similar trend was observed in patients without diabetes. CONCLUSIONS Previous studies have reported that ESR and CRP are predictive of OM. However, this study suggests that neuropathy influences the predictive value of inflammatory biomarkers. The underlying mechanisms require further study.
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Affiliation(s)
- Easton Ryan
- *Department of Plastic Surgery, University of Texas Southwestern Medical Center, Dallas, TX
| | - Junho Ahn
- †Department of Orthopedic Surgery, University of Texas Southwestern Medical Center, Dallas, TX
| | - Dane K Wukich
- †Department of Orthopedic Surgery, University of Texas Southwestern Medical Center, Dallas, TX
| | - Javier La Fontaine
- *Department of Plastic Surgery, University of Texas Southwestern Medical Center, Dallas, TX
| | - Peter A Crisologo
- *Department of Plastic Surgery, University of Texas Southwestern Medical Center, Dallas, TX
| | - Matthew Malone
- §South West Sydney Limb Preservation and Wound Research Academic Unit, South Western Sydney Local Health District, Sydney, Australia
| | - Orhan K Oz
- ‖Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX
| | - Lawrence A Lavery
- *Department of Plastic Surgery, University of Texas Southwestern Medical Center, Dallas, TX
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15
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Hypoglycemia, Vascular Disease and Cognitive Dysfunction in Diabetes: Insights from Text Mining-Based Reconstruction and Bioinformatics Analysis of the Gene Networks. Int J Mol Sci 2021; 22:ijms222212419. [PMID: 34830301 PMCID: PMC8620086 DOI: 10.3390/ijms222212419] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Revised: 11/14/2021] [Accepted: 11/16/2021] [Indexed: 12/16/2022] Open
Abstract
Hypoglycemia has been recognized as a risk factor for diabetic vascular complications and cognitive decline, but the molecular mechanisms of the effect of hypoglycemia on target organs are not fully understood. In this work, gene networks of hypoglycemia and cardiovascular disease, diabetic retinopathy, diabetic nephropathy, diabetic neuropathy, cognitive decline, and Alzheimer's disease were reconstructed using ANDSystem, a text-mining-based tool. The gene network of hypoglycemia included 141 genes and 2467 interactions. Enrichment analysis of Gene Ontology (GO) biological processes showed that the regulation of insulin secretion, glucose homeostasis, apoptosis, nitric oxide biosynthesis, and cell signaling are significantly enriched for hypoglycemia. Among the network hubs, INS, IL6, LEP, TNF, IL1B, EGFR, and FOS had the highest betweenness centrality, while GPR142, MBOAT4, SLC5A4, IGFBP6, PPY, G6PC1, SLC2A2, GYS2, GCGR, and AQP7 demonstrated the highest cross-talk specificity. Hypoglycemia-related genes were overrepresented in the gene networks of diabetic complications and comorbidity; moreover, 14 genes were mutual for all studied disorders. Eleven GO biological processes (glucose homeostasis, nitric oxide biosynthesis, smooth muscle cell proliferation, ERK1 and ERK2 cascade, etc.) were overrepresented in all reconstructed networks. The obtained results expand our understanding of the molecular mechanisms underlying the deteriorating effects of hypoglycemia in diabetes-associated vascular disease and cognitive dysfunction.
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16
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Lang M, Song Y, Li Y, Xiang X, Ni L, Miao J. Purification, identification, and molecular mechanism of DPP-IV inhibitory peptides from defatted Antarctic krill powder. J Food Biochem 2021; 45:e13872. [PMID: 34296449 DOI: 10.1111/jfbc.13872] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Revised: 06/22/2021] [Accepted: 06/28/2021] [Indexed: 11/27/2022]
Abstract
Dipeptidyl peptidase-IV (DPP-IV) inhibitors can reduce the blood sugar levels of diabetic patients by preventing the rapid decomposition of incretin hormone and prolonging its physiological effects. In this study, DPP-IV inhibitory peptides FAGDDAPR and LAPPRGSL were isolated from defatted Antarctic krill powder (DAKP) protein by the sequential purification of ultrafiltration, gel filtration chromatography, and RP-HPLC, and IC50 values of the two peptides were 349.70 ± 3.66 μM and 461.14 ± 0.87 μM, respectively. The FAGDDAPR and LAPPRGSL were identified by LC-MS/MS method, and the molecular models of DPP-IV and the two peptides were further constructed by AutoDock Vina software, the results revealed that the inhibition activity of FAGDDAPR and LAPPRGSL was mainly attributed to the formation of strong hydrophobic interactions and hydrogen bonds with amino acids of DPP-IV. PRACTICAL APPLICATIONS: DAKP is an economical by-product produced in the production of krill oil and contains high-quality protein, but these products were mainly used as fish feed and had low utility value in the past. DPP-IV inhibitors are an efficacious drug employed in the treatment of hyperglycemia processes. However, these drugs can cause undesirable side effects. Thus, the development of new natural hypoglycemic drugs with low side effects is a valuable strategy to be applied in therapeutic interventions.
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Affiliation(s)
- Meng Lang
- College of Food Science and Technology, Shanghai Ocean University, Shanghai, P. R. China
| | - Yishan Song
- College of Food Science and Technology, Shanghai Ocean University, Shanghai, P. R. China
| | - Yan Li
- College of Food Science and Technology, Shanghai Ocean University, Shanghai, P. R. China
| | - Xi Xiang
- College of Food Science and Technology, Shanghai Ocean University, Shanghai, P. R. China
| | - Ling Ni
- College of Food Science and Technology, Shanghai Ocean University, Shanghai, P. R. China
| | - Junjian Miao
- College of Food Science and Technology, Shanghai Ocean University, Shanghai, P. R. China
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17
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Bargieł W, Cierpiszewska K, Maruszczak K, Pakuła A, Szwankowska D, Wrzesińska A, Gutowski Ł, Formanowicz D. Recognized and Potentially New Biomarkers-Their Role in Diagnosis and Prognosis of Cardiovascular Disease. MEDICINA (KAUNAS, LITHUANIA) 2021; 57:medicina57070701. [PMID: 34356982 PMCID: PMC8305174 DOI: 10.3390/medicina57070701] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Revised: 07/03/2021] [Accepted: 07/04/2021] [Indexed: 01/08/2023]
Abstract
Atherosclerosis and its consequences are the leading cause of mortality in the world. For this reason, we have reviewed atherosclerosis biomarkers and selected the most promising ones for review. We focused mainly on biomarkers related to inflammation and oxidative stress, such as the highly sensitive C-reactive protein (hs-CRP), interleukin 6 (IL-6), and lipoprotein-associated phospholipase A2 (Lp-PLA2). The microRNA (miRNA) and the usefulness of the bone mineralization, glucose, and lipid metabolism marker osteocalcin (OC) were also reviewed. The last biomarker we considered was angiogenin (ANG). Our review shows that due to the multifactorial nature of atherosclerosis, no single marker is known so far, the determination of which would unambiguously assess the severity of atherosclerosis and help without any doubt in the prognosis of cardiovascular risk.
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Affiliation(s)
- Weronika Bargieł
- Faculty of Medicine, Poznan University of Medical Sciences, 60-812 Poznan, Poland; (W.B.); (K.C.); (K.M.); (A.P.); (D.S.); (A.W.)
| | - Katarzyna Cierpiszewska
- Faculty of Medicine, Poznan University of Medical Sciences, 60-812 Poznan, Poland; (W.B.); (K.C.); (K.M.); (A.P.); (D.S.); (A.W.)
| | - Klara Maruszczak
- Faculty of Medicine, Poznan University of Medical Sciences, 60-812 Poznan, Poland; (W.B.); (K.C.); (K.M.); (A.P.); (D.S.); (A.W.)
| | - Anna Pakuła
- Faculty of Medicine, Poznan University of Medical Sciences, 60-812 Poznan, Poland; (W.B.); (K.C.); (K.M.); (A.P.); (D.S.); (A.W.)
| | - Dominika Szwankowska
- Faculty of Medicine, Poznan University of Medical Sciences, 60-812 Poznan, Poland; (W.B.); (K.C.); (K.M.); (A.P.); (D.S.); (A.W.)
| | - Aleksandra Wrzesińska
- Faculty of Medicine, Poznan University of Medical Sciences, 60-812 Poznan, Poland; (W.B.); (K.C.); (K.M.); (A.P.); (D.S.); (A.W.)
| | - Łukasz Gutowski
- Department of Medical Chemistry and Laboratory Medicine, Poznan University of Medical Sciences, Rokietnicka 8, 60-806 Poznan, Poland;
| | - Dorota Formanowicz
- Department of Medical Chemistry and Laboratory Medicine, Poznan University of Medical Sciences, Rokietnicka 8, 60-806 Poznan, Poland;
- Correspondence:
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18
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Zhao H, Zhang LD, Liu LF, Li CQ, Song WL, Pang YY, Zhang YL, Li D. Blood Levels of Glycated Hemoglobin, D-Dimer, and Fibrinogen in Diabetic Retinopathy. Diabetes Metab Syndr Obes 2021; 14:2483-2488. [PMID: 34103957 PMCID: PMC8180300 DOI: 10.2147/dmso.s309068] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Accepted: 05/05/2021] [Indexed: 12/12/2022] Open
Abstract
PURPOSE This study aimed to describe the levels of glycated hemoglobin (HbA1c), D-dimer (D-D), and fibrinogen (FIB) in different types of diabetic retinopathy (DR). METHODS A total of 61 patients with diabetes, who were treated in our department between November 2017 and May 2019, were selected. According to their non-mydriatic fundus photography and fundus angiography results, patients were divided into three groups, ie, the non-DR (NDR) group (n=23), the non-proliferative DR (NPDR) group (n=17), and the proliferative DR (PDR) group (n=21). A control group of 20 people who had tested negative for diabetes was also included. The levels of HbA1c, D-D, and FIB were measured and compared, respectively. RESULTS The mean values of HbA1c were 6.8% (5.2%, 7.7%), 7.4% (5.8%, 9.0%), and 8.5% (6.3%, 9.7%) in the NDR, NPDR, and PDR groups, respectively. The control group values were 4.9% (4.1%, 5.8%). These results indicated a significant statistical difference between groups. The mean values of D-D were 0.39 ± 0.21 mg/L, 1.06 ± 0.54 mg/L, and 1.39 ± 0.59 mg/L in the NDR, NPDR, and PDR groups, respectively. The control group result was 0.36 ± 0.17 mg/L. The values of the NPDR and PDR groups were significantly higher than those of the NDR and control groups, and the value of the PDR group was significantly higher than that of the NPDR group, indicating a significant difference between the groups (P < 0.001). The mean values of FIB were 3.07 ± 0.42 g/L, 4.38 ± 0.54 g/L, and 4.46 ± 1.09 g/L in the NDR, NPDR, and PDR groups, respectively. The control group result was 2.97 ± 0.67 g/L. The difference between the groups was statistically significant (P < 0.05). CONCLUSION Blood levels of HbA1c, D-D, and FIB in the PDR group were significantly higher than in the NPDR group.
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Affiliation(s)
- Heng Zhao
- Endocrinology Laboratory, The First Central Hospital of Baoding, Baoding, Hebei Province, 071000, People’s Republic of China
| | - Li-Dan Zhang
- Department of Nuclear Medicine, The First Central Hospital of Baoding, Baoding, Hebei Province, 071000, People’s Republic of China
| | - Li-Fang Liu
- Endocrinology Laboratory, The First Central Hospital of Baoding, Baoding, Hebei Province, 071000, People’s Republic of China
| | - Chun-Qing Li
- Outpatient Department, The First Central Hospital of Baoding, Baoding, Hebei Province, 071000, People’s Republic of China
| | - Wei-Li Song
- Outpatient Department, The First Central Hospital of Baoding, Baoding, Hebei Province, 071000, People’s Republic of China
| | - Yong-Yang Pang
- Endocrinology Laboratory, The First Central Hospital of Baoding, Baoding, Hebei Province, 071000, People’s Republic of China
| | - Yun-Liang Zhang
- Endocrinology Laboratory, The First Central Hospital of Baoding, Baoding, Hebei Province, 071000, People’s Republic of China
| | - Dan Li
- Department of Ophthalmology, Affiliated Hospital of Hebei University, Baoding, Hebei Province, 071000, People’s Republic of China
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Liberale L, Montecucco F, Tardif JC, Libby P, Camici GG. Inflamm-ageing: the role of inflammation in age-dependent cardiovascular disease. Eur Heart J 2021; 41:2974-2982. [PMID: 32006431 DOI: 10.1093/eurheartj/ehz961] [Citation(s) in RCA: 189] [Impact Index Per Article: 47.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2019] [Revised: 09/10/2019] [Accepted: 01/09/2020] [Indexed: 12/12/2022] Open
Abstract
The ongoing worldwide increase in life expectancy portends a rising prevalence of age-related cardiovascular (CV) diseases in the coming decades that demands a deeper understanding of their molecular mechanisms. Inflammation has recently emerged as an important contributor for CV disease development. Indeed, a state of chronic sterile low-grade inflammation characterizes older organisms (also known as inflamm-ageing) and participates pivotally in the development of frailty, disability, and most chronic degenerative diseases including age-related CV and cerebrovascular afflictions. Due to chronic activation of inflammasomes and to reduced endogenous anti-inflammatory mechanisms, inflamm-ageing contributes to the activation of leucocytes, endothelial, and vascular smooth muscle cells, thus accelerating vascular ageing and atherosclerosis. Furthermore, inflamm-ageing promotes the development of catastrophic athero-thrombotic complications by enhancing platelet reactivity and predisposing to plaque rupture and erosion. Thus, inflamm-ageing and its contributors or molecular mediators might furnish targets for novel therapeutic strategies that could promote healthy ageing and conserve resources for health care systems worldwide. Here, we discuss recent findings in the pathophysiology of inflamm-ageing, the impact of these processes on the development of age-related CV diseases, results from clinical trials targeting its components and the potential implementation of these advances into daily clinical practice.
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Affiliation(s)
- Luca Liberale
- Center for Molecular Cardiology, University of Zürich, Wagistrasse 12, Schlieren CH-8952, Switzerland.,Department of Internal Medicine, First Clinic of Internal Medicine, University of Genoa, v.le Benedetto XV 10, 16132 Genoa, Italy
| | - Fabrizio Montecucco
- IRCCS Ospedale Policlinico San Martino Genoa - Italian Cardiovascular Network, L.go Rosanna Benzi 10, 16132 Genoa, Italy.,First Clinic of Internal Medicine, Department of Internal Medicine and Centre of Excellence for Biomedical Research (CEBR), University of Genoa, v.le Benedetto XV 10, 16132 Genoa, Italy
| | - Jean-Claude Tardif
- Montreal Heart Institute, Université de Montreal, Rue Bélanger 5000, Montreal, QC H1T 1C8, Canada
| | - Peter Libby
- Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Francis Street 75, Boston, MA 02115, USA
| | - Giovanni G Camici
- Center for Molecular Cardiology, University of Zürich, Wagistrasse 12, Schlieren CH-8952, Switzerland.,Department of Cardiology, University Heart Center, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland.,Department of Research and Education, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland
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Lichtenauer M, Jirak P, Paar V, Sipos B, Kopp K, Berezin AE. Heart Failure and Diabetes Mellitus: Biomarkers in Risk Stratification and Prognostication. APPLIED SCIENCES 2021; 11:4397. [DOI: 10.3390/app11104397] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/15/2024]
Abstract
Heart failure (HF) and type 2 diabetes mellitus (T2DM) have a synergistic effect on cardiovascular (CV) morbidity and mortality in patients with established CV disease (CVD). The aim of this review is to summarize the knowledge regarding the discriminative abilities of conventional and novel biomarkers in T2DM patients with established HF or at higher risk of developing HF. While conventional biomarkers, such as natriuretic peptides and high-sensitivity troponins demonstrate high predictive ability in HF with reduced ejection fraction (HFrEF), this is not the case for HF with preserved ejection fraction (HFpEF). HFpEF is a heterogeneous disease with a high variability of CVD and conventional risk factors including T2DM, hypertension, renal disease, older age, and female sex; therefore, the extrapolation of predictive abilities of traditional biomarkers on this population is constrained. New biomarker-based approaches are disputed to be sufficient for improving risk stratification and the prediction of poor clinical outcomes in patients with HFpEF. Novel biomarkers of biomechanical stress, fibrosis, inflammation, oxidative stress, and collagen turn-over have shown potential benefits in determining prognosis in T2DM patients with HF regardless of natriuretic peptides, but their role in point-to-care and in routine practice requires elucidation in large clinical trials.
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Dipeptidyl peptidase-IV inhibitory activity of millet protein peptides and the related mechanisms revealed by molecular docking. Lebensm Wiss Technol 2021. [DOI: 10.1016/j.lwt.2020.110587] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
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Resanović I, Zarić B, Radovanović J, Sudar-Milovanović E, Gluvić Z, Jevremović D, Isenović ER. Hyperbaric Oxygen Therapy and Vascular Complications in Diabetes Mellitus. Angiology 2020; 71:876-885. [PMID: 32638622 DOI: 10.1177/0003319720936925] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Vascular complications in patients with diabetes mellitus (DM) are common. Since impaired oxygen balance in plasma plays an important role in the pathogenesis of chronic DM-associated complications, the administration of hyperbaric oxygen therapy (HBOT) has been recommended to influence development of vascular complications. Hyperbaric oxygen therapy involves inhalation of 100% oxygen under elevated pressure from 1.6 to 2.8 absolute atmospheres in hyperbaric chambers. Hyperbaric oxygen therapy increases plasma oxygen solubility, contributing to better oxygen diffusion to distant tissues and preservation of the viability of tissues reversibly damaged by atherosclerosis-induced ischemia, along with microcirculation restoration. Hyperbaric oxygen therapy exerts antiatherogenic, antioxidant, and cardioprotective effects by altering the level and composition of plasma fatty acids and also by promoting signal transduction through membranes, which are impaired by hyperglycemia and hypoxia. In addition, HBOT affects molecules involved in the regulation of nitric oxide synthesis and in that way exerts anti-inflammatory and angiogenic effects in patients with DM. In this review, we explore the recent literature related to the effects of HBOT on DM-related vascular complications.
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Affiliation(s)
- Ivana Resanović
- Department of Radiobiology and Molecular Genetics, "VINČA" Institute of Nuclear Sciences - National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Božidarka Zarić
- Department of Radiobiology and Molecular Genetics, "VINČA" Institute of Nuclear Sciences - National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Jelena Radovanović
- Department of Radiobiology and Molecular Genetics, "VINČA" Institute of Nuclear Sciences - National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Emina Sudar-Milovanović
- Department of Radiobiology and Molecular Genetics, "VINČA" Institute of Nuclear Sciences - National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Zoran Gluvić
- Department of Endocrinology and Diabetes, Zemun Clinical Hospital, School of Medicine, University of Belgrade, Serbia
| | - Danimir Jevremović
- Faculty of Stomatology in Pancevo, University Business Academy, Novi Sad, Serbia
| | - Esma R Isenović
- Department of Radiobiology and Molecular Genetics, "VINČA" Institute of Nuclear Sciences - National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia
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Cutaș A, Drugan C, Roman G, Rusu A, Istrate D, Achimaș-Cadariu A, Drugan T. Inflammatory response and timeline of chronic complications in patients with type 1 and 2 diabetes mellitus. Int J Diabetes Dev Ctries 2020. [DOI: 10.1007/s13410-020-00824-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/24/2022] Open
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Ma T, Liu T, Xie P, Jiang S, Yi W, Dai P, Guo X. UPLC-MS-based urine nontargeted metabolic profiling identifies dysregulation of pantothenate and CoA biosynthesis pathway in diabetic kidney disease. Life Sci 2020; 258:118160. [PMID: 32730837 DOI: 10.1016/j.lfs.2020.118160] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Revised: 07/16/2020] [Accepted: 07/24/2020] [Indexed: 12/13/2022]
Abstract
AIMS Diabetic kidney disease (DKD) is a major prevalent chronic microvascular complication of type 2 diabetes (T2D). However, the present diagnostic indicators have limitations in the early diagnosis of DKD. This study concentrated on the sensitive and specific biomarkers in early diagnosis of DKD by metabolomics. MATERIALS AND METHODS In this cross-sectional study, we performed a UPLC-MS based nontargeted metabolomics assay to profile the urinary metabolites in patients with DKD. Principal Component Analysis (PCA) and orthogonal partial least square discriminant analysis (OPLS-DA) were used for screening out the metabolomic variables. KEY FINDINGS A total of 147 urinary metabolites were identified and 5 metabolic pathways were correlated with DKD pathophysiology. Pantothenate and coenzyme A biosynthesis pathway alteration was found the most prominent in DKD subjects. 4 metabolites, including dihydrouracil, ureidopropionic acid, pantothenic acid (PA), and adenosine 3',5'-diphosphate involved in pantothenate and CoA biosynthesis were significantly down-regulated. SIGNIFICANCE Our finding indicates that PA would be served as a novel predictive biomarker associated with DKD development and progression. Furthermore, our results provide a promising prospect that PA and CoA biosynthesis pathway can be potential therapeutic targets for DKD treatment.
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Affiliation(s)
- Tao Ma
- Dongfang Hospital of Beijing University of Chinese Medicine, Beijing 100078, China
| | - Tonghua Liu
- Key Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Peifeng Xie
- Dongfang Hospital of Beijing University of Chinese Medicine, Beijing 100078, China
| | - Sheng Jiang
- The First Teaching Hospital of Xinjiang Medical University, Urumuqi 830013, China
| | - Wenming Yi
- Dongfang Hospital of Beijing University of Chinese Medicine, Beijing 100078, China
| | - Pei Dai
- Dongfang Hospital of Beijing University of Chinese Medicine, Beijing 100078, China
| | - Xiangyu Guo
- Dongfang Hospital of Beijing University of Chinese Medicine, Beijing 100078, China.
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Lu Z, Luo Z, Jia A, Muhammad I, Zeng W, Shiganmo A, Chen X, Song Y. Effects of ABCA1 gene polymorphisms on risk factors, susceptibility and severity of coronary artery disease. Postgrad Med J 2020; 96:666-673. [PMID: 31911446 DOI: 10.1136/postgradmedj-2019-136917] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2019] [Revised: 11/21/2019] [Accepted: 12/16/2019] [Indexed: 11/03/2022]
Abstract
BACKGROUND The relationships between the rs1800976, rs4149313 and rs2230806 polymorphisms in ATP binding cassette protein A1 and severity of coronary artery disease (CAD) remain unclear. METHODS Four hundred and forty-two patients with CAD and 217 CAD-free subjects were enrolled in this study. The rs1800976, rs4149313 and rs2230806 polymorphisms were genotyped by PCR-RFLP. Severity of CAD was evaluated by Gensini score system, number of stenotic coronary vessels and extent of coronary stenosis. RESULTS C allele of the rs1800976 polymorphism, G allele of the rs4149313 polymorphism and A allele of the rs2230806 polymorphism were found to be risk alleles for CAD (p<0.05 for all). In patients with CAD, C allele of the rs1800976 polymorphism was associated with high levels of hypersensitive C reactive protein (hs-CRP) and cystatin c (CysC), and its frequency increased with percentiles of Gensini score, number of stenotic coronary vessels and extent of coronary stenosis (p<0.05 for all). The subjects with GA genotype of the rs4149313 polymorphism had higher levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B and hs-CRP than those with AA genotype (p<0.05 for all). The subjects with AA genotype of the rs2230806 polymorphism had higher levels of TC, LDL-C and uric acid than those with GA genotype (p<0.05 for all). No associations between the rs4149313 or rs2230806 polymorphism and severity of CAD were detected. CONCLUSIONS The rs1800976 polymorphism is significantly associated with the occurrence and severity of CAD, which is possibly mediated by hs-CRP and CysC.
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Affiliation(s)
- Zhan Lu
- Department of Cardiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Zhi Luo
- Department of Cardiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Aimei Jia
- School of Preclinical Medicine, North Sichuan Medical College, Nanchong, Sichuan, China
| | - Irfan Muhammad
- Department of Cardiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Wei Zeng
- Department of Cardiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Azhe Shiganmo
- School of Medical Imaging, North Sichuan Medical College, Nanchong, Sichuan, China
| | - Xueli Chen
- Department of Anaesthesiology, North Sichuan Medical College, Nanchong, Sichuan, China
| | - Yongyan Song
- Scool of Preclinical Medicine, and Nanchong Key Laboratory of Metabolic Drugs and Biological Products, North Sichuan Medical College, Nanchong, China
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Inflammation, Frailty and Cardiovascular Disease. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2020; 1216:55-64. [PMID: 31894547 DOI: 10.1007/978-3-030-33330-0_7] [Citation(s) in RCA: 152] [Impact Index Per Article: 30.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Chronic inflammation, which is called "inflamm-aging" , is characterized by an increased level of inflammatory cytokines in response to physiological and environmental stressors, and causes the immune system to function consistently at a low level, even though it is not effective. Possible causes of inflammaging include genetic susceptibility, visceral obesity, changes in gut microbiota and permeability, chronic infections and cellular senescence. Inflammation has a role in the development of many age-related diseases, such as frailty. Low grade chronic inflammation can also increase the risk of atherosclerosis and insulin resistance which are the leading mechanisms in the development of cardiovascular diseases (CVD). As it is well known that the risk of CVD is higher in older people with frailty and the risk of frailty is higher in patients with CVD, there may be relationship between inflammation and the development of CVD and frailty. Therefore, this important issue will be discussed in this chapter.
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Desai P, Donovan L, Janowitz E, Kim JY. The Clinical Utility of Salivary Biomarkers in the Identification of Type 2 Diabetes Risk and Metabolic Syndrome. Diabetes Metab Syndr Obes 2020; 13:3587-3599. [PMID: 33116710 PMCID: PMC7553598 DOI: 10.2147/dmso.s265879] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Accepted: 09/04/2020] [Indexed: 12/12/2022] Open
Abstract
Type 2 diabetes is traditionally diagnosed by the use of an oral glucose tolerance test and/or HbA1c, both of which require serum collection. Various biomarkers, which are measurable biological substances that provide clinical insight on disease state, have also been effective in the early identification and risk prediction of inflammatory diseases. Measuring biomarker concentrations has traditionally been obtained through serum collection as well. However, numerous biomarkers are detectable in saliva. Salivary analysis has more recently been introduced into research as a potential non-invasive, cost-effective diagnostic for the early identification of type 2 diabetes risk in adults and youth. Therefore, the purpose of this review was to compare 6 established inflammatory biomarkers of type 2 diabetes, in serum and saliva, and determine if similar diagnostic effectiveness is seen in saliva. A lack of standardized salivary analysis, processing, and collection accounts for errors and inconsistencies in conclusive data amongst studies. Proposing a national standardization in salivary analysis, coupled with increased data and research on the utility of saliva as a diagnostic, poses the potential for salivary analysis to be used in diagnostic settings.
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Affiliation(s)
- Priya Desai
- Department of Exercise Science, Syracuse University, Syracuse, NY, USA
| | - Lorin Donovan
- Department of Exercise Science, Syracuse University, Syracuse, NY, USA
| | | | - Joon Young Kim
- Department of Exercise Science, Syracuse University, Syracuse, NY, USA
- Correspondence: Joon Young KimDepartment of Exercise Science, Syracuse University, Women’s Building 204E, 820 Comstock Ave, Syracuse, NY13244, USATel +1 315-443-1411Fax +1 315-443-9375 Email
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Liu L, Gao B, Wang J, Yang C, Wu S, Wu Y, Chen S, Li Q, Zhang H, Wang G, Chen M, Zhao MH, Zhang L. Reduction in Serum High-Sensitivity C-Reactive Protein Favors Kidney Outcomes in Patients with Impaired Fasting Glucose or Diabetes. J Diabetes Res 2020; 2020:2720905. [PMID: 32587865 PMCID: PMC7303740 DOI: 10.1155/2020/2720905] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Revised: 05/22/2020] [Accepted: 05/27/2020] [Indexed: 12/15/2022] Open
Abstract
OBJECTIVE We aimed to evaluate whether the reduction in serum high-sensitivity C-reactive protein (hs-CRP) favors kidney outcomes. METHODS This study was a subanalysis including patients with impaired fasting glucose or diabetes of the Kailuan cohort study. The predictor was based on two consecutive visits of hs-CRP levels in 2006 and 2008. A total of 3924 patients with hs-CRP ≥ 3 mg/L in 2006 were divided into two groups according to whether the levels of hs-CRP were reduced in 2008: Group 1: no reduction: hs-CRP ≥ 3 mg/L in 2008; Group 2: reduction: hs-CRP < 3 mg/L in 2008. Kidney outcomes include kidney function decline and development and progression of proteinuria and were followed up until the end of 2015. RESULTS There were 3905, 2049, and 493 patients included into our analysis for the outcomes of kidney function decline and the development and progression of proteinuria, respectively. A total of 398, 297, and 47 events occurred after 5 years of follow-up, respectively. Cox regression revealed that patients with reduction in hs-CRP have lower risk of kidney function decline (HR 0.71, 95% CI 0.57-0.89, and P = 0.002) and development of proteinuria (0.77, 0.61-0.99, and P = 0.038) after controlling for potential confounders as compared to those with no reduction in hs-CRP levels. CONCLUSIONS Reduction in serum hs-CRP levels favors kidney outcomes in patients with impaired fasting glucose or diabetes.
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Affiliation(s)
- Lili Liu
- Renal Division, Department of Medicine, Peking University First Hospital, Peking University Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education, Beijing 100034, China
| | - Bixia Gao
- Renal Division, Department of Medicine, Peking University First Hospital, Peking University Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education, Beijing 100034, China
| | - Jinwei Wang
- Renal Division, Department of Medicine, Peking University First Hospital, Peking University Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education, Beijing 100034, China
| | - Chao Yang
- Renal Division, Department of Medicine, Peking University First Hospital, Peking University Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education, Beijing 100034, China
| | - Shouling Wu
- Department of Cardiology, Kailuan General Hospital, Tangshan 063001, China
| | - Yuntao Wu
- Department of Cardiology, Kailuan General Hospital, Tangshan 063001, China
| | - Shuohua Chen
- Department of Health Care Center, Kailuan General Hospital, Tangshan 063001, China
| | - Qiuyun Li
- Department of Endocrinology, Kailuan General Hospital, Tangshan 063001, China
| | - Huifen Zhang
- Department of Laboratory, Kailuan General Hospital, Tangshan 063001, China
| | - Guodong Wang
- Department of Cardiology, Kailuan General Hospital, Tangshan 063001, China
| | - Min Chen
- Renal Division, Department of Medicine, Peking University First Hospital, Peking University Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education, Beijing 100034, China
| | - Ming-hui Zhao
- Renal Division, Department of Medicine, Peking University First Hospital, Peking University Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education, Beijing 100034, China
- Peking-Tsinghua Center for Life Sciences, Beijing 100034, China
| | - Luxia Zhang
- Renal Division, Department of Medicine, Peking University First Hospital, Peking University Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education, Beijing 100034, China
- National Institute of Health Data Science at Peking University, Beijing 100191, China
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Wang YS, Ye J, Yang X, Zhang GP, Cao YH, Zhang R, Dai W, Zhang Q. Association of retinol binding protein-4, cystatin C, homocysteine and high-sensitivity C-reactive protein levels in patients with newly diagnosed type 2 diabetes mellitus. Arch Med Sci 2019; 15:1203-1216. [PMID: 31572465 PMCID: PMC6764307 DOI: 10.5114/aoms.2018.79565] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2018] [Accepted: 09/30/2018] [Indexed: 01/17/2023] Open
Abstract
INTRODUCTION To investigate the serum retinol binding protein (RBP)-4, cystatin C (Cys C), homocysteine (HCY) and high-sensitivity C-reactive protein (hs-CRP) levels in newly diagnosed type 2 diabetes mellitus (NT2DM) patients, prediabetes mellitus (PDM) subjects and normal controls, as well as their correlation with clinical and laboratory indexes, such as blood pressure and lipoprotein. MATERIAL AND METHODS A total of 242 subjects, including 141 NT2DM patients, 48 PDM subjects and 53 healthy controls, were recruited in the present study. Serum RBP-4, Cys C and hs-CRP concentrations were measured by enzyme-linked immunosorbent assay (ELISA). HCY concentration was determined by the chemical luminescence method. RESULTS There were significant differences in Cys C and hs-CRP among NT2DM patients, PDM subjects and normal controls. In comparison to controls, there were significantly elevated Cys C and hs-CRP levels in PDM (both p < 0.001), and a significantly increased Cys C level in NT2DM (p < 0.001); however, there were no significant differences in Cys C and hs-CRP levels between NT2DM and PDM, and no significant differences of hs-CRP levels between NT2DM and normal controls. No significant differences of RBP-4 and HCY levels among NT2DM, PDM and normal control groups were observed. CONCLUSIONS Aberrant Cys C expression and its clinical associations in NT2DM suggest their important role in this disease.
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Affiliation(s)
- Yun-Sheng Wang
- Department of Endocrinology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
- Department of Endocrinology, the Second Hospital of Hefei City, Hefei, Anhui, China
| | - Jun Ye
- Department of Endocrinology, the Second Hospital of Hefei City, Hefei, Anhui, China
| | - Xiao Yang
- Department of Ultrasonography, the Second Hospital of Hefei City, Hefei, Anhui, China
| | - Gui-Ping Zhang
- Department of Ultrasonography, the Second Hospital of Hefei City, Hefei, Anhui, China
| | - Yong-Hong Cao
- Department of Endocrinology, the Second Hospital of Hefei City, Hefei, Anhui, China
| | - Rong Zhang
- Department of Endocrinology, the Second Hospital of Hefei City, Hefei, Anhui, China
| | - Wu Dai
- Department of Endocrinology, the Second Hospital of Hefei City, Hefei, Anhui, China
| | - Qiu Zhang
- Department of Endocrinology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
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Suyoto PST, Aulia B. Low muscle mass and inflammation among patients with type 2 diabetes mellitus in Indonesia. Diabetol Int 2019; 10:219-224. [PMID: 31275789 PMCID: PMC6592986 DOI: 10.1007/s13340-018-0384-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2018] [Accepted: 11/11/2018] [Indexed: 12/12/2022]
Abstract
INTRODUCTION Chronic inflammation, as observed in type 2 diabetes mellitus (T2DM), is associated with complications. How chronic inflammation influences body composition in patients with T2DM remains to be investigated. Our study aimed to evaluate the difference of skeletal muscle mass between patients with and without inflammation indicated by plasma high sensitivity C-reactive protein (hs-CRP). METHODS Patients with T2DM were recruited from primary health care in Sleman district, Indonesia. Measurements were performed to obtain information on body weight, body mass index, waist circumference, waist-to-height ratio, total body fat, subcutaneous fat, visceral fat, mid-upper arm circumference, and muscle mass. Spearman's rank correlation was performed to test the correlation between hs-CRP level and several components of body composition. To test the difference of percent skeletal muscle mass between subjects with and without inflammation (hs-CRP ≥ 3 or < 3 mg/dL), general linear model was utilized with adjustment for several variables. Analysis with p value of less than 0.05 is considered statistically significant. RESULT In all subjects, hs-CRP is correlated with skeletal muscle mass (r: - 0.343; p = 0.04), total body fat (r: 0.353; p = 0.04), and subcutaneous fat (r: 0.369; p = 0.02) but not visceral fat (p: - 0.065; p = ns). Significant difference of skeletal muscle mass between subjects with and without inflammation was found in all and female subjects after adjustment for covariates. CONCLUSION There was a negative correlation between skeletal muscle mass percentage and inflammation indicated by hs-CRP in type 2 diabetes patients.
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Affiliation(s)
- Perdana Samekto Tyasnugroho Suyoto
- Department of Nutrition and Health, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia
- Faculty of Medicine, Center for Health and Human Nutrition, Universitas Gadjah Mada, Yogyakarta, Indonesia
| | - Bianda Aulia
- Faculty of Medicine, Center for Health and Human Nutrition, Universitas Gadjah Mada, Yogyakarta, Indonesia
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Jonas JB, Wei WB, Xu L, Wang YX. Systemic inflammation and eye diseases. The Beijing Eye Study. PLoS One 2018; 13:e0204263. [PMID: 30281641 PMCID: PMC6169913 DOI: 10.1371/journal.pone.0204263] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2018] [Accepted: 08/14/2018] [Indexed: 02/07/2023] Open
Abstract
Purpose Systemic inflammation is potentially associated with ocular diseases such as late age-related macular degeneration (AMD). Using the serum concentration of high-sensitive C-reactive protein (hs-CRP) as surrogate of systemic inflammation, we examined potential associations between the serum hs-CRP concentration and the presence and degree of eye diseases. Methods The population-based Beijing Eye Study included 3468 Chinese individuals. The study participants underwent a standardized interview and a detailed ophthalmic examination. The serum concentration of hs-CRP was determined. Results Out of 3468 participants, 2452 (70.7%) individuals (mean age:63.4±9.4 year; range:50–91 years) had hs-CRP measurements (mean:1.96±4.07mg/L). In multivariate analysis, higher serum concentration of hs-CRP was significantly (regression coefficient r: 0.21) associated with a higher level of diabetic retinopathy (P = 0.007; standardized regression coefficient beta:0.06; non-standardized regression coefficient B:1.35; 95% confidence interval (CI):0.37,2.22) and polypoidal choroidal vasculopathy (P = 0.002;beta:0.06;B:6.22;95%CI:2.24,10.2) after adjusting for higher serum concentration of high-density lipoproteins (P<0.001;beta:-0.12;B:-1.31;95%CI:-1.77,-0.85), higher body mass index (P = 0.01;beta:0.06;B:0.06;95%CI:0.01, 0.11), lower level of education (P = 0.04;beta:-0.06;B:-0.22;95%CI:-0.42,-0.02), lower cognitive function score (P = 0.01;beta:-0.07;B:-0.08;95%CI:-0.13,-0.02). If the presences of other ocular diseases were added to the model, the presence of glaucoma (P = 0.99), open-angle glaucoma (P = 0.80), angle-closure glaucoma (P = 0.67), pseudoexfoliation (P = 0.18), nuclear cataract (P = 0.30), cortical cataract (P = 0.15), subcapsular cataract (P = 0.59), retinal vein occlusions (P = 0.33), central serous choroidopathy (P = 0.44), early stage of age-related macular degeneration (AMD) (P = 0.46), intermediate stage of AMD (P = 0.20) and late stage of AMD (P = 0.91) including geographic atrophy (P = 0.60) or neovascular AMD (P = 0.68) were not significantly associated with the serum concentration of hs-CRP. Conclusions In Chinese aged 50+ years, higher serum concentration of hs-CRP was significantly associated with a higher level of diabetic retinopathy and higher frequency of polypoidal choroidal vasculopathy. Other major ocular disorders, namely glaucoma including open-angle glaucoma and angle-closure glaucoma, pseudoexfoliation, nuclear, cortical or subcapsular cataract, retinal vein occlusions, central serous choroidopathy, early, intermediate or late stage of AMD including geographic atrophy, were not significantly associated with hs-CRP serum concentrations. It suggests that these diseases, in contrast to diabetic retinopathy and polypoidal choroidal vasculopathy, were not associated with a major systemic inflammatory component.
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Affiliation(s)
- Jost B. Jonas
- Beijing Institute of Ophthalmology, Beijing Key Laboratory of Ophthalmology and Visual Sciences, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University; Beijing, China
- Department of Ophthalmology, Medical Faculty Mannheim of the Ruprecht-Karls-University, Mannheim, Germany
| | - Wen Bin Wei
- Beijing Tongren Eye Center, Beijing key Laboratory of Intraocular Tumor Diagnosis and Treatment, Beijing Tongren Hospital, Capital Medical University, Beijing, China
- * E-mail: (YXW); (WBW)
| | - Liang Xu
- Beijing Institute of Ophthalmology, Beijing Key Laboratory of Ophthalmology and Visual Sciences, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University; Beijing, China
| | - Ya Xing Wang
- Beijing Institute of Ophthalmology, Beijing Key Laboratory of Ophthalmology and Visual Sciences, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University; Beijing, China
- * E-mail: (YXW); (WBW)
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Abstract
Most older individuals develop inflammageing, a condition characterized by elevated levels of blood inflammatory markers that carries high susceptibility to chronic morbidity, disability, frailty, and premature death. Potential mechanisms of inflammageing include genetic susceptibility, central obesity, increased gut permeability, changes to microbiota composition, cellular senescence, NLRP3 inflammasome activation, oxidative stress caused by dysfunctional mitochondria, immune cell dysregulation, and chronic infections. Inflammageing is a risk factor for cardiovascular diseases (CVDs), and clinical trials suggest that this association is causal. Inflammageing is also a risk factor for chronic kidney disease, diabetes mellitus, cancer, depression, dementia, and sarcopenia, but whether modulating inflammation beneficially affects the clinical course of non-CVD health problems is controversial. This uncertainty is an important issue to address because older patients with CVD are often affected by multimorbidity and frailty - which affect clinical manifestations, prognosis, and response to treatment - and are associated with inflammation by mechanisms similar to those in CVD. The hypothesis that inflammation affects CVD, multimorbidity, and frailty by inhibiting growth factors, increasing catabolism, and interfering with homeostatic signalling is supported by mechanistic studies but requires confirmation in humans. Whether early modulation of inflammageing prevents or delays the onset of cardiovascular frailty should be tested in clinical trials.
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Affiliation(s)
- Luigi Ferrucci
- Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD, USA.
| | - Elisa Fabbri
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
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