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Huang X, Huang L, Tao H, Ren M, Yan L. Nonlinear association between hemoglobin glycation index and mortality in ischemic stroke Patients: Insights from the MIMIC-IV database. Diabetes Res Clin Pract 2025; 224:112105. [PMID: 40096948 DOI: 10.1016/j.diabres.2025.112105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2025] [Revised: 03/02/2025] [Accepted: 03/13/2025] [Indexed: 03/19/2025]
Abstract
AIMS Hemoglobin glycation index (HGI) is closely associated with adverse outcomes in several diseases. However, few studies have investigated the correlation between HGI and prognosis in patients with critical ischemic stroke. METHODS A cohort of patients was established from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Kaplan-Meier analysis, multivariate regression models, and restricted cubic splines (RCS) were used to investigate the associations between HGI and different outcomes. Mediation models were constructed to determine the mediating role of white blood cell (WBC) counts. RESULTS This study included 2,332 participants. In-hospital mortality differs significantly across HGI groups (24.43 %, 11.82 %, and 10.14 %, P < 0.001). Multivariate regression analyses found that lower HGI was significantly associated with greater mortality risk. Nonlinear analyses revealed an L-shaped association between HGI and short-term mortality (30-day and in-hospital), while a reverse J-shaped relationship emerged for long-term (365-day) mortality. Mediation analysis revealed that WBC counts mediated the association with proportions (%) of 33.73, 19.65, and 30.00, respectively. CONCLUSION Lower HGI is consistently related to poorer outcomes in patients with critical ischemic stroke. Higher HGI could be a protective factor in the short term but might increase mortality risk in the long term. WBC counts significantly mediate the association.
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Affiliation(s)
- Xuhang Huang
- Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou 510120, China; Guangdong Clinical Research Center for Metabolic Diseases, Guangzhou Key Laboratory for Metabolic Diseases, Guangzhou 510120, China
| | - Lejun Huang
- Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou 510120, China; Guangdong Clinical Research Center for Metabolic Diseases, Guangzhou Key Laboratory for Metabolic Diseases, Guangzhou 510120, China
| | - Haoran Tao
- Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou 510120, China; Guangdong Clinical Research Center for Metabolic Diseases, Guangzhou Key Laboratory for Metabolic Diseases, Guangzhou 510120, China
| | - Meng Ren
- Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou 510120, China; Guangdong Clinical Research Center for Metabolic Diseases, Guangzhou Key Laboratory for Metabolic Diseases, Guangzhou 510120, China.
| | - Li Yan
- Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou 510120, China; Guangdong Clinical Research Center for Metabolic Diseases, Guangzhou Key Laboratory for Metabolic Diseases, Guangzhou 510120, China.
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Bibi S, Naeem M, Schipf S, Bahls M, Dörr M, Friedrich N, Nauck M, Bülow R, Völzke H, Markus MRP, Ittermann T. Body composition markers are more strongly associated with type 2 diabetes than inflammatory markers-Results from the study of health in Pomerania. Eur J Clin Invest 2025; 55:e70005. [PMID: 39921528 PMCID: PMC11891827 DOI: 10.1111/eci.70005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2024] [Accepted: 01/27/2025] [Indexed: 02/10/2025]
Abstract
BACKGROUND AND AIMS Evidence links body composition and inflammatory markers with type 2 diabetes (T2D). However, the comparative analysis of body composition markers derived from different modalities and inflammatory markers in relation to T2D remains unexplored. This study aims to evaluate and compare the association of body composition and inflammatory markers with T2D. METHODS We included 4043 participants (2081 female, 51.4%) aged 20-84 enrolled in the population-based Study of Health in Pomerania. Multivariable logistic regression models adjusted for confounding were used to analyse associations of standardized body composition markers derived from classic anthropometry, bioelectrical impedance analysis, magnetic resonance imaging as well as inflammatory markers C-reactive protein, white blood cell count, fibrinogen, ferritin and CRP-to-albumin ratio with prevalent T2D. RESULTS Body composition markers were more strongly associated with T2D than inflammatory markers. Waist circumference exhibited the strongest association with T2D (female: odds ratio (OR) = 2.55; 95% confidence interval [CI]: 2.17-3.00; male: OR = 2.20; 95% CI: 1.86-2.60). Similarly, body weight (female: 2.07; 1.78-2.41; male: OR = 1.99; 95% CI = 1.71-2.31), waist-to-height ratio (female: OR = 2.39; 95% CI = 2.05-2.77; male: 2.28; 1.92-2.70) and visceral adipose tissue (female: 3.02; 95% CI = 2.11-4.32; male: 1.50; 1.19-1.89) showed strong associations with T2D. Among inflammatory markers, white blood cell count in male and CRP-to-albumin ratio in female exhibit the strongest association with T2D. CONCLUSIONS Body composition markers seem to be more tightly associated with prevalent T2D compared to inflammatory markers.
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Affiliation(s)
- Saima Bibi
- Institute for Community Medicine – Department SHIP/ Clinical‐Epidemiological ResearchUniversity Medicine GreifswaldGreifswaldGermany
| | - Muhammad Naeem
- Institute for Community Medicine – Department SHIP/ Clinical‐Epidemiological ResearchUniversity Medicine GreifswaldGreifswaldGermany
- Department of ZoologyUniversity of MalakandChakdara Dir (L)Pakistan
| | - Sabine Schipf
- Institute for Community Medicine – Department SHIP/ Clinical‐Epidemiological ResearchUniversity Medicine GreifswaldGreifswaldGermany
- German Center for Diabetes Research (DZD) Partner Site GreifswaldGreifswaldGermany
| | - Martin Bahls
- Department of Internal Medicine B – Cardiology, Intensive Care, Pulmonary Medicine and Infectious DiseasesUniversity Medicine GreifswaldGreifswaldGermany
- German Centre for Cardiovascular Research (DZHK), Partner Site GreifswaldGreifswaldGermany
| | - Marcus Dörr
- Department of Internal Medicine B – Cardiology, Intensive Care, Pulmonary Medicine and Infectious DiseasesUniversity Medicine GreifswaldGreifswaldGermany
- German Centre for Cardiovascular Research (DZHK), Partner Site GreifswaldGreifswaldGermany
| | - Nele Friedrich
- German Centre for Cardiovascular Research (DZHK), Partner Site GreifswaldGreifswaldGermany
- Institute of Clinical Chemistry and Laboratory MedicineUniversity Medicine GreifswaldGreifswaldGermany
| | - Matthias Nauck
- German Centre for Cardiovascular Research (DZHK), Partner Site GreifswaldGreifswaldGermany
- Institute of Clinical Chemistry and Laboratory MedicineUniversity Medicine GreifswaldGreifswaldGermany
| | - Robin Bülow
- Institute for Radiology and NeuroradiologyUniversity Medicine GreifswaldGreifswaldGermany
| | - Henry Völzke
- Institute for Community Medicine – Department SHIP/ Clinical‐Epidemiological ResearchUniversity Medicine GreifswaldGreifswaldGermany
- German Centre for Cardiovascular Research (DZHK), Partner Site GreifswaldGreifswaldGermany
| | - Marcello Ricardo Paulista Markus
- German Center for Diabetes Research (DZD) Partner Site GreifswaldGreifswaldGermany
- Department of Internal Medicine B – Cardiology, Intensive Care, Pulmonary Medicine and Infectious DiseasesUniversity Medicine GreifswaldGreifswaldGermany
- German Centre for Cardiovascular Research (DZHK), Partner Site GreifswaldGreifswaldGermany
| | - Till Ittermann
- Institute for Community Medicine – Department SHIP/ Clinical‐Epidemiological ResearchUniversity Medicine GreifswaldGreifswaldGermany
- German Centre for Cardiovascular Research (DZHK), Partner Site GreifswaldGreifswaldGermany
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Soremekun C, Jjingo D, Kateete D, Nash O, Nitsch D, Nyirenda M, Gill D, Zeggini E, Grallert H, Peters A, Chikowore T, Batini C, Soremekun O, Fatumo S. Mendelian randomization study highlights the role of hematological traits on Type-2 diabetes mellitus in African ancestry individuals. Front Pharmacol 2025; 16:1436972. [PMID: 40230699 PMCID: PMC11994964 DOI: 10.3389/fphar.2025.1436972] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Accepted: 03/03/2025] [Indexed: 04/16/2025] Open
Abstract
Introduction Observational studies have identified associations between hematological traits and type-2 diabetes mellitus (T2D). However, it is difficult to infer causal effects due to the potential of confounding. Our study utilizes the Mendelian randomization (MR) approach to address the above limitation and investigate the causal effect of hematological traits such as white blood cell (WBC), platelets (PLT), and red blood cell (RBC) on T2D in individuals of African ancestry. Methods The participating cohorts included participants of African ancestry in the Blood Cell consortium and the Million Veteran Program dataset. Using GWAS summary statistics, we applied a univariable and multivariable Two-sample MR to estimate the causal relationship between hematological traits and T2D. Results In the main IVW MR estimates, genetically predicted levels of mean corpuscular hemoglobin concentration (MCHC), mean corpuscular hemoglobin (MCH), and mean corpuscular volume (MCV) were associated with decreased risk of T2D. We also observed a decreased risk of T2D with genetically predicted total WBC count and neutrophil count (NEU), for the WBC traits. The multivariable analysis further supported the direct associations of genetically predicted MCH, MCHC, and MCV levels with a decreased risk of T2D. For the European ancestry, a similar pattern of association was observed for MCH and MCV. Discussion These findings indicate that hematological traits may differentially play a role in the development of T2D and be affected by T2D. However, further research is needed to validate and explore the biological pathways and mechanisms involved in these associations.
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Affiliation(s)
- Chisom Soremekun
- The African Computational Genomics (TACG) Research Group, MRC/UVRI and LSHTM Uganda Research Unit, Entebbe, Uganda
- Department of Immunology and Molecular Biology, School of Biomedical Sciences, Makerere University College of Health Sciences, Kampala, Uganda
- Centre for Genomics Research and Innovation, NABDA/FMST, Abuja, Nigeria
- Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Institute of Epidemiology, Neuherberg, Germany
| | - Daudi Jjingo
- African Center of Excellence in Bioinformatics and Data-Intensive Sciences, Kampala, Uganda
- Department of Computer Science, Makerere University, Kampala, Uganda
- Infectious Diseases Institute, Kampala, Uganda
| | - David Kateete
- Department of Immunology and Molecular Biology, School of Biomedical Sciences, Makerere University College of Health Sciences, Kampala, Uganda
| | - Oyekanmi Nash
- Centre for Genomics Research and Innovation, NABDA/FMST, Abuja, Nigeria
| | - Dorothea Nitsch
- Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London School of Hygiene and Tropical Medicine, United Kingdom
| | - Moffat Nyirenda
- Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London School of Hygiene and Tropical Medicine, United Kingdom
- MRC/UVRI and LSHTM Uganda Research Unit, Entebbe, Uganda
| | - Dipender Gill
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom
| | - Eleftheria Zeggini
- Institute of Translational Genomics, Helmholtz Zentrum München – German Research Center for Environmental Health, Neuherberg, Germany
- TUM School of Medicine, Technical University of Munich and Klinikum Rechts der Isar, Munich, Germany
| | - Harald Grallert
- Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Institute of Epidemiology, Neuherberg, Germany
- German Center for Diabetes Research (DZD), München-Neuherberg, Neuherberg, Germany
| | - Annette Peters
- Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Institute of Epidemiology, Neuherberg, Germany
- German Center for Diabetes Research (DZD), München-Neuherberg, Neuherberg, Germany
- Chair of Epidemiology, Institute for Medical Information Processing, Biometry and Epidemiology, Medical Faculty, Ludwig-Maximilians-Universität München, Munich, Germany
| | - Tinashe Chikowore
- Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School Boston, Boston, MA, United States
- Wits Donald Gordon Medical Centre, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Chiara Batini
- Department of Population Health Sciences, University of Leicester, Leicester, United Kingdom
- University Hospitals of Leicester NHS Trust, Leicester, United Kingdom
| | - Opeyemi Soremekun
- Institute of Translational Genomics, Helmholtz Zentrum München – German Research Center for Environmental Health, Neuherberg, Germany
- Molecular Bio-computation and Drug Design Laboratory, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
| | - Segun Fatumo
- The African Computational Genomics (TACG) Research Group, MRC/UVRI and LSHTM Uganda Research Unit, Entebbe, Uganda
- Precision Healthcare University Research Institute, Queen Mary University of London, United Kingdom
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Geng XQ, Chen SF, Wang FY, Yang HJ, Zhao YL, Xu ZR, Yang Y. Correlation between key indicators of continuous glucose monitoring and the risk of diabetic foot. World J Diabetes 2025; 16:99277. [PMID: 40093283 PMCID: PMC11885981 DOI: 10.4239/wjd.v16.i3.99277] [Citation(s) in RCA: 1] [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: 07/18/2024] [Revised: 11/09/2024] [Accepted: 12/23/2024] [Indexed: 01/21/2025] Open
Abstract
BACKGROUND Continuous glucose monitoring (CGM) metrics, such as time in range (TIR) and glycemic risk index (GRI), have been linked to various diabetes-related complications, including diabetic foot (DF). AIM To investigate the association between CGM-derived indicators and the risk of DF in individuals with type 2 diabetes mellitus (T2DM). METHODS A total of 591 individuals with T2DM (297 with DF and 294 without DF) were enrolled. Relevant clinical data, complications, comorbidities, hematological parameters, and 72-hour CGM data were collected. Logistic regression analysis was employed to examine the relationship between these measurements and the risk of DF. RESULTS Individuals with DF exhibited higher mean blood glucose (MBG) levels and increased proportions of time above range (TAR), TAR level 1, and TAR level 2, but lower TIR (all P < 0.001). Patients with DF had significantly lower rates of achieving target ranges for TIR, TAR, and TAR level 2 than those without DF (all P < 0.05). Logistic regression analysis revealed that GRI, MBG, and TAR level 1 were positively associated with DF risk, while TIR was inversely correlated (all P < 0.05). Achieving TIR and TAR was inversely correlated with white blood cell count and glycated hemoglobin A1c levels (P < 0.05). Additionally, achieving TAR was influenced by fasting plasma glucose, body mass index, diabetes duration, and antidiabetic medication use. CONCLUSION CGM metrics, particularly TIR and GRI, are significantly associated with the risk of DF in T2DM, emphasizing the importance of improved glucose control.
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Affiliation(s)
- Xin-Qian Geng
- Department of Endocrinology, Affiliated Hospital of Yunnan University, Second People’s Hospital of Yunnan Province, Kunming 650021, Yunnan Province, China
| | - Shun-Fang Chen
- Department of Endocrinology, Affiliated Hospital of Yunnan University, Second People’s Hospital of Yunnan Province, Kunming 650021, Yunnan Province, China
| | - Fei-Ying Wang
- Department of Endocrinology, Affiliated Hospital of Yunnan University, Second People’s Hospital of Yunnan Province, Kunming 650021, Yunnan Province, China
| | - Hui-Jun Yang
- Department of Endocrinology, Affiliated Hospital of Yunnan University, Second People’s Hospital of Yunnan Province, Kunming 650021, Yunnan Province, China
| | - Yun-Li Zhao
- Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, Yunnan University, Kunming 650500, Yunnan Province, China
| | - Zhang-Rong Xu
- The Diabetic Center of PLA, The Ninth Medical Center of PLA General Hospital (306th Hosp PLA), Beijing 100101, China
| | - Ying Yang
- Department of Endocrinology and Metabolism, Affiliated Hospital of Yunnan University, Second People’s Hospital of Yunnan Province, Kunming 650021, Yunnan Province, China
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Nawal CL, Singh A, Saini HL, Rankawat G. Impact of Blood Glucose Level on Hematological Indices in Patients with Type 2 Diabetes Mellitus. THE JOURNAL OF THE ASSOCIATION OF PHYSICIANS OF INDIA 2025; 73:16-20. [PMID: 39927992 DOI: 10.59556/japi.73.0851] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/11/2025]
Abstract
BACKGROUND The severity and complications of type 2 diabetes mellitus (T2DM) are the most important preventable health burdens. This study was undertaken to assess the impact of hyperglycemia on hematological indices in patients with T2DM. MATERIALS AND METHODS This study was conducted on 300 patients with T2DM, which included group A having controlled diabetes [hemoglobin A1c (HbA1c) <7%] and group B having uncontrolled diabetes (HbA1c >7%). Information concerning medical history, physical examination, diabetic parameters, hematological indices, and laboratory findings was extracted for interpretation and association between both groups. RESULTS About 115 patients (38.33%) had HbA1c <7% and 185 patients (61.67%) had HbA1c >7%. Total leukocyte count (TLC), monocytes, basophils, red cell distribution width (RDW-CV), platelet distribution width (PDW), mean platelet volume (MPV), platelet large cell ratio (P-LCR), plateletcrit (PCT), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were significantly higher among patients with uncontrolled T2DM compared to those with controlled T2DM (p < 0.05), while red blood cells (RBC) count, hemoglobin, mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH) were significantly lower in the uncontrolled diabetic group compared to the controlled diabetic group (p < 0.05). HbA1c had a significant positive correlation coefficient with TLC, neutrophil count, basophil count, PDW, MPV, PCT, PLR, and NLR, while RBC count, hemoglobin, hematocrit (HCT), and MCV showed significant negative correlation coefficients (p < 0.05). CONCLUSION This study concluded that inflammation, tendency to coagulation, and thrombosis can be detected with easily accessible and inexpensive hematological indices. Therefore, hematological indices can be used as a direct measure to detect the severity of T2DM and its complications.
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Affiliation(s)
- C L Nawal
- Senior Professor, Department of General Medicine, SMS Medical College, Jaipur, Rajasthan, India
| | - Aradhana Singh
- Professor, Department of Rheumatology, SMS Medical College, Jaipur, Rajasthan, India
| | - Hazari Lal Saini
- Assistant Professor, Department of General Medicine, SMS Medical College, Jaipur, Rajasthan, India
| | - Govind Rankawat
- Assistant Professor, Department of General Medicine, SMS Medical College, Jaipur, Rajasthan, India, Corresponding Author
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Le TN, Bright R, Truong V, Li J, Juneja R, Vasilev K. Key biomarkers in type 2 diabetes patients: A systematic review. Diabetes Obes Metab 2025; 27:7-22. [PMID: 39355932 PMCID: PMC11618249 DOI: 10.1111/dom.15991] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Revised: 09/10/2024] [Accepted: 09/19/2024] [Indexed: 10/03/2024]
Abstract
Type 2 diabetes mellitus (T2DM) is not just a local health issue but a significant global health burden, affecting patient outcomes and clinical management worldwide. Despite the wealth of studies reporting T2DM biomarkers, there is an urgent need for a comparative review. This review aims to provide a comprehensive analysis based on the reported T2DM biomarkers and how these are linked with other conditions, such as inflammation and wound healing. A comparative review was conducted on 24 001 study participants, including 10 024 T2DM patients and 13 977 controls (CTL; age 30-90 years). Four main profiles were extracted and analysed from the clinical reports over the past 11 years: haematological (1084 cases vs. 1458 CTL), protein (6753 cases vs. 9613 CTL), cytokine (975 cases vs. 1350 CTL) and lipid (1212 cases vs. 1556 CTL). This review provides a detailed analysis of the haematological profile in T2DM patients, highlighting fundamental changes such as increased white blood cells and platelet counts, accompanied by decreases in red blood cell counts and iron absorption. In the serum protein profile, a reduction in albumin and anti-inflammatory cytokines was noted along with an increase in globulin levels and pro-inflammatory cytokines. Furthermore, changes in lipid profiles were discussed, specifically the decreases in high-density lipoprotein (HDL) and the increases in low-density lipoprotein (LDL) and triglycerides. Understanding the changes in these four biomarker profiles is essential for developing innovative strategies to create diagnostic and prognostic tools for diabetes management.
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Affiliation(s)
- Thien Ngoc Le
- College of Medicine and Public HealthFlinders UniversityAdelaideSouth AustraliaAustralia
| | - Richard Bright
- College of Medicine and Public HealthFlinders UniversityAdelaideSouth AustraliaAustralia
| | - Vi‐Khanh Truong
- College of Medicine and Public HealthFlinders UniversityAdelaideSouth AustraliaAustralia
| | - Jordan Li
- College of Medicine and Public HealthFlinders UniversityAdelaideSouth AustraliaAustralia
- Department of Renal Medicine, Flinders Medical CentreBedford ParkSouth AustraliaAustralia
| | - Rajiv Juneja
- College of Medicine and Public HealthFlinders UniversityAdelaideSouth AustraliaAustralia
- Department of Renal Medicine, Flinders Medical CentreBedford ParkSouth AustraliaAustralia
| | - Krasimir Vasilev
- College of Medicine and Public HealthFlinders UniversityAdelaideSouth AustraliaAustralia
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Luna-Marco C, Devos D, Cacace J, Fernandez-Reyes M, Díaz-Pozo P, Salazar JD, Solá E, Morillas C, Rocha M, Víctor VM, Rovira-Llopis S. Molecular circadian clock disruption in the leukocytes of individuals with type 2 diabetes and overweight, and its relationship with leukocyte-endothelial interactions. Diabetologia 2024; 67:2316-2328. [PMID: 38981930 PMCID: PMC11446997 DOI: 10.1007/s00125-024-06219-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Accepted: 05/22/2024] [Indexed: 07/11/2024]
Abstract
AIMS/HYPOTHESIS Alterations in circadian rhythms increase the likelihood of developing type 2 diabetes and CVD. Circadian rhythms are controlled by several core clock genes, which are expressed in nearly every cell, including immune cells. Immune cells are key players in the pathophysiology of type 2 diabetes, and participate in the atherosclerotic process that underlies cardiovascular risk in these patients. The role of the core clock in the leukocytes of people with type 2 diabetes and the inflammatory process associated with it are unknown. We aimed to evaluate whether the molecular clock system is impaired in the leukocytes of type 2 diabetes patients and to explore the mechanism by which this alteration leads to an increased cardiovascular risk in this population. METHODS This is an observational cross-sectional study performed in 25 participants with type 2 diabetes and 28 healthy control participants. Clinical and biochemical parameters were obtained. Peripheral blood leukocytes were isolated using magnetic bead technology. RNA and protein lysates were obtained to assess clock-related gene transcript and protein levels using real-time PCR and western blot, respectively. Luminex XMAP technology was used to assess levels of inflammatory markers. Leukocyte-endothelial interaction assays were performed by perfusing participants' leukocytes or THP-1 cells (with/without CLK8) over a HUVEC monolayer in a parallel flow chamber using a dynamic adhesion system. RESULTS Participants with type 2 diabetes showed increased BMAL1 and NR1D1 mRNA levels and decreased protein levels of circadian locomotor output cycles kaput (CLOCK), cryptochrome 1 (CRY1), phosphorylated basic helix-loop-helix ARNT like 1 (p-BMAL1) and period circadian protein homologue 2 (PER2). Correlation studies revealed that these alterations in clock proteins were negatively associated with glucose, HbA1c, insulin and HOMA-IR levels and leukocyte cell counts. The leukocyte rolling velocity was reduced and rolling flux and adhesion were enhanced in individuals with type 2 diabetes compared with healthy participants. Interestingly, inhibition of CLOCK/BMAL1 activity in leukocytes using the CLOCK inhibitor CLK8 mimicked the effects of type 2 diabetes on leukocyte-endothelial interactions. CONCLUSIONS/INTERPRETATION Our study demonstrates alterations in the molecular clock system in leukocytes of individuals with type 2 diabetes, manifested in increased mRNA levels and decreased protein levels of the core clock machinery. These alterations correlated with the impaired metabolic and proinflammatory profile of the participants with type 2 diabetes. Our findings support a causal role for decreased CLOCK/BMAL1 activity in the increased level of leukocyte-endothelial interactions. Overall, our data suggest that alterations in core clock proteins accelerate the inflammatory process, which may ultimately precipitate the onset of CVD in patients with type 2 diabetes.
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Affiliation(s)
- Clara Luna-Marco
- Service of Endocrinology and Nutrition, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain
- Department of Physiology, University of Valencia, INCLIVA (Biomedical Research Institute Valencia), Valencia, Spain
| | - Deédeni Devos
- Service of Endocrinology and Nutrition, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain
| | - Julia Cacace
- Service of Endocrinology and Nutrition, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain
| | - Meylin Fernandez-Reyes
- Service of Endocrinology and Nutrition, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain
| | - Pedro Díaz-Pozo
- Service of Endocrinology and Nutrition, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain
| | - Juan D Salazar
- Service of Endocrinology and Nutrition, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain
| | - Eva Solá
- Service of Endocrinology and Nutrition, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain
| | - Carlos Morillas
- Service of Endocrinology and Nutrition, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain
| | - Milagros Rocha
- Service of Endocrinology and Nutrition, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain
- CIBERehd - Department of Pharmacology, University of Valencia, Valencia, Spain
| | - Víctor M Víctor
- Service of Endocrinology and Nutrition, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain.
- Department of Physiology, University of Valencia, INCLIVA (Biomedical Research Institute Valencia), Valencia, Spain.
- CIBERehd - Department of Pharmacology, University of Valencia, Valencia, Spain.
| | - Susana Rovira-Llopis
- Service of Endocrinology and Nutrition, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain.
- Department of Physiology, University of Valencia, INCLIVA (Biomedical Research Institute Valencia), Valencia, Spain.
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Xian J, Du R, Yuan H, Li J, Pei Q, Hao Y, Zeng X, Wang J, Ye T. The application of predictive value of diabetes autoantibody profile combined with clinical data and routine laboratory indexes in the classification of diabetes mellitus. Front Endocrinol (Lausanne) 2024; 15:1349117. [PMID: 39247917 PMCID: PMC11377899 DOI: 10.3389/fendo.2024.1349117] [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: 12/04/2023] [Accepted: 07/24/2024] [Indexed: 09/10/2024] Open
Abstract
Objective Currently, distinct use of clinical data, routine laboratory indicators or the detection of diabetic autoantibodies in the diagnosis and management of diabetes mellitus is limited. Hence, this study was aimed to screen the indicators, and to establish and validate a multifactorial logistic regression model nomogram for the non-invasive differential prediction of type 1 diabetes mellitus. Methods Clinical data, routine laboratory indicators, and diabetes autoantibody profiles of diabetic patients admitted between September 2018 and December 2022 were retrospectively analyzed. Logistic regression was used to select the independent influencing factors, and a prediction nomogram based on the multiple logistic regression model was constructed using these independent factors. Moreover, the predictive accuracy and clinical application value of the nomogram were evaluated using Receiver Operating Characteristic (ROC) curves, calibration curves, decision curve analysis (DCA), and clinical impact curves (CIC). Results A total of 522 diabetic patients were included in this study. These patients were randomized into training and validation sets in a 7:3 ratio. The predictors screened included age, prealbumin (PA), high-density lipoprotein cholesterol (HDL-C), islet cells autoantibodies (ICA), islets antigen 2 autoantibodies (IA-2A), glutamic acid decarboxylase antibody (GADA), and C-peptide levels. Based on these factors, a multivariate model nomogram was constructed, which had an Area Under Curve (AUC) of 0.966 and 0.961 for the training set and validation set, respectively. Subsequently, the calibration curves demonstrated a strong accuracy of the graph; the DCA and CIC results indicated that the graph could be used as a non-invasive valid predictive tool for the differential diagnosis of type 1 diabetes mellitus, clinically. Conclusion The established prediction model combining patient's age, PA, HDL-C, ICA, IA-2A, GADA, and C-peptide can assist in differential diagnosis of type 1 diabetes mellitus and type 2 diabetes mellitus and provides a basis for the clinical as well as therapeutic management of the disease.
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Affiliation(s)
- Jiawen Xian
- Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Sichuan, China
| | - Rongrong Du
- Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Sichuan, China
| | - Hui Yuan
- School of Basic Medical Sciences and School of Stomatology, Mudanjiang Medical University, Heilongjiang, China
| | - Jingyuan Li
- Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Sichuan, China
| | - Qin Pei
- Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Sichuan, China
| | - Yongjie Hao
- Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Sichuan, China
| | - Xi Zeng
- Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Sichuan, China
| | - Jingying Wang
- Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Sichuan, China
| | - Ting Ye
- Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Sichuan, China
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Zhao L, Wei Y, Liu Q, Cai J, Mo X, Tang X, Wang X, Qin L, Liang Y, Cao J, Huang C, Lu Y, Zhang T, Luo L, Rong J, Wu S, Jin W, Guan Q, Teng K, Li Y, Qin J, Zhang Z. Association between multiple-heavy-metal exposures and systemic immune inflammation in a middle-aged and elderly Chinese general population. BMC Public Health 2024; 24:1192. [PMID: 38679723 PMCID: PMC11057124 DOI: 10.1186/s12889-024-18638-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: 01/22/2024] [Accepted: 04/17/2024] [Indexed: 05/01/2024] Open
Abstract
BACKGROUND Exposure to heavy metals alone or in combination can promote systemic inflammation. The aim of this study was to investigate potential associations between multiple plasma heavy metals and markers of systemic immune inflammation. METHODS Using a cross-sectional study, routine blood tests were performed on 3355 participants in Guangxi, China. Eight heavy metal elements in plasma were determined by inductively coupled plasma mass spectrometry. Immunoinflammatory markers were calculated based on peripheral blood WBC and its subtype counts. A generalised linear regression model was used to analyse the association of each metal with the immunoinflammatory markers, and the association of the metal mixtures with the immunoinflammatory markers was further assessed using weighted quantile sum (WQS) regression. RESULTS In the single-metal model, plasma metal Fe (log10) was significantly negatively correlated with the levels of immune-inflammatory markers SII, NLR and PLR, and plasma metal Cu (log10) was significantly positively correlated with the levels of immune-inflammatory markers SII and PLR. In addition, plasma metal Mn (log10 conversion) was positively correlated with the levels of immune inflammatory markers NLR and PLR. The above associations remained after multiple corrections. In the mixed-metal model, after WQS regression analysis, plasma metal Cu was found to have the greatest weight in the positive effects of metal mixtures on SII and PLR, while plasma metals Mn and Fe had the greatest weight in the positive effects of metal mixtures on NLR and LMR, respectively. In addition, blood Fe had the greatest weight in the negative effects of the metal mixtures for SII, PLR and NLR. CONCLUSION Plasma metals Cu and Mn were positively correlated with immunoinflammatory markers SII, NLR and PLR. While plasma metal Fe was negatively correlated with immunoinflammatory markers SII, NLR, and PLR.
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Affiliation(s)
- Linhai Zhao
- Department of Occupational and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Yanfei Wei
- Department of Epidemiology, School of Public Health (Guangdong Provincial Key Laboratory of Tropical Disease Research), Southern Medical University, Guangzhou, Guangdong, China
| | - Qiumei Liu
- Department of Occupational and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Jiansheng Cai
- School of Public Health, Guilin Medical University, Guilin, Guangxi Zhuang Autonomous Region, China
- Guangxi Key Laboratory of Entire Lifecycle Health and Care, Guilin Medical University, Guilin, Guangxi Zhuang Autonomous Region, China
| | - Xiaoting Mo
- Department of Occupational and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Xu Tang
- Department of Occupational and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Xuexiu Wang
- Department of Occupational and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Lidong Qin
- Department of Occupational and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Yujian Liang
- Department of Occupational and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Jiejing Cao
- Department of Occupational and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Chuwu Huang
- Department of Occupational and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Yufu Lu
- Department of Occupational and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Tiantian Zhang
- Department of Occupational and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Lei Luo
- Department of Occupational and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Jiahui Rong
- Department of Occupational and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Songju Wu
- Department of Occupational and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Wenjia Jin
- Department of Occupational and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Qinyi Guan
- Department of Occupational and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Kaisheng Teng
- Department of Occupational and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
| | - You Li
- School of Public Health, Guilin Medical University, Guilin, Guangxi Zhuang Autonomous Region, China
| | - Jian Qin
- Department of Occupational and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China.
- Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China.
- Guangxi Key Laboratory of Environment and Health Research, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China.
- Key Laboratory of Longevity and Aging-related Diseases of Chinese Ministry of Education, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China.
| | - Zhiyong Zhang
- Department of Occupational and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China.
- School of Public Health, Guilin Medical University, Guilin, Guangxi Zhuang Autonomous Region, China.
- Guangxi Key Laboratory of Entire Lifecycle Health and Care, Guilin Medical University, Guilin, Guangxi Zhuang Autonomous Region, China.
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Lv X, Luo J, Huang W, Guo H, Bai X, Yan P, Jiang Z, Zhang Y, Jing R, Chen Q, Li M. Identifying diagnostic indicators for type 2 diabetes mellitus from physical examination using interpretable machine learning approach. Front Endocrinol (Lausanne) 2024; 15:1376220. [PMID: 38562414 PMCID: PMC10982324 DOI: 10.3389/fendo.2024.1376220] [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: 01/25/2024] [Accepted: 02/29/2024] [Indexed: 04/04/2024] Open
Abstract
Background Identification of patients at risk for type 2 diabetes mellitus (T2DM) can not only prevent complications and reduce suffering but also ease the health care burden. While routine physical examination can provide useful information for diagnosis, manual exploration of routine physical examination records is not feasible due to the high prevalence of T2DM. Objectives We aim to build interpretable machine learning models for T2DM diagnosis and uncover important diagnostic indicators from physical examination, including age- and sex-related indicators. Methods In this study, we present three weighted diversity density (WDD)-based algorithms for T2DM screening that use physical examination indicators, the algorithms are highly transparent and interpretable, two of which are missing value tolerant algorithms. Patients Regarding the dataset, we collected 43 physical examination indicator data from 11,071 cases of T2DM patients and 126,622 healthy controls at the Affiliated Hospital of Southwest Medical University. After data processing, we used a data matrix containing 16004 EHRs and 43 clinical indicators for modelling. Results The indicators were ranked according to their model weights, and the top 25% of indicators were found to be directly or indirectly related to T2DM. We further investigated the clinical characteristics of different age and sex groups, and found that the algorithms can detect relevant indicators specific to these groups. The algorithms performed well in T2DM screening, with the highest area under the receiver operating characteristic curve (AUC) reaching 0.9185. Conclusion This work utilized the interpretable WDD-based algorithms to construct T2DM diagnostic models based on physical examination indicators. By modeling data grouped by age and sex, we identified several predictive markers related to age and sex, uncovering characteristic differences among various groups of T2DM patients.
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Affiliation(s)
- Xiang Lv
- College of Chemistry, Sichuan University, Chengdu, China
| | - Jiesi Luo
- Basic Medical College, Southwest Medical University, Luzhou, China
| | - Wei Huang
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, China
- Metabolic Vascular Disease Key Laboratoryof Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Hui Guo
- College of Chemistry, Sichuan University, Chengdu, China
| | - Xue Bai
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, China
- Metabolic Vascular Disease Key Laboratoryof Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Pijun Yan
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, China
- Metabolic Vascular Disease Key Laboratoryof Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Zongzhe Jiang
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, China
- Metabolic Vascular Disease Key Laboratoryof Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Yonglin Zhang
- Department of Pharmacy, The Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Runyu Jing
- School of Cyber Science and Engineering, Sichuan University, Chengdu, China
| | - Qi Chen
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, China
- Metabolic Vascular Disease Key Laboratoryof Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou, China
- Department of Nursing, The Affiliated Hospital of Southwest Medical University, Luzhou, China
- School of Nursing, Southwest Medical University, Luzhou, China
| | - Menglong Li
- College of Chemistry, Sichuan University, Chengdu, China
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Adepoju FO, Sokolova KV, Gette IF, Danilova IG, Tsurkan MV, Mondragon AC, Kovaleva EG, Miranda JM. Protective Effect of Betulin on Streptozotocin-Nicotinamide-Induced Diabetes in Female Rats. Int J Mol Sci 2024; 25:2166. [PMID: 38396842 PMCID: PMC10888537 DOI: 10.3390/ijms25042166] [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: 01/06/2024] [Revised: 02/03/2024] [Accepted: 02/08/2024] [Indexed: 02/25/2024] Open
Abstract
Type 2 diabetes is characterized by hyperglycemia and a relative loss of β-cell function. Our research investigated the antidiabetic potential of betulin, a pentacyclic triterpenoid found primarily in birch bark and, intriguingly, in a few marine organisms. Betulin has been shown to possess diverse biological activities, including antioxidant and antidiabetic activities; however, no studies have fully explored the effects of betulin on the pancreas and pancreatic islets. In this study, we investigated the effect of betulin on streptozotocin-nicotinamide (STZ)-induced diabetes in female Wistar rats. Betulin was prepared as an emulsion, and intragastric treatments were administered at doses of 20 and 50 mg/kg for 28 days. The effect of treatment was assessed by analyzing glucose parameters such as fasting blood glucose, hemoglobin A1C, and glucose tolerance; hepatic and renal biomarkers; lipid peroxidation; antioxidant enzymes; immunohistochemical analysis; and hematological indices. Administration of betulin improved the glycemic response and decreased α-amylase activity in diabetic rats, although insulin levels and homeostatic model assessment for insulin resistance (HOMA-IR) scores remained unchanged. Furthermore, betulin lowered the levels of hepatic biomarkers (aspartate aminotransferase, alanine aminotransferase, and alpha-amylase activities) and renal biomarkers (urea and creatine), in addition to improving glutathione levels and preventing the elevation of lipid peroxidation in diabetic animals. We also found that betulin promoted the regeneration of β-cells in a dose-dependent manner but did not have toxic effects on the pancreas. In conclusion, betulin at a dose of 50 mg/kg exerts a pronounced protective effect against cytolysis, diabetic nephropathy, and damage to the acinar pancreas and may be a potential treatment option for diabetes.
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Affiliation(s)
- Feyisayo O. Adepoju
- Department of Technology for Organic Synthesis, Institute of Chemical Technology, Ural Federal University, Mira 19, 620002 Yekaterinburg, Russia; (F.O.A.); (K.V.S.); (I.F.G.); (I.G.D.)
| | - Ksenia V. Sokolova
- Department of Technology for Organic Synthesis, Institute of Chemical Technology, Ural Federal University, Mira 19, 620002 Yekaterinburg, Russia; (F.O.A.); (K.V.S.); (I.F.G.); (I.G.D.)
- Institute of Immunology and Physiology, Russian Academy of Sciences, 620049 Yekaterinburg, Russia
| | - Irina F. Gette
- Department of Technology for Organic Synthesis, Institute of Chemical Technology, Ural Federal University, Mira 19, 620002 Yekaterinburg, Russia; (F.O.A.); (K.V.S.); (I.F.G.); (I.G.D.)
- Institute of Immunology and Physiology, Russian Academy of Sciences, 620049 Yekaterinburg, Russia
| | - Irina G. Danilova
- Department of Technology for Organic Synthesis, Institute of Chemical Technology, Ural Federal University, Mira 19, 620002 Yekaterinburg, Russia; (F.O.A.); (K.V.S.); (I.F.G.); (I.G.D.)
- Institute of Immunology and Physiology, Russian Academy of Sciences, 620049 Yekaterinburg, Russia
| | | | - Alicia C. Mondragon
- Departamento de Química Analítica, Nutrición y Bromatología, Campus Terra, Universidade da Santiago de Compostela, 27002 Lugo, Spain;
| | - Elena G. Kovaleva
- Department of Technology for Organic Synthesis, Institute of Chemical Technology, Ural Federal University, Mira 19, 620002 Yekaterinburg, Russia; (F.O.A.); (K.V.S.); (I.F.G.); (I.G.D.)
| | - Jose Manuel Miranda
- Departamento de Química Analítica, Nutrición y Bromatología, Campus Terra, Universidade da Santiago de Compostela, 27002 Lugo, Spain;
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12
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Kresovich JK, O’Brien KM, Xu Z, Weinberg CR, Sandler DP, Taylor JA. Circulating Leukocyte Subsets Before and After a Breast Cancer Diagnosis and Therapy. JAMA Netw Open 2024; 7:e2356113. [PMID: 38358741 PMCID: PMC10870180 DOI: 10.1001/jamanetworkopen.2023.56113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Accepted: 12/21/2023] [Indexed: 02/16/2024] Open
Abstract
Importance Changes in leukocyte composition often precede chronic disease onset. Patients with a history of breast cancer (hereinafter referred to as breast cancer survivors) are at increased risk for subsequent chronic diseases, but the long-term changes in peripheral leukocyte composition following a breast cancer diagnosis and treatment remain unknown. Objective To examine longitudinal changes in peripheral leukocyte composition in women who did and did not develop breast cancer and identify whether differences in breast cancer survivors were associated with specific treatments. Design, Setting, and Participants In this prospective cohort study, paired blood samples were collected from 2315 women enrolled in The Sister Study, a US-nationwide prospective cohort study of 50 884 women, at baseline (July 2003 to March 2009) and follow-up (October 2013 to March 2015) home visits, with a mean (SD) follow-up interval of 7.6 (1.4) years. By design, approximately half of the included women had been diagnosed and treated for breast cancer after enrollment and before the second blood draw. A total of 410 women were included in the present study, including 185 breast cancer survivors and 225 who remained free of breast cancer over a comparable follow-up period. Data were analyzed from April 21 to September 9, 2022. Exposures Breast cancer status and, among breast cancer survivors, cancer treatment type (chemotherapy, radiotherapy, endocrine therapy, or surgery). Main Outcomes and Measures Blood DNA methylation data were generated in 2019 using a genome-wide methylation screening tool and deconvolved to estimate percentages of 12 circulating leukocyte subsets. Results Of the 410 women included in the analysis, the mean (SD) age at enrollment was 56 (9) years. Compared with breast cancer-free women, breast cancer survivors had decreased percentages of circulating eosinophils (-0.45% [95% CI, -0.87% to -0.03%]; P = .03), total CD4+ helper T cells (-1.50% [95% CI, -2.56% to -0.44%]; P = .01), and memory B cells (-0.22% [95% CI, -0.34% to -0.09%]; P = .001) and increased percentages of circulating naive B cells (0.46% [95% CI, 0.17%-0.75%]; P = .002). In breast cancer survivor-only analyses, radiotherapy was associated with decreases in total CD4+ T cell levels, whereas chemotherapy was associated with increases in naive B cell levels. Surgery and endocrine therapy were not meaningfully associated with leukocyte changes. Conclusions and Relevance In this cohort study of 410 women, breast cancer survivors experienced lasting changes in peripheral leukocyte composition compared with women who remained free of breast cancer. These changes may be related to treatment with chemotherapy or radiotherapy and could influence future chronic disease risk.
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Affiliation(s)
- Jacob K. Kresovich
- Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida
- Department of Breast Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida
- Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health (NIH), Research Triangle Park, North Carolina
| | - Katie M. O’Brien
- Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health (NIH), Research Triangle Park, North Carolina
| | - Zongli Xu
- Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health (NIH), Research Triangle Park, North Carolina
| | - Clarice R. Weinberg
- Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina
| | - Dale P. Sandler
- Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health (NIH), Research Triangle Park, North Carolina
| | - Jack A. Taylor
- Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health (NIH), Research Triangle Park, North Carolina
- Epigenetic and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina
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Kour B, Shukla N, Bhargava H, Sharma D, Sharma A, Singh A, Valadi J, Sadasukhi TC, Vuree S, Suravajhala P. Identification of Plausible Candidates in Prostate Cancer Using Integrated Machine Learning Approaches. Curr Genomics 2023; 24:287-306. [PMID: 38235353 PMCID: PMC10790336 DOI: 10.2174/0113892029240239231109082805] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 10/17/2023] [Accepted: 10/19/2023] [Indexed: 01/19/2024] Open
Abstract
Background Currently, prostate-specific antigen (PSA) is commonly used as a prostate cancer (PCa) biomarker. PSA is linked to some factors that frequently lead to erroneous positive results or even needless biopsies of elderly people. Objectives In this pilot study, we undermined the potential genes and mutations from several databases and checked whether or not any putative prognostic biomarkers are central to the annotation. The aim of the study was to develop a risk prediction model that could help in clinical decision-making. Methods An extensive literature review was conducted, and clinical parameters for related comorbidities, such as diabetes, obesity, as well as PCa, were collected. Such parameters were chosen with the understanding that variations in their threshold values could hasten the complicated process of carcinogenesis, more particularly PCa. The gathered data was converted to semi-binary data (-1, -0.5, 0, 0.5, and 1), on which machine learning (ML) methods were applied. First, we cross-checked various publicly available datasets, some published RNA-seq datasets, and our whole-exome sequencing data to find common role players in PCa, diabetes, and obesity. To narrow down their common interacting partners, interactome networks were analysed using GeneMANIA and visualised using Cytoscape, and later cBioportal was used (to compare expression level based on Z scored values) wherein various types of mutation w.r.t their expression and mRNA expression (RNA seq FPKM) plots are available. The GEPIA 2 tool was used to compare the expression of resulting similarities between the normal tissue and TCGA databases of PCa. Later, top-ranking genes were chosen to demonstrate striking clustering coefficients using the Cytoscape-cytoHubba module, and GEPIA 2 was applied again to ascertain survival plots. Results Comparing various publicly available datasets, it was found that BLM is a frequent player in all three diseases, whereas comparing publicly available datasets, GWAS datasets, and published sequencing findings, SPFTPC and PPIMB were found to be the most common. With the assistance of GeneMANIA, TMPO and FOXP1 were found as common interacting partners, and they were also seen participating with BLM. Conclusion A probabilistic machine learning model was achieved to identify key candidates between diabetes, obesity, and PCa. This, we believe, would herald precision scale modeling for easy prognosis.
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Affiliation(s)
- Bhumandeep Kour
- Department of Biotechnology, Lovely Professional University, Jalandhar, Punjab, India
- Bioclues.org, India
| | - Nidhi Shukla
- Bioclues.org, India
- Department of Biotechnology and Bioinformatics, Birla Institute of Scientific Research, Jaipur, Rajasthan, India
| | - Harshita Bhargava
- Department of Computer Science, IIS University, Jaipur, Rajasthan, India
| | - Devendra Sharma
- Urology and Renal Transplant Department of Renal Sciences, Rukmani Birla Hospital, Jaipur, Rajasthan, India
| | - Amita Sharma
- Department of Computer Science, IIS University, Jaipur, Rajasthan, India
| | - Anjuvan Singh
- Department of Biotechnology, School of Bioengineering and Biosciences, Lovely Professional University, Punjab, Phagwara, 144001, India
| | - Jayaraman Valadi
- Department of Computer Science, FLAME University, Pune, Maharashtra, India
| | - Trilok Chand Sadasukhi
- Department of Urology and Renal Transplant, Mahatma Gandhi University of Medical Sciences and Technology, Jaipur, Rajasthan, India
| | - Sugunakar Vuree
- Bioclues.org, India
- MNR Foundation for Research & Innovation, MNR Medical College and Hospital, MNR University, Telangana, India
| | - Prashanth Suravajhala
- Bioclues.org, India
- Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam, Kerala, India
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Kharaty S, Harrington JM, Millar SR, Perry IJ, Phillips CM. Plant-based dietary indices and biomarkers of chronic low-grade inflammation: a cross-sectional analysis of adults in Ireland. Eur J Nutr 2023; 62:3397-3410. [PMID: 37658860 PMCID: PMC10611858 DOI: 10.1007/s00394-023-03242-5] [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: 01/13/2023] [Accepted: 08/21/2023] [Indexed: 09/05/2023]
Abstract
PURPOSE There is increasing interest in the health benefits of plant-based diets (PBDs). Evidence reports favourable associations with inflammatory profiles and reduced cardiovascular disease risk. However, limited studies have examined relationships between PBD indices (PDIs) and inflammatory biomarkers. We explored overall PDI, healthful PDI (hPDI) and unhealthful PDI (uPDI) associations with inflammatory biomarker profiles. METHODS This cross-sectional analysis included 1986 middle- to older-aged adults from the Mitchelstown Cohort. PDI scores were calculated using validated food frequency questionnaires. PDI score associations with inflammatory biomarkers were assessed via linear regression analysis, with adjustment for potential confounders. RESULTS Comparison of quintiles (Q5 vs Q1) revealed lower concentrations of C-reactive protein (CRP), interleukin 6 (IL-6), white blood cells (WBCs), neutrophils and monocytes, and the leptin-to-adiponectin ratio (PDI and hPDI P < 0.05); lower leptin (PDI, P < 0.05), and complement component 3 (C3), tumour necrosis factor alpha (TNF-α), plasminogen activator inhibitor 1, lymphocytes and eosinophils (hPDI, P < 0.05); and higher concentrations of adiponectin (PDI and hPDI, P < 0.05). Conversely, higher concentrations of C3, CRP, IL-6, TNF-α, resistin, WBCs, neutrophils, lymphocytes, monocytes and eosinophils, and the neutrophil-to-lymphocyte ratio, and lower adiponectin concentrations were observed comparing uPDI quintiles (P < 0.05). In fully adjusted regression models, higher hPDI scores were associated with lower concentrations of C3, TNF-α, WBCs, neutrophils and monocytes (all P < 0.01). Higher uPDI scores were associated with higher C3 and TNF-α concentrations (all P < 0.01). CONCLUSION This study provides evidence that a more healthful PBD is associated with a more favourable inflammatory profile and that a more unhealthful PBD is associated with the reverse.
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Affiliation(s)
- Soraeya Kharaty
- School of Public Health, Physiotherapy and Sports Science, University College Dublin, Dublin 4, Ireland
| | | | - Seán R Millar
- School of Public Health, University College Cork, Cork, Ireland
| | - Ivan J Perry
- School of Public Health, University College Cork, Cork, Ireland
| | - Catherine M Phillips
- School of Public Health, Physiotherapy and Sports Science, University College Dublin, Dublin 4, Ireland.
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Essawi K, Dobie G, Shaabi MF, Hakami W, Saboor M, Madkhali AM, Hamami AAH, Allallah WH, Akhter MS, Mobarki AA, Hamali HA. Comparative Analysis of Red Blood Cells, White Blood Cells, Platelet Count, and Indices in Type 2 Diabetes Mellitus Patients and Normal Controls: Association and Clinical Implications. Diabetes Metab Syndr Obes 2023; 16:3123-3132. [PMID: 37822802 PMCID: PMC10563775 DOI: 10.2147/dmso.s422373] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2023] [Accepted: 09/04/2023] [Indexed: 10/13/2023] Open
Abstract
Background Diabetes mellitus (DM) is a major health burden affecting 537 million adults worldwide, characterized by chronic metabolic disorder and various complications. This case control study aimed to assess the impact of type 2 diabetes mellitus (T2DM), including hyperglycemia levels, on hematological parameters and complete blood count (CBC) derived parameters. Methods A total of 250 known diabetic patients from the Jazan Diabetic Center, Saudi Arabia, between January 2021 and December 2022, along with 175 healthy adult controls were recruited from Jazan Hospital's blood donation center. Demographic characteristics, medical histories, and relevant factors such as gender, age, BMI, treatment, disease duration, and comorbidities were collected with informed consent. Results The results of the red blood cell (RBC) count, RBC indices, and mean platelet volume showed significant differences between patients and controls, while the white cell (WBC) and platelet count were comparable between the two groups. CBC-derived parameters, especially neutrophil/lymphocyte ratio (NLR), and platelet/neutrophil ratio (PNR) exhibited significant differences. Conclusion CBC and derived parameters serve as inexpensive tools for T2DM patients monitoring, indicating early blood cell alterations and potential development of anemia. Further studies are needed to explore their role in predicting T2DM pathogenesis and progression, aiming to reduce severe complications, mortality and morbidity.
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Affiliation(s)
- Khaled Essawi
- Department of Medical Laboratory Technology, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia
| | - Gasim Dobie
- Department of Medical Laboratory Technology, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia
| | - Misk F Shaabi
- Department of Medical Laboratory Technology, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia
| | - Waleed Hakami
- Department of Medical Laboratory Technology, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia
| | - Muhammad Saboor
- Department of Medical Laboratory Sciences, College of Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
| | - Aymen M Madkhali
- Department of Medical Laboratory Technology, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia
| | - Abdullah A H Hamami
- Department of Laboratory & Blood Bank, Prince Mohammed bin Nasser Hospital, Ministry of Health, Jazan, Saudi Arabia
| | - Wael H Allallah
- Department of Laboratory & Blood Bank, Prince Mohammed bin Nasser Hospital, Ministry of Health, Jazan, Saudi Arabia
| | - Mohammad S Akhter
- Department of Medical Laboratory Technology, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia
| | - Abdullah A Mobarki
- Department of Medical Laboratory Technology, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia
| | - Hassan A Hamali
- Department of Medical Laboratory Technology, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia
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16
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Abbas AB, Hazeb A, Al-Badani R, Al-Thmary B, Mokaram R, Al-Najjar S, Mothna S, Kssiam A, Esmail A, Al-Rashidi A. A case-control study to evaluate hematological indices in blood of diabetic and non-diabetic individuals in Ibb City, Yemen. Sci Rep 2023; 13:16730. [PMID: 37794107 PMCID: PMC10550932 DOI: 10.1038/s41598-023-43973-3] [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: 07/08/2023] [Accepted: 09/30/2023] [Indexed: 10/06/2023] Open
Abstract
Diabetes mellitus (DM) is a chronic, metabolic illness characterized by an elevation of blood sugar levels. Patients with diabetes show changes in hematological indices. The study aimed to determine hematological indices, ESR, CRP, blood pressure (BP), and weight and their relationship with a fasting blood sugar (FBS) level and different variables in diabetic mellitus patients (DM) compared with healthy control (HC). A total of 202 participants (102 DM group and 100 HC group) were selected randomly. Data were collected using a questionnaire. Blood samples were collected from different places and investigated in Zain Medical Laboratories in Ibb City, Yemen (September 2022 to May 2023). GraphPad Prim was used to analyze the results. P-value ≤ 0.05 was considered statistically significant. The mean and standard deviation of age, weight, gender, residence, marital status, education levels, economic status, regular exercise, following a strict diet, and family history of diabetes revealed significant differences between DM and HC groups (P < 0.0001, P = 0001, P = 0.0027, P = 0.0002, P < 0.0001, P < 0.0001, P = 0.0002, P = 0.0011, P < 0.0001 and P = 0.0001, respectively). FBS results, systolic and diastolic BP, MCV, WBCs, monocytes, eosinophils, and platelets displayed significant differences between both groups (P < 0.0001, P < 0.0001 and P = 0.0404, P = 0.0191, P < 0.0001, P = 0.0253, P < 0.0001, and P = 0.0229, respectively). ESR exhibited statistical significance (P < 0.0001), while CRP displayed no significance. A Pearson's correlation showed that weight, Hb, RBCs, PCV, and WBCs were statistically negatively correlated with FBS whereas other hematological indices showed no correlation with FBS. In conclusion, DM patients had relatively higher levels of MCV, WBCs, eosinophils, platelets and ESR than the control group.
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Affiliation(s)
- Abdul Baset Abbas
- Medical Laboratories Department, Faculty of Medicine and Health Sciences, Ibb University, Ibb City, Yemen.
- Department of Medical Laboratories, Faculty of Medical Sciences, Aljazeera University, Ibb City, Yemen.
| | - Alia Hazeb
- Department of Medical Laboratories, Faculty of Medical Sciences, Aljazeera University, Ibb City, Yemen
| | - Rawan Al-Badani
- Department of Medical Laboratories, Faculty of Medical Sciences, Aljazeera University, Ibb City, Yemen
| | - Boshra Al-Thmary
- Department of Medical Laboratories, Faculty of Medical Sciences, Aljazeera University, Ibb City, Yemen
| | - Rasha Mokaram
- Department of Medical Laboratories, Faculty of Medical Sciences, Aljazeera University, Ibb City, Yemen
| | - Somayah Al-Najjar
- Department of Medical Laboratories, Faculty of Medical Sciences, Aljazeera University, Ibb City, Yemen
| | - Shifa Mothna
- Department of Medical Laboratories, Faculty of Medical Sciences, Aljazeera University, Ibb City, Yemen
| | - Aziza Kssiam
- Department of Medical Laboratories, Faculty of Medical Sciences, Aljazeera University, Ibb City, Yemen
| | - Abeer Esmail
- Department of Medical Laboratories, Faculty of Medical Sciences, Aljazeera University, Ibb City, Yemen
- Department of Medical Microbiology, Faculty of Sciences, Ibb University, Ibb City, Yemen
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17
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Lv K, Cui C, Fan R, Zha X, Wang P, Zhang J, Zhang L, Ke J, Zhao D, Cui Q, Yang L. Detection of diabetic patients in people with normal fasting glucose using machine learning. BMC Med 2023; 21:342. [PMID: 37674168 PMCID: PMC10483877 DOI: 10.1186/s12916-023-03045-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Accepted: 08/23/2023] [Indexed: 09/08/2023] Open
Abstract
BACKGROUND Diabetes mellitus (DM) is a chronic metabolic disease that could produce severe complications threatening life. Its early detection is thus quite important for the timely prevention and treatment. Normally, fasting blood glucose (FBG) by physical examination is used for large-scale screening of DM; however, some people with normal fasting glucose (NFG) actually have suffered from diabetes but are missed by the examination. This study aimed to investigate whether common physical examination indexes for diabetes can be used to identify the diabetes individuals from the populations with NFG. METHODS The physical examination data from over 60,000 individuals with NFG in three Chinese cohorts were used. The diabetes patients were defined by HbA1c ≥ 48 mmol/mol (6.5%). We constructed the models using multiple machine learning methods, including logistic regression, random forest, deep neural network, and support vector machine, and selected the optimal one on the validation set. A framework using permutation feature importance algorithm was devised to discover the personalized risk factors. RESULTS The prediction model constructed by logistic regression achieved the best performance with an AUC, sensitivity, and specificity of 0.899, 85.0%, and 81.1% on the validation set and 0.872, 77.9%, and 81.0% on the test set, respectively. Following feature selection, the final classifier only requiring 13 features, named as DRING (diabetes risk of individuals with normal fasting glucose), exhibited reliable performance on two newly recruited independent datasets, with the AUC of 0.964 and 0.899, the balanced accuracy of 84.2% and 81.1%, the sensitivity of 100% and 76.2%, and the specificity of 68.3% and 86.0%, respectively. The feature importance ranking analysis revealed that BMI, age, sex, absolute lymphocyte count, and mean corpuscular volume are important factors for the risk stratification of diabetes. With a case, the framework for identifying personalized risk factors revealed FBG, age, and BMI as significant hazard factors that contribute to an increased incidence of diabetes. DRING webserver is available for ease of application ( http://www.cuilab.cn/dring ). CONCLUSIONS DRING was demonstrated to perform well on identifying the diabetes individuals among populations with NFG, which could aid in early diagnosis and interventions for those individuals who are most likely missed.
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Affiliation(s)
- Kun Lv
- Key Laboratory of Non-Coding RNA Transformation Research of Anhui Higher Education Institutes, Wuhu, China.
- Central Laboratory, First Affiliated Hospital of Wannan Medical College, Wuhu, People's Republic of China.
| | - Chunmei Cui
- Department of Biomedical Informatics, State Key Laboratory of Vascular Homeostasis and Remodeling, School of Basic Medical Sciences, Peking University, Beijing, People's Republic of China.
| | - Rui Fan
- Department of Biomedical Informatics, State Key Laboratory of Vascular Homeostasis and Remodeling, School of Basic Medical Sciences, Peking University, Beijing, People's Republic of China
| | - Xiaojuan Zha
- Laboratory Medicine, First Affiliated Hospital of Wannan Medical College, Wuhu, People's Republic of China
| | - Pengyu Wang
- Department of Pathophysiology, Harbin Medical University, Harbin, People's Republic of China
| | - Jun Zhang
- Medical College of Shihezi University, Shihezi, People's Republic of China
| | - Lina Zhang
- Department of Laboratory Diagnosis, Daqing Oil Field General Hospital, Daqing, People's Republic of China
| | - Jing Ke
- Beijing Key Laboratory of Diabetes Research and Care, Center for Endocrine Metabolism and Immune Diseases, Beijing Luhe Hospital, Capital Medical University, Beijing, People's Republic of China
| | - Dong Zhao
- Beijing Key Laboratory of Diabetes Research and Care, Center for Endocrine Metabolism and Immune Diseases, Beijing Luhe Hospital, Capital Medical University, Beijing, People's Republic of China.
| | - Qinghua Cui
- Department of Biomedical Informatics, State Key Laboratory of Vascular Homeostasis and Remodeling, School of Basic Medical Sciences, Peking University, Beijing, People's Republic of China.
| | - Liming Yang
- Department of Pathophysiology, Harbin Medical University, Harbin, People's Republic of China.
- National Key Laboratory of Frigid Zone Cardiovascular Diseases (NKLFZCD), Harbin Medical University, Harbin, People's Republic of China.
- NHC Key Laboratory of Cell Transplantation, The First Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China.
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18
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Asiimwe OH, Rubaihayo J, Sulaiman SO, Osuwat LO, Kasozi KI. A protein restricted diet induces a stable increased fat storage phenotype in flies. Toxicol Rep 2023; 10:706-713. [PMID: 37396850 PMCID: PMC10313861 DOI: 10.1016/j.toxrep.2023.06.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Revised: 06/02/2023] [Accepted: 06/05/2023] [Indexed: 07/04/2023] Open
Abstract
Background Scientific evidence has revealed possible confounders in diet induced obesity models of Drosophila melanogaster. High Sugar Diet (HSD) induction of obesity in flies has been associated with fly hyperosmolarity and glucotoxicity, while High Fat Diet (HFD) induction has been associated with lipotoxicity. The objective of this study was to assess for a healthy obesity phenotype by comparison of fly survival, physio-chemical and biochemical changes associated with HSD, HFD and Protein Restricted Diet (PRD) obesity induction models of male Drosophila melanogaster. Here, we provide information on a PRD as the plausible option in obesity research not involving cancer, diabetes, glucotoxicity and lipotoxicity studies. Methods Obesity was induced by exposing Drosophila melanogaster white mutant w1118 to four experimental diets for four weeks. Group 1 was fed regular food (control), group 2 was fed a 0.5% less yeast than in regular feed (PRD), group 3 was fed a 30% w/v sucrose to regular cornmeal food (HSD) and group 4 was fed a 10% w/v food-grade coconut oil to regular cornmeal food (HFD). Peristaltic waves were measured on 3rd instar larvae of all experimental groups. Negative geotaxis, fly survival, body mass, catalase activity, triglycerides (TG/TP), sterol, and total protein were measured in adult Drosophila melanogaster after four weeks. Results Triglycerides (TG/TP) and total protein levels were significantly higher in HSD phenotype. Sterols were higher in HFD phenotype. Though catalase enzyme activity was highest in PRD phenotype, this activity was not statistically significant when compared to that of HSD and HFD phenotypes. However, PRD phenotype had the lowest mass, highest survival rate and the highest negative geotaxis, thus demonstrating a balanced, stable and more viable metabolic status in the experimental model. Conclusion A protein restricted diet induces a stable increased fat storage phenotype in Drosophila melanogaster.
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Affiliation(s)
- Oscar Hilary Asiimwe
- Faculty of Health Sciences, Mountains of the Moon University, Box 837, Fort Portal, Uganda
- Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, International Campus, Zhejiang University, Haining, China
| | - John Rubaihayo
- Faculty of Health Sciences, Mountains of the Moon University, Box 837, Fort Portal, Uganda
| | - Sheu Oluwadare Sulaiman
- Graduate Program in Cell Biology, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, Brazil
- Department of Physiology, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, Huye, Rwanda
| | | | - Keneth Iceland Kasozi
- School of Medicine, Kabale University, Box 317, Kabale, Uganda
- Infection Medicine, Deanery of Biomedical Sciences, College of Medicine and Veterinary Medicine, University of Edinburgh, EH8 9JZ, Edinburgh, United Kingdom
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19
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Li J, Niu Q, Wu A, Zhang Y, Hong L, Wang H. Causal relationship between circulating immune cells and the risk of type 2 diabetes: a Mendelian randomization study. Front Endocrinol (Lausanne) 2023; 14:1210415. [PMID: 37305035 PMCID: PMC10247959 DOI: 10.3389/fendo.2023.1210415] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2023] [Accepted: 05/09/2023] [Indexed: 06/13/2023] Open
Abstract
Objectives Though type 2 diabetes (T2D) has been known as a metabolic disease caused by multiple factors, the etiology remains insufficiently understood. Here, we aimed to figure out whether circulating immune cell profiles causally impact T2D liability. Methods We applied one genome-wide association study (GWAS) summary statistics of blood traits in 563,085 participants from the Blood Cell Consortium and another GWAS of flow cytometric profile of lymphocyte subsets comprising 3,757 Sardinians to identify genetically predicted blood immune cells. We also obtained GWAS summary statistics in 898,130 individuals from the DIAGRAM Consortium to evaluate genetically predicted T2D. We primarily used inverse variance weighted (IVW) and weighted median methods to perform Mendelian randomization analyses and sensitivity analyses to evaluate heterogeneity and pleiotropy. Results For circulating blood leukocyte and its subpopulations, the increase of genetically predicted circulating monocyte count was causally correlated with a higher risk of T2D [odds ratio (OR) = 1.06, 95% confidence interval (CI) = 1.02-1.10, p = 0.0048]. For lymphocyte subsets, CD8+ T cell and CD4+ CD8dim T cell count were identified with causal effect on T2D susceptibility (CD8+ T cell: OR = 1.09, 95% CI = 1.03-1.17, p = 0.0053; CD4+ CD8dim T cell: OR = 1.04, 95% CI = 1.01-1.08, p = 0.0070). No pleiotropy was determined. Conclusions These findings demonstrated that higher circulating monocyte and T-lymphocyte subpopulation predicted increased T2D susceptibility, which confirmed the immunity predisposition for T2D. Our results may have the potential to provide new therapeutic targets for the diagnosis and treatment of T2D.
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Affiliation(s)
| | | | | | | | | | - Hu Wang
- *Correspondence: Hu Wang, ; Liquan Hong,
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20
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Rafaqat S, Rafaqat S. Role of hematological parameters in pathogenesis of diabetes mellitus: A review of the literature. World J Hematol 2023; 10:25-41. [DOI: 10.5315/wjh.v10.i3.25] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Revised: 01/03/2023] [Accepted: 03/09/2023] [Indexed: 03/22/2023] Open
Affiliation(s)
- Sana Rafaqat
- Department of Biotechnology, Lahore College for Women University, Lahore 5400, Pakistan
| | - Saira Rafaqat
- Department of Zoology, Lahore College for Women University, Lahore 5400, Pakistan
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21
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Li R, Li L, Liu B, Luo D, Xiao S. Associations of levels of peripheral blood leukocyte and subtypes with type 2 diabetes: A longitudinal study of Chinese government employees. Front Endocrinol (Lausanne) 2023; 14:1094022. [PMID: 37033252 PMCID: PMC10080122 DOI: 10.3389/fendo.2023.1094022] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Accepted: 02/28/2023] [Indexed: 04/11/2023] Open
Abstract
OBJECTIVES Available evidence suggests that type 2 diabetes (T2D) may be associated with inflammation and that leukocytes are a topical clinical, biological indicator of inflammation. This study investigates the associations between peripheral blood leukocyte and subtypes levels with T2D. METHODS A total of 5,475 individuals were included in the baseline examination from January 2018 to April 2020, with incidence data updated to April 30, 2021, and follow-up to 5,362 individuals. T2D was defined according to the Chinese guidelines for preventing and treating type 2 diabetes. Physiological and biochemical indicators, including leukocyte and subtypes, were obtained from the physical examination results of the tertiary care hospitals relied on at the cohort sites. Covariates such as demographic characteristics and lifestyle were collected by questionnaire. Binary logistic regression and Cox proportional hazard models were used to explore the correlations. Receiver Operating Characteristic (ROC) curves and time-dependent ROC curves were used to estimate the predictive diagnosis of T2D across the subtype of leukocytes. RESULTS The mean follow-up time was 12 months, and the cumulative incidence density of T2D was 4.0/1000 person-years. Cross-sectional results at baseline showed that the levels of peripheral blood leukocyte and its subtypes were higher in the T2D group than in the non-T2D group. Total leukocyte count and subtypes levels were grouped by quintile. After adjusting for age, sex, family history of diabetes, lifestyle score, and triglyceride levels, all were compared with the lowest quintile of each group. Logistic regression model results showed that the corrected OR for those with the highest quintile level of leukocyte was 2.01 (95% CI: 1.02-3.98). The longitudinal analysis showed that the adjusted HR was 8.43 (95%CI: 1.06-66.92) for those with the highest quintile level of leukocytes at baseline after controlling for the effects of the above covariates. For those with the highest quintile level of neutrophils at baseline, the adjusted HR was 5.05 (95%CI: 1.01-25.29). The leukocyte and subtypes had predictive values for T2D. CONCLUSION Patients with T2D have a higher level of peripheral blood leukocyte and subtypes than those without the disease. Elevated leukocyte and neutrophil counts may link to a higher risk of T2D.
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22
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Hsieh CY, Lee WH, Liu YH, Lu CC, Chen SC, Su HM. Significant impact of body mass index on the relationship between increased white blood cell count and new-onset diabetes. Int J Med Sci 2023; 20:359-365. [PMID: 36860675 PMCID: PMC9969508 DOI: 10.7150/ijms.80207] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Accepted: 01/21/2023] [Indexed: 02/04/2023] Open
Abstract
An elevated white blood cell (WBC) count has been linked to incident diabetes. WBC count has been positively associated with body mass index (BMI), and elevated BMI has been reported to be a strong predictor of future diabetes. Hence, the association of increased WBC count with the subsequent development of diabetes may be mediated by increased BMI. This study was designed to address this issue. We selected subjects from the 104,451 participants enrolled from 2012 to 2018 in the Taiwan Biobank. We only included those with complete data at baseline and follow-up and those without diabetes at baseline. Finally, 24,514 participants were enrolled in this study. During an average 3.88 years of follow-up, 248 (1.0%) of the participants had new-onset diabetes. After adjusting for demographic, clinical, and biochemical parameters, increased WBC count was associated with new-onset diabetes in all of these participants (p ≤ 0.024). After further adjustment for BMI, the association became insignificant (p = 0.096). In addition, subgroup analysis of 23,430 subjects with a normal WBC count (range: 3500-10500/µl) demonstrated that increased WBC count was significantly associated with new-onset diabetes after adjusting for demographic, clinical, and biochemical parameters (p ≤ 0.016). After further adjustment for BMI, this association was attenuated (p = 0.050). In conclusion, our results showed that BMI had a significant impact on the relationship between increased WBC count and new-onset diabetes in all study participants, and BMI also attenuated the association in those with a normal WBC count. Hence, the association between increased WBC count and the future development of diabetes may be mediated by BMI.
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Affiliation(s)
- Chieh-Yu Hsieh
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wen-Hsien Lee
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yi-Hsueh Liu
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chun-Chi Lu
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Szu-Chia Chen
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ho-Ming Su
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
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23
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Yang T, Zhao B, Guan X, Pei D. White cell count trajectory and type 2 diabetes in health management population: a retrospective cohort study. BMJ Open 2022; 12:e057966. [PMID: 36127085 PMCID: PMC9490632 DOI: 10.1136/bmjopen-2021-057966] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
Abstract
OBJECTIVE The purposes of current research were to investigate the time-dependent dynamic alteration of white cell count (WCC) in health management populations and to analyse its association with the type 2 diabetes mellitus (T2DM). DESIGN Retrospective cohort research. SETTING Shengjing Hospital of China Medical University in China's Shenyang. PARTICIPANTS The number of non-diabetic subjects (median age: 40 years) totaled 7924 in the present work. PRIMARY AND SECONDARY OUTCOME MEASURES Assessment and grouping of changes in WCC between 2016 and 2019 were accomplished through group-based trajectory modelling. Newly diagnosed incidence associated with T2DM was estimated based on varying trajectories of WCC by the Kaplan-Meier method. Statistical differences in the incidences of new-onset T2DM among various WCC trajectory groups were examined through log-rank test. The influence of WCC trajectory alterations on the new-onset T2DM was evaluated with a multiparameter Cox (proportional-hazards) model. RESULTS During a 3-year (2016-2019) period, the T2DM development was noted in 3.14% (249) of the subjects. The trajectory model of WCC change was divided into four groups. For participants with low stability (trajectory 1), medium stability (trajectory 2), medium stability (trajectory 3) and high stability (trajectory 4), the incidence of T2DM was separately 2.2%, 2.62%, 4.82% and 7.4%, respectively. After adjusting for the underlying confounders, new-onset T2DM HRs (95% CIs) for trajectories 3 and 4 were separately 1.94 (1.32 to 2.83) and 3.08 (1.82 to 5.21) compared with the trajectory 1, implying that the T2DM risks were statistically significantly high. CONCLUSION The 3-year T2DM incidence was impacted independently by the WCC trajectory fluctuations. The grouping trajectory can reflect the dynamic change of WCC over time, which is more representative than the measured WCC at a single time point.
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Affiliation(s)
- Tengfei Yang
- Departments of Health Management, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Bo Zhao
- Department of Pulmonary and Critical Care Medicine, Shengjing Hospital of China Medical University, Shenyang, China
| | - Xuelai Guan
- Department of An-Ning-Zhuang Outpatient, Chinese PLA General Hospital, Beijing, China
| | - Dongmei Pei
- Departments of Health Management, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
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24
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Ebrahim H, Fiseha T, Ebrahim Y, Bisetegn H. Comparison of hematological parameters between type 2 diabetes mellitus patients and healthy controls at Dessie comprehensive specialized hospital, Northeast Ethiopia: Comparative cross-sectional study. PLoS One 2022; 17:e0272145. [PMID: 35895700 PMCID: PMC9328522 DOI: 10.1371/journal.pone.0272145] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Accepted: 07/13/2022] [Indexed: 11/23/2022] Open
Abstract
Background Diabetes mellitus (DM) is a chronic condition associated with raised levels of blood glucose due to the body cannot produce any or enough insulin hormone or cannot be effectively utilized the produced insulin by the body. Patients with poorly controlled diabetes show a significant alteration in various parameters including metabolic, cellular, immunological, and hematological disturbances that leads to vascular complications. Thus, the main aim of this study is to compare hematological parameters between type 2 diabetes mellitus (T2DM) patients and healthy controls. Methods A comparative cross-sectional study was conducted in Dessie comprehensive specialized hospital from January to June 2021. A total of 240 study participants consisting of 120 T2DM patients and 120 healthy controls were recruited using a systematic random sampling technique. Hematological parameters were determined using the DIRUI BF6500 automated hematology analyzer. Independent T-test was used to compare the mean of hematological parameters between T2DM patients and healthy controls. Pearson correlation test was used to determine the correlation between FBG, BMI, SBP, DBP, and hematological parameters in T2DM patients. Multivariate logistic regression was used to assess the association between socio-demographic and clinical variables with anemia. The result was expressed in mean and standard deviation and presented in texts and tables. P-value < 0.05 was considered to be statistically significant. Results The mean and standard deviation of monocyte count, basophil count, monocyte %, basophil %, RBC count, hematocrit, MCV, MCH, RDW-SD, MPV, PDW, PLC-R, and plateletcrit showed a significant difference between T2DM patients and healthy control group. Pearson correlation coefficient showed that the total WBC count, neutrophil count, monocyte count, basophil count, RDW-CV, PDW, MPV, PLC-R, and plateletcrit were statistically positively correlated with FBG whereas RBC count, Hgb, hematocrit, MCV, MCH, and RDW-SD were statistically negatively correlated with FBG in T2DM patients. Moreover, total WBC count, neutrophil count, monocyte count, basophil count, Hgb, and plateletcrit were statistically positively correlated with BMI while RBC count, Hgb, hematocrit, MCV, MCH, and RDW-SD were statistically negatively correlated with BMI in T2DM patients. On the other hand, DBP was significantly positively correlated with platelet count and RDW-CV whereas SBP also significantly positively correlated with total WBC count, neutrophil count, basophil count, and PDW. Besides, DBP and SBP showed statistically significant negative correlations with RBC count, Hgb level, and Hct value in T2DM patients. The overall prevalence of anemia was 25.8% in T2DM patients with a higher prevalence of anemia (16.7%) in female patients. Multivariate logistic regression revealed that being non-employee worker (AOR: 3.6, 95% CI, 1.4–46.0, P = 0.002), presence of neuropathy (AOR: 13.40, 95% CI, 6.83–26.28, P = 0.00), and duration of the disease ≥ 5 years (AOR = 3.2, 95% CI, 1.2–15.3, P = 0.03) have had statistically significant association with anemia inT2DM patients. Conclusions Patients with T2DM may have significant alterations in various hematological parameters. Hematological parameters should be regularly tested for early diagnosis and proper management of diabetes-related complications.
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Affiliation(s)
- Hussen Ebrahim
- Department of Medical Laboratory Sciences, College of Medicine and Health Sciences, Wollo University, Dessie, Ethiopia
- * E-mail:
| | - Temesgen Fiseha
- Department of Medical Laboratory Sciences, College of Medicine and Health Sciences, Wollo University, Dessie, Ethiopia
| | - Yesuf Ebrahim
- Department of Medical Laboratory Sciences, Dessie Health Science College, Dessie, Ethiopia
| | - Habtye Bisetegn
- Department of Medical Laboratory Sciences, College of Medicine and Health Sciences, Wollo University, Dessie, Ethiopia
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Culver MN, McMillan NK, Cross BL, Robinson AT, Montoye AH, Riemann BL, Flatt AA, Grosicki GJ. Sleep duration irregularity is associated with elevated blood pressure in young adults. Chronobiol Int 2022; 39:1320-1328. [PMID: 35844152 DOI: 10.1080/07420528.2022.2101373] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Sleep irregularity (i.e., highly variable sleep patterns) is an emerging risk factor for cardiometabolic disease. Though irregular sleep patterns are common among young adults, the cardiometabolic health (CMH) repercussions of sleep irregularity in this population are unclear. We examined associations between sleep duration and irregularity with measures of CMH in 44 (24 M/20 F, 23 ± 5y, BMI 26 ± 4 kg/m2, blood pressure (BP): 125/71 ± 14/9 mmHg) young adults. Participants wore actigraphy monitors for seven-days and sleep duration irregularity was operationalized as the standard deviation of nightly sleep duration (sleep SD). CMH variables of interest included brachial and aortic BP, arterial stiffness (cf-PWV), augmentation index (AIx75), and fasting blood glucose and lipids. Associations between sleep duration and sleep SD with CMH variables were assessed via correlations adjusted for sex and BMI. Sleep duration generally was not associated with CMH indices. However, sleep SD was associated with brachial systolic (r = 0.433, p = .027) and diastolic BP (r = 0.415, p = .035). Similarly, sleep duration SD was associated with aortic systolic BP (r = 0.447, p = .022). Our findings show that sleep irregularity, but not duration, is associated with higher brachial and central BP in young adults.Abbreviations: AIx75: augmentation index at a heart rate of 75 beats per minute; BP: blood pressure; CMH: cardiometabolic health; cf-PWV: carotid-femoral pulse wave velocity; DXA: dual x-ray absorptiometry; mg/dl: milligrams per deciliter; PWA: pulse wave analysis; PWV: pulse wave velocity; sleep duration SD: standard deviation of nightly sleep duration.
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Affiliation(s)
- Meral N Culver
- Biodynamics and Human Performance Center, Georgia Southern University (Armstrong Campus), Savannah, Georgia, USA.,Neurovascular Physiology Laboratory, School of Kinesiology, Auburn University, Auburn, Alabama, USA
| | - Nathan K McMillan
- Biodynamics and Human Performance Center, Georgia Southern University (Armstrong Campus), Savannah, Georgia, USA
| | - Brett L Cross
- Biodynamics and Human Performance Center, Georgia Southern University (Armstrong Campus), Savannah, Georgia, USA
| | - Austin T Robinson
- Neurovascular Physiology Laboratory, School of Kinesiology, Auburn University, Auburn, Alabama, USA
| | - Alexander Hk Montoye
- Department of Integrative Physiology and Health Science, Alma College, Alma, Michigan, USA
| | - Bryan L Riemann
- Biodynamics and Human Performance Center, Georgia Southern University (Armstrong Campus), Savannah, Georgia, USA
| | - Andrew A Flatt
- Biodynamics and Human Performance Center, Georgia Southern University (Armstrong Campus), Savannah, Georgia, USA
| | - Gregory J Grosicki
- Biodynamics and Human Performance Center, Georgia Southern University (Armstrong Campus), Savannah, Georgia, USA
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Tsai KZ, Su FY, Cheng WC, Lin YP, Lin GM. Association of hepatic and systemic inflammation with localized stage II/III periodontitis in young males: The CHIEF oral health study. J Clin Periodontol 2022; 49:458-466. [PMID: 34611936 DOI: 10.1111/jcpe.13556] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 09/13/2021] [Accepted: 09/19/2021] [Indexed: 12/22/2022]
Abstract
AIM To clarify the association between systemic and hepatic inflammation and localized periodontitis which has been reported to vary among races. MATERIALS AND METHODS The study included 1112 military males, aged 18-40 years, in Taiwan. Participants were classified as periodontally healthy/stage I (n = 796) or stage II/III periodontitis (n = 316), according to the 2017 world workshop criteria. Systemic and hepatic inflammation were defined by the highest tertiles of blood leukocyte counts (7.51 × 103 /μl) and alanine aminotransferase (30 U/L), respectively. Multiple logistic regression analysis with adjustments for age, metabolic syndrome, betel nut consumption and smoking was carried out. RESULTS There was a significant association between high systemic inflammation, irrespective of hepatic inflammation severity, and localized stage II/III periodontitis (odds ratio [OR], 1.62 [1.09-2.42] and 1.47 [1.00-2.15], respectively, in the presence of high or no hepatic inflammation. However, no significant association was found among participants with low systemic inflammation, irrespective of the severity of hepatic inflammation (OR, 1.31 [0.91-1.91]). CONCLUSIONS An association between hepatic inflammation and localized periodontitis in Taiwanese was observed only if systemic inflammation coexisted, possibly accounting for the reported differences in the association between Japanese and non-Asian populations in prior studies.
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Affiliation(s)
- Kun-Zhe Tsai
- Department of Medicine, Hualien Armed Forces General Hospital, Hualien, Taiwan
- Department of Dentistry, Tri-Service General Hospital, Taipei, Taiwan
- Graduate Institute of Dental Science, National Defense Medical Center, Taipei, Taiwan
- School of Dentistry, National Defense Medical Center, Taipei, Taiwan
| | - Fang-Ying Su
- Institute of Statistics, National Chiao Tung University, Hsinchu City, Taiwan
| | - Wan-Chien Cheng
- Department of Dentistry, Tri-Service General Hospital, Taipei, Taiwan
- Graduate Institute of Dental Science, National Defense Medical Center, Taipei, Taiwan
- School of Dentistry, National Defense Medical Center, Taipei, Taiwan
- Biotechnology R&D Center, National Taiwan University Hospital Hsinchu Branch, Hsinchu County, Taiwan
| | - Yen-Po Lin
- Department of Critical Care Medicine, Taipei Tzu-Chi Hospital, New Taipei, Taiwan
| | - Gen-Min Lin
- Department of Medicine, Hualien Armed Forces General Hospital, Hualien, Taiwan
- Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
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Yang T, Zhao B, Pei D. Relationship between the ApoB/ApoA-I ratio trajectory and risk of type 2 diabetes in China: a retrospective cohort study. Endocrine 2022; 76:36-43. [PMID: 35032012 DOI: 10.1007/s12020-021-02961-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Accepted: 12/08/2021] [Indexed: 11/27/2022]
Abstract
PURPOSE Little research has investigated the correlation of changes in long-term apolipoprotein B/apolipoprotein A-I (ApoB/ApoA-I) ratio with risk of new-onset type 2 diabetes (T2D) among ordinary people. Therefore, the research took long-term ApoB/ApoA-I ratio trajectories as independent variables for exploring their association with the risk of newly diagnosed T2D. METHODS Altogether 5362 non-diabetic participants with a median age of 49 were enrolled in the cohort study. Their ApoB/ApoA-I ratio trajectories from 2016 to 2019 were analyzed and grouped using group-based trajectory modeling. The Kaplan-Meier approach was employed for calculating the newly diagnosed T2D-related incidence with different ApoB/ApoA-I ratio trajectories. A log-rank test was conducted for testing the presence of statistical difference in new-onset T2D incidence among the different ApoB/ApoA-I ratio trajectory groups. A multivariate Cox proportional hazards regression model was adopted for analyzing how ApoB/ApoA-I ratio trajectory changes affected new-onset T2D. RESULTS From 2016 to 2019, 199 patients developed T2D (3% in 3 years). The incidence of T2D was 2.0%, 3.28%, 5.86%, and 6.92% for low, middle, upper, and high ApoB/ApoA-I ratio trajectories, respectively. Following adjustment of underlying confounding factors, in contrast to low ApoB/ApoA-I ratio trajectory, new-onset T2D risk ratios and hazard ratio (HR) (95% confidence intervals [CI]) for the middle lower ApoB/ApoA-I ratio trajectory, and upper middle and high ApoB/ApoA-I ratio trajectories were [HR (95% CI)] 1.35(0.88-2.08), 1.98(1.27-3.09) and 2.42(1.35-4.34), respectively, indicating high and statistically significant risks of T2D. CONCLUSION Variations of the ApoB/ApoA-I ratio trajectory exerted independent effects on the 3-year incidence of T2D. Long-term monitoring on the ApoB/ApoA-I ratio locus may help improve the identification on patients with T2D.
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Affiliation(s)
- Tengfei Yang
- Department of Health Management, Shengjing Hospital of China Medical University, Shenyang, China
| | - Bo Zhao
- Department of Pulmonary and Critical Care Medicine, Shengjing Hospital of China Medical University, Shenyang, China
| | - Dongmei Pei
- Department of Health Management, Shengjing Hospital of China Medical University, Shenyang, China.
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Chen JY, Chen YH, Lee YC, Tsou MT. The Association Between White Blood Cell Count and Insulin Resistance in Community-Dwelling Middle-Aged and Older Populations in Taiwan: A Community-Based Cross-Sectional Study. Front Med (Lausanne) 2022; 9:813222. [PMID: 35252251 PMCID: PMC8892182 DOI: 10.3389/fmed.2022.813222] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Accepted: 01/27/2022] [Indexed: 12/11/2022] Open
Abstract
BackgroundInsulin resistance (IR) is a major pathophysiological factor in the development and progression of diabetes mellitus (DM). DM is highly prevalent in Taiwan and has become one of the most common health problems in family medicine and primary care. We aimed to use white blood cell count (WBC), a common physiological parameter, to develop a simple clinical prediction rule for IR in the middle-aged and old Taiwanese population.MethodsIn this cross-sectional community-based study, the participants completed a questionnaire comprising personal and medical history data and underwent anthropometric measurements and blood sampling. IR was defined as a HOMA-IR index ≥2. Independent t-test, Mann–Whitney U test, chi-square test, Pearson's correlation test, multivariate binary logistic regression, and receiver operating characteristic curves were used to evaluate the association between the WBC count and IR.ResultsA total of 398 community-dwelling middle-aged and older persons (34.9% men) with a mean age of 64.43 ± 8.45 years were enrolled for the analysis. A significant association was identified between the WBC counts and IR, with a Pearson's correlation coefficient of 0.37 (p-value <0.001). Multivariate logistic regression revealed that WBC count (OR = 1.50; 95% CI = 1.25–1.81) was an independent risk factor for IR after adjusting for confounding variables. The area under the receiver operating characteristic curve for WBC count was 0.67, and the optimal threshold value was 5.65 1,000/uL.ConclusionA high WBC count is positively related to an increased risk of IR among middle-aged and older people in Taiwan.
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Affiliation(s)
- Jau-Yuan Chen
- Department of Family Medicine, Chang-Gung Memorial Hospital, Taoyuan City, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Yun-Hung Chen
- Department of Family Medicine, Chang-Gung Memorial Hospital, Taoyuan City, Taiwan
| | - Yu-Chien Lee
- Department of Family Medicine, Chang-Gung Memorial Hospital, Taoyuan City, Taiwan
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States
| | - Meng-Ting Tsou
- Department of Family Medicine, Mackay Memorial Hospital, Taipei City, Taiwan
- Department of Occupation Medicine, Mackay Memorial Hospital, Taipei City, Taiwan
- Department of MacKay Junior College of Medicine, Nursing, and Management, New Taipei City, Taiwan
- *Correspondence: Meng-Ting Tsou
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Night shift work characteristics are associated with several elevated metabolic risk factors and immune cell counts in a cross-sectional study. Sci Rep 2022; 12:2022. [PMID: 35132155 PMCID: PMC8821707 DOI: 10.1038/s41598-022-06122-w] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Accepted: 01/21/2022] [Indexed: 11/25/2022] Open
Abstract
Night shift work is associated with increased health risks. Here we examined the association of metabolic risk factors and immune cell counts, with both night shift work and particular characteristics thereof: frequency, duration and consecutive night shifts. We performed a cross-sectional study using data from 10,201 non-shift workers and 1062 night shift workers of the Lifelines Cohort study. Linear regression analyses, adjusted for demographic, lifestyle and occupational factors, were used to study associations of night shift work characteristics with metabolic risk factors and immune cell counts. Night shift workers had an increased BMI, waist circumference and immune cell counts compared to non-shift workers. This was especially seen in night shift workers who had a higher frequency of night shifts per month (≥ 5: BMI: B = 0.81 kg/m2 (95%-CI = 0.43–1.10); waist circumference: B = 1.58 cm (95%-Cl = 0.34–1.71; leukocytes: B = 0.19 × 109 cells/L (95%-CI = 0.04–0.34 × 109)) and worked more consecutive night shifts (> 3: BMI: B = 0.92 kg/m2 (95%-CI = 0.41–1.43); waist circumference: B = 1.85 cm (95%-Cl = 0.45–3.24); leukocytes: B = 0.32 × 109 cells/L (95%-CI = 0.09–0.55 × 109)). This association was less pronounced in long-term night shift workers (≥ 20 years). Our findings provide evidence for the association between night shift work characteristics and BMI, waist circumference and leukocytes (including, monocytes, lymphocytes, and basophil granulocytes).
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Haematological, renal, and hepatic function changes among Rayong oil spill clean-up workers: a longitudinal study. Int Arch Occup Environ Health 2022; 95:1481-1489. [DOI: 10.1007/s00420-022-01834-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2021] [Accepted: 01/07/2022] [Indexed: 11/05/2022]
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Lo T, Haridas RS, Rudge EJM, Chase RP, Heshmati K, Lucey EM, Weigl AM, Iyoha-Bello OJ, Ituah CO, Benjamin EJ, McNutt SW, Sathe L, Farnam L, Raby BA, Tavakkoli A, Croteau-Chonka DC, Sheu EG. Early Changes in Immune Cell Count, Metabolism, and Function Following Sleeve Gastrectomy: A Prospective Human Study. J Clin Endocrinol Metab 2022; 107:e619-e630. [PMID: 34514501 PMCID: PMC8764221 DOI: 10.1210/clinem/dgab673] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Indexed: 01/22/2023]
Abstract
OBJECTIVE To characterize longitudinal changes in blood biomarkers, leukocyte composition, and gene expression following laparoscopic sleeve gastrectomy (LSG). BACKGROUND LSG is an effective treatment for obesity, leading to sustainable weight loss and improvements in obesity-related comorbidities and inflammatory profiles. However, the effects of LSG on immune function and metabolism remain uncertain. METHODS Prospective data were collected from 23 enrolled human subjects from a single institution. Parameters of weight, comorbidities, and trends in blood biomarkers and leukocyte subsets were observed from preoperative baseline to 1 year postsurgery in 3-month follow-up intervals. RNA sequencing was performed on pairs of whole blood samples from the first 6 subjects of the study (baseline and 3 months postsurgery) to identify genome-wide gene expression changes associated with undergoing LSG. RESULTS LSG led to a significant decrease in mean total body weight loss (18.1%) at 3 months and among diabetic subjects a reduction in hemoglobin A1c. Improvements in clinical inflammatory and hormonal biomarkers were demonstrated as early as 3 months after LSG. A reduction in neutrophil-lymphocyte ratio was observed, driven by a reduction in absolute neutrophil counts. Gene set enrichment analyses of differential whole blood gene expression demonstrated that after 3 months LSG induced transcriptomic changes not only in inflammatory cytokine pathways but also in several key metabolic pathways related to energy metabolism. CONCLUSIONS LSG induces significant changes in the composition and metabolism of immune cells as early as 3 months postoperatively. Further evaluation is required of bariatric surgery's effects on immunometabolism and the consequences for host defense and metabolic disease.
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Affiliation(s)
- Tammy Lo
- Laboratory for Surgical and Metabolic Research, Department of Surgery, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
| | - Renuka S Haridas
- Laboratory for Surgical and Metabolic Research, Department of Surgery, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
| | - Eleanor J M Rudge
- Laboratory for Surgical and Metabolic Research, Department of Surgery, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
| | - Robert P Chase
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
| | - Keyvan Heshmati
- Laboratory for Surgical and Metabolic Research, Department of Surgery, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
| | - Elizabeth M Lucey
- Center for Clinical Investigation, Brigham and Women’s Hospital, Boston, MA, USA
| | - Alison M Weigl
- Center for Clinical Investigation, Brigham and Women’s Hospital, Boston, MA, USA
| | | | - Chelsea O Ituah
- Center for Clinical Investigation, Brigham and Women’s Hospital, Boston, MA, USA
| | - Emily J Benjamin
- Center for Clinical Investigation, Brigham and Women’s Hospital, Boston, MA, USA
| | - Seth W McNutt
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
| | - Leena Sathe
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
| | - Leanna Farnam
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
| | - Benjamin A Raby
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
- Division of Pulmonary Medicine, Boston Children’s Hospital and Harvard Medical School, Boston, MA, USA
| | - Ali Tavakkoli
- Laboratory for Surgical and Metabolic Research, Department of Surgery, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
| | - Damien C Croteau-Chonka
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
| | - Eric G Sheu
- Laboratory for Surgical and Metabolic Research, Department of Surgery, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
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Shapiro M, Arbel C, Zucker I, Balmor GR, Lutski M, Derazne E, Beer Z, Pinhas-Hamiel O, Mosenzon O, Tzur D, Afek A, Tirosh A, Cukierman-Yaffe T, Gerstein HC, Rosenberg V, Chodick G, Raz I, Twig G. Asthma in Youth and Early-onset Type 2 Diabetes: A Nationwide Study of 1.72 Million Israeli Adolescents. J Clin Endocrinol Metab 2021; 106:e5043-e5053. [PMID: 34291806 DOI: 10.1210/clinem/dgab542] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND The prevalence of both asthma and early-onset diabetes is on the rise; however, the association between them remains unclear. We examined a possible association of asthma at adolescence with type 2 diabetes in young adulthood. METHODS This is a nationwide, population-based study of 1 718 541 Israeli adolescents (57% males; mean age 17.3 years; range 16-19 years), examined before compulsory military service between 1992 and 2016, with data linked to the Israeli National Diabetes Registry. Asthma diagnosis and severity were determined by a board-certified pulmonologist and based on spirometry tests. RESULTS Type 2 diabetes developed in 58/9090 (0.64%), 507/97 059 (0.52%), 114/23 332 (0.49%), and 7095/1 589 060 (0.44%) persons with moderate-to-severe, mild, inactive, and no history of asthma, respectively, during a mean follow-up >13 years. The respective odds ratios (ORs) were 1.33 (95% CI, 1.02-1.74), 1.17 (1.06-1.28), and 1.09 (0.9-1.31), considering those without asthma history as the reference, in a model adjusted for birth year, sex, body mass index, and other sociodemographic variables. The association persisted when the analysis accounted for coexisting morbidities, and when persons without asthma, individually matched by age, sex, birth year, and body mass index were the reference. Both mild and moderate-to-severe asthma were associated with type 2 diabetes before age 35 years: ORs 1.18 (1.05-1.34) and 1.44 (1.05-2.00), respectively. The strength of the association was accentuated over time. The effect was unchanged when adjusted for oral and inhaled glucocorticoid use. CONCLUSION Adolescents with active asthma have higher risk to develop type 2 diabetes. This seems related to disease severity, independent of adolescent obesity status, apparent before age 35 years, and more pronounced in recent years.
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Affiliation(s)
- Michael Shapiro
- Department of Internal Medicine T, Tel Aviv Sourasky Medical Center, Tel Aviv 6492601, Israel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
- Israel Defense Forces Medical Corps, Ramat Gan 5510802, Israel
| | - Chen Arbel
- Israel Defense Forces Medical Corps, Ramat Gan 5510802, Israel
- Department of Military Medicine, Hebrew University of Jerusalem, Faculty of Medicine, Jerusalem 9112102, Israel
| | - Inbar Zucker
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
- The Israel Center for Disease Control, Ministry of Health, Ramat Gan 5262160, Israel
| | - Gingy Ronen Balmor
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
- Shamir (Assaf-Harofeh) Medical Center, Zerifin 70300, Israel
| | - Miri Lutski
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
- The Israel Center for Disease Control, Ministry of Health, Ramat Gan 5262160, Israel
| | - Estela Derazne
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
| | - Zivan Beer
- Israel Defense Forces Medical Corps, Ramat Gan 5510802, Israel
- Department of Military Medicine, Hebrew University of Jerusalem, Faculty of Medicine, Jerusalem 9112102, Israel
| | - Orit Pinhas-Hamiel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
- Department of Pediatric Endocrinology, Safra Children Hospital, Sheba Medical Center, Tel Hashomer, Ramat Gan 5266202, Israel
| | - Ofri Mosenzon
- The Diabetes Unit, Department of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem 91120, Israel
| | - Dorit Tzur
- Israel Defense Forces Medical Corps, Ramat Gan 5510802, Israel
- Department of Military Medicine, Hebrew University of Jerusalem, Faculty of Medicine, Jerusalem 9112102, Israel
| | - Arnon Afek
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
- Central Management, Sheba Medical Center, Tel Hashomer, Ramat Gan 5266202, Israel
| | - Amir Tirosh
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
- Institute of Endocrinology, Sheba Medical Center, Tel Hashomer, Ramat Gan 5266202, Israel
| | - Tali Cukierman-Yaffe
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
- Institute of Endocrinology, Sheba Medical Center, Tel Hashomer, Ramat Gan 5266202, Israel
| | - Hertzel C Gerstein
- Department of Medicine, McMaster University, Hamilton, Ontario L8S 4M1, Canada
| | - Vered Rosenberg
- Maccabitech Research Institute, Maccabi Healthcare Services, Tel Aviv 6801296, Israel
| | - Gabriel Chodick
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
- Maccabitech Research Institute, Maccabi Healthcare Services, Tel Aviv 6801296, Israel
| | - Itamar Raz
- The Diabetes Unit, Department of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem 91120, Israel
| | - Gilad Twig
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
- Israel Defense Forces Medical Corps, Ramat Gan 5510802, Israel
- Department of Military Medicine, Hebrew University of Jerusalem, Faculty of Medicine, Jerusalem 9112102, Israel
- Institute of Endocrinology, Sheba Medical Center, Tel Hashomer, Ramat Gan 5266202, Israel
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Ratter-Rieck JM, Maalmi H, Trenkamp S, Zaharia OP, Rathmann W, Schloot NC, Straßburger K, Szendroedi J, Herder C, Roden M. Leukocyte Counts and T-Cell Frequencies Differ Between Novel Subgroups of Diabetes and Are Associated With Metabolic Parameters and Biomarkers of Inflammation. Diabetes 2021; 70:2652-2662. [PMID: 34462259 DOI: 10.2337/db21-0364] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Accepted: 08/19/2021] [Indexed: 11/13/2022]
Abstract
Frequencies of circulating immune cells are altered in those with type 1 and type 2 diabetes compared with healthy individuals and are associated with insulin sensitivity, glycemic control, and lipid levels. This study aimed to determine whether specific immune cell types are associated with novel diabetes subgroups. We analyzed automated white blood cell counts (n = 669) and flow cytometric data (n = 201) of participants in the German Diabetes Study with recent-onset (<1 year) diabetes, who were allocated to five subgroups based on data-driven analysis of clinical variables. Leukocyte numbers were highest in severe insulin-resistant diabetes (SIRD) and mild obesity-related diabetes (MOD) and lowest in severe autoimmune diabetes (SAID). CD4+ T-cell frequencies were higher in SIRD versus SAID, MOD, and mild age-related diabetes (MARD), and frequencies of CCR4+ regulatory T cells were higher in SIRD versus SAID and MOD and in MARD versus SAID. Pairwise differences between subgroups were partially explained by differences in clustering variables. Frequencies of CD4+ T cells were positively associated with age, BMI, HOMA2 estimate of β-cell function (HOMA2-B), and HOMA2 estimate of insulin resistance (HOMA2-IR), and frequencies of CCR4+ regulatory T cells with age, HOMA2-B, and HOMA2-IR. In conclusion, different leukocyte profiles exist between novel diabetes subgroups and suggest distinct inflammatory processes in these diabetes subgroups.
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Affiliation(s)
- Jacqueline M Ratter-Rieck
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
- German Center for Diabetes Research, Partner Düsseldorf, München-Neuherberg, Germany
| | - Haifa Maalmi
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
- German Center for Diabetes Research, Partner Düsseldorf, München-Neuherberg, Germany
| | - Sandra Trenkamp
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
- German Center for Diabetes Research, Partner Düsseldorf, München-Neuherberg, Germany
| | - Oana-Patricia Zaharia
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
- German Center for Diabetes Research, Partner Düsseldorf, München-Neuherberg, Germany
- Department of Endocrinology and Diabetology, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
| | - Wolfgang Rathmann
- German Center for Diabetes Research, Partner Düsseldorf, München-Neuherberg, Germany
- Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
| | - Nanette C Schloot
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
| | - Klaus Straßburger
- German Center for Diabetes Research, Partner Düsseldorf, München-Neuherberg, Germany
- Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
| | - Julia Szendroedi
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
- German Center for Diabetes Research, Partner Düsseldorf, München-Neuherberg, Germany
- Department of Endocrinology and Diabetology, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
| | - Christian Herder
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
- German Center for Diabetes Research, Partner Düsseldorf, München-Neuherberg, Germany
- Department of Endocrinology and Diabetology, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
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Abstract
Mitochondrial DNA (mtDNA) is present in multiple copies in human cells. We evaluated cross-sectional associations of whole blood mtDNA copy number (CN) with several cardiometabolic disease traits in 408,361 participants of multiple ancestries in TOPMed and UK Biobank. Age showed a threshold association with mtDNA CN: among younger participants (<65 years of age), each additional 10 years of age was associated with 0.03 standard deviation (s.d.) higher level of mtDNA CN (P = 0.0014) versus a 0.14 s.d. lower level of mtDNA CN (P = 1.82 × 10-13) among older participants (≥65 years). At lower mtDNA CN levels, we found age-independent associations with increased odds of obesity (P = 5.6 × 10-238), hypertension (P = 2.8 × 10-50), diabetes (P = 3.6 × 10-7), and hyperlipidemia (P = 6.3 × 10-5). The observed decline in mtDNA CN after 65 years of age may be a key to understanding age-related diseases.
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Hoopes EK, D'Agata MN, Berube FR, Ranadive SM, Patterson F, Farquhar WB, Edwards DG, Witman MA. Consistency where it counts: Sleep regularity is associated with circulating white blood cell count in young adults. Brain Behav Immun Health 2021; 13:100233. [PMID: 34589748 PMCID: PMC8474608 DOI: 10.1016/j.bbih.2021.100233] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2020] [Revised: 01/20/2021] [Accepted: 02/24/2021] [Indexed: 02/09/2023] Open
Abstract
Background Sleep irregularity is predictive of poor health outcomes, and particularly those of cardiometabolic origins. The immune system is implicated in the pathogenesis of cardiometabolic diseases, however the relation between sleep regularity and immune cell profile is unclear. Methods and results Forty-two healthy young adults (20 ± 2 years) completed 14 days of 24-h wrist actigraphy followed by a morning blood sample to evaluate circulating white blood cells (WBC) and subtypes (neutrophils, lymphocytes, monocytes). Sleep regularity was operationalized as the standard deviation (SD) of nightly sleep duration and SD of sleep onset time. Every 60-min increase in sleep duration SD was associated with an estimated 2.7 ± 0.60 x103 cells/μL (p<0.001) increase in total WBC count, while every 60-min increase in sleep onset SD was associated with an estimated 2.4 ± 0.60 x103 cells/μL (p<0.001) increase in WBCs. Sleep duration SD was also associated with lymphocyte count (11.5 ± 3.8 cells/μL per 1-min increase, p<0.01), while sleep onset SD was associated with neutrophil (34.7 ± 9.8 cells/μL per 1-min increase, p<0.01) and monocyte counts (3.0 ± 0.9 cells/μL per 1-min increase, p<0.01). Sleep regularity metrics remained significantly associated with WBCs in a series of regressions which adjusted for sex, body mass index, resting blood pressure, mean sleep duration, physical activity, dietary sodium, and alcohol consumption. Conclusions Unfavorable associations between irregular sleep patterns and circulating immune cells are apparent in young adulthood. These findings contribute to the growing body of evidence suggesting that consistent sleep schedules are an important dimension of sleep and circadian health and may reduce excess chronic disease risk.
Young adults with irregular sleep patterns have higher total white blood cell count. Sleep irregularity is also associated with neutrophils, lymphocytes, and monocytes. Associations remain significant after adjusting for several key confounders. Consistent sleep patterns may assist in preventing inflammatory-mediated diseases.
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Affiliation(s)
- Elissa K Hoopes
- Department of Kinesiology and Applied Physiology, College of Health Sciences, University of Delaware, Newark, DE, USA
| | - Michele N D'Agata
- Department of Kinesiology and Applied Physiology, College of Health Sciences, University of Delaware, Newark, DE, USA
| | - Felicia R Berube
- Department of Kinesiology and Applied Physiology, College of Health Sciences, University of Delaware, Newark, DE, USA
| | - Sushant M Ranadive
- Department of Kinesiology, School of Public Health, University of Maryland, College Park, MD, USA
| | - Freda Patterson
- Department of Behavioral Health and Nutrition, College of Health Sciences, University of Delaware, Newark, DE, USA
| | - William B Farquhar
- Department of Kinesiology and Applied Physiology, College of Health Sciences, University of Delaware, Newark, DE, USA
| | - David G Edwards
- Department of Kinesiology and Applied Physiology, College of Health Sciences, University of Delaware, Newark, DE, USA
| | - Melissa A Witman
- Department of Kinesiology and Applied Physiology, College of Health Sciences, University of Delaware, Newark, DE, USA
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Kheradmand M, Ranjbaran H, Alizadeh-Navaei R, Yakhkeshi R, Moosazadeh M. Association between White Blood Cells Count and Diabetes Mellitus in Tabari Cohort Study: A Case-Control Study. Int J Prev Med 2021; 12:121. [PMID: 34760132 PMCID: PMC8551773 DOI: 10.4103/ijpvm.ijpvm_336_19] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2020] [Accepted: 09/20/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND White Blood Cells (WBC) can be a useful marker to predict diabetes. In this study, we aimed to investigate the association between WBC count with type 2 diabetes in a large-scaled population-based cohort study. METHODS In the present study we used a subset of data collected in enrolment phase of Tabari cohort study. Participants with fasting blood glucose ≥126 or those who report as having diabetes or taking glucose-lowering medications were selected as case group (1765 participants) and control group included participants who did not report as having diabetes (1765 participants) and they randomly selected from the baseline population. Hematology indices were measured for all participants using Celltac Alpha MEK-6510 K. Chi-squared and independent t-test were used to compare categorical and continuous variables, respectively. RESULTS The mean of WBC in diabetic patients and control group was 6.89 ± 1.67 and 6.37 ± 1.49 respectively (P ≤ 0.001). The odds of diabetes based on WBC count in crud model was 1.23 [CI 95% 1.181.28] and after adjustment for all possible confounding factor was 1.17 [CI 95% 1.111.23]. CONCLUSIONS Results of the present study showed a significant association between WBC count and diabetes. This association remained significant after adjustment for all possible confounders.
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Affiliation(s)
- Motahareh Kheradmand
- Health Sciences Research Center, Addiction Institute, Mazandaran University of Medical Sciences, Sari, Iran
| | - Hossein Ranjbaran
- Immunogenetic Research Center, Mazandaran University of Medical Sciences, Sari, Iran
| | - Reza Alizadeh-Navaei
- Gastrointestinal Cancer Research Center, Mazandaran University of Medical Sciences, Sari, Iran
| | - Reza Yakhkeshi
- Gastrointestinal Cancer Research Center, Non-communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran
| | - Mahmood Moosazadeh
- Health Sciences Research Center, Addiction Institute, Mazandaran University of Medical Sciences, Sari, Iran
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Hung SC, Yang CC, Liu CF, Kung CT, Lee WH, Ho CK, Chuang HY, Yu HS. The Association Pattern between Ambient Temperature Change and Leukocyte Counts. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph18136971. [PMID: 34209878 PMCID: PMC8296857 DOI: 10.3390/ijerph18136971] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 06/25/2021] [Accepted: 06/25/2021] [Indexed: 11/16/2022]
Abstract
Ambient temperature change is one of the risk factors of human health. Moreover, links between white blood cell counts (WBC) and diseases have been revealed in the literature. Still, we do not know of any association between ambient temperature change and WBC counts. The aim of our study is to investigate the relationship between ambient temperature change and WBC counts. We conducted this two-year population-based observational study in Kaohsiung city, recruiting voluntary community participants. Total WBC and differential counts, demographic data and health hazard habits were collected and matched with the meteorological data of air-quality monitoring stations with participants’ study dates and addresses. Generalized additive models (GAM) with penalized smoothing spline functions were performed for the trend of temperature changes and WBC counts. There were 9278 participants (45.3% male, aged 54.3 ± 5.9 years-old) included in analysis. Compared with stable weather conditions, the WBC counts were statistically higher when the one-day lag temperature changed over 2 degrees Celsius, regardless of whether colder or hotter. We found a V-shaped pattern association between WBC counts and temperature changes in GAM. The ambient temperature change was associated with WBC counts, and might imply an impact on systematic inflammation response.
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Affiliation(s)
- Shih-Chiang Hung
- Department of Public Health, College of Health Sciences, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (S.-C.H.); (C.-K.H.)
- Department of Emergency Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan; (C.-F.L.); (C.-T.K.); (W.-H.L.)
| | - Chen-Cheng Yang
- Department of Occupational Medicine and Family Medicine, Kaohsiung Municipal Siaogang Hospital and Kaohsiung Medical University, Kaohsiung 807, Taiwan;
| | - Chu-Feng Liu
- Department of Emergency Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan; (C.-F.L.); (C.-T.K.); (W.-H.L.)
| | - Chia-Te Kung
- Department of Emergency Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan; (C.-F.L.); (C.-T.K.); (W.-H.L.)
| | - Wen-Huei Lee
- Department of Emergency Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan; (C.-F.L.); (C.-T.K.); (W.-H.L.)
| | - Chi-Kung Ho
- Department of Public Health, College of Health Sciences, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (S.-C.H.); (C.-K.H.)
- Department of Occupational and Environmental Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
| | - Hung-Yi Chuang
- Department of Occupational and Environmental Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
- Department of Public Health and Environmental Medicine, Research Center for Environmental Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Correspondence: ; Tel.: +886-7312-1101
| | - Hsin-Su Yu
- College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan;
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Verdoia M, Nardin M, Rolla R, Negro F, Gioscia R, Afifeh AMS, Viglione F, Suryapranata H, Marcolongo M, De Luca G. Association of lower vitamin D levels with inflammation and leucocytes parameters in patients with and without diabetes mellitus undergoing coronary angiography. Eur J Clin Invest 2021; 51:e13439. [PMID: 33112413 DOI: 10.1111/eci.13439] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2020] [Revised: 10/18/2020] [Accepted: 10/19/2020] [Indexed: 12/15/2022]
Abstract
BACKGROUND Diabetes mellitus has been associated with a chronic low-grade inflammation and a higher risk of cardiovascular and infectious disease, that could be prevented by the effects of vitamin D. We aimed at evaluating the impact of vitamin D levels on the biomarkers of acute-phase response, inflammation and glucose metabolism in a large cohort of diabetic patients with cardiovascular disease. MATERIALS AND METHODS Consecutive patients undergoing coronary angiography were included. Diabetes mellitus was defined as previous diagnosis, specific treatment administration (oral drug or insulin), fasting glycaemia >6.99 mmol/L or HbA1c >48 mmol/L. Glucose parameters, white blood cells, Neutrophil-to-Lymphocyte Ratio (NLR), Monocyte-to-Lymphocyte Ratio (MLR), C-reactive protein (CRP) and vitamin D were measured at admission. Vitamin D levels were measured by chemiluminescence immunoassay kit LIAISON® Vitamin D assay (Diasorin Inc). RESULTS We included 1472 diabetic patients and 2499 non-diabetic patients that were divided according to vitamin D tertiles. Among diabetic patients, lower levels of vitamin D were associated with female gender (P = .02), obesity (P = .004), active smoking and acute presentation (P < .001) and with a more atherogenic metabolic profile. The levels of white blood cells, leucocytes subfamilies, and inflammatory parameters significantly correlated with vitamin D levels in both patients with and without diabetes (diabetic: P = .012 for WBC, P = .004 for NLR and P < .001 for MLR and C-reactive protein, non-diabetic: P < .001 for WBC; NLR, MLR and C-reactive protein, respectively). Among diabetic patients, results were confirmed at multivariate analysis with no significant interaction according to glycaemic control. CONCLUSION The present study demonstrates that, among patients with cardiovascular disease, vitamin D deficiency is associated with metabolic dysregulation and with an elevation of cellular and humoural inflammatory parameters, especially among diabetics, although not being dependent from glycaemic control.
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Affiliation(s)
- Monica Verdoia
- Division of Cardiology, Ospedale degli Infermi, ASL Biella, Biella, Italy.,Department of Translational Medicine, Eastern Piedmont University, Novara, Italy
| | - Matteo Nardin
- Department of Translational Medicine, Eastern Piedmont University, Novara, Italy
| | - Roberta Rolla
- Department of Translational Medicine, Eastern Piedmont University, Novara, Italy
| | - Federica Negro
- Department of Translational Medicine, Eastern Piedmont University, Novara, Italy
| | - Rocco Gioscia
- Department of Translational Medicine, Eastern Piedmont University, Novara, Italy
| | | | - Filippo Viglione
- Department of Translational Medicine, Eastern Piedmont University, Novara, Italy
| | | | - Marco Marcolongo
- Division of Cardiology, Ospedale degli Infermi, ASL Biella, Biella, Italy
| | - Giuseppe De Luca
- Department of Translational Medicine, Eastern Piedmont University, Novara, Italy
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Park JM, Lee HS, Park JY, Jung DH, Lee JW. White Blood Cell Count as a Predictor of Incident Type 2 Diabetes Mellitus Among Non-Obese Adults: A Longitudinal 10-Year Analysis of the Korean Genome and Epidemiology Study. J Inflamm Res 2021; 14:1235-1242. [PMID: 33833545 PMCID: PMC8021258 DOI: 10.2147/jir.s300026] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Accepted: 03/16/2021] [Indexed: 12/24/2022] Open
Abstract
Purpose Limited evidence is available on whether the white blood cell (WBC) count is a predictor of type 2 diabetes mellitus (T2DM) in non-obese individuals. This study aimed to determine whether WBC count could be used as an indicator for the prediction of incident T2DM among non-obese individuals using a large, community-based Korean cohort that was observed over 10 years. Patients and methods A total of 4211 non-obese adults without diabetes aged 40-69 years were selected from the Korean Genome and Epidemiology Study. The participants were divided into four groups according to WBC count quartiles. We prospectively assessed the hazard ratios (HRs) with 95% confidence intervals (CIs) for incident T2DM, based on the American Diabetes Association criteria, using multivariate Cox proportional hazards regression models over 10 years after the baseline survey. Results During the follow-up period, 592 (14.1%) participants had newly developed T2DM. The higher quartile of WBC count groups showed significantly higher cumulative T2DM incidence over 10 years after the baseline survey (log-rank test, P < 0.001). Compared with the HRs for individuals in the referent lowest quartile, the HR (95% CI) for incident T2DM in individuals in the highest quartile was 1.55 (1.10-2.18) after adjusting for confounding variables. Conclusion A higher WBC count predicts future incident T2DM among community-dwelling non-obese Korean adults. This study suggests that WBC count could facilitate the prediction of non-obese individuals susceptible to T2DM.
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Affiliation(s)
- Jae-Min Park
- Department of Family Medicine, Yonsei University College of Medicine, Gangnam Severance Hospital, Seoul, Republic of Korea.,Department of Medicine, Graduate School of Medicine, Yonsei University, Seoul, Republic of Korea
| | - Hye Sun Lee
- Biostatistics Collaboration Unit, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Ju-Young Park
- Department of Statistics and Data Science, Yonsei University, Seoul, Republic of Korea
| | - Dong-Hyuk Jung
- Department of Family Medicine, Yonsei University College of Medicine, Yongin Severance Hospital, Gyeonggi-do, Republic of Korea
| | - Ji-Won Lee
- Department of Family Medicine, Yonsei University College of Medicine, Gangnam Severance Hospital, Seoul, Republic of Korea
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Tian X, Li Y, Liu J, Lin Q, Yang Q, Tu J, Wang J, Li J, Ning X. Epidemiology of Isolated Impaired Glucose Tolerance Among Adults Aged Above 50 Years in Rural China. Diabetes Metab Syndr Obes 2021; 14:4067-4078. [PMID: 34557009 PMCID: PMC8453426 DOI: 10.2147/dmso.s330470] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Accepted: 09/04/2021] [Indexed: 11/26/2022] Open
Abstract
INTRODUCTION Isolated impaired glucose tolerance (i-IGT) is a subtype of prediabetes in which an individual demonstrates elevated 2-h post-glucose load glucose levels but normal fasting plasma glucose levels. However, few studies have explored the prevalence and risk factors of i-IGT among adults in rural China. Thus, we aimed to explore the prevalence and risk factors of i-IGT among adults ≥50 years old in a low-income, rural population in China. MATERIALS AND METHODS Individuals aged ≥50 years with normal fasting plasma glucose levels were included in the final analysis. Fasting and 2-h venous blood samples were collected to assess the selected parameter measurements. RESULTS A total of 2175 individuals were included in this study. The i-IGT prevalence was 22.9% and significantly higher among females than among males (P<0.05). Older age [odds ratio (OR), 1.606; 95% confidence interval (CI), 1.101-2.342; P=0.014), hypertension (OR, 1.554; 95% CI, 1.152-2.019; P=0.004), and central obesity (OR, 1.395; 95% CI, 1.099-1.771; P=0.006) were associated with i-IGT. Moreover, white blood cell (OR, 1.089; 95% CI, 1.009-1.175; P=0.029), high-sensitivity C-reactive protein (OR, 1.049; 95% CI, 1.020-1.078; P=0.001), serum uric acid (OR, 1.0003; 95% CI, 1.001-1.004; P=0.001), triglyceride (OR, 1.540; 95% CI, 1.105-2.147; P=0.011), and alanine aminotransferase (OR, 1.012; 95% CI, 1.004-1.021; P=0.004) levels were also linked to i-IGT in the analyzed population. CONCLUSION Health promotion education and a standardized approach to managing body weight, BP, and lipid and uric acid levels would benefit this low-income population in rural China for reducing the risk of cardiovascular disease.
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Affiliation(s)
- Xiaobing Tian
- Department of Neurology, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China
| | - Yan Li
- Center of Clinical Epidemiology & Evidence-Based Medicine, The Jizhou People’s Hospital, Tianjin, People’s Republic of China
- Department of Anesthesiology, The Jizhou People’s Hospital, Tianjin, People’s Republic of China
| | - Jie Liu
- Department of Neurology, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China
- Center of Clinical Epidemiology & Evidence-Based Medicine, The Jizhou People’s Hospital, Tianjin, People’s Republic of China
- Laboratory of Epidemiology, Tianjin Neurological Institute, Tianjin, People’s Republic of China
- Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, People’s Republic of China
| | - Qiuxing Lin
- Department of Neurology, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China
- Center of Clinical Epidemiology & Evidence-Based Medicine, The Jizhou People’s Hospital, Tianjin, People’s Republic of China
- Laboratory of Epidemiology, Tianjin Neurological Institute, Tianjin, People’s Republic of China
- Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, People’s Republic of China
| | - Qiaoxia Yang
- Department of Cardiology, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China
| | - Jun Tu
- Department of Neurology, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China
- Center of Clinical Epidemiology & Evidence-Based Medicine, The Jizhou People’s Hospital, Tianjin, People’s Republic of China
- Laboratory of Epidemiology, Tianjin Neurological Institute, Tianjin, People’s Republic of China
- Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, People’s Republic of China
| | - Jinghua Wang
- Department of Neurology, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China
- Center of Clinical Epidemiology & Evidence-Based Medicine, The Jizhou People’s Hospital, Tianjin, People’s Republic of China
- Laboratory of Epidemiology, Tianjin Neurological Institute, Tianjin, People’s Republic of China
- Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, People’s Republic of China
| | - Jidong Li
- Center of Clinical Epidemiology & Evidence-Based Medicine, The Jizhou People’s Hospital, Tianjin, People’s Republic of China
- Department of Neurosurgery, The Jizhou People’s Hospital, Tianjin, People’s Republic of China
| | - Xianjia Ning
- Department of Neurology, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China
- Center of Clinical Epidemiology & Evidence-Based Medicine, The Jizhou People’s Hospital, Tianjin, People’s Republic of China
- Laboratory of Epidemiology, Tianjin Neurological Institute, Tianjin, People’s Republic of China
- Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, People’s Republic of China
- Correspondence: Xianjia Ning; Jidong Li Email ;
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Whole blood co-expression modules associate with metabolic traits and type 2 diabetes: an IMI-DIRECT study. Genome Med 2020; 12:109. [PMID: 33261667 PMCID: PMC7708171 DOI: 10.1186/s13073-020-00806-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Accepted: 11/11/2020] [Indexed: 01/04/2023] Open
Abstract
Background The rising prevalence of type 2 diabetes (T2D) poses a major global challenge. It remains unresolved to what extent transcriptomic signatures of metabolic dysregulation and T2D can be observed in easily accessible tissues such as blood. Additionally, large-scale human studies are required to further our understanding of the putative inflammatory component of insulin resistance and T2D. Here we used transcriptomics data from individuals with (n = 789) and without (n = 2127) T2D from the IMI-DIRECT cohorts to describe the co-expression structure of whole blood that mainly reflects processes and cell types of the immune system, and how it relates to metabolically relevant clinical traits and T2D. Methods Clusters of co-expressed genes were identified in the non-diabetic IMI-DIRECT cohort and evaluated with regard to stability, as well as preservation and rewiring in the cohort of individuals with T2D. We performed functional and immune cell signature enrichment analyses, and a genome-wide association study to describe the genetic regulation of the modules. Phenotypic and trans-omics associations of the transcriptomic modules were investigated across both IMI-DIRECT cohorts. Results We identified 55 whole blood co-expression modules, some of which clustered in larger super-modules. We identified a large number of associations between these transcriptomic modules and measures of insulin action and glucose tolerance. Some of the metabolically linked modules reflect neutrophil-lymphocyte ratio in blood while others are independent of white blood cell estimates, including a module of genes encoding neutrophil granule proteins with antibacterial properties for which the strongest associations with clinical traits and T2D status were observed. Through the integration of genetic and multi-omics data, we provide a holistic view of the regulation and molecular context of whole blood transcriptomic modules. We furthermore identified an overlap between genetic signals for T2D and co-expression modules involved in type II interferon signaling. Conclusions Our results offer a large-scale map of whole blood transcriptomic modules in the context of metabolic disease and point to novel biological candidates for future studies related to T2D.
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Moghbeli M, Khedmatgozar H, Yadegari M, Avan A, Ferns GA, Ghayour Mobarhan M. Cytokines and the immune response in obesity-related disorders. Adv Clin Chem 2020; 101:135-168. [PMID: 33706888 DOI: 10.1016/bs.acc.2020.06.004] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The increasing prevalence of obesity and the associated morbidity and mortality are important public health problems globally. There is an important relationship between an unhealthy lifestyle and increased serum inflammatory cytokines. Adipocytes secrete several pro-inflammatory cytokines involved in the recruitment and activation of macrophages resulting in chronic low-grade inflammation. Increased cytokines in obese individual are related to the progression of several disorders including cardiovascular disease, hypertension, and insulin resistance. In present review we have summarized the crucial roles of cytokines and their inflammatory functions in obesity-related immune disorders.
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Affiliation(s)
- Meysam Moghbeli
- Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hamed Khedmatgozar
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mehran Yadegari
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amir Avan
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Student Research Committee and Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Science, Mashhad, Iran
| | - Gordon A Ferns
- Division of Medical Education, Brighton and Sussex Medical School, Brighton, United Kingdom
| | - Majid Ghayour Mobarhan
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
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Hu W, Zhang P, Su Q, Li D, Hang Y, Ye X, Guan P, Dong J, Lu Y. Peripheral leukocyte counts vary with lipid levels, age and sex in subjects from the healthy population. Atherosclerosis 2020; 308:15-21. [PMID: 32795745 DOI: 10.1016/j.atherosclerosis.2020.07.009] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2020] [Revised: 06/22/2020] [Accepted: 07/15/2020] [Indexed: 01/21/2023]
Abstract
BACKGROUND AND AIMS Disorders in blood lipid metabolism and leukocyte-mediated inflammation are considered the main mechanisms of the pathogenesis of atherosclerosis. This study aims to show whether and how peripheral leukocyte counts are associated with serum lipid levels. METHODS This is a cross-sectional study of 175,079 subjects from the healthy population. RESULTS Age and sex are two key factors dictating the relationship between peripheral leukocyte counts and serum lipid levels. The log-transformed level of triglycerides (LnTG) was positively associated with all leukocyte counts in males except monocyte count in younger subjects. LnTG was positively associated with total leukocyte count in females regardless of age, and it was positively associated with lymphocyte and monocyte counts and neutrophil count only in elderly and young women, respectively. Total cholesterol levels were positively associated with total leukocyte, neutrophil and lymphocyte counts only in young males and with lymphocyte counts only in elderly women. LDL-C was negatively associated with monocyte count in males regardless of age; by contrast, it was positively associated with total leukocyte and lymphocyte counts in females regardless of age range and neutrophil and LnEosinophil counts only in young women. HDL-C was negatively associated with total leukocyte, lymphocyte and monocyte counts in both young men and young women; was negatively associated with monocyte count in elderly men and women; and was negatively associated with LnEosinophil count only in older men. CONCLUSIONS Peripheral leukocyte counts are extensively associated with serum lipid levels, with patterns differing by sex, age, lipid and leukocyte subset.
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Affiliation(s)
- Wei Hu
- Department of Cardiology, Minhang Hospital, Fudan University, 170 Xinsong Road, Minhang District, Shanghai, 201199, PR China.
| | - Peng Zhang
- Department of Cardiology, Minhang Hospital, Fudan University, 170 Xinsong Road, Minhang District, Shanghai, 201199, PR China
| | - Qian Su
- Department of Cardiology, Minhang Hospital, Fudan University, 170 Xinsong Road, Minhang District, Shanghai, 201199, PR China
| | - Dandan Li
- Department of Cardiology, Minhang Hospital, Fudan University, 170 Xinsong Road, Minhang District, Shanghai, 201199, PR China
| | - Yanwen Hang
- Department of Cardiology, Minhang Hospital, Fudan University, 170 Xinsong Road, Minhang District, Shanghai, 201199, PR China
| | - Xiaomiao Ye
- Department of Cardiology, Minhang Hospital, Fudan University, 170 Xinsong Road, Minhang District, Shanghai, 201199, PR China
| | - Ping Guan
- Department of Cardiology, Minhang Hospital, Fudan University, 170 Xinsong Road, Minhang District, Shanghai, 201199, PR China
| | - Jian Dong
- Department of Cardiology, Minhang Hospital, Fudan University, 170 Xinsong Road, Minhang District, Shanghai, 201199, PR China
| | - Yi Lu
- Department of Cardiology, Minhang Hospital, Fudan University, 170 Xinsong Road, Minhang District, Shanghai, 201199, PR China
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Prediabetes Is Independently Associated with Subclinical Carotid Atherosclerosis: An Observational Study in a Non-Urban Mediterranean Population. J Clin Med 2020; 9:jcm9072139. [PMID: 32645918 PMCID: PMC7408832 DOI: 10.3390/jcm9072139] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2020] [Revised: 06/29/2020] [Accepted: 07/06/2020] [Indexed: 12/14/2022] Open
Abstract
This was a prospective, observational study to compare the burden of subclinical atherosclerosis as measured by carotid ultrasonography in a cohort of subjects with prediabetes vs. subjects with normal glucose tolerance (NGT) from a non-urban Mediterranean population. Atherosclerosis was assessed through carotid intima-media thickness (c-IMT), the presence/absence of carotid plaques, and plaque number. Among 550 subjects included, 224 (40.7%) had prediabetes. The mean c-IMT and the prevalence of carotid plaque were significantly higher in the prediabetes group compared to the NGT group (0.72 vs. 0.67 mm, p < 0.001; and 37.9% vs. 19.6%; p < 0.001, respectively). Older age, male gender, and increased systolic blood pressure were positively correlated with c-IMT and were independent predictors of the presence of plaques. In contrast, prediabetes and low-density lipoprotein (LDL)-c were predictors of the presence of plaque (odds ratio [OR] = 1.64; 95% confidence interval [CI] = 1.05-2.57; p = 0.03 and OR = 1.01; 95% CI = 1.00-1.02; p = 0.006, respectively) together with tobacco exposure and the leukocyte count (OR = 1.77; 95% CI = 1.08-2.89; p = 0.023 and OR = 1.20; 95% CI = 1.05-1.38; p = 0.008, respectively). In a non-urban Mediterranean population, prediabetes was associated with established subclinical carotid atherosclerosis. These findings could have implications for the prevention and treatment of CV risk in these subjects before the first symptoms of cardiovascular disease appear.
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Yang XJ, Tian S, Ma QH, Sun HP, Xu Y, Pan CW. Leukocyte-related parameters in older adults with metabolic syndrome. Endocrine 2020; 68:312-319. [PMID: 32140984 DOI: 10.1007/s12020-020-02243-2] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2019] [Accepted: 02/24/2020] [Indexed: 12/11/2022]
Abstract
PURPOSE We aimed to examine the association between leukocyte-related parameters and the risk of metabolic syndrome (MetS) in community-dwelling older Chinese adults, with a special focus on assessing the diagnostic ability of leukocyte-related parameters in detecting MetS and the potential interaction effect of sex in the leukocyte-MetS relationship. METHODS Study sample was from the Weitang Geriatric Diseases Study, which included 4579 individuals aged 60 years or above. MetS was diagnosed based on the Adult Treatment Panel III criteria. Leukocyte-related parameters were assessed using an automated hematology analyzer. RESULTS The adjusted odds ratio (95% confidence interval (CI)) of MetS for the highest quartile of leukocyte-related parameters (leukocyte, lymphocyte, neutrophil, monocyte, eosinophil, and basophil), when compared with the lowest quartile were 2.87 (2.30, 3.59), 2.69 (2.15, 3.36), 2.09 (1.67, 2.62), 2.12 (1.71, 2.64), 1.62 (1.31, 2.00), and 1.36 (1.11, 1.65), respectively. Adding leukocyte, lymphocyte, monocyte, and neutrophil to a model containing conventional risk factors improved risk prediction for MetS. Furthermore, significant interactions between leukocyte, monocyte, neutrophil, and sex on MetS were observed (all P value for interaction <0.01). CONCLUSION The numbers of total leukocytes, lymphocyte, monocyte, neutrophil, and eosinophil counts were elevated in older adults with MetS, suggesting that leukocyte-related parameters may be meaningful biomarkers for MetS. Adding leukocyte-related parameters to the conventional models increased the ability of predicting MetS among older adults. These parameters may be useful biomarkers for further risk appraisal of MetS in older adults.
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Affiliation(s)
- Xue-Jiao Yang
- School of Public Health, Medical College of Soochow University, Suzhou, China
| | - Shun Tian
- School of Public Health, Medical College of Soochow University, Suzhou, China
| | - Qing-Hua Ma
- The 3rd People's Hospital of Xiangcheng District, Suzhou, China
| | - Hong-Peng Sun
- School of Public Health, Medical College of Soochow University, Suzhou, China
| | - Yong Xu
- School of Public Health, Medical College of Soochow University, Suzhou, China
| | - Chen-Wei Pan
- School of Public Health, Medical College of Soochow University, Suzhou, China.
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Duru KC, Mukhlynina EA, Moroz GA, Gette IF, Danilova IG, Kovaleva EG. Anti-diabetic effect of isoflavone rich kudzu root extract in experimentally induced diabetic rats. J Funct Foods 2020. [DOI: 10.1016/j.jff.2020.103922] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
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Lin SH, Loftfield E, Sampson JN, Zhou W, Yeager M, Freedman ND, Chanock SJ, Machiela MJ. Mosaic chromosome Y loss is associated with alterations in blood cell counts in UK Biobank men. Sci Rep 2020; 10:3655. [PMID: 32108144 PMCID: PMC7046668 DOI: 10.1038/s41598-020-59963-8] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2019] [Accepted: 02/04/2020] [Indexed: 12/31/2022] Open
Abstract
Mosaic loss of Y chromosome (mLOY) is the most frequently detected somatic copy number alteration in leukocytes of men. In this study, we investigate blood cell counts as a potential mechanism linking mLOY to disease risk in 206,353 UK males. Associations between mLOY, detected by genotyping arrays, and blood cell counts were assessed by multivariable linear models adjusted for relevant risk factors. Among the participants, mLOY was detected in 39,809 men. We observed associations between mLOY and reduced erythrocyte count (−0.009 [−0.014, −0.005] × 1012 cells/L, p = 2.75 × 10−5) and elevated thrombocyte count (5.523 [4.862, 6.183] × 109 cells/L, p = 2.32 × 10−60) and leukocyte count (0.218 [0.198, 0.239] × 109 cells/L, p = 9.22 × 10−95), particularly for neutrophil count (0.174 × [0.158, 0.190]109 cells/L, p = 1.24 × 10−99) and monocyte count (0.021 [0.018 to 0.024] × 109 cells/L, p = 6.93 × 10−57), but lymphocyte count was less consistent (0.016 [0.007, 0.025] × 109 cells/L, p = 8.52 × 10−4). Stratified analyses indicate these associations are independent of the effects of aging and smoking. Our findings provide population-based evidence for associations between mLOY and blood cell counts that should stimulate investigation of the underlying biological mechanisms linking mLOY to cancer and chronic disease risk.
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Affiliation(s)
- Shu-Hong Lin
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, 9609 Medical Center Drive MSC 9776, Bethesda, Maryland, 20892, USA
| | - Erikka Loftfield
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, 9609 Medical Center Drive MSC 9776, Bethesda, Maryland, 20892, USA
| | - Josh N Sampson
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, 9609 Medical Center Drive MSC 9776, Bethesda, Maryland, 20892, USA
| | - Weiyin Zhou
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, 9609 Medical Center Drive MSC 9776, Bethesda, Maryland, 20892, USA.,Cancer Genomics Research Laboratory, Frederick National Laboratory for Cancer Research, Frederick, Maryland, 8717 Grovemont Circle, Gaithersburg, MD, 20877, USA
| | - Meredith Yeager
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, 9609 Medical Center Drive MSC 9776, Bethesda, Maryland, 20892, USA.,Cancer Genomics Research Laboratory, Frederick National Laboratory for Cancer Research, Frederick, Maryland, 8717 Grovemont Circle, Gaithersburg, MD, 20877, USA
| | - Neal D Freedman
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, 9609 Medical Center Drive MSC 9776, Bethesda, Maryland, 20892, USA
| | - Stephen J Chanock
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, 9609 Medical Center Drive MSC 9776, Bethesda, Maryland, 20892, USA
| | - Mitchell J Machiela
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, 9609 Medical Center Drive MSC 9776, Bethesda, Maryland, 20892, USA.
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Zhang X, Liu J, Shao S, Yang Y, Qi D, Wang C, Lin Q, Liu Y, Tu J, Wang J, Ning X, Cui J. Sex Differences in the Prevalence of and Risk Factors for Abnormal Glucose Regulation in Adults Aged 50 Years or Older With Normal Fasting Plasma Glucose Levels. Front Endocrinol (Lausanne) 2020; 11:531796. [PMID: 33679598 PMCID: PMC7933576 DOI: 10.3389/fendo.2020.531796] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2020] [Accepted: 12/29/2020] [Indexed: 12/17/2022] Open
Abstract
AIMS Abnormal glucose regulation, which can present as diabetes and prediabetes, has become one of the most common chronic conditions. However, sex differences in the prevalence of and factors associated with abnormal glucose regulation remain unclear. Thus, we aimed to explore sex differences in the prevalence of and factors associated with abnormal glucose regulation in low-income adults in China aged ≥50 years with normal fasting plasma glucose levels. MATERIALS AND METHODS A total of 2,175 individuals aged ≥50 years with normal fasting plasma glucose levels were recruited into this study. After an overnight fast of at least 10 h, individuals underwent an oral glucose tolerance test. Fasting and 2-h plasma glucose levels were measured to determine the state of glucose regulation. RESULTS Women were more likely than men to have isolated-impaired glucose tolerance (i-IGT) overall (24.7% vs 20.8%; P= 0.034), among individuals aged <65 years (21.7% vs 15.9%; P= 0.012). Among men, independent risk factors for i-IGT were an age of ≥65 years, hypertension, and high serum uric acid (SUA) and triglyceride levels; independent risk factors for diabetes mellitus (DM) were an age of ≥75 years and alcohol consumption. Among women, independent risk factors for i-IGT were central obesity and high levels of high-sensitivity C-reactive protein and SUA; independent risk factors for DM were low education and an elevated white blood cell count. CONCLUSIONS Our findings suggest that conventional cardiovascular disease risk factors (i.e., age, hypertension, and dyslipidemia) associated with high risk of developing DM in men, but poor life style (i.e., obesity) and low education attainment in women. It is necessary for delay or stopping the development of DM among low-income adults in China to implement the personalized scheme of prevention DM between men and women, especially highlight control the risk factors in young and middle aged women.
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Affiliation(s)
- Xinxin Zhang
- Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China
| | - Jie Liu
- Department of Neurology, Tianjin Medical University General Hospital, Tianjin, China
- Laboratory of Epidemiology, Tianjin Neurological Institute, Tianjin, China
- Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neuro-repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, China
| | - Shuang Shao
- Department of Endocrinology and Metabolism, The Second Hospital of Tianjin Medical University, Tianjin, China
| | - Yuan Yang
- Department of Neurology, Tianjin Medical University General Hospital, Tianjin, China
| | - Dongwang Qi
- Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China
| | - Conglin Wang
- Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin, China
| | - Qiuxing Lin
- Department of Neurology, Tianjin Medical University General Hospital, Tianjin, China
- Laboratory of Epidemiology, Tianjin Neurological Institute, Tianjin, China
- Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neuro-repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, China
| | - Yue Liu
- Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China
| | - Jun Tu
- Department of Neurology, Tianjin Medical University General Hospital, Tianjin, China
- Laboratory of Epidemiology, Tianjin Neurological Institute, Tianjin, China
- Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neuro-repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, China
| | - Jinghua Wang
- Department of Neurology, Tianjin Medical University General Hospital, Tianjin, China
- Laboratory of Epidemiology, Tianjin Neurological Institute, Tianjin, China
- Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neuro-repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, China
- *Correspondence: Jingqiu Cui, ; Xianjia Ning, ; Jinghua Wang,
| | - Xianjia Ning
- Department of Neurology, Tianjin Medical University General Hospital, Tianjin, China
- Laboratory of Epidemiology, Tianjin Neurological Institute, Tianjin, China
- Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neuro-repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, China
- *Correspondence: Jingqiu Cui, ; Xianjia Ning, ; Jinghua Wang,
| | - Jingqiu Cui
- Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China
- *Correspondence: Jingqiu Cui, ; Xianjia Ning, ; Jinghua Wang,
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Laboratory Parameters of Hemostasis, Adhesion Molecules, and Inflammation in Type 2 Diabetes Mellitus: Correlation with Glycemic Control. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:ijerph17010300. [PMID: 31906326 PMCID: PMC6982208 DOI: 10.3390/ijerph17010300] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/24/2019] [Revised: 12/28/2019] [Accepted: 12/30/2019] [Indexed: 12/25/2022]
Abstract
Background: Type 2 diabetes mellitus (T2DM) is characterized by a prothrombotic state, predisposing to vascular complications. Some related markers, linking thrombophilia to hemostasis and inflammation, however, have been poorly explored in relation to patients’ glycemia. We therefore investigated the association of laboratory hemostatic parameters, circulating adhesion molecules (ADMs), white blood cell (WBC) count, and neutrophil/lymphocyte ratio (NLR) with T2DM and glycemic control. Research design: In this study, 82 subjects, grouped into T2DM patients (n = 41) and healthy individuals (n = 41) were enrolled. To evaluate glycemic control, the T2DM cohort was expanded to 133 patients and sub-classified according to glycated hemoglobin (HbA1c) <7% and ≥ 7% (n = 58 and n = 75, respectively). We assessed glycemia, HbA1c, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, plasminogen activator inhibitor-1 (PAI-1), platelet and leukocyte parameters, vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), and selectins (E-, P-, L-). Results: PT % activity, PAI-1, VCAM-1, WBC, and neutrophil counts were significantly higher in T2DM patients than in healthy subjects. Poor glycemic control (HbA1c ≥ 7%) was correlated with increased PT activity (p = 0.015), and higher levels of E-selectin (p = 0.009), P-selectin (p = 0.012), and NLR (p = 0.019). Conclusions: Both T2DM and poor glycemic control affect some parameters of hemostasis, inflammation, and adhesion molecules. Further studies are needed to establish their clinical utility as adjuvant markers for cardio-vascular risk in T2DM patients.
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Kashima S, Inoue K, Matsumoto M, Akimoto K. White Blood Cell Count and C-Reactive Protein Independently Predicted Incident Diabetes: Yuport Medical Checkup Center Study. Endocr Res 2019; 44:127-137. [PMID: 30895902 DOI: 10.1080/07435800.2019.1589494] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
Aim: White blood cell (WBC) count or C-reactive protein (CRP) level alone may not fully indicate the chronic inflammation causing type 2 diabetes. We examined both WBC count and CRP level, independently and in combination, as predictive markers for type 2 diabetes and also considered the influence of obesity and other individual characteristics on the relationship. Materials and Methods: In total, 9,706 participants were enrolled with WBC < 10*109/L and CRP < 10 mg/L using data from the Yuport Medical Checkup Center Study. The cumulative incidence of type 2 diabetes [defined either as known diabetes, fasting plasma glucose ≥ 7.0 mmol/L, or HbA1c ≥ 6.5% (47.5 mmol/mol)] was measured. Hazard ratios (HRs) were estimated using a Cox proportional hazards model. Results: During study period, 272 men (5.5%) and 113 women (2.4%) progressed to diabetes. The progression to diabetes was predicted by both increased baseline levels of WBC count [adjusted HR = 1.29 (95% CI: 1.04-1.60)] and CRP level [1.39 (1.10-1.74)], even after adjusting for possible confounders. The combined presence was more predictive of diabetes than either alone in a four-groups analysis [1.75 (1.28-2.40)]. In addition, the elevated HRs of either or both higher WBC and CRP levels were observed across four subgroups of body mass index (BMI), including low BMI, and people who had at least one occurrence of dyslipidemia. Conclusion: Increased WBC counts and CRP levels were predictive for type 2 diabetes and the combination augmented the risk of diabetes, regardless of whether the BMI was high or low.
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Affiliation(s)
- Saori Kashima
- Department of Public Health and Health Policy, Graduate School of Biomedical and Health Sciences, Hiroshima University , Minami-ku, Hiroshima Japan
| | - Kazuo Inoue
- Department of Community Medicine, Chiba Medical Center, Teikyo University School of Medicine , Ichihara, Chiba , Japan
| | - Masatoshi Matsumoto
- Department of Community Based Medical System, Graduate School of Biomedical and Health Sciences, Hiroshima University , Minami-ku, Hiroshima , Japan
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