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Hayes CA, Thorpe RJ, Dhamoon M, Heitman E, Norris KC, Beech BM, Bruce M, Walker B, Reneker JC. Stroke Incidence and High-Sensitivity C-Reactive Protein Among African Americans: The Jackson Heart Study. Ethn Dis 2025; 35:1-7. [PMID: 40124641 PMCID: PMC11928021 DOI: 10.18865/ethndis-2023-78] [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: 03/25/2025] Open
Abstract
Background Strokes are a leading cause of death and disability among African Americans in the United States. Biological markers to predict stroke remain elusive; thus, our objective was to investigate whether inflammation, as measured by high-sensitivity C-reactive protein (hs-CRP), was associated with stroke incidence among African Americans enrolled in the Jackson Heart Study (JHS). Methods Baseline hs-CRP levels were categorized in quintiles: quintile 1 (0.0084 mg/L); quintile 2 (0.0085-0.0189 mg/L); quintile 3 (0.0190-0.036 mg/L); quintile 4 (0.037-0.0675 mg/L); quintile 5 (≥0.0676 mg/L). Nonfatal stroke incidence was ascertained from passive community surveillance through annual phone calls and adjudicated via hospital records. At baseline, stroke risk factors/covariates were compared across quintiles using a one-way analysis of variance and a chi-square test. The association between baseline hs-CRP levels and stroke incidence was determined using a Cox regression analysis to estimate hazard ratios (HRs) and 95% confidence intervals (CI). Results In the unadjusted model, hs-CRP levels in quintile 2 (HR, 1.48; 95% CI, 0.96-2.29), quintile 3 (HR, 1.44; 95% CI, 0.93-2.24), and quintile 4 (HR, 1.09; 95% CI, 0.68-1.74) were not associated with stroke incidence when compared with quintile 1 (reference). However, individuals within quintile 5 (HR, 1.78; 95% CI, 1.17-2.72) exhibited a significantly increased risk for stroke compared with those in the reference quintile. This risk persisted after adjusting for stroke risk factors (demographics, anthropometrics, health condition covariates, health behavioral risk factors, and cardiovascular disease history) for quintile 5 (HR, 1.87; 95% CI, 1.17-2.98) compared with reference quintile 1. Conclusions An increased and independent risk of nonfatal stroke appears at the highest quintile of hs-CRP values (≥0.0676 mg/L) among JHS participants.
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Affiliation(s)
- Cellas A. Hayes
- Department of Epidemiology and Population Health, Stanford University School of Medicine, Palo Alto, CA
- Department of Biomolecular Sciences, University of Mississippi School of Pharmacy, University, MS
| | - Roland J. Thorpe
- Program for Research on Men’s Health, Johns Hopkins Center for Health Disparities Solutions, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
| | - Mandip Dhamoon
- Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Elizabeth Heitman
- Program in Ethics in Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX
| | - Keith C. Norris
- Program for Research on Men’s Health, Johns Hopkins Center for Health Disparities Solutions, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
- David Geffen School of Medicine, University of California, Los Angeles, CA
| | - Bettina M. Beech
- Program for Research on Men’s Health, Johns Hopkins Center for Health Disparities Solutions, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
- UH Population Health, University of Houston, Houston, TX
| | - Marino Bruce
- Program for Research on Men’s Health, Johns Hopkins Center for Health Disparities Solutions, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
- Research Training, Education, and Mentoring Collaboratory, UH Population Health University of Houston, Houston, TX
- Department of Population Health Science, John D. Bower School of Population Health, University of Mississippi Medical Center, Jackson, MS
| | - Benjamin Walker
- Department of Population Health Science, John D. Bower School of Population Health, University of Mississippi Medical Center, Jackson, MS
| | - Jennifer C. Reneker
- Department of Population Health Science, John D. Bower School of Population Health, University of Mississippi Medical Center, Jackson, MS
- Department of Family and Community Medicine, Northeast Ohio Medical University, Rootstown, Ohio
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Huang Q, An C, Tang S, Leng Y, Zhang Y, Wan B, Han Y, Luo Y, Xie C. Mendelian randomization analysis reveals causal factors behind diabetic nephropathy: evidence, opportunities, and challenges. Front Endocrinol (Lausanne) 2024; 15:1444808. [PMID: 39735650 PMCID: PMC11671268 DOI: 10.3389/fendo.2024.1444808] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2024] [Accepted: 11/25/2024] [Indexed: 12/31/2024] Open
Abstract
Diabetic nephropathy (DN), as the most serious minor vascular complication of diabetes, imposes a significant socioeconomic and medical cost around the world, and its prevention and treatment are a major challenge in the current medical community. Observational studies and randomized controlled trials have revealed protective and risk factors for some DN. However, the conclusions of these researches may be influenced by several types of confounding. Mendelian randomization is a new epidemiological method mainly used to infer the causal relationship between exposure and outcome. Many Mendelian randomization studies have found potential causal relationships between DN and some diseases and lifestyle habits, thus providing valuable data for future mechanistic studies as well as the development and implementation of clinical prevention strategies. As a result, the purpose of this review is to evaluate the published Mendelian randomization study of DN, using the bibliometric research method, analyze the current research status and hot spots, and further summarize the genetic evidence about the potential protection of DN and risk factors to provide new inspiration for the etiology of DN and as a reference for clinical intervention.
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Affiliation(s)
- Qinchuan Huang
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Chen An
- Wangjing Hospital Affiliated to China Academy of Chinese Medical Sciences, Beijing, China
| | - Shiyun Tang
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
- Department of Endocrinology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Yulin Leng
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
- Department of Endocrinology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Yaowen Zhang
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Bin Wan
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Yutong Han
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Yue Luo
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Chunguang Xie
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
- Department of Endocrinology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
- Traditional Chinese Medicine (TCM) Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Chengdu, Sichuan, China
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Zhang M, Ye S, Li J, Zhang M, Tan L, Wang Y, Xie P, Peng H, Li S, Chen S, Wen Q, Chan KW, Tang SCW, Li B, Chen W. Association of systemic immune-inflammation index with all-cause and cardio-cerebrovascular mortality in individuals with diabetic kidney disease: evidence from NHANES 1999-2018. Front Endocrinol (Lausanne) 2024; 15:1399832. [PMID: 39659615 PMCID: PMC11628304 DOI: 10.3389/fendo.2024.1399832] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Accepted: 11/11/2024] [Indexed: 12/12/2024] Open
Abstract
Background Emerging evidence suggests a potential role of immune response and inflammation in the pathogenesis of diabetic kidney disease (DKD). The systemic immune-inflammation index (SII) offers a comprehensive measure of inflammation; however, its relationship with the prognosis of DKD patients remains unclear. Methods Using data from the National Health and Nutrition Examination Survey (NHANES) spanning 1999 to 2018, this cross-sectional study involved adults diagnosed with DKD. Cox proportional hazards models were utilized to assess the associations between SII and all-cause or cardio-cerebrovascular disease mortality. Additionally, restricted cubic spline, piecewise linear regression, and subgroup analyses were performed. Results Over a median follow-up duration of 6.16 years, 1338 all-cause deaths were recorded. After adjusting for covariates, elevated SII levels were significantly associated with increased risks of all-cause and cardio-cerebrovascular disease mortality. Specifically, per one-unit increment in natural log-transformed SII (lnSII), there was a 29% increased risk of all-cause mortality (P < 0.001) and a 23% increased risk of cardio-cerebrovascular disease mortality (P = 0.01) in the fully adjusted model. Similar results were observed when SII was analyzed as a categorical variable (quartiles). Moreover, nonlinear association was identified between SII and all-cause mortality (P < 0.001) through restricted cubic spline analysis, with threshold value of 5.82 for lnSII. The robustness of these findings was confirmed in subgroup analyses. Likewise, the statistically significant correlation between SII levels and cardio-cerebrovascular disease mortality persisted in individuals with DKD. Conclusion Increased SII levels, whether examined as continuous variables or categorized, demonstrate a significant association with elevated risks of all-cause and cardio-cerebrovascular disease mortality among DKD patients. These findings imply that maintaining SII within an optimal range could be crucial in reducing mortality risk.
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Affiliation(s)
- Manhuai Zhang
- Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- National Health Commission (NHC) Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, China
| | - Siyang Ye
- Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- National Health Commission (NHC) Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, China
| | - Jianbo Li
- Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- National Health Commission (NHC) Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, China
| | - Meng Zhang
- Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- National Health Commission (NHC) Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, China
| | - Li Tan
- Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- National Health Commission (NHC) Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, China
| | - Yiqin Wang
- Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- National Health Commission (NHC) Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, China
| | - Peichen Xie
- Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- National Health Commission (NHC) Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, China
| | - Huajing Peng
- Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- National Health Commission (NHC) Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, China
| | - Suchun Li
- Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- National Health Commission (NHC) Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, China
| | - Sixiu Chen
- Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- National Health Commission (NHC) Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, China
| | - Qiong Wen
- Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- National Health Commission (NHC) Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, China
| | - Kam Wa Chan
- School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, Hong Kong SAR, China
| | - Sydney C. W. Tang
- Division of Nephrology, Department of Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Bin Li
- Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- National Health Commission (NHC) Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, China
| | - Wei Chen
- Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- National Health Commission (NHC) Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, China
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Okuma H, Tsutsumi T, Ichijo M, Kobayashi T, Tsuchiya K. Factors Involved in the Development of Diabetic Kidney Disease in Patients With Slowly Progressive Type 1 Diabetes Mellitus: A Retrospective Cohort Study. Cureus 2024; 16:e71055. [PMID: 39512972 PMCID: PMC11541163 DOI: 10.7759/cureus.71055] [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] [Accepted: 10/08/2024] [Indexed: 11/15/2024] Open
Abstract
Introduction The duration of diabetes mellitus (DM), blood pro-inflammatory markers, and dipeptidyl peptidase 4 (DPP4) activity are known predictors of diabetic kidney disease (DKD) progression in acute-onset type 1 DM (AT1DM) and type 2 DM. However, predictors of DKD progression in slowly progressive type 1 insulin-dependent DM (SPIDDM) have been less frequently studied. Patients and methods This retrospective cohort study included 60 patients with SPIDDM (definite) (26 men/34 women). We utilized Cox proportional hazard analyses to determine whether characteristics and laboratory findings at the time of the SPIDDM diagnosis were associated with subsequent DKD progression. The urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) at the last outpatient clinic visit served as indicators of renal function. Also, to compare blood markers in patients with SPIDDM, we included 21 patients diagnosed with AT1DM at the same department during the same period and 50 healthy adult volunteers. Results In patients with SPIDDM (definite), the multivariate Cox proportional hazard analysis revealed that the body mass index (BMI), high-sensitivity C-reactive protein (hs-CRP) levels at diagnosis, and the duration of DM prior to SPIDDM diagnosis were associated with the new onset of albuminuria and systolic blood pressure (SBP) at diagnosis, and the duration of DM prior to SPIDDM diagnosis was associated with a decline in eGFR to less than 60 ml/min/1.73 m². Additionally, serum hs-CRP levels were significantly higher in the SPIDDM (definite) group compared to both the AT1DM patients and healthy controls, suggesting a higher inflammatory state in patients with SPIDDM at the time of diagnosis. In patients with SPIDDM (definite) who were not treated with a DPP4 inhibitor, plasma DPP4 activity was associated with the new onset of albuminuria. Conclusions BMI, SBP, hs-CRP levels, DPP4 activity at SPIDDM diagnosis, and the duration of DM prior to SPIDDM diagnosis are associated with subsequent progression of DKD in SPIDDM. Also, we found that the patients with SPIDDM are often already being treated as DM for a long period of time at the time of diagnosis, which may be linked to their already high inflammatory status at the time of SPIDDM diagnosis and contribute to DKD progression. These findings underscore the importance of early diagnosis and management in preventing DKD progression in this population.
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Affiliation(s)
- Hideyuki Okuma
- Department of Diabetes and Endocrinology, Graduate School of Interdisciplinary Research, Faculty of Medicine, University of Yamanashi, Yamanashi, JPN
| | - Takahiro Tsutsumi
- Department of Diabetes and Endocrinology, Graduate School of Interdisciplinary Research, Faculty of Medicine, University of Yamanashi, Yamanashi, JPN
| | - Masashi Ichijo
- Department of Diabetes and Endocrinology, Graduate School of Interdisciplinary Research, Faculty of Medicine, University of Yamanashi, Yamanashi, JPN
| | - Tetsuro Kobayashi
- Department of Endocrinology and Metabolism, Toranomon Hospital, Tokyo, JPN
| | - Kyoichiro Tsuchiya
- Diabetes and Endocrinology, University of Yamanashi Hospital, Yamanashi, JPN
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Ren J, Qu Y, Gao Y, Ma H, Zhang P, Guo Z, Yang Y. Beat-to-Beat Blood Pressure Variability Within 24 Hours of Ischemic Stroke Onset: A Potential Predictor of Functional Prognosis. J Am Heart Assoc 2024; 13:e034575. [PMID: 39023075 PMCID: PMC11964061 DOI: 10.1161/jaha.124.034575] [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: 03/25/2024] [Accepted: 06/25/2024] [Indexed: 07/20/2024]
Abstract
BACKGROUND Beat-to-beat blood pressure variability (BPV) is based on each heartbeat and represents a dynamic equilibrium process modulated by artery and cardiac involvement of pressure-receptive reflexes. To date, there remains a lack of prospective studies illustrating the clinical value of beat-to-beat BPV within 24 hours of acute ischemic stroke onset. METHODS AND RESULTS This study prospectively monitored beat-to-beat blood pressure and heart rate in patients with acute ischemic stroke within 24 hours of onset using a noninvasive plethysmograph and calculated beat-to-beat BPV, heart rate variability, and the cross-correlation baroreflex sensitivity. A modified Rankin Scale score of ≥2 at 90 days was defined as an unfavorable prognosis. Multivariate logistic regression was performed, and the nomogram model was developed by adding the beat-to-beat BPV to the traditional model for predicting prognosis. Beat-to-beat BPV increased significantly in the unfavorable outcome group (P<0.05) compared with that in the favorable outcome group, whereas no difference was observed in beat-to-beat heart rate variability and cross-correlation baroreflex sensitivity between both groups (P>0.05). Furthermore, beat-to-beat BPV within 24 hours of acute ischemic stroke onset was independently associated with unfavorable outcome at 90 days (P<0.005). The addition of beat-to-beat BPV to the traditional model for predicting prognosis enhanced the area under the receiver operating characteristic curve from 0.816 to 0.830. CONCLUSIONS Increased beat-to-beat BPV within 24 hours of acute ischemic stroke onset was independently associated with a poor prognosis at 90 days and may be a potential predictor for discriminating unfavorable prognosis.
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Affiliation(s)
- Jia‐Xin Ren
- Stroke Center, Department of NeurologyThe First Hospital of Jilin UniversityChang ChunChina
| | - Yang Qu
- Stroke Center, Department of NeurologyThe First Hospital of Jilin UniversityChang ChunChina
| | - Yi Gao
- Stroke Center, Department of NeurologyThe First Hospital of Jilin UniversityChang ChunChina
| | - Hong‐Yin Ma
- Stroke Center, Department of NeurologyThe First Hospital of Jilin UniversityChang ChunChina
| | - Peng Zhang
- Stroke Center, Department of NeurologyThe First Hospital of Jilin UniversityChang ChunChina
| | - Zhen‐Ni Guo
- Stroke Center, Department of NeurologyThe First Hospital of Jilin UniversityChang ChunChina
- Neuroscience Research Center, Department of NeurologyThe First Hospital of Jilin UniversityChang ChunChina
| | - Yi Yang
- Stroke Center, Department of NeurologyThe First Hospital of Jilin UniversityChang ChunChina
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Xie J, Liu Z, Ma W, Ren L, He L, Lu S, Meng X, Xia R, Liu Y, Liu N. Association between glucose levels and all-cause mortality in cancer survivors: findings from NHANES 1999-2018. BMC Public Health 2024; 24:2002. [PMID: 39061034 PMCID: PMC11282799 DOI: 10.1186/s12889-024-19545-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Accepted: 07/22/2024] [Indexed: 07/28/2024] Open
Abstract
BACKGROUND Hyperglycemia is a rapidly increasing risk factor for cancer mortality worldwide. However, the dose‒response relationship between glucose levels and all-cause mortality in cancer survivors is still uncertain. METHODS We enrolled 4,491 cancer survivors (weighted population 19,465,739) from the 1999-2019 National Health and Nutrition Examination Survey (NHANES). Cancer survivors were defined based on the question of whether they had ever been diagnosed with cancer by a doctor or a health professional. Hemoglobin A1c (HbA1c) was selected in this study as a stable marker of glucose level. Mortality was ascertained by linkage to National Death Index records until December 31, 2019. Cox proportional hazard, Kaplan‒Meier survival curves and Restricted cubic spline regression models were used to evaluate the associations between HbA1c and all-cause mortality risk in cancer survivors. RESULTS In NHANES, after adjusting for confounders, HbA1c had an independent nonlinear association with increased all-cause mortality in cancer survivors (nonlinear P value < 0.05). The threshold value for HbA1c was 5.4%, and the HRs (95% CI) below and above the threshold value were 0.917 (0.856,0.983) and 1.026 (1.010,1.043), respectively. Similar associations were found between fasting glucose and all-cause mortality in cancer survivors, and the threshold value was 5.7 mmol/L. CONCLUSIONS HbA1c was nonlinearly associated with all-cause mortality in cancer survivors, and the critical value of HbA1c in decreased mortality was 5.4%, suggesting optimal glucose management in cancer survivors may be a key to preventing premature death in cancer survivors.
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Affiliation(s)
- Jing Xie
- Department of Pharmacy, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Zeye Liu
- Department of Cardiac Surgery, Peking University People's Hospital, Peking University, Beijing, China
| | - Wanlu Ma
- Department of Endocrinology, China-Japan Friendship Hospital, Beijing, China
| | - Liqun Ren
- Department of Gerontology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Liyun He
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Shan Lu
- Department of Geriatrics, The First Affiliated Hospital, Nanjing Medical University, Nanjing, China
| | - Xiangzhi Meng
- Department of Thoracic Surgical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ruibing Xia
- Department of Medicine, University Hospital Munich, Ludwig-Maximilians-University Munich (LMU), Munich, Germany
| | - Yun Liu
- Department of Information, The First Affiliated Hospital, Nanjing Medical University, Nanjing, China.
- Department of Medical Informatics, School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, China.
| | - Naifeng Liu
- Department of Pharmacy, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
- Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
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Liu C, Zhang J, Wei X, Shi J, Fang Q, Zhou W, Sun L, Hu Z, Hong J, Gu W, Wang W, Peng Y, Zhang Y. Effects of sleep duration and changes in body mass index on diabetic kidney disease: a prospective cohort study. Front Endocrinol (Lausanne) 2023; 14:1278665. [PMID: 37964958 PMCID: PMC10641014 DOI: 10.3389/fendo.2023.1278665] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Accepted: 10/06/2023] [Indexed: 11/16/2023] Open
Abstract
Aims To examine the associations of sleep duration and changes in BMI with the onset of diabetic kidney disease (DKD). Materials and methods 2,959 participants with type 2 diabetes were divided into three groups based on sleep duration: short (<7 h/day), intermediate (7-9 h/day), or long (>9 h/day). Changes in BMI during follow-up were trisected into loss, stable, or gain groups. DKD was defined as either the urinary albumin/creatinine ratio (UACR) ≥ 3.39 mg/mmol or the estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m², or both. Cox regression models were used to assess hazard ratios (HRs) and 95% confidence intervals (CIs). Results During a mean follow-up of 2.3 years, DKD occurred in 613 participants (20.7%). A J-shaped curve was observed between sleep duration and DKD. Compared to intermediate sleep duration, long sleep duration was associated with higher risks of DKD (HR 1.47; 95% CI: 1.19-1.81). In the joint analyses, compared to participants with intermediate sleep duration and stable BMI, long sleep duration with BMI gain had the highest risks of DKD (HR 2.04; 95% CI: 1.48-2.83). In contrast, short or intermediate sleep duration accompanied by decrease in BMI was associated with a reduced risk of DKD, with HRs of 0.50 (95% CI: 0.31-0.82) and 0.61 (95% CI:0.47-0.80), respectively. Conclusions Long sleep duration is significantly associated with an increased risk of DKD, which is further amplified by obesity or BMI gain. These findings suggest that both proper sleep duration and weight control are essential to preventing DKD.
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Affiliation(s)
- Cong Liu
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jia Zhang
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xing Wei
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Juan Shi
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qianhua Fang
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Weiwei Zhou
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Lin Sun
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhuomeng Hu
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jie Hong
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Weiqiong Gu
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Weiqing Wang
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ying Peng
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yifei Zhang
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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8
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Zhou C, She X, Gu C, Hu Y, Ma M, Qiu Q, Sun T, Xu X, Chen H, Zheng Z. FTO fuels diabetes-induced vascular endothelial dysfunction associated with inflammation by erasing m6A methylation of TNIP1. J Clin Invest 2023; 133:e160517. [PMID: 37781923 PMCID: PMC10541204 DOI: 10.1172/jci160517] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Accepted: 08/01/2023] [Indexed: 10/03/2023] Open
Abstract
Endothelial dysfunction is a critical and initiating factor of the vascular complications of diabetes. Inflammation plays an important role in endothelial dysfunction regulated by epigenetic modifications. N6-methyladenosine (m6A) is one of the most prevalent epigenetic modifications in eukaryotic cells. In this research, we identified an m6A demethylase, fat mass and obesity-associated protein (FTO), as an essential epitranscriptomic regulator in diabetes-induced vascular endothelial dysfunction. We showed that enhanced FTO reduced the global level of m6A in hyperglycemia. FTO knockdown in endothelial cells (ECs) resulted in less inflammation and compromised ability of migration and tube formation. Compared with EC Ftofl/fl diabetic mice, EC-specific Fto-deficient (EC FtoΔ/Δ) diabetic mice displayed less retinal vascular leakage and acellular capillary formation. Furthermore, methylated RNA immunoprecipitation sequencing (MeRIP-Seq) combined with RNA-Seq indicated that Tnip1 served as a downstream target of FTO. Luciferase activity assays and RNA pull-down demonstrated that FTO repressed TNIP1 mRNA expression by erasing its m6A methylation. In addition, TNIP1 depletion activated NF-κB and other inflammatory factors, which aggravated retinal vascular leakage and acellular capillary formation, while sustained expression of Tnip1 by intravitreal injection of adeno-associated virus alleviated endothelial impairments. These findings suggest that the FTO-TNIP1-NF-κB network provides potential targets to treat diabetic vascular complications.
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Affiliation(s)
- Chuandi Zhou
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China
| | - Xinping She
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China
| | - Chufeng Gu
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China
| | - Yanan Hu
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China
| | - Mingming Ma
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China
| | - Qinghua Qiu
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China
| | - Tao Sun
- Shanghai Eye Diseases Prevention and Treatment Center, Shanghai Eye Hospital, Shanghai General Hospital, National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, China
| | - Xun Xu
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China
| | - Haibing Chen
- Department of Endocrinology and Metabolism, Shanghai 10th People’s Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Zhi Zheng
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China
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9
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Zhou P, Hao Z, Xu W, Yu J. Effects of Niaoduqing granules on inflammatory response of diabetic kidney disease: A meta‑analysis. Exp Ther Med 2023; 26:494. [PMID: 37745039 PMCID: PMC10515115 DOI: 10.3892/etm.2023.12193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Accepted: 07/20/2023] [Indexed: 09/26/2023] Open
Abstract
Diabetic kidney disease (DKD) is one of the most severe chronic microvascular complications of diabetes and the leading cause of end-stage kidney disease worldwide. The mechanism of inflammation underlying DKD has been attracting attention over recent years, but effective therapeutic strategies have remained elusive. Niaoduqing (NDQ) granules are one of the most commonly used drugs for the treatment of DKD in China, and it has therapeutic effects against inflammation in DKD. Therefore, the aim of the present analysis was to evaluate the inflammatory response outcomes and safety of NDQ granules for the treatment of DKD. The following databases were searched from their inception to 31st of May 2023 to obtain published accounts of relevant randomized controlled trials: China National Knowledge Infrastructure, China Science and Technology Journal, Wanfang, The Chinese Biomedicine, PubMed, Web of Science and Cochrane Library. The 'risk of bias' evaluation tool produced by the Cochrane Collaboration Handbook was used for evaluating the quality, whereas Revman software (version 5.3) was used for meta-analysis. In total, 16 studies were included into the present study according to criteria, with a total of 1,526 patients. Compared with those in the control group, the results of the meta-analysis revealed that the combination of conventional treatment and NDQ granules may further decrease C-reactive protein [standardized mean difference (SMD), -1.33; 95% confidence interval (CI), -1.76, -0.91; P<0.00001], TNF-α (SMD, -1.90; 95% CI, -2.35,-1.45; P<0.00001) and IL-6 (SMD, -1.72; 95% CI, -2.52,-0.91; P<0.0001) levels, whilst increasing the clinical effective rate (risk ratio, 1.22; 95% CI, 1.14,1.29; P<0.00001), in patients with DKD. In terms of safety, a total of 34 and 39 patients included in the intervention and in the control group, respectively, developed adverse reactions. Results from the present analysis suggest that NDQ granules may be beneficial in suppressing inflammation caused by DKD when used in combination with conventional treatment, potentially guiding future directions in clinical practice. However, further high-quality studies are needed to confirm the anti-inflammation response in the future.
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Affiliation(s)
- Peipei Zhou
- Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210000, P.R. China
- The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210000, P.R. China
| | - Zhenning Hao
- Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210000, P.R. China
- The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210000, P.R. China
| | - Weilong Xu
- Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210000, P.R. China
- The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210000, P.R. China
| | - Jiangyi Yu
- Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210000, P.R. China
- The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210000, P.R. China
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10
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Lyu X, Du Y, Liu G, Mai T, Li Y, Zhang Z, Bei C. Prevalence and influencing factors of hyperuricemia in middle-aged and older adults in the Yao minority area of China: a cross-sectional study. Sci Rep 2023; 13:10185. [PMID: 37349536 PMCID: PMC10287663 DOI: 10.1038/s41598-023-37274-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2023] [Accepted: 06/19/2023] [Indexed: 06/24/2023] Open
Abstract
Hyperuricemia (HUA) endangers human health, and its prevalence has increased rapidly in recent decades. The current study investigated HUA's prevalence and influencing factors in Gongcheng, southern China. A cross-sectional investigation was conducted; 2128 participants aged 30-93 years were included from 2018 to 2019. Univariate and multivariate logistic regression models were used to screen HUA variables. A Bayesian network model was constructed using the PC algorithm to evaluate the association between influencing factors and HUA. The prevalence of HUA was 15.6% (23.2% in men, 10.7% in women). After screening the variables using a logistic regression analysis model, fatty liver disease (FLD), dyslipidemia, abdominal obesity, creatinine (CREA), somatotype, bone mass, drinking, and physical activity level at work were included in the Bayesian network model. The model results showed that dyslipidemia, somatotype, CREA, and drinking were directly related to HUA. Bone mass and FLD were indirectly associated with HUA by affecting the somatotype. The prevalence of HUA in Gongcheng was high in China. The prevalence of HUA was related to somatotype, drinking, bone mass, physical activity level at work, and other metabolic diseases. A good diet and moderate exercise are recommended to maintain a healthy somatotype and reduce the prevalence rate of HUA.
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Affiliation(s)
- Xiao Lyu
- Department of Epidemiology and Health Statistics, School of Public Health, Guilin Medical University, Huan Cheng North 2nd Road 109, Guilin, 541004, Guangxi, China
| | - Yuanxiao Du
- Department of Epidemiology and Health Statistics, School of Public Health, Guilin Medical University, Huan Cheng North 2nd Road 109, Guilin, 541004, Guangxi, China
| | - Guoyu Liu
- Department of Epidemiology and Health Statistics, School of Public Health, Guilin Medical University, Huan Cheng North 2nd Road 109, Guilin, 541004, Guangxi, China
| | - Tingyu Mai
- Department of Environmental and Occupational Health, School of Public Health, Guilin Medical University, Huan Cheng North 2nd Road 109, Guilin, 541004, Guangxi, China
| | - You Li
- Department of Environmental and Occupational Health, School of Public Health, Guilin Medical University, Huan Cheng North 2nd Road 109, Guilin, 541004, Guangxi, China
| | - Zhiyong Zhang
- Department of Environmental and Occupational Health, School of Public Health, Guilin Medical University, Huan Cheng North 2nd Road 109, Guilin, 541004, Guangxi, China.
- Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Heath, Guangxi Health Commission Key Laboratory of Entire Lifecycle Health and Care, School of Public Health, Guilin Medical University, Guilin, China.
| | - Chunhua Bei
- Department of Epidemiology and Health Statistics, School of Public Health, Guilin Medical University, Huan Cheng North 2nd Road 109, Guilin, 541004, Guangxi, China.
- Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Heath, Guangxi Health Commission Key Laboratory of Entire Lifecycle Health and Care, School of Public Health, Guilin Medical University, Guilin, China.
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11
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Booker R, Holmes ME, Newton RL, Norris KC, Thorpe RJ, Carnethon MR. Compositional analysis of movement behaviors' association on high-sensitivity c-reactive protein: the Jackson heart study. Ann Epidemiol 2022; 76:7-12. [PMID: 36210008 PMCID: PMC9879574 DOI: 10.1016/j.annepidem.2022.09.009] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Revised: 09/22/2022] [Accepted: 09/29/2022] [Indexed: 01/28/2023]
Abstract
PURPOSE Movement behaviors (i.e. physical activity [PA], sedentary behavior [SB], and sleep) are intrinsically codependent, an issue resolved using compositional data analysis (CoDA). High-sensitivity C-reactive protein (hs-CRP) is a nonspecific inflammatory marker positively associated with cardiovascular diseases and affected by movement behaviors. Examine the relation between movement behaviors using CoDA and how time reallocation between two movement behaviors was associated with hs-CRP concentration. METHODS The Jackson Heart Study was designed to investigate cardiovascular disease risk factors among African American participants in the Jackson, MS area. PA and sleep were self-reported with SB calculated as the remaining time in the day. RESULTS The median untransformed hs-CRP concentration was 0.28 mg·dL-1 (interquartile range; 0.11, 0.61). Reallocating 15 minutes of PA with SB, the hypothetical change in log hs-CRP concentration was 0.08 mg·dL-1 (95% CIs; 0.04, 0.11) greater than the average log hs-CRP concentration. Substituting 15 minutes of SB or sleep with PA was associated with a hypothetical change in log hs-CRP concentration difference of -0.05 mg·dL-1 (-0.08, -0.03) and -0.06 mg·dL-1 (-0.08, -0.03), respectively. Reallocations between SB and sleep were not associated with the hypothetical difference in log hs-CRP concentration. CONCLUSIONS Modeling estimates suggest replacing 15 minutes of SB with PA is associated with lower inflammation.
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Affiliation(s)
- Robert Booker
- Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.
| | - Megan E Holmes
- Department of Kinesiology, Mississippi State University, Mississippi State, MS
| | | | - Keith C Norris
- Division of General Internal Medicine and Health Services Research, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA
| | - Roland J Thorpe
- Program for Research on Men's Health, Hopkins Center for Health Disparities Solutions, John Hopkins Bloomberg School of Public Health, Baltimore, MD
| | - Mercedes R Carnethon
- Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL
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12
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Theofilis P, Sagris M, Oikonomou E, Antonopoulos AS, Siasos G, Tsioufis K, Tousoulis D. The Anti-Inflammatory Effect of Novel Antidiabetic Agents. Life (Basel) 2022; 12:1829. [PMID: 36362984 PMCID: PMC9696750 DOI: 10.3390/life12111829] [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: 09/07/2022] [Revised: 09/28/2022] [Accepted: 11/05/2022] [Indexed: 08/10/2023] Open
Abstract
The incidence of type 2 diabetes (T2DM) has been increasing worldwide and remains one of the leading causes of atherosclerotic disease. Several antidiabetic agents have been introduced in trying to regulate glucose control levels with different mechanisms of action. These agents, and sodium-glucose cotransporter-2 inhibitors in particular, have been endorsed by contemporary guidelines in patients with or without T2DM. Their widespread usage during the last three decades has raised awareness in the scientific community concerning their pleiotropic mechanisms of action, including their putative anti-inflammatory effect. In this review, we delve into the anti-inflammatory role and mechanism of the existing antidiabetic agents in the cardiovascular system and their potential use in other chronic sterile inflammatory conditions.
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Affiliation(s)
- Panagiotis Theofilis
- 1st Cardiology Department, “Hippokration” General Hospital, University of Athens Medical School, 11527 Athens, Greece
| | - Marios Sagris
- 3rd Cardiology Department, Thoracic Diseases Hospital “Sotiria”, University of Athens Medical School, 11527 Athens, Greece
| | - Evangelos Oikonomou
- 1st Cardiology Department, “Hippokration” General Hospital, University of Athens Medical School, 11527 Athens, Greece
- 3rd Cardiology Department, Thoracic Diseases Hospital “Sotiria”, University of Athens Medical School, 11527 Athens, Greece
| | - Alexios S. Antonopoulos
- 1st Cardiology Department, “Hippokration” General Hospital, University of Athens Medical School, 11527 Athens, Greece
| | - Gerasimos Siasos
- 1st Cardiology Department, “Hippokration” General Hospital, University of Athens Medical School, 11527 Athens, Greece
- 3rd Cardiology Department, Thoracic Diseases Hospital “Sotiria”, University of Athens Medical School, 11527 Athens, Greece
| | - Kostas Tsioufis
- 1st Cardiology Department, “Hippokration” General Hospital, University of Athens Medical School, 11527 Athens, Greece
| | - Dimitris Tousoulis
- 1st Cardiology Department, “Hippokration” General Hospital, University of Athens Medical School, 11527 Athens, Greece
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13
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Banait T, Wanjari A, Danade V, Banait S, Jain J. Role of High-Sensitivity C-reactive Protein (Hs-CRP) in Non-communicable Diseases: A Review. Cureus 2022; 14:e30225. [PMID: 36381804 PMCID: PMC9650935 DOI: 10.7759/cureus.30225] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2022] [Accepted: 10/10/2022] [Indexed: 11/06/2022] Open
Abstract
Non-communicable diseases like cardiovascular diseases, cerebrovascular diseases, diabetes mellitus, and cancer are very common causes of death worldwide. Therefore, the need to search for novel, affordable, and easily accessible biomarkers and risk factors for non-communicable diseases continues, which can predict the future risk of having these diseases with greater accuracy and precision. In this context, among available biomarkers, high-sensitivity C-reactive protein (Hs-CRP) is considered to be the best-suited marker. Various drug intervention trials demonstrated positive results in reducing Hs-CRP in individuals with raised levels. Numerous pharmacological and non-pharmacologic interventions in the form of lifestyle modifications, exercise, and cessation of smoking are being investigated to study their effect on reducing serum C-reactive protein (CRP) levels. This review article discusses the role of Hs-CRP and its isoforms in the pathogenesis of various disease conditions, factors affecting its serum concentration, its prognostic value, and its comparison with other risk factors. Further, its clinical significance in chronic inflammatory and degenerative diseases of the nervous system and other common non-communicable diseases, including recent advances in the management of various diseases, has also been discussed.
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14
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Umeukeje EM, Washington JT, Nicholas SB. Etiopathogenesis of kidney disease in minority populations and an updated special focus on treatment in diabetes and hypertension. J Natl Med Assoc 2022; 114:S3-S9. [PMID: 35589418 DOI: 10.1016/j.jnma.2022.05.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
Diabetes and hypertension are the most common causes of chronic kidney disease (CKD) in the general population as well as in the Black and African American population, who also suffer from high rates of CKD and CKD progression compared to the White population. Progression of CKD can lead to kidney failure, and patients with progressive kidney disease have a high risk of premature mortality, particularly from cardiovascular disease. Screening for early detection of CKD is important as it facilitates the initiation of medications that have been shown to delay the progression of diabetes-related as well as non-diabetes-related CKD, and reduce rates of death from both kidney and cardiovascular disease. The potential adverse effects from use of some of the newer reno- and cardio-protective glucose-lowering medications, such as the sodium glucose cotransporter-2 inhibitors, may be effectively avoided with detailed patient education and monitoring by the healthcare provider. It is important to note that lifestyle modification including regular exercise, diet, and smoking cessation are first-line in the management of diabetes and hypertension. When CKD occurs, co-management by providers using a comprehensive strategy may avert early complications and facilitate appropriate early referral for nephrology specialty care.
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Affiliation(s)
- Ebele M Umeukeje
- Division of Nephrology, Vanderbilt University Medical Center, Vanderbilt Center for Kidney Disease, United States
| | | | - Susanne B Nicholas
- David Geffen School of Medicine at University of California, 7-155 Factor Bldg. 10833 LeConte Blvd, Los Angeles, CA 90095, United States.
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15
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La Grotta R, de Candia P, Olivieri F, Matacchione G, Giuliani A, Rippo MR, Tagliabue E, Mancino M, Rispoli F, Ferroni S, Berra CC, Ceriello A, Prattichizzo F. Anti-inflammatory effect of SGLT-2 inhibitors via uric acid and insulin. Cell Mol Life Sci 2022; 79:273. [PMID: 35503137 PMCID: PMC9064844 DOI: 10.1007/s00018-022-04289-z] [Citation(s) in RCA: 66] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Revised: 03/16/2022] [Accepted: 04/04/2022] [Indexed: 02/07/2023]
Abstract
Sodium-glucose cotransporter 2 (SGLT-2) inhibitors (i) reduce cardiovascular and renal events in patients with and without type 2 diabetes (T2D). However, the underlying mechanisms are debated. Low-grade inflammation (LGI) is a key driver of vascular complications, suggested to be attenuated by SGLT-2i in animal models. Based on a specific working hypothesis, here we investigated the net effect of SGLT-2i on LGI in patients with T2D and the possible underlying mechanism. We enrolled patients with T2D treated either with a stable therapy with SGLT-2i or with other glucose-lowering drugs (GLD) (n = 43 per group after matching for a range of pro-inflammatory variables), and tested hs-CRP and interleukin (IL)-6 as primary variables of interest. Patients treated with SGLT-2i had lower circulating levels of IL-6, a prototypical marker of LGI, but also of uric acid and fasting insulin, compared with patients treated with other GLD. Then, to explore whether uric acid and insulin might mediate the effect of SGLT-2i on IL-6, we tested physiologically pertinent doses of these two molecules (i.e. 0.5 mM uric acid and 1 nM insulin) in two in vitro models of LGI, i.e. monocytes (THP-1) treated with LPS and endothelial cells (HUVEC) exposed to hyperglycaemia. Results from in vitro models supported a pro-inflammatory role for uric acid and its combination with insulin in monocytes and for uric acid alone in hyperglycaemia-stimulated endothelial cells. On the contrary, we observed no drug-intrinsic, anti-inflammatory effect for dapagliflozin, empagliflozin, and canagliflozin in the same models. Overall, these results suggest that SGLT-2i possess a tangible activity against LGI, an effect possibly mediated by their ability to lower uric acid and insulin concentrations and that juxtaposes other proposed mechanisms in explaining the observed benefit of this class on cardiovascular and renal endpoints.
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Affiliation(s)
| | - Paola de Candia
- Department of Molecular Medicine and Medical Biotechnology, University of Naples "Federico II", Naples, Italy
| | - Fabiola Olivieri
- Department of Clinical and Molecular Sciences, DISCLIMO, Università Politecnica Delle Marche, Ancona, Italy.,Center of Clinical Pathology and Innovative Therapy, IRCCS INRCA, Ancona, Italy
| | - Giulia Matacchione
- Department of Clinical and Molecular Sciences, DISCLIMO, Università Politecnica Delle Marche, Ancona, Italy
| | - Angelica Giuliani
- Department of Clinical and Molecular Sciences, DISCLIMO, Università Politecnica Delle Marche, Ancona, Italy
| | - Maria Rita Rippo
- Department of Clinical and Molecular Sciences, DISCLIMO, Università Politecnica Delle Marche, Ancona, Italy
| | - Elena Tagliabue
- Value-Based Healthcare Unit, IRCCS MultiMedica, Sesto San Giovanni, MI, Italy
| | - Monica Mancino
- Value-Based Healthcare Unit, IRCCS MultiMedica, Sesto San Giovanni, MI, Italy
| | | | - Sabina Ferroni
- Department of Endocrinology, Nutrition and Metabolic Diseases, IRCCS MultiMedica, Via Milanese 300, 20099, Sesto San Giovanni, MI, Italy
| | - Cesare Celeste Berra
- Department of Endocrinology, Nutrition and Metabolic Diseases, IRCCS MultiMedica, Via Milanese 300, 20099, Sesto San Giovanni, MI, Italy.
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16
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Ma Q, Bian L, Zhao X, Tian X, Yin H, Wang Y, Shi A, Wu J. Novel glucose-responsive nanoparticles based on p-hydroxyphenethyl anisate and 3-acrylamidophenylboronic acid reduce blood glucose and ameliorate diabetic nephropathy. Mater Today Bio 2021; 13:100181. [PMID: 34927045 PMCID: PMC8649392 DOI: 10.1016/j.mtbio.2021.100181] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Revised: 12/01/2021] [Accepted: 12/02/2021] [Indexed: 11/22/2022] Open
Abstract
An insulin delivery system that self-regulates blood sugar levels, mimicking the human pancreas, can improve hyperglycaemia. At present, a glucose-responsive insulin delivery system combining AAPBA with long-acting slow release biomaterials has been developed. However, the safety of sustained-release materials and the challenges of preventing diabetic complications remain. In this study, we developed a novel polymer slow release material using a plant extract—p-hydroxyphenylethyl anisate (HPA). After block copolymerisation with AAPBA, the prepared nanoparticles had good pH sensitivity, glucose sensitivity, insulin loading rate and stability under physiological conditions and had high biocompatibility. The analysis of streptozotocin-induced diabetic nephropathy (DN) mouse model showed that the insulin-loaded injection of nanoparticles stably regulated the blood glucose levels of DN mice within 48 h. Importantly, with the degradation of the slow release material HPA in vivo, the renal function improved, the inflammatory response reduced, and antioxidation levels in DN mice improved. This new type of nanoparticles provides a new idea for hypoglycaemic nano-drug delivery system and may have potential in the prevention and treatment of diabetic complications.
We established a new glucose-responsive intelligent system with HPA. p(AAPBA-b-HPA) shows good pH and glucose sensitivity. p(AAPBA-b-HPA) nanoparticles can slowly release HPA and insulin. This system can be used to regulate blood glucose. p(AAPBA-b-HPA) nanoparticles can aid in diabetic nephropathy prevention and treatment.
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Affiliation(s)
- Qiong Ma
- The Key Laboratory of Microcosmic Syndrome Differentiation, Education Department of Yunnan, Yunnan University of Chinese Medicine, Kunming, Yunnan, 650500, PR China
| | - Ligong Bian
- Department of Medical Biology, College of Basic Medicine, Yunnan University of Chinese Medicine, Kunming, Yunnan, 650500, PR China
| | - Xi Zhao
- The Key Laboratory of Microcosmic Syndrome Differentiation, Education Department of Yunnan, Yunnan University of Chinese Medicine, Kunming, Yunnan, 650500, PR China
| | - Xuexia Tian
- The Key Laboratory of Microcosmic Syndrome Differentiation, Education Department of Yunnan, Yunnan University of Chinese Medicine, Kunming, Yunnan, 650500, PR China
| | - Hang Yin
- The Key Laboratory of Microcosmic Syndrome Differentiation, Education Department of Yunnan, Yunnan University of Chinese Medicine, Kunming, Yunnan, 650500, PR China
| | - Yutian Wang
- The Key Laboratory of Microcosmic Syndrome Differentiation, Education Department of Yunnan, Yunnan University of Chinese Medicine, Kunming, Yunnan, 650500, PR China
| | - Anhua Shi
- The Key Laboratory of Microcosmic Syndrome Differentiation, Education Department of Yunnan, Yunnan University of Chinese Medicine, Kunming, Yunnan, 650500, PR China
| | - Junzi Wu
- The Key Laboratory of Microcosmic Syndrome Differentiation, Education Department of Yunnan, Yunnan University of Chinese Medicine, Kunming, Yunnan, 650500, PR China
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Oluyombo R, Banjo Oguntade H, Soje M, Obajolowo O, Karim M. Obesity and CKD in Sub-Saharan Africa: A Narrative Review. Kidney Med 2021; 4:100403. [PMID: 35243313 PMCID: PMC8861962 DOI: 10.1016/j.xkme.2021.11.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
Obesity is a major public health problem in the developed world, where it has reached an epidemic status over the last few decades. In parallel with this, the prevalence of chronic kidney disease (CKD) has increased. Although obesity is a risk factor for hypertension and diabetes, it is also independently associated with the development and progression of CKD. Two-third of patients with CKD worldwide will be residents of developing countries by the year 2030. Risk factors for CKD are prevalent in the sub-Saharan Africa region; this review discusses the available data regarding the relationship between obesity and CKD. The prevalence of CKD appears to correlate with increasing adiposity in sub-Saharan Africa; however, limited data are currently available, and the analysis of this association is further complicated by a variety of parameters used to define obesity. (eg, body mass index vs waist circumference). Longer, large-scale studies are needed to inform the prevalence and kidney implications of obesity in sub-Saharan Africa.
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Li M, Fan R, Peng X, Huang J, Zou H, Yu X, Yang Y, Shi X, Ma D. Association of ANGPTL8 and Resistin With Diabetic Nephropathy in Type 2 Diabetes Mellitus. Front Endocrinol (Lausanne) 2021; 12:695750. [PMID: 34603198 PMCID: PMC8479106 DOI: 10.3389/fendo.2021.695750] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Accepted: 08/30/2021] [Indexed: 12/22/2022] Open
Abstract
Background Previous studies showed altered angiopoietin-like protein-8 (ANGPTL-8) and resistin circulating levels in type 2 diabetes mellitus (T2DM). Whether or not the alteration in ANGPTL-8 and resistin level can be a predictive maker for increased diabetic nephropathy risk remains unclear. Aim To Investigate the possible association of ANGPTL-8 and resistin with DN, and whether this association is affected by NAFLD status. Methods A total of 278 T2DM patients were enrolled. Serum levels of ANGPTL8, resistin, BMI, blood pressure, duration of diabetes, glycosylated hemoglobin (HbA1c), fasting blood glucose (FPG), hypersensitive C-reactive protein (hs-CRP), lipid profile, liver, and kidney function tests were assessed. The relationship between DN with ANGPTL8 and resistin was analyzed in the unadjusted and multiple-adjusted regression models. Results Serum levels of ANGPTL8 and resistin were significantly higher in DN compared with T2DM subjects without DN (respectively; P <0.001), especially in non-NAFLD populations. ANGPTL8 and resistin showed positive correlation with hs-CRP (respectively; P<0.01), and negative correlation with estimated GFR (eGFR) (respectively; P=<0.001) but no significant correlation to HOMA-IR(respectively; P>0.05). Analysis showed ANGPTL8 levels were positively associated with resistin but only in T2DM patients with DN(r=0.1867; P<0.05), and this significant correlation disappeared in T2DM patients without DN. After adjusting for confounding factors, both ANGPTL8(OR=2.095, 95%CI 1.253-3.502 P=0.005) and resistin (OR=2.499, 95%CI 1.484-4.208 P=0.001) were risk factors for DN. Data in non-NAFLD population increased the relationship between ANGPTL8 (OR=2.713, 95% CI 1.494-4.926 P=0.001), resistin (OR=4.248, 95% CI 2.260-7.987 P<0.001)and DN. The area under the curve (AUC) on receiver operating characteristic (ROC) analysis of the combination of ANGPTL8 and resistin was 0.703, and the specificity was 70.4%. These data were also increased in non-NAFLD population, as the AUC (95%CI) was 0.756, and the specificity was 91.2%. Conclusion This study highlights a close association between ANGPTL8, resistin and DN, especially in non-NAFLD populations. These results suggest that ANGPTL-8 and resistin may be risk predictors of DN.
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Affiliation(s)
- Mengni Li
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Rongping Fan
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xuemin Peng
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jiaojiao Huang
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Huajie Zou
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xuefeng Yu
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Wuhan Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, China
| | - Yan Yang
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Wuhan Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, China
| | - Xiaoli Shi
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Wuhan Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, China
| | - DeLin Ma
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Wuhan Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, China
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Piko N, Bevc S, Ekart R, Petreski T, Vodošek Hojs N, Hojs R. Diabetic patients with chronic kidney disease: Non-invasive assessment of cardiovascular risk. World J Diabetes 2021; 12:975-996. [PMID: 34326949 PMCID: PMC8311487 DOI: 10.4239/wjd.v12.i7.975] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 03/04/2021] [Accepted: 04/26/2021] [Indexed: 02/06/2023] Open
Abstract
The prevalence and burden of diabetes mellitus and chronic kidney disease on global health and socioeconomic development is already heavy and still rising. Diabetes mellitus by itself is linked to adverse cardiovascular events, and the presence of concomitant chronic kidney disease further amplifies cardiovascular risk. The culmination of traditional (male gender, smoking, advanced age, obesity, arterial hypertension and dyslipidemia) and non-traditional risk factors (anemia, inflammation, proteinuria, volume overload, mineral metabolism abnormalities, oxidative stress, etc.) contributes to advanced atherosclerosis and increased cardiovascular risk. To decrease the morbidity and mortality of these patients due to cardiovascular causes, timely and efficient cardiovascular risk assessment is of huge importance. Cardiovascular risk assessment can be based on laboratory parameters, imaging techniques, arterial stiffness parameters, ankle-brachial index and 24 h blood pressure measurements. Newer methods include epigenetic markers, soluble adhesion molecules, cytokines and markers of oxidative stress. In this review, the authors present several non-invasive methods of cardiovascular risk assessment in patients with diabetes mellitus and chronic kidney disease.
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Affiliation(s)
- Nejc Piko
- Department of Dialysis, Clinic for Internal Medicine, University Medical Centre Maribor, Maribor 2000, Slovenia
| | - Sebastjan Bevc
- Department of Nephrology, Clinic for Internal Medicine, University Medical Centre Maribor, Maribor 2000, Slovenia
- Medical Faculty, University of Maribor, Maribor 2000, Slovenia
| | - Robert Ekart
- Department of Dialysis, Clinic for Internal Medicine, University Medical Centre Maribor, Maribor 2000, Slovenia
- Medical Faculty, University of Maribor, Maribor 2000, Slovenia
| | - Tadej Petreski
- Department of Nephrology, Clinic for Internal Medicine, University Medical Centre Maribor, Maribor 2000, Slovenia
- Medical Faculty, University of Maribor, Maribor 2000, Slovenia
| | - Nina Vodošek Hojs
- Department of Nephrology, Clinic for Internal Medicine, University Medical Centre Maribor, Maribor 2000, Slovenia
| | - Radovan Hojs
- Department of Nephrology, Clinic for Internal Medicine, University Medical Centre Maribor, Maribor 2000, Slovenia
- Medical Faculty, University of Maribor, Maribor 2000, Slovenia
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Prattichizzo F, de Candia P, Ceriello A. Diabetes and kidney disease: emphasis on treatment with SGLT-2 inhibitors and GLP-1 receptor agonists. Metabolism 2021; 120:154799. [PMID: 34029597 DOI: 10.1016/j.metabol.2021.154799] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Revised: 05/06/2021] [Accepted: 05/17/2021] [Indexed: 12/12/2022]
Abstract
Kidney disease is a frequent microvascular complication of both type 1 and type 2 diabetes. Historic trials have demonstrated that a tight glycaemic control is the most powerful approach to decrease the chances of developing diabetic nephropathy. However, having an HbA1c < 7% does not completely suppress the risk of kidney disease. The observed residual risk is likely ascribable to two phenomena: 1- the presence of risk factors and alterations additive to and independent of glycaemia, and 2- the activation of long-lasting imbalances by periods of exposure to uncontrolled glycemia, a phenomenon referred to as metabolic memory or legacy effect. Long-lasting oxidative stress, epigenetic alterations, cellular senescence, and the resulting chronic low-grade inflammation are all candidate mechanisms explaining the development of nephropathy despite proper control of risk factors. Recently, two classes of drugs, i.e. glucagon-like peptide (GLP) 1 receptor agonists (RA) and sodium-glucose transporter 2 inhibitors (SGLT-i) have changed this scenario. Indeed, cardiovascular outcome and other trials have clearly shown a renoprotective effect for these drugs, well-beyond their glucose-lowering properties. In this review, we summarize: 1- selected key trials and mechanisms underlying the development of diabetic kidney disease and 2- the results relative to renal endpoints in clinical trials of GLP-1 RA and SGLT-2i. Then, we briefly discuss some of the hypotheses posited to explain the marked renoprotective properties of these two classes, evidencing the still existing gaps in knowledge and proposing future directions to further implement the use of these powerful, disease-modifying drugs.
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21
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Nicholas SB. Novel Anti-inflammatory and Anti-fibrotic Agents for Diabetic Kidney Disease-From Bench to Bedside. Adv Chronic Kidney Dis 2021; 28:378-390. [PMID: 34922694 DOI: 10.1053/j.ackd.2021.09.010] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Revised: 08/30/2021] [Accepted: 09/17/2021] [Indexed: 02/08/2023]
Abstract
Chronic low-grade inflammation, now coined by the new paradigm as "metaflammation" or "metainflammation", has been linked to chronic kidney disease and its progression. In diabetes, altered metabolism denotes factors associated with the metabolic syndrome and hyperglycemia, among others. The interplay among hyperglycemia, oxidative stress, and inflammation in the pathogenesis of diabetic kidney disease (DKD) has been broadly explored. Identification of mediators of inflammatory processes involving macrophage infiltration, production of inflammasomes, release of cytokines, and activation of pertinent signaling pathways including mitogen-activated protein kinase, Jun N-terminal kinase, Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway (JAK/STAT), and apoptosis signal-regulating kinase 1 signaling mechanisms have enabled the development of therapeutic agents for DKD. This review describes the evidence supporting the contribution of the inflammatory response and fibrotic changes and focuses on selected, novel, promising drugs as well as repurposed drugs that have made it to phase 2, 3, or 4 of clinical trials in adults with type 2 diabetes mellitus and their potential to become an important part of our armamentarium to improve the management of DKD. Importantly, drugs that solely target inflammatory processes may be insufficient to fully optimize care of patients with DKD because of the complex nature of the disease.
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Zhang N, Wu X, Tian M, Wang X, Ding J, Tian Y, Liang C, Zeng Z, Xiang H, Tan H. Additive interaction between potentially modifiable risk factors and ethnicity among individuals in the Han, Tujia and Miao populations with first-ever ischaemic stroke. BMC Public Health 2021; 21:1059. [PMID: 34082746 PMCID: PMC8173719 DOI: 10.1186/s12889-021-11115-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2020] [Accepted: 05/23/2021] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND As a country with one-fifth of the global population, China has experienced explosive growth in ischaemic stroke (IS) burden with significant ethnic and geographic disparities. The aim of this study was to examine the differences in potentially modifiable risk factors for ischaemic stroke among the Han population and two ethnic minorities (Tujia and Miao). METHODS A case-control study was conducted with 324 cases of first-ever ischaemic stroke from the hospitals of the Xiangxi Tujia and Miao Autonomous Prefecture and 394 controls from communities covering the same area between May 1, 2018, and April 30, 2019. Structured questionnaires were administered, and physical examinations were performed in the same manner for cases and controls. Univariate and multivariate logistic regression analyses with adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were used to examine the association between risk factors and ischaemic stroke. An additive model was used to study the interaction between the modifiable risk factors and ethnicity with R software. RESULTS Higher high-sensitivity C-reactive protein levels (OR 50.54, 95%CI 29.76-85.85), higher monthly family income (4.18, 2.40-7.28), increased frequency of hot pot consumption (2.90, 1.21-6.93), diabetes mellitus (2.62, 1.48-4.62), a higher apolipoprotein (Apo)B/ApoA1 ratio (2.60, 1.39-4.85), hypertension (2.52, 1.45-4.40) and moderate-intensity physical activity (0.50, 0.28-0.89) were associated with ischaemic stroke. There was an additive interaction between the ApoB/ApoA1 ratio and ethnicity in the Tujia and Miao populations with first-ever ischaemic stroke (the relative excess risk due to the interaction was 5.75, 95% CI 0.58 ~ 10.92; the attributable proportion due to the interaction was 0.65, 95% CI 0.38 ~ 0.91; the synergy index was 3.66, 95% CI 1.35 ~ 9.93). CONCLUSIONS This is the first case-control study examining modifiable risk factors for ischaemic stroke among the Han population and two ethnic minorities (Tujia and Miao) in China. Some differences were observed in the impact of risk factors among these ethnic groups. Our results may help interpret health-related data, including surveillance and research, when developing strategies for stroke prevention.
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Affiliation(s)
- Na Zhang
- Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, Changsha, Hunan, China.,Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, Hunan, China.,Hunan Provincial Institute of Geriatrics, Hunan Provincial People's Hospital (the First Affiliated Hospital of Hunan Normal University), Changsha, Hunan, China
| | - Xinrui Wu
- Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, Changsha, Hunan, China.,Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, Hunan, China
| | - Mengyuan Tian
- Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, Changsha, Hunan, China.,Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, Hunan, China
| | - Xiaolei Wang
- Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, Changsha, Hunan, China.,Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, Hunan, China
| | - Jian Ding
- Hunan Provincial Institute of Geriatrics, Hunan Provincial People's Hospital (the First Affiliated Hospital of Hunan Normal University), Changsha, Hunan, China
| | - Yong Tian
- Department of Neurology, the First Affiliated Hospital of Jishou University, the Tujia-Miao autonomous prefecture of Xiangxi, Hunan, China
| | - Chengcai Liang
- Department of Neurology, the First Affiliated Hospital of Jishou University, the Tujia-Miao autonomous prefecture of Xiangxi, Hunan, China
| | - Zhi Zeng
- Department of Neurology, the First Affiliated Hospital of Jishou University, the Tujia-Miao autonomous prefecture of Xiangxi, Hunan, China
| | - Hua Xiang
- Interventional Radiology Center, Hunan Provincial People's Hospital (the First Affiliated Hospital of Hunan Normal University), Changsha, Hunan, China.
| | - Hongzhuan Tan
- Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, Changsha, Hunan, China. .,Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, Hunan, China.
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Qian X, He S, Wang J, Gong Q, An Y, Li H, Chen Y, Li G. Prediction of 10-year mortality using hs-CRP in Chinese people with hyperglycemia: Findings from the Da Qing diabetes prevention outcomes study. Diabetes Res Clin Pract 2021; 173:108668. [PMID: 33453295 DOI: 10.1016/j.diabres.2021.108668] [Citation(s) in RCA: 8] [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] [Received: 09/15/2020] [Revised: 12/24/2020] [Accepted: 01/07/2021] [Indexed: 12/29/2022]
Abstract
AIMS To examine whether high-sensitivity C-reactive protein (hs-CRP) can predict all-cause death in Chinese adults with hyperglycemia. METHODS All the 237 diabetes and 49 prediabetes recruited in the study were evolved from the participants with impaired glucose tolerance in the original Da Qing Diabetes Study. Blood hs-CRP level was measured at 2006. Ten-year outcome of death was traced from 2006 to 2016. Cox model was used to analyse the association between hs-CRP level and the risk of all-cause death occurred over the subsequent 10 years. RESULTS During the follow-up, death occurred in 36 (37.9%) subjects in the highest hs-CRP tertile group (hs-CRP > 2.16 mg/L) and 19 (20.0%) in the lowest hs-CRP tertile group (hs-CRP < 0.82 mg/L, p < 0.05). The corresponding incidence of all-cause death (per 1,000 person-years) was 44.7 (95% CI 30.1-59.3) and 21.6 (95% CI 11.9-31.3) in the two groups respectively (p < 0.0001). The highest hs-CRP tertile was associated with the increased risk of all-cause death significantly (hazard ratio 1.88, 95% CI 1.07-3.32) after controlling for traditional risk factors. CONCLUSIONS Serum hs-CRP was predictive of 10-year all-cause death in Chinese adults with hyperglycemia, suggesting the impact of low-grade inflammation on mortality deserves more attention.
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Affiliation(s)
- Xin Qian
- Endocrinology and Cardiovascular Metabolism Centre, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Siyao He
- Endocrinology and Cardiovascular Metabolism Centre, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jinping Wang
- Department of Cardiology, Da Qing First Hospital, Daqing, China
| | - Qiuhong Gong
- Endocrinology and Cardiovascular Metabolism Centre, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yali An
- Endocrinology and Cardiovascular Metabolism Centre, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hui Li
- Department of Cardiology, Da Qing First Hospital, Daqing, China
| | - Yanyan Chen
- Endocrinology and Cardiovascular Metabolism Centre, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Guangwei Li
- Endocrinology and Cardiovascular Metabolism Centre, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
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Fernandes Silva L, Vangipurapu J, Smith U, Laakso M. Metabolite Signature of Albuminuria Involves Amino Acid Pathways in 8661 Finnish Men Without Diabetes. J Clin Endocrinol Metab 2021; 106:143-152. [PMID: 32992327 PMCID: PMC7765644 DOI: 10.1210/clinem/dgaa661] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Accepted: 09/28/2020] [Indexed: 12/29/2022]
Abstract
OBJECTIVE To investigate the metabolite signature of albuminuria in individuals without diabetes or chronic kidney disease to identify possible mechanisms that result in increased albuminuria and elevated risk of type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS The study cohort was a population-based Metabolic Syndrome In Men (METSIM) study including 8861 middle-aged and elderly Finnish men without diabetes or chronic kidney disease at baseline. A total of 5504 men participated in a 7.5-year follow-up study, and 5181 of them had metabolomics data measured by Metabolon's ultrahigh performance liquid chromatography-tandem mass spectroscopy. RESULTS We found 32 metabolites significantly (P < 5.8 × 10-5) and positively associated with the urinary albumin excretion (UAE) rate. These metabolites were especially downstream metabolites in the amino acid metabolism pathways (threonine, phenylalanine, leucine, arginine). In our 7.5-year follow-up study, UAE was significantly associated with a 19% increase (hazard ratio 1.19; 95% confidence interval, 1.13-1.25) in the risk of T2D after the adjustment for confounding factors. Conversion to diabetes was more strongly associated with a decrease in insulin secretion than a decrease in insulin sensitivity. CONCLUSIONS Metabolic signature of UAE included multiple metabolites, especially from the amino acid metabolism pathways known to be associated with low-grade inflammation, and accumulation of reactive oxygen species that play an important role in the pathogenesis of UAE. These metabolites were primarily associated with an increase in UAE and were secondarily associated with a decrease in insulin secretion and insulin sensitivity, resulting in an increased risk of incident T2D.
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Affiliation(s)
- Lilian Fernandes Silva
- Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, Finland
| | - Jagadish Vangipurapu
- Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, Finland
| | - Ulf Smith
- Lundberg Laboratory for Diabetes Research, Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Markku Laakso
- Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, Finland
- Kuopio University Hospital, Kuopio, Finland
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Sha Q, Lyu J, Zhao M, Li H, Guo M, Sun Q. Multi-Omics Analysis of Diabetic Nephropathy Reveals Potential New Mechanisms and Drug Targets. Front Genet 2020; 11:616435. [PMID: 33362869 PMCID: PMC7759603 DOI: 10.3389/fgene.2020.616435] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Accepted: 11/23/2020] [Indexed: 12/21/2022] Open
Abstract
Diabetic nephropathy (DN) is one of the most common diabetic complications, which is the major course of end-stage renal disease (ESRD). However, the systematical molecular characterizations during DN pathogenesis and progression has not been not well understood. To identify the fundamental mediators of the pathogenesis and progression of DN. we performed a combination RNASeq, proteomics, and metabolomics analyses of both patients' derived kidney biopsy samples and kidneys from in vivo DN model. As a result, molecular changes of DN contain extracellular matrix accumulation, abnormal activated inflamed microenvironment, and metabolism disorders, bringing about glomerular sclerosis and tubular interstitial fibrosis. Specificity, Further integration analyses have identified that the linoleic acid metabolism and fatty-acids β-oxidation are significantly inhibited during DN pathogenesis and progression, the transporter protein ABCD3, the fatty acyl-CoA activated enzymes ACOX1, ACOX2, and ACOX3, and some corresponding metabolites such as 13'-HODE, stearidonic acid, docosahexaenoic acid, (±)10(11)-EpDPA were also significantly reduced. Our study thus provides potential molecular mechanisms for DN progression and suggests that targeting the key enzymes or supplying some lipids may be a promising avenue in the treatment of DN, especially advanced-stage DN.
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Affiliation(s)
- Qian Sha
- Department of Pharmacy, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China
| | - Jinxiu Lyu
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China
| | - Meng Zhao
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China
| | - Haijuan Li
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China
| | - Mengzhe Guo
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China
| | - Qiang Sun
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China
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Prattichizzo F, Giuliani A, Sabbatinelli J, Matacchione G, Ramini D, Bonfigli AR, Rippo MR, de Candia P, Procopio AD, Olivieri F, Ceriello A. Prevalence of residual inflammatory risk and associated clinical variables in patients with type 2 diabetes. Diabetes Obes Metab 2020; 22:1696-1700. [PMID: 32394604 DOI: 10.1111/dom.14081] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Revised: 04/25/2020] [Accepted: 05/04/2020] [Indexed: 02/06/2023]
Abstract
Residual inflammatory risk (RIR) is defined as persistent circulating levels of high sensitivity C-reactive protein (hs-CRP) >2 mg/L despite an optimal (<70 mg/dL) control of LDL-cholesterol (LDL-C) and represents an emerging risk factor for the development of cardiovascular events in patients at high risk of atherosclerosis. Sparse data are available regarding the prevalence of RIR in patients with type 2 diabetes (T2D) and the clinical variables associated with hs-CRP elevation. Here, we report data from a well-characterized cohort of patients with T2D (n = 511) stratified for statins use, LDL-C goal attainment and prevalent T2D complications. Statins use and having at-target LDL-C partially affect the number of patients with inflammatory risk when compared with the whole T2D population, with an RIR prevalence of 39.2%. Among the spectra of complications, only patients with nephropathy had a higher prevalence of inflammatory risk. Total cholesterol, non-HDL-cholesterol, triglycerides, body mass index and waist-hip ratio were associated with hs-CRP, with an increased magnitude in at-target patients. Conversely, glucose-related variables were strongly associated with hs-CRP only in at-target patients, overall suggesting glycaemic control, insulin resistance, non-LDL-C lipid variables and especially central obesity as possible contributors to RIR in patients with T2D and LDL-C <70 mg/dL.
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Affiliation(s)
| | - Angelica Giuliani
- Department of Clinical and Molecular Sciences (DISCLIMO), Università Politecnica delle Marche, Ancona, Italy
| | - Jacopo Sabbatinelli
- Department of Clinical and Molecular Sciences (DISCLIMO), Università Politecnica delle Marche, Ancona, Italy
| | - Giulia Matacchione
- Department of Clinical and Molecular Sciences (DISCLIMO), Università Politecnica delle Marche, Ancona, Italy
| | - Deborah Ramini
- Department of Clinical and Molecular Sciences (DISCLIMO), Università Politecnica delle Marche, Ancona, Italy
| | | | - Maria Rita Rippo
- Department of Clinical and Molecular Sciences (DISCLIMO), Università Politecnica delle Marche, Ancona, Italy
| | | | - Antonio Domenico Procopio
- Department of Clinical and Molecular Sciences (DISCLIMO), Università Politecnica delle Marche, Ancona, Italy
- Center of Clinical Pathology and Innovative Therapy, IRCCS INRCA, Ancona, Italy
| | - Fabiola Olivieri
- Department of Clinical and Molecular Sciences (DISCLIMO), Università Politecnica delle Marche, Ancona, Italy
- Center of Clinical Pathology and Innovative Therapy, IRCCS INRCA, Ancona, Italy
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Lee M, Park HS, Choi MY, Kim HZ, Moon SJ, Ha JY, Choi AR, Park YW, Park JS, Shin EC, Ahn CW, Kang S. Significance of Soluble CD93 in Type 2 Diabetes as a Biomarker for Diabetic Nephropathy: Integrated Results from Human and Rodent Studies. J Clin Med 2020; 9:jcm9051394. [PMID: 32397261 PMCID: PMC7290306 DOI: 10.3390/jcm9051394] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2020] [Accepted: 04/27/2020] [Indexed: 01/06/2023] Open
Abstract
Cluster of differentiation 93 (CD93) is a glycoprotein expressed in activated endothelial cells. The extracellular portion of CD93 can be secreted as a soluble form (sCD93) under inflammatory conditions. As diabetic nephropathy (DN) is a well-known inflammatory disease, we hypothesized that sCD93 would be a new biomarker for DN. We prospectively enrolled 97 patients with type 2 diabetes and evaluated the association between serum sCD93 and DN prevalence. The association between CD93 and development of DN was investigated using human umbilical cord endothelial cells (HUVECs) in vitro and diabetic db/db mice in vivo. Subjects with higher sCD93 levels had a lower estimated glomerular filtration rate (eGFR). The sCD93 level was an independent determinant of both the albumin-to-creatinine ratio (ACR) and the eGFR. The risk of prevalent DN was higher in the high sCD93 group (adjusted odds ratio 7.212, 95% confidence interval 1.244-41.796, p = 0.028). In vitro, CD93 was highly expressed in HUVECs and both CD93 expression and secretion were upregulated after lipopolysaccharides (LPS) stimulation. In vivo, peritoneal and urine sCD93 levels and the renal glomerular expression of CD93 were significantly higher in the db/db mice than in the control db/m+ mice. These results suggest the potential of sCD93 as a candidate biomarker associated with DN.
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Affiliation(s)
- Minyoung Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea;
| | - Ho Seon Park
- Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Korea; (H.S.P.); (M.Y.C.); (H.Z.K.); (J.Y.H.); (A.C.); (J.S.P.); (C.W.A.)
| | - Min Yeong Choi
- Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Korea; (H.S.P.); (M.Y.C.); (H.Z.K.); (J.Y.H.); (A.C.); (J.S.P.); (C.W.A.)
| | - Hak Zoo Kim
- Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Korea; (H.S.P.); (M.Y.C.); (H.Z.K.); (J.Y.H.); (A.C.); (J.S.P.); (C.W.A.)
- Severance Institute for Vascular and Metabolic Research, Yonsei University College of Medicine, Seoul 03722, Korea
| | - Sung Jin Moon
- Department of Internal Medicine, International St. Mary’s Hospital, Catholic Kwandong University College of Medicine, Incheon 22711, Korea;
| | - Ji Yoon Ha
- Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Korea; (H.S.P.); (M.Y.C.); (H.Z.K.); (J.Y.H.); (A.C.); (J.S.P.); (C.W.A.)
| | - ARim Choi
- Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Korea; (H.S.P.); (M.Y.C.); (H.Z.K.); (J.Y.H.); (A.C.); (J.S.P.); (C.W.A.)
| | | | - Jong Suk Park
- Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Korea; (H.S.P.); (M.Y.C.); (H.Z.K.); (J.Y.H.); (A.C.); (J.S.P.); (C.W.A.)
- Severance Institute for Vascular and Metabolic Research, Yonsei University College of Medicine, Seoul 03722, Korea
| | - Eui-Cheol Shin
- Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Korea;
| | - Chul Woo Ahn
- Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Korea; (H.S.P.); (M.Y.C.); (H.Z.K.); (J.Y.H.); (A.C.); (J.S.P.); (C.W.A.)
- Severance Institute for Vascular and Metabolic Research, Yonsei University College of Medicine, Seoul 03722, Korea
| | - Shinae Kang
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea;
- Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Korea; (H.S.P.); (M.Y.C.); (H.Z.K.); (J.Y.H.); (A.C.); (J.S.P.); (C.W.A.)
- Severance Institute for Vascular and Metabolic Research, Yonsei University College of Medicine, Seoul 03722, Korea
- Correspondence: ; Tel.: +82-2-2019-3335; Fax: +82-2-3463-3882
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