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Wang H, Ye J, Chen Y, Sun Y, Gong X, Deng H, Dong Z, Xu L, Li X, Zhong B. High sensitivity C-reactive protein implicates heterogeneous metabolic phenotypes and severity in metabolic dysfunction associated-steatotic liver disease. BMC Gastroenterol 2025; 25:231. [PMID: 40200156 PMCID: PMC11980055 DOI: 10.1186/s12876-025-03778-2] [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: 09/09/2024] [Accepted: 03/12/2025] [Indexed: 04/10/2025] Open
Abstract
BACKGROUND Whether include high-sensitivity C-reactive protein (Hs-CRP) in diagnostic flow remains debatable during the updated definition to metabolic dysfunction-associated steatotic liver disease (MASLD) despite systemic inflammation contributes to the disease development and progression. We aimed to identify values of hs-CRP compared to other inflammatory markers derived from routine blood tests in MASLD. MATERIALS AND METHODS This cross-sectional study included consecutive participants (ultrasound-diagnosed MASLD: 1,006, healthy controls: 582), and 175 patients received liver biopsy., with 733 and 310 patients underwent magnetic resonance imaging proton density fat fraction for liver fat content (LFC) quantification and two-dimensional shear-wave elastography liver stiffness measurements (LSM), respectively. RESULTS Multiple linear regression analysis revealed a significant positive association between hs-CRP and LFC among overweight/obesity group patients (β 0.19, P = 0.03), and LSM among lean/normal weight group (β 0.30, P < 0.001). For the metabolic dysfunction-associated steatohepatitis (MASH), the hs-CRP and the ratio of monocytes to high-density lipoprotein both performed well in the overweight/obesity group and type 2 diabetes group (Overweight/obesity group, hs-CPR AUC 0.65 and 0.74, P = 0.02), bu no valuable inflammatory indicators were observed in MASH and liver fibrosis. CONCLUSION Hs-CRP levels are associated with LFC in overweight/obese MASLD and liver stiffness in lean MASLD patients, yet the reported AUC values suggest weak predictive ability. TRIAL REGISTRATION The study protocol was registered at the Chinese Clinical Trial Registry, (ChiCTR-ChiCTR2000034197), approved by the First Affiliated Hospital of Sun Yat-sen University institutional with the regional medical ethics committees (Approval number: [2020] No. 187), and performed in accordance with the ethical standards of the 1964 Declaration of Helsinki. Written informed consent was obtained from all the patients.
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Affiliation(s)
- Hao Wang
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Yuexiu District, No. 58 Zhongshan II Road, Guangzhou, 510080, China
- Department of Infectious Diseases, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, 518107, China
| | - Junzhao Ye
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Yuexiu District, No. 58 Zhongshan II Road, Guangzhou, 510080, China
| | - Youpeng Chen
- Department of Infectious Diseases, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, 518107, China
| | - Yanhong Sun
- Department of Clinical Laboratory, The East Division of the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China
| | - Xiaorong Gong
- Department of Gastroenterology, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510000, Guangdong, China
| | - Hong Deng
- Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Zhiyong Dong
- The First Affiliated Hospital of Jinan University, Guangzhou, 510632, China
| | - Lishu Xu
- Department of Gastroenterology and Hepatology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, and Guangdong Provincial Geriatrics Institute, No. 106 Zhongshan II Road, Yuexiu District, Guangzhou, China
| | - Xin Li
- Department of Gastroenterology, The Tenth Affiliated of Southern Medical University (Dongguan People'S Hospital), Dongguan, 516000, Guangdong, China.
| | - Bihui Zhong
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Yuexiu District, No. 58 Zhongshan II Road, Guangzhou, 510080, China.
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Xie S, Kutalik Z, Thomas A, Perrais M, Vaucher J, Marques-Vidal P. Urinary Copper Is Associated with Dyslipidemia, and This Association Is Mediated by Inflammation. Biol Trace Elem Res 2025:10.1007/s12011-025-04581-6. [PMID: 40172775 DOI: 10.1007/s12011-025-04581-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2025] [Accepted: 03/12/2025] [Indexed: 04/04/2025]
Abstract
Dyslipidemia is an important public health issue. Copper may influence lipid metabolism, possibly via inflammation, but the mechanisms remain unclear. This study aimed to assess the association between urinary copper concentrations and blood lipids (total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG)), and the possible mediating role of inflammation, assessed via high-sensitivity C-reactive protein (hs-CRP). We conducted a cross-sectional, population-based study using baseline data from Switzerland's CoLaus|PsyCoLaus cohort. Urinary copper was measured from spot urine using inductively coupled plasma mass spectrometry and adjusted for creatinine. Lipid markers and hs-CRP were measured using standardized biochemical assays. Multiple linear regression assessed associations, and mediation effects were evaluated using the SGmediation2 package. A total of 6284 adults (mean age 52.6 years, 53.4% female) were included. Urinary copper was positively associated with TG (beta=0.08, 95%CI 0.04, 0.12) and negatively associated with HDL-C (- 0.04, 95%CI - 0.07, - 0.003). Additionally, urinary copper was positively associated with hs-CRP (0.51, 95%CI 0.42, 0.60), which in turn was positively associated with TG (0.05, 95%CI 0.04, 0.06) and negatively associated with HDL-C (- 0.04, 95%CI - 0.05, - 0.03). Mediation analysis revealed that urinary copper exerts partial indirect effects on TG (mediation effect 31.4%) and HDL-C (56.9%) through hs-CRP. hs-CRP partially mediated the associations between urinary copper and HDL-C and TG, with a robust effect for TG but statistical uncertainty for HDL-C. No mediation was observed for TC or LDL-C. These findings suggest hs-CRP's role in lipid metabolism, especially in TG regulation.
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Grants
- grants 33CSCO-122661, 33CS30-139468, 33CS30-148401, 33CS30_177535, 31003A-182420, and 3247730_204523 Swiss National Science Foundation
- grants 33CSCO-122661, 33CS30-139468, 33CS30-148401, 33CS30_177535, 31003A-182420, and 3247730_204523 Swiss National Science Foundation
- grants 33CSCO-122661, 33CS30-139468, 33CS30-148401, 33CS30_177535, 31003A-182420, and 3247730_204523 Swiss National Science Foundation
- grants 33CSCO-122661, 33CS30-139468, 33CS30-148401, 33CS30_177535, 31003A-182420, and 3247730_204523 Swiss National Science Foundation
- grant 2018DRI01 Swiss Personalized Health Network
- grant 2018DRI01 Swiss Personalized Health Network
- grant 2018DRI01 Swiss Personalized Health Network
- grant 2018DRI01 Swiss Personalized Health Network
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Affiliation(s)
- Sisi Xie
- Department of Medicine, Internal Medicine, Lausanne University Hospital (CHUV) and University of Lausanne, Rue du Bugnon 46, 1011, Lausanne, Switzerland
| | - Zoltan Kutalik
- Department of Computational Biology, University of Lausanne, 1015, Lausanne, Switzerland
- Center for Primary Care and Public Health, University of Lausanne, 1010, Lausanne, Switzerland
- Swiss Institute of Bioinformatics, 1015, Lausanne, Switzerland
| | - Aurélien Thomas
- Unit of Forensic Chemistry and Toxicology, University Centre of Legal Medicine Lausanne-Geneva, Geneva University Hospital and University of Geneva, Rue Michel-Servet 1, 1211, Geneva, Switzerland
- Faculty Unit of Toxicology, University Centre of Legal Medicine Lausanne-Geneva, Lausanne University Hospital and University of Lausanne, Chemin de La Vulliette 4, 1000, Lausanne, Switzerland
| | - Maïwenn Perrais
- Unit of Forensic Chemistry and Toxicology, University Centre of Legal Medicine Lausanne-Geneva, Geneva University Hospital and University of Geneva, Rue Michel-Servet 1, 1211, Geneva, Switzerland
- Faculty Unit of Toxicology, University Centre of Legal Medicine Lausanne-Geneva, Lausanne University Hospital and University of Lausanne, Chemin de La Vulliette 4, 1000, Lausanne, Switzerland
| | - Julien Vaucher
- Department of Medicine, Internal Medicine, Lausanne University Hospital (CHUV) and University of Lausanne, Rue du Bugnon 46, 1011, Lausanne, Switzerland
- Department of Internal Medicine and Specialties, Internal Medicine, Fribourg Hospital and University of Fribourg, Fribourg, Switzerland
| | - Pedro Marques-Vidal
- Department of Medicine, Internal Medicine, Lausanne University Hospital (CHUV) and University of Lausanne, Rue du Bugnon 46, 1011, Lausanne, Switzerland.
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Wang T, Zhang M, Shi W, Li Y, Zhang T, Shi W. Atherogenic index of plasma, high sensitivity C-reactive protein and incident diabetes among middle-aged and elderly adults in China: a national cohort study. Cardiovasc Diabetol 2025; 24:103. [PMID: 40045300 PMCID: PMC11883954 DOI: 10.1186/s12933-025-02653-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2024] [Accepted: 02/17/2025] [Indexed: 03/09/2025] Open
Abstract
BACKGROUND The atherogenic index of plasma (AIP) and systematic inflammation, as measured by high-sensitivity C-reactive protein (hsCRP), are predictors of diabetes, but their combined impacts on incident diabetes are poorly understood. Using a nationally representative cohort in China, we aimed to investigate the association of AIP and hsCRP with incident diabetes among middle-aged and elderly adults. METHODS This cohort comprised 9,112 participants aged at least 45 years from 125 cities in the China Health and Retirement Longitudinal Study who were free of diabetes at baseline in 2011. Of these, 5,048 participants were followed up until 2015. The AIP was calculated as Log10[TG (mg/dL)/HDL-C(mg/dL)]. Multivariate logistic regression and linear mixed-effect (LME) models were performed to evaluate the associations of AIP, hsCRP, and incident diabetes as well as glycemic biomarkers. Receiver operating characteristic (ROC) curves were used to evaluate their diagnostic values. We conducted a mediation analysis to assess the direct and indirect associations between AIP and hsCRP with diabetes. RESULTS 489 (9.7%) cases developed diabetes during four years. Higher levels of AIP and hsCRP were independently associated with diabetes. Compared to the lowest quartile of AIP or hsCRP, the highest quartile of AIP (adjusted odds ratio, aOR 2.53, 95% CI: 1.90-3.38) and hsCRP (aOR 2.38, 1.79-3.16) was significantly associated with incident diabetes. The joint effects showed that participants with higher levels of AIP and hsCRP had significantly higher aOR of 2.76 (2.13-3.57). The LME models showed AIP and hsCRP were related to an increased level of fasting blood glucose and glycated hemoglobin. The combination of AIP and hsCRP has better predictive efficacy (area under the curve, AUC: 0.628, 0.601-0.654) for incident diabetes than alone. Mediation analyses showed that high AIP significantly mediated 25.4% of the association between hsCRP and diabetes, and hsCRP simultaneously mediated 5.7% of the association between AIP and diabetes. CONCLUSIONS This cohort suggests combined effects and mutual mediation between the AIP and hsCRP on incident diabetes in China. Our findings provide clinical implications for monitoring and managing AIP and hsCRP levels to mitigate the development of diabetes.
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Affiliation(s)
- Tongshuai Wang
- Hongqiao International Institute of Medicine, Shanghai Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200336, China
- Clinical Research Unit Office, Tongren Hospital Shanghai Jiao Tong University School of Medicine, 200336, Shanghai, China
| | - Mengru Zhang
- Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, Jiangsu, China
| | - Wenxing Shi
- Department of Pharmaceutical and Biomedical Engineering, Clinical College of Anhui Medical University, Anhui, 230031, China
| | - Yongzhen Li
- Clinical Nutrition Department, Starkids Children's Hospital, Shanghai, New Hong Qiao Campus for Children's Hospital of Fudan University, Shanghai, 201106, China
- School of Public Health, Peking University, Beijing, 100191, China
| | - Tiantian Zhang
- School of Public Health, Fudan University, Shanghai, 200032, China
| | - Wenming Shi
- Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, No. 2699 West Gaoke Road, Pudong New District, Shanghai, 201204, China.
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Shi WP, Jiang YP, Wu TY, Wang YZ, Zhang YZ, Li T. Does obesity affect the diagnostic value of various biomarkers for periprosthetic joint infections? A single center retrospective study. Front Cell Infect Microbiol 2025; 15:1483503. [PMID: 40041151 PMCID: PMC11876556 DOI: 10.3389/fcimb.2025.1483503] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Accepted: 01/23/2025] [Indexed: 03/06/2025] Open
Abstract
Objective The aim of this study was to examine the impact of obesity on the diagnosis of periprosthetic joint infections (PJI) by assessing the levels and diagnostic efficacy of biomarkers. Methods A total of 254 patients were divided into obese group (n=59) and non-obese group (n=195) according to BMI. Each group was further divided into the PJI group and the AF group. Data on CRP, ESR, fibrinogen, D-dimer, CRP-albumin ratio (CAR), CRP-lymphocyte ratio (CLR), and CRP-monocyte ratio (CMR) were collected from all patients. ROC curve was performed to evaluate the diagnostic values of these biomarkers. Results The levels of biomarkers were significantly higher in PJI patients compared to the AF patients in both the obese and non-obese groups (P < 0.001), but the levels of biomarkers were similar between the obese and non-obese groups. In the obese group, CRP exhibited the highest diagnostic value (AUC=0.982). In the non-obese group, CAR demonstrated the highest diagnostic value (AUC =0.935). Subgroup analysis showed no significant differences in biomarker levels (P > 0.05). Conclusions Obesity did not affect biomarker levels in patients with PJI. But for obese patients, the diagnostic thresholds for CRP and ESR are higher, and clinical diagnosis should be careful to avoid false positives. CRP and CAR were identified as the most effective biomarkers for diagnosing PJI in the obese and non-obese groups, respectively.
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Affiliation(s)
- Wei-peng Shi
- Department of Orthopaedic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Ya-ping Jiang
- Department of Oral Implantology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Ting-yu Wu
- Department of Orthopaedic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Ying-zhen Wang
- Department of Orthopaedic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Ying-ze Zhang
- Department of Orthopaedic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
- Department of Orthopaedics, The Third Hospital of Hebei Medical University, Shijiazhuang, China
| | - Tao Li
- Department of Orthopaedic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
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Pan J, Cai X, Chen J, Xu M, Hu J, Mao Y, Chen T, Li L, Jin M, Chen L. Association Between High-Sensitivity C-Reactive Protein Trajectories and the Incidence of Metabolic Syndrome:A Retrospective Cohort Study. J Inflamm Res 2024; 17:8501-8511. [PMID: 39534057 PMCID: PMC11556323 DOI: 10.2147/jir.s493111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Accepted: 11/01/2024] [Indexed: 11/16/2024] Open
Abstract
Purpose Understanding the role of systemic inflammation in the development of Metabolic Syndrome (MetS) is crucial for identifying individuals at a higher risk of this cluster of conditions that increase the risk of heart disease, stroke, and diabetes. Patients and Methods A retrospective cohort study was conducted with 4,312 participants who were free from MetS at the study's onset and had high-sensitivity C-reactive protein (hsCRP) levels measured. Latent class trajectory modeling was utilized to identify distinct hsCRP trajectory patterns. Multivariable regression and proportional hazards analyses were employed to evaluate the predictive value of hsCRP trajectories for the development of MetS. Results During the 1.63-year follow-up period, 1,308 participants developed metabolic syndrome (MetS). Individuals with high hsCRP levels exhibited a significantly increased risk of developing MetS compared to those with low hsCRP levels (HR = 1.062, 95% CI 1.103-1.113). The hsCRP trajectory analysis identified three distinct groups: low-stable, increasing, and decreasing. The decreasing and increasing hsCRP trajectory groups demonstrated a 1.408-fold (95% CI 1.115-1.779) and a 1.618-fold (95% CI 1.288-2.033) increased risk of MetS, respectively. Conclusion This study suggests that participants with higher baseline hsCRP levels and increasing hsCRP trajectories are associated with a progression toward MetS. Long-term hsCRP trajectories may serve as useful tools for identifying individuals at higher risk of MetS who could benefit from targeted preventive and therapeutic interventions.
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Affiliation(s)
- JianJiang Pan
- Department of General Practice, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310020, People’s Republic of China
| | - XiXuan Cai
- Department of General Practice, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310020, People’s Republic of China
| | - JieRu Chen
- Department of General Practice, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310020, People’s Republic of China
| | - MingYing Xu
- Department of General Practice, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310020, People’s Republic of China
| | - JingYu Hu
- Department of General Practice, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310020, People’s Republic of China
| | - YueChun Mao
- Department of General Practice, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310020, People’s Republic of China
| | - Tao Chen
- Department of General Practice, Jianqiao Community Health Service Center, Hangzhou, Zhejiang, 310021, People’s Republic of China
| | - LuSha Li
- Department of General Practice, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310020, People’s Republic of China
| | - MengQi Jin
- Department of General Practice, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310020, People’s Republic of China
| | - LiYing Chen
- Department of General Practice, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310020, People’s Republic of China
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Yu L, Que T, Zhou Y, Liu Z. Dose-response relationship of serum ferritin and dietary iron intake with metabolic syndrome and non-alcoholic fatty liver disease incidence: a systematic review and meta-analysis. Front Nutr 2024; 11:1437681. [PMID: 39410926 PMCID: PMC11476413 DOI: 10.3389/fnut.2024.1437681] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Accepted: 09/09/2024] [Indexed: 10/19/2024] Open
Abstract
Aim This study aims to assess the dose-response impact of iron load on systemic and hepatic metabolic disorders including metabolic syndrome (MetS) and non-alcoholic fatty liver disease (NAFLD). Methods Serum ferritin (SF) and dietary iron intake were selected to represent the indicators of iron load in the general population. PubMed, EMBASE and Web of Science databases were searched for epidemiological studies assessing the impact of SF/dietary iron intake on MetS/NAFLD occurrence. All literature was published before September 1st, 2023 with no language restrictions. Results Fifteen and 11 papers were collected with a focus on connections between SF and MetS/NAFLD, respectively. Eight papers focusing on dietary iron and MetS were included in the following meta-analysis. For the impact of SF on MetS, the pooled odds ratio (OR) of MetS was 1.88 (95% CI: 1.58-2.24) for the highest versus lowest SF categories. In males, the OR was 1.15 (95% CI: 1.10-1.21) per incremental increase in SF of 50 μg/L, while for females, each 50 μg/L increase in SF was associated with a 1.50-fold higher risk of MetS (95% CI: 1.15-1.94). For connections between SF and NAFLD, we found higher SF levels were observed in NAFLD patients compared to the control group [standardized mean difference (SMD) 0.71; 95% CI: 0.27-1.15], NASH patients against control group (SMD1.05; 95% CI:0.44-1.66), NASH patients against the NAFLD group (SMD 0.6; 95% CI: 0.31-1.00), each 50 μg/L increase in SF was associated with a 1.08-fold higher risk of NAFLD (95% CI: 1.07-1.10). For the impact of dietary iron on MetS, Pooled OR of MetS was 1.34 (95% CI: 1.10-1.63) for the highest versus lowest dietary iron categories. Conclusion Elevated SF levels is a linear relation between the incidence of MetS/NAFLD. In addition, there is a positive association between dietary iron intake and metabolic syndrome. The association between serum ferritin and metabolic syndrome may be confounded by body mass index and C-reactive protein levels.
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Affiliation(s)
- Lu Yu
- School of Medicine, Zhejiang Chinese Medical University, Hangzhou, China
- Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
- Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
- Shulan (Hangzhou) Hospital, Hangzhou, China
| | - Ting Que
- Birth Defects Prevention and Control Institute, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
| | - Yifeng Zhou
- Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
| | - Zhengtao Liu
- Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
- Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
- Shulan (Hangzhou) Hospital, Hangzhou, China
- NHC Key Laboratory of Combined Multi-organ Transplantation, Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, School of Medicine, Chinese Academy of Medical Sciences, First Affiliated Hospital, Zhejiang University, Hangzhou, China
- Key Laboratory of Organ Transplantation, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
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Gholami M, Coleman-Fuller N, Salehirad M, Darbeheshti S, Motaghinejad M. Neuroprotective Effects of Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors (Gliflozins) on Diabetes-Induced Neurodegeneration and Neurotoxicity: A Graphical Review. Int J Prev Med 2024; 15:28. [PMID: 39239308 PMCID: PMC11376549 DOI: 10.4103/ijpvm.ijpvm_5_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Accepted: 02/20/2024] [Indexed: 09/07/2024] Open
Abstract
Diabetes is a chronic endocrine disorder that negatively affects various body systems, including the nervous system. Diabetes can cause or exacerbate various neurological disorders, and diabetes-induced neurodegeneration can involve several mechanisms such as mitochondrial dysfunction, activation of oxidative stress, neuronal inflammation, and cell death. In recent years, the management of diabetes-induced neurodegeneration has relied on several types of drugs, including sodium-glucose cotransporter-2 (SGLT2) inhibitors, also called gliflozins. In addition to exerting powerful effects in reducing blood glucose, gliflozins have strong anti-neuro-inflammatory characteristics that function by inhibiting oxidative stress and cell death in the nervous system in diabetic subjects. This review presents the molecular pathways involved in diabetes-induced neurodegeneration and evaluates the clinical and laboratory studies investigating the neuroprotective effects of gliflozins against diabetes-induced neurodegeneration, with discussion about the contributing roles of diverse molecular pathways, such as mitochondrial dysfunction, oxidative stress, neuro-inflammation, and cell death. Several databases-including Web of Science, Scopus, PubMed, Google Scholar, and various publishers, such as Springer, Wiley, and Elsevier-were searched for keywords regarding the neuroprotective effects of gliflozins against diabetes-triggered neurodegenerative events. Additionally, anti-neuro-inflammatory, anti-oxidative stress, and anti-cell death keywords were applied to evaluate potential neuronal protection mechanisms of gliflozins in diabetes subjects. The search period considered valid peer-reviewed studies published from January 2000 to July 2023. The current body of literature suggests that gliflozins can exert neuroprotective effects against diabetes-induced neurodegenerative events and neuronal dysfunction, and these effects are mediated via activation of mitochondrial function and prevention of cell death processes, oxidative stress, and inflammation in neurons affected by diabetes. Gliflozins can confer neuroprotective properties in diabetes-triggered neurodegeneration, and these effects are mediated by inhibiting oxidative stress, inflammation, and cell death.
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Affiliation(s)
- Mina Gholami
- Chronic Respiratory Disease Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Natalie Coleman-Fuller
- Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN, USA
| | - Mahsa Salehirad
- Chronic Respiratory Disease Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sepideh Darbeheshti
- Chronic Respiratory Disease Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Majid Motaghinejad
- Chronic Respiratory Disease Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Mesa RA, Damas OM, Schneiderman N, Palacio AM, Gallo LC, Talavera GA, Sotres-Alvarez D, Daviglus ML, Pirzada A, Llabre MM, Elfassy T. Association Between High-Sensitivity C-Reactive Protein and Metabolic Syndrome Among Hispanic/Latino Participants of the Hispanic Community Health Study/Study of Latinos. Metab Syndr Relat Disord 2024; 22:327-336. [PMID: 38563777 DOI: 10.1089/met.2023.0298] [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: 04/04/2024] Open
Abstract
Purpose: To determine whether high-sensitivity C-reactive protein (hsCRP) is associated with incident Metabolic Syndrome (MetS) among U.S. Hispanic/Latino adults. Patients and Methods: The Hispanic Community Health Study/Study of Latinos is a longitudinal observational cohort assessing cardiovascular health among diverse U.S. Hispanic/Latino adults. hsCRP was measured at visit 1 (2008-2011) and classified as low, moderate, or high, based on the Centers for Disease Control and Prevention and American Heart Association (CDC/AHA) guidelines. All MetS components [abdominal obesity, triglycerides, high-density lipoprotein (HDL) cholesterol, blood pressure, and fasting glucose] were measured at visit 1 and visit 2 (2014-2017). MetS was defined as the presence of three or more components based on the 2005 definition from the modified Third Report of the National Cholesterol Education Program Adult Treatment Panel (modified NCEP ATP III). Participants free of MetS at visit 1 and with complete data on hsCRP and all MetS components were included (n = 6121 participants). We used Poisson regression analysis to determine whether hsCRP was associated with incident MetS after adjusting for demographic, behavioral, and clinical factors. All analyses accounted for the complex survey design of the study. Results: In fully adjusted models, moderate versus low hsCRP was associated with a 33% increased risk of MetS [incidence rate ratio (IRR): 1.33, 95% confidence interval (CI): 1.10-1.61], while high versus low hsCRP was associated with a 89% increased risk of MetS (IRR: 1.89, 95% CI: 1.58-2.25). Conclusions: Greater levels of hsCRP were associated with new onset of MetS in a diverse sample of U.S. Hispanic/Latino adults. Results suggest that hsCRP may be an independent risk factor for MetS.
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Affiliation(s)
- Robert A Mesa
- Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Oriana M Damas
- Division of Gastroenterology, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA
| | | | - Ana M Palacio
- Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Linda C Gallo
- Department of Psychology, San Diego State University, San Diego, California, USA
| | - Gregory A Talavera
- Department of Psychology, Graduate School of Public Health, San Diego State University, San Diego, California, USA
| | - Daniela Sotres-Alvarez
- Collaborative Studies Coordinating Center, Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Martha L Daviglus
- Institute for Minority Health Research, University of Illinois Chicago, Chicago, Illinois, USA
| | - Amber Pirzada
- Institute for Minority Health Research, University of Illinois Chicago, Chicago, Illinois, USA
| | - Maria M Llabre
- Department of Psychology, University of Miami, Miami, Florida, USA
| | - Tali Elfassy
- Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA
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9
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Rolver MG, Emanuelsson F, Nordestgaard BG, Benn M. Contributions of elevated CRP, hyperglycaemia, and type 2 diabetes to cardiovascular risk in the general population: observational and Mendelian randomization studies. Cardiovasc Diabetol 2024; 23:165. [PMID: 38730445 PMCID: PMC11088022 DOI: 10.1186/s12933-024-02207-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Accepted: 03/18/2024] [Indexed: 05/12/2024] Open
Abstract
OBJECTIVE To investigate the contributions of low-grade inflammation measured by C-reactive protein (CRP), hyperglycaemia, and type 2 diabetes to risk of ischemic heart disease (IHD) and cardiovascular disease (CVD) death in the general population, and whether hyperglycaemia and high CRP are causally related. RESEARCH DESIGN AND METHODS Observational and bidirectional, one-sample Mendelian randomization (MR) analyses in 112,815 individuals from the Copenhagen General Population Study and the Copenhagen City Heart Study, and bidirectional, two-sample MR with summary level data from two publicly available consortia, CHARGE and MAGIC. RESULTS Observationally, higher plasma CRP was associated with stepwise higher risk of IHD and CVD death, with hazard ratios and 95% confidence intervals (95%CI) of 1.50 (1.38, 1.62) and 2.44 (1.93, 3.10) in individuals with the 20% highest CRP concentrations. The corresponding hazard ratios for elevated plasma glucose were 1.10 (1.02, 1.18) and 1.22 (1.01, 1.49), respectively. Cumulative incidences of IHD and CVD death were 365% and 592% higher, respectively, in individuals with both type 2 diabetes and plasma CRP ≥ 2 mg/L compared to individuals without either. Plasma CRP and glucose were observationally associated (β-coefficient: 0.02 (0.02, 0.03), p = 3 × 10- 20); however, one- and two-sample MR did not support a causal effect of CRP on glucose (-0.04 (-0.12, 0.32) and - 0.03 (-0.13, 0.06)), nor of glucose on CRP (-0.01 (-0.08, 0.07) and - 0.00 (-0.14, 0.13)). CONCLUSIONS Elevated concentrations of plasma CRP and glucose are predictors of IHD and CVD death in the general population. We found no genetic association between CRP and glucose, or vice versa, suggesting that lowering glucose pharmacologically does not have a direct effect on low-grade inflammation.
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Affiliation(s)
- Monica G Rolver
- Department of Clinical Biochemistry, Copenhagen University Hospital - Herlev Gentofte, Borgmester Ib Juuls Vej 1, Herlev, 2730, Denmark
- Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, Copenhagen, 2200, Denmark
| | - Frida Emanuelsson
- Department of Clinical Biochemistry, Copenhagen University Hospital - Herlev Gentofte, Borgmester Ib Juuls Vej 1, Herlev, 2730, Denmark
- Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, Copenhagen, 2200, Denmark
| | - Børge G Nordestgaard
- Department of Clinical Biochemistry, Copenhagen University Hospital - Herlev Gentofte, Borgmester Ib Juuls Vej 1, Herlev, 2730, Denmark
- Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, Copenhagen, 2200, Denmark
- Department of Clinical Biochemistry, Copenhagen University Hospital - Herlev Gentofte, Borgmester Ib Juuls Vej 1, Herlev, 2730, Denmark
- The Copenhagen General Population Study, Copenhagen University Hospital - Herlev Gentofte, Borgmester Ib Juuls Vej 1, Herlev, 2730, Denmark
| | - Marianne Benn
- Department of Clinical Biochemistry, Copenhagen University Hospital - Herlev Gentofte, Borgmester Ib Juuls Vej 1, Herlev, 2730, Denmark.
- Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, Copenhagen, 2200, Denmark.
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10
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Bernhardsen GP, Thomas O, Mäntyselkä P, Niskanen L, Vanhala M, Koponen H, Lehto SM. Metabolites and depressive symptoms: Network- and longitudinal analyses from the Finnish Depression and Metabolic Syndrome in Adults (FDMSA) Study. J Affect Disord 2024; 347:199-209. [PMID: 38000471 DOI: 10.1016/j.jad.2023.11.070] [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: 03/16/2023] [Revised: 10/20/2023] [Accepted: 11/18/2023] [Indexed: 11/26/2023]
Abstract
BACKGROUND Depression is associated with metabolic abnormalities linked to metabolic syndrome and tissue inflammation, but the interplay between metabolic markers and their association with subsequent depression is unknown. Therefore, we aimed to describe the network of metabolites and their prospective association with depressive symptoms. METHODS The Finnish Depression and Metabolic Syndrome in Adults (FDMSA) cohort, originally a prospective case-control study, comprised a group with Beck Depression Inventory (BDI)-I scores ≥10 at baseline, and controls (n = 319, BDI-I < 10); mean (sd) follow-up time: 7.4 (0.7) years. Serum metabolic biomarkers were determined by proton nuclear magnetic resonance (NMR), and depressive symptoms sum-score by using the BDI-I. We examined the prospective associations between metabolites at baseline and BDI score at follow-up utilizing multivariate linear regression, parsimonious predictions models and network analysis. RESULTS Some metabolites tended to be either negatively (e.g. histidine) or positively associated (e.g. glycoprotein acetylation, creatinine and triglycerides in very large high density lipoproteins [XL-HDL-TG]) with depressive symptoms. None of the associations were significant after correction for multiple testing. The network analysis suggested high correlation among the metabolites, but that none of the metabolites directly influenced subsequent depressive symptoms. LIMITATIONS Although the sample size may be considered satisfactory in a prospective context, we cannot exclude the possibility that our study was underpowered. CONCLUSIONS Our results suggest that the investigated metabolic biomarkers are not a driving force in the development of depressive symptoms. These findings should be confirmed in studies with larger samples and studies that account for the heterogeneity of depressive disorders.
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Affiliation(s)
- Guro Pauck Bernhardsen
- Department of Research and Development, Division of Mental Health Services, Akershus University Hospital, Lørenskog, Norway.
| | - Owen Thomas
- Division of Research and Innovation, Akershus University Hospital, Lørenskog, Norway
| | - Pekka Mäntyselkä
- Institute of Public Health and Clinical Nutrition, General Practice, University of Eastern Finland, Kuopio, Finland; Clinical Research and Trials Centre, Kuopio University Hospital, Wellbeing Services County of North Savo, Kuopio, Finland
| | - Leo Niskanen
- Institute of Public Health and Clinical Nutrition, General Practice, University of Eastern Finland, Kuopio, Finland; Departments of Internal Medicine, Endocrinology/Diabetology, Päijät-Häme Central Hospital, Lahti, Finland; Eira Medical Center and Hospital, Helsinki, Finland
| | - Mauno Vanhala
- Institute of Public Health and Clinical Nutrition, General Practice, University of Eastern Finland, Kuopio, Finland
| | - Hannu Koponen
- Psychiatry, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Soili M Lehto
- Department of Research and Development, Division of Mental Health Services, Akershus University Hospital, Lørenskog, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Psychiatry, University of Helsinki, Helsinki, Finland
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11
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Seo CW, Park EA, Yoon TH. The associations of health behaviors and working hours with high-sensitivity C-reactive protein levels in Korean wage workers: a cross-sectional study. Osong Public Health Res Perspect 2023; 14:356-367. [PMID: 37920893 PMCID: PMC10626320 DOI: 10.24171/j.phrp.2023.0052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Revised: 07/10/2023] [Accepted: 07/17/2023] [Indexed: 11/04/2023] Open
Abstract
BACKGROUND We investigated differences in high-sensitivity C-reactive protein (hs-CRP) levels by age group according to working hours, socioeconomic level, health behavior and status, and occupational class, and aimed to identify factors affecting hs-CRP levels in various age groups using data from the Korean National Health and Nutrition Examination from 2016 to 2018. METHODS The study included a total of 4,786 male wage workers across the nation, aged between 19 and 65. Data from 4,674 workers were analyzed using multiple logistic regression analysis. RESULTS Obesity, metabolic syndrome, and weekly working hours were associated with hs-CRP, a biomarker of inflammation. Participants with a body mass index (BMI) ≥25.0 kg/m2 showed significantly higher hs-CRP levels than those with a BMI 23.0 to 25.0 kg/m2. Workers with high-risk drinking and metabolic syndrome showed significantly higher hs-CRP levels in the 50 to 65 years group. Obesity, walking 0 to 149 min/wk, and working ≥61 hours a week were associated with significantly higher hs-CRP levels in the 35 to 49 years group. The factors that significantly affected hs-CRP levels were different among age groups. CONCLUSION Plans to adjust working hours should be considered health behaviors, such as drinking and physical activity, and health conditions, such as metabolic syndrome and obesity, according to workers' age.
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Affiliation(s)
- Choong-Won Seo
- Department of Biomedical Laboratory Science, Dong-Eui Institute of Technology, Busan, Republic of Korea
| | - Eun-A Park
- Department of Nursing, Hwasung Medi-Science University, Hwaseong, Republic of Korea
| | - Tae-Hyung Yoon
- Department of Occupational Therapy, Dongseo University, Busan, Republic of Korea
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12
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Gouju J, Legeay S. Pharmacokinetics of obese adults: Not only an increase in weight. Biomed Pharmacother 2023; 166:115281. [PMID: 37573660 DOI: 10.1016/j.biopha.2023.115281] [Citation(s) in RCA: 42] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Accepted: 08/04/2023] [Indexed: 08/15/2023] Open
Abstract
Obesity is a pathophysiological state defined by a body mass index > 30 kg/m2 and characterized by an adipose tissue accumulation leading to an important weight increased. Several pathologies named comorbidities such as cardiovascular disease, type 2 diabetes and cancer make obesity the fifth cause of death in the world. Physiological changes impact the four main phases of pharmacokinetics of some drugs and leads to an inappropriate drug-dose. For absorption, the gastrointestinal transit is accelerated, and the gastric empty time is shortened, that can reduce the solubilization and absorption of some oral drugs. The drug distribution is probably the most impacted by the obesity-related changes because the fat mass (FM) increases at the expense of the lean body weight (LBW), leading to an important increase of the volume of distribution for lipophilic drugs and a low or moderately increase of this parameter for hydrophilic drugs. This modification of the distribution may require drug-dose adjustments. By various mechanisms, the metabolism and elimination of drugs are impacted by obesity and should be considered as similar or lower than that non-obese patients. To better understand the necessary drug-dose adjustments in obese patients, a narrative review of the literature was conducted to highlight the main elements to consider in the therapeutic management of adult obese patients.
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Affiliation(s)
- Julien Gouju
- MINT, INSERM U1066, CNRS 6021, UNIV Angers, SFR-ICAT 4208, IBS-CHU Angers, 4 rue Larrey, Angers 49933 Cedex 9, France; CHU Angers, 4 rue Larrey, Angers 49933 Cedex 9, France.
| | - Samuel Legeay
- MINT, INSERM U1066, CNRS 6021, UNIV Angers, SFR-ICAT 4208, IBS-CHU Angers, 4 rue Larrey, Angers 49933 Cedex 9, France
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13
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Lyzwinski L, Elgendi M, Shokurov AV, Cuthbert TJ, Ahmadizadeh C, Menon C. Opportunities and challenges for sweat-based monitoring of metabolic syndrome via wearable technologies. COMMUNICATIONS ENGINEERING 2023; 2:48. [PMCID: PMC10955995 DOI: 10.1038/s44172-023-00097-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Accepted: 06/30/2023] [Indexed: 10/05/2024]
Abstract
Metabolic syndrome is a prevalent condition in adults over the age of 65 and is a risk factor for developing cardiovascular disease and type II diabetes. Thus, methods to track the condition, prevent complications and assess symptoms and risk factors are needed. Here we discuss sweat-based wearable technologies as a potential monitoring tool for patients with metabolic syndrome. We describe several key symptoms that can be evaluated that could employ sweat patches to assess inflammatory markers, glucose, sodium, and cortisol. We then discuss the challenges with material property, sensor integration, and sensor placement and provide feasible solutions to optimize them. Together with a list of recommendations, we propose a pathway toward successfully developing and implementing reliable sweat-based technologies to monitor metabolic syndrome. Metabolic syndrome is a risk factor for developing cardiovascular disease and type II diabetes. Lyzwinski, Elgendi and colleagues discuss the potential role of sweat-based wearable technologies for monitoring metabolic syndrome along with engineering challenges towards implementation and optimization
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Affiliation(s)
- Lynnette Lyzwinski
- Menrva Research Group, Schools of Mechatronic Systems Engineering and Engineering Science, Simon Fraser University, Metro Vancouver, BC Canada
| | - Mohamed Elgendi
- Biomedical and Mobile Health Technology Lab, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland
| | - Alexander V. Shokurov
- Biomedical and Mobile Health Technology Lab, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland
| | - Tyler J. Cuthbert
- Biomedical and Mobile Health Technology Lab, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland
| | - Chakaveh Ahmadizadeh
- Biomedical and Mobile Health Technology Lab, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland
| | - Carlo Menon
- Menrva Research Group, Schools of Mechatronic Systems Engineering and Engineering Science, Simon Fraser University, Metro Vancouver, BC Canada
- Biomedical and Mobile Health Technology Lab, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland
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14
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Karami F, Jamaati H, Coleman-Fuller N, Zeini MS, Hayes AW, Gholami M, Salehirad M, Darabi M, Motaghinejad M. Is metformin neuroprotective against diabetes mellitus-induced neurodegeneration? An updated graphical review of molecular basis. Pharmacol Rep 2023; 75:511-543. [PMID: 37093496 DOI: 10.1007/s43440-023-00469-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2022] [Revised: 02/21/2023] [Accepted: 02/23/2023] [Indexed: 04/25/2023]
Abstract
Diabetes mellitus (DM) is a metabolic disease that activates several molecular pathways involved in neurodegenerative disorders. Metformin, an anti-hyperglycemic drug used for treating DM, has the potential to exert a significant neuroprotective role against the detrimental effects of DM. This review discusses recent clinical and laboratory studies investigating the neuroprotective properties of metformin against DM-induced neurodegeneration and the roles of various molecular pathways, including mitochondrial dysfunction, oxidative stress, inflammation, apoptosis, and its related cascades. A literature search was conducted from January 2000 to December 2022 using multiple databases including Web of Science, Wiley, Springer, PubMed, Elsevier Science Direct, Google Scholar, the Core Collection, Scopus, and the Cochrane Library to collect and evaluate peer-reviewed literature regarding the neuroprotective role of metformin against DM-induced neurodegenerative events. The literature search supports the conclusion that metformin is neuroprotective against DM-induced neuronal cell degeneration in both peripheral and central nervous systems, and this effect is likely mediated via modulation of oxidative stress, inflammation, and cell death pathways.
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Affiliation(s)
- Fatemeh Karami
- Chronic Respiratory Disease Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamidreza Jamaati
- Chronic Respiratory Disease Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Natalie Coleman-Fuller
- Department of Veterinary and Biomedical Sciences, University of Minnesota, Saint Paul, MN, 55108, USA
| | - Maryam Shokrian Zeini
- Chronic Respiratory Disease Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - A Wallace Hayes
- University of South Florida College of Public Health and Institute for Integrative Toxicology, Michigan State University, East Lansing, USA
| | - Mina Gholami
- Chronic Respiratory Disease Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mahsa Salehirad
- Cognitive and Neuroscience Research Center (CNRC), Amir-Almomenin Hospital, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Mohammad Darabi
- Chronic Respiratory Disease Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Majid Motaghinejad
- Chronic Respiratory Disease Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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15
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Arjmand MH. The association between visceral adiposity with systemic inflammation, oxidative stress, and risk of post-surgical adhesion. Arch Physiol Biochem 2022; 128:869-874. [PMID: 32141779 DOI: 10.1080/13813455.2020.1733617] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Abdominal and pelvic adhesions are common post-operative complications. Despite new medical technologies, these adhesions are appearing to be unavoidable and little is known about their causation; for example, why certain patients/or tissues are more prone to adhesions. There have been no clinical studies about increasing the risk adhesions in obese patients, but there is some evidence about the molecular mechanisms involving visceral fat (VF) that may lead to profibrotic conditions. VF is an endocrine/inflammatory organ which produces many biologically active molecules such as adipokines and inflammatory cytokines. Inflammatory conditions, oxidative stress, and the expression some fibrotic molecules in the VF may induce pathological conditions in the abdominal cavity that predispose to the formation of fibrotic bands.
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Affiliation(s)
- Mohammad-Hassan Arjmand
- Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
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16
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Long DL, Guo B, McClure LA, Jaeger BC, Tison S, Howard G, Judd SE, Howard VJ, Plante TB, Zakai NA, Koh I, Cheung KL, Cushman M. Biomarkers as MEDiators of racial disparities in risk factors (BioMedioR): Rationale, study design, and statistical considerations. Ann Epidemiol 2022; 66:13-19. [PMID: 34742867 PMCID: PMC8920757 DOI: 10.1016/j.annepidem.2021.10.010] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Revised: 10/06/2021] [Accepted: 10/26/2021] [Indexed: 02/03/2023]
Abstract
PURPOSE Relative to White adults, Black adults have a substantially higher prevalence of hypertension and diabetes, both key risk factors for stroke, cardiovascular disease, cognitive impairment, and dementia. Blood biomarkers have shown promise in identifying contributors to racial disparities in many chronic diseases. METHODS We outline the study design and related statistical considerations for a nested cohort study, the Biomarker Mediators of Racial Disparities in Risk Factors (BioMedioR) study, within the 30,239-person biracial REasons for Geographic And Racial Differences in Stroke (REGARDS) study (2003-present). Selected biomarkers will be assessed for contributions to racial disparities in risk factor development over median 9.4 years of follow-up, with initial focus on hypertension, and diabetes. Here we outline study design decisions and statistical considerations for the sampling of 4,400 BioMedioR participants. RESULTS The population for biomarker assessment was selected using a random sample study design balanced across race and sex to provide the optimal opportunity to describe association of biomarkers with the development of hypertension and diabetes. Descriptive characteristics of the BioMedioR sample and analytic plans are provided for this nested cohort study. CONCLUSIONS This nested biomarker study will examine pathways with the target to help explain racial differences in hypertension and diabetes incidence.
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Affiliation(s)
- D. Leann Long
- Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama
| | - Boyi Guo
- Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama
| | - Leslie A. McClure
- Department of Epidemiology and Biostatistics, Drexel University, Philadelphia, Pennsylvania
| | - Byron C. Jaeger
- Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama
| | - Stephanie Tison
- Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama
| | - George Howard
- Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama
| | - Suzanne E. Judd
- Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama
| | - Virginia J. Howard
- Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama
| | - Timothy B. Plante
- Department of Medicine, Larner College of Medicine at the University of Vermont
| | - Neil A. Zakai
- Department of Medicine, Larner College of Medicine at the University of Vermont,Department of Pathology & Laboratory Medicine, Larner College of Medicine at the University of Vermont
| | - Insu Koh
- Department of Pathology & Laboratory Medicine, Larner College of Medicine at the University of Vermont
| | - Katharine L. Cheung
- Department of Medicine, Larner College of Medicine at the University of Vermont
| | - Mary Cushman
- Department of Medicine, Larner College of Medicine at the University of Vermont,Department of Pathology & Laboratory Medicine, Larner College of Medicine at the University of Vermont
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17
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Xue Q, Yang X, Huang Y, Zhu D, Wang Y, Wen Y, Zhao J, Liu Y, Yang CX, Pan J, Yan T, Pan XF. Association between baseline and changes in high-sensitive C-reactive protein and metabolic syndrome: a nationwide cohort study and meta-analysis. Nutr Metab (Lond) 2022; 19:2. [PMID: 34991636 PMCID: PMC8734319 DOI: 10.1186/s12986-021-00632-6] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Accepted: 11/30/2021] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND We aimed to prospectively evaluate the associations between the baseline and changes in high-density C-reactive protein (hs-CRP) and incident metabolic syndrome (MetS) in China and update the evidence based on a meta-analysis of cohort studies in different populations. METHODS Data from the China Health and Retirement Longitudinal Study among adults aged 45 years or older were analyzed. Participants who were recruited in the study in 2011-2012 without MetS and successfully followed up to 2015-2016 were included in our final analysis. Logistic regressions were applied to examine the prospective associations of baseline and changes in hs-CRP with incident MetS and estimate corresponding odds ratios (ORs) and 95% confidence intervals (95% CIs). A meta-analysis was conducted to synthesize effect estimates from our findings and other cohort studies on this topic. RESULTS Among 4,116 participants, 535 developed MetS after a 4-year follow-up. Compared with the participants with hs-CRP in the lowest quartile, those with hs-CRP in the second, third, and highest quartiles had higher odds of MetS, with multivariable-adjusted ORs (95% CIs) of 1.51 (1.12, 2.06), 1.50 (1.11, 2.04), and 1.83 (1.37, 2.47). For the hs-CRP changes, ORs (95% CIs) were 3.24 (2.51, 4.02), 3.34 (2.56, 4.38), and 3.34 (2.54, 4.40) respectively. One unit (log of 1 mg/L) increase in hs-CRP was associated with 23% higher risk of MetS (OR 1.23; 95% CI 1.10, 1.38). In a meta-analysis of 6 cohort studies, the pooled relative risk for MetS was 1.63 (1.38, 1.93) for the highest versus lowest level of hs-CRP. In addition, the pooled relative risk for MetS was 1.29 (1.05, 1.59) for each unit increase of hs-CRP after log-transformation. CONCLUSIONS Both higher baseline hs-CRP and longitudinal hs-CRP increases were associated with higher risks of incident MetS. Individuals with high hs-CRP levels may need to be closely monitored for future risk of MetS.
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Affiliation(s)
- Qingping Xue
- Department of Epidemiology and Biostatistics, School of Public Health, Chengdu Medical College, Chengdu, Sichuan, China
- HEOA Group, Institute for Healthy Cities and West China Research Center for Rural Health Development, Sichuan University, Chengdu, Sichuan, China
| | - Xue Yang
- Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Yuli Huang
- Department of Cardiology, Shunde Hospital, Southern Medical University, Foshan, Guangdong, China
- The George Institute for Global Health, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia
| | - Dongshan Zhu
- Center for Health Management and Policy Research, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China
| | - Yi Wang
- Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health and State Key Laboratory of Environmental Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Ying Wen
- Department of Communicable Diseases Control and Prevention, Shenzhen Center for Disease Control and Prevention, Shenzhen, Guangdong, China
| | - Jian Zhao
- The Ministry of Education - Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yanjun Liu
- Center of Gastrointestinal and Minimally Invasive Surgery, Department of General Surgery, The Third People's Hospital of Chengdu and The Affiliated Hospital of Southwest Jiaotong University, Chengdu, Sichuan, China
- Center for Obesity and Metabolic Health, The Third People's Hospital of Chengdu and The Affiliated Hospital of Southwest Jiaotong University, Chengdu, Sichuan, China
| | - Chun-Xia Yang
- Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Jay Pan
- HEOA Group, Institute for Healthy Cities and West China Research Center for Rural Health Development, Sichuan University, Chengdu, Sichuan, China
- Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Tong Yan
- Center for Obesity and Metabolic Health, The Third People's Hospital of Chengdu and The Affiliated Hospital of Southwest Jiaotong University, Chengdu, Sichuan, China.
| | - Xiong-Fei Pan
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.
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18
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Mohamad MN, Ismail LC, Stojanovska L, Apostolopoulos V, Feehan J, Jarrar AH, Al Dhaheri AS. The prevalence of diabetes amongst young Emirati female adults in the United Arab Emirates: A cross-sectional study. PLoS One 2021; 16:e0252884. [PMID: 34138882 PMCID: PMC8211155 DOI: 10.1371/journal.pone.0252884] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Accepted: 05/24/2021] [Indexed: 01/21/2023] Open
Abstract
AIMS The prevalence of type 2 diabetes is rapidly increasing in the United Arab Emirates (UAE). The purpose of this study was to investigate the prevalence of prediabetes and diabetes using FPG and HbA1c and to examine their relationships with obesity and other risk factors in young female Emirati college students. METHODS In this cross-sectional study we recruited 555 female college students aged 17-25, enrolled at United Arab Emirates University in Al Ain, UAE. Anthropometric analysis, blood pressure, and various biochemical markers were measured using standard methods. Type 2 Diabetes, impaired fasting plasma glucose (FPG), and elevated HbA1c levels were examined in the study population as per the standards of medical care in diabetes, set out by the American Diabetes Association in 2020. RESULTS Based on the HbA1c test, the prevalence of pre-diabetes and diabetes were 24% and 8.6%, respectively. Based on the FPG test, the prevalence of pre-diabetes and diabetes were 9.2% and 0.5%, respectively. The kappa statistic of concordance between HbA1c and FPG was 0.287, P < 0.001. Abnormal glycemic status was significantly associated with decreased high-density lipoprotein (HDL) level (< 50 mg/dl) (p = 0.002) and elevated high-sensitivity C-reactive protein (Hs-CRP) level (≥ 2.0 mg/L) (P < 0.001). CONCLUSIONS Using FPG to evaluate glycemic control seems to underestimate the burden of undiagnosed diabetes which could have a significant impact on clinical practice. Our data indicates an association between abnormal glycemic status with HDL and Hs-CRP. Further evaluation is needed to assess the impact of using HbA1c as a diagnostic test for diabetes in the UAE.
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Affiliation(s)
- Maysm N. Mohamad
- Department of Nutrition and Health, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates
| | - Leila Cheikh Ismail
- Clinical Nutrition and Dietetics Department, College of Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
- Nuffield Department of Women’s & Reproductive Health, University of Oxford, Oxford, United Kingdom
| | - Lily Stojanovska
- Department of Nutrition and Health, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates
- Institute for Health and Sport, Victoria University, Melbourne, VIC, Australia
| | | | - Jack Feehan
- Institute for Health and Sport, Victoria University, Melbourne, VIC, Australia
- Department of Medicine–Western Health, The University of Melbourne, Melbourne, VIC, Australia
| | - Amjad H. Jarrar
- Department of Nutrition and Health, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates
| | - Ayesha S. Al Dhaheri
- Department of Nutrition and Health, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates
- * E-mail:
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Cohen E, Margalit I, Shochat T, Goldberg E, Krause I. Markers of Chronic Inflammation in Overweight and Obese Individuals and the Role of Gender: A Cross-Sectional Study of a Large Cohort. J Inflamm Res 2021; 14:567-573. [PMID: 33658829 PMCID: PMC7920597 DOI: 10.2147/jir.s294368] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Accepted: 02/13/2021] [Indexed: 01/08/2023] Open
Abstract
Objective During the last decade, obesity has become an epidemic. As obesity is now considered a state of low-grade inflammation, the purpose of this study was to assess the prevalence of four common elements of inflammation, in individuals with increased BMI. These findings were compared to those of subjects with normal BMI. The effect of gender was also noted. Methods Data were collected from medical records of individuals examined at a screening center in Israel between the years 2000–2014. Cross-sectional analysis was carried out on 7526 men and 3219 women. White blood cell count (WBC); platelet (PLT) count; erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were assessed in four BMI categories: normal, overweight, obese and morbidly obese. Results Mean (SD) age of the study sample was 47.5 (9.7) and 46.7 (9.8) years for men and women, respectively. The prevalence of each inflammatory marker increased significantly when comparing abnormal to normal BMI (p<0.0001). The odds ratio (OR) of the prevalence of increased inflammatory markers was compared between subjects with overweight, obese and morbid obesity and subjects with normal BMI. This study showed that the higher the BMI, the higher the OR. For those in the morbid obesity group, the OR for the different inflammatory markers adjusting for age, diabetes mellitus hypertension and kidney function were as follows: WBC levels, 5.1 (2.9–8.7) and 4.7 (2.4–9.1) for men and women, respectively; PLT levels, 1.7 (0.3–8.5) and 2.0 (0.6–7.2) for men and women, respectively; ESR levels, 4.2 (3.2–5.4) and 4.6 (3.2–6.6) for men and women, respectively, and CRP levels, 13.4 (10.0–18.2) and 19.2 (12.9–28.6) for men and women, respectively. Conclusion Inflammatory markers are significantly higher in subjects with abnormal compared to normal BMI. This difference was found to be greater in women than in men.
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Affiliation(s)
- Eytan Cohen
- Department of Medicine F - Recanati, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel
| | - Ili Margalit
- Department of Medicine F - Recanati, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel
| | - Tzippy Shochat
- Statistical Counselling Unit, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel
| | - Elad Goldberg
- Department of Medicine F - Recanati, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel
| | - Ilan Krause
- Department of Medicine F - Recanati, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel
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The Herbal Medicine Scutellaria-Coptis Alleviates Intestinal Mucosal Barrier Damage in Diabetic Rats by Inhibiting Inflammation and Modulating the Gut Microbiota. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2020; 2020:4568629. [PMID: 33224253 PMCID: PMC7669352 DOI: 10.1155/2020/4568629] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/25/2020] [Revised: 10/16/2020] [Accepted: 10/23/2020] [Indexed: 02/06/2023]
Abstract
Recent studies have confirmed that increased intestinal permeability and gut-origin lipopolysaccharide (LPS) translocation are important causes of metabolic inflammation in type 2 diabetes (T2D), but there are no recognized therapies for targeting this pathological state. Scutellaria baicalensis and Coptis chinensis are a classic herbal pair often used to treat diabetes and various intestinal diseases, and repair of intestinal barrier damage may be at the core of their therapeutic mechanism. This study investigated the effects of oral administration of Scutellaria-Coptis (SC) on the intestinal mucosal barrier in diabetic rats and explored the underlying mechanism from the perspective of anti-inflammatory and gut microbiota-modulatory effects. The main results showed that, in addition to regulating glycolipid metabolism disorders and inhibiting serum inflammatory factors, SC could also upregulate the expression levels of the tight junction proteins claudin-1, occludin, and zonula occludens (ZO-1), significantly improve intestinal epithelial damage, and inhibit excessive LPS translocation into the blood circulation. Furthermore, it was found that SC could reduce the levels of the inflammatory factors interleukin-1β (IL-1β), IL-6, and tumour necrosis factor-α (TNF-α) in intestinal tissue and that the anti-inflammatory effects involved the TLR-4/TRIF and TNFR-1/NF-κB signalling pathways. Moreover, SC had a strong inhibitory effect on some potential enteropathogenic bacteria and LPS-producing bacteria, such as Proteobacteria, Enterobacteriaceae, Enterobacter, Escherichia-Shigella, and Enterococcus, and could also promote the proliferation of butyrate-producing bacteria, such as Lachnospiraceae and Prevotellaceae. Taken together, the hypoglycaemic effects of SC were related to the protection of the intestinal mucosal barrier, and the mechanisms might be related to the inhibition of intestinal inflammation and the regulation of the gut microbiota.
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21
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Mitrofanova A, Fontanella AM, Merscher S, Fornoni A. Lipid deposition and metaflammation in diabetic kidney disease. Curr Opin Pharmacol 2020; 55:60-72. [PMID: 33137677 DOI: 10.1016/j.coph.2020.09.004] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Revised: 07/16/2020] [Accepted: 09/09/2020] [Indexed: 12/14/2022]
Abstract
A critical link between metabolic disorders and a form of low-grade systemic and chronic inflammation has been recently established and named 'Metaflammation'. Metaflammation has been recognized as a key mediator of both microvascular and macrovascular complications of diabetes and as a significant contributor to the development of diabetic kidney disease (DKD). The goal of this review is to summarize the contribution of diabetes-induced inflammation and the related signaling pathways to diabetic complications, with a particular focus on how innate immunity and lipid metabolism influence each other.
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Affiliation(s)
- Alla Mitrofanova
- Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami, Miller School of Medicine, Miami, FL, USA; Peggy and Harold Katz Family Drug Discovery Center, University of Miami, Miller School of Medicine, Miami, FL, USA; Department of Surgery, University of Miami, Miller School of Medicine, Miami, FL, USA
| | - Antonio M Fontanella
- Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami, Miller School of Medicine, Miami, FL, USA; Peggy and Harold Katz Family Drug Discovery Center, University of Miami, Miller School of Medicine, Miami, FL, USA
| | - Sandra Merscher
- Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami, Miller School of Medicine, Miami, FL, USA; Peggy and Harold Katz Family Drug Discovery Center, University of Miami, Miller School of Medicine, Miami, FL, USA
| | - Alessia Fornoni
- Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami, Miller School of Medicine, Miami, FL, USA; Peggy and Harold Katz Family Drug Discovery Center, University of Miami, Miller School of Medicine, Miami, FL, USA.
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Abstract
Objective: This study evaluated the effect of melatonin on the response of patients suffering from metabolic syndrome (MEBS) treated with metformin. Design: This study used two-armed groups in a double-blind, randomized controlled clinical trial. Materials and Methods: A randomized double-blind placebo-controlled study was carried out on female patients diagnosed as having MEBS, according to the International Diabetes Federation (IDF) diagnosing criteria of MEBS (2005), from the outpatient clinic in Al-Zahraa Teaching Hospital/Kut, Iraq. They were diagnosed utilizing laboratory and clinical investigations, then randomized into two groups. The first group (group A) was treated with metformin (500 mg) twice daily, in addition to a placebo formula once daily at bedtime for three months. The second group (group B) was treated with metformin (500 mg) twice daily after meals, in addition to melatonin (10 mg) once daily at bedtime for three months. Results: The treatment of patients with MEBS using metformin–melatonin showed an improvement in most MEBS components such as fasting serum glucose (FSG), lipid profile, and body mass index (BMI), in addition to a reduction in insulin resistance and hyperinsulinemia. Simultaneously, there were increments in serum uric acid (UA), leptin, prolactin (PRL), and estradiol levels, while serum progesterone level decreased. Furthermore, patients treated with metformin–placebo showed less improvement in the studied parameters compared to that produced due to the inclusion of melatonin in the treatment protocol. Conclusion: Melatonin improves the effect of metformin on several components of MEBS such as FSG, lipid profile, and BMI, in addition to insulin resistance and hyperinsulinemia, compared to metformin alone.
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Sun F, Zhao Z, Li Q, Zhou X, Li Y, Zhang H, Yan Z, He H, Ke Z, Gao Y, Li F, Tong W, Zhu Z. Detrimental Effect of C-Reactive Protein on the Cardiometabolic Cells and Its Rectifying by Metabolic Surgery in Obese Diabetic Patients. Diabetes Metab Syndr Obes 2020; 13:1349-1358. [PMID: 32425567 PMCID: PMC7195578 DOI: 10.2147/dmso.s250294] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Accepted: 04/03/2020] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND High-sensitivity C-reactive protein (hs-CRP) has been regarded as a biomarker of low-degree inflammation in illness; however, whether CRP exerts its pathogenic effect on the cardiometabolic system remains unknown. Aside from the beneficial effects of metabolic surgery on cardiometabolic system, its impact on inflammation still worth examining. Thus, this study aims to investigate the effect of CRP on adipose and vascular cells, and their responses to metabolic surgery in obese diabetic patients. PATIENTS AND METHODS The expression of CRP and RAS- and ERK-related factors in the adipocytes and VSMCs were measured. Obese patients with type 2 diabetes who underwent metabolic surgery were followed up for 2 years thereafter. Laboratory tests, which included serum hs-CRP levels and visceral fat thickness (VFT), were obtained before and after surgery. RESULTS CRP administration significantly and dose-dependently increased the intracellular-free calcium concentration ([Ca2+]i) in cultured adipocytes and in the VSMCs. CRP administration significantly increased ACE, Ang II, AT1R and p-ERK expressions, but reduced ACE2 expression in both the adipocytes and VSMCs. Clinical study showed that VFT was closely associated with serum hs-CRP. Furthermore, VFT and serum hs-CRP were found to be highly associated with blood pressure. Finally, metabolic surgery remarkably decreased blood pressure, visceral fat and serum hs-CRP levels. CONCLUSION CRP has a detrimental effect on cardiometabolic cells, aside from functioning merely as a biomarker. Serum hs-CRP levels are highly associated with hypertension and visceral obesity, which can be antagonized by metabolic surgery in obese diabetic patients.
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Affiliation(s)
- Fang Sun
- Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Center for Hypertension and Metabolic Diseases, Chongqing Institute of Hypertension, Chongqing400042, People’s Republic of China
| | - Zhigang Zhao
- Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Center for Hypertension and Metabolic Diseases, Chongqing Institute of Hypertension, Chongqing400042, People’s Republic of China
| | - Qiang Li
- Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Center for Hypertension and Metabolic Diseases, Chongqing Institute of Hypertension, Chongqing400042, People’s Republic of China
| | - Xunmei Zhou
- Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Center for Hypertension and Metabolic Diseases, Chongqing Institute of Hypertension, Chongqing400042, People’s Republic of China
| | - Yingsha Li
- Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Center for Hypertension and Metabolic Diseases, Chongqing Institute of Hypertension, Chongqing400042, People’s Republic of China
| | - Hexuan Zhang
- Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Center for Hypertension and Metabolic Diseases, Chongqing Institute of Hypertension, Chongqing400042, People’s Republic of China
| | - Zhencheng Yan
- Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Center for Hypertension and Metabolic Diseases, Chongqing Institute of Hypertension, Chongqing400042, People’s Republic of China
| | - Hongbo He
- Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Center for Hypertension and Metabolic Diseases, Chongqing Institute of Hypertension, Chongqing400042, People’s Republic of China
| | - Zhigang Ke
- Department of General Surgery, Daping Hospital, Third Military Medical University, Chongqing400042, People’s Republic of China
| | - Yu Gao
- Department of General Surgery, Daping Hospital, Third Military Medical University, Chongqing400042, People’s Republic of China
| | - Fan Li
- Department of General Surgery, Daping Hospital, Third Military Medical University, Chongqing400042, People’s Republic of China
| | - Weidong Tong
- Department of General Surgery, Daping Hospital, Third Military Medical University, Chongqing400042, People’s Republic of China
| | - Zhiming Zhu
- Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Center for Hypertension and Metabolic Diseases, Chongqing Institute of Hypertension, Chongqing400042, People’s Republic of China
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Assem S, Abdelbaki TN, Mohy-El Dine SH, Ketat AF, Abdelmonsif DA. SERPINE-1 Gene Methylation and Protein as Molecular Predictors of Laparoscopic Sleeve Gastrectomy Outcome. Obes Surg 2020; 30:2620-2630. [PMID: 32170551 DOI: 10.1007/s11695-020-04533-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
BACKGROUND Body weight is subjected to genetic and epigenetic modifiers that might affect the success of weight loss interventions. Because of its possible complications and disparity in patients' response, identification of predictors to the outcome of bariatric surgery is indispensable. OBJECTIVES This prospective study aims to investigate serpin peptidase inhibitor type 1 (SERPINE-1) protein and gene methylation as molecular predictors to the outcome of bariatric surgery. PATIENTS AND METHODS One hundred participants were enrolled and divided to control group (n = 50) and obese patients who underwent laparoscopic sleeve gastrectomy (LSG) (n = 50). Anthropometric measurements were assessed and blood samples were collected preoperatively and 6 months postoperatively for assessment of SERPINE-1 protein and gene methylation, C-reactive protein (CRP), and homeostatic model assessment of insulin resistance (HOMA-IR). Moreover, subjects were followed for 2 years for weight loss parameters. RESULTS Patients with obesity showed high baseline SERPINE-1 protein and gene hypermethylation where LSG was followed by a drop in SERPINE-1 protein level but not gene hypermethylation. Baseline SERPINE-1 gene methylation was negatively related to postoperative weight loss and was the independent predictor to weight loss after LSG. Likewise, postoperative SERPINE-1 protein was negatively related to weight loss with independent expression from its gene methylation state. Furthermore, postoperative SERPINE-1 gene methylation correlated to CRP and HOMA-IR. CONCLUSION Baseline SERPINE-1 gene methylation might be a predictor of weight loss after LSG. Meanwhile, postoperative SERPINE-1 protein could be a predictor to weight loss maintenance after LSG. Lastly, postoperative SERPINE-1 gene methylation might serve as an index to postoperative changes in obesity-related comorbidities.
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Affiliation(s)
- Sara Assem
- Department of Medical Biochemistry, Faculty of Medicine, University of Alexandria, Alexandria, Egypt
| | - Tamer N Abdelbaki
- Department of Surgery, Faculty of Medicine, University of Alexandria, Alexandria, Egypt
| | - Safaa H Mohy-El Dine
- Department of Medical Biochemistry, Faculty of Medicine, University of Alexandria, Alexandria, Egypt
| | - Amel F Ketat
- Department of Medical Biochemistry, Faculty of Medicine, University of Alexandria, Alexandria, Egypt
| | - Doaa A Abdelmonsif
- Department of Medical Biochemistry, Faculty of Medicine, University of Alexandria, Alexandria, Egypt. .,Molecular Biology Lab. and Nanomedicine Lab., Center of Excellence for Research in Regenerative Medicine and Applications, University of Alexandria, Alexandria, Egypt.
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Body mass index is independently associated with xanthine oxidase activity in overweight/obese population. Eat Weight Disord 2020; 25:9-15. [PMID: 29470797 DOI: 10.1007/s40519-018-0490-5] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2018] [Accepted: 02/14/2018] [Indexed: 01/05/2023] Open
Abstract
PURPOSE The pathophysiological mechanism of the relationship between xanthine oxidase (XO) activity and obesity has not been completely elucidated. Since inflammation and oxidative stress are regarded as key determinants of enlarged adipose tissue, we aimed to investigate the association between oxidative stress (as measured with XO activity), inflammation [as measured with high-sensitivity C-reactive protein (hsCRP)] and obesity [as measured with body mass index (BMI)]. In addition, we wanted to examine whether hsCRP itself plays an independent role in XO activity increase or it is only mediated through obesity. METHODS A total of 118 overweight/obese volunteers (mean age 54.76 ± 15.13 years) were included in the current cross-sectional study. Anthropometric, biochemical parameters, and blood pressure were obtained. RESULTS Significant differences between age, BMI, waist circumference, concentrations of uric acid and hsCRP, as well as xanthine dehydrogenase (XDH) activities were evident among XO tertile groups. Multiple linear regression analysis revealed that BMI (beta = 0.241, p = 0.012) and XDH (beta = - 0.489, p < 0.001) are the independent predictors of XO activity (R2-adjusted = 0.333), whereas hsCRP lost its independent role in XO activity prediction. CONCLUSION Obesity (as determined with increased BMI) is an independent predictor of high XO activity in overweight/obese population. LEVEL OF EVIDENCE Level V: cross-sectional descriptive study.
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Hong GB, Gao PC, Chen YY, Xia Y, Ke XS, Shao XF, Xiong CX, Chen HS, Xiao H, Ning J, Zou HQ. High-Sensitivity C-Reactive Protein Leads to Increased Incident Metabolic Syndrome in Women but Not in Men: A Five-Year Follow-Up Study in a Chinese Population. Diabetes Metab Syndr Obes 2020; 13:581-590. [PMID: 32184637 PMCID: PMC7055523 DOI: 10.2147/dmso.s241774] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Accepted: 02/15/2020] [Indexed: 12/13/2022] Open
Abstract
PURPOSE Metabolic syndrome (MetS), characterized by a constellation of insulin resistance, central obesity, hypertension, and hyperlipidemia, is a global health threat. High-sensitivity C-reactive protein (hs-CRP) has been shown to be associated with type 2 diabetes and cardiovascular disease; however, its association with incident MetS is less known. Therefore, the aim of this study was to examine the prospective association between hs-CRP and MetS among a Chinese population in a 5-year follow-up study. PATIENTS AND METHODS The levels of hs-CRP were measured using serum samples collected at baseline recruitment in 2012 from 886 participants without MetS. Follow-up interviews were conducted in 2018, and MetS was diagnosed by 2017 criteria from the Chinese Diabetes Society. Multivariate logistic regression models were used to assess the overall and sex-specific associations between hs-CRP and incident MetS. The odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were computed with adjustment for demographic, socioeconomic, clinical, and lifestyle factors. RESULTS After a mean follow-up duration of 5.40 ± 0.56 years, 116 (13.3%) participants developed MetS. In the total study population, increased hs-CRP levels were associated with a higher risk of MetS (OR comparing extreme quartiles of hs-CRP: 4.06 [95% CI: 1.91-8.65]) in the fully-adjusted model. When stratified by sex, the positive association was only observed in women (OR: 4.82 [1.89-12.3]) but not in men (OR: 3.15 [0.82-12.1]; P-interaction = 0.039). CONCLUSION In this study of a Chinese population, a positive association between hs-CRP and incident MetS was found only in women and not in men. Sex-specific prediction and intervention of MetS using hs-CRP as a target should be further evaluated.
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Affiliation(s)
- Guo-bao Hong
- Department of Nephrology, Institute of Nephrology and Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong510630, People’s Republic of China
- Department of Nephrology, The Affiliated Nanhai Hospital of Southern Medical University, Foshan528200, People’s Republic of China
| | - Pei-chun Gao
- Department of Nephrology, Institute of Nephrology and Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong510630, People’s Republic of China
- School of Public Health, Southern Medical University, Guangzhou, Guangdong510630, People’s Republic of China
| | - Yun-yin Chen
- Department of Nephrology, Institute of Nephrology and Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong510630, People’s Republic of China
| | - Yue Xia
- Department of Nephrology, Institute of Nephrology and Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong510630, People’s Republic of China
| | - Xiao-su Ke
- Department of Nephrology, Institute of Nephrology and Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong510630, People’s Republic of China
| | - Xiao-fei Shao
- Department of Nephrology, Institute of Nephrology and Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong510630, People’s Republic of China
| | - Chong-xiang Xiong
- Department of Nephrology, Institute of Nephrology and Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong510630, People’s Republic of China
| | - Hai-shan Chen
- Department of Nephrology, Institute of Nephrology and Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong510630, People’s Republic of China
| | - Hua Xiao
- Department of Nephrology, Institute of Nephrology and Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong510630, People’s Republic of China
| | - Jing Ning
- Department of Nephrology, Institute of Nephrology and Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong510630, People’s Republic of China
| | - He-qun Zou
- Department of Nephrology, Institute of Nephrology and Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong510630, People’s Republic of China
- Correspondence: He-qun Zou Department of Nephrology, Institute of Nephrology and Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong510630, People’s Republic of ChinaTel +86-20-6278-4391 Email
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Benjamin EJ, Muntner P, Alonso A, Bittencourt MS, Callaway CW, Carson AP, Chamberlain AM, Chang AR, Cheng S, Das SR, Delling FN, Djousse L, Elkind MSV, Ferguson JF, Fornage M, Jordan LC, Khan SS, Kissela BM, Knutson KL, Kwan TW, Lackland DT, Lewis TT, Lichtman JH, Longenecker CT, Loop MS, Lutsey PL, Martin SS, Matsushita K, Moran AE, Mussolino ME, O'Flaherty M, Pandey A, Perak AM, Rosamond WD, Roth GA, Sampson UKA, Satou GM, Schroeder EB, Shah SH, Spartano NL, Stokes A, Tirschwell DL, Tsao CW, Turakhia MP, VanWagner LB, Wilkins JT, Wong SS, Virani SS. Heart Disease and Stroke Statistics-2019 Update: A Report From the American Heart Association. Circulation 2019; 139:e56-e528. [PMID: 30700139 DOI: 10.1161/cir.0000000000000659] [Citation(s) in RCA: 5783] [Impact Index Per Article: 963.8] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Olubamwo OO, Virtanen JK, Pihlajamäki J, Tuomainen TP. Association of fatty liver disease with mortality outcomes in an Eastern Finland male cohort. BMJ Open Gastroenterol 2019; 6:e000219. [PMID: 31275580 PMCID: PMC6577350 DOI: 10.1136/bmjgast-2018-000219] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2018] [Revised: 11/25/2018] [Accepted: 12/15/2018] [Indexed: 12/18/2022] Open
Abstract
Objective Fatty liver disease (FLD) has been associated with extrahepatic morbidity outcomes. However, reports on the association of FLD, assessed using fatty liver index (FLI), with mortality outcomes have been inconsistent. Our objective was to examine the effect of metabolic factors (blood pressure, insulin, fasting glucose, lipoproteins) on the associations of FLI with mortality outcomes among middle-aged men. Study design Prospective cohort study. Methods Our subjects were 1893 men at baseline from 1984 to 1989 in the Kuopio Ischaemic Heart Disease Risk Factor Study cohort. Multivariable Cox regression models were used to analyse the association of baseline FLI, with the HRs for all-cause, disease, cardiovascular, non-cardiovascular and cancer mortality outcomes. Results The mean FLI in the FLI categories were 16.2 in the low and reference category (FLI<30), 43.4 in the intermediate FLI category (FLI=30–<60) and 77.5 in the high FLI (FLD) category (FLI≥60). Over an average follow-up of 20 years, 848 disease deaths were recorded through Finnish national cause of death register. In models adjusted for constitutional, lifestyle and inflammatory factors, for the high (FLI≥60) vs low (FLI<30) FLI category, the HRs (95% CI) for mortality outcomes were 1.50 (1.26–1.78) for all-cause mortality; 1.56 (1.31–2.86) for disease mortality; 1.51 (1.18–1.94) for cardiovascular disease (CVD) mortality; 1.42 (1.12–1.80) for non-CVD mortality and 1.45 (1.02–2.07) for cancer mortality. With further adjustment for metabolic factors, the HRs were 1.25 (1.01–1.53) for all-cause mortality; 1.26 (1.02–1.56) for disease mortality; 1.06 (0.78–1.43) for CVD mortality; 1.46 (1.09–1.94) for non-CVD mortality and 1.49 (0.97–2.29) for cancer mortality. Conclusion High FLI (FLD) is associated with increased risks of mortality outcomes. The FLI-CVD mortality association can be largely explained by metabolic factors. Persons with FLD should be monitored for metabolic deterioration and extrahepatic morbidity to improve their prognoses.
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Affiliation(s)
- Olubunmi O Olubamwo
- Institute of Public Health and Clinical Nutrition, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland
| | - Jyrki K Virtanen
- Institute of Public Health and Clinical Nutrition, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland
| | - Jussi Pihlajamäki
- Institute of Public Health and Clinical Nutrition, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland.,Clinical Nutrition and Obesity Center, Kuopio University Hospital, Kuopio, Finland
| | - Tomi-Pekka Tuomainen
- Institute of Public Health and Clinical Nutrition, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland
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López-Alarcón M, Inda-Icaza P, Márquez-Maldonado MC, Armenta-Álvarez A, Barbosa-Cortés L, Maldonado-Hernández J, Piña-Aguero M, Barradas-Vázquez A, Núñez-García BA, Rodríguez-Cruz M, Fernández JR. A randomized control trial of the impact of LCPUFA-ω3 supplementation on body weight and insulin resistance in pubertal children with obesity. Pediatr Obes 2019; 14:e12499. [PMID: 30590877 PMCID: PMC8513132 DOI: 10.1111/ijpo.12499] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2018] [Accepted: 11/16/2018] [Indexed: 12/30/2022]
Abstract
BACKGROUND Paediatric obesity and insulin resistance (IR) are potentially reversible inflammatory conditions. Long chain polyunsaturated fatty acids omega-3 (LCPUFA-ω3) show anti-inflammatory and metabolic properties, but their clinical efficacy is unclear. OBJECTIVE The objective of this study is to evaluate whether supplementation with LCPUFA-ω3 for 3 months reduces insulin resistance and weight to adolescents with obesity. METHODS Double-blind trial of 366 adolescents with obesity randomly assigned to 1.2-g LCPUFA-ω3 (DO3) or 1-g sunflower oil (DP) daily for 3 months; both groups received an energy-restricted diet. Children attended monthly for anthropometric, dietary, and clinical measurements. Basal and final blood samples were obtained to measure metabolic markers and erythrocytes fatty acids. Regression models were used for analysis. RESULTS A total of 119 DO3 and 126 DP children completed follow-up. At baseline, 92% of children presented IR, 66% hypertriglyceridemia, 37% low-grade inflammation, and 32% metabolic syndrome. Despite erythrocytes LCPUFA-ω3 increased more in DO3 (Median differences = 0.984 w/w%; 95 IC = 0.47, 1.53, P < 0.001), body weight, insulin, and HOMA changed similarly in both groups at the end of intervention. Adjusting for basal values, changes in weight, insulin, and HOMA was not related with supplementation. CONCLUSIONS Supplementation with LCPUFA-ω3 does not affect body weight or insulin in adolescents with obesity.
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Affiliation(s)
- M. López-Alarcón
- Unidad de Investigación Médica en Nutrición, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico
| | - P. Inda-Icaza
- Unidad de Investigación Médica en Nutrición, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico,Facultad de Ciencias de la Salud, Universidad Anáhuac, Anahuac, Mexico
| | - M. C. Márquez-Maldonado
- Unidad de Investigación Médica en Nutrición, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico
| | - A. Armenta-Álvarez
- Unidad de Investigación Médica en Nutrición, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico
| | - L. Barbosa-Cortés
- Unidad de Investigación Médica en Nutrición, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico
| | - J. Maldonado-Hernández
- Unidad de Investigación Médica en Nutrición, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico
| | - M. Piña-Aguero
- Unidad de Investigación Médica en Nutrición, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico
| | - A. Barradas-Vázquez
- Unidad de Investigación Médica en Nutrición, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico
| | - B. A. Núñez-García
- Unidad de Investigación Médica en Nutrición, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico
| | - M. Rodríguez-Cruz
- Unidad de Investigación Médica en Nutrición, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico
| | - J. R. Fernández
- Department of Nutrition Sciences and Department of Biostatistics, University of Alabama at Birmingham, Birmingham, Alabama, USA
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Hosseininasab Nodoushan SA, Nabavi A. The Interaction of Helicobacter pylori Infection and Type 2 Diabetes Mellitus. Adv Biomed Res 2019; 8:15. [PMID: 30993085 PMCID: PMC6425747 DOI: 10.4103/abr.abr_37_18] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Helicobacter pylori is one of the most common human pathogens that can cause gastrointestinal (GI) disorders, including simple gastritis, gastric ulcer, and malignant gastritis. In some cases, such as immunodeficiency and underlying diseases, it can be problematic as opportunistic infections. Diabetes mellitus (type 2) (T2DM) is one of the H. pylori underlying diseases. Since GI problems are observed in diabetic patients, it is necessary to treat H. pylori infection. In this review, we aimed to evaluate the possible relationship between H. pylori and T2DM according to epidemiological surveys of 70 studies retrieved from databases, including Scopus, PubMed, and Google Scholar about the relationship between H. pylori and T2DM, and discuss the reported background mechanisms of this correlation. According to the results of our study, the different studies have shown that H. pylori is more prevalent in Type 2 diabetic patients than healthy individuals or nondiabetic patients. The reason is development of H. pylori infection-induced inflammation and production of inflammatory cytokines as well as different hormonal imbalance by this bacterium, which are associated with diabetes mellitus. On the other hand, by tracing anti-H. pylori antibodies in patients with diabetes mellitus and occurrence of symptoms such as digestive problems in >75% of these patients, it can be concluded that there is a relationship between this bacterium and T2DM. Considering the evidence, it is crucially important that the probability of infection with H. pylori is evaluated in patients with T2DM so that medical process of the patient is followed with higher cautious.
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Affiliation(s)
| | - Amin Nabavi
- Department of Biochemistry, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
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Song Y, Yang SK, Kim J, Lee DC. Association between C-Reactive Protein and Metabolic Syndrome in Korean Adults. Korean J Fam Med 2018; 40:116-123. [PMID: 30373358 PMCID: PMC6444090 DOI: 10.4082/kjfm.17.0075] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2017] [Accepted: 10/17/2017] [Indexed: 01/09/2023] Open
Abstract
Background The prevalence of metabolic syndrome (MetS) is increasing, and obesity, insulin resistance, and inflammation are the known risk factors. However, results of previous studies regarding the relationship between MetS and inflammation have not been consistent. This study aimed to identify the associations between C-reactive protein (CRP) and MetS and its components in obese and non-obese men and women. Methods This was a cross-sectional study based on the 6th Korea National Health and Nutrition Examination Survey (2015), and a nationally representative sample of 3,013 Korean adults aged 40–78 years were included. Those with cardiovascular disease, cancer, CRP level >10 mg/L, white blood cell count >10,000/mm3 , chronic kidney disease, and lung/liver disease were excluded. Results Approximately 11.0%, 50.0%, 8.4%, and 48.8% of non-obese men, obese men, non-obese women, and obese women presented with MetS (P<0.001), respectively. In all four groups, those who presented with MetS or its components showed a higher high-sensitivity (hs-CRP) average than those without. Multivariate regression analysis showed the increased risk of developing MetS with higher quartiles of hs-CRP level in obese (3rd and 4th quartiles: odds ratios [ORs], 3.87 and 2.57, respectively) and non-obese women (4th quartile: OR, 2.63). The different components also showed increased ORs in the four groups. However, no statistically significant trend in the relationship was found in men. Conclusion Low-grade inflammation may increase the risk of MetS in Korean women independent of adiposity. However, due to the cross-sectional design of the present study, further studies must be conducted to identify the causal relationship between inflammation and metabolic disorders.
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Affiliation(s)
- Youhyun Song
- Department of Family Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Soo Kyung Yang
- Department of Family Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Jungeun Kim
- Department of Family Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Duk-Chul Lee
- Department of Family Medicine, Yonsei University College of Medicine, Seoul, Korea
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Huang HH, Chen YL, Chen JS, Lin JD, Hsieh CH, Pei D, Wu CZ. Relationships Among C-Reactive Protein, Alanine Aminotransferase, and Metabolic Syndrome in Apparently Healthy Chinese Subjects. Metab Syndr Relat Disord 2018; 16:232-239. [PMID: 29688806 DOI: 10.1089/met.2017.0059] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
AIM Elevated levels of C-reactive protein (CRP) and alanine aminotransferase (ALT) are tightly associated with metabolic syndrome (MetS). However, it is unclear whether the combination of normal CRP and ALT increases probability of the presence of MetS. MATERIALS AND METHODS We enrolled 433 Chinese in health screening with both CRP and ALT in normal range. They were divided into four groups: both low (BL, both low baseline CRP and ALT), only high CRP (HCRP), only high ALT (HALT), and both high (BH, both high baseline CRP and ALT) in different genders. The receiver operating characteristic curve was used for comparing the sensitivity and assessing the cutoff point. RESULTS The BH group had more numbers of MetS components than the BL group. Addition of CRP and ALT did not further increase the accuracy of predicting MetS with a sensitivity of 65.1% and a specificity of 59.1% in men, and a sensitivity of 77.8% and a specificity of 60.2% in women. The area under curve for ALT was greater than that for CRP (0.62 vs. 0.524 in men; 0.663 vs. 0.598 in women). After adjusting for age, ALT could significantly predict the incidental MetS in both genders; nevertheless, CRP failed to demonstrate prediction. The formula of probability of occurrence of MetS was established on CRP and ALT. CONCLUSIONS Healthy subjects with high baseline ALT may be at risk of developing MetS, and early recognition and prevention are important for health providers. We concluded that local liver inflammation is significantly associated with the presence of MetS compared with systemic inflammation in health screening subjects.
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Affiliation(s)
- Hsin-Hung Huang
- 1 Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center , Taipei, Taiwan, Republic of China
| | - Yen-Lin Chen
- 2 Department of Pathology, Cardinal Tien Hospital, Medical School, Catholic Fu Jen University , Xindian, Taiwan, Republic of China
| | - Jin-Shuen Chen
- 3 Division of Nephrology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center , Taipei, Taiwan, Republic of China
| | - Jiunn-Diann Lin
- 4 Division of Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University , Taipei, Taiwan, Republic of China .,5 Division of Endocrinology and Metabolism, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University , Taipei, Taiwan, Republic of China
| | - Chang-Hsun Hsieh
- 6 Division of Endocrinology and Metabolism, Department of Internal Medicine, National Defense Medical Center , Tri-Service General Hospital, Taipei, Taiwan, Republic of China
| | - Dee Pei
- 7 Division of Endocrinology and Metabolism, Department of Internal Medicine, Cardinal Tien Hospital, Medical School, Catholic Fu Jen University , Xindian, Taiwan, Republic of China
| | - Chung-Ze Wu
- 4 Division of Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University , Taipei, Taiwan, Republic of China .,5 Division of Endocrinology and Metabolism, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University , Taipei, Taiwan, Republic of China
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Fayh APT, Borges K, Cunha GS, Krause M, Rocha R, de Bittencourt PIH, Moreira JCF, Friedman R, da Silva Rossato J, Fernandes JR, Reischak-Oliveira A. Effects of n-3 fatty acids and exercise on oxidative stress parameters in type 2 diabetic: a randomized clinical trial. J Int Soc Sports Nutr 2018; 15:18. [PMID: 29713249 PMCID: PMC5914016 DOI: 10.1186/s12970-018-0222-2] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2017] [Accepted: 04/12/2018] [Indexed: 12/21/2022] Open
Abstract
Background The relationship between diabetes and oxidative stress has been previously reported. Exercise represents a useful non-pharmacological strategy for the treatment in type 2 diabetic (T2DM) patients, but high intensity exercise can induce a transient inflammatory state and increase oxidative stress. Nutritional strategies that may contribute to the reduction of oxidative stress induced by acute exercise are necessary. The aim of this study was to examine if n-3 PUFA supplementation intervention can attenuate the inflammatory response and oxidative stress associated with high intensity exercise in this population. As a primary outcome, lipoperoxidation measurements (TBARS and F2-isoprostanes) were selected. Methods Thirty T2DM patients, without chronic complications, were randomly allocated into two groups: placebo (gelatin capsules) or n-3 PUFA (capsules containing 180 mg of eicosapentaenoic acid and 120 mg of docosahexaenoic acid). Blood samples were collected fasting before and after 8 weeks supplementation. In the beginning and at the end of protocol, an acute exercise was performed (treadmill), and new blood samples were collected before and immediately after the exercise for measurements of oxidative stress and high-sensitivity C-reactive protein (hs-CRP). Results After the supplementation period, a decrease in triglycerides levels was observed only in n-3 PUFA supplementation group (mean difference and 95% CI of 0.002 (0.000–0.004), p = 0.005). Supplementation also significantly reduced TRAP levels after exercise (mean difference and 95% CI to 9641 (− 20,068–39,351) for − 33,884 (− 56,976 - -10,793), p = 0.004, Cohen’s d effect size = 1.12), but no significant difference was observed in n-3 PUFA supplementation group in lipoperoxidation parameters as TBARS (mean difference and 95% CI to − 3.8 (− 10–2.4) for − 2.9 (− 1.6–7.4) or F2-isoprostanes (mean difference and 95% CI -0.05 (− 0.19–0.10) for − 0.02 (− 0.19–0.16), p > 0.05 for both. Conclusion PUFA n-3 supplementation reduced triglycerides as well as TRAP levels after exercise, without a significant effect on inflammatory and oxidative stress markers. This study is registered at ClinicalTrials.gov with the registration number of NCT03182712.
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Affiliation(s)
- Ana Paula Trussardi Fayh
- Departament of Nutrition, Health Sciences Center, Federal University of State of Rio Grande do Norte, Avenida Senador Salgado Filho, n° 3000, Natal, RN 59078-970 Brazil
| | - Katiuce Borges
- 2Laboratório de Pesquisa do Exercício, Escola de Educação Física, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90690-200 Brazil
| | - Giovani Santos Cunha
- 2Laboratório de Pesquisa do Exercício, Escola de Educação Física, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90690-200 Brazil
| | - Mauricio Krause
- 3Laboratory of Inflammation, Metabolism and Exercise Research (LAPIMEX) and Laboratory of Cellular Physiology, Departamento de Fisiologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90050-170 Brazil
| | - Ricardo Rocha
- 4Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-000 Brazil
| | - Paulo Ivo Homem de Bittencourt
- 3Laboratory of Inflammation, Metabolism and Exercise Research (LAPIMEX) and Laboratory of Cellular Physiology, Departamento de Fisiologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90050-170 Brazil
| | - José Cláudio Fonseca Moreira
- 4Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-000 Brazil
| | - Rogério Friedman
- 5Endocrine Unit, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-000 Brazil
| | - Juliane da Silva Rossato
- 3Laboratory of Inflammation, Metabolism and Exercise Research (LAPIMEX) and Laboratory of Cellular Physiology, Departamento de Fisiologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90050-170 Brazil
| | - Jõao Roberto Fernandes
- 2Laboratório de Pesquisa do Exercício, Escola de Educação Física, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90690-200 Brazil
| | - Alvaro Reischak-Oliveira
- 2Laboratório de Pesquisa do Exercício, Escola de Educação Física, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90690-200 Brazil
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Association of high sensitivity C-reactive protein concentrations and metabolic syndrome among Thai adults. ASIAN BIOMED 2018. [DOI: 10.2478/abm-2010-0047] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Abstract
Background: Limited information is available regarding associations of metabolic syndrome with C-reactive protein (CRP) concentrations among Asian populations. Objective: Investigate the association of high sensitivity CRP (hsCRP) concentrations and metabolic syndrome among Thai adults. Methods: This cross-sectional study was comprised of 467 Thai participants (209 men and 258 women) receiving annual health check-up. Spearman’s rank correlation coefficients were used to assess the associations between metabolic parameters (age, waist circumference, blood pressure, triglycerides, HDL-C, fasting plasma glucose, fasting insulin and uric acid) with hsCRP concentrations for men and women, respectively. Multivariable logistic regression procedures were used to estimate the risk (odds ratios (OR), and 95% confidence intervals (CI) of metabolic syndrome according to low, moderate, and high hsCRP concentrations (<1.0, 1.0-3.0, and >3.0 mg/L, respectively). Results: Measures of adiposity and fasting insulin were positively and significantly correlated with hsCRP concentrations among women with and without metabolic syndrome. Similar associations were observed among men without metabolic syndrome. After controlling for confounders, moderately elevated hsCRP concentrations were associated with a 2.38-fold increased risk of metabolic syndrome (OR=2.38, 95%CI=1.20-4.72) among men. Men with high hsCRP concentrations had a 5.45-fold increased risk of metabolic syndrome (OR=5.45, 95%CI=2.24- 13.27) when compared with those who had low hsCRP concentrations. The corresponding OR for women with moderately elevated and high hsCRP concentrations were 4.92 (OR=4.92, 95%CI=2.34-10.35) and 11.93 (OR=11.93, 95%CI=5.54-25.72), respectively. Conclusions: These findings are consistent with the literature suggesting a role of hsCRP as a biomarker for metabolic syndrome.
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Benjamin EJ, Virani SS, Callaway CW, Chamberlain AM, Chang AR, Cheng S, Chiuve SE, Cushman M, Delling FN, Deo R, de Ferranti SD, Ferguson JF, Fornage M, Gillespie C, Isasi CR, Jiménez MC, Jordan LC, Judd SE, Lackland D, Lichtman JH, Lisabeth L, Liu S, Longenecker CT, Lutsey PL, Mackey JS, Matchar DB, Matsushita K, Mussolino ME, Nasir K, O'Flaherty M, Palaniappan LP, Pandey A, Pandey DK, Reeves MJ, Ritchey MD, Rodriguez CJ, Roth GA, Rosamond WD, Sampson UKA, Satou GM, Shah SH, Spartano NL, Tirschwell DL, Tsao CW, Voeks JH, Willey JZ, Wilkins JT, Wu JH, Alger HM, Wong SS, Muntner P. Heart Disease and Stroke Statistics-2018 Update: A Report From the American Heart Association. Circulation 2018; 137:e67-e492. [PMID: 29386200 DOI: 10.1161/cir.0000000000000558] [Citation(s) in RCA: 4758] [Impact Index Per Article: 679.7] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Winter L, Wong LA, Jerums G, Seah JM, Clarke M, Tan SM, Coughlan MT, MacIsaac RJ, Ekinci EI. Use of Readily Accessible Inflammatory Markers to Predict Diabetic Kidney Disease. Front Endocrinol (Lausanne) 2018; 9:225. [PMID: 29910771 PMCID: PMC5992400 DOI: 10.3389/fendo.2018.00225] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2018] [Accepted: 04/20/2018] [Indexed: 12/18/2022] Open
Abstract
Diabetic kidney disease is a common complication of type 1 and type 2 diabetes and is the primary cause of end-stage renal disease in developed countries. Early detection of diabetic kidney disease will facilitate early intervention aimed at reducing the rate of progression to end-stage renal disease. Diabetic kidney disease has been traditionally classified based on the presence of albuminuria. More recently estimated glomerular filtration rate has also been incorporated into the staging of diabetic kidney disease. While albuminuric diabetic kidney disease is well described, the phenotype of non-albuminuric diabetic kidney disease is now widely accepted. An association between markers of inflammation and diabetic kidney disease has previously been demonstrated. Effector molecules of the innate immune system including C-reactive protein, interleukin-6, and tumor necrosis factor-α are increased in patients with diabetic kidney disease. Furthermore, renal infiltration of neutrophils, macrophages, and lymphocytes are observed in renal biopsies of patients with diabetic kidney disease. Similarly high serum neutrophil and low serum lymphocyte counts have been shown to be associated with diabetic kidney disease. The neutrophil-lymphocyte ratio is considered a robust measure of systemic inflammation and is associated with the presence of inflammatory conditions including the metabolic syndrome and insulin resistance. Cross-sectional studies have demonstrated a link between high levels of the above inflammatory biomarkers and diabetic kidney disease. Further longitudinal studies will be required to determine if these readily available inflammatory biomarkers can accurately predict the presence and prognosis of diabetic kidney disease, above and beyond albuminuria, and estimated glomerular filtration rate.
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Affiliation(s)
- Lauren Winter
- Endocrine Centre of Excellence, Austin Health, Melbourne, VIC, Australia
- Department of Medicine, Austin Health, University of Melbourne, Melbourne, VIC, Australia
| | - Lydia A. Wong
- Endocrine Centre of Excellence, Austin Health, Melbourne, VIC, Australia
| | - George Jerums
- Endocrine Centre of Excellence, Austin Health, Melbourne, VIC, Australia
| | - Jas-mine Seah
- Endocrine Centre of Excellence, Austin Health, Melbourne, VIC, Australia
| | - Michele Clarke
- Endocrine Centre of Excellence, Austin Health, Melbourne, VIC, Australia
| | - Sih Min Tan
- Department of Diabetes, Central Clinical School, Monash University, Melbourne, VIC, Australia
| | - Melinda T. Coughlan
- Department of Diabetes, Central Clinical School, Monash University, Melbourne, VIC, Australia
| | - Richard J. MacIsaac
- Department of Endocrinology and Diabetes, St Vincent’s Health, Melbourne, VIC, Australia
- Department of Medicine, St Vincent’s Health, University of Melbourne, Melbourne, VIC, Australia
| | - Elif I. Ekinci
- Endocrine Centre of Excellence, Austin Health, Melbourne, VIC, Australia
- Department of Medicine, Austin Health, University of Melbourne, Melbourne, VIC, Australia
- *Correspondence: Elif I. Ekinci,
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Chan PC, Wang YC, Chen YL, Hsu WN, Tian YF, Hsieh PS. Importance of NADPH oxidase-mediated redox signaling in the detrimental effect of CRP on pancreatic insulin secretion. Free Radic Biol Med 2017; 112:200-211. [PMID: 28778482 DOI: 10.1016/j.freeradbiomed.2017.07.032] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2017] [Revised: 07/02/2017] [Accepted: 07/31/2017] [Indexed: 10/19/2022]
Abstract
Elevations in C-reactive protein (CRP) levels are positively correlated with the progress of type 2 diabetes mellitus. However, the effect of CRP on pancreatic insulin secretion is unknown. Here, we showed that purified human CRP impaired insulin secretion in isolated mouse islets and NIT-1 insulin-secreting cells in dose- and time-dependent manners. CRP increased NADPH oxidase-mediated ROS (reactive oxygen species) production, which simultaneously promoted the production of nitrotyrosine (an indicator of RNS, reactive nitrogen species) and TNFα, to diminish cell viability, insulin secretion in islets and insulin-secreting cells. These CRP-mediated detrimental effects on cell viability and insulin secretion were significantly reversed by adding NAC (a potent antioxidant), apocynin (a selective NADPH oxidase inhibitor), L-NAME (a non-selective nitric oxide synthase (NOS) inhibitor), aminoguanidine (a selective iNOS inhibitor), PDTC (a selective NFκB inhibitor) or Enbrel (an anti-TNFα fusion protein). However, CRP-induced ROS production failed to change after adding L-NAME, aminoguanidine or PDTC. In isolated islets and NIT-1 cells, the elevated nitrotyrosine contents by CRP pretreatment were significantly suppressed by adding L-NAME but not PDTC. Conversely, CRP-induced increases in TNF-α production were significantly reversed by administration of PDTC but not L-NAME. In addition, wild-type mice treated with purified human CRP showed significant decreases in the insulin secretion index (HOMA-β cells) and the insulin stimulation index in isolated islets that were reversed by the addition of L-NAME, aminoguanidine or NAC. It is suggested that CRP-activated NADPH-oxidase redox signaling triggers iNOS-mediated RNS and NFκB-mediated proinflammatory cytokine production to cause β cell damage in state of inflammation.
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Affiliation(s)
- Pei-Chi Chan
- Department of Physiology and Biophysics, National Defense Medical Center, Taipei, Taiwan
| | - Ya-Chin Wang
- Department of Physiology and Biophysics, National Defense Medical Center, Taipei, Taiwan
| | - Yi-Ling Chen
- Department of Physiology and Biophysics, National Defense Medical Center, Taipei, Taiwan
| | - Wan-Ning Hsu
- Department of Physiology and Biophysics, National Defense Medical Center, Taipei, Taiwan
| | - Yu-Feng Tian
- Division of General Surgery, Department of Surgery, Yung Kung campus, Chi-Mei Medical Center, Tainan, Taiwan
| | - Po-Shiuan Hsieh
- Department of Physiology and Biophysics, National Defense Medical Center, Taipei, Taiwan; Institute of Preventive Medicine, National Defense Medical Center, Sanxia, Taiwan; Department of Medical Research, Tri-Service General Hospital, Taipei, Taiwan.
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Van Dyke AL, Lang Kuhs KA, Shiels MS, Koshiol J, Trabert B, Loftfield E, Purdue MP, Wentzensen N, Pfeiffer RM, Katki HA, Hildesheim A, Kemp TJ, Pinto LA, Chaturvedi AK, Safaeian M. Associations between self-reported diabetes and 78 circulating markers of inflammation, immunity, and metabolism among adults in the United States. PLoS One 2017; 12:e0182359. [PMID: 28753646 PMCID: PMC5533447 DOI: 10.1371/journal.pone.0182359] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2017] [Accepted: 07/17/2017] [Indexed: 12/13/2022] Open
Abstract
Inflammation is increasingly thought to be associated with diabetes; however, only a few inflammation markers have been assessed concurrently in relation to history of diabetes. In the most comprehensive evaluation of inflammation markers and diabetes to date using a Luminex bead-based assay, we measured 78 inflammation-, immune-, and metabolic-related markers detectable in at least 10% of serum samples collected from participants from the Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) screening trial (n = 1,814). At baseline, 6.6% (n = 120) of PLCO participants self-reported a history of diabetes. Cross-sectional associations between these markers and self-reported diabetes were assessed using weighted logistic regression adjusting for sex, smoking status, blood draw age and year, body mass index, and cohort sub-study. Including chemokines [C-C motif ligand (CCL) 19, CCL20, CCL21, C-X-C motif ligand (CXCL) 6, CXCL10, and CXCL11] and soluble cytokine and chemokine receptors [soluble (s) interleukin (IL) 6 receptor (R), soluble tumor necrosis factor receptor (sTNFR) 1, sTNFR2, and sIL-R2], ten inflammation-related markers, were nominally associated with diabetes (P<0.05). In addition to these associations, higher levels of insulin, gastric inhibitory polypeptide, and pancreatic polypeptide remained significantly associated with self-reported diabetes with a false discovery rate <5%, indicating that the assay was able to detect markers associated with diabetes. In summary, self-reported diabetes was nominally associated with circulating cytokines, chemokines, and soluble cytokine and chemokine receptors in the most expansive examination of diabetes and inflammation- and immune-related markers to date. These results highlight the need to explore in future prospective studies the role of inflammation markers in diabetes.
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Affiliation(s)
- Alison L. Van Dyke
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland, United States of America
| | - Krystle A. Lang Kuhs
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland, United States of America
| | - Meredith S. Shiels
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland, United States of America
| | - Jill Koshiol
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland, United States of America
| | - Britton Trabert
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland, United States of America
| | - Erikka Loftfield
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland, United States of America
| | - Mark P. Purdue
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland, United States of America
| | - Nicolas Wentzensen
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland, United States of America
| | - Ruth M. Pfeiffer
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland, United States of America
| | - Hormuzd A. Katki
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland, United States of America
| | - Allan Hildesheim
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland, United States of America
| | - Troy J. Kemp
- Human Papilloma Virus Immunology Laboratory, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America
| | - Ligia A. Pinto
- Human Papilloma Virus Immunology Laboratory, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America
| | - Anil K. Chaturvedi
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland, United States of America
| | - Mahboobeh Safaeian
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland, United States of America
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Rovira-Llopis S, Bañuls C, de Marañon AM, Diaz-Morales N, Jover A, Garzon S, Rocha M, Victor VM, Hernandez-Mijares A. Low testosterone levels are related to oxidative stress, mitochondrial dysfunction and altered subclinical atherosclerotic markers in type 2 diabetic male patients. Free Radic Biol Med 2017; 108:155-162. [PMID: 28359952 DOI: 10.1016/j.freeradbiomed.2017.03.029] [Citation(s) in RCA: 82] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2017] [Revised: 03/11/2017] [Accepted: 03/25/2017] [Indexed: 12/29/2022]
Abstract
INTRODUCTION Low testosterone levels in men are associated with type 2 diabetes and cardiovascular risk. However, the role of testosterone in mitochondrial function and leukocyte-endothelium interactions is unknown. Our aim was to evaluate the relationship between testosterone levels, metabolic parameters, oxidative stress, mitochondrial function, inflammation and leukocyte-endothelium interactions in type 2 diabetic patients. MATERIALS AND METHODS The study was performed in 280 male type 2 diabetic patients and 50 control subjects. Anthropometric and metabolic parameters, testosterone levels, reactive oxygen species (ROS) production, mitochondrial membrane potential, TNFα, adhesion molecules and leukocyte-endothelium cell interactions were evaluated. RESULTS Testosterone levels were lower in diabetic patients. Total and mitochondrial ROS were increased and mitochondrial membrane potential, SOD and GSR expression levels were reduced in diabetic patients. TNFα, ICAM-1 and VCAM-1 levels, leukocyte rolling flux and adhesion were all enhanced in diabetic patients, while rolling velocity was reduced. Testosterone levels correlated negatively with glucose, HOMA-IR, HbA1c, triglycerides, nonHDL-c, ApoB, hs-CRP and AIP, and positively with HDL-c and ApoA1. The multivariable regression model showed that HDL-c, HOMA-IR and age were independently associated with testosterone. Furthermore, testosterone levels correlated positively with membrane potential and rolling velocity and negatively with ROS production, VCAM-1, rolling flux and adhesion. CONCLUSIONS Our data highlight that low testosterone levels in diabetic men are related to impaired metabolic profile and mitochondrial function and enhanced inflammation and leukocyte-endothelium cell interaction, which leaves said patients at risk of cardiovascular events.
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Affiliation(s)
- Susana Rovira-Llopis
- Service of Endocrinology and Nutrition, University Hospital Doctor Peset-FISABIO, Valencia, Spain
| | - Celia Bañuls
- Service of Endocrinology and Nutrition, University Hospital Doctor Peset-FISABIO, Valencia, Spain
| | - Aranzazu M de Marañon
- Service of Endocrinology and Nutrition, University Hospital Doctor Peset-FISABIO, Valencia, Spain
| | - Noelia Diaz-Morales
- Service of Endocrinology and Nutrition, University Hospital Doctor Peset-FISABIO, Valencia, Spain
| | - Ana Jover
- Service of Endocrinology and Nutrition, University Hospital Doctor Peset-FISABIO, Valencia, Spain
| | - Sandra Garzon
- Service of Endocrinology and Nutrition, University Hospital Doctor Peset-FISABIO, Valencia, Spain
| | - Milagros Rocha
- Service of Endocrinology and Nutrition, University Hospital Doctor Peset-FISABIO, Valencia, Spain; CIBER CB06/04/0071 Research Group, CIBER Hepatic and Digestive Diseases, Department of Pharmacology, University of Valencia, Valencia, Spain
| | - Victor M Victor
- Service of Endocrinology and Nutrition, University Hospital Doctor Peset-FISABIO, Valencia, Spain; CIBER CB06/04/0071 Research Group, CIBER Hepatic and Digestive Diseases, Department of Pharmacology, University of Valencia, Valencia, Spain; Department of Physiology, University of Valencia, Valencia, Spain.
| | - Antonio Hernandez-Mijares
- Service of Endocrinology and Nutrition, University Hospital Doctor Peset-FISABIO, Valencia, Spain; Department of Medicine, University of Valencia, Valencia, Spain.
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Benjamin EJ, Blaha MJ, Chiuve SE, Cushman M, Das SR, Deo R, de Ferranti SD, Floyd J, Fornage M, Gillespie C, Isasi CR, Jiménez MC, Jordan LC, Judd SE, Lackland D, Lichtman JH, Lisabeth L, Liu S, Longenecker CT, Mackey RH, Matsushita K, Mozaffarian D, Mussolino ME, Nasir K, Neumar RW, Palaniappan L, Pandey DK, Thiagarajan RR, Reeves MJ, Ritchey M, Rodriguez CJ, Roth GA, Rosamond WD, Sasson C, Towfighi A, Tsao CW, Turner MB, Virani SS, Voeks JH, Willey JZ, Wilkins JT, Wu JH, Alger HM, Wong SS, Muntner P. Heart Disease and Stroke Statistics-2017 Update: A Report From the American Heart Association. Circulation 2017; 135:e146-e603. [PMID: 28122885 PMCID: PMC5408160 DOI: 10.1161/cir.0000000000000485] [Citation(s) in RCA: 6341] [Impact Index Per Article: 792.6] [Reference Citation Analysis] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Kaspersen KA, Dinh KM, Erikstrup LT, Burgdorf KS, Pedersen OB, Sørensen E, Petersen MS, Hjalgrim H, Rostgaard K, Nielsen KR, Ullum H, Erikstrup C. Low-Grade Inflammation Is Associated with Susceptibility to Infection in Healthy Men: Results from the Danish Blood Donor Study (DBDS). PLoS One 2016; 11:e0164220. [PMID: 27701463 PMCID: PMC5049789 DOI: 10.1371/journal.pone.0164220] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2016] [Accepted: 09/21/2016] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION The aim of this study was to examine whether low-grade inflammation (LGI) is associated with a subsequently increased risk of infection. METHODS We included 15,754 healthy participants from the Danish Blood Donor Study, who completed a questionnaire on health-related items. LGI was defined as a C-reactive protein level between 3 and 10 mg/L. Infections were identified by ICD-10 codes in the Danish National Patient Register and ATC-codes in the Danish Prescription Register. Multivariable Cox proportional hazard analysis was used as the statistical model. RESULTS During 53,302 person-years of observation, 571 participants were hospitalized for infection. Similarly, during 26,125 person-years of observation, 7,276 participants filled a prescription of antimicrobials. LGI was associated with increased risk of hospital-based treatment for infection only among men (hazard ratio = 1.60, 95% confidence interval (CI): 1.10-2.34) and specifically infections were abscesses and infections of the skin and subcutaneous tissue. Similarly, LGI was associated with the overall use of antimicrobials among men, and particularly with phenoxymethylpenicillin and broad-spectrum antimicrobials for treatment of urinary tract infections. The difference between men and women was not statistically significant. CONCLUSIONS In a large cohort of healthy individuals, LGI was associated with an increased risk of infection among healthy male blood donors.
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Affiliation(s)
| | - Khoa Manh Dinh
- Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark
| | | | | | | | - Erik Sørensen
- Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen S, Denmark
| | | | - Henrik Hjalgrim
- Department of Epidemiology Research, Statens Serum Institut, Copenhagen S, Denmark
| | - Klaus Rostgaard
- Department of Epidemiology Research, Statens Serum Institut, Copenhagen S, Denmark
| | - Kaspar Rene Nielsen
- Department of Clinical Immunology, Aalborg University Hospital, Aalborg, Denmark
| | - Henrik Ullum
- Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen S, Denmark
| | - Christian Erikstrup
- Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark
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Liu C, Feng X, Li Q, Wang Y, Li Q, Hua M. Adiponectin, TNF-α and inflammatory cytokines and risk of type 2 diabetes: A systematic review and meta-analysis. Cytokine 2016; 86:100-109. [PMID: 27498215 DOI: 10.1016/j.cyto.2016.06.028] [Citation(s) in RCA: 319] [Impact Index Per Article: 35.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2016] [Revised: 06/28/2016] [Accepted: 06/29/2016] [Indexed: 12/11/2022]
Abstract
AIMS There has been growing evidence that adiponectin, tumor necrosis factor-α (TNF-α) and inflammatory cytokines involved in insulin resistance and may be attractive candidates for assessing risk of the incident type 2 diabetes (T2DM). A systematic review and meta-analysis of prospective studies was conducted to assess the associations of levels of serum adiponectin, TNF-α and inflammatory markers (Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6), Interleukin-18 (IL-18), C-reactive protein (CRP)) with risk of T2DM. MATERIALS/METHODS We searched PubMed, ISI Web of Knowledge, EMBASE, and Cochrane Library databases up until February 1, 2016 for eligible studies which were matched to search subjects. Either fixed-effects or random-effects models were used to estimate the summary risk incorporated between study variations. RESULTS 19 studies comprising a total of 39,136 participants and 7924 cases were included in the meta-analysis. Our findings showed that an obvious association of elevated CRP levels with T2DM risk (relative risk [RR] 1.48 [95% CI 1.26-1.71]), with the absence of publication bias. For IL-6, the meta-analysis involved 16 cohorts with a total of 24,929 participants and 4751 cases. Using data from all trials, a strong positive correlation (1.32 [1.14, 1.51]) was observed between basal plasma IL-6 and T2DM, whereas relatively lower relation between TNF-α (1.16 [0.87, 1.45]), IL-18 (1.45 [1.16, 1.73]), IL-1β (0.87, [0.59, 1.15]) and independently increased risk to occurrence of T2DM. Conversely, we also found that the level of adiponectin decreased significantly in patients with T2DM. Sensitivity analyses further supported the associations. CONCLUSIONS This meta-analysis indicates that T2DM risk as whole was strongly associated with elevated levels of inflammatory cytokines (IL-1β, IL-6, IL-18, CRP), TNF-α and low levels of adiponectin. Despite an overall detectable association in the meta-analysis, considerable heterogeneity existed between studies. Further work is needed, it seems clear that a complex interplay of inflammation and the development of DM. Moreover, these biomarkers are predictors of T2DM subjects and should take more attention to measure levels of these as well as to target therapy/interventions.
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Affiliation(s)
- Chenxiao Liu
- Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
| | - Xiu Feng
- Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
| | - Qi Li
- Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
| | - Ying Wang
- Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
| | - Qian Li
- Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
| | - Majian Hua
- Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
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Hwu CM, Lin YC, Lin MW. High Levels of C-Reactive Protein Are Positively Associated with Isolated Postchallenge Hyperglycemia in Postmenopausal Women. Metab Syndr Relat Disord 2016; 14:334-339. [PMID: 27304050 DOI: 10.1089/met.2015.0118] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Isolated postchallenge hyperglycemia (IPH) is an early form of type 2 diabetes with fasting glucose <126 mg/dL and 2-hr postchallenge glucose ≥200 mg/dL. The purpose of this study was to explore the relationships of high-sensitivity C-reactive protein (hsCRP) with IPH. METHODS We recruited 476 naturally postmenopausal women without a history of diabetes mellitus for the study. Fasting blood samples were collected for the measurements of hsCRP and biochemistry. All participants received a 75 g oral glucose tolerance test to examine if they had IPH. The relative contributions of body mass index (BMI) and homeostasis model assessment of insulin resistance (HOMA-IR) to the association of hsCRP with IPH were evaluated by logistic regression. RESULTS There was an increasing trend in prevalence of IPH with increasing quartiles of hsCRP (2.9%, 3.6%, 5.9%, and 7.6% in quartile 1-4, respectively) (P = 0.001). BMI and HOMA-IR were the most important determinants of hsCRP in this cohort. We observed a significant and positive association between high hsCRP levels and IPH in our subjects. Compared with subjects in the lowest quartile group, individuals with high levels of hsCRP (the 3rd and the 4th quartiles) were 2-2.5 times more likely associated with IPH, before and after adjustments for BMI and HOMA-IR values (all P < 0.05). CONCLUSION Our results demonstrated that chronic inflammation, measured by elevated serum hsCRP levels, was positively associated with IPH in postmenopausal women. This finding was independent of obesity and insulin resistance.
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Affiliation(s)
- Chii-Min Hwu
- 1 Section of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital , Taipei, Taiwan
- 2 Faculty of Medicine, National Yang-Ming University School of Medicine , Taipei, Taiwan
| | - Yi-Chun Lin
- 1 Section of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital , Taipei, Taiwan
- 2 Faculty of Medicine, National Yang-Ming University School of Medicine , Taipei, Taiwan
| | - Ming-Wei Lin
- 3 Institute of Public Health, National Yang-Ming University School of Medicine , Taipei, Taiwan
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Emerging Cardiovascular Disease Biomarkers and Incident Diabetes Mellitus Risk in Statin-Treated Patients With Coronary Artery Disease (from the Treating to New Targets [TNT] Study). Am J Cardiol 2016; 118:494-8. [PMID: 27328952 DOI: 10.1016/j.amjcard.2016.05.044] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2016] [Revised: 05/05/2016] [Accepted: 05/05/2016] [Indexed: 01/19/2023]
Abstract
Whether biomarkers associated with cardiovascular disease risk also predict incident diabetes mellitus (DM) is unknown. Our objective was to determine if a panel of 18 biomarkers previously associated with risk of cardiovascular disease also predicts incident DM in statin-treated patients with coronary artery disease (CAD). The Treating to New Targets (TNT) study is a randomized trial that compared the efficacy of high (80 mg) versus low (10 mg) dose atorvastatin for the secondary prevention of coronary heart disease events. Fasting plasma levels of standard lipids and of 18 emerging CAD risk biomarkers were obtained after an 8-week run-in period on atorvastatin 10 mg in a random sample of 1,424 TNT patients. After exclusion of patients with DM at baseline (n = 253), 101 patients developed DM during the median follow-up of 4.9 years. Patients with incident DM had lower levels of total and high-molecular weight adiponectin, lipoprotein-associated phospholipase A2 (Lp-PLA2), soluble receptor of advanced glycation end products, and vitamin D compared with patients without incident DM. In contrast, insulin, soluble CD40 ligand, and soluble intercellular adhesion molecule-1 levels were higher in patients with incident DM compared with those without. Plasma levels of C-reactive protein, cystatin C, lipoprotein(a), monocyte chemotactic protein-1, matrix metalloproteinase-9, myeloperoxidase, neopterin, N-terminal fragment of pro-B-type natriuretic peptide, osteopontin, and soluble vascular cell adhesion molecule-1 were comparable in patients with and without incident DM. After multivariate adjustment, total and high-molecular weight adiponectin as well as Lp-PLA2 were negatively associated with incident DM. Results of this study suggest that plasma lipids and some emerging CAD risk biomarkers, such as adiponectin and Lp-PLA2, may be useful for predicting incident DM in statin-treated patients with stable CAD.
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Al-Jiffri OH, Al-Sharif FM, Al-Jiffri EH, Uversky VN. Intrinsic disorder in biomarkers of insulin resistance, hypoadiponectinemia, and endothelial dysfunction among the type 2 diabetic patients. INTRINSICALLY DISORDERED PROTEINS 2016; 4:e1171278. [PMID: 28232897 DOI: 10.1080/21690707.2016.1171278] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/02/2015] [Revised: 03/15/2016] [Accepted: 03/17/2016] [Indexed: 02/06/2023]
Abstract
Type 2 diabetes mellitus (T2DM) is a chronic and progressive disease that is strongly associated with various complications including cardiovascular diseases and related mortality. The present study aimed to analyze the abundance and functionality of intrinsically disordered regions in several biomarkers of insulin resistance, adiponectin, and endothelial dysfunction found in the T2DM patients. In fact, in comparison to controls, obese T2DM patients are known to have significantly higher levels of inter-cellular adhesion molecule (iCAM-1), vascular cell adhesion molecule (vCAM-1), and E-selectin, whereas their adiponectin levels are relatively low. Bioinformatics analysis revealed that these selected biomarkers (iCAM-1, vCAM-1, E-selectin, and adiponectin) are characterized by the noticeable levels of intrinsic disorder propensity and high binding promiscuity, which are important features expected for proteins serving as biomarkers. Within the limit of studied groups, there is an association between insulin resistance and both hypoadiponectinemia and endothelial dysfunction.
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Affiliation(s)
- Osama H Al-Jiffri
- Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University , Jeddah, Saudi Arabia
| | - Fadwa M Al-Sharif
- Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University , Jeddah, Saudi Arabia
| | - Essam H Al-Jiffri
- Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University , Jeddah, Saudi Arabia
| | - Vladimir N Uversky
- Faculty of Science, Department of Biological Science, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Molecular Medicine and USF Health Byrd Alzheimer Research Institute, Morsani College of Medicine, University of South Florida, Tampa, FL, USA; Laboratory of Structural Dynamics, Stability and Folding of Proteins, Institute of Cytology, Russian Academy of Sciences, St. Petersburg, Russia
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Kim DH, Yoo SD, Chon J, Yun DH, Kim HS, Park HJ, Kim SK, Chung JH, Kang JK, Lee SA. Interleukin-6 Receptor Polymorphisms Contribute to the Neurological Status of Korean Patients with Ischemic Stroke. J Korean Med Sci 2016; 31:430-4. [PMID: 26955245 PMCID: PMC4779869 DOI: 10.3346/jkms.2016.31.3.430] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2015] [Accepted: 09/23/2015] [Indexed: 11/26/2022] Open
Abstract
To investigate the contribution of the interleukin-6 receptor (IL-6R) gene single nucleotide polymorphisms (SNPs) to the neurological status of Korean patients with ischemic stroke (IS), two SNPs of the IL-6R gene (rs4845617, 5 UTR; rs2228144, Ala31Ala) were selected. IS patients were classified into clinical phenotypes according to two well-defined scores: the National Institutes of Health Stroke Survey (NIHSS) and the Modified Barthel Index scores. There were 121 IS patients and 291 control subjects. The SNP rs4845617 significantly contributed to the neurological status of patients with IS (P = 0.011 in codominant model 2, P = 0.006 in recessive model, and P = 0.008 in log-additive model). Allele frequencies of rs4845617 and rs2228144 demonstrated no significant difference in IS patients and controls. The AG and GG haplotypes differed between the NIHSS 1 (NIHSS scores < 6) group and the NIHSS 2 (NIHSS scores ≥ 6) group in patients with IS (P = 0.014, P = 0.0024). These results suggest that rs4845617 of the IL-6R gene is associated with the neurologic status of Korean patients with IS.
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Affiliation(s)
- Dong Hwan Kim
- Department of Physical Medicine & Rehabilitation, College of Medicine, Kyung Hee University, Seoul, Korea
| | - Seung Don Yoo
- Department of Physical Medicine & Rehabilitation, College of Medicine, Kyung Hee University, Seoul, Korea
| | - Jinmann Chon
- Department of Physical Medicine & Rehabilitation, College of Medicine, Kyung Hee University, Seoul, Korea
| | - Dong Hwan Yun
- Department of Physical Medicine & Rehabilitation, College of Medicine, Kyung Hee University, Seoul, Korea
| | - Hee-Sang Kim
- Department of Physical Medicine & Rehabilitation, College of Medicine, Kyung Hee University, Seoul, Korea
| | - Hae Jeong Park
- Kohwang Medical Research Institute, Kyung Hee University, Seoul, Korea
| | - Su Kang Kim
- Kohwang Medical Research Institute, Kyung Hee University, Seoul, Korea
| | - Joo-Ho Chung
- Kohwang Medical Research Institute, Kyung Hee University, Seoul, Korea
| | - Jin Kyu Kang
- Department of Physical Medicine & Rehabilitation, College of Medicine, Kyung Hee University, Seoul, Korea
| | - Seung Ah Lee
- Department of Physical Medicine & Rehabilitation, College of Medicine, Kyung Hee University, Seoul, Korea
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Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, Das SR, de Ferranti S, Després JP, Fullerton HJ, Howard VJ, Huffman MD, Isasi CR, Jiménez MC, Judd SE, Kissela BM, Lichtman JH, Lisabeth LD, Liu S, Mackey RH, Magid DJ, McGuire DK, Mohler ER, Moy CS, Muntner P, Mussolino ME, Nasir K, Neumar RW, Nichol G, Palaniappan L, Pandey DK, Reeves MJ, Rodriguez CJ, Rosamond W, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Woo D, Yeh RW, Turner MB. Heart Disease and Stroke Statistics-2016 Update: A Report From the American Heart Association. Circulation 2015; 133:e38-360. [PMID: 26673558 DOI: 10.1161/cir.0000000000000350] [Citation(s) in RCA: 3803] [Impact Index Per Article: 380.3] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Kurl S, Laaksonen DE, Jae SY, Mäkikallio TH, Zaccardi F, Kauhanen J, Ronkainen K, Laukkanen JA. Metabolic syndrome and the risk of sudden cardiac death in middle-aged men. Int J Cardiol 2015; 203:792-7. [PMID: 26595786 DOI: 10.1016/j.ijcard.2015.10.218] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2015] [Revised: 10/07/2015] [Accepted: 10/27/2015] [Indexed: 12/20/2022]
Abstract
BACKGROUND Little is known about the relationship between metabolic syndrome and sudden cardiac death (SCD). We examined the association of metabolic syndrome, as defined by World Health Organization (WHO), International Diabetes Federation (IDF), National Cholesterol Education Program (NCEP) and American Heart Association (AHA)--IDF interim criteria, with incident SCD. We also assessed the association of a continuous metabolic risk score with SCD. METHODS A total of 1466 middle-aged men participating in a prospective population-based cohort study from eastern Finland with no history of coronary heart disease or diabetes at baseline were included. RESULTS During the average follow-up of 21 years 85 SCDs occurred. Men with the metabolic syndrome as defined by the WHO, NCEP, IDF and interim criteria had a 2.2-2.6 fold, increased risk for SCD, after adjusting for lifestyle and traditional cardiovascular risk factors not included in the metabolic syndrome definition (P<0.001-0.011). A one-standard deviation increase in the metabolic risk score (composed of the sum of Z-scores for waist circumference, insulin, glucose, high-density lipoprotein (HDL) cholesterol, triglycerides, and blood pressure) was associated with a 1.68-fold higher (95% CI 1.33-2.11) risk of SCD. Even when adjusting further for systolic blood pressure, HDL cholesterol and body mass index, the association remained significant for the interim criteria and the metabolic risk score, but not for WHO, NCEP, or IDF definitions. CONCLUSIONS Men with metabolic syndrome are at increased risk for SCD. Incident SCD associated with the IDF/AHA interim criteria and metabolic risk clustering estimated by a score is not explained by obesity or traditional cardiovascular risk factors. KEY MESSAGES Men with metabolic syndrome are at increased risk for sudden cardiac death. Incident sudden cardiac death associated with metabolic risk clustering estimated by a score in not explained by obesity or traditional cardiovascular risk factors. Prevention of the metabolic syndrome may help reduce the health burden of SCD.
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Affiliation(s)
- Sudhir Kurl
- Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
| | - David E Laaksonen
- Institute of Clinical Medicine, Department of Medicine, Kuopio University Hospital, Kuopio, Finland
| | - Sae Young Jae
- Department of Sports Informatics, College of Arts and Physical Education, University of Seoul, South Korea
| | - Timo H Mäkikallio
- Division of Cardiology, Department of Internal Medicine, University Hospital of Oulu, Oulu, Finland
| | - Francesco Zaccardi
- Internal Medicine and Diabetes Care Unit, Policlinico Gemelli Hospital, Catholic University of Sacred Heart, Rome, Italy
| | - Jussi Kauhanen
- Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
| | - Kimmo Ronkainen
- Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
| | - Jari A Laukkanen
- Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland; Jyväskylä Central Hospital, Jyväskylä, Finland
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Najafi L, Malek M, Valojerdi AE, Khamseh ME. Acute phase proteins and diabetes microvascular complications. Int J Diabetes Dev Ctries 2015. [DOI: 10.1007/s13410-015-0389-x] [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: 11/28/2022] Open
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Oda E. High-sensitivity C-reactive protein, but not white blood cell count, independently predicted incident diabetes in a Japanese health screening population. Acta Diabetol 2015; 52:983-90. [PMID: 26159115 DOI: 10.1007/s00592-015-0788-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2015] [Accepted: 06/19/2015] [Indexed: 01/04/2023]
Abstract
AIMS To compare high-sensitivity C-reactive protein (hs-CRP) and white blood cell count (WBC) as a predictor of incident diabetes in a population where obesity is not prevalent. METHODS This is a retrospective 6-year follow-up study in a Japanese health screening population including 1874 men and 1094 women. Using Cox regression methods, hazard ratios (HRs) of incident diabetes for hs-CRP and WBC adjusting for fasting plasma glucose (FPG), hemoglobin A1c (HbA1c) and other confounders were calculated, and using areas under receiver operating characteristic curve (AUCs), diabetes-predicting abilities of hs-CRP and WBC were compared. Diabetes was defined as FPG ≥ 126 mg/dL and HbA1c ≥ 6.5 % or use of antidiabetic medication. RESULTS During the 6-year follow-up period (mean ± SD, 4.8 ± 1.7 years), 71 men (3.8 %) and 19 women (1.7 %) developed incident diabetes. The fully adjusted HRs [95 % confidence intervals (CIs)] of incident diabetes for each 1 SD increase in log hs-CRP and WBC were 1.20 (0.92-1.56) (p = 0.174) and 1.01 (0.78-1.30) (p = 0.946), respectively. The fully adjusted HRs (95 % CIs) of incident diabetes for the highest tertile of hs-CRP and WBC compared with the lowest tertile were 2.57 (1.05-6.27) (p = 0.039) and 1.20 (0.53-2.70) (p = 0.665), respectively. The AUCs (95 % CIs) of hs-CRP and WBC for the discrimination of incident diabetes were 0.73 (0.68-0.77) and 0.67 (0.62-0.72), respectively. CONCLUSIONS Hs-CRP, but not WBC, was independently associated with incident diabetes in a Japanese health screening population where obesity is not prevalent.
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Affiliation(s)
- Eiji Oda
- Medical Check-up Center, Tachikawa Medical Center, Nagachou 2-2-16, Nagaoka, Niigata, 940-0053, Japan.
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