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Yan Q, Liu G, Wang R, Li D, Wang D. Fibrinogen/albumin ratio is associated with first-ever cardiovascular events in patients with peritoneal dialysis. Ann Med 2025; 57:2499025. [PMID: 40304666 PMCID: PMC12044904 DOI: 10.1080/07853890.2025.2499025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Revised: 11/02/2023] [Accepted: 02/11/2025] [Indexed: 05/02/2025] Open
Abstract
OBJECTIVE The fibrinogen/albumin ratio (FAR) is a novel inflammatory indicator, which has been associated with cardiovascular disease. However, the relationship between FAR and cardiovascular event (CVE) in patients with peritoneal dialysis (PD) remains unclear. This study aims to clarify the relationship between FAR and first-ever CVE in patients with PD. METHODS A total of 278 patients were enrolled between January 2012 and June 2021. They were defined as the high FAR group and the low FAR group based on the median FAR value (0.107). The primary outcome was the occurrence of first-ever CVE. Kaplan-Meier's curves and Cox regression analysis were used to analyse the relationship between FAR and first-ever CVE in patients with PD. Forest plots were employed to depict the relationship between FAR and first-ever CVE in each subgroup. RESULTS The average follow-up period was 40.26 ± 28.27 months. A total of 101 (36.3%) patients developed first-ever CVE. Kaplan-Meier's analysis showed that there was a higher risk of first-ever CVE (p = .002) in the high FAR group. Multivariate Cox regression analysis showed that FAR ≥ 0.107 and age were independently associated with the risk of first-ever CVE in patients with PD. Receiver operating characteristic (ROC) analysis showed that FAR had a greater predicting value on the first-ever CVE. CONCLUSIONS High levels of FAR are independently associated with an increased risk of first-ever CVE in patients with PD.
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Affiliation(s)
- Qiqi Yan
- Department of Nephrology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China
- Institute of Kidney Disease, Inflammation & Immunity Mediated Diseases, The Second Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Guiling Liu
- Department of Nephrology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China
- Institute of Kidney Disease, Inflammation & Immunity Mediated Diseases, The Second Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Ruifeng Wang
- Department of Nephrology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China
- Institute of Kidney Disease, Inflammation & Immunity Mediated Diseases, The Second Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Dandan Li
- Department of Nephrology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China
- Institute of Kidney Disease, Inflammation & Immunity Mediated Diseases, The Second Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Deguang Wang
- Department of Nephrology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China
- Institute of Kidney Disease, Inflammation & Immunity Mediated Diseases, The Second Affiliated Hospital of Anhui Medical University, Hefei, China
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Hu X, Wang J, Ye Y, Chen X, Abulikemu S, Yu J, Zhao Y, Hu T, Peng Y. Associations between fibrinogen levels and the risk of all-cause mortality: a long-term cohort study. J Thromb Thrombolysis 2025; 58:514-525. [PMID: 40266502 DOI: 10.1007/s11239-025-03087-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/15/2025] [Indexed: 04/24/2025]
Abstract
Although prior research has investigated the link between fibrinogen and mortality risk, there is a notable lack of long-term cohort studies. This study seeks to examine the relationship between plasma fibrinogen levels and all-cause mortality. Fibrinogen levels were divided into low and high groups based on the median and further categorized into quartiles. Kaplan-Meier analysis was employed for survival analysis, and hazard ratios (HRs) were calculated using the Cox proportional hazards model. Our study included 5,690 participants, divided into a lower fibrinogen group (fibrinogen ≤ 370 mg/dL, N = 2,851) and a higher fibrinogen group (fibrinogen > 370 mg/dL, N = 2,839). The survival probability of the lower fibrinogen group was higher than that of the higher group (70.98% vs. 47.98%, P < 0.0001). All-cause mortality was higher in the higher fibrinogen group compared to the low fibrinogen group (HR 1.26, 95% CI 1.09-1.45, P = 0.002). Compared to Q1, mortality risk increased in Q2 (HR 1.26, 95% CI 1.00-1.59, P = 0.05), Q3 (HR 1.39, 95% CI 1.15-1.69, P < 0.001), and Q4 (HR 1.51, 95% CI 1.23-1.87, P < 0.001). Higher fibrinogen levels correlate with an elevated risk of all-cause mortality, suggesting fibrinogen is a potential biomarker for mortality risk.
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Affiliation(s)
- Xinru Hu
- Department of Cardiology, West China Hospital, Sichuan University, 37 Guoxue Street, Chengdu, 610041, China
| | - Junwen Wang
- Department of Cardiology, West China Hospital, Sichuan University, 37 Guoxue Street, Chengdu, 610041, China
| | - Yuyang Ye
- Department of Cardiology, West China Hospital, Sichuan University, 37 Guoxue Street, Chengdu, 610041, China
| | - Xuefeng Chen
- Department of Cardiology, West China Hospital, Sichuan University, 37 Guoxue Street, Chengdu, 610041, China
| | - Simayi Abulikemu
- Department of Cardiology, West China Hospital, Sichuan University, 37 Guoxue Street, Chengdu, 610041, China
| | - Jiang Yu
- Department of Cardiology, West China Hospital, Sichuan University, 37 Guoxue Street, Chengdu, 610041, China
| | - Yifei Zhao
- Department of Cardiology, West China Hospital, Sichuan University, 37 Guoxue Street, Chengdu, 610041, China
| | - Teng Hu
- Department of Cardiology, West China Hospital, Sichuan University, 37 Guoxue Street, Chengdu, 610041, China
| | - Yong Peng
- Department of Cardiology, West China Hospital, Sichuan University, 37 Guoxue Street, Chengdu, 610041, China.
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Toaima DN, Abdel-Maksoud KS, Atef HM, Salah NY. Magnesium, fibrinolysis and clotting interplay among children and adolescents with type 1 diabetes mellitus; potential mediators of diabetic microangiopathy. Nutr Diabetes 2025; 15:13. [PMID: 40169565 PMCID: PMC11961714 DOI: 10.1038/s41387-025-00368-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Revised: 01/14/2025] [Accepted: 02/20/2025] [Indexed: 04/03/2025] Open
Abstract
BACKGROUND AND AIM Hypomagnesemia and clotting disorders have been reported among people with diabetes especially those with type 2 diabetes (T2DM). Magnesium plays a crucial role in hemostasis and hypomagnesemia was found to increase the thrombotic risk. The patho-mechanism linking magnesium, clotting disorders, and diabetic microangiopathy in T1DM remains to be unraveled. Hence this study aimed to assess the magnesium level among children and adolescents with T1DM compared to healthy controls and to correlate it with coagulopathy markers and diabetic microangiopathy. METHODS Forty-six children and adolescents with T1DM & 46 controls were assessed for serum magnesium, prothrombin time (PT), activated-partial thromboplastin time (aPTT), plasminogen activator inhibitor-1 (PAI-1) and HbA1c. The Toronto clinical scoring system, fundus, urinary microalbumin, and serum fasting lipids were used to assess diabetic microangiopathy. RESULTS Children and adolescents with T1DM have significantly lower magnesium, PT, aPTT, and significantly higher PAI-1 than controls (p<0.001), this is more evident in those having microangiopathy than those without (p<0.001). Serum magnesium is positively correlated with PT, aPTT, and HDL and negatively correlated with insulin daily dose, PAI-1, HbA1c, triglycerides, and urinary microalbumin. Multivariate-logistic regression revealed that diabetes duration, HbA1c, PT, aPTT, PAI-1, and urinary microalbumin were independently associated with serum magnesium among children and adolescents with T1DM (p<0.05). CONCLUSION Children and adolescents with T1DM have lower magnesium levels than controls; that is more pronounced among those having microangiopathy. Low serum magnesium is associated with poor glycemic control, coagulopathy, and diabetic microangiopathy among children and adolescents with T1DM. Magnesium supplementation combined with standard insulin therapy in pediatric patients with T1DM is recommended for better glycemic control and prevention of diabetic microangiopathy.
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Affiliation(s)
- Dalia N Toaima
- Department of Pediatrics, Faculty of Medicine, Ain shams University, Cairo, Egypt
| | | | - Heba M Atef
- Department of Clinical Pathology, Faculty of Medicine, Ain shams University, Cairo, Egypt
| | - Nouran Y Salah
- Department of Pediatrics, Faculty of Medicine, Ain shams University, Cairo, Egypt.
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Wang X, Guo R, Huang M, Li Z, Lai Z, Yang R, Li L, Gao S, Yu C. Fibrinogen-to-Albumin Ratio and Glucose Metabolic States in Patients With Coronary Heart Disease. Angiology 2025; 76:271-280. [PMID: 37939004 DOI: 10.1177/00033197231206235] [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] [Indexed: 11/10/2023]
Abstract
This study investigated the relationship between fibrinogen-to-albumin ratio (FAR) and glucose metabolic state in patients with coronary heart disease (CHD). A total of 52,062 patients were enrolled in this study. Patients were classified according to FAR tertiles (T1: FAR < 0.0073; T2: 0.0073 ≤ FAR ≤ 0.0886; T3: FAR ≥ 0.0887). Patients were also classified into the normal glucose regulation (NGR) and elevated blood glucose (EBG) groups. The relationship between FAR and EBG was analyzed using logistic regression, and the association was evaluated according to sex and age. Among the participants, 32,471 (62.4%) had EBG, which was positively associated with FAR (odds ratio [OR], 1.19; 95% confidence interval [CI] 1.15-1.23). The OR of the FAR for EBG in males was higher than that in females (1.25; 95% CI 1.18-1.33 vs 1.15; 95% CI 1.10-1.20). Moreover, the OR of FAR for EBG was greater in patients aged 60 or younger (OR: 1.25; 95% CI 1.18-1.33) than in the elderly patients (over 60 years of age) (OR: 1.15; 95% CI 1.10-1.20). The results indicated a significant relationship between FAR and EBG and this association was higher in males and middle-aged patients.
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Affiliation(s)
- Xu Wang
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Ruiying Guo
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Mengnan Huang
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Zhu Li
- Zhejiang Chinese Medical University, Zhejiang, China
| | - Ziqin Lai
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Rongrong Yang
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Lin Li
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Shan Gao
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Chunquan Yu
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
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Le TN, Bright R, Truong V, Li J, Juneja R, Vasilev K. Key biomarkers in type 2 diabetes patients: A systematic review. Diabetes Obes Metab 2025; 27:7-22. [PMID: 39355932 PMCID: PMC11618249 DOI: 10.1111/dom.15991] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Revised: 09/10/2024] [Accepted: 09/19/2024] [Indexed: 10/03/2024]
Abstract
Type 2 diabetes mellitus (T2DM) is not just a local health issue but a significant global health burden, affecting patient outcomes and clinical management worldwide. Despite the wealth of studies reporting T2DM biomarkers, there is an urgent need for a comparative review. This review aims to provide a comprehensive analysis based on the reported T2DM biomarkers and how these are linked with other conditions, such as inflammation and wound healing. A comparative review was conducted on 24 001 study participants, including 10 024 T2DM patients and 13 977 controls (CTL; age 30-90 years). Four main profiles were extracted and analysed from the clinical reports over the past 11 years: haematological (1084 cases vs. 1458 CTL), protein (6753 cases vs. 9613 CTL), cytokine (975 cases vs. 1350 CTL) and lipid (1212 cases vs. 1556 CTL). This review provides a detailed analysis of the haematological profile in T2DM patients, highlighting fundamental changes such as increased white blood cells and platelet counts, accompanied by decreases in red blood cell counts and iron absorption. In the serum protein profile, a reduction in albumin and anti-inflammatory cytokines was noted along with an increase in globulin levels and pro-inflammatory cytokines. Furthermore, changes in lipid profiles were discussed, specifically the decreases in high-density lipoprotein (HDL) and the increases in low-density lipoprotein (LDL) and triglycerides. Understanding the changes in these four biomarker profiles is essential for developing innovative strategies to create diagnostic and prognostic tools for diabetes management.
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Affiliation(s)
- Thien Ngoc Le
- College of Medicine and Public HealthFlinders UniversityAdelaideSouth AustraliaAustralia
| | - Richard Bright
- College of Medicine and Public HealthFlinders UniversityAdelaideSouth AustraliaAustralia
| | - Vi‐Khanh Truong
- College of Medicine and Public HealthFlinders UniversityAdelaideSouth AustraliaAustralia
| | - Jordan Li
- College of Medicine and Public HealthFlinders UniversityAdelaideSouth AustraliaAustralia
- Department of Renal Medicine, Flinders Medical CentreBedford ParkSouth AustraliaAustralia
| | - Rajiv Juneja
- College of Medicine and Public HealthFlinders UniversityAdelaideSouth AustraliaAustralia
- Department of Renal Medicine, Flinders Medical CentreBedford ParkSouth AustraliaAustralia
| | - Krasimir Vasilev
- College of Medicine and Public HealthFlinders UniversityAdelaideSouth AustraliaAustralia
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Xie E, Wu Y, Ye Z, Gao Y, Zheng J. High Fibrinogen Levels with Diabetes Mellitus are Associated with All-Cause and Cardiovascular Mortality in Patients with End-Stage Renal Disease and Acute Coronary Syndrome. J Inflamm Res 2024; 17:7409-7422. [PMID: 39440271 PMCID: PMC11493824 DOI: 10.2147/jir.s483001] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2024] [Accepted: 10/10/2024] [Indexed: 10/25/2024] Open
Abstract
Objective As a biomarker of inflammation and a core component in the coagulation pathway, fibrinogen contributes to atherosclerosis and subsequent adverse cardiovascular events and is modified by the occurrence of diabetes mellitus. However, the association between fibrinogen, diabetes status, and mortality in patients with end-stage renal disease (ESRD) and acute coronary syndrome (ACS) remains scarce. Methods A multi-center cohort study enrolled 1079 patients with ESRD and ACS between January 2015 and June 2021. Patients were classified into three groups based on fibrinogen tertiles and were further categorized by diabetes status. The primary outcome was all-cause mortality, while the secondary outcome was cardiovascular mortality. Results During a median 21.5 months of follow-up, 386 cases of all-cause mortality were recorded, including 262 cases of cardiovascular mortality. Multivariable Cox regression model revealed that patients with the third tertile of fibrinogen and those with diabetes experienced a significantly increased risk of all-cause mortality (fibrinogen: hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.32-2.19; diabetes: HR, 1.36; 95% CI, 1.10-1.68). When patients were stratified by both fibrinogen levels and diabetes status, patients in the third fibrinogen tertile with diabetes had the highest risk of all-cause mortality (HR 2.43, 95% CI 1.69-3.48) compared to those in the first fibrinogen tertile without diabetes. Similar associations were observed for cardiovascular mortality. Notably, incorporating the combined fibrinogen and diabetes status into the Global Registry of Acute Coronary Events (GRACE) score or baseline risk model led to significant improvements in the C-statistics for predicting mortality, surpassing the advancements achieved with any single biomarker. Conclusion In patients with ESRD and ACS, elevated fibrinogen and diabetes were associated with an increased risk of all-cause and cardiovascular mortality. Categorizing patients based on fibrinogen levels and diabetes status could provide valuable information for risk stratification of these patients.
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Affiliation(s)
- Enmin Xie
- Department of Cardiology, China-Japan Friendship Hospital, Beijing, People’s Republic of China
- China-Japan Friendship Hospital (Institute of Clinical Medical Sciences), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China
| | - Yaxin Wu
- Department of Cardiology, Henan Provincial People’s Hospital, Fuwai Central China Cardiovascular Hospital, Zhengzhou, People’s Republic of China
| | - Zixiang Ye
- Department of Cardiology, China-Japan Friendship Hospital, Beijing, People’s Republic of China
- Department of Cardiology, Peking University China-Japan Friendship School of Clinical Medicine, Beijing, People’s Republic of China
| | - Yanxiang Gao
- Department of Cardiology, China-Japan Friendship Hospital, Beijing, People’s Republic of China
| | - Jingang Zheng
- Department of Cardiology, China-Japan Friendship Hospital, Beijing, People’s Republic of China
- China-Japan Friendship Hospital (Institute of Clinical Medical Sciences), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China
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Atia YA, Mohammed ST, Abdullah SS, Abbas AS, Fawzi HA. Effects of subclinical hypothyroidism in type II diabetes mellitus patients on biochemical, coagulation, and fibrinolysis status. J Adv Pharm Technol Res 2024; 15:130-134. [PMID: 38903550 PMCID: PMC11186545 DOI: 10.4103/japtr.japtr_89_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Revised: 04/01/2024] [Accepted: 04/05/2024] [Indexed: 06/22/2024] Open
Abstract
The aim of the currnet study to examine the effect of subclinical hypothyroidism (SCH) in diabetic patients on coagulation parameters. This retrospective case-control study involves 130 patients diagnosed with type 2 diabetes mellitus (T2DM), divided into 65 T2DM with newly diagnosed SCH and 65 euthyroid (EUT) T2DM patients without SCH. Fibrinogen (FIB) was significantly higher in SCH (508.2 ± 63.0 mg/dL) than EUT (428.1 ± 44.8 mg/dL). In the SCH patients, FIB correlated with several parameters, such as age (β = 0.396), body mass index (β = 0.578), glycated hemoglobin (β = 0.281), and activated partial thromboplastin time (β = 0.276). In conclusion SCH in DM patients appears to increase the magnitude of coagulopathy.
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Affiliation(s)
- Yasir Abbas Atia
- Department of Biochemistry, University of Baghdad Al-Kindy College of Medicine, Baghdad, Iraq
| | - Suhad Taha Mohammed
- Department of Biochemistry, University of Baghdad Al-Kindy College of Medicine, Baghdad, Iraq
| | | | - Ahmed Saad Abbas
- Department of Medicine, Al-Kindi Teaching Hospital, Baghdad, Iraq
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Dou ZY, Xia B, Wang CY, Xu YJ, Zhang YZ. Influence of diabetes mellitus on the biochemical parameters and outcomes of multiple myeloma. Hematology 2023; 28:2179218. [PMID: 36799658 DOI: 10.1080/16078454.2023.2179218] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/18/2023] Open
Abstract
OBJECTIVE The incidence of MM in most registries remains stable or showing only a slightly increase. However, prevalence of MM is increasing due to the increase in overall survival in the last two decades. The aim of this study was to observe changes in biochemical parameters during the diagnosis and treatment of MM. METHODS A retrospective analysis was made of the biochemical indicators, survival time, and related adverse events of 196 patients with MM. RESULTS Of the 196 patients with MM, 26 were diagnosed with DM (DM-MM group) at the first diagnosis, 31 with steroid-induced diabetes mellitus (SID-MM group) during treatment, and 139 without DM (MM group). There was no significant difference between the three groups in the mean age of onset, sex ratio, incidence of hypercalcemia, renal dysfunction, anemia, abnormal lactate dehydrogenase, and median value of D-dimer and fibrinogen during diagnosis and treatment. There was no significant difference in survival time between the SID-MM and MM groups, but there was a significant difference between the DM-MM and MM groups. CONCLUSION There was no significant difference between the three groups in the incidence of hypercalcemia, anemia, and renal function impairment. The survival time of patients with DM was shorter than that of patients without DM.
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Affiliation(s)
- Zheng-Yue Dou
- Department of Medical Oncology, Affiliated Hospital of Hebei University, Baoding, People's Republic of China
| | - Bing Xia
- Department of Hematology, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin, People's Republic of China
| | - Chao-Yu Wang
- Department of Hematology, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin, People's Republic of China
| | - Yan-Jie Xu
- Department of Hematology, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin, People's Republic of China
| | - Yi-Zhuo Zhang
- Department of Hematology, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin, People's Republic of China
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9
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Su H, Cao Y, Chen Q, Ye T, Cui C, Chen X, Yang S, Qi L, Long Y, Xiong S, Cai L. The association between fibrinogen levels and severity of coronary artery disease and long-term prognosis following percutaneous coronary intervention in patients with type 2 diabetes mellitus. Front Endocrinol (Lausanne) 2023; 14:1287855. [PMID: 38093962 PMCID: PMC10716187 DOI: 10.3389/fendo.2023.1287855] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2023] [Accepted: 11/07/2023] [Indexed: 12/18/2023] Open
Abstract
Background Fibrinogen is a potential risk factor for the prognosis of CAD and is associated with the complexity of CAD. There is limited research specifically investigating the predictive role of fibrinogen in determining the severity of CAD among patients with T2DM, as well as its impact on the prognosis following PCI. Methods The study included 675 T2DM patients who underwent PCI at the Third People's Hospital of Chengdu between April 27, 2018, and February 5, 2021, with 540 of them remaining after exclusions. The complexity of CAD was assessed using the SYNTAX score. The primary endpoint of the study was the incidence of MACCEs. Results After adjusting for multiple confounding factors, fibrinogen remained a significant independent risk factor for mid/high SYNTAX scores (SYNTAX score > 22, OR 1.184, 95% CI 1.022-1.373, P = 0.025). Additionally, a dose-response relationship between fibrinogen and the risk of complicated CAD was observed (SYNTAX score > 22; nonlinear P = 0.0043). The area under the receiver operating characteristic curve(AUROC) of fibrinogen for predicting mid/high SYNTAX score was 0.610 (95% CI 0.567-0.651, P = 0.0002). The high fibrinogen group (fibrinogen > 3.79 g/L) had a higher incidence of calcified lesions and an elevated trend of more multivessel disease and chronic total occlusion. A total of 116 patients (21.5%) experienced MACCEs during the median follow-up time of 18.5 months. After adjustment, multivariate Cox regression analysis confirmed that fibrinogen (HR, 1.138; 95% CI 1.010-1.284, P = 0.034) remained a significant independent risk factor for MACCEs. The AUROC of fibrinogen for predicting MACCEs was 0.609 (95% CI 0.566-0.650, P = 0.0002). Individuals with high fibrinogen levels (fibrinogen > 4.28 g/L) had a higher incidence of acute myocardial infarction (P < 0.001), MACCEs (P < 0.001), all-cause death (P < 0.001), stroke (P = 0.030), and cardiac death (P = 0.002). Kaplan-Meier analysis revealed a higher incidence of MACCEs in the high fibrinogen group (Log-Rank test: P < 0.001). Conclusions Elevated fibrinogen levels were associated with increased coronary anatomical complexity (as quantified by the SYNTAX score) and a higher incidence of MACCEs after PCI in patients with T2DM.
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Affiliation(s)
- Hong Su
- Department of Cardiology, The Southwest Medical University, Luzhou, Sichuan, China
| | - Yi Cao
- Department of Cardiology, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, Chengdu Cardiovascular Disease Research Institute, Chengdu, Sichuan, China
| | - Qiang Chen
- Department of Cardiology, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, Chengdu Cardiovascular Disease Research Institute, Chengdu, Sichuan, China
| | - Tao Ye
- Department of Cardiology, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, Chengdu Cardiovascular Disease Research Institute, Chengdu, Sichuan, China
| | - Caiyan Cui
- Department of Cardiology, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, Chengdu Cardiovascular Disease Research Institute, Chengdu, Sichuan, China
| | - Xu Chen
- Department of Cardiology, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, Chengdu Cardiovascular Disease Research Institute, Chengdu, Sichuan, China
| | - Siqi Yang
- Department of Cardiology, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, Chengdu Cardiovascular Disease Research Institute, Chengdu, Sichuan, China
| | - Lingyao Qi
- Department of Cardiology, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, Chengdu Cardiovascular Disease Research Institute, Chengdu, Sichuan, China
| | - Yu Long
- Department of Cardiology, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, Chengdu Cardiovascular Disease Research Institute, Chengdu, Sichuan, China
| | - Shiqiang Xiong
- Department of Cardiology, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, Chengdu Cardiovascular Disease Research Institute, Chengdu, Sichuan, China
| | - Lin Cai
- Department of Cardiology, The Southwest Medical University, Luzhou, Sichuan, China
- Department of Cardiology, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, Chengdu Cardiovascular Disease Research Institute, Chengdu, Sichuan, China
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10
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Dludla PV, Mabhida SE, Ziqubu K, Nkambule BB, Mazibuko-Mbeje SE, Hanser S, Basson AK, Pheiffer C, Kengne AP. Pancreatic β-cell dysfunction in type 2 diabetes: Implications of inflammation and oxidative stress. World J Diabetes 2023; 14:130-146. [PMID: 37035220 PMCID: PMC10075035 DOI: 10.4239/wjd.v14.i3.130] [Citation(s) in RCA: 86] [Impact Index Per Article: 43.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Revised: 11/26/2022] [Accepted: 02/28/2023] [Indexed: 03/15/2023] Open
Abstract
Insulin resistance and pancreatic β-cell dysfunction are major pathological mechanisms implicated in the development and progression of type 2 diabetes (T2D). Beyond the detrimental effects of insulin resistance, inflammation and oxidative stress have emerged as critical features of T2D that define β-cell dysfunction. Predominant markers of inflammation such as C-reactive protein, tumor necrosis factor alpha, and interleukin-1β are consistently associated with β-cell failure in preclinical models and in people with T2D. Similarly, important markers of oxidative stress, such as increased reactive oxygen species and depleted intracellular antioxidants, are consistent with pancreatic β-cell damage in conditions of T2D. Such effects illustrate a pathological relationship between an abnormal inflammatory response and generation of oxidative stress during the progression of T2D. The current review explores preclinical and clinical research on the patho-logical implications of inflammation and oxidative stress during the development of β-cell dysfunction in T2D. Moreover, important molecular mechanisms and relevant biomarkers involved in this process are discussed to divulge a pathological link between inflammation and oxidative stress during β-cell failure in T2D. Underpinning the clinical relevance of the review, a systematic analysis of evidence from randomized controlled trials is covered, on the potential therapeutic effects of some commonly used antidiabetic agents in modulating inflammatory makers to improve β-cell function.
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Affiliation(s)
- Phiwayinkosi V Dludla
- Biomedical Research and Innovation Platform, South African Medical Research Council, Cape Town 7505, South Africa
- Department of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa 3880, South Africa
| | - Sihle E Mabhida
- Biomedical Research and Innovation Platform, South African Medical Research Council, Cape Town 7505, South Africa
| | - Khanyisani Ziqubu
- Department of Biochemistry, North-West University, Mmabatho 2745, South Africa
| | - Bongani B Nkambule
- School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban 4000, South Africa
| | | | - Sidney Hanser
- Department of Physiology and Environmental Health, University of Limpopo, Sovenga 0727, South Africa
| | - Albert Kotze Basson
- Department of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa 3880, South Africa
| | - Carmen Pheiffer
- Biomedical Research and Innovation Platform, South African Medical Research Council, Cape Town 7505, South Africa
| | - Andre Pascal Kengne
- Department of Medicine, University of Cape Town, Cape Town 7500, South Africa
- Non-Communicable Diseases Research Unit, South African Medical Research Council, Tygerberg 7505, South Africa
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11
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Huang R, Dai Q, Chang L, Wang Z, Chen J, Gu R, Zheng H, Hu L, Xu B, Wang L. The association between fibrinogen-to-albumin ratio (FAR) and adverse prognosis in patients with acute decompensated heart failure at different glucose metabolic states. Cardiovasc Diabetol 2022; 21:241. [PMID: 36371183 PMCID: PMC9655790 DOI: 10.1186/s12933-022-01662-x] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Accepted: 10/06/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Circulating fibrinogen-to-albumin ratio (FAR) has been proposed as a novel inflammatory biomarker and a cardiovascular disease risk predictor. However, its prognostic value in patients with acute decompensated heart failure (ADHF) and different glycemic metabolic states remains ambiguous. METHODS A total of 1031 hospitalized patients with ADHF from January 2018 to May 2021 were included in the study. The primary endpoints were the major adverse cardiac and cerebral events (MACCEs). Patients were categorized into high-level FAR (FAR-H) and low-level FAR (FAR-L) groups based on the optimal cut-off value of FAR obtained from restricted cubic spline function analysis. The Kaplan-Meier plots and three multivariate-adjusted Cox proportional hazard models were used to determine the association between FAR and the risk of developing MACCEs in patients with ADHF at different glycemic metabolic states. RESULTS MACCEs occurred in 483 (46.8%) patients during a median follow-up time of 520 days. The optimal FAR cut-off value was 0.079. Upon analyzing the Kaplan-Meier plots, the incidence of MACCEs was significantly different between the FAR groups in all patients and patients with diabetes mellitus (p < 0.05). After adjusting for the confounding factors, the hazard ratio (HR) for MACCEs in the FAR-H group was 1.29 compared with the FAR-L group in all patients (Model 3: 95% CI 1.07-1.56, p = 0.007). Additionally, high FAR was associated with MACCEs in three multivariate Cox models (Model 1, HR = 1.52, 95% CI 1.17-1.96, p = 0.002; Model 2, HR = 1.46, 95% CI 1.13-1.89, p = 0.004; Model 3, HR = 1.48, 95% CI 1.14-1.92, p = 0.003) in DM patients. But no significant differences were found between the FAR groups for prediabetes mellitus (Pre-DM) and normal glucose regulation (NGR) using the three Cox models (all p-values were > 0.05). CONCLUSIONS Elevated FAR was independently associated with poor prognosis in patients with ADHF and DM and thus could be used as a risk stratification tool and a potential therapeutic target in the future.
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Affiliation(s)
- Rong Huang
- grid.428392.60000 0004 1800 1685Department of Cardiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008 Jiangsu China
| | - Qing Dai
- grid.428392.60000 0004 1800 1685Department of Cardiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008 Jiangsu China
| | - Lei Chang
- grid.428392.60000 0004 1800 1685Department of Cardiology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, 210008 Jiangsu China
| | - Ziyan Wang
- grid.428392.60000 0004 1800 1685Department of Cardiology, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing, 210008 Jiangsu China
| | - Jianzhou Chen
- grid.428392.60000 0004 1800 1685Department of Cardiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008 Jiangsu China
| | - Rong Gu
- grid.428392.60000 0004 1800 1685Department of Cardiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008 Jiangsu China
| | - Hongyan Zheng
- grid.428392.60000 0004 1800 1685Department of Cardiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008 Jiangsu China
| | - Lei Hu
- grid.428392.60000 0004 1800 1685Department of Cardiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008 Jiangsu China
| | - Biao Xu
- grid.428392.60000 0004 1800 1685Department of Cardiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008 Jiangsu China ,grid.428392.60000 0004 1800 1685Department of Cardiology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, 210008 Jiangsu China
| | - Lian Wang
- grid.428392.60000 0004 1800 1685Department of Cardiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008 Jiangsu China ,grid.428392.60000 0004 1800 1685Department of Cardiology, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing, 210008 Jiangsu China
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12
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Pan L, Wo M, Xu C, Wu Y, Ye Y, Han F, Fei X, Zhu F. Predictive significance of joint plasma fibrinogen and urinary alpha-1 microglobulin-creatinine ratio in patients with diabetic kidney disease. PLoS One 2022; 17:e0271181. [PMID: 35802685 PMCID: PMC9269903 DOI: 10.1371/journal.pone.0271181] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Accepted: 06/24/2022] [Indexed: 11/19/2022] Open
Abstract
Background
Although many biomarkers have high diagnostic and predictive power for diabetic kidney disease (DKD), less studies were performed for the predictive assessment in DKD and its progression with combined blood and urinary biomarkers. This study aims to explore the predictive significance of joint plasma fibrinogen (FIB) concentration and urinary alpha-1 microglobulin-creatinine (α1-MG/CR) ratio in DKD.
Methods
A total of 234 patients with type 2 diabetes were enrolled, and their clinical and laboratory data were retrospectively assessed. A ROC curve analysis was performed to evaluate the power of plasma FIB and urinary α1-MG/CR ratio for identifying DKD and advanced DKD, respectively. The predictive power for DKD and advanced DKD was analyzed by regression analysis.
Results
Plasma FIB and urinary α1-MG/CR levels were higher in patients with DKD than with pure T2D (p<0.001). The multivariate-adjusted odds ratios (ORs) were 5.047 (95%CI: 2.276–10.720) and 2.192 (95%CI: 1.539–3.122) (p<0.001) for FIB and α1-MG/CR as continuous variables for DKD prediction, respectively. The optimal cut-off values were 3.21 g/L and 2.11mg/mmol for identifying DKD, and 5.58 g/L and 11.07 mg/mmol for advanced DKD from ROC curves. At these cut-off values, the sensitivity and specificity of joint FIB and α1-MG/CR were 0.95 and 0.92 for identifying DKD, and 0.62 and 0.67 for identifying advanced DKD, respectively. The area under curve was 0.972 (95%CI: 0.948–0.995) (p<0.001) and 0.611, 95%CI: 0.488–0.734) (p>0.05). The multivariate-adjusted ORs for joint FIB and α1-MG/CR at the cut-off values were 214.500 (95%CI: 58.054–792.536) and 3.252 (95%CI: 1.040–10.175) (p<0.05), respectively.
Conclusion
The present study suggests that joint plasma FIB concentration and urinary α1-MG/CR ratio can be used as a powerful predictor for general DKD, but it is less predictive for advanced DKD.
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Affiliation(s)
- Lianlian Pan
- Department of Laboratory Medicine, Sanmen People’s Hospital, Sanmen, Zhejiang, China
| | - Mingyi Wo
- Department of Clinical Laboratory, Laboratory Medicine Center, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China
| | - Chan Xu
- Department of Laboratory Medicine, Affiliated Third Hospital of Zhejiang Traditional Chinese Medicine University, Hangzhou, Zhejiang, China
| | - Yan Wu
- Department of Laboratory Medicine, Lin’an First People’s Hospital, Hangzhou, Zhejiang, China
| | - Yali Ye
- Department of Laboratory Medicine, Sanmen People’s Hospital, Sanmen, Zhejiang, China
| | - Fan Han
- Department of Clinical Laboratory, Laboratory Medicine Center, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China
| | - Xianming Fei
- Department of Clinical Laboratory, Laboratory Medicine Center, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China
- * E-mail: (FZ); (XF)
| | - Fengjiao Zhu
- Department of Laboratory Medicine, Sanmen People’s Hospital, Sanmen, Zhejiang, China
- * E-mail: (FZ); (XF)
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13
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Biophysical changes in methylglyoxal modified fibrinogen and its role in the immunopathology of type 2 diabetes mellitus. Int J Biol Macromol 2022; 202:199-214. [PMID: 34999047 DOI: 10.1016/j.ijbiomac.2021.12.161] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Revised: 11/10/2021] [Accepted: 12/24/2021] [Indexed: 12/20/2022]
Abstract
Methylglyoxal (MG), a highly reactive dicarbonyl metabolite gets generated during glucose oxidation and lipid peroxidation, which contributes to glycation. In type 2 diabetes mellitus (T2DM), non-enzymatic glycosylation of proteins mediated by hyperglycemia results in the pathogenesis of diabetes-associated secondary complications via the generation of AGEs. Under in vitro conditions, MG altered the tertiary structure of fibrinogen. High-performance liquid chromatography (HPLC) and liquid chromatography mass spectroscopy (LCMS) studies confirmed the generation of N-(carboxymethyl) lysine, N-(carboxyethyl) lysine, hydroimidazolone, pentosidine and argpyrimidine in the modified protein. The altered fibrinogen structure upon glycation was further confirmed by confocal microscopy and nuclear magnetic resonance spectra (NMR). MG-Fib was found to be more immunogenic, as compared to its native analogue, in the immunological studies conducted on experimental rabbits. Our results reflect the presence of neo-antigenic determinants on modified fibrinogen. Competitive inhibition enzyme-linked immunosorbent assay suggested the presence of neo-epitopes with marked immunogenicity eliciting specific immune response. Binding studies on purified immunoglobulin G (IgG) confirmed the enhanced and specific immunogenicity of MG-Fib. Studies on interaction of MG-Fib with the circulating auto-antibodies from T2DM patients showed high affinity of serum antibodies toward MG-Fib. This study suggests a potent role of glycoxidatively modified fibrinogen in the generation of auto-immune response in T2DM patients.
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14
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Yuan D, Jiang P, Zhu P, Jia S, Zhang C, Liu Y, Liu R, Xu J, Tang X, Zhao X, Gao R, Yang Y, Xu B, Gao Z, Yuan J. Prognostic value of fibrinogen in patients with coronary artery disease and prediabetes or diabetes following percutaneous coronary intervention: 5-year findings from a large cohort study. Cardiovasc Diabetol 2021; 20:143. [PMID: 34271936 PMCID: PMC8283976 DOI: 10.1186/s12933-021-01335-1] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Accepted: 07/05/2021] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Fibrinogen (FIB) is an independent risk factor for mortality and cardiovascular events in the general population. However, the relationship between FIB and long-term mortality among CAD patients undergoing PCI remains unclear, especially in individuals complicated with diabetes mellitus (DM) or prediabetes (Pre-DM). METHODS 6,140 patients with CAD undergoing PCI were included in the study and subsequently divided into three groups according to FIB levels (FIB-L, FIB-M, FIB-H). These patients were further grouped by glycemic status [normoglycemia (NG), Pre-DM, DM]. The primary endpoint was all-cause mortality. The secondary endpoint was cardiac mortality. RESULTS FIB was positively associated with hemoglobin A1c (HbA1c) and fasting blood glucose (FBG) in CAD patients with and without DM (P < 0.001). During a median follow-up of 5.1 years (interquartile range 5.0-5.2 years), elevated FIB was significantly associated with long-term all-cause mortality (adjusted HR: 1.86; 95% CI 1.28-2.69; P = 0.001) and cardiac mortality (adjusted HR: 1.82; 95% CI 1.15-2.89; P = 0.011). Similarly, patients with DM, but not Pre-DM, had increased risk of all-cause and cardiac mortality compared with NG group (all P < 0.05). When grouped by both FIB levels and glycemic status, diabetic patients with medium and high FIB levels had higher risk of mortality [(adjusted HR: 2.57; 95% CI 1.12-5.89), (adjusted HR: 3.04; 95% CI 1.35-6.82), all P < 0.05]. Notably, prediabetic patients with high FIB also had higher mortality risk (adjusted HR: 2.27; 95% CI 1.01-5.12). CONCLUSIONS FIB was independently associated with long-term all-cause and cardiac mortality among CAD patients undergoing PCI, especially in those with DM and Pre-DM. FIB test may help to identify high-risk individuals in this specific population.
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Affiliation(s)
- Deshan Yuan
- State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No 167, Beilishi Road, Xicheng District, Beijing, 100037, China
| | - Ping Jiang
- State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No 167, Beilishi Road, Xicheng District, Beijing, 100037, China
| | - Pei Zhu
- State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No 167, Beilishi Road, Xicheng District, Beijing, 100037, China
| | - Sida Jia
- State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No 167, Beilishi Road, Xicheng District, Beijing, 100037, China
| | - Ce Zhang
- State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No 167, Beilishi Road, Xicheng District, Beijing, 100037, China
| | - Yue Liu
- State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No 167, Beilishi Road, Xicheng District, Beijing, 100037, China
| | - Ru Liu
- State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No 167, Beilishi Road, Xicheng District, Beijing, 100037, China
| | - Jingjing Xu
- State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No 167, Beilishi Road, Xicheng District, Beijing, 100037, China
| | - Xiaofang Tang
- State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No 167, Beilishi Road, Xicheng District, Beijing, 100037, China
| | - Xueyan Zhao
- State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No 167, Beilishi Road, Xicheng District, Beijing, 100037, China
| | - Runlin Gao
- State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No 167, Beilishi Road, Xicheng District, Beijing, 100037, China
| | - Yuejin Yang
- State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No 167, Beilishi Road, Xicheng District, Beijing, 100037, China
| | - Bo Xu
- State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No 167, Beilishi Road, Xicheng District, Beijing, 100037, China
| | - Zhan Gao
- State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No 167, Beilishi Road, Xicheng District, Beijing, 100037, China
| | - Jinqing Yuan
- State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No 167, Beilishi Road, Xicheng District, Beijing, 100037, China.
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15
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Huang Y, Kyriakides TR. The role of extracellular matrix in the pathophysiology of diabetic wounds. Matrix Biol Plus 2020; 6-7:100037. [PMID: 33543031 PMCID: PMC7852307 DOI: 10.1016/j.mbplus.2020.100037] [Citation(s) in RCA: 52] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2020] [Revised: 04/13/2020] [Accepted: 04/14/2020] [Indexed: 12/29/2022] Open
Abstract
Impaired healing leading to the formation of ulcerated wounds is a critical concern in patients with diabetes. Abnormalities in extracellular matrix (ECM) production and remodeling contribute to tissue dysfunction and delayed healing. Specifically, diabetes-induced changes in the expression and/or activity of structural proteins, ECM-modifying enzymes, proteoglycans, and matricellular proteins have been reported. In this review, we provide a summary of the key ECM molecules and associated changes in skin and diabetic wounds. Such information should allow for new insights in the understanding of impaired wound healing and lead to the development of ECM-based therapeutic strategies.
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Affiliation(s)
- Yaqing Huang
- Vascular Biology and Therapeutics Program, Yale University, New Haven, CT 06519, USA.,Department of Pathology, Yale University, New Haven, CT 06519, USA
| | - Themis R Kyriakides
- Vascular Biology and Therapeutics Program, Yale University, New Haven, CT 06519, USA.,Department of Pathology, Yale University, New Haven, CT 06519, USA.,Department of Biomedical Engineering, Yale University, New Haven, CT 06519, USA
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16
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Manzoor S, Ganie MA, Amin S, Shah ZA, Bhat IA, Yousuf SD, Jeelani H, Kawa IA, Fatima Q, Rashid F. Oral contraceptive use increases risk of inflammatory and coagulatory disorders in women with Polycystic Ovarian Syndrome: An observational study. Sci Rep 2019; 9:10182. [PMID: 31308416 PMCID: PMC6629878 DOI: 10.1038/s41598-019-46644-4] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2018] [Accepted: 06/21/2019] [Indexed: 12/14/2022] Open
Abstract
Polycystic ovarian syndrome (PCOS) is a multispectral disorder requiring lifelong management. Its pathophysiology is still being explored which makes its treatment options restrained. Present study explores impact of oral contraceptive mode of treatment on metabolic, hormonal, inflammation and coagulation profile of PCOS women. 50 subjects diagnosed with Rotterdam criteria receiving no drug treatment served as controls whereas 50 subjects receiving only OCPs (Ethinyl estradiol 0.03 mg, Levonorgestrel 0.15 mg) as a mode of treatment at least for six-months served as cases. Ferriman-Gallwey score and hormonal profile improved on OCP treatment. However, parameters like weight, Body mass index, waist-hip ratio, Oral glucose tolerance test, lipid profile, insulin, HOMA-IR, adiponectin, interleukin1β, visfatin, resistin, tissue factor, PT and APTT showed considerable derangements in OCP group. All above parameters are associated with the risk of diabetes mellitus, dyslipidemia, coronary vascular disease, cancers, hypercoagulable state, venous thromboembolism and thrombotic events. Long-term use of OCPs needs to be considered carefully for PCOS patients who are already burdened with associated risk factors. This study was conducted in a region where women do not have much access to high-end screening and diagnostic facilities that further exacerbates their clinical outcomes. Large scale, long-term studies need to be designed to further evaluate safety use of OCPs in PCOS women.
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Affiliation(s)
- Saika Manzoor
- Department of Clinical Biochemistry/Biochemistry, University of Kashmir, Srinagar, J&K, India
| | - Mohd Ashraf Ganie
- Department of Endocrinology and Metabolism, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, J&K, India
| | - Shajrul Amin
- Department of Clinical Biochemistry/Biochemistry, University of Kashmir, Srinagar, J&K, India
| | - Zaffar A Shah
- Department of Immunology and Molecular Medicine, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, J&K, India
| | - Imtiyaz A Bhat
- Department of Immunology and Molecular Medicine, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, J&K, India
| | - S Douhath Yousuf
- Department of Clinical Biochemistry/Biochemistry, University of Kashmir, Srinagar, J&K, India
| | - Humira Jeelani
- Department of Clinical Biochemistry/Biochemistry, University of Kashmir, Srinagar, J&K, India
| | - Iram A Kawa
- Department of Clinical Biochemistry/Biochemistry, University of Kashmir, Srinagar, J&K, India
| | - Qudsia Fatima
- Department of Clinical Biochemistry/Biochemistry, University of Kashmir, Srinagar, J&K, India
| | - Fouzia Rashid
- Department of Clinical Biochemistry/Biochemistry, University of Kashmir, Srinagar, J&K, India.
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17
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Zhang L, Xu C, Liu J, Bai X, Li R, Wang L, Zhou J, Wu Y, Yuan Z. Baseline plasma fibrinogen is associated with haemoglobin A1c and 2-year major adverse cardiovascular events following percutaneous coronary intervention in patients with acute coronary syndrome: a single-centre, prospective cohort study. Cardiovasc Diabetol 2019; 18:52. [PMID: 31014348 PMCID: PMC6480802 DOI: 10.1186/s12933-019-0858-5] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Accepted: 04/10/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Despite revascularisation, a large proportion of acute coronary syndrome (ACS) patients continue to experience major adverse cardiovascular events (MACEs), which are worsened by diabetes mellitus (DM). Fibrinogen (FIB) is a risk factor for MACEs in coronary artery disease and often elevated in DM. However, the relationships between FIB, glucose metabolism (haemoglobin A1c [HbA1c] and fasting blood glucose [FBG]) and MACEs following percutaneous coronary intervention (PCI) in DM, non-DM or whole patients with ACS remains unknown. METHODS A total of 411 ACS patients undergoing PCI were enrolled in this study. We compared baseline FIB levels between DM (n = 103) and non-DM (n = 308) patients and divided participants into three groups according to FIB level, i.e. FIB-L, FIB-M and FIB-H, to compare baseline characteristics and MACEs. Linear regression analysis of the relationship between glucose metabolism and FIB, Cox regression, survival and landmark analyses of MACEs were also performed over a median of 27.55 months of follow-up. RESULTS Patients with DM had higher FIB levels than non-DM patients (3.56 ± 0.99 mg/dL vs. 3.34 ± 0.80 mg/dL, P < 0.05). HbA1c and FBG were significantly positively correlated with FIB in whole and DM patients but not in non-DM patients (all P < 0.05). Compared with the FIB-L group, the FIB-M (hazard ratio [HR] 1.797, 95% CI 1.117-2.892, P = 0.016) and FIB-H (HR 1.664, 95% CI 1.002-2.763, P = 0.049) groups were associated with higher MACEs in whole; the FIB-M (HR 7.783, 95% CI 1.012-59.854, P = 0.049) was associated with higher MACEs in DM patients. FIB was not associated with MACEs in non-DM patients. During landmark analysis, FIB showed better predictive value for MACEs after PCI in the first 30 months of follow up than in the subsequent period. CONCLUSION In this study from China, FIB was positively associated with glucose metabolism (HbA1c and FBG) in whole and DM populations with ACS. Moreover, elevated baseline FIB levels may be an important and independent predictor of MACEs following PCI, especially amongst those with DM. However, as the follow-up period increased, the baseline FIB levels lost their ability to predict MACEs.
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Affiliation(s)
- Lisha Zhang
- Department of Cardiovascular Medicine, The First Affiliated Hospital, Xi'an Jiaotong University, 277 West Yanta Rd., Xi'an, 710061, Shaanxi, People's Republic of China
| | - Chenbo Xu
- Department of Cardiovascular Medicine, The First Affiliated Hospital, Xi'an Jiaotong University, 277 West Yanta Rd., Xi'an, 710061, Shaanxi, People's Republic of China
| | - Junhui Liu
- Department of Clinical Laboratory, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China
| | - Xiaofang Bai
- Department of Cardiovascular Medicine, The First Affiliated Hospital, Xi'an Jiaotong University, 277 West Yanta Rd., Xi'an, 710061, Shaanxi, People's Republic of China
| | - Ruifeng Li
- Department of Cardiovascular Medicine, The First Affiliated Hospital, Xi'an Jiaotong University, 277 West Yanta Rd., Xi'an, 710061, Shaanxi, People's Republic of China
| | - Lijun Wang
- Department of Cardiovascular Medicine, The First Affiliated Hospital, Xi'an Jiaotong University, 277 West Yanta Rd., Xi'an, 710061, Shaanxi, People's Republic of China
| | - Juan Zhou
- Department of Cardiovascular Medicine, The First Affiliated Hospital, Xi'an Jiaotong University, 277 West Yanta Rd., Xi'an, 710061, Shaanxi, People's Republic of China.,Key Laboratory of Molecular Cardiology, Shaanxi Province, Xi'an, Shaanxi, People's Republic of China
| | - Yue Wu
- Department of Cardiovascular Medicine, The First Affiliated Hospital, Xi'an Jiaotong University, 277 West Yanta Rd., Xi'an, 710061, Shaanxi, People's Republic of China. .,Key Laboratory of Molecular Cardiology, Shaanxi Province, Xi'an, Shaanxi, People's Republic of China.
| | - Zuyi Yuan
- Department of Cardiovascular Medicine, The First Affiliated Hospital, Xi'an Jiaotong University, 277 West Yanta Rd., Xi'an, 710061, Shaanxi, People's Republic of China. .,Key Laboratory of Molecular Cardiology, Shaanxi Province, Xi'an, Shaanxi, People's Republic of China. .,Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an, Shaanxi, People's Republic of China.
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18
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Agarwal C, Bansal K, Pujani M, Singh K, Chauhan V, Rana D, Lukhmana S. Association of coagulation profile with microvascular complications and glycemic control in type 2 diabetes mellitus - a study at a tertiary care center in Delhi. Hematol Transfus Cell Ther 2019; 41:31-36. [PMID: 30793102 PMCID: PMC6371197 DOI: 10.1016/j.htct.2018.05.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2018] [Accepted: 05/14/2018] [Indexed: 12/05/2022] Open
Abstract
Introduction Type 2 diabetes mellitus, characterized by insulin resistance, corresponds to approximately 90% of cases of diabetes worldwide. Hyperglycemia in diabetes contributes to hyperfibrinogenemia and activates the coagulation cascade thereby producing atherothrombotic events. Objectives This study was designed to evaluate the coagulation profile (activated partial thromboplastin time, prothrombin time and fibrinogen) in Type 2 diabetes and to analyze correlations between body mass index, fasting blood glucose, glycated hemoglobin and duration of diabetes with coagulation parameters. Methods This study included 60 type 2 diabetics and 30 controls. Diabetic patients were grouped in two sets based on the presence or absence of microvascular complications. The demographic profile and clinical details were recorded. Fasting blood glucose, glycated hemoglobin, coagulation parameters such as prothrombin time, activated partial thromboplastin time and fibrinogen along with other biochemical parameters were investigated. Results There were statistically significant differences in the coagulation parameters between the two groups of diabetics (with and without complications). The present study also found significant correlations between age and the duration of diabetes with and without complications and coagulation parameters such as the activated partial thromboplastin time, which was found to be significantly lower, and fibrinogen, which was found to be significantly higher in subjects with complications compared to subjects without complications. Conclusion Clinical tests for prothrombin time, activated partial thromboplastin time and fibrinogen are relatively inexpensive and readily available. The present study shows that shortened prothrombin time, activated partial thromboplastin time and increased fibrinogen levels might be useful hemostatic markers in diabetic patients, especially in those at high-risk for thrombotic complications.
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Affiliation(s)
- Charu Agarwal
- Department of Pathology, Employees State Insurance Corporation (ESIC) Medical College, Faridabad, Haryana, India
| | - Kashish Bansal
- Employees State Insurance Corporation (ESIC) Medical College, Faridabad, Haryana, India
| | - Mukta Pujani
- Department of Pathology, Employees State Insurance Corporation (ESIC) Medical College, Faridabad, Haryana, India.
| | - Kanika Singh
- Department of Pathology, Employees State Insurance Corporation (ESIC) Medical College, Faridabad, Haryana, India
| | - Varsha Chauhan
- Department of Pathology, Employees State Insurance Corporation (ESIC) Medical College, Faridabad, Haryana, India
| | - Deepshikha Rana
- Department of Pathology, Employees State Insurance Corporation (ESIC) Medical College, Faridabad, Haryana, India
| | - Shveta Lukhmana
- Department of Community medicine, Employees State Insurance Corporation (ESIC) Medical College, Faridabad, Haryana, India
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Hood JE, Yesudasan S, Averett RD. Glucose Concentration Affects Fibrin Clot Structure and Morphology as Evidenced by Fluorescence Imaging and Molecular Simulations. Clin Appl Thromb Hemost 2018; 24:104S-116S. [PMID: 30114949 PMCID: PMC6714860 DOI: 10.1177/1076029618792304] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
Although in vivo studies have been conducted in the past to determine hyperglycemic effects and influence on clotting risk in patients with diabetes, the true extent of hyperglycemia on unstable and spontaneous clot formation remains highly debated. Factors such as increased glycation, elevated fibrinogen concentration, elevated prothrombin levels, and decreased plasminogen are known to influence fibrin conversion, clot morphology, and thrombus formation in these individuals. In this regard, the isolated effects of hyperglycemia on irregular fibrin clot formation were investigated in a controlled fibrinogen system. In this study, fibrin clot characteristic differences at 3 glucose concentrations were analyzed to determine the effects of glucose concentration on fibrinogen glycation and fibrin clot morphology using confocal microscopy, glycation quantification, molecular simulations, and image processing methods. Algorithms coupled with statistical analysis support in vivo findings that hyperglycemia increases fibrinogen glycation, with ensuing altered fibrin clot structure characteristics. Our experimental and molecular simulation results consistently show an increased glucose adsorption by fibrinogen with increased glucose concentration. Significant differences in clot structure characteristics were observed, and the results of this work can be used to further develop diagnostic tools for evaluating clotting risk in individuals with hypercoagulable and hyperglycemic conditions.
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Affiliation(s)
- Jacob E Hood
- School of Chemical, Materials, and Biomedical Engineering, College of Engineering, University of Georgia, Athens, GA, USA
| | - Sumith Yesudasan
- School of Chemical, Materials, and Biomedical Engineering, College of Engineering, University of Georgia, Athens, GA, USA
| | - Rodney D Averett
- School of Chemical, Materials, and Biomedical Engineering, College of Engineering, University of Georgia, Athens, GA, USA
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20
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Egorov AI, Griffin SM, Converse RR, Styles JN, Sams EA, Wilson A, Jackson LE, Wade TJ. Vegetated land cover near residence is associated with reduced allostatic load and improved biomarkers of neuroendocrine, metabolic and immune functions. ENVIRONMENTAL RESEARCH 2017; 158:508-521. [PMID: 28709033 PMCID: PMC5941947 DOI: 10.1016/j.envres.2017.07.009] [Citation(s) in RCA: 90] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/07/2017] [Revised: 07/03/2017] [Accepted: 07/04/2017] [Indexed: 05/21/2023]
Abstract
BACKGROUND Greater exposure to urban green spaces has been linked to reduced risks of depression, cardiovascular disease, diabetes and premature death. Alleviation of chronic stress is a hypothesized pathway to improved health. Previous studies linked chronic stress with a biomarker-based composite measure of physiological dysregulation known as allostatic load. OBJECTIVE This study's objective was to assess the relationship between vegetated land cover near residences and allostatic load. METHODS This cross-sectional population-based study involved 206 adult residents of the Durham-Chapel Hill, North Carolina metropolitan area. Exposure was quantified using high-resolution metrics of trees and herbaceous vegetation within 500m of each residence derived from the U.S. Environmental Protection Agency's EnviroAtlas land cover dataset. Eighteen biomarkers of immune, neuroendocrine, and metabolic functions were measured in serum or saliva samples. Allostatic load was defined as a sum of potentially unhealthy biomarker values dichotomized at 10th or 90th percentile of sample distribution. Regression analysis was conducted using generalized additive models with two-dimensional spline smoothing function of geographic coordinates, weighted measures of vegetated land cover allowing decay of effects with distance, and geographic and demographic covariates. RESULTS An inter-quartile range increase in distance-weighted vegetated land cover was associated with 37% (95% Confidence Limits 46%; 27%) reduced allostatic load; significantly reduced adjusted odds of having low level of norepinephrine, dopamine, and dehydroepiandrosterone, and high level of epinephrine, fibrinogen, vascular cell adhesion molecule-1, and interleukin-8 in serum, and α-amylase in saliva; and reduced odds of previously diagnosed depression. CONCLUSIONS The observed effects of vegetated land cover on allostatic load and individual biomarkers are consistent with prevention of depression, cardiovascular disease and premature mortality.
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Affiliation(s)
- Andrey I Egorov
- National Health and Environmental Effects Research Laboratory, United States Environmental Protection Agency, Research Triangle Park, NC, USA.
| | - Shannon M Griffin
- National Exposure Research Laboratory, United States Environmental Protection Agency, Cincinnati, OH, USA
| | - Reagan R Converse
- Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Jennifer N Styles
- National Health and Environmental Effects Research Laboratory, United States Environmental Protection Agency, Research Triangle Park, NC, USA; National Exposure Research Laboratory, United States Environmental Protection Agency, Cincinnati, OH, USA
| | - Elizabeth A Sams
- National Health and Environmental Effects Research Laboratory, United States Environmental Protection Agency, Research Triangle Park, NC, USA
| | - Anthony Wilson
- Association of Schools and Programs of Public Health fellow at the United States Environmental Protection Agency, Research Triangle Park, NC, USA
| | - Laura E Jackson
- National Health and Environmental Effects Research Laboratory, United States Environmental Protection Agency, Research Triangle Park, NC, USA
| | - Timothy J Wade
- National Health and Environmental Effects Research Laboratory, United States Environmental Protection Agency, Research Triangle Park, NC, USA
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Igari K, Kudo T, Toyofuku T, Inoue Y. The use of dielectric blood coagulometry in the evaluation of coagulability in patients with peripheral arterial disease. BMC Clin Pathol 2017; 17:14. [PMID: 28852324 PMCID: PMC5569553 DOI: 10.1186/s12907-017-0054-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2017] [Accepted: 08/17/2017] [Indexed: 11/13/2022] Open
Abstract
Background Platelets and coagulation proteins contribute to the development of peripheral arterial disease, especially atherosclerotic disease. Several experimental studies have proven a significant correlation between hypercoagulability and atherosclerosis. We used dielectric blood coagulometry, which was initially designed to evaluate the coagulable status, to examine the coagulability of peripheral arterial disease patients, and investigated the factors that were significantly correlated with the results. Methods We performed dielectric blood coagulometry in 49 peripheral arterial disease patients. In addition, we recorded the patients’ demographic information, including the presence of comorbidities, hemodynamic status, and laboratory findings. To investigate coagulability, we calculated the Tmax value, which indicates the time from recalcification to maximum normalized permittivity. Results The Tmax values of diabetes mellitus patients were significantly lower than those of non-diabetic patients (1 MHz, P = 0.010; 10 MHz, 0.011). Furthermore, the Tmax value was statistically correlated with the activated partial thromboplastin time (1 MHz, ρ = 0.286, P = 0.048; 10 MHz, ρ = 0.301, P = 0.037). Conclusions Dielectric blood coagulometry detected the hypercoagulable status in diabetes mellitus patients, and reflected their level of coagulability, which was also evaluated by the activated partial thromboplastin time.
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Affiliation(s)
- Kimihiro Igari
- Division of Vascular and Endovascular Surgery, Department of Surgery, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519 Japan
| | - Toshifumi Kudo
- Division of Vascular and Endovascular Surgery, Department of Surgery, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519 Japan
| | - Takahiro Toyofuku
- Division of Vascular and Endovascular Surgery, Department of Surgery, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519 Japan
| | - Yoshinori Inoue
- Division of Vascular and Endovascular Surgery, Department of Surgery, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519 Japan
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Yang SH, Du Y, Zhang Y, Li XL, Li S, Xu RX, Zhu CG, Guo YL, Wu NQ, Qing P, Gao Y, Cui CJ, Dong Q, Sun J, Li JJ. Serum fibrinogen and cardiovascular events in Chinese patients with type 2 diabetes and stable coronary artery disease: a prospective observational study. BMJ Open 2017; 7:e015041. [PMID: 28601829 PMCID: PMC5734258 DOI: 10.1136/bmjopen-2016-015041] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2016] [Revised: 04/06/2017] [Accepted: 04/06/2017] [Indexed: 11/06/2022] Open
Abstract
OBJECTIVES The aim of this study was to investigate the association of serum fibrinogen with cardiovascular events (CVE) in Chinese patients with type 2 diabetes mellitus (T2DM) and stable coronary artery disease (CAD). DESIGN An observational study. SETTING FuWai Hospital in Beijing, China. PARTICIPANTS A cohort of 1466 patients with T2DM and angiographic-proven stable CAD was evaluated. OUTCOME MEASURES Baseline serum fibrinogen levels were measured and trisected into 'low', 'middle' and 'high'. Their association with CVE was explored using Cox proportional hazard models. RESULTS With 20.2 months (average) follow-up, 44 (3%) were lost to follow-up and 96 patients developed CVE. Compared with the patients without CVE, the ones who developed CVE had higher levels of fibrinogen. Univariable regression revealed a significant relation of fibrinogen to CVE (HR (HR) 1.25, 95% CI 1.06 to 1.47, p=0.010) per SD increase of fibrinogen at baseline. After adjusting for multiple established cardiovascular disease (CVD) risk factors, the association persisted (HR 1.30, 95% CI 1.02 to 1.66, p=0.037). Moreover, after adjusting for CVD risk factors, the HRs for middle-serum and high-serum fibrinogen concentration, using 'low' group as reference, were 1.23 (95% CI 0.69 to 2.20) and 2.20 (95% CI 1.11 to 3.36, p=0.049). CONCLUSIONS We first indicated that elevated fibrinogen level was independently associated with increased CVE in Chinese patients with T2DMand stable CAD.
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Affiliation(s)
- Sheng-Hua Yang
- Division of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Ying Du
- Division of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Yan Zhang
- Division of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Xiao-Lin Li
- Division of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Sha Li
- Division of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Rui-Xia Xu
- Division of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Cheng-Gang Zhu
- Division of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Yuan-Lin Guo
- Division of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Na-Qiong Wu
- Division of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Ping Qing
- Division of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Ying Gao
- Division of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Chuan-Jue Cui
- Division of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Qian Dong
- Division of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Jing Sun
- Division of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Jian-Jun Li
- Division of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
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Kotbi S, Mjabber A, Chadli A, El Hammiri A, El Aziz S, Oukkache B, Mifdal H, Nourichafi N, Kamal N, Habbal R, Ghalim N, Farouqi A, Kabine M. Correlation between the plasma fibrinogen concentration and coronary heart disease severity in Moroccan patients with type 2 diabetes. Prospective study. ANNALES D'ENDOCRINOLOGIE 2016; 77:606-614. [PMID: 26903037 DOI: 10.1016/j.ando.2015.02.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/28/2014] [Revised: 01/10/2015] [Accepted: 02/04/2015] [Indexed: 11/17/2022]
Abstract
AIM The present study aims at determining the relationship between the plasma fibrinogen concentration and the severity of coronary heart disease in type 2 diabetic patients. METHODS Prospective analytical survey, based on a sample of 120 subjects divided in four groups: 30 non diabetic coronary patients (G1), 30 coronary diabetic patients (G2), 30 non-coronary diabetic patients (G3), and 30 healthy subjects (G4). RESULTS The average age was 59.58±7.88 years; female gender predominated by 52.5%. The plasma fibrinogen concentration corresponded to 3.46g/L±0.86 in G1; 3.73g/L±1.11 in G2; 3.06g/L±0.98 in G3 and 2.46g/L±0.51 in G4; with a significant difference between the four groups (P=0.001). The plasma fibrinogen concentration increased in parallel with the cardiovascular risk (P=0.0001); there was also a significant correlation between the plasma fibrinogen concentration and the clinical and para-clinical coronary disease severity (respectively P=0.005 and P=0.0001). A positive correlation between the plasma fibrinogen concentration and hyperglycemia (P=0.035) was found in G4. But no correlation with the lipids parameters, except for the low density-lipoproteins in G3 (P=0.035). CONCLUSION In the Moroccan population, the plasma fibrinogen concentration was positively and significantly correlated with the coronary heart disease severity.
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Affiliation(s)
- Souad Kotbi
- Department of Biology, Laboratory of Biochemistry and Molecular Biology, Ain chock Faculty of Science, Km 9, El Jadida road, Box 5366 Maarif, Casablanca, Morocco
| | - Amal Mjabber
- Endocrinology and Metabolic Diseases department, Ibn Rochd, University Hospital Center 1, Hospitals part, Casablanca, Morocco
| | - Asma Chadli
- Endocrinology and Metabolic Diseases department, Ibn Rochd, University Hospital Center 1, Hospitals part, Casablanca, Morocco.
| | - Ayoub El Hammiri
- Cardiology department, Ibn Rochd university, Hospital Center, 1, Hospitals part, Casablanca, Morocco
| | - Siham El Aziz
- Endocrinology and Metabolic Diseases department, Ibn Rochd, University Hospital Center 1, Hospitals part, Casablanca, Morocco
| | - Bouchra Oukkache
- Regional blood transfusion centre, 1, Mohamed El Fidouzi-ex Jenner street, Casablanca, Morocco
| | - Hassan Mifdal
- Hematology laboratory, Ibn Rochd university, Hospital Center, Hospitals part, Casablanca, Morocco
| | - Nadia Nourichafi
- Hematology laboratory, Ibn Rochd university, Hospital Center, Hospitals part, Casablanca, Morocco
| | - Nabiha Kamal
- Laboratory of biochemistry, Ibn Rochd university, Hospital Center, 1, Hospitals part, Casablanca, Morocco
| | - Rachida Habbal
- Cardiology department, Ibn Rochd university, Hospital Center, 1, Hospitals part, Casablanca, Morocco
| | - Norredine Ghalim
- Department of medical biology, Pasteur Institute of Morocco, 1, place Louis-Pasteur, 20360 Casablanca, Morocco
| | - Ahmed Farouqi
- Endocrinology and Metabolic Diseases department, Ibn Rochd, University Hospital Center 1, Hospitals part, Casablanca, Morocco
| | - Mostafa Kabine
- Department of Biology, Laboratory of Biochemistry and Molecular Biology, Ain chock Faculty of Science, Km 9, El Jadida road, Box 5366 Maarif, Casablanca, Morocco
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Arpaci D, Saglam F, Ozdemir D, Ersoy R, Cakir B. Does glycemic regulation affect hypercoagulable states in diabetic patients? Int J Diabetes Dev Ctries 2015. [DOI: 10.1007/s13410-015-0311-6] [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: 11/27/2022] Open
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Glycogen Fuels Survival During Hyposmotic-Anoxic Stress in Caenorhabditis elegans. Genetics 2015; 201:65-74. [PMID: 26116152 PMCID: PMC4566277 DOI: 10.1534/genetics.115.179416] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2015] [Accepted: 06/18/2015] [Indexed: 11/18/2022] Open
Abstract
Oxygen is an absolute requirement for multicellular life. Animals that are deprived of oxygen for sufficient periods of time eventually become injured and die. This is largely due to the fact that, without oxygen, animals are unable to generate sufficient quantities of energy. In human diseases triggered by oxygen deprivation, such as heart attack and stroke, hyposmotic stress and cell swelling (edema) arise in affected tissues as a direct result of energetic failure. Edema independently enhances tissue injury in these diseases by incompletely understood mechanisms, resulting in poor clinical outcomes. Here, we present investigations into the effects of osmotic stress during complete oxygen deprivation (anoxia) in the genetically tractable nematode Caenorhabditis elegans. Our findings demonstrate that nematode survival of a hyposmotic environment during anoxia (hyposmotic anoxia) depends on the nematode’s ability to engage in glycogen metabolism. We also present results of a genome-wide screen for genes affecting glycogen content and localization in the nematode, showing that nematode survival of hyposmotic anoxia depends on a large number of these genes. Finally, we show that an inability to engage in glycogen synthesis results in suppression of the enhanced survival phenotype observed in daf-2 insulin-like pathway mutants, suggesting that alterations in glycogen metabolism may serve as a basis for these mutants’ resistance to hyposmotic anoxia.
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Fan NK, Keegan PM, Platt MO, Averett RD. Experimental and imaging techniques for examining fibrin clot structures in normal and diseased states. J Vis Exp 2015:e52019. [PMID: 25867016 PMCID: PMC4401406 DOI: 10.3791/52019] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023] Open
Abstract
Fibrin is an extracellular matrix protein that is responsible for maintaining the structural integrity of blood clots. Much research has been done on fibrin in the past years to include the investigation of synthesis, structure-function, and lysis of clots. However, there is still much unknown about the morphological and structural features of clots that ensue from patients with disease. In this research study, experimental techniques are presented that allow for the examination of morphological differences of abnormal clot structures due to diseased states such as diabetes and sickle cell anemia. Our study focuses on the preparation and evaluation of fibrin clots in order to assess morphological differences using various experimental assays and confocal microscopy. In addition, a method is also described that allows for continuous, real-time calculation of lysis rates in fibrin clots. The techniques described herein are important for researchers and clinicians seeking to elucidate comorbid thrombotic pathologies such as myocardial infarctions, ischemic heart disease, and strokes in patients with diabetes or sickle cell disease.
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Affiliation(s)
- Natalie K Fan
- Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology & Emory University School of Medicine
| | - Philip M Keegan
- Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology & Emory University School of Medicine
| | - Manu O Platt
- Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology & Emory University School of Medicine; Parker H. Petit Institute for Bioengineering & Bioscience, Georgia Institute of Technology
| | - Rodney D Averett
- Parker H. Petit Institute for Bioengineering & Bioscience, Georgia Institute of Technology; George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology;
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Baber U, Auguste U. Patients with chronic kidney disease/diabetes mellitus: the high-risk profile in acute coronary syndrome. Curr Cardiol Rep 2014; 15:386. [PMID: 23843182 DOI: 10.1007/s11886-013-0386-y] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Chronic kidney disease (CKD) and diabetes mellitus (DM) are highly prevalent, morbid diseases that are very common among patients presenting with acute coronary syndromes (ACS). Despite significant reductions in cardiovascular morbidity and mortality over the last half century, residual vascular risk remains disproportionately high in these populations. In large part, this is attributable to pre-existing vascular morbidity and substantial enrichment of traditional risk factors among those with either CKD or DM. Other factors, such as less aggressive therapeutic intervention and a unique atherothrombotic phenotype, are also contributory. The introduction of novel antiplatelet and antithrombotic agents over the last several years provides fresh opportunities to improve the adverse prognosis among patients with CKD or DM and concomitant ACS.
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Affiliation(s)
- Usman Baber
- The Zena and Michael A. Wiener Cardiovascular Institute, The Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1030, New York, NY 10029-6574, USA.
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Kok MGM, Meijers JCM, Pinto-Sietsma SJ. Individuals with coronary artery disease at a young age and features of the metabolic syndrome have an increased prothrombotic potential. Thromb Haemost 2013; 111:458-64. [PMID: 24306178 DOI: 10.1160/th13-07-0587] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2013] [Accepted: 10/15/2013] [Indexed: 11/05/2022]
Abstract
The relation between coagulation and atherosclerosis has been extensively described, pointing towards a hypercoagulable state in patients with atherosclerosis, especially in young individuals. However, not all studies were conclusive. It is known that the metabolic syndrome (MetS), a risk factor for coronary artery disease (CAD), is related to a higher incidence of thrombo-embolic events. We hypothesised that individuals with CAD at a young age and MetS have an increased prothrombotic potential. It was the study objective to analyse the endogenous thrombin potential (ETP) and related thrombin generation parameters in patients with CAD before the age of 51 in men and 56 in women with and without MetS features and their healthy first-degree relatives. In this case-control study we included 118 CAD patients and 50 first-degree relatives (controls). Parameters of thrombin generation were obtained with calibrated automated thrombinography. An adjusted general linear model (GLM) showed a positive association between the peak thrombin levels and the presence of CAD at a young age. Based on the NCEP criteria we divided our patient group in CAD patients with and without MetS, and compared them to the controls without MetS. We showed that CAD patients with MetS have increased ETP levels, both in comparison with healthy first-degree relatives and with CAD patients without MetS. There were no differences in ETP between patients without MetS and healthy controls. In conclusion, this study shows that individuals with CAD at a young age and MetS features have an increased prothrombotic potential, compared to CAD patients without MetS.
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Affiliation(s)
| | | | - S-J Pinto-Sietsma
- Dr. Sara-Joan Pinto-Sietsma, MD, PhD,, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, Postbus 22660, Amsterdam 1100 DD, The Netherlands, E-mail:
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Sapkota B, Shrestha SK, Poudel S. Association of activated partial thromboplastin time and fibrinogen level in patients with type II diabetes mellitus. BMC Res Notes 2013; 6:485. [PMID: 24274772 PMCID: PMC4222085 DOI: 10.1186/1756-0500-6-485] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2013] [Accepted: 11/23/2013] [Indexed: 11/28/2022] Open
Abstract
Background Patients with diabetes mellitus have a high risk of atherothrombotic events. Diabetes contributes for initiation and progression of microvascular and macrovascular complications. Shortened activated partial thromboplastin time (aPTT) values may reflect hypercoaguable state, which is associated with increased thrombotic risk and adverse cardiovascular events. Increased level of fibrinogen is common in type II diabetes. The present study was conducted to study the aPTT and fibrinogen levels in diabetics in a tertiary care Teaching Hospital of Nepal. Methods Observational study was performed at out-patients visiting Pathology Department at Tribhuvan University Teaching Hospital from August 5 to September 7, 2012. Research protocol was approved by Institutional Review Board at Tribhuvan University Institute of Medicine. Altogether 90 people who came to the hospital during study period and who met inclusion criteria were selected, out of which 72 were diabetics and 18 were normal controls. Diabetic cases were identified via verbal interview with patients themselves and review of laboratory findings and diagnosis performed by their physicians. Diabetics with a diabetic history of more than one year and stabilized with antidiabetic medicines such as insulin, metformin, glibenclamide, and gliclazide and diabetics with controlled diabetes as revealed by HbA1c in the range 6.2-7% were taken for the study purpose. Data were analyzed with chi square test and Fischer’s exact test (when each cell frequency was less than 5) using Statistical Package for Social Sciences 17. Results Maximum (53; 73.6%) diabetics and all non-diabetics had aPTT in the range 26–40 seconds. Maximum (51; 70.8%) patients had fibrinogen beyond 351 whereas all non-diabetics had fibrinogen in the range 151–350. Mean aPTT values of the diabetic patients and non-diabetic persons were 29.88 ± 4.89 seconds and 32.44 ± 2.25 seconds respectively. Mean fibrinogen values of the diabetic patients and non-diabetic persons were 388.57 ± 60.90 mg/dL and 320.89 ± 10.20 mg/dL respectively. Test data identified in results were statistically significant for aPTT (p value 0.000) and fibrinogen (p value 0.000) between the diabetics and non-diabetics. Conclusions Diabetics have an increased level of fibrinogen and relatively shortened aPTT as compared to the non-diabetic patients.
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Affiliation(s)
- Binaya Sapkota
- Kathmandu University School of Science, Dhulikhel, Kavre, Nepal.
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Llorach R, Urpi-Sarda M, Tulipani S, Garcia-Aloy M, Monagas M, Andres-Lacueva C. Metabolomic fingerprint in patients at high risk of cardiovascular disease by cocoa intervention. Mol Nutr Food Res 2013; 57:962-73. [PMID: 23637065 DOI: 10.1002/mnfr.201200736] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2012] [Revised: 03/01/2013] [Accepted: 03/15/2013] [Indexed: 02/05/2023]
Abstract
SCOPE Metabolomics approach is focused on identifying all metabolites present in a biological sample (metabolome). Consumption of cocoa products has been related to health benefits including positive effect on cardiovascular health. METHODS AND RESULTS Twenty volunteers were included in this randomized, crossover, and controlled clinical trial. After a 2-wk washout period, subjects received 40 g/day of cocoa powder with 500 mL skimmed milk (cocoa with skimmed milk intervention) or 500 mL/day of skimmed milk (skimmed milk intervention) for 4-wk. Urine (24 h) samples were collected at baseline and after each intervention and were analyzed by HPLC-hybrid quadrupole TOF in negative and positive ionization modes followed by multivariate analysis. This analysis revealed a marked separation between the cocoa with skimmed milk intervention and skimmed milk intervention and baseline periods. Thirty-nine compounds linked with cocoa intake, including alkaloid metabolites, polyphenol host and gut microbial metabolites (hydroxyphenylvalerolactones and hydroxyphenylvaleric acids), diketopiperazines and N-phenylpropenoyl-l-amino acids were identified. In the case of endogenous metabolites, putative identifications suggested that metabolites linked with carnitine metabolism and sulfation of tyrosine were decreased by the consumption of cocoa. CONCLUSION LC-MS metabolomics strategy allows the defining of a complex metabolic profile derived from cocoa phytochemicals. Likewise, the identification of endogenous markers could lead to new hypotheses to unravel the relationship between cocoa intake and cardiovascular diseases.
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Affiliation(s)
- Rafael Llorach
- Department of Nutrition and Food Science, XaRTA, INSA, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain
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Zhao Y, Zhang J, Zhang J, Wu J. Diabetes mellitus is associated with shortened activated partial thromboplastin time and increased fibrinogen values. PLoS One 2011; 6:e16470. [PMID: 21297995 PMCID: PMC3030587 DOI: 10.1371/journal.pone.0016470] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2010] [Accepted: 12/16/2010] [Indexed: 11/19/2022] Open
Abstract
OBJECTIVE This study was designed to examine the relationship between shortened activated partial thromboplastin time (APTT) and increased fibrinogen values with diabetes mellitus. METHODS APTT, prothrombin time (PT), fibrinogen, fasting plasma glucose (FPG) and glycosylated hemoglobin A1c (HbA1c) levels were measured in 1,300 patients. Patients were divided into three groups according to their HbA1c and FPG levels. RESULTS When participants were grouped according to their HbA1c levels, we found significantly shorter APTT values (26.9±5.6 s) and increased fibrinogen levels (3.1, 1.9-6.3 g/L) in the diabetes group when compared with the other two groups. When participants were grouped according to their FPG levels, we found significantly shorter APTT values (26.9±6.2 s) and increased fibrinogen levels (3.1, 1.8-6.2 g/L) in the diabetes group when compared with the euglycemic group. CONCLUSIONS Shorter APTT and increased fibrinogen levels might be useful hemostatic markers in patients with diabetes and in patients at high risk for diabetes.
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Affiliation(s)
- Ying Zhao
- Department of Laboratory Medicine, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Jie Zhang
- Department of Laboratory Medicine, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Juanwen Zhang
- Department of Laboratory Medicine, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- * E-mail:
| | - Jianping Wu
- Department of Laboratory Medicine, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
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Ukinc K, Ersoz HO, Erem C, Hacihasanoglu AB, Karti SS. Effects of one year simvastatin and atorvastatin treatments on acute phase reactants in uncontrolled type 2 diabetic patients. Endocrine 2009; 35:380-8. [PMID: 19259830 DOI: 10.1007/s12020-009-9157-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2008] [Revised: 12/13/2008] [Accepted: 01/09/2009] [Indexed: 10/21/2022]
Abstract
Type 2 diabetes mellitus is the leading cause of macrovascular diseases and related death. Additionally, diabetes mellitus is frequently complicated by other cardiovascular risk factors, such as hypercholesterolemia, hypertension, obesity, hypercoagulability, and inflammation. We wanted to evaluate and compare the effects of treating with a one-year course of atorvastatin or simvastatin on inflammatory markers such as high sensitive C-reactive protein (hsCRP), fibrinogen, and ferritin in uncontrolled type 2 diabetic patients. Also, we planned to investigate the correlation between inflammatory markers and metabolic parameters. Fifty type 2 diabetic patients (30 women, 20 men; mean age: 49.9 +/- 8.5 years) were enrolled into the study. Twenty healthy subjects, matched on body mass index and age, were also included in the study as a control group. Diabetic patients were divided into two groups and received simvastatin or atorvastatin (Group S and A, respectively). After 1 year of statin treatment (Group A), there were significant decreases in total cholesterol (217.3 +/- 46.5-173.8 +/- 37.2 mg/dl; P < 0.0001), LDL-cholesterol (146.7 +/- 50.3-102.3 +/- 31.1 mg/dl, P < 0.0001), hsCRP (0.88 +/- 0.62-0.35 +/- 0.18 mg/dl, P < 0.0001), fibrinogen (258.2 +/- 16.9-215.5 +/- 10.6 mg/l; P < 0.0001), and ferritin (118.2 +/- 73.9-81.2 +/- 72.5 ng/ml, P < 0.0001) levels compared to basal values. In the S group, there were significant decreases in total cholesterol (224.4 +/- 61.2-175.0 +/- 47.8 mg/dl; P < 0.0001), LDL-cholesterol (140.9 +/- 56.7-110.9 +/- 42.2 mg/dl, P < 0.0001), hsCRP (0.98 +/- 1.3-0.46 +/- 0.25 mg/dl, P < 0.0001), fibrinogen (265.7 +/- 26.8-222.1 +/- 20.6 mg/l; P < 0.0001), and ferritin (136.7 +/- 101.1-85.6 +/- 32.1 ng/ml, P < 0.0001) levels compared to basal values. At the end of the study, hsCRP, fibrinogen, and ferritin levels were correlated with LDL (r = 0.42; P = 0.005, with hsCRP), (r = 0.40; P = 0.008, with fibrinogen), (r = 0.46; P = 0.002, with ferritin) and HDL (r = -0.50; P < 0.0001, with hsCRP), (r = -0.32; p = 0.042, with fibrinogen), (r = -0.48; P < 0.0001, with ferritin) cholesterol levels. Atorvastatin and simvastatin treatments were found to be effective for the control of hypercholesterolemia and resulted in a significant decrease in acute phase reactants in uncontrolled type 2 diabetic patients.
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Affiliation(s)
- Kubilay Ukinc
- Department of Endocrinology and Metabolism, Karadeniz Technical University, Trabzon, Turkey.
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Tang H, Fu Y, Cui Y, He Y, Zeng X, Ploplis VA, Castellino FJ, Luo Y. Fibrinogen has chaperone-like activity. Biochem Biophys Res Commun 2009; 378:662-7. [PMID: 19059206 PMCID: PMC2663026 DOI: 10.1016/j.bbrc.2008.11.112] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2008] [Accepted: 11/21/2008] [Indexed: 10/21/2022]
Abstract
Partially or completely unfolded polypeptides are highly prone to aggregation due to nonspecific interactions between their exposed hydrophobic surfaces. Extracellular proteins are continuously subjected to stresses conditions, but the existence of extracellular chaperones remains largely unexplored. The results presented here demonstrate that one of the most abundant extracellular proteins, fibrinogen has chaperone-like activity. Fibrinogen can specifically bind to nonnative form of citrate synthase and inhibit its thermal aggregation and inactivation in an ATP-independent manner. Interestingly, fibrinogen maintains thermal-denatured luciferase in a refolding competent state allowing luciferase to be refolded in cooperation with rabbit reticulocyte lysate. Fibrinogen also inhibits fibril formation of yeast prion protein Sup35 (NM). Furthermore, fibrinogen rescues thermal-induced protein aggregation in the plasma of fibrinogen-deficient mice. Our studies demonstrate the chaperone-like activity of fibrinogen, which not only provides new insights into the extracellular chaperone protein system, but also suggests potential diagnostic and therapeutic approaches to fibrinogen-related pathological conditions.
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Affiliation(s)
- Huadong Tang
- National Engineering Laboratory for Anti-tumor Protein Therapeutics Tsinghua University, Beijing 100084, China
- Beijing Key Laboratory for Protein Therapeutics Tsinghua University, Beijing 100084, China
- Laboratory of Protein Chemistry, Department of Biological Sciences & Biotechnology, Tsinghua University, Beijing 100084, China
| | - Yan Fu
- National Engineering Laboratory for Anti-tumor Protein Therapeutics Tsinghua University, Beijing 100084, China
- Beijing Key Laboratory for Protein Therapeutics Tsinghua University, Beijing 100084, China
- Laboratory of Protein Chemistry, Department of Biological Sciences & Biotechnology, Tsinghua University, Beijing 100084, China
| | - Yujie Cui
- National Engineering Laboratory for Anti-tumor Protein Therapeutics Tsinghua University, Beijing 100084, China
- Beijing Key Laboratory for Protein Therapeutics Tsinghua University, Beijing 100084, China
- Laboratory of Protein Chemistry, Department of Biological Sciences & Biotechnology, Tsinghua University, Beijing 100084, China
| | - Yingbo He
- Laboratory of Protein Chemistry, Department of Biological Sciences & Biotechnology, Tsinghua University, Beijing 100084, China
| | - Xing Zeng
- Laboratory of Protein Chemistry, Department of Biological Sciences & Biotechnology, Tsinghua University, Beijing 100084, China
| | - Victoria A. Ploplis
- W.M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, IN 46556, USA
| | - Francis J. Castellino
- W.M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, IN 46556, USA
| | - Yongzhang Luo
- National Engineering Laboratory for Anti-tumor Protein Therapeutics Tsinghua University, Beijing 100084, China
- Beijing Key Laboratory for Protein Therapeutics Tsinghua University, Beijing 100084, China
- Laboratory of Protein Chemistry, Department of Biological Sciences & Biotechnology, Tsinghua University, Beijing 100084, China
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Pieters M, Covic N, van der Westhuizen FH, Nagaswami C, Baras Y, Toit Loots D, Jerling JC, Elgar D, Edmondson KS, van Zyl DG, Rheeder P, Weisel JW. Glycaemic control improves fibrin network characteristics in type 2 diabetes - a purified fibrinogen model. Thromb Haemost 2008; 99:691-700. [PMID: 18392327 PMCID: PMC2854507 DOI: 10.1160/th07-11-0699] [Citation(s) in RCA: 48] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Diabetic subjects have been shown to have altered fibrin network structures. One proposed mechanism for this is non-enzymatic glycation of fibrinogen due to high blood glucose. We investigated whether glycaemic control would result in altered fibrin network structures due to decreased fibrinogen glycation. Twenty uncontrolled type 2 diabetic subjects were treated with insulin in order to achieve glycaemic control. Twenty age- and body mass index (BMI)-matched non-diabetic subjects were included as a reference group. Purified fibrinogen, isolated from plasma samples was used for analysis. There was a significant decrease in fibrinogen glycation (6.81 to 5.02 mol glucose/mol fibrinogen) with a corresponding decrease in rate of lateral aggregation (5.86 to 4.62) and increased permeability (2.45 to 2.85 x 10(-8) cm(2)) and lysis rate (3.08 to 3.27 microm/min) in the diabetic subjects after glycaemic control. These variables correlated with markers of glycaemic control. Fibrin clots of non-diabetic subjects had a significantly higher ratio of inelastic to elastic deformation than the diabetic subjects (0.10 vs. 0.09). Although there was no difference in median fiber diameter between diabetic and non-diabetic subjects, there was a small increase in the proportion of thicker fibers in the diabetic samples after glycaemic control. Results from SDS-PAGE indicated no detectable difference in factor XIIIa-crosslinking of fibrin clots between uncontrolled and controlled diabetic samples. Diabetic subjects may have altered fibrin network formation kinetics which contributes to decreased pore size and lysis rate of fibrin clots. Achievement of glycaemic control and decreased fibrinogen glycation level improves permeability and lysis rates in a purified fibrinogen model.
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Affiliation(s)
- Marlien Pieters
- School of Physiology, Nutrition and Consumer Science, Department Nutrition, North-West University, Potchefstroom Campus, Private Bag X6001, Potchefstroom 2520, South Africa.
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Li XC, Zhuo JL. Targeting glucagon receptor signalling in treating metabolic syndrome and renal injury in Type 2 diabetes: theory versus promise. Clin Sci (Lond) 2007; 113:183-93. [PMID: 17623014 PMCID: PMC2277524 DOI: 10.1042/cs20070040] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Pancreatic bi-hormones insulin and glucagon are the Yin and Yang in the regulation of glucose metabolism and homoeostasis. Insulin is synthesized primarily by pancreatic beta-cells and is released in response to an increase in blood glucose levels (hyperglycaemia). By contrast, glucagon is synthesized by pancreatic alpha-cells and is released in response to a decrease in blood glucose (hypoglycaemia). The principal role of glucagon is to counter the actions of insulin on blood glucose homoeostasis, but it also has diverse non-hyperglycaemic actions. Although Type 1 diabetes is caused by insulin deficiency (insulin-dependent) and can be corrected by insulin replacement, Type 2 diabetes is a multifactorial disease and its treatment is not dependent on insulin therapy alone. Type 2 diabetes in humans is characterized by increased insulin resistance, increased fasting blood glucose, impaired glucose tolerance and the development of glomerular hyperfiltration and microalbuminuria, ultimately leading to diabetic nephropathy and end-stage renal disease. Clinical studies have suggested that an inappropriate increase in hyperglycaemic glucagon (hyperglucagonaemia) over hypoglycaemic insulin (not insulin deficiency until advanced stages) plays an important role in the pathogenesis of Type 2 diabetes. However, for decades, research efforts and resources have been devoted overwhelmingly to studying the role of insulin and insulin-replacement therapy. By contrast, the implication of glucagon and its receptor signalling in the development of Type 2 diabetic metabolic syndromes and end-organ injury has received little attention. The aim of this review is to examine the evidence as to whether glucagon and its receptor signalling play any role(s) in the pathogenesis of Type 2 diabetic renal injury, and to explore whether targeting glucagon receptor signalling remains only a theoretical antidiabetic strategy in Type 2 diabetes or may realize its promise in the future.
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Affiliation(s)
- Xiao C Li
- Laboratory of Receptor and Signal Transduction, Division of Hypertension and Vascular Research, Henry Ford Hospital, Detroit, MI 48202, USA
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The Changes of Coagulation Parameters and Microvascular Complications in Diabetes Mellitus. ACTA ACUST UNITED AC 2007. [DOI: 10.1097/ten.0b013e31813435c1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Tessari P, Kiwanuka E, Barazzoni R, Vettore M, Zanetti M. Diabetic nephropathy is associated with increased albumin and fibrinogen production in patients with type 2 diabetes. Diabetologia 2006; 49:1955-61. [PMID: 16703327 DOI: 10.1007/s00125-006-0288-2] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2005] [Accepted: 03/29/2006] [Indexed: 10/24/2022]
Abstract
AIMS/HYPOTHESIS Hyperfibrinogenaemia and albuminuria are cardiovascular risk factors, often coexisting in diabetic and non-diabetic people. Albuminuria in turn is associated with a compensatory albumin overproduction in non-diabetic patients. It is not known whether the presence of albuminuria in patients with type 2 diabetes mellitus is associated with greater albumin and fibrinogen production rates than in normoalbuminuric patients. SUBJECTS, MATERIALS, AND METHODS: Using leucine isotope methods, we measured fractional and absolute synthesis rates (FSR, ASR) of albumin and fibrinogen in post-absorptive type 2 diabetic patients with either normal (n=11) or increased (n=10) urinary albumin excretion. RESULTS In albuminuric patients, albumin FSR (16.2+/-1.5%/day) and ASR (20.5+/-1.9 g/day) were greater (p<0.02 and p<0.05, respectively) than in normoalbuminuric patients (FSR=11.5+/-1.1%/day; ASR=15.7+/-1.2 g/day). Fibrinogen FSR was similar between patients with normal and increased albumin excretion, but concentration, the circulating pool and ASR of fibrinogen were 40 to 50% greater (p<0.035) in patients with albuminuria. Albuminuria was positively correlated with albumin ASR, with fibrinogen concentration, the fibrinogen pool and ASR, whereas albumin synthesis was inversely correlated with calculated oncotic pressure. CONCLUSIONS/INTERPRETATION Synthesis of albumin and fibrinogen is upregulated in type 2 diabetic patients with increased urinary albumin excretion. Albuminuria is associated with enhanced fibrinogen and albumin synthesis.
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Affiliation(s)
- P Tessari
- Department of Clinical and Experimental Medicine, Metabolism Division, University of Padua, Padua, Italy.
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Tessari P, Kiwanuka E, Millioni R, Vettore M, Puricelli L, Zanetti M, Gucciardi A, Tosolini M, Cogo P, Carnielli V, Tiengo A, Barazzoni R. Albumin and fibrinogen synthesis and insulin effect in type 2 diabetic patients with normoalbuminuria. Diabetes Care 2006; 29:323-8. [PMID: 16443881 DOI: 10.2337/diacare.29.02.06.dc05-0226] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Insulin stimulates albumin synthesis but inhibits that of fibrinogen in both type 1 diabetic and healthy subjects. In type 2 diabetes, fibrinogen production is increased both in the postabsorptive state and in response to hyperinsulinemia. No data exist on the rate of albumin synthesis and its response to insulin in type 2 diabetes. RESEARCH DESIGN AND METHODS We measured fractional synthesis rates (FSRs) and absolute synthesis rates (ASRs) of both albumin and fibrinogen in postabsorptive normoalbuminuric type 2 diabetic patients at their spontaneous glucose levels (study A), as well as albumin FSR and ASR before and after a hyperinsulinemic-euglycemic euaminoacidemic clamp (study B), using leucine isotope methods. RESULTS In postabsorptive type 2 diabetes (study A), albumin FSR (11.2 +/- 0.9%/day) and albumin ASR (15.4 +/- 1.2 g/day) were not different from control values (albumin FSR: 9.4 +/- 0.7%/day; albumin ASR: 13.8 +/- 1.2 g/day, P > 0.1 for both). In contrast, in the type 2 diabetic subjects, both fibrinogen FSR (24.9 +/- 2.1%/day) and ASR (2.4 +/- 0.2 g/day) were greater (P < 0.025 and P < 0.007, respectively) compared with the control subjects (FSR: 18.6 +/- 1.51%/day; ASR: 1.6 +/- 0.2 g/day). Worse metabolic control in the type 2 diabetic patients was associated with hyperfibrinogenemia and increased leucine rate of appearance, whereas neither the (increased) fibrinogen ASR nor the (normal) albumin production was affected. In study B, after hyperinsulinemia (raised to approximately 860 nmol/l), albumin FSR and ASR increased by approximately 25% versus basal (P < 0.04) and to the same extent in both type 2 diabetic and control subjects. CONCLUSIONS In normoalbuminuric type 2 diabetic patients, postabsorptive albumin synthesis and its response to insulin were normal, whereas fibrinogen synthesis was increased, irrespective of metabolic control. Furthermore, in normoalbuminuric type 2 diabetic patients, a normal insulin sensitivity with respect to albumin production but a selective hepatic dysregulation of fibrinogen metabolism were present.
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Affiliation(s)
- Paolo Tessari
- Department of Clinical and Experimental Medicine, Chair of Metabolism, Policlinico Universitario, Via Giustiniani 2, 35128 Padova, Italy.
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Barazzoni R, Kiwanuka E, Zanetti M, Cristini M, Vettore M, Tessari P. Insulin acutely increases fibrinogen production in individuals with type 2 diabetes but not in individuals without diabetes. Diabetes 2003; 52:1851-6. [PMID: 12829656 DOI: 10.2337/diabetes.52.7.1851] [Citation(s) in RCA: 40] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Fibrinogen is an acute-phase reactant and an independent cardiovascular risk factor. Insulin without amino acid replacement acutely suppressed fibrinogen production in nondiabetic and type 1 diabetic individuals. Fibrinogen production and plasma concentration increase in insulin-resistant type 2 diabetes. It is not known whether altered response to insulin contributes to hyperfibrinogenemia in type 2 diabetes. Fibrinogen fractional (FSR) and absolute (ASR) synthesis rates were measured using a leucine isotopic model in type 2 diabetic men (n = 7; age = 51 +/- 3 years; BMI = 26.7 +/- 1 kg/m(2)) compared with matched nondiabetic subjects under basal conditions and following a 4-h euglycemic-, euaminoacidemic-hyperinsulinemic clamp. Basal fibrinogen concentration (+35%, P < 0.05) and ASR (+35%, P < 0.05) were greater in the diabetic subjects. Following clamp, fibrinogen FSR and ASR were unchanged in the control subjects. In contrast, fibrinogen FSR and ASR increased by 41 and 43%, respectively (P < 0.05), in the diabetic subjects. Thus, fibrinogen production is acutely increased by insulin when euglycemia and euaminoacidemia are maintained in type 2 diabetic individuals but not in nondiabetic individuals. Enhanced fibrinogen production by insulin is likely to be a key alteration contributing to hyperfibrinogenemia and therefore cardiovascular risk in type 2 diabetes. Unchanged fibrinogen production in nondiabetic individuals suggests a role of plasma amino acids in regulating fibrinogen production in humans.
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Affiliation(s)
- Rocco Barazzoni
- Department of Clinical and Experimental Medicine, University of Padova, Padua, Italy
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