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Ball BK, Hyun Park J, Proctor EA, Brubaker DK. Cross-disease modeling of peripheral blood identifies biomarkers of type 2 diabetes predictive of Alzheimer's disease. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.12.11.627991. [PMID: 39713369 PMCID: PMC11661382 DOI: 10.1101/2024.12.11.627991] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2024]
Abstract
Type 2 diabetes (T2D) is a significant risk factor for Alzheimer's disease (AD). Despite multiple studies reporting this connection, the mechanism by which T2D exacerbates AD is poorly understood. It is challenging to design studies that address co-occurring and comorbid diseases, limiting the number of existing evidence bases. To address this challenge, we expanded the applications of a computational framework called Translatable Components Regression (TransComp-R), initially designed for cross-species translation modeling, to perform cross-disease modeling to identify biological programs of T2D that may exacerbate AD pathology. Using TransComp-R, we combined peripheral blood-derived T2D and AD human transcriptomic data to identify T2D principal components predictive of AD status. Our model revealed genes enriched for biological pathways associated with inflammation, metabolism, and signaling pathways from T2D principal components predictive of AD. The same T2D PC predictive of AD outcomes unveiled sex-based differences across the AD datasets. We performed a gene expression correlational analysis to identify therapeutic hypotheses tailored to the T2D-AD axis. We identified six T2D and two dementia medications that induced gene expression profiles associated with a non-T2D or non-AD state. Finally, we assessed our blood-based T2DxAD biomarker signature in post-mortem human AD and control brain gene expression data from the hippocampus, entorhinal cortex, superior frontal gyrus, and postcentral gyrus. Using partial least squares discriminant analysis, we identified a subset of genes from our cross-disease blood-based biomarker panel that significantly separated AD and control brain samples. Our methodological advance in cross-disease modeling identified biological programs in T2D that may predict the future onset of AD in this population. This, paired with our therapeutic gene expression correlational analysis, also revealed alogliptin, a T2D medication that may help prevent the onset of AD in T2D patients.
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Affiliation(s)
- Brendan K. Ball
- Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA
| | - Jee Hyun Park
- Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA
| | - Elizabeth A. Proctor
- Department of Neurosurgery, Penn State College of Medicine, Hershey, PA, USA
- Department of Pharmacology, Penn State College of Medicine, Hershey, PA, USA
- Department of Biomedical Engineering, Penn State University, State College, PA, USA
- Center for Neural Engineering, Penn State University, State College, PA, USA
- Department of Engineering Science & Mechanics, Penn State University, State College, PA, USA
| | - Douglas K. Brubaker
- Center for Global Health & Diseases, Department of Pathology, School of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, USA
- Blood Heart Lung Immunology Research Center, University Hospitals, Cleveland, OH, USA
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Podgórski R, Galiniak S, Mazur A, Domin A, Podgórska D. Serum levels of leptin, ghrelin putative peptide YY-3 in patients with fetal alcohol spectrum disorders. Sci Rep 2024; 14:14971. [PMID: 38951515 PMCID: PMC11217397 DOI: 10.1038/s41598-024-66052-7] [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: 02/21/2024] [Accepted: 06/26/2024] [Indexed: 07/03/2024] Open
Abstract
Fetal alcohol spectrum disorders (FASD) are a severe developmental condition resulting from exposure to alcohol during pregnancy. The aim of this study was to examine the concentrations of hormones involved in appetite regulation-ghrelin, leptin, and putative peptide YY-3 (PYY)-in the serum of individuals with FASD. Additionally, we investigated the relationship between these hormone levels and clinical indicators. We conducted an enzyme-linked immunosorbent assay on samples collected from 62 FASD patients and 23 individuals without the condition. Our results revealed a significant decrease in leptin levels among FASD patients compared to the control group (5.124 vs. 6.838 ng/mL, p = 0.002). We revealed no statistically significant differences in the levels of other hormones studied (ghrelin and PYY). Comparisons of hormone levels were also conducted in three subgroups: FAS, neurobehavioral disorders associated with prenatal alcohol exposure and FASD risk, as well as by sex. Assignment to FASD subgroups indicated changes only for leptin. Sex had no effect on the levels of hormones. Moreover, the levels of leptin showed a negative correlation with cortisol levels and a positive correlation with BMI and proopiomelanocortin. Alterations in appetite regulation can contribute to the improper development of children with FASD, which might be another factor that should be taken into consideration in the proper treatment of patients.
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Affiliation(s)
- Rafał Podgórski
- Department of Biochemistry, Institute of Medical Sciences, Medical College of Rzeszow University, Warzywna 1a, 35-310, Rzeszow, Poland.
| | - Sabina Galiniak
- Department of Biochemistry, Institute of Medical Sciences, Medical College of Rzeszow University, Warzywna 1a, 35-310, Rzeszow, Poland
| | - Artur Mazur
- Department of Pediatric, Institute of Medical Sciences, Medical College of Rzeszow University, 35-310, Rzeszow, Poland
| | - Agnieszka Domin
- Department of Pediatric, Institute of Medical Sciences, Medical College of Rzeszow University, 35-310, Rzeszow, Poland
| | - Dominika Podgórska
- Department of Rheumatology, Institute of Medical Sciences, Medical College of Rzeszow University, 35-310, Rzeszow, Poland
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Franco C, Canzoniero LMT. Zinc homeostasis and redox alterations in obesity. Front Endocrinol (Lausanne) 2024; 14:1273177. [PMID: 38260166 PMCID: PMC10800374 DOI: 10.3389/fendo.2023.1273177] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2023] [Accepted: 12/18/2023] [Indexed: 01/24/2024] Open
Abstract
Impairment of both cellular zinc and redox homeostasis is a feature of several chronic diseases, including obesity. A significant two-way interaction exists between redox metabolism and the relatively redox-inert zinc ion. Redox metabolism critically influences zinc homeostasis and controls its cellular availability for various cellular functions by regulating zinc exchange from/to zinc-binding proteins. Zinc can regulate redox metabolism and exhibits multiple pro-antioxidant properties. On the other hand, even minor disturbances in zinc status and zinc homeostasis affect systemic and cellular redox homeostasis. At the cellular level, zinc homeostasis is regulated by a multi-layered machinery consisting of zinc-binding molecules, zinc sensors, and two selective families of zinc transporters, the Zinc Transporter (ZnT) and Zrt, Irt-like protein (ZIP). In the present review, we summarize the current state of knowledge on the role of the mutual interaction between zinc and redox homeostasis in physiology and pathophysiology, pointing to the role of zinc in the alterations responsible for redox stress in obesity. Since zinc transporters primarily control zinc homeostasis, we describe how changes in the expression and activity of these zinc-regulating proteins are associated with obesity.
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Fuller KN, Bohne EM, Mey JT, Blackburn BK, Miranda VR, Varady KA, Danielson KK, Haus JM. Plasma undercarboxylated osteocalcin dynamics with glycemic stress reflects insulin sensitivity and beta-cell function in humans with and without T2DM. Metabol Open 2023; 20:100264. [PMID: 38115864 PMCID: PMC10728569 DOI: 10.1016/j.metop.2023.100264] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2023] [Revised: 11/15/2023] [Accepted: 11/22/2023] [Indexed: 12/21/2023] Open
Abstract
This study aimed to better understand the relationship between bone-related biomarkers and nutrient stress in the context of metabolic health. We investigated plasma osteocalcin (OC) during an oral glucose challenge and experimental hyperinsulinemia in Type 2 diabetes (T2DM) and lean healthy controls (LHC). Older individuals with obesity and T2DM (n = 9) and young LHCs (n = 9) underwent a 75g oral glucose tolerance test (OGTT) and a 40 mU/m2/min hyperinsulinemic-euglycemic clamp. Plasma undercarboxylated OC (ucOC) and total OC were measured at baseline, 60mins, and 120mins of the OGTT and clamp via ELISA. In addition, plasma alkaline phosphatase (ALP), leptin, adiponectin, Vitamin D and insulin were measured and indices of insulin sensitivity and β-cell function were derived. The T2DM group had lower (p<0.05) ucOC and ucOC:total OC ratio than LHC during both the OGTT and clamp. Further, baseline ucOC was positively correlated to indices of β-cell function and negatively correlated to indices of insulin resistance when both groups were combined (all p<0.05). Suppression of OC observed in T2DM may be related to glucose intolerance and insulin resistance. Similarly, our data suggest that the observed phenotypic differences between groups are likely a product of long-term glucose dysregulation rather than acute flux in glucose or insulin.
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Affiliation(s)
- Kelly N.Z. Fuller
- Department of Pediatrics, Section of Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Erin M. Bohne
- Department of Kinesiology and Nutrition, University of Illinois at Chicago, IL, USA
| | - Jacob T. Mey
- Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA
| | - Brian K. Blackburn
- Applied Health Sciences and Kinesiology, Humboldt State University, Arcata, CA, USA
| | | | - Krista A. Varady
- Department of Kinesiology and Nutrition, University of Illinois at Chicago, IL, USA
| | - Kirstie K. Danielson
- Division of Endocrinology and Metabolism, University of Illinois at Chicago, IL, USA
| | - Jacob M. Haus
- School of Kinesiology, University of Michigan, Ann Arbor, MI, USA
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Khoramipour K, Rezaei MH, Madadizadeh E, Hosseini MS, Soltani Z, Schierbauer J, Moser O. High Intensity Interval Training can Ameliorate Hypothalamic Appetite Regulation in Male Rats with Type 2 Diabetes: The Role of Leptin. Cell Mol Neurobiol 2023; 43:4295-4307. [PMID: 37828299 PMCID: PMC11407713 DOI: 10.1007/s10571-023-01421-w] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Accepted: 09/27/2023] [Indexed: 10/14/2023]
Abstract
Disruption of leptin (LEP) signaling in the hypothalamus caused by type 2 diabetes (T2D) can impair appetite regulation. The aim of this study was to investigate whether the improvement in appetite regulation induced by high-intensity interval training (HIIT) in rats with T2D can be mediated by LEP signaling. In this study, 20 male Wister rats were randomly assigned to one of four groups: CO (non-type 2 diabetes control), T2D (type 2 diabetes), EX (non-type 2 diabetes exercise), and T2D + EX (type 2 diabetes + exercise).To induce T2D, a combination of a high-fat diet for 2 months and a single dose of streptozotocin (35 mg/kg) was administered. Rats in the EX and T2D + EX groups performed 4-10 intervals of treadmill running at 80-100% of their maximum velocity (Vmax). Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), serum levels of insulin (INS) and LEP (LEPS) as well as hypothalamic expression of LEP receptors (LEP-R), Janus kinase 2 (JAK-2), signal transducer and activator of transcription 3 (STAT-3), neuropeptide Y (NPY), agouti-related protein (AGRP), pro-opiomelanocortin cocaine (POMC), amphetamine-related transcript (CART), suppressor of cytokine signaling (SOCS3), forkhead box protein O1 (FOXO1) were assessed. ANOVA and Tukey post hoc tests were used to compare the results between the groups. The levels of LEPS and INS, as well as the levels of LEP-R, JAK-2, STAT-3, POMC, and CART in the hypothalamus were found to be higher in the T2D + EX group compared to the T2D group. On the other hand, the levels of HOMA-IR, NPY, AGRP, SOCS3, and FOXO1 were lower in the T2D + EX group compared to the T2D group (P < 0.0001). The findings of this study suggest that HIIT may improve appetite regulation in rats with T2D, and LEP signaling may play a crucial role in this improvement. Graphical abstract (leptin signaling in the hypothalamus), Leptin (LEP), Leptin receptor (LEP-R), Janus kinase 2 (JAK2), Signal transducer and activator of transcription 3 (STAT3), expressing Neuropeptide Y (NPY), Agouti-related protein (AGRP), anorexigenic neurons (expressing pro-opiomelanocortin cocaine (POMC), Amphetamine-related transcript (CART), suppressor of cytokine signaling (SOCS3), forkhead box protein O1 (FOXO1).
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Affiliation(s)
- Kayvan Khoramipour
- Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
| | - Maryam Hossein Rezaei
- Department of Exercise Physiology, Faculty of Physical Education, Shahid Bahonar University, Kerman, Iran
| | - Elham Madadizadeh
- Department of Exercise Physiology, Faculty of Physical Education, Shahid Bahonar University, Kerman, Iran
| | - Mahdieh Sadat Hosseini
- Student Research Committee, Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Zahra Soltani
- Student Research Committee, Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Janis Schierbauer
- Exercise Physiology and Metabolism (Sports Medicine), BaySpo-Bayreuth Centre of Sports Science, University of Bayreuth, Bayreuth, Germany
| | - Othmar Moser
- Exercise Physiology and Metabolism (Sports Medicine), BaySpo-Bayreuth Centre of Sports Science, University of Bayreuth, Bayreuth, Germany
- Interdisciplinary Metabolic Medicine Trials Unit, Medical University of Graz, Graz, Austria
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Widyawati T, Syahputra RA, Syarifah S, Sumantri IB. Analysis of Antidiabetic Activity of Squalene via In Silico and In Vivo Assay. Molecules 2023; 28:molecules28093783. [PMID: 37175192 PMCID: PMC10180456 DOI: 10.3390/molecules28093783] [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: 03/15/2023] [Revised: 04/10/2023] [Accepted: 04/20/2023] [Indexed: 05/15/2023] Open
Abstract
Squalene has been tested widely in pharmacological activity including anticancer, antiinflammatory, antioxidant, and antidiabetic properties. This study aims to examine antidiabetic activity of squalene in silico and in vivo models. In the in silico model, the PASS server was used to evaluate squalene antidiabetic properties. Meanwhile, the in vivo model was conducted on a Type 2 Diabetes Mellitus (T2DM) with the rats separated into three groups. These include squalene (160 mg/kgbw), metformin (45 mg/kgbw), and diabetic control (DC) (aquades 10 mL/kgbw) administered once daily for 14 days. Fasting Blood Glucose Level (FBGL), Dipeptidyl Peptidase IV (DPPIV), leptin, and Superoxide Dismutase (SOD) activity were measured to analysis antidiabetic and antioxidant activity. Additionally, the pancreas was analysed through histopathology to examine the islet cell. The results showed that in silico analysis supported squalene antidiabetic potential. In vivo experiment demonstrated that squalene decreased FBGL levels to 134.40 ± 16.95 mg/dL. The highest DPPIV level was in diabetic control- (61.26 ± 15.06 ng/mL), while squalene group showed the lowest level (44.09 ± 5.29 ng/mL). Both metformin and squalene groups showed minor pancreatic rupture on histopathology. Leptin levels were significantly higher (p < 0.05) in diabetic control group (15.39 ± 1.77 ng/mL) than both squalene- (13.86 ± 0.47 ng/mL) and metformin-treated groups (9.22 ± 0.84 ng/mL). SOD activity were higher in both squalene- and metformin-treated group, particularly 22.42 ± 0.27 U/mL and 22.81 ± 0.08 U/mL than in diabetic control (21.88 ± 0.97 U/mL). In conclusion, in silico and in vivo experiments provide evidence of squalene antidiabetic and antioxidant properties.
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Affiliation(s)
- Tri Widyawati
- Department of Pharmacology and Therapeutic, Faculty of Medicine, Universitas Sumatera Utara, Medan 20155, Sumatera Utara, Indonesia
| | - Rony Abdi Syahputra
- Department of Pharmacology, Faculty of Pharmacy, Universitas Sumatera Utara, Medan 20155, Sumatera Utara, Indonesia
| | - Siti Syarifah
- Department of Pharmacology and Therapeutic, Faculty of Medicine, Universitas Sumatera Utara, Medan 20155, Sumatera Utara, Indonesia
| | - Imam Bagus Sumantri
- Department of Pharmaceutical Biology, Faculty of Pharmacy, Universitas Sumatera Utara, Medan 20155, Sumatera Utara, Indonesia
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Ruan GT, Xie HL, Hu CL, Liu CA, Zhang HY, Zhang Q, Wang ZW, Zhang X, Ge YZ, Lin SQ, Tang M, Song MM, Zhang XW, Liu XY, Zhang KP, Yang M, Yu KY, Wang KH, Hu W, Deng L, Cong MH, Shi HP. Comprehensive prognostic effects of systemic inflammation and Insulin resistance in women with breast cancer with different BMI: a prospective multicenter cohort. Sci Rep 2023; 13:4303. [PMID: 36922570 PMCID: PMC10017691 DOI: 10.1038/s41598-023-31450-w] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Accepted: 03/11/2023] [Indexed: 03/17/2023] Open
Abstract
To investigate the prognostic value of systemic inflammation and insulin resistance in women with breast cancer with different body mass index (BMI). This multicenter, prospective study included 514 women with breast cancer. Multivariate survival analysis showed that patients with high C-reactive protein (CRP), high CRP to albumin ratio (CAR), high lymphocyte to CRP ratio (LCR), high low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (LHR), and high triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-c) were significantly associated with worse prognosis. The mortality rate of patients with both high CAR and high LHR or both low LCR and high LHR were 3.91-fold or 3.89-fold higher than patients with both low CAR and low LHR or both high LCR and low LHR, respectively. Furthermore, the combination of LCR and LHR significantly predicted survival in patients within the high BMI group. The CRP, CAR, LCR, LHR, and TG/HDL-c were associated with poor survival in women with breast cancer. The combination of CAR and LHR or LCR and LHR could better predict the prognostic outcomes of women with breast cancer, while the combination of LCR and LHR could better predict the prognosis of those patients with overweight or obese patients.
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Affiliation(s)
- Guo-Tian Ruan
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China
- National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China
- Key Laboratory of Cancer FSMP for State Market Regulation, 10 Tie Yi Road, Beijing, 100038, China
| | - Hai-Lun Xie
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China
- National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China
- Key Laboratory of Cancer FSMP for State Market Regulation, 10 Tie Yi Road, Beijing, 100038, China
| | - Chun-Lei Hu
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China
- National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China
- Key Laboratory of Cancer FSMP for State Market Regulation, 10 Tie Yi Road, Beijing, 100038, China
| | - Chen-An Liu
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China
- National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China
- Key Laboratory of Cancer FSMP for State Market Regulation, 10 Tie Yi Road, Beijing, 100038, China
| | - He-Yang Zhang
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China
- National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China
- Key Laboratory of Cancer FSMP for State Market Regulation, 10 Tie Yi Road, Beijing, 100038, China
| | - Qi Zhang
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China
- National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China
- Key Laboratory of Cancer FSMP for State Market Regulation, 10 Tie Yi Road, Beijing, 100038, China
| | - Zi-Wen Wang
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China
- National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China
- Key Laboratory of Cancer FSMP for State Market Regulation, 10 Tie Yi Road, Beijing, 100038, China
| | - Xi Zhang
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China
- National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China
- Key Laboratory of Cancer FSMP for State Market Regulation, 10 Tie Yi Road, Beijing, 100038, China
| | - Yi-Zhong Ge
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China
- National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China
- Key Laboratory of Cancer FSMP for State Market Regulation, 10 Tie Yi Road, Beijing, 100038, China
| | - Shi-Qi Lin
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China
- National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China
- Key Laboratory of Cancer FSMP for State Market Regulation, 10 Tie Yi Road, Beijing, 100038, China
| | - Meng Tang
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China
- National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China
- Key Laboratory of Cancer FSMP for State Market Regulation, 10 Tie Yi Road, Beijing, 100038, China
| | - Meng-Meng Song
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China
- National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China
- Key Laboratory of Cancer FSMP for State Market Regulation, 10 Tie Yi Road, Beijing, 100038, China
| | - Xiao-Wei Zhang
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China
- National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China
- Key Laboratory of Cancer FSMP for State Market Regulation, 10 Tie Yi Road, Beijing, 100038, China
| | - Xiao-Yue Liu
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China
- National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China
- Key Laboratory of Cancer FSMP for State Market Regulation, 10 Tie Yi Road, Beijing, 100038, China
| | - Kang-Ping Zhang
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China
- National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China
- Key Laboratory of Cancer FSMP for State Market Regulation, 10 Tie Yi Road, Beijing, 100038, China
| | - Ming Yang
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China
- National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China
- Key Laboratory of Cancer FSMP for State Market Regulation, 10 Tie Yi Road, Beijing, 100038, China
| | - Kai-Ying Yu
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China
- National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China
- Key Laboratory of Cancer FSMP for State Market Regulation, 10 Tie Yi Road, Beijing, 100038, China
| | - Kun-Hua Wang
- Yunnan University, Kunming, 650091, China
- General Surgery Clinical Medical Center of Yunnan Province, Kunming, 650032, China
| | - Wen Hu
- Clinical Nutrition Department, Sichuan University West China Hospital, Chengdu, 610041, Sichuan, China
| | - Li Deng
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China.
- National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China.
- Key Laboratory of Cancer FSMP for State Market Regulation, 10 Tie Yi Road, Beijing, 100038, China.
| | - Ming-Hua Cong
- Comprehensive Oncology Department, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100038, China.
| | - Han-Ping Shi
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China.
- National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China.
- Key Laboratory of Cancer FSMP for State Market Regulation, 10 Tie Yi Road, Beijing, 100038, China.
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Chiu A, Sharma D, Zhao F. Tissue Engineering-Based Strategies for Diabetic Foot Ulcer Management. Adv Wound Care (New Rochelle) 2023; 12:145-167. [PMID: 34939837 PMCID: PMC9810358 DOI: 10.1089/wound.2021.0081] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Accepted: 10/26/2021] [Indexed: 01/13/2023] Open
Abstract
Significance: Diabetic foot ulcers (DFU) are a mounting problem with the increasingly frail population. Injuries that would otherwise heal are kept open by risk factors such as diabetes, obesity, and age-related conditions, which interferes with the natural wound healing processes. Recent Advances: This review summarizes recent advancements in the field of tissue engineering for the treatment of DFUs. FDA-approved approaches, including signaling-based therapies, stem cell therapies, and skin substitutes are summarized and cutting-edge experimental technologies that have the potential to manage chronic wounds, such as skin printing, skin organogenesis, skin self-assembly, and prevascularization, are discussed. Critical Issues: The standard of care for chronic wounds involves wound debridement, wound dressings, and resolving the underlying cause such as lowering the glycemic index and reducing wound pressure. Current DFU treatments are limited by low wound closure rates and poor regrown skin quality. New adjuvant therapies that facilitate wound closure in place of or in conjunction with standard care are critically needed. Future Directions: Tissue engineering strategies are limited by the plasticity of adult human cells. In addition to traditional techniques, genetic modification, although currently an emerging technology, has the potential to unlock human regeneration and can be incorporated in future therapeutics.
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Affiliation(s)
- Alvis Chiu
- Department of Biomedical Engineering, Texas A&M University, College Station, Texas, USA
| | - Dhavan Sharma
- Department of Biomedical Engineering, Texas A&M University, College Station, Texas, USA
| | - Feng Zhao
- Department of Biomedical Engineering, Texas A&M University, College Station, Texas, USA
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9
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Naaman SC, Shen S, Zeytinoglu M, Iyengar NM. Obesity and Breast Cancer Risk: The Oncogenic Implications of Metabolic Dysregulation. J Clin Endocrinol Metab 2022; 107:2154-2166. [PMID: 35453151 PMCID: PMC9282365 DOI: 10.1210/clinem/dgac241] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Indexed: 12/18/2022]
Abstract
CONTEXT Breast cancer is increasing in prevalence in parallel with rising rates of obesity worldwide. Obesity is recognized as a leading modifiable risk factor for the development of breast cancer; however, this association varies considerably by clinicopathologic features, and the underlying mechanisms are complex. EVIDENCE ACQUISITION Pubmed literature search using combinations of "obesity," "breast cancer risk," "diet," "exercise," "weight gain," "weight loss," "adipose tissue inflammation," "crown-like structure," "immune markers," "metformin," "gliflozins," "SGLT-2i," "GLP1-RA," and related terms. EVIDENCE SYNTHESIS Elevated body mass index and weight gain are associated with increased risk of postmenopausal, hormone receptor-positive breast cancer. Emerging evidence suggests that adverse measures of body composition in individuals of any weight can also confer increased breast cancer risk. Mechanistically, various factors including altered adipokine balance, dysfunctional adipose tissue, dysregulated insulin signaling, and chronic inflammation contribute to tumorigenesis. Weight loss and more specifically fat mass loss through lifestyle and pharmacologic interventions improve serum metabolic and inflammatory markers, sex hormone levels, and measures of breast density, suggesting a link to decreased breast cancer risk. CONCLUSION Incorporating markers of metabolic health and body composition measures with body mass index can capture breast cancer risk more comprehensively. Further studies of interventions targeting body fat levels are needed to curb the growing prevalence of obesity-related cancer.
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Affiliation(s)
| | - Sherry Shen
- Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | | | - Neil M Iyengar
- Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Weill Cornell Medical Center, New York, NY, USA
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10
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Trim WV, Walhin JP, Koumanov F, Bouloumié A, Lindsay MA, Travers RL, Turner JE, Thompson D. The Impact of Long-term Physical Inactivity on Adipose Tissue Immunometabolism. J Clin Endocrinol Metab 2022; 107:177-191. [PMID: 34480570 PMCID: PMC8684473 DOI: 10.1210/clinem/dgab647] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Indexed: 01/02/2023]
Abstract
CONTEXT Adipose tissue and physical inactivity both influence metabolic health and systemic inflammation, but how adipose tissue responds to chronic physical inactivity is unknown. OBJECTIVE This work aimed to characterize the impact of chronic physical inactivity on adipose tissue in healthy, young males. METHODS We collected subcutaneous adipose tissue from 20 healthy, young men before and after 60 days of complete bed rest with energy intake reduced to maintain energy balance and fat mass. We used RNA sequencing, flow cytometry, ex vivo tissue culture, and targeted protein analyses to examine adipose tissue phenotype. RESULTS Our results indicate that the adipose tissue transcriptome, stromal cellular compartment, and insulin signaling protein abundance are largely unaffected by bed rest when fat mass is kept stable. However, there was an increase in the circulating concentration of several adipokines, including plasma leptin, which was associated with inactivity-induced increases in plasma insulin and absent from adipose tissue cultured ex vivo under standardized culture conditions. CONCLUSION Physical inactivity-induced disturbances to adipokine concentrations such as leptin, without changes to fat mass, could have profound metabolic implications outside a clinical facility when energy intake is not tightly controlled.
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Affiliation(s)
- William V Trim
- Centre for Nutrition, Exercise and Metabolism (CNEM), Department for Health, University of Bath, Bath, UK
| | - Jean-Philippe Walhin
- Centre for Nutrition, Exercise and Metabolism (CNEM), Department for Health, University of Bath, Bath, UK
| | - Francoise Koumanov
- Centre for Nutrition, Exercise and Metabolism (CNEM), Department for Health, University of Bath, Bath, UK
| | | | - Mark A Lindsay
- Department of Pharmacy and Pharmacology, University of Bath, Bath, UK
| | - Rebecca L Travers
- Centre for Nutrition, Exercise and Metabolism (CNEM), Department for Health, University of Bath, Bath, UK
| | - James E Turner
- Centre for Nutrition, Exercise and Metabolism (CNEM), Department for Health, University of Bath, Bath, UK
| | - Dylan Thompson
- Centre for Nutrition, Exercise and Metabolism (CNEM), Department for Health, University of Bath, Bath, UK
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11
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Kim TJ, Lee H. Benefits of Helicobacter pylori Eradication on Extragastric Diseases. THE KOREAN JOURNAL OF HELICOBACTER AND UPPER GASTROINTESTINAL RESEARCH 2021. [DOI: 10.7704/kjhugr.2021.0041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Helicobacter pylori (H. pylori) eradication can reduce the risk of gastric diseases such as gastritis, gastric ulcer, and gastric adenocarcinoma. Since H. pylori was discovered more than 30 years ago, many studies have reported associations between H. pylori infection and extragastric diseases such as immune thrombocytopenia and iron-deficiency anemia. Thus, recent guidelines recommended H. pylori eradication in patients with those diseases. In contrast, although the role of H. pylori eradication in other extragastric diseases remains controversial, there is growing evidence of its benefit on them, especially cardiovascular (ischemic heart disease and stroke), metabolic (dyslipidemia, diabetes mellitus, and non-alcoholic fatty liver disease), neurodegenerative (Parkinson’s disease and Alzheimer’s disease), autoimmune (Graves’ disease, Hashimoto’s thyroiditis, Raynaud’s syndrome, rosacea, and chronic urticaria), and other (cap polyposis, colorectal mucosa-associated lymphoid tissue lymphoma, periodontal disease, hyperemesis gravidarum, and osteoporosis) conditions. A recent prospective randomized study reported that H. pylori eradication improved insulin resistance and dyslipidemia. These findings were consistent with the results of a recent meta-analysis. Therefore, well-designed prospective interventional studies are needed to examine the effects of H. pylori eradication on various extragastric diseases.
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12
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Ashraf R, Khan MS, Bhat MH, Shabir I, Rashid S, Majid S. Leptins: association and clinical correlation in pre-diabetics. Int J Diabetes Dev Ctries 2021. [DOI: 10.1007/s13410-021-01017-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
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13
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Šimják P, Anderlová K, Cinkajzlová A, Pařízek A, Kršek M, Haluzík M. The possible role of endocrine dysfunction of adipose tissue in gestational diabetes mellitus. MINERVA ENDOCRINOL 2021; 45:228-242. [PMID: 33000620 DOI: 10.23736/s0391-1977.20.03192-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Gestational diabetes mellitus (GDM) is diabetes that is first diagnosed in the second or third trimester of pregnancy in patients who did not have a history of diabetes before pregnancy. Consequences of GDM include increased risk of macrosomia and birth complications in the infant and an increased risk of maternal type 2 diabetes mellitus (T2DM) after pregnancy. There is also a longer-term risk of obesity, T2DM, and cardiovascular diseases in the child. GDM is the result of impaired glucose tolerance due to pancreatic β-cell dysfunction on a background of insulin resistance that physiologically increases during pregnancy. The strongest clinical predictors of GDM are overweight and obesity. The fact that women with GDM are more likely to be overweight or obese suggests that adipose tissue dysfunction may be involved in the pathogenesis of GDM, similarly to T2DM. Adipose tissue is not only involved in energy storage but also functions as an active endocrine organ secreting adipokines (specific hormones and cytokines) with the ability to alter insulin sensitivity. Recent evidence points to a crucial role of numerous adipokines produced by fat in the development of GDM. The following text summarizes the current knowledge about a possible role of selected adipokines in the development of GDM.
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Affiliation(s)
- Patrik Šimják
- Department of Gynecology and Obstetrics, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic
| | - Kateřina Anderlová
- Department of Gynecology and Obstetrics, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.,Third Department of Medicine, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic
| | - Anna Cinkajzlová
- Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Antonín Pařízek
- Department of Gynecology and Obstetrics, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic
| | - Michal Kršek
- Third Department of Medicine, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic
| | - Martin Haluzík
- Diabetes Center, Institute for Clinical and Experimental Medicine, Prague, Czech Republic -
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14
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Hyder KM, Mohan J, Varma V, Ponnusankar S, Raja D. Impact of prediabetes education program on Knowledge, attitude and practice among prediabetic population of south India. Prev Med Rep 2021; 23:101395. [PMID: 34040932 PMCID: PMC8141460 DOI: 10.1016/j.pmedr.2021.101395] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Revised: 04/10/2021] [Accepted: 05/07/2021] [Indexed: 11/18/2022] Open
Abstract
A Prediabetes prevalence of 10.5% alarms the need for prediabetes management programs. KAP-PAQ was found to be an efficient tool to conduct KAP survey among prediabetes. Implementation of Prediabetes Education Program increased the self management skills among the prediabetes. Education plays a vital role not only in the management of diabetes but also for the effective prevention of diabetes and its complications. Prediabetes awareness and knowledge is grossly inadequate in India and massive prediabetic screening and management programs are urgently needed. This study was an initiative to conduct education program among the prediabetic subjects after assessment of their knowledge attitude and practice using a newly developed and validated prediabetes questionnaire. A total of 308 prediabetic participants were recruited through prediabetes screening camps conducted in the selected districts of Kerala and Tamilnadu. A newly developed and validated KAP-PAQ Questionnaire was used to analyze the Knowledge Attitude and Practice among the prediabetic population. The impact of Prediabetes Education Program was assessed by administration of questionnaire before and after PEP with an interval period of 30 days. Baseline assessment of knowledge among prediabetics shown that 90% had poor knowledge but after PEP program 43% had average knowledge and 44% could score good knowledge. Baseline assessment of attitude exhibited 30% with negative attitude but after counseling 68% shown positive attitude. Regarding practice assessment 35% had very poor and 52% shown poor practice but after PEP 71% shown good practice and 15% shown very good practice. Baseline KAP survey shows the need for health literacy among the newly diagnosed prediabetics. Prediabetes education program could bring significant improvement in knowledge attitude and practice and KAP-PAQ was found to be an efficient tool to conduct survey among the newly diagnosed prediabetics of south India.
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Affiliation(s)
- K. Mohsina Hyder
- Department of Pharmacy Practice, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty – 643 001, The Nilgiris, Tamil Nadu, India
| | - Jithin Mohan
- Department of General Medicine, Aster Wayanad Specialty Hospital, Meppadi, Wayanad, Kerala, India
| | - Visakh Varma
- Department of Podiatry, Aster Wayanad Specialty Hospital, Meppadi, Wayanad, Kerala, India
| | - S. Ponnusankar
- Department of Pharmacy Practice, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty – 643 001, The Nilgiris, Tamil Nadu, India
- Corresponding author.
| | - D. Raja
- Consultant, GITS Academy, Bengaluru, India
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15
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Adiga U, Banawalikar N, Mayur S, Bansal R, Ameera N, Rao S. Association of insulin resistance and leptin receptor gene polymorphism in type 2 diabetes mellitus. J Chin Med Assoc 2021; 84:383-388. [PMID: 33660621 DOI: 10.1097/jcma.0000000000000507] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
BACKGROUND Type 2 diabetes mellitus (T2DM) is a chronic disease that is characterized by impaired glucose metabolism and insulin resistance. The objectives of the study were to evaluate the pattern of leptin receptor gene polymorphism Gln223Arg in T2DM and to identify its association with the serum leptin and insulin levels as well as with insulin resistance in diabetes. METHODS In this cross-sectional study, genotyping of leptin receptor was done for Gln223Arg alleles by PCR-restriction fragment length polymorphism in 39 patients with type 2 diabetes. Serum leptin and insulin levels were assayed using enzyme linked sorbent assay in 39 cases and 45 nondiabetic controls. Insulin resistance was calculated by the homeostasis model assessment of insulin resistance (HOMA-IR) formula. Statistical analysis was performed with Graph pad Instat version 3. RESULTS Hardy-Weinberg Equilibrium for the leptin receptor (LEPR) gene variants showed that alleles were in equilibrium. Leptin levels were insignificantly low in patients with diabetes compared to those in controls. Women in the control group showed significantly higher leptin levels (p < 0.05) compared with men. There was a significant difference in the serum insulin levels and insulin resistance (HOMA-IR) among patients with different genotypes (p = 0.04 and p = 0.0378, respectively). CONCLUSION Leptin receptor gene polymorphism affected glucose metabolism by altering insulin resistance and pancreatic beta cells. Thus, single-nucleotide polymorphism of LEPR may affect the pathogenesis of T2DM.
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Affiliation(s)
- Usha Adiga
- Department of Biochemistry, KS Hegde Medical Academy, NITTE-Deemed to be University, Mangalore, Karnataka, India
| | - Nandit Banawalikar
- Central Research Laboratory, K S Hegde Medical Academy, NITTE-Deemed to be University, Mangalore, Karnataka, India
| | - Sriprajna Mayur
- Central Research Laboratory, K S Hegde Medical Academy, NITTE-Deemed to be University, Mangalore, Karnataka, India
| | - Radhika Bansal
- Central Research Laboratory, K S Hegde Medical Academy, NITTE-Deemed to be University, Mangalore, Karnataka, India
| | - Nafeesath Ameera
- Central Research Laboratory, K S Hegde Medical Academy, NITTE-Deemed to be University, Mangalore, Karnataka, India
| | - Sudhindra Rao
- Department of Medicine, KS Hegde Medical Academy, NITTE-Deemed to be University, Mangalore, Karnataka, India
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16
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Pearsey HM, Henson J, Sargeant JA, Davies MJ, Khunti K, Suzuki T, Bowden-Davies KA, Cuthbertson DJ, Yates TE. Zinc-alpha2-glycoprotein, dysglycaemia and insulin resistance: a systematic review and meta-analysis. Rev Endocr Metab Disord 2020; 21:569-575. [PMID: 32377863 PMCID: PMC7557496 DOI: 10.1007/s11154-020-09553-w] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
To systematically review the current literature investigating associations between zinc-alpha2-glycoprotein (ZAG) and dysglycaemia (including type 2 diabetes (T2DM), poly-cystic-ovary syndrome (PCOS), pre-diabetes or insulin resistance). This included relationships between ZAG and continuous measures of insulin and glucose. Additionally, we performed a meta-analysis to estimate the extent that ZAG differs between individuals with or without dysglycaemia; whilst examining the potential influence of adiposity. A systematic search was performed on four databases for studies on circulating ZAG concentrations in adult human populations, comparing healthy controls to individuals with dysglycaemia. Key characteristics, including the mean ZAG concentrations (mg∙L-1), and any correlational statistics between ZAG and continuous measures of glucose, glycated haemoglobin (HbA1c) or insulin were extracted. Meta-analyses were performed to compare metabolically healthy controls to cases, and on studies that compared controls and cases considered overweight or obese (body mass index (BMI) ≥25 kg.m2). 1575 papers were identified and 14 studies (16 cohorts) were considered eligible for inclusion. Circulating ZAG was lower in individuals with dysglycaemia compared to metabolically healthy controls (-4.14 [-8.17, -0.11] mg.L-1; I2 = 98.5%; p < 0.001). When using data from only studies with overweight or obese groups with or without dysglycaemia (three studies (four cohorts); pooled n = 332), the difference in circulating ZAG was no longer significant (-0.30 [-3.67, 3.07] mg. L-1; I2 = 28.0%; p = 0.225). These data suggest that ZAG may be implicated in dysglycaemia, although there was significant heterogeneity across different studies and the mediating effect of adiposity cannot be excluded. Therefore, more research is needed before robust conclusions can be drawn.
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Affiliation(s)
- Harriet M Pearsey
- Diabetes Research Centre, Leicester General Hospital, Gwendolen Road, Leicester, LE5 4PW, UK.
- NIHR Leicester Biomedical Research Centre, Leicester, UK.
- Department of Health Science, University of Leicester, Leicester, UK.
| | - Joseph Henson
- Diabetes Research Centre, Leicester General Hospital, Gwendolen Road, Leicester, LE5 4PW, UK
- NIHR Leicester Biomedical Research Centre, Leicester, UK
| | - Jack A Sargeant
- Diabetes Research Centre, Leicester General Hospital, Gwendolen Road, Leicester, LE5 4PW, UK
- NIHR Leicester Biomedical Research Centre, Leicester, UK
| | - Melanie J Davies
- Diabetes Research Centre, Leicester General Hospital, Gwendolen Road, Leicester, LE5 4PW, UK
- NIHR Leicester Biomedical Research Centre, Leicester, UK
| | - Kamlesh Khunti
- Diabetes Research Centre, Leicester General Hospital, Gwendolen Road, Leicester, LE5 4PW, UK
- NIHR ARC East Midlands, Leicester, UK
| | - Toru Suzuki
- NIHR Leicester Biomedical Research Centre, Leicester, UK
- Cardiovascular Sciences Unit, Leicester Glenfeild Hospital, Leicester, UK
| | | | - Daniel J Cuthbertson
- Clinical Sciences Centre, Aintree University Hospitals NHS Foundation Trust, Liverpool, UK
- Faculty of Health and Life Sciences, University of Liverpool, Liverpool, UK
| | - Thomas E Yates
- Diabetes Research Centre, Leicester General Hospital, Gwendolen Road, Leicester, LE5 4PW, UK
- NIHR Leicester Biomedical Research Centre, Leicester, UK
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17
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Development of an Immune-Related Risk Signature in Patients with Bladder Urothelial Carcinoma. BIOMED RESEARCH INTERNATIONAL 2020; 2020:5848493. [PMID: 32884943 PMCID: PMC7455840 DOI: 10.1155/2020/5848493] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 07/20/2020] [Accepted: 08/04/2020] [Indexed: 02/02/2023]
Abstract
With recent advances in immunooncology and tumor microenvironment, the treatment landscape of bladder urothelial carcinoma has been changing dramatically. We aim to construct an immune gene-related signature which can predict BLCA patients' overall survival. Transcriptomic data of BLCA patients was downloaded from The Cancer Genome Atlas database, and immune-related genes were downloaded from the Immunology Database and Analysis Portal database. Prognostic immune-related genes were identified. We then constructed and validated an immune gene-related signature. Tumor-related transcription factors were downloaded from the Cistrome database, and a network between them and prognostic immune-related genes was generated. Cox's proportional hazards model and the Kaplan–Meier survival analysis were performed to assess our signature's prognostic ability. Relationship between the signature and patients' clinicopathologic features was then explored to validate its clinical value. We further downloaded concentration of six types of immune cells from the Tumor Immune Estimation Resource database to explore immune-related potential mechanisms of the signature.
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18
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Hansson LK, Hansen RB, Pletscher-Frankild S, Berzins R, Hansen DH, Madsen D, Christensen SB, Christiansen MR, Boulund U, Wolf XA, Kjærulff SK, van de Bunt M, Tulin S, Jensen TS, Wernersson R, Jensen JN. Semantic text mining in early drug discovery for type 2 diabetes. PLoS One 2020; 15:e0233956. [PMID: 32542027 PMCID: PMC7295186 DOI: 10.1371/journal.pone.0233956] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2019] [Accepted: 05/15/2020] [Indexed: 11/18/2022] Open
Abstract
Background Surveying the scientific literature is an important part of early drug discovery; and with the ever-increasing amount of biomedical publications it is imperative to focus on the most interesting articles. Here we present a project that highlights new understanding (e.g. recently discovered modes of action) and identifies potential drug targets, via a novel, data-driven text mining approach to score type 2 diabetes (T2D) relevance. We focused on monitoring trends and jumps in T2D relevance to help us be timely informed of important breakthroughs. Methods We extracted over 7 million n-grams from PubMed abstracts and then clustered around 240,000 linked to T2D into almost 50,000 T2D relevant ‘semantic concepts’. To score papers, we weighted the concepts based on co-mentioning with core T2D proteins. A protein’s T2D relevance was determined by combining the scores of the papers mentioning it in the five preceding years. Each week all proteins were ranked according to their T2D relevance. Furthermore, the historical distribution of changes in rank from one week to the next was used to calculate the significance of a change in rank by T2D relevance for each protein. Results We show that T2D relevant papers, even those not mentioning T2D explicitly, were prioritised by relevant semantic concepts. Well known T2D proteins were therefore enriched among the top scoring proteins. Our ‘high jumpers’ identified important past developments in the apprehension of how certain key proteins relate to T2D, indicating that our method will make us aware of future breakthroughs. In summary, this project facilitated keeping up with current T2D research by repeatedly providing short lists of potential novel targets into our early drug discovery pipeline.
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Affiliation(s)
- Lena K. Hansson
- Novo Nordisk Research Centre Oxford, Novo Nordisk Ltd., Oxford, United Kingdom
| | | | | | | | | | | | | | | | | | | | | | | | | | | | - Rasmus Wernersson
- Intomics A/S, Kgs. Lyngby, Denmark
- DTU Health Tech, Technical University of Denmark, Kgs. Lyngby, Denmark
- * E-mail:
| | - Jan Nygaard Jensen
- Novo Nordisk Research Centre Oxford, Novo Nordisk Ltd., Oxford, United Kingdom
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19
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The Novel Perspectives of Adipokines on Brain Health. Int J Mol Sci 2019; 20:ijms20225638. [PMID: 31718027 PMCID: PMC6887733 DOI: 10.3390/ijms20225638] [Citation(s) in RCA: 65] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2019] [Revised: 11/05/2019] [Accepted: 11/06/2019] [Indexed: 12/13/2022] Open
Abstract
First seen as a fat-storage tissue, the adipose tissue is considered as a critical player in the endocrine system. Precisely, adipose tissue can produce an array of bioactive factors, including cytokines, lipids, and extracellular vesicles, which target various systemic organ systems to regulate metabolism, homeostasis, and immune response. The global effects of adipokines on metabolic events are well defined, but their impacts on brain function and pathology remain poorly defined. Receptors of adipokines are widely expressed in the brain. Mounting evidence has shown that leptin and adiponectin can cross the blood–brain barrier, while evidence for newly identified adipokines is limited. Significantly, adipocyte secretion is liable to nutritional and metabolic states, where defective circuitry, impaired neuroplasticity, and elevated neuroinflammation are symptomatic. Essentially, neurotrophic and anti-inflammatory properties of adipokines underlie their neuroprotective roles in neurodegenerative diseases. Besides, adipocyte-secreted lipids in the bloodstream can act endocrine on the distant organs. In this article, we have reviewed five adipokines (leptin, adiponectin, chemerin, apelin, visfatin) and two lipokines (palmitoleic acid and lysophosphatidic acid) on their roles involving in eating behavior, neurotrophic and neuroprotective factors in the brain. Understanding and regulating these adipokines can lead to novel therapeutic strategies to counteract metabolic associated eating disorders and neurodegenerative diseases, thus promote brain health.
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20
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Moura J, Madureira P, Leal EC, Fonseca AC, Carvalho E. Immune aging in diabetes and its implications in wound healing. Clin Immunol 2019; 200:43-54. [PMID: 30735729 PMCID: PMC7322932 DOI: 10.1016/j.clim.2019.02.002] [Citation(s) in RCA: 63] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2019] [Revised: 02/04/2019] [Accepted: 02/04/2019] [Indexed: 02/06/2023]
Abstract
Immune systems have evolved to recognize and eliminate pathogens and damaged cells. In humans, it is estimated to recognize 109 epitopes and natural selection ensures that clonally expanded cells replace unstimulated cells and overall immune cell numbers remain stationary. But, with age, it faces continuous repertoire restriction and concomitant accumulation of primed cells. Changes shaping the aging immune system have bitter consequences because, as inflammatory responses gain intensity and duration, tissue-damaging immunity and inflammatory disease arise. During inflammation, the glycolytic flux cannot cope with increasing ATP demands, limiting the immune response's extent. In diabetes, higher glucose availability stretches the glycolytic limit, dysregulating proteostasis and increasing T-cell expansion. Long-term hyperglycemia exerts an accumulating effect, leading to higher inflammatory cytokine levels and increased cytotoxic mediator secretion upon infection, a phenomenon known as diabetic chronic inflammation. Here we review the etiology of diabetic chronic inflammation and its consequences on wound healing.
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Affiliation(s)
- J Moura
- Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; INEB - Instituto Nacional de Engenharia Biomédica, University of Porto, Porto, Portugal; i3S - Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal.
| | - P Madureira
- i3S - Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal; IBMC - Instituto de Biologia Celular e Molecular, University of Porto, Porto, Portugal; Immunethep, Biocant Park, Cantanhede, Portugal
| | - E C Leal
- Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal
| | - A C Fonseca
- Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal
| | - E Carvalho
- Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; Instituto de Investigação Interdisciplinar, University of Coimbra, Coimbra, Portugal; Department of Geriatrics, University of Arkansas for Medical Sciences and Arkansas Children's Research Institute, Little Rock, AR, United States
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21
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Hosseininasab Nodoushan SA, Nabavi A. The Interaction of Helicobacter pylori Infection and Type 2 Diabetes Mellitus. Adv Biomed Res 2019; 8:15. [PMID: 30993085 PMCID: PMC6425747 DOI: 10.4103/abr.abr_37_18] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Helicobacter pylori is one of the most common human pathogens that can cause gastrointestinal (GI) disorders, including simple gastritis, gastric ulcer, and malignant gastritis. In some cases, such as immunodeficiency and underlying diseases, it can be problematic as opportunistic infections. Diabetes mellitus (type 2) (T2DM) is one of the H. pylori underlying diseases. Since GI problems are observed in diabetic patients, it is necessary to treat H. pylori infection. In this review, we aimed to evaluate the possible relationship between H. pylori and T2DM according to epidemiological surveys of 70 studies retrieved from databases, including Scopus, PubMed, and Google Scholar about the relationship between H. pylori and T2DM, and discuss the reported background mechanisms of this correlation. According to the results of our study, the different studies have shown that H. pylori is more prevalent in Type 2 diabetic patients than healthy individuals or nondiabetic patients. The reason is development of H. pylori infection-induced inflammation and production of inflammatory cytokines as well as different hormonal imbalance by this bacterium, which are associated with diabetes mellitus. On the other hand, by tracing anti-H. pylori antibodies in patients with diabetes mellitus and occurrence of symptoms such as digestive problems in >75% of these patients, it can be concluded that there is a relationship between this bacterium and T2DM. Considering the evidence, it is crucially important that the probability of infection with H. pylori is evaluated in patients with T2DM so that medical process of the patient is followed with higher cautious.
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Affiliation(s)
| | - Amin Nabavi
- Department of Biochemistry, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
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22
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Heiston EM, Malin SK. Impact of Exercise on Inflammatory Mediators of Metabolic and Vascular Insulin Resistance in Type 2 Diabetes. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2019; 1134:271-294. [PMID: 30919343 DOI: 10.1007/978-3-030-12668-1_15] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The development of obesity is cornerstone in the etiology of metabolic and vascular insulin resistance and consequently exacerbates glycemic control. Exercise is an efficacious first-line therapy for type 2 diabetes that improves insulin action through, in part, reducing hormone mediated inflammation. Together, improving the coordination of skeletal muscle metabolism with vascular delivery of glucose will be required for optimizing type 2 diabetes and cardiovascular disease treatment.
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Affiliation(s)
- Emily M Heiston
- Department of Kinesiology, University of Virginia, Charlottesville, VA, USA
| | - Steven K Malin
- Department of Kinesiology, University of Virginia, Charlottesville, VA, USA.
- Division of Endocrinology and Metabolism, University of Virginia, Charlottesville, VA, USA.
- Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA, USA.
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Exercise Increases Adiponectin and Reduces Leptin Levels in Prediabetic and Diabetic Individuals: Systematic Review and Meta-Analysis of Randomized Controlled Trials. Med Sci (Basel) 2018; 6:medsci6040097. [PMID: 30380802 PMCID: PMC6318757 DOI: 10.3390/medsci6040097] [Citation(s) in RCA: 52] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2018] [Revised: 10/23/2018] [Accepted: 10/25/2018] [Indexed: 11/17/2022] Open
Abstract
It is speculated that lifestyle interventions known to improve diabetic metabolic state may exert their effects via adipokines. The aim of this systematic review and meta-analysis was to evaluate the chronic effects of physical exercise on adiponectin and leptin levels in adult prediabetic and diabetic individuals. PubMed, Embase, Scopus, The Cochrane Library, clinicaltrials.gov, and WHO Clinical Trials Registry were searched for randomized controlled trials. Pooled effects of interventions were assessed as mean difference (MD) with random effects model. Sensitivity analysis was conducted to test data robustness and subgroup analysis for study heterogeneity. Twenty-two trials with 2996 individuals were included in the meta-analysis. Physical exercise increased levels of adiponectin (MD: 0.42 µg/mL; 95% confidence interval (CI), 0.23, 0.60, p < 0.00001, n = 19 trials) and reduced leptin levels (MD: −1.89 ng/mL; 95% CI, −2.64, −1.14, p < 0.00001, n = 14 trials). These results were robust and remained significant after sensitivity analysis. Study heterogeneity was generally high. As for physical exercise modalities, aerobic exercise, but not other modalities, increased adiponectin and reduced leptin levels. In conclusion, physical exercise and, specifically, aerobic exercise, leads to higher adiponectin and lower leptin levels in prediabetic and diabetic adults. However, cautious interpretation of current findings is warranted.
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Framnes SN, Arble DM. The Bidirectional Relationship Between Obstructive Sleep Apnea and Metabolic Disease. Front Endocrinol (Lausanne) 2018; 9:440. [PMID: 30127766 PMCID: PMC6087747 DOI: 10.3389/fendo.2018.00440] [Citation(s) in RCA: 56] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2018] [Accepted: 07/17/2018] [Indexed: 12/22/2022] Open
Abstract
Obstructive sleep apnea (OSA) is a common sleep disorder, effecting 17% of the total population and 40-70% of the obese population (1, 2). Multiple studies have identified OSA as a critical risk factor for the development of obesity, diabetes, and cardiovascular diseases (3-5). Moreover, emerging evidence indicates that metabolic disorders can exacerbate OSA, creating a bidirectional relationship between OSA and metabolic physiology. In this review, we explore the relationship between glycemic control, insulin, and leptin as both contributing factors and products of OSA. We conclude that while insulin and leptin action may contribute to the development of OSA, further research is required to determine the mechanistic actions and relative contributions independent of body weight. In addition to increasing our understanding of the etiology, further research into the physiological mechanisms underlying OSA can lead to the development of improved treatment options for individuals with OSA.
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Affiliation(s)
| | - Deanna M. Arble
- Department of Biological Sciences, Marquette University, Milwaukee, WI, United States
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25
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Oikonomou EK, Antoniades C. Immunometabolic Regulation of Vascular Redox State: The Role of Adipose Tissue. Antioxid Redox Signal 2018; 29:313-336. [PMID: 28657335 DOI: 10.1089/ars.2017.7017] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
SIGNIFICANCE Vascular oxidative stress plays a crucial role in atherogenesis and cardiovascular disease (CVD). Recent evidence suggests that vascular redox state is under the control of complex pathophysiological mechanisms, ranging from inflammation to obesity and insulin resistance (IR). Recent Advances: Adipose tissue (AT) is now recognized as a dynamic endocrine and paracrine organ that secretes several bioactive molecules, called adipokines. AT has recently been shown to regulate vascular redox state in both an endocrine and a paracrine manner through the secretion of adipokines, therefore providing a mechanistic link for the association between obesity, IR, inflammation, and vascular disease. Importantly, AT behaves as a sensor of cardiovascular oxidative stress, modifying its secretory profile in response to cardiovascular oxidative injury. CRITICAL ISSUES The present article presents an up-to-date review of the association between AT and vascular oxidative stress. We focus on the effects of individual adipokines on modulating reactive oxygen species production and scavenging in the vascular wall. In addition, we highlight how inflammation, obesity, and IR alter the biology and secretome of AT leading to a more pro-oxidant phenotype with a particular focus on the local regulatory mechanisms of perivascular AT driven by vascular oxidation. FUTURE DIRECTIONS The complex and dynamic biology of AT, as well as its importance in the regulation of vascular redox state, provides numerous opportunities for the development of novel, targeted treatments in the management of CVD. Therapeutic modulation of AT biology could improve vascular redox state affecting vascular disease pathogenesis. Antioxid. Redox Signal. 29, 313-336.
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Affiliation(s)
- Evangelos K Oikonomou
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford , Oxford, United Kingdom
| | - Charalambos Antoniades
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford , Oxford, United Kingdom
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26
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Becic T, Studenik C. Effects of Omega-3 Supplementation on Adipocytokines in Prediabetes and Type 2 Diabetes Mellitus: Systematic Review and Meta-Analysis of Randomized Controlled Trials. Diabetes Metab J 2018; 42:101-116. [PMID: 29676540 PMCID: PMC5911513 DOI: 10.4093/dmj.2018.42.2.101] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2017] [Accepted: 03/28/2018] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND The objective of this systematic review and meta-analysis was to determine the effects of omega-3 supplementation on adipocytokine levels in adult prediabetic and diabetic individuals. METHODS We searched PubMed, Medline, EMBASE, Scopus, Web of Science, Google Scholar, Cochrane Trial Register, World Health Organization Clinical Trial Registry Platform, and Clinicaltrial.gov Registry from inception to August 1, 2017 for randomized controlled trials. Pooled effects of interventions were assessed as mean difference using random effects model. We conducted a sensitivity, publication bias and subgroup analysis. RESULTS Fourteen studies individuals (n=685) were included in the meta-analysis. Omega-3 supplementation increased levels of adiponectin (0.48 μg/mL; 95% confidence interval [CI], 0.27 to 0.68; P<0.00001, n=10 trials), but effects disappeared after sensitivity analysis. Tumor necrosis factor α (TNF-α) levels were reduced (-1.71; 95% CI, -3.38 to -0.14; P=0.03, n=8 trials). Treatment duration shorter than 12 weeks was associated with greater reduction than longer treatment duration. Levels of other adipocytokines were not significantly affected. Publication bias could generally not be excluded. CONCLUSION Eicosapentaenoic acid and docosahexaenoic acid supplementation may increase adiponectin and reduce TNF-α levels in this population group. However, due to overall study heterogeneity and potential publication bias, a cautious interpretation is needed.
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Affiliation(s)
- Tarik Becic
- Department of Pharmacology and Toxicology, Faculty of Life Sciences, University of Vienna, Vienna, Austria.
| | - Christian Studenik
- Department of Pharmacology and Toxicology, Faculty of Life Sciences, University of Vienna, Vienna, Austria
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Ulyanova O, Baigenzhin A, Doskaliyev Z, Karibekov T, Kozina L, Saparbayev S, Trimova R. Transforming Growth Factor β1 in Patients with Type 2 Diabetes Mellitus After Fetal Pancreatic Stem Cell Transplant. EXP CLIN TRANSPLANT 2018. [PMID: 29528020 DOI: 10.6002/ect.tond-tdtd2017.p49] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES Our objective was to determine transforming growth factor β1 levels in patients with type 2 diabetes mellitus after fetal pancreatic stem cell transplant. MATERIALS AND METHODS We examined 10 patients (age range, 41-65 y) with type 2 diabetes mellitus, which we subsequently divided into 2 groups. Group 1 comprised 5 patients who received fetal pancreatic stem cell transplant (cells were 16-18 wk gestation) performed by intravenous infusion. Group 2 comprised 5 patients (control group) who were on hypoglycemic tablet therapy or insulin therapy. The quantity of fetal stem cells infused was 5 to 6 × 106. We analyzed transforming growth factor β1, C-peptide, and glycated hemoglobin levels in patients before and 3 months after fetal pancreatic stem cell transplant. RESULTS In patients with type 2 diabetes mellitus, fetal pancreatic stem cell transplant led to a significant increase in transforming growth factor β1 levels, from 16 364.8 to 35 730.4 ng/mL (P = .008), with trend in decreased glycated hemoglobin levels, from 7.96% to 6.98% (P = .088) after 3 months. CONCLUSIONS Transforming growth factor β1 levels increased significantly within 3 months after fetal pancreatic stem cell transplant in patients with type 2 diabetes mellitus.
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Affiliation(s)
- Olga Ulyanova
- Department of Endocrine Disturbances, National Scientific Medical Research Center, Astana, Kazakhstan
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28
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Kim JH, Yoon NY, Kim DH, Jung M, Jun M, Park HY, Chung CH, Lee K, Kim S, Park CS, Liu KH, Choi EH. Impaired permeability and antimicrobial barriers in type 2 diabetes skin are linked to increased serum levels of advanced glycation end-product. Exp Dermatol 2018; 27:815-823. [PMID: 29151267 DOI: 10.1111/exd.13466] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/10/2017] [Indexed: 12/17/2022]
Abstract
The incidence of type 2 diabetes mellitus (DM) has been increasing rapidly, and the disease has become a serious sociomedical problem. Many skin problems, such as xerosis, pruritus, skin infections and delayed wound healing, that might be related to chronic impairment of skin barrier function decrease the quality of life in patients with DM. However, the status of the permeability and antimicrobial barrier of the skin in DM remains unknown. This study aimed to elucidate skin barrier impairment in patients with type 2 DM and its pathomechanisms using classic animal models of type 2 DM. Functional studies of the skin barrier and an analysis of stratum corneum (SC) lipids were compared between patients with type 2 DM and age- and sex-matched non-diabetes controls. Also, functional studies on the skin barrier, epidermal lipid analyses, and electron microscopy and biomolecular studies were performed using type 2 DM animal models, db/db and ob/ob mice. Patients with type 2 DM presented with epidermal barrier impairments, including SC hydration, which was influenced by blood glucose control (HbA1c level). In the lipid analysis of SC, ceramides, fatty acids and cholesterol were significantly decreased in patients with type 2 DM compared with controls. Type 2 DM murine models presented with severe hyperglycaemia, impairment of skin barrier homeostasis, decreases in epidermal proliferation and epidermal lipid synthesis, decreases in lamellar body (LB) and epidermal antimicrobial peptides (AMPs), an increase in receptors for advanced glycation end-product (AGE) in the epidermis and an increase in serum AGE. Impairment of the skin barrier was observed in type 2 DM, which results in part from a decrease in epidermal proliferation. Serum AGE and its epidermal receptors were increased in type 2 diabetic mice which display impaired skin barrier parameters such as epidermal lipid synthesis, LB production, epidermal AMP and SC lipids.
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Affiliation(s)
- Jae-Hong Kim
- Department of Dermatology, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Na Young Yoon
- Department of Dermatology, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Dong Hye Kim
- Department of Dermatology, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Minyoung Jung
- Department of Dermatology, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Myungsoo Jun
- Department of Dermatology, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Hwa-Young Park
- Department of Dermatology, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Choon Hee Chung
- Department of Internal medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Kyohoon Lee
- Department of Chemical and Biochemical Engineering, Dongguk University, Seoul, Korea
| | - Sunki Kim
- Department of Chemical and Biochemical Engineering, Dongguk University, Seoul, Korea
| | - Chang Seo Park
- Department of Chemical and Biochemical Engineering, Dongguk University, Seoul, Korea
| | - Kwang-Hyeon Liu
- College of Pharmacy and Research, Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, Korea
| | - Eung Ho Choi
- Department of Dermatology, Yonsei University Wonju College of Medicine, Wonju, Korea
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Rostás I, Pótó L, Mátrai P, Hegyi P, Tenk J, Garami A, Illés A, Solymár M, Pétervári E, Szűcs Á, Párniczky A, Pécsi D, Rumbus Z, Zsiborás C, Füredi N, Balaskó M. In middle-aged and old obese patients, training intervention reduces leptin level: A meta-analysis. PLoS One 2017; 12:e0182801. [PMID: 28809927 PMCID: PMC5557366 DOI: 10.1371/journal.pone.0182801] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2016] [Accepted: 07/25/2017] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Leptin is one of the major adipokines in obesity that indicates the severity of fat accumulation. It is also an important etiological factor of consequent cardiometabolic and autoimmune disorders. Aging has been demonstrated to aggravate obesity and to induce leptin resistance and hyperleptinemia. Hyperleptinemia, on the other hand, may promote the development of age-related abnormalities. While major weight loss has been demonstrated to ameliorate hyperleptinemia, obese people show a poor tendency to achieve lasting success in this field. The question arises whether training intervention per se is able to reduce the level of this adipokine. OBJECTIVES We aimed to review the literature on the effects of training intervention on peripheral leptin level in obesity during aging, in order to evaluate the independent efficacy of this method. In the studies that were included in our analysis, changes of adiponectin levels (when present) were also evaluated. DATA SOURCES 3481 records were identified through searching of PubMed, Embase and Cochrane Library Database. Altogether 19 articles were suitable for analyses. STUDY ELIGIBILITY CRITERIA Empirical research papers were eligible provided that they reported data of middle-aged or older (above 45 years of age) overweight or obese (body mass index above 25) individuals and included physical training intervention or at least fitness status of groups together with corresponding blood leptin values. STATISTICAL METHODS We used random effect models in each of the meta-analyses calculating with the DerSimonian and Laird weighting methods. I-squared indicator and Q test were performed to assess heterogeneity. To assess publication bias Egger's test was applied. In case of significant publication bias, the Duval and Tweedie's trim and fill algorithm was used. RESULTS Training intervention leads to a decrease in leptin level of middle-aged or older, overweight or obese male and female groups, even without major weight loss, indicated by unchanged serum adiponectin levels. Resistance training appears to be more efficient in reducing blood leptin level than aerobic training alone. CONCLUSIONS Physical training, especially resistance training successfully reduces hyperleptinemia even without diet or major weight loss.
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Affiliation(s)
- Ildikó Rostás
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
| | - László Pótó
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
- Institute of Bioanalysis, Medical School, University of Pécs, Pécs, Hungary
| | - Péter Mátrai
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
- Institute of Bioanalysis, Medical School, University of Pécs, Pécs, Hungary
| | - Péter Hegyi
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
- Hungarian Academy of Sciences - University of Szeged, Momentum Gastroenterology Multidisciplinary Research Group, Szeged, Hungary
- Division of Gastroenterology, First Department of Internal Medicine, University of Pécs, Pécs, Hungary
| | - Judit Tenk
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
| | - András Garami
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
| | - Anita Illés
- Division of Gastroenterology, First Department of Internal Medicine, University of Pécs, Pécs, Hungary
| | - Margit Solymár
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
| | - Erika Pétervári
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
| | - Ákos Szűcs
- First Department of Surgery, Semmelweis University, Budapest, Hungary
| | | | - Dániel Pécsi
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
| | - Zoltán Rumbus
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
| | - Csaba Zsiborás
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
| | - Nóra Füredi
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
| | - Márta Balaskó
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
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Magnussen LV, Andersen PE, Diaz A, Ostojic J, Højlund K, Hougaard DM, Christensen AN, Nielsen TL, Andersen M. MR spectroscopy of hepatic fat and adiponectin and leptin levels during testosterone therapy in type 2 diabetes: a randomized, double-blinded, placebo-controlled trial. Eur J Endocrinol 2017; 177:157-168. [PMID: 28522646 DOI: 10.1530/eje-17-0071] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2017] [Revised: 04/30/2017] [Accepted: 05/18/2017] [Indexed: 01/06/2023]
Abstract
BACKGROUND Men with type 2 diabetes mellitus (T2D) often have lowered testosterone levels and an increased risk of cardiovascular disease (CVD). Ectopic fat increases the risk of CVD, whereas subcutaneous gluteofemoral fat protects against CVD and has a beneficial adipokine-secreting profile. HYPOTHESIS Testosterone replacement therapy (TRT) may reduce the content of ectopic fat and improve the adipokine profile in men with T2D. DESIGN AND METHODS A randomized, double-blinded, placebo-controlled study in 39 men aged 50-70 years with T2D and bioavailable testosterone levels <7.3 nmol/L. Patients were randomized to TRT (n = 20) or placebo gel (n = 19) for 24 weeks. Thigh subcutaneous fat area (TFA, %fat of total thigh volume), subcutaneous abdominal adipose tissue (SAT, % fat of total abdominal volume) and visceral adipose tissue (VAT, % fat of total abdominal volume) were measured by magnetic resonance (MR) imaging. Hepatic fat content was estimated by single-voxel MR spectroscopy. Adiponectin and leptin levels were measured by in-house immunofluorometric assay. Coefficients (b) represent the placebo-controlled mean effect of intervention. RESULTS TFA (b = -3.3 percentage points (pp), P = 0.009), SAT (b = -3.0 pp, P = 0.006), levels of adiponectin (b = -0.4 mg/L, P = 0.045), leptin (b = -4.3 µg/mL, P < 0.001), leptin:adiponectin ratio (b = -0.53, P = 0.001) and HDL cholesterol (b = -0.11 mmol/L, P = 0.009) decreased during TRT compared with placebo. Hepatic fat content and VAT were unchanged. CONCLUSIONS The effects of TRT on cardiovascular risk markers were ambiguous. We observed potentially harmful changes in cardiovascular risk parameters, markedly reduced subcutaneous fat and unchanged ectopic fat during TRT and a reduction in adiponectin levels. On the other hand, the decrease in leptin and leptin:adiponectin ratio assessments could reflect an amelioration of the cardiovascular risk profile linked to hyperleptinaemia in ageing men with T2D.
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Affiliation(s)
| | - P E Andersen
- Departments of Radiology, Odense University Hospital, Odense, Denmark
- Clinical Institute, University of Southern Denmark, Odense, Denmark
| | - A Diaz
- Departments of Radiology, Odense University Hospital, Odense, Denmark
| | - J Ostojic
- Centre of Radiology, Clinical Centre of Vojvodina, Faculty of Medicine-University of Novi Sad, Novi Sad, Serbia
| | - K Højlund
- Departments of Endocrinology and Metabolism
- Section of Molecular Diabetes & Metabolism, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark
| | - D M Hougaard
- Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark
| | - A N Christensen
- Department of Applied Mathematics and Computer Science, Technical University of Denmark, Lyngby, Denmark
| | | | - M Andersen
- Departments of Endocrinology and Metabolism
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Billeter AT, Vittas S, Israel B, Scheurlen KM, Hidmark A, Fleming TH, Kopf S, Büchler MW, Müller-Stich BP. Gastric bypass simultaneously improves adipose tissue function and insulin-dependent type 2 diabetes mellitus. Langenbecks Arch Surg 2017; 402:901-910. [DOI: 10.1007/s00423-017-1601-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2017] [Accepted: 06/29/2017] [Indexed: 01/06/2023]
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Zaki M, Kamal S, Ezzat W, Hassan N, Yousef W, Ryad H, Mohamed R, Youness E, Basha W, Elhosary Y. Serum apelin levels and metabolic risk markers in obese women. J Genet Eng Biotechnol 2017; 15:423-429. [PMID: 30647682 PMCID: PMC6296620 DOI: 10.1016/j.jgeb.2017.05.002] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2016] [Revised: 04/06/2017] [Accepted: 05/27/2017] [Indexed: 12/25/2022]
Abstract
Background Adipose tissue hormones, Adipokines, play an important role in obesity-associated complications. Apelin has recently been added to the family of adipokines. The aim of this study was to evaluate the relationship between serum apelin levels and metabolic abnormal parameters in Egyptian obese women. Materials and methods The study included 400 unrelated women; they were 200 obese women and 200 non- obese matched healthy women. All participants underwent clinical, anthropometric and biochemical examinations. Insulin resistance (IR) was determined by the homeostasis model assessment of insulin resistance (HOMA-IR). Serum apelin levels and obesity biomarkers were measured using enzyme-linked immunoassay (ELISA) kits. Fat mass was measured by Tanita Body Composition Analyzer. Results Obese women showed significant higher levels of serum apelin, leptin, triglycerides, LDL-C, total cholesterol, fasting insulin HOMA-IR and blood pressure levels than controls. Significant positive correlations between apelin and leptin levels with abnormal metabolic markers were noted in obese women. Conclusion The present study suggests the significant role that might be mediated by apelin for developing abnormal metabolic parameters among Egyptian obese women.
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Affiliation(s)
- Moushira Zaki
- Biological Anthropology Department, Medical Research Division, Giza, Egypt
| | - Sanaa Kamal
- Biological Anthropology Department, Medical Research Division, Giza, Egypt
| | - Wafaa Ezzat
- Internal Medicine Department, Medical Research Division, Giza, Egypt
| | - Naglaa Hassan
- Biological Anthropology Department, Medical Research Division, Giza, Egypt
| | - Walaa Yousef
- Biological Anthropology Department, Medical Research Division, Giza, Egypt
| | - Hanaa Ryad
- Biological Anthropology Department, Medical Research Division, Giza, Egypt
| | - Ramy Mohamed
- Biological Anthropology Department, Medical Research Division, Giza, Egypt
| | - Eman Youness
- Medical Biochemistry Department, Medical Research Division, National Research Centre, Giza, Egypt
| | - Walaa Basha
- Biological Anthropology Department, Medical Research Division, Giza, Egypt
| | - Yasser Elhosary
- Internal Medicine Department, Medical Research Division, Giza, Egypt
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Kołodziejski PA, Pruszyńska-Oszmałek E, Strowski MZ, Nowak KW. Long-term obestatin treatment of mice type 2 diabetes increases insulin sensitivity and improves liver function. Endocrine 2017; 56:538-550. [PMID: 28477305 DOI: 10.1007/s12020-017-1309-2] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2016] [Accepted: 04/19/2017] [Indexed: 01/02/2023]
Abstract
PURPOSE Obestatin and ghrelin are peptides encoded by the preproghrelin gene. Obestatin inhibits food intake, in addition to regulation of glucose and lipid metabolism. Here, we test the ability of obestatin at improving metabolic control and liver function in type 2 diabetic animals (type 2 diabetes mellitus). METHODS The effects of chronic obestatin treatment of mice with experimentally induced type 2 diabetes mellitus on serum levels of glucose and lipids, and insulin sensitivity are characterized. In addition, alterations of hepatic lipid and glycogen contents are evaluated. RESULTS Obestatin reduced body weight and decreased serum glucose, fructosamine, and β-hydroxybutyrate levels, as well as total and low-density lipoprotein fractions of cholesterol. In addition, obestatin increased high-density lipoproteins cholesterol levels and enhanced insulin sensitivity in mice with type 2 diabetes mellitus. Moreover, obestatin diminished liver mass, hepatic triglycerides and cholesterol contents, while glycogen content was higher in livers of healthy and mice with type 2 diabetes mellitus treated with obestatin. These changes were accompanied by reduction of increased alanine aminotransferase, aspartate aminotransferase, and gamma glutamyl transpeptidase in T2DM mice with type 2 diabetes mellitus. Obestatin increased adiponectin levels and reduced leptin concentration. Obestatin influenced the expression of genes involved in lipid and carbohydrate metabolism by increasing Fabp5 and decreasing G6pc, Pepck, Fgf21 mRNA in the liver. Obestatin increased both, AKT and AMPK phosphorylation, and sirtuin 1 (SIRT1) protein levels as well as mRNA expression in the liver. CONCLUSION Obestatin improves metabolic abnormalities in type 2 diabetes mellitus, restores hepatic lipid contents and decreases hepatic enzymes. Therefore, obestatin could potentially have a therapeutic relevance in treating of insulin resistance and metabolic dysfunctions in type 2 diabetes mellitus.
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Affiliation(s)
- Paweł A Kołodziejski
- Department of Animal Physiology and Biochemistry, Poznan University of Life Sciences, Wolynska Street 35, 60-637, Poznan, Poland.
| | - Ewa Pruszyńska-Oszmałek
- Department of Animal Physiology and Biochemistry, Poznan University of Life Sciences, Wolynska Street 35, 60-637, Poznan, Poland
| | - Mathias Z Strowski
- Department of Hepatology and Gastroenterology & the Interdisciplinary Centre of Metabolism: Endocrinology, Diabetes and Metabolism, Charité-University Medicine Berlin, 13353, Berlin, Germany
- Park-Klinik Weissensee, Internal Medicine - Gastroenterology, Berlin, 13086, Germany
| | - Krzysztof W Nowak
- Department of Animal Physiology and Biochemistry, Poznan University of Life Sciences, Wolynska Street 35, 60-637, Poznan, Poland
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Haleem DJ, Sheikh S, Fawad A, Haleem MA. Fasting leptin and glucose in normal weight, over weight and obese men and women diabetes patients with and without clinical depression. Metab Brain Dis 2017; 32:757-764. [PMID: 28197877 DOI: 10.1007/s11011-017-9964-9] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2016] [Accepted: 01/31/2017] [Indexed: 01/05/2023]
Abstract
A large number of diabetes patients suffer from major depression and are at high risk of mortality. In view of a role of leptin in diabetes, depression and energy homeostasis, the present study concerns circulating levels of leptin in different BMI groups of un-depressed and depressed diabetes patients. Six hundred thirty male and female patients with a primary diagnosis of diabetes were grouped according to BMI and with or without clinical symptoms of depression. Age matched healthy, normal weight male and female volunteers without clinical symptoms of depression or diabetes were taken as controls. Blood samples were obtained after an overnight fast of 12 h. Serum was stored for the determination of leptin and glucose. We found that there were more female than male diabetes patients with comorbid depression. Fasting leptin was higher in normal weight non-diabetes women than men; but comparable in normal weight men and women diabetes patients. Fasting glucose levels were higher in diabetes than non diabetes groups; values were comparable in men and women. Depression was associated with a decrease and increase in leptin respectively in normal-overweight and obese men and women diabetes patients. Glucose levels were also higher in obese depressed than un-depressed diabetes patients. The results suggested that the female gender is at greater risk to comorbid diabetes with depression. Adipo-insular axis plays an important role in diabetes, associated depression and in the greater risk of the female gender to comorbid diabetes with depression.
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Affiliation(s)
- Darakhshan Jabeen Haleem
- Neuroscience Research Laboratory, Dr. Panjwani Center for Molecular Medicine and Drug Research, University of Karachi, Karachi, 75270, Pakistan
| | - Shehnaz Sheikh
- Department of Biochemistry, Liaquat National Hospital & Medical College, Karachi, Pakistan
| | - Asher Fawad
- Baqai Institute of Diabetology and Endocrinology, Karachi, Pakistan
| | - Muhammad A Haleem
- Department of Biomedical Engineering, Sir Syed University of Engineering and Technology, Karachi, 75300, Pakistan
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Shool F, Ostadrahimi A, Lotfi H, Abbasi Majdi M, Mahmoudi R, Niknam Moghanloo M, Ghafarian Alipour F, Porfaraj S, Zarghami N. Correlation between adiponectin level with common variant (rs9939609) of fat mass and obesity-associated gene in obese type 2 diabetic women. J Nephropharmacol 2017. [DOI: 10.15171/npj.2017.19] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
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Booth A, Magnuson A, Fouts J, Foster MT. Adipose tissue: an endocrine organ playing a role in metabolic regulation. Horm Mol Biol Clin Investig 2017; 26:25-42. [PMID: 26910750 DOI: 10.1515/hmbci-2015-0073] [Citation(s) in RCA: 94] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2015] [Accepted: 01/01/2016] [Indexed: 12/14/2022]
Abstract
Adipose tissue is a complex endocrine organ with an intricate role in whole body homeostasis. Beyond storing energy, adipose tissue is fundamental in numerous processes including, but not limited to, metabolism, food intake and immune cell function. Adipokines and cytokines are the signaling factors from adipose tissue. These factors play a role in maintaining health, but are also candidates for pathologies associated with obesity. Indeed excessive adiposity causes dysregulation of these factors which negatively affect health and contribute to numerous obesity-induced co-morbidities. In particular, adipokines are fundamental in regulation of glucose homeostasis and insulin signaling, thus aberrant production of these adipose derived hormones correlates with the development and progression of type 2 diabetes. Therefore, elucidation of adipose regulation is crucial for understanding the pathophysiological basis of obesity and metabolic diseases such as type 2 diabetes. In the present review, we summarize current data on the relation between adipokines and adipose depot derived cytokines in the maintenance of glucose homeostasis. Specifically, physiological and molecular functions of several adipokines are defined with particular focus on interactions within the insulin-signaling pathway and subsequent regulation of glucose uptake in both standard and obesity-induced dysregulated conditions. This same relation will be discussed for cytokines and inflammation as well.
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Ulyanova O, Baigenzhin A, Taubaldieva Z, Tuganbekova S, Kozina L, Saparbayev S. Leptin Levels in Patients with Type 1 Diabetes Mellitus After Fetal Pancreatic Stem Cell Transplant. EXP CLIN TRANSPLANT 2017; 15:194-195. [PMID: 28260466 DOI: 10.6002/ect.mesot2016.p77] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES Our objective was to determine leptin levels in patients with type 1 diabetes mellitus after fetal pancreatic stem cell transplant. MATERIALS AND METHODS Seven patients, aged 20 to 42 years, with type 1 diabetes mellitus received a fetal pancreatic stem cell transplant by intravenous infusion. The quantity of fetal stem cells infused was ≥ 5 × 10⁶, and the cells were of 12 to 14 weeks of gestation. We analyzed the levels of leptin, C-peptide, and antibodies to the islets of Langerhans before and 3 months after the transplant procedure. RESULTS Fetal pancreatic stem cell transplant led to significant increases in leptin and C-peptide levels, from 4.63 ± 1.17 ng/mL and 0.09 ± 0.02 ng/mL to 7.71 ± 1.45 ng/mL (P < .05) and 0.22 ± 0.05 ng/mL (P < .005), respectively, without an increase in antibodies to the islets of Langerhans, which measured 0.64 ± 0.13 U/mL before transplant and 0.57 ± 0.18 U/mL 3 months later (P > .05). CONCLUSIONS Leptin levels increase significantly within 3 months of fetal pancreatic stem cell transplant in patients with type 1 diabetes mellitus.
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Affiliation(s)
- Olga Ulyanova
- Department of Internal Medicine, National Scientific Medical Research Center, Astana, Kazakhstan
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Effects of Helicobacter pylori eradication on insulin resistance and metabolic parameters: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol 2017; 29:153-159. [PMID: 27832037 DOI: 10.1097/meg.0000000000000774] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Previous studies have shown a close relationship between Helicobacter pylori (H. pylori), insulin resistance, and altered metabolic parameters. However, the effects of H. pylori eradication on these conditions remain controversial. We carried out a systematic review and meta-analysis to evaluate the effects of H. pylori eradication on insulin resistance and metabolic parameters. METHODS We searched CENTRAL, MEDLINE, and EMBASE databases from their inception to July 2016. Insulin resistance (HOMA-IR), body weight (BW), BMI, waist circumference, triglycerides (TG), high-density and low-density lipoprotein-cholesterol (HDL-C and LDL-C), and fasting blood glucose (FBG) were compared between patients with and without H. pylori eradication using a random-effects model. We reported pooled mean differences (MD) and 95% confidence intervals (CI) for the change in outcomes. RESULTS Data from five studies showed no difference in HOMA-IR after H. pylori eradication (pooled MD=-0.52, 95% CI: -1.47 to 0.42). Eradication significantly increased BMI (MD=0.36, 95% CI: 0.11-0.60) and BW (MD=1.1, 95% CI: 0.8-1.5), but had no significant effects on TG, LDL-C, HDL-C, or FBG. CONCLUSION H. pylori eradication does not improve insulin resistance, TG, HDL-C, LDL-C, or FBG, but may increase BW and BMI. Further studies are needed to clarify the effect of H. pylori eradication on metabolism.
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Sundararaghavan V, Mazur MM, Evans B, Liu J, Ebraheim NA. Diabetes and bone health: latest evidence and clinical implications. Ther Adv Musculoskelet Dis 2017; 9:67-74. [PMID: 28344668 DOI: 10.1177/1759720x16687480] [Citation(s) in RCA: 62] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
As the prevalence of diabetes is increasing worldwide, research on some of the lesser-known effects, including impaired bone health, are gaining a lot of attention. The two most common forms of diabetes are type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). These two differ in their physiology, with T1DM stemming from an inability to produce insulin, and T2DM involving an insufficient response to the insulin that is produced. This review aims to highlight the most current information regarding diabetes as it relates to bone health. It looks at biochemical changes that characterize diabetic bone; notably increased adiposity, altered bone metabolism, and variations in bone mineral density (BMD). Then several hypotheses are analyzed, concerning how these changes may be detrimental to the highly orchestrated processes that are involved in bone formation and turnover, and ultimately result in the distinguishing features of diabetic bone. The review proceeds by explaining the effects of antidiabetes medications on bone health, then highlighting several ways that diabetes can play a part in other clinical treatment outcomes. With diabetes negatively affecting bone health and creating other clinical problems, and its treatment options potentiating these effects, physicians should consider the use of anti-osteoporotic drugs to supplement standard anti-diabetes medications in patients suffering with diabetic bone loss.
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Affiliation(s)
| | - Matthew M Mazur
- Department of Orthopaedic Surgery, University of Toledo Medical Center, Toledo, OH, USA
| | - Brad Evans
- Department of Orthopaedic Surgery, University of Toledo Medical Center, Toledo, OH, USA
| | - Jiayong Liu
- Department of Orthopaedic Surgery, University of Toledo Medical Center, 3065 Arlington Avenue, Toledo, OH 43614, USA
| | - Nabil A Ebraheim
- Department of Orthopaedic Surgery, University of Toledo Medical Center, Toledo, OH, USA
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Randy A, Kim M, Nho CW. Ligularia fischeri and its constituent 3,4-dicaffeoylquinic acid improve obesity-induced nonalcoholic fatty liver disease by regulating lipid metabolism and activating AMPK. J Funct Foods 2016. [DOI: 10.1016/j.jff.2016.08.050] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
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EXP CLIN TRANSPLANTExp Clin Transplant 2016; 14. [DOI: 10.6002/ect.tondtdtd2016.o22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register]
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Osegbe I, Okpara H, Azinge E. Relationship between serum leptin and insulin resistance among obese Nigerian women. Ann Afr Med 2016; 15:14-9. [PMID: 26857932 PMCID: PMC5452686 DOI: 10.4103/1596-3519.158524] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Background: Leptin is a hormone produced directly from adipocytes and has been associated with type 2 diabetes mellitus (T2DM) which is characterized by insulin resistance (IR). Due to the increasing prevalence of obesity in sub-Saharan Africa, serum leptin can be explored as a predictive risk factor for T2DM. Therefore, the aim of this study was to determine the relationship between serum leptin and IR among obese women. Methods: This was a cross-sectional study of obese, adult Nigerian females. Participants with body mass index (BMI) ≥30 kg/m2 and nondiabetic were recruited as subjects. Fasting serum leptin, insulin, and plasma glucose were determined. IR was calculated using the formula: Homeostatic model assessment-IR (HOMA-IR) = (glucose × insulin)/22.5. Statistical analyses were performed using SPSS and P < 0.05 was considered to be significant. Results: Eighty obese females with mean ± standard deviation BMI 39.1 ± 7.2 kg/m2 and serum leptin level 48.4 ± 24.4 ng/ml participated in study. Prevalence of hyperleptinemia was 92.5% (confidence interval: 87.3–97.7%). The relationship between leptin and HOMA-IR among the subjects was: BMI 30–34.9 kg/m2: n = 27, r = 0.18, P = 0.42; BMI 35–39.9 kg/m2: n = 24, r = 0.36, P = 0.11; BMI ≥ 40 kg/m2: n = 29, r = 0.52, P = 0.004*; and after controlling for BMI (n = 29, r = 0.46, P = 0.014*). Multiple linear regression showed that leptin did not predict for IR (P = 0.837). Conclusion: Serum leptin levels were positively correlated with IR, which was significant among the Class III (morbid) obesity class. However, leptin was not a predictive factor for IR in obese Nigerian women.
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Affiliation(s)
- Ifeyinwa Osegbe
- Department of Chemical Pathology, University of Nigeria Teaching Hospital, Enugu, Nigeria
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Talton OO, Pennington KA, Pollock KE, Bates K, Ma L, Ellersieck MR, Schulz LC. Maternal Hyperleptinemia Improves Offspring Insulin Sensitivity in Mice. Endocrinology 2016; 157:2636-48. [PMID: 27145007 DOI: 10.1210/en.2016-1039] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
Maternal obesity and gestational diabetes are prevalent worldwide. Offspring of mothers with these conditions weigh more and are predisposed to metabolic syndrome. A hallmark of both conditions is maternal hyperleptinemia, but the role of elevated leptin levels during pregnancy on developmental programming is largely unknown. We previously found that offspring of hyperleptinemic mothers weighed less and had increased activity. The goal of this study was to determine whether maternal leptin affects offspring insulin sensitivity by investigating offspring glucose metabolism and lipid accumulation. Offspring from two maternal hyperleptinemic models were compared. The first model of hyperleptinemia is the Lepr(db/+) mouse, which has a mutation in one copy of the gene that encodes the leptin receptor, resulting in a truncated long form of the receptor, and hyperleptinemia. Wild-type females served as the control for the Lepr(db/+) females. For the second hyperleptinemic model, wild-type females were implanted with miniosmotic pumps, which released leptin (350 ng/h) or saline (as the control) just prior to mating and throughout gestation. In the offspring of these dams, we measured glucose tolerance; serum leptin, insulin, and triglyceride levels; liver triglycerides; pancreatic α- and β-cell numbers; body composition; incidence of nonalcoholic fatty liver disease; and the expression of key metabolic genes in the liver and adipose tissue. We found that the offspring of hyperleptinemic dams exhibited improved glucose tolerance, reduced insulin and leptin concentrations, reduced liver triglycerides, and a lower incidence of nonalcoholic fatty liver disease. Overall, maternal hyperleptinemia was beneficial for offspring glucose and lipid metabolism.
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Affiliation(s)
- Omonseigho O Talton
- Departments of Obstetrics, Gynecology, and Women's Health (O.O.T., K.A.P., K.E.P., K.B., L.C.S.) and Radiology (L.M.) and Divisions of Biological Sciences (O.O.T., K.B., L.C.S.) and Animal Sciences (K.E.P., M.R.E., L.C.S.), University of Missouri, Columbia, Missouri 65212; and Biomolecular Imaging Center (L.M.), Harry S. Truman Veterans Affairs Hospital, Columbia, Missouri 65201
| | - Kathleen A Pennington
- Departments of Obstetrics, Gynecology, and Women's Health (O.O.T., K.A.P., K.E.P., K.B., L.C.S.) and Radiology (L.M.) and Divisions of Biological Sciences (O.O.T., K.B., L.C.S.) and Animal Sciences (K.E.P., M.R.E., L.C.S.), University of Missouri, Columbia, Missouri 65212; and Biomolecular Imaging Center (L.M.), Harry S. Truman Veterans Affairs Hospital, Columbia, Missouri 65201
| | - Kelly E Pollock
- Departments of Obstetrics, Gynecology, and Women's Health (O.O.T., K.A.P., K.E.P., K.B., L.C.S.) and Radiology (L.M.) and Divisions of Biological Sciences (O.O.T., K.B., L.C.S.) and Animal Sciences (K.E.P., M.R.E., L.C.S.), University of Missouri, Columbia, Missouri 65212; and Biomolecular Imaging Center (L.M.), Harry S. Truman Veterans Affairs Hospital, Columbia, Missouri 65201
| | - Keenan Bates
- Departments of Obstetrics, Gynecology, and Women's Health (O.O.T., K.A.P., K.E.P., K.B., L.C.S.) and Radiology (L.M.) and Divisions of Biological Sciences (O.O.T., K.B., L.C.S.) and Animal Sciences (K.E.P., M.R.E., L.C.S.), University of Missouri, Columbia, Missouri 65212; and Biomolecular Imaging Center (L.M.), Harry S. Truman Veterans Affairs Hospital, Columbia, Missouri 65201
| | - Lixin Ma
- Departments of Obstetrics, Gynecology, and Women's Health (O.O.T., K.A.P., K.E.P., K.B., L.C.S.) and Radiology (L.M.) and Divisions of Biological Sciences (O.O.T., K.B., L.C.S.) and Animal Sciences (K.E.P., M.R.E., L.C.S.), University of Missouri, Columbia, Missouri 65212; and Biomolecular Imaging Center (L.M.), Harry S. Truman Veterans Affairs Hospital, Columbia, Missouri 65201
| | - Mark R Ellersieck
- Departments of Obstetrics, Gynecology, and Women's Health (O.O.T., K.A.P., K.E.P., K.B., L.C.S.) and Radiology (L.M.) and Divisions of Biological Sciences (O.O.T., K.B., L.C.S.) and Animal Sciences (K.E.P., M.R.E., L.C.S.), University of Missouri, Columbia, Missouri 65212; and Biomolecular Imaging Center (L.M.), Harry S. Truman Veterans Affairs Hospital, Columbia, Missouri 65201
| | - Laura C Schulz
- Departments of Obstetrics, Gynecology, and Women's Health (O.O.T., K.A.P., K.E.P., K.B., L.C.S.) and Radiology (L.M.) and Divisions of Biological Sciences (O.O.T., K.B., L.C.S.) and Animal Sciences (K.E.P., M.R.E., L.C.S.), University of Missouri, Columbia, Missouri 65212; and Biomolecular Imaging Center (L.M.), Harry S. Truman Veterans Affairs Hospital, Columbia, Missouri 65201
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Adipokine Imbalance in the Pericardial Cavity of Cardiac and Vascular Disease Patients. PLoS One 2016; 11:e0154693. [PMID: 27139713 PMCID: PMC4854456 DOI: 10.1371/journal.pone.0154693] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2016] [Accepted: 04/18/2016] [Indexed: 01/09/2023] Open
Abstract
Aim Obesity and especially hypertrophy of epicardial adipose tissue accelerate coronary atherogenesis. We aimed at comparing levels of inflammatory and atherogenic hormones from adipose tissue in the pericardial fluid and circulation of cardiovascular disease patients. Methods and Results Venous plasma (P) and pericardial fluid (PF) were obtained from elective cardiothoracic surgery patients (n = 37). Concentrations of leptin, adipocyte fatty acid-binding protein (A-FABP) and adiponectin (APN) were determined by enzyme-linked immunosorbent assays (ELISA). The median concentration of leptin in PF (4.3 (interquartile range: 2.8–9.1) μg/L) was comparable to that in P (5.9 (2.2–11) μg/L) and these were significantly correlated to most of the same patient characteristics. The concentration of A-FABP was markedly higher (73 (28–124) versus 8.4 (5.2–14) μg/L) and that of APN was markedly lower (2.8 (1.7–4.2) versus 13 (7.2–19) mg/L) in PF compared to P. APN in PF was unlike in P not significantly related to age, body mass index, plasma triglycerides or coronary artery disease. PF levels of APN, but not A-FABP, were related to the size of paracardial adipocytes. PF levels of APN and A-FABP were not related to the immunoreactivity of paracardial adipocytes for these proteins. Conclusion In cardiac and vascular disease patients, PF is enriched in A-FABP and poor in APN. This adipokine microenvironment is more likely determined by the heart than by the circulation or paracardial adipose tissue.
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Abstract
Caloric intake and energy balance are highly regulated to maintain metabolic homeostasis and weight. However, hedonic-motivated food intake, in particular consumption of highly rewarding foods, may act to override hemostatic signaling and contribute to overconsumption, weight gain, and obesity. Here, we review human neuroimaging literature that has delivered valuable insight into the neural correlates of hedonic-motivated ingestive behavior, weight gain, weight loss, and metabolic status. Our primary focus is the brain regions that are thought to encode aspects of food hedonics, gustatory and somatosensory processing, and executive functioning. Further, we discuss the variability of regional brain response as a function of obesity, weight gain, behavioral and surgical weight loss, as well as in type 2 diabetes.
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Affiliation(s)
- Kyle S Burger
- Department of Nutrition, University of North Carolina at Chapel Hill, 2204 McGravran-Greenberg Hall, CB 7461, Chapel Hill, NC, 27599, USA.
| | | | - Abigail J Sanders
- Department of Nutrition, University of North Carolina at Chapel Hill, 2204 McGravran-Greenberg Hall, CB 7461, Chapel Hill, NC, 27599, USA
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Lee SS, Yoo JH, So YS. Effect of the low- versus high-intensity exercise training on endoplasmic reticulum stress and GLP-1 in adolescents with type 2 diabetes mellitus. J Phys Ther Sci 2015; 27:3063-8. [PMID: 26644644 PMCID: PMC4668135 DOI: 10.1589/jpts.27.3063] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2015] [Accepted: 07/06/2015] [Indexed: 12/17/2022] Open
Abstract
[Purpose] The primary objective of this study was to investigate the effect of low-intensity exercise training compare with high-intensity exercise training on endoplasmic reticulum stress and glucagon-like peptide-1 in adolescents with type 2 diabetes mellitus. [Subjects and Methods] The low-intensity exercise training group performed aerobic exercise training at an intensity of ≤ 45% of the heart rate reserve. The high-intensity interval exercise training group performed interval exercise training at an intensity of ≥ 80% of the heart rate reserve. The exercise-related energy consumption was determined for both groups on a per-week basis (1,200 kcal/week). [Results] Both groups showed improvement in the glucose-regulated protein 78 and dipeptidyl peptidase-4, but the size of the between-group effect was not statistically significant. The high-intensity interval exercise training group showed a significant reduction in percentage body fat. The C-peptide level increased after the 12-weeks programs and was significantly different, between the groups. Fasting glucose, insulin resistance in the fasting state according to homeostasis model assessment, and leptin decreased after the 12-weeks exercise program and were significantly different between the groups, and glucagon-like peptide-1 increased after the 12-week exercise programs and was significantly different between the groups. [Conclusion] In conclusion high-intensity interval exercise training, as defined in this study, may lead to improvements in body composition, glycemic control, endoplasmic reticulum stress, and the glucagon-like peptide-1 in adolescents with type 2 diabetes mellitus.
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Affiliation(s)
- Sung Soo Lee
- Department of Coaching, Dong-A University, Republic of
Korea
| | - Jae Ho Yoo
- Department of Pediatric, College of Medicine, Dong-A
University Medical Center, Repulic of Korea
| | - Yong Seok So
- Department of Physical Education, Dong-A University, Repulic of Korea
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Tang-Péronard JL, Heitmann BL, Jensen TK, Vinggaard AM, Madsbad S, Steuerwald U, Grandjean P, Weihe P, Nielsen F, Andersen HR. Prenatal exposure to persistent organochlorine pollutants is associated with high insulin levels in 5-year-old girls. ENVIRONMENTAL RESEARCH 2015; 142:407-13. [PMID: 26232659 PMCID: PMC4609268 DOI: 10.1016/j.envres.2015.07.009] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/04/2015] [Revised: 07/02/2015] [Accepted: 07/16/2015] [Indexed: 05/02/2023]
Abstract
BACKGROUND Several persistent organochlorine pollutants (POPs) possess endocrine disrupting abilities, thereby potentially leading to an increased risk of obesity and metabolic diseases, especially if the exposure occurs during prenatal life. We have previously found associations between prenatal POP exposures and increased BMI, waist circumference and change in BMI from 5 to 7 years of age, though only among girls with overweight mothers. OBJECTIVES In the same birth cohort, we investigated whether prenatal POP exposure was associated with serum concentrations of insulin and leptin among 5-year-old children, thus possibly mediating the association with overweight and obesity at 7 years of age. METHODS The analyses were based on a prospective Faroese Birth Cohort (n=656), recruited between 1997 and 2000. Major POPs, polychlorinated biphenyls (PCBs), p,p'-dichlorodiphenyldichloroethylene (DDE) and hexachlorobenzene (HCB), were measured in maternal pregnancy serum and breast milk. Children were followed-up at the age of 5 years where a non-fasting blood sample was drawn; 520 children (273 boys and 247 girls) had adequate serum amounts available for biomarker analyses by Luminex® technology. Insulin and leptin concentrations were transformed from continuous to binary variables, using the 75th percentile as a cut-off point. Multiple logistic regression was used to investigate associations between prenatal POP exposures and non-fasting serum concentrations of insulin and leptin at age 5 while taking into account confounders. RESULTS Girls with highest prenatal POP exposure were more likely to have high non-fasting insulin levels (PCBs 4th quartile: OR=3.71; 95% CI: 1.36, 10.01. DDE 4th quartile: OR=2.75; 95% CI: 1.09, 6.90. HCB 4th quartile: OR=1.98; 95% CI: 1.06, 3.69) compared to girls in the lowest quartile. No significant associations were observed with leptin, or among boys. A mediating effect of insulin or leptin on later obesity was not observed. CONCLUSION These findings suggest, that for girls, prenatal exposure to POPs may play a role for later development of metabolic diseases by affecting the level of insulin.
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Affiliation(s)
- Jeanett L Tang-Péronard
- Department of Environmental Medicine, Institute of Public Health, University of Southern Denmark, J.B. Winsløws Vej 17, 5000 Odense C, Denmark; The Parker Institute and Institute of Preventive Medicine, Research Unit for Dietary Studies, Bispebjerg and Frederiksberg Hospitals, The Capital Region, Nordre Fasanvej 57, Hovedvejen, Entrance 5, 1st floor, 2000 Frederiksberg, Denmark.
| | - Berit L Heitmann
- The Parker Institute and Institute of Preventive Medicine, Research Unit for Dietary Studies, Bispebjerg and Frederiksberg Hospitals, The Capital Region, Nordre Fasanvej 57, Hovedvejen, Entrance 5, 1st floor, 2000 Frederiksberg, Denmark; The Boden Institute of Obesity, Nutrition, Exercise & Eating Disorders, Sydney Medical School, Sydney, Australia; National Institute of Public Health, University of Southern Denmark, Østerfarimagsgade 5A, 2, 1353 Copenhagen K, Denmark
| | - Tina K Jensen
- Department of Environmental Medicine, Institute of Public Health, University of Southern Denmark, J.B. Winsløws Vej 17, 5000 Odense C, Denmark
| | - Anne M Vinggaard
- National Food Institute, Division of Toxicology and Risk Assessment, Technical University of Denmark, Mørkhøj Bygade 19, 2860 Søborg, Denmark
| | - Sten Madsbad
- Department of Endocrinology, Hvidovre University Hospital, Kettegård Allé 30, 2650 Hvidovre, Denmark
| | - Ulrike Steuerwald
- Department of Occupational Medicine and Public Health, The Faroese Hospital System, Sigmundargøta 5, 100 Tórshavn, Faroe Islands; Neonatal Screening Laboratories, PO-Box 911009, d-30430 Hannover, Germany
| | - Philippe Grandjean
- Department of Environmental Medicine, Institute of Public Health, University of Southern Denmark, J.B. Winsløws Vej 17, 5000 Odense C, Denmark; Harvard School of Public Health, Boston, MA 02215, United States
| | - Pál Weihe
- Department of Occupational Medicine and Public Health, The Faroese Hospital System, Sigmundargøta 5, 100 Tórshavn, Faroe Islands
| | - Flemming Nielsen
- Department of Environmental Medicine, Institute of Public Health, University of Southern Denmark, J.B. Winsløws Vej 17, 5000 Odense C, Denmark
| | - Helle R Andersen
- Department of Environmental Medicine, Institute of Public Health, University of Southern Denmark, J.B. Winsløws Vej 17, 5000 Odense C, Denmark
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Gutwenger I, Hofer G, Gutwenger AK, Sandri M, Wiedermann CJ. Pilot study on the effects of a 2-week hiking vacation at moderate versus low altitude on plasma parameters of carbohydrate and lipid metabolism in patients with metabolic syndrome. BMC Res Notes 2015; 8:103. [PMID: 25885799 PMCID: PMC4383206 DOI: 10.1186/s13104-015-1066-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2014] [Accepted: 03/18/2015] [Indexed: 02/08/2023] Open
Abstract
Background Hypoxic and hypobaric conditions may augment the beneficial influence of training on cardiovascular risk factors. This pilot study aimed to explore for effects of a two-week hiking vacation at moderate versus low altitude on adipokines and parameters of carbohydrate and lipid metabolism in patients with metabolic syndrome. Methods Fourteen subjects (mean age: 55.8 years, range: 39 – 69) with metabolic syndrome participated in a 2-week structured training program (3 hours of guided daily hiking 4 times a week, training intensity at 55-65% of individual maximal heart rate; total training time, 24 hours). Participants were divided for residence and training into two groups, one at moderate altitude (1,900 m; n = 8), and the other at low altitude (300 m; n = 6). Anthropometric, cardiovascular and metabolic parameters were measured before and after the training period. Results In study participants, training overall reduced circulating levels of total cholesterol (p = 0.024), low-density lipoprotein cholesterol (p = 0.025) and adiponectin (p < 0.001). In the group training at moderate altitude (n = 8), lowering effects on circulating levels were significant not only for total cholesterol, low-density-lipoprotein cholesterol and adiponectin (all, p < 0.05) but also for triglycerides (p = 0.025) and leptin (p = 0.015), whereas in the low altitude group (n = 6), none of the lipid parameters was significantly changed (each p > 0.05). Hiking-induced relative changes of triglyceride levels were positively associated with reductions in leptin levels (p = 0.006). As compared to 300 m altitude, training at 1,900 m showed borderline significant differences in the pre-post mean reduction rates of triglyceride (p = 0.050) and leptin levels (p = 0.093). Conclusions Preliminary data on patients with metabolic syndrome suggest that a 2-week hiking vacation at moderate altitude may be more beneficial for adipokines and parameters of lipid metabolism than training at low altitude. In order to draw firm conclusions regarding better corrections of dyslipidemia and metabolic syndrome by physical exercise under mild hypobaric and hypoxic conditions, a sufficiently powered randomized clinical trial appears warranted. Trial registration ClinicalTrials.gov ID NCT02013947 (first received November 6, 2013).
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Affiliation(s)
- Ivana Gutwenger
- Department of Anesthesiology, Hospital of Bressanone
- Brixen, Bressanone
- Brixen (BZ), Italy.
| | - Georg Hofer
- Department of Anesthesiology, Hospital of Silandro, Schlanders (BZ), Italy.
| | - Anna K Gutwenger
- Department of Internal Medicine, Hospital of Silandro
- Schlanders, Silandro
- Schlanders (BZ), Italy.
| | - Marco Sandri
- Data, Methods and Systems Statistical Laboratory, University of Brescia, Brescia (BS), Italy.
| | - Christian J Wiedermann
- Department of Internal Medicine, Central Hospital of Bolzano
- Bozen, Bolzano
- Bozen (BZ), Italy. .,Interdisciplinary Medical Research Center South Tyrol (IMREST), Bolzano
- Bozen (BZ), Italy.
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Karalliedde J, Gnudi L. Diabetes mellitus, a complex and heterogeneous disease, and the role of insulin resistance as a determinant of diabetic kidney disease. Nephrol Dial Transplant 2014; 31:206-13. [PMID: 25550448 DOI: 10.1093/ndt/gfu405] [Citation(s) in RCA: 65] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2014] [Accepted: 12/02/2014] [Indexed: 12/13/2022] Open
Abstract
Diabetes mellitus (DM) is increasingly recognized as a heterogeneous condition. The individualization of care and treatment necessitates an understanding of the individual patient's pathophysiology of DM that underpins their DM classification and clinical presentation. Classical type-2 diabetes mellitus is due to a combination of insulin resistance and an insulin secretory defect. Type-1 diabetes is characterized by a near-absolute deficiency of insulin secretion. More recently, advances in genetics and a better appreciation of the atypical features of DM has resulted in more categories of diabetes. In the context of kidney disease, patients with DM and microalbuminuria are more insulin resistant, and insulin resistance may be a pathway that results in accelerated progression of diabetic kidney disease. This review summarizes the updated classification of DM, including more rarer categories and their associated renal manifestations that need to be considered in patients who present with atypical features. The benefits and limitations of the tests utilized to make a diagnosis of DM are discussed. We also review the putative pathways and mechanisms by which insulin resistance drives the progression of diabetic kidney disease.
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Affiliation(s)
- Janaka Karalliedde
- Unit for Metabolic Medicine, Department of Diabetes and Endocrinology, Cardiovascular Division, School of Life Science & Medicine, King's College, London, UK
| | - Luigi Gnudi
- Unit for Metabolic Medicine, Department of Diabetes and Endocrinology, Cardiovascular Division, School of Life Science & Medicine, King's College, London, UK
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Metabolic syndrome is associated with increased breast cancer risk: a systematic review with meta-analysis. Int J Breast Cancer 2014; 2014:189384. [PMID: 25653879 PMCID: PMC4295135 DOI: 10.1155/2014/189384] [Citation(s) in RCA: 73] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2014] [Revised: 11/24/2014] [Accepted: 11/26/2014] [Indexed: 12/29/2022] Open
Abstract
Background. Although individual metabolic risk factors are reported to be associated with breast cancer risk, controversy surrounds risk of breast cancer from metabolic syndrome (MS). We report the first systematic review and meta-analysis of the association between MS and breast cancer risk in all adult females. Methods. Studies were retrieved by searching four electronic reference databases [PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, and ProQuest through June 30, 2012] and cross-referencing retrieved articles. Eligible for inclusion were longitudinal studies reporting associations between MS and breast cancer risk among females aged 18 years and older. Relative risks and 95% confidence intervals were calculated for each study and pooled using random-effects models. Publication bias was assessed quantitatively (Trim and Fill) and qualitatively (funnel plots). Heterogeneity was examined using Q and I2 statistics. Results. Representing nine independent cohorts and 97,277 adult females, eight studies met the inclusion criteria. A modest, positive association was observed between MS and breast cancer risk (RR: 1.47, 95% CI, 1.15–1.87; z = 3.13; p = 0.002; Q = 26.28, p = 0.001; I2 = 69.55%). No publication bias was observed. Conclusions. MS is associated with increased breast cancer risk in adult women.
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