|
1
|
Chen TY, Chen MJ, Lien KH. Association of Polycystic Ovary Syndrome With Sensorineural Hearing Loss: A Systematic Review and Meta-analysis. Otolaryngol Head Neck Surg 2025; 172:1121-1132. [PMID: 39720938 DOI: 10.1002/ohn.1081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2024] [Revised: 11/13/2024] [Accepted: 11/22/2024] [Indexed: 12/26/2024]
Abstract
OBJECTIVE Despite certain studies indicating hearing impairments in individuals with polycystic ovary syndrome (PCOS), the correlation between PCOS and sensorineural hearing loss (SNHL) remains inconclusive. This study aimed to investigate the association between PCOS and SNHL. DATA SOURCES A systematic literature search was conducted using PubMed, MEDLINE, EMBASE, and the Cochrane Library from inception to June 24, 2024. REVIEW METHODS This meta-analysis included cross-sectional, case-control, or cohort studies examining the association between PCOS and SNHL without language or regional restrictions. Case reports, case series, animal studies, and in vitro studies were excluded. We adhered to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines and utilized the Newcastle-Ottawa Scale to assess the risk of bias in the included studies. RESULTS After performing the systematic review, we conducted a meta-analysis that included 489 patients from 5 studies: 349 patients with PCOS and 140 age- and sex-matched controls without PCOS. The meta-analysis compared the mean differences in frequency-specific pure-tone thresholds between patients with PCOS and matched controls, providing 95% confidence intervals for these differences. Given the expected clinical heterogeneity, we employed the DerSimonian and Laird random-effects model. Our results revealed significant hearing loss at specific frequencies (1000, 4000, 8000, 10,000, 12,000, 14,000, 16,000, 18,000, and 20,000 Hz) in the PCOS group compared to the control group (P < .05). Furthermore, the degree of hearing loss is greater at higher frequencies. CONCLUSION This meta-analysis demonstrated an association between PCOS and SNHL, particularly at higher frequencies.
Collapse
Affiliation(s)
- Tai-Yu Chen
- Department of Otolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Mei-Jou Chen
- Department of Obstetrics and Gynecology, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan
- Livia Shan-Yu Wan Chair Professor of Obstetrics and Gynecology, National Taiwan University, Taipei, Taiwan
| | - Kuang-Hsu Lien
- Department of Otolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| |
Collapse
|
|
2
|
Altuntas E, Tırnaksız AE, Sadıkoğlu K, Aslan S, Demirci G, Yalcın AA, Kalkan AK, Uzun F, Aktürk IF, Celik O, Ertürk M. Prognostic Value of the Triglycerides-glucose Index for Major Adverse Cardiac Events in Severe Aortic Stenosis Patients After TAVI. Angiology 2025:33197251328773. [PMID: 40126369 DOI: 10.1177/00033197251328773] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/25/2025]
Abstract
The present study aimed to evaluate whether the Triglycerides-Glucose (TyG) index has a prognostic value for major adverse cardiac events (MACEs), including stroke, necessity of pacemaker, acute kidney failure, and short-term all-cause mortality at 12 months, in aortic stenosis (AS) patients who underwent transcatheter aortic valve implantation (TAVI). A total of 380 patients who underwent TAVI due to severe AS were retrospectively included in the study. The main outcome of the study was MACEs at 12 months. The TyG index was found to be higher in TAVI patients who developed MACEs than in those who did not develop them. Multivariate Cox regression analysis revealed that TyG (P < .001) was an independent predictor of MACEs in AS patients after TAVI. A TyG index value of >4.77 following TAVI had 50% sensitivity and 50% specificity (AUC [area under the curve]: 0.694, P < .001) for MACEs. This is the first study to show that a high pre-procedural TyG index has a predictive value for MACEs in AS patients undergoing TAVI.
Collapse
Affiliation(s)
- Emine Altuntas
- Department of Cardiology, University of Health Sciences, Istanbul Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, Istanbul, Türkiye
| | - Abidin Emre Tırnaksız
- Department of Cardiology, University of Health Sciences, Istanbul Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, Istanbul, Türkiye
| | - Kadir Sadıkoğlu
- Department of Cardiology, University of Health Sciences, Istanbul Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, Istanbul, Türkiye
| | - Serkan Aslan
- Department of Cardiology, University of Health Sciences, Istanbul Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, Istanbul, Türkiye
| | - Gökhan Demirci
- Department of Cardiology, University of Health Sciences, Istanbul Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, Istanbul, Türkiye
| | - Ahmet Arif Yalcın
- Department of Cardiology, University of Health Sciences, Istanbul Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, Istanbul, Türkiye
| | - Ali Kemal Kalkan
- Department of Cardiology, University of Health Sciences, Istanbul Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, Istanbul, Türkiye
| | - Fatih Uzun
- Department of Cardiology, University of Health Sciences, Istanbul Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, Istanbul, Türkiye
| | - Ibrahim Faruk Aktürk
- Department of Cardiology, University of Health Sciences, Istanbul Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, Istanbul, Türkiye
| | - Omer Celik
- Department of Cardiology, University of Health Sciences, Istanbul Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, Istanbul, Türkiye
| | - Mehmet Ertürk
- Department of Cardiology, University of Health Sciences, Istanbul Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, Istanbul, Türkiye
| |
Collapse
|
|
3
|
Zhou H, Ding X, Lan Y, Fang W, Yuan X, Tian Y, Chen S, Wu S, Wu D. Dual-trajectory of TyG levels and lifestyle scores and their associations with ischemic stroke in a non-diabetic population: a cohort study. Cardiovasc Diabetol 2024; 23:225. [PMID: 38943172 PMCID: PMC11214241 DOI: 10.1186/s12933-024-02313-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2024] [Accepted: 06/16/2024] [Indexed: 07/01/2024] Open
Abstract
BACKGROUND The Triglyceride-glucose (TyG) index, a surrogate marker of insulin resistance, has been implicated in the risk of ischemic stroke. However, the interplay between TyG levels, lifestyle factors, and their collective impact on stroke risk in non-diabetic populations remains inadequately explored. This study aims to evaluate the association of ischemic stroke with the joint development of the TyG index and lifestyle in the non-diabetic population. METHODS In this prospective cohort study, data was collected across three consecutive biennial surveys of the Kailuan Study from 2006 to 2011. The dual-trajectory model was used to determine the temporal development of TyG levels and lifestyle scores. Statistical analysis involved Cox regression models to evaluate the association between TyG-lifestyle trajectories and ischemic stroke risk, adjusting for potential confounders. RESULTS A total of 44,403 participants were included, with five distinct TyG levels and lifestyle scores trajectory subtypes identified. In the multivariable-adjusted analyses, significant differences in ischemic stroke risk among the trajectory subtypes. Group 5, characterized by the highest TyG levels and moderate lifestyle scores, exhibited the greatest ischemic stroke risk (HR = 1.81, 95% CI: 1.51-2.18), while group 4, with moderate TyG levels and higher lifestyle scores, demonstrated the lowest risk (HR = 1.19, 95% CI: 1.04-1.37), compared with group 3. Participants with elevated TyG levels were at an increased risk of ischemic stroke in cases of pronounced insulin resistance, even with a healthy lifestyle. CONCLUSIONS This study reveals the significant associations between the identified TyG and lifestyle trajectories and the stratification of ischemic stroke risk among non-diabetics. The TyG index is a valuable indicator for assessing insulin resistance. However, the potential benefits of lifestyle changes for those with significantly high TyG levels need to be clarified by more research to develop more effective stroke prevention strategies.
Collapse
Affiliation(s)
- Hui Zhou
- Xiangya School of Nursing, Central South University, Changsha, China
| | - Xiong Ding
- School of Public Health, Wuhan University, Wuhan, China
- Global Health Research Center, Duke Kunshan University, Suzhou, China
| | - Yulong Lan
- The Second Affiliated Hospital of Shantou University Medical College, Shantou, China
- Centre for Precision Health, School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia
| | - Wei Fang
- Department of Cardiology, Second Affiliated Hospital of Air Force Medical University, Xi'an, China
| | - Xiaojie Yuan
- Department of Epidemiology, Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Air Force Medical University, Xi'an, China
| | - Yan Tian
- School of Public Health, North China University of Science and Technology, Tangshan, China
| | - Shuohua Chen
- Department of Cardiology, Kailuan General Hospital, 57 Xinhua East Rd, Tangshan, China
| | - Shouling Wu
- Department of Cardiology, Kailuan General Hospital, 57 Xinhua East Rd, Tangshan, China.
| | - Dan Wu
- The Second Affiliated Hospital of Shantou University Medical College, Shantou, China.
- Centre for Precision Health, School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia.
- Department of Endocrinology, The First Affiliated Hospital of Shantou University Medical College, Shantou, China.
| |
Collapse
|
|
4
|
Xiong J, Wu Y, Huang L, Zheng X. Association of Triglyceride-Glucose Index with the Risk of Hyperhomocysteinemia Among Chinese Male Bus Drivers: A Longitudinal Study. Int J Gen Med 2023; 16:2857-2866. [PMID: 37426516 PMCID: PMC10329442 DOI: 10.2147/ijgm.s416230] [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: 04/07/2023] [Accepted: 06/27/2023] [Indexed: 07/11/2023] Open
Abstract
Background Insulin resistance (IR) and hyperhomocysteinemia (HHcy) are significant risk factors for cardiovascular disease (CVD). As an important marker for IR, Triglyceride-Glucose (TyG) index maybe a significant predictor for HHcy progression, reflecting cardiovascular risk. However, the relationship between TyG index and HHcy has been unknown, especially for the high-risk occupation group of male bus drivers. This longitudinal study was initially conducted to explore the outcome of TyG index in predicting HHcy among male bus drivers. Methods In total, 1018 Chinese male bus drivers with Hcy data and regular follow-up from 2017 to 2021 were screened, and 523 non-HHcy subjects at baseline were included in the longitudinal cohort. A restricted cubic spline (RCS) was performed to investigate the possible non-linear relationship between TyG index and the progression of HHcy. A multivariate logistic regression model was used to explore the association between TyG index and developing HHcy via assessing the value of odds ratio (OR) and 95% confidence interval (CI). Results After the median follow up time of 2.12 years, approximately 27.7% of male bus drivers (mean age: 48.1 years) was identified as new incidents HHcy. Multivariate logistic regression found that the higher level of TyG was associated with an increased risk of new onset HHcy (OR = 1.47; 95% CI: 1.11-1.94); and the association seemed to be strong among male bus drivers with elevated low-density lipoprotein cholesterol (LDL-C) (P for interaction < 0.05). Conclusion As a higher risk occupation group for HHcy, male bus drivers should cause much more attentions from policy makers, employers, and health professionals in China. Identifying male bus drivers with HHcy is of significance at an earlier stage in the primary care setting. Being a significant predictive factor for HHcy, TyG index could be used to monitor and prevent Chinese male bus drivers from HHcy, especially for individuals with elevated LDL-C.
Collapse
Affiliation(s)
- Juan Xiong
- Medical School, Shenzhen University, Shenzhen, 518060, People’s Republic of China
| | - Yanxia Wu
- Department of Health Management, Shenzhen People’s Hospital, Shenzhen City, People’s Republic of China
| | - Lingling Huang
- Medical School, Shenzhen University, Shenzhen, 518060, People’s Republic of China
| | - Xujuan Zheng
- Medical School, Shenzhen University, Shenzhen, 518060, People’s Republic of China
| |
Collapse
|
|
5
|
Cai W, Xu J, Wu X, Chen Z, Zeng L, Song X, Zeng Y, Yu F. Association between triglyceride-glucose index and all-cause mortality in critically ill patients with ischemic stroke: analysis of the MIMIC-IV database. Cardiovasc Diabetol 2023; 22:138. [PMID: 37312120 DOI: 10.1186/s12933-023-01864-x] [Citation(s) in RCA: 74] [Impact Index Per Article: 37.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Accepted: 05/25/2023] [Indexed: 06/15/2023] Open
Abstract
BACKGROUND The triglyceride-glucose (TyG) index was significantly associated with insulin resistance (IR). Several studies have validated the effect of TyG index on cerebrovascular disease. However, the value of TyG index in patients with severe stroke requiring ICU admission remains unclear. The aim of this study was to investigate the association between the TyG index and clinical prognosis of critically ill patients with ischemic stroke (IS). METHODS This study identified patients with severe IS requiring ICU admission from the Medical Information Mart for Intensive Care (MIMIC-IV) database, and divided them into quartiles based on TyG index level. The outcomes included in-hospital mortality and ICU mortality. The association between the TyG index and clinical outcomes in critically ill patients with IS was elucidated using Cox proportional hazards regression analysis and restricted cubic splines. RESULTS A total of 733 patients (55.8% male) were enrolled. The hospital mortality and intensive care unit (ICU) mortality reached 19.0% and 14.9%, respectively. Multivariate Cox proportional hazards analysis showed that the elevated TyG index was significantly related to all-cause death. After confounders adjusting, patients with an elevated TyG index had a significant association with hospital mortality (adjusted hazard ratio, 1.371; 95% confidence interval, 1.053-1.784; P = 0.013) and ICU mortality (adjusted hazard ratio, 1.653; 95% confidence interval, 1.244-2.197; P = 0.001). Restricted cubic splines revealed that a progressively increasing risk of all-cause mortality was related to an elevated TyG index. CONCLUSION The TyG index has a significant association with hospital and ICU all-cause death in critically ill patients with IS. This finding demonstrates that the TyG index might be useful in identifying patients with IS at high risk of all-cause death.
Collapse
Affiliation(s)
- Weimin Cai
- Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China
| | - Jun Xu
- Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China
| | - Xiao Wu
- Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China
| | - Zhuoyan Chen
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Wenzhou Medical University, No. 2, Fuxue Lane, Wenzhou, 325000, China
| | - Liuwei Zeng
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Wenzhou Medical University, No. 2, Fuxue Lane, Wenzhou, 325000, China
| | - Xian Song
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Wenzhou Medical University, No. 2, Fuxue Lane, Wenzhou, 325000, China
| | - Yuan Zeng
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Wenzhou Medical University, No. 2, Fuxue Lane, Wenzhou, 325000, China.
| | - Fujun Yu
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Wenzhou Medical University, No. 2, Fuxue Lane, Wenzhou, 325000, China.
| |
Collapse
|
|
6
|
Regidor PA, de la Rosa X, Müller A, Mayr M, Gonzalez Santos F, Gracia Banzo R, Rizo JM. PCOS: A Chronic Disease That Fails to Produce Adequately Specialized Pro-Resolving Lipid Mediators (SPMs). Biomedicines 2022; 10:biomedicines10020456. [PMID: 35203665 PMCID: PMC8962413 DOI: 10.3390/biomedicines10020456] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Revised: 02/08/2022] [Accepted: 02/10/2022] [Indexed: 12/31/2022] Open
Abstract
Introduction: Polycystic ovary syndrome (PCOS) is an endocrinological disorder that affects 5–15% of women of their reproductive age and is a frequent cause of infertility. Major symptoms include hyperandrogenism, ovulatory dysfunction, and often obesity and/or insulin resistance. PCOS also represents a state of chronic low-grade inflammation that is closely interlinked with the metabolic features. “Classical” pro-inflammatory lipid mediators such as prostaglandins (PG), leukotrienes (LT), or thromboxanes (TX) are derived from arachidonic acid (AA) and are crucial for the initial response. Resolution processes are driven by four families of so-called specialized pro-resolving mediators (SPMs): resolvins, maresins, lipoxins, and protectins. The study aimed to establish lipid mediator profiles of PCOS patients compared to healthy women to identify differences in their resolutive and pro-inflammatory lipid parameters. Material and Methods: Fifteen female patients (18–45 years) were diagnosed with PCOS according to Rotterdam criteria, and five healthy women, as a comparator group, were recruited for the study. The main outcome measures were: pro-inflammatory lipid mediators (PG, LT, TX) and their precursor AA, SPMs (resolvins, maresins, protectins, lipoxins), their precursors EPA, DHA, DPA, and their active biosynthesis pathway intermediates (18-HEPE, 17-HDHA, 14-HDHA). Results: The level of pro-inflammatory parameters in serum was significantly higher in PCOS-affected women. The ratio (sum of pro-inflammatory molecules)/(sum of SPMs plus hydroxylated intermediates) reflecting the inflammatory state was significantly lower in the group of healthy women. Conclusion: There is a strong pro-inflammatory state in PCOS patients. Further research will clarify whether supplementation with SPMs or their precursors may improve this state.
Collapse
Affiliation(s)
- Pedro-Antonio Regidor
- Exeltis Healthcare, Adalperostr. 84, 85737 Ismaning, Germany; (A.M.); (M.M.)
- OTC Chemo, Manuel Pombo Angulo 28-4th Floor, 28050 Madrid, Spain;
- Correspondence: ; Tel.: +49-894-5205-2919 or +49-173-893-8132; Fax: +49-8945-2052-9819
| | - Xavier de la Rosa
- Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital and Harvard Medical School, 60 Fenwood Road Boston, Boston, MA 02115, USA;
| | - Anna Müller
- Exeltis Healthcare, Adalperostr. 84, 85737 Ismaning, Germany; (A.M.); (M.M.)
| | - Manuela Mayr
- Exeltis Healthcare, Adalperostr. 84, 85737 Ismaning, Germany; (A.M.); (M.M.)
| | | | - Rafael Gracia Banzo
- Solutex GC SL, Parque Empresarial Utebo, Avda. Miguel Servet n° 81, 50180 Utebo, Spain;
| | - Jose Miguel Rizo
- OTC Chemo, Manuel Pombo Angulo 28-4th Floor, 28050 Madrid, Spain;
| |
Collapse
|
|
7
|
Hashemi Moghanjoughi P, Neshat S, Rezaei A, Heshmat-Ghahdarijani K. Is the Neutrophil-to-lymphocyte ratio an exceptional indicator for metabolic syndrome disease and outcomes? Endocr Pract 2021; 28:342-348. [PMID: 34838762 DOI: 10.1016/j.eprac.2021.11.083] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2021] [Revised: 11/09/2021] [Accepted: 11/17/2021] [Indexed: 12/11/2022]
Abstract
Metabolic syndrome is a syndrome compromised of elevated fasting blood glucose, increased blood pressure, central obesity, decreased high density lipoprotein, and increased triglyceride levels. Because of its growing incidence and prevalence, and the effect that it has on developing other non-communicable disease, the importance gets even more value. Prediction and control of this disease in early stages and in the cheapest way, is a crucial need these days. Due to role of chronic low-grade inflammation in metabolic syndrome, cytokines and inflammatory factors like interleukin-6 and Tumor necrosis factor-a have a critical effect on this phenomenon. Neutrophil to lymphocyte (NLR) ratio is an inflammatory marker that has an unchallenging availability, and has a reasonable price. NLR has a relation with obesity, type 2 diabetes, hypertension (HTN), blood cholesterol levels. This states that there should be a relation between NLR and metabolic syndrome. NLR as a low-grade inflammation marker indicates a positive relationship with central obesity. Also, studies indicate that diabetes' incidence, its severity, and its control contribute a relation with NLR. Hypertension, and hyperlipidemia, both can be noticed with higher NLRs. In this rapid review we are going to assess the association between metabolic syndrome and NLR.
Collapse
Affiliation(s)
| | - Sina Neshat
- M.D., School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Abbas Rezaei
- M.D., School of Medicine, Boushehr University of Medical Sciences, Boushehr, Iran
| | - Kiyan Heshmat-Ghahdarijani
- M.D., Assistant Professor, Heart Failure Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran.
| |
Collapse
|
|
8
|
Kumar S, Behl T, Sachdeva M, Sehgal A, Kumari S, Kumar A, Kaur G, Yadav HN, Bungau S. Implicating the effect of ketogenic diet as a preventive measure to obesity and diabetes mellitus. Life Sci 2020; 264:118661. [PMID: 33121986 DOI: 10.1016/j.lfs.2020.118661] [Citation(s) in RCA: 82] [Impact Index Per Article: 16.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Revised: 10/17/2020] [Accepted: 10/22/2020] [Indexed: 12/15/2022]
Abstract
Obesity and diabetes are the two major metabolic complications linked with bad eating habits and the sedentary (lazy) lifestyle. In the worst-case situation, metabolic problems are a causative factor for numerous other conditions. There is also an increased demand to control the emergence of such diseases. Dietary and lifestyle improvements contribute to their leadership at an elevated level. The present review, therefore, recommends the use of the ketogenic diet (KD) in obesity and diabetes treatment. The KD involves a diet that replaces glucose sugar with ketone bodies and is effective in numerous diseases, such as metabolic disorders, epileptic seizures, autosomal dominant polycystic disease of the kidney, cancers, peripheral neuropathy, and skeletal muscle atrophy. A lot of high profile pathways are available for KD action, including sustaining the metabolic actions on glucose sugar, suppressing insulin-like growth factor-1 (IGF1) and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathways, altering homeostasis of the systemic ketone bodies, contributing to lowering diabetic hyperketonemia, and others. The KD regulates the level of glucose sugar and insulin and can thus claim to be an effective diabetes approach. Thus, a stopgap between obesity and diabetes treatment can also be evidenced by KD.
Collapse
Affiliation(s)
- Sachin Kumar
- Department of Pharmaceutical Sciences & Technology, Maharaja Ranjit Singh Punjab Technical University, Bathinda, Punjab, India
| | - Tapan Behl
- Chitkara College of Pharmacy, Chitkara University, Punjab, India.
| | - Monika Sachdeva
- Fatimah College of Health Sciences, Al Ain, United Arab Emirates
| | - Aayush Sehgal
- Chitkara College of Pharmacy, Chitkara University, Punjab, India
| | - Shilpa Kumari
- Department of Pharmaceutical Sciences & Technology, Maharaja Ranjit Singh Punjab Technical University, Bathinda, Punjab, India
| | - Arun Kumar
- Chitkara College of Pharmacy, Chitkara University, Punjab, India
| | - Gagandeep Kaur
- Chitkara College of Pharmacy, Chitkara University, Punjab, India
| | | | - Simona Bungau
- Department of Pharmacy, Faculty of Pharmacy, University of Oradea, Romania
| |
Collapse
|
|
9
|
Affiliation(s)
- Zachary Bloomgarden
- Department of Medicine, Division of Endocrinology, Diabetes, and Bone DiseaseIcahn School of Medicine at Mount Sinai
New York
New York
| |
Collapse
|
|
10
|
Alissa EM, Algarni SA, Khaffji AJ, Al Mansouri NM. Impact of interlukin-6 on central obesity measures in women with polycystic ovarian syndrome. J OBSTET GYNAECOL 2020; 40:1133-1137. [PMID: 32157932 DOI: 10.1080/01443615.2019.1697219] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
Our aim was to investigate the relationship between plasma interleukin-6 (IL-6) levels with different measures of central obesity among Saudi women with and without polycystic ovarian syndrome (PCOS). One hundred and sixty-four Saudi females, between 22 and 38 years of age, with and without PCOS were enrolled in this case-control study. Physical examination and laboratory tests were completed for every subject. 2/3 of the study population were obese. Fasting serum insulin, plasma IL-6 levels and insulin resistance show significant increase among POCS than the controls (p<.05). Based on linear regression analysis, C-reactive protein (hs-CRP) was the only independent predictor of plasma IL-6 levels, accounting for 4% of the variability in plasma IL-6 (β = 0.217, p=.005, 95% CI: 0.049-0.275). Coexistence of metabolic and inflammatory factors in PCOS females is accompanied by central obesity which overpowers the effect of insulin resistance, contributing to higher plasma levels of IL-6 and CRP.Impact statementWhat is already known on this subject? Polycystic ovary syndrome (PCOS) is a cluster of many cardiovascular risk factors, but is also known as an inflammatory condition. Insulin resistance and abdominal obesity are classic components of PCOS. High circulatory levels of inflammatory markers in PCOS patients have been reported but it remains unclear whether their elevation is related to PCOS itself, or are a function of abdominal adiposity.What the results of this study add? The relationship between plasma interleukin-6 levels and different measures of central obesity was investigated among Saudi women with and without PCOS. Elevations of proinflammatory cytokines and inflammatory markers were reported in PCOS patients independently of insulin resistance. It remains to be established whether the proinflammatory state in PCOS is primarily due to inflamed adipose tissue.What the implications are of these findings for clinical practice and/or further research? The present study demonstrates that coexistence of metabolic and inflammatory factors in PCOS females are accompanied by central obesity which overpowers the effect of insulin resistance, contributing to higher plasma levels of IL-6 and CRP. Future studies including a larger population are needed to investigate the mechanisms by which IL-6 and hs-CRP promote cardiovascular risk in PCOS patients.
Collapse
Affiliation(s)
- Eman M Alissa
- Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.,Elemental Spectroscopy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Samiah A Algarni
- Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Azza J Khaffji
- Obstetrics and Gynecology in King Abdulaziz Hospital and Oncology Center, Jeddah, Saudi Arabia
| | | |
Collapse
|
|
11
|
Islam MN, Griffin TP, Sander E, Rocks S, Qazi J, Cabral J, McCaul J, McMorrow T, Griffin MD. Human mesenchymal stromal cells broadly modulate high glucose-induced inflammatory responses of renal proximal tubular cell monolayers. Stem Cell Res Ther 2019; 10:329. [PMID: 31744554 PMCID: PMC6862760 DOI: 10.1186/s13287-019-1424-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2019] [Revised: 09/08/2019] [Accepted: 09/24/2019] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND Renal proximal tubular epithelial cells (RPTEC) are dysfunctional in diabetic kidney disease (DKD). Mesenchymal stromal cells (MSC) may modulate DKD pathogenesis through anti-inflammatory mediators. This study aimed to investigate the pro-inflammatory effect of extended exposure to high glucose (HG) concentration on stable RPTEC monolayers and the influence of MSC on this response. METHODS Morphologically stable human RPTEC/TERT1 cell monolayers were exposed to 5 mM and 30 mM (HG) D-glucose or to 5 mM D-glucose + 25 mM D-mannitol (MAN) for 5 days with sequential immunoassays of supernatants and end-point transcriptomic analysis by RNA sequencing. Under the same conditions, MSC-conditioned media (MSC-CM) or MSC-containing transwells were added for days 4-5. Effects of CM from HG- and MAN-exposed RPTEC/MSC co-cultures on cytokine secretion by monocyte-derived macrophages were determined. RESULTS After 72-80 h, HG resulted in increased RPTEC/TERT1 release of interleukin (IL)-6, IL-8, monocyte chemoattractant protein (MCP)-1 and neutrophil gelatinase-associated lipocalin (NGAL). The HG pro-inflammatory effect was attenuated by concentrated (10×) MSC-CM and, to a greater extent, by MSC transwell co-culture. Bioinformatics analysis of RNA sequencing data confirmed a predominant effect of HG on inflammation-related mediators and biological processes/KEGG pathways in RPTEC/TERT1 stable monolayers as well as the non-contact-dependent anti-inflammatory effect of MSC. Finally, CM from HG-exposed RPTEC/MSC transwell co-cultures was associated with attenuated secretion of inflammatory mediators by macrophages compared to CM from HG-stimulated RPTEC alone. CONCLUSIONS Stable RPTEC monolayers demonstrate delayed pro-inflammatory response to HG that is attenuated by close proximity to human MSC. In DKD, this MSC effect has potential to modulate hyperglycemia-associated RPTEC/macrophage cross-talk.
Collapse
Affiliation(s)
- Md Nahidul Islam
- Regenerative Medicine Institute (REMEDI) at CÚRAM Centre for Research in Medical Devices, School of Medicine, National University of Ireland Galway, Galway, REMEDI, Biomedical Sciences, Corrib Village, Dangan, Galway, H91 TK33, Ireland
| | - Tomás P Griffin
- Regenerative Medicine Institute (REMEDI) at CÚRAM Centre for Research in Medical Devices, School of Medicine, National University of Ireland Galway, Galway, REMEDI, Biomedical Sciences, Corrib Village, Dangan, Galway, H91 TK33, Ireland.,Centre for Endocrinology, Diabetes and Metabolism, Galway University Hospitals, Galway, Ireland
| | - Elizabeth Sander
- Regenerative Medicine Institute (REMEDI) at CÚRAM Centre for Research in Medical Devices, School of Medicine, National University of Ireland Galway, Galway, REMEDI, Biomedical Sciences, Corrib Village, Dangan, Galway, H91 TK33, Ireland
| | - Stephanie Rocks
- Regenerative Medicine Institute (REMEDI) at CÚRAM Centre for Research in Medical Devices, School of Medicine, National University of Ireland Galway, Galway, REMEDI, Biomedical Sciences, Corrib Village, Dangan, Galway, H91 TK33, Ireland
| | - Junaid Qazi
- Regenerative Medicine Institute (REMEDI) at CÚRAM Centre for Research in Medical Devices, School of Medicine, National University of Ireland Galway, Galway, REMEDI, Biomedical Sciences, Corrib Village, Dangan, Galway, H91 TK33, Ireland
| | - Joana Cabral
- Regenerative Medicine Institute (REMEDI) at CÚRAM Centre for Research in Medical Devices, School of Medicine, National University of Ireland Galway, Galway, REMEDI, Biomedical Sciences, Corrib Village, Dangan, Galway, H91 TK33, Ireland
| | - Jasmin McCaul
- School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Dublin, Ireland
| | - Tara McMorrow
- School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Dublin, Ireland
| | - Matthew D Griffin
- Regenerative Medicine Institute (REMEDI) at CÚRAM Centre for Research in Medical Devices, School of Medicine, National University of Ireland Galway, Galway, REMEDI, Biomedical Sciences, Corrib Village, Dangan, Galway, H91 TK33, Ireland.
| |
Collapse
|
|
12
|
Teng F, Wu J, Wei M, Yang Y. Expression of intercellular adhesion molecule-1 in umbilical vascular of pregnant women with gestational diabetes mellitus and the clinical significance. Exp Ther Med 2018; 15:914-918. [PMID: 29399099 PMCID: PMC5772894 DOI: 10.3892/etm.2017.5475] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2017] [Accepted: 11/01/2017] [Indexed: 01/11/2023] Open
Abstract
The purpose of this study was to investigate the expression of intercellular adhesion molecule-1 (ICAM-1) in umbilical vascular of pregnant women with gestational diabetes mellitus (GDM) and the clinical significance. A total of 103 pregnant women with GDM were selected in the First Hospital of Lanzhou University and the Second Affiliated Hospital of Xi'an Jiaotong University from January 2016 to December 2016 as GDM group. At the same time, 106 normal pregnant women were selected as control group. i) General information of the two groups of pregnant women including age, gestational age, gravida, parity, BMI, systolic blood pressure and diastolic blood pressure were compared; ii) the laboratory indicators of the two groups of pregnant women including fasting blood glucose, glycosylated hemoglobin (HbA1c), umbilical cord arterial pH, partial pressure of oxygen (pO2) and carbon dioxide (pCO2) in umbilical artery were compared; iii) expression of ICAM-1 in umbilical vascular was detected by immunohistochemistry; iv) expression levels of ICAM-1 in umbilical vascular of the two groups of patients were compared. i) There was no significant difference in the age, smoking, gestational age, gravida, parity, BMI, systolic blood pressure and diastolic blood pressure between the two groups (p>0.05); ii) no significant differences in HbA1c, umbilical cord arterial pH, pO2 and pCO2 were found between the groups (p>0.05); iii) ICAM-1 was expressed in umbilical vessels of both groups of pregant women; iv) no significant differences in expression levels of ICAM-1 in umbilical artery and umbilical vein endothelial cells were found between the groups (p>0.05). Therefore, GDM patients with good blood glucose control have no umbilical cord endothelial cell damage.
Collapse
Affiliation(s)
- Fei Teng
- Department of Obstetrics and Gynecology, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China
| | - Jinfang Wu
- Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China
| | - Min Wei
- Department of Obstetrics and Gynecology, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China
| | - Yongxiu Yang
- Department of Obstetrics and Gynecology, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China
| |
Collapse
|
|
13
|
New Insights into the Mechanisms of Chinese Herbal Products on Diabetes: A Focus on the "Bacteria-Mucosal Immunity-Inflammation-Diabetes" Axis. J Immunol Res 2017; 2017:1813086. [PMID: 29164155 PMCID: PMC5661076 DOI: 10.1155/2017/1813086] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2017] [Revised: 06/27/2017] [Accepted: 07/25/2017] [Indexed: 12/25/2022] Open
Abstract
Diabetes, especially type 2, has been rapidly increasing all over the world. Although many drugs have been developed and used to treat diabetes, side effects and long-term efficacy are of great challenge. Therefore, natural health product and dietary supplements have been of increasing interest alternatively. In this regard, Chinese herbs and herbal products have been considered a rich resource of product development. Although increasing evidence has been produced from various scientific studies, the mechanisms of action are lacking. Here, we have proposed that many herbal monomers and formulae improve glucose homeostasis and diabetes through the BMID axis; B represents gut microbiota, M means mucosal immunity, I represents inflammation, and D represents diabetes. Chinese herbs have been traditionally used to treat diabetes, with minimal side and toxic effects. Here, we reviewed monomers such as berberine, ginsenoside, M. charantia extract, and curcumin and herbal formulae such as Gegen Qinlian Decoction, Danggui Liuhuang Decoction, and Huanglian Wendan Decoction. This review was intended to provide new perspectives and strategies for future diabetes research and product.
Collapse
|
|
14
|
Kim HM, Kim YM, Huh JH, Lee ES, Kwon MH, Lee BR, Ko HJ, Chung CH. α-Mangostin ameliorates hepatic steatosis and insulin resistance by inhibition C-C chemokine receptor 2. PLoS One 2017; 12:e0179204. [PMID: 28598982 PMCID: PMC5466328 DOI: 10.1371/journal.pone.0179204] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2017] [Accepted: 05/25/2017] [Indexed: 12/22/2022] Open
Abstract
Obesity induces various metabolic diseases such as dyslipidemia, nonalcoholic fatty liver disease (NAFLD), and type 2 diabetes. Fat expansion in adipose tissue induces adipose tissue dysfunction and inflammation, insulin resistance, and other metabolic syndromes. α-Mangostin (α-MG) has been previously studied for its anti-cancer, anti-inflammatory, and antioxidant activities. In this study, we investigated the effects of α-MG on adipose tissue inflammation and hepatic steatosis. We categorized study animals into four groups: regular diet control mice, RD mice treated with α-MG, high fat diet-induced obese mice, and HFD mice treated with α-MG. α-MG treatment significantly reduced not only the body, liver, and fat weights, but also plasma glucose, insulin, and triglyceride levels in HFD mice. Additionally, adiponectin levels of α-MG-treated mice were significantly higher than those of control HFD mice. Immunohistochemistry of liver and adipose tissue showed that CD11c expression was reduced in α-MG fed obese mice. α-MG treatment of HFD mice down-regulated the adipose-associated inflammatory cytokines and CCR2 in both liver and adipose tissue. Moreover, glucose tolerance and insulin sensitivity were significantly improved in α-MG fed obese mice. α-Mangostin ameliorates adipose inflammation and hepatic steatosis in HFD-induced obese mice.
Collapse
Affiliation(s)
- Hong Min Kim
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - You Mi Kim
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Ji Hye Huh
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Eun Soo Lee
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Mi Hye Kwon
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Bo Ra Lee
- Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon, Korea
| | - Hyun-Jeong Ko
- Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon, Korea
| | - Choon Hee Chung
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
- * E-mail:
| |
Collapse
|
|
15
|
Tziastoudi M, Stefanidis I, Hadjigeorgiou GM, Stravodimos K, Zintzaras E. A systematic review and meta-analysis of genetic association studies for the role of inflammation and the immune system in diabetic nephropathy. Clin Kidney J 2017; 10:293-300. [PMID: 28616206 PMCID: PMC5466089 DOI: 10.1093/ckj/sfx008] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2016] [Accepted: 01/09/2017] [Indexed: 12/15/2022] Open
Abstract
Background: Despite the certain contribution of metabolic and haemodynamic factors in diabetic nephropathy (DN), many lines of evidence highlight the role of immunologic and inflammatory mechanisms. To elucidate the contribution of the immune system in the development of DN, we explored the contribution of gene variants (polymorphisms) in relevant pathophysiologic pathways. Methods: We selected six major pathways related to immune response from the Kyoto Encyclopaedia of Genes and Genomes database and thereafter we traced all available genetic association studies (GASs) involving gene variants in these pathways from PubMed and HuGE Navigator. Finally, we used meta-analytic methods for synthesizing the results of the GASs. Results: One hundred three GASs were retrieved that included 443 variants from 75 genes. Of those variants, 138 were meta-analysed and 61 produced significant results; seven variants were investigated in single GASs and showed significant association. Variants in CCL2, CCR5, IL6, IL8, EPO, IL1A, IL1B, IL100, IL1RN, GHRL, MMP9, TGFB1, VEGFA, MMP3, MMP12, IL12RB1, PRKCE, TNF and TNFRSF19 genes were associated with an increased risk of DN. Conclusions: There is evidence that variants related with immunologic response affect the course of DN. However, the present results should be interpreted with caution since the current number of available GASs is limited.
Collapse
Affiliation(s)
- Maria Tziastoudi
- Department of Biomathematics, School of Medicine, University of Thessaly, Larissa, Greece
| | - Ioannis Stefanidis
- Department of Nephrology, School of Medicine, University of Thessaly, Larissa, Greece
| | | | - Konstantinos Stravodimos
- 1st University Department of Urology, Laiko General Hospital, National and Kapodistrian Athens University, Athens, Greece
| | - Elias Zintzaras
- Department of Biomathematics, School of Medicine, University of Thessaly, Larissa, Greece.,Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Tufts University School of Medicine, Boston, MA, USA
| |
Collapse
|
|
16
|
C-C chemokine receptor 2 inhibitor ameliorates hepatic steatosis by improving ER stress and inflammation in a type 2 diabetic mouse model. PLoS One 2015; 10:e0120711. [PMID: 25816097 PMCID: PMC4376739 DOI: 10.1371/journal.pone.0120711] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2014] [Accepted: 01/26/2015] [Indexed: 12/11/2022] Open
Abstract
Hepatic steatosis is the accumulation of excess fat in the liver. Recently, hepatic steatosis has become more important because it occurs in the patients with obesity, type 2 diabetes, and hyperlipidemia and is associated with endoplasmic reticulum (ER) stress and insulin resistance. C-C chemokine receptor 2 (CCR2) inhibitor has been reported to improve inflammation and glucose intolerance in diabetes, but its mechanisms remained unknown in hepatic steatosis. We examined whether CCR2 inhibitor improves ER stress-induced hepatic steatosis in type 2 diabetic mice. In this study, db/db and db/m (n = 9) mice were fed CCR2 inhibitor (2 mg/kg/day) for 9 weeks. In diabetic mice, CCR2 inhibitor decreased plasma and hepatic triglycerides levels and improved insulin sensitivity. Moreover, CCR2 inhibitor treatment decreased ER stress markers (e.g., BiP, ATF4, CHOP, and XBP-1) and inflammatory cytokines (e.g., TNFα, IL-6, and MCP-1) while increasing markers of mitochondrial biogenesis (e.g., PGC-1α, Tfam, and COX1) in the liver. We suggest that CCR2 inhibitor may ameliorate hepatic steatosis by reducing ER stress and inflammation in type 2 diabetes mellitus.
Collapse
|
|
17
|
Currie G, McKay G, Delles C. Biomarkers in diabetic nephropathy: Present and future. World J Diabetes 2014; 5:763-776. [PMID: 25512779 PMCID: PMC4265863 DOI: 10.4239/wjd.v5.i6.763] [Citation(s) in RCA: 81] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2014] [Revised: 10/03/2014] [Accepted: 10/27/2014] [Indexed: 02/05/2023] Open
Abstract
Diabetic nephropathy (DN) is the leading cause of end stage renal disease in the Western world. Microalbuminuria (MA) is the earliest and most commonly used clinical index of DN and is independently associated with cardiovascular risk in diabetic patients. Although MA remains an essential tool for risk stratification and monitoring disease progression in DN, a number of factors have called into question its predictive power. Originally thought to be predictive of future overt DN in 80% of patients, we now know that only around 30% of microalbuminuric patients progress to overt nephropathy after 10 years of follow up. In addition, advanced structural alterations in the glomerular basement membrane may already have occurred by the time MA is clinically detectable.Evidence in recent years suggests that a significant proportion of patients with MA can revert to normoalbuminuria and the concept of nonalbuminuric DN is well-documented, reflecting the fact that patients with diabetes can demonstrate a reduction in glomerular filtration rate without progressing from normo-to MA. There is an unmet clinical need to identify biomarkers with potential for earlier diagnosis and risk stratification in DN and recent developments in this field will be the focus of this review article.
Collapse
|
|
18
|
García-García PM, Getino-Melián MA, Domínguez-Pimentel V, Navarro-González JF. Inflammation in diabetic kidney disease. World J Diabetes 2014; 5:431-443. [PMID: 25126391 PMCID: PMC4127580 DOI: 10.4239/wjd.v5.i4.431] [Citation(s) in RCA: 95] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2013] [Revised: 02/24/2014] [Accepted: 06/11/2014] [Indexed: 02/05/2023] Open
Abstract
Diabetes mellitus entails significant health problems worldwide. The pathogenesis of diabetes is multifactorial, resulting from interactions of both genetic and environmental factors that trigger a complex network of pathophysiological events, with metabolic and hemodynamic alterations. In this context, inflammation has emerged as a key pathophysiology mechanism. New pathogenic pathways will provide targets for prevention or future treatments. This review will focus on the implications of inflammation in diabetes mellitus, with special attention to inflammatory cytokines.
Collapse
|
|
19
|
Soewondo P, Ferrario A, Tahapary DL. Challenges in diabetes management in Indonesia: a literature review. Global Health 2013. [PMID: 24299164 DOI: 10.1186/1744-8603-9-63/tables/5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/20/2023] Open
Abstract
BACKGROUND AND OBJECTIVES The expanding diabetes epidemic worldwide could have potentially devastating effects on the development of healthcare systems and economies in emerging countries, both in terms of direct health care costs and loss of working time and disability. This study aims to review evidence on the burden, expenditure, complications, treatment, and outcomes of diabetes in Indonesia and its implications on the current health system developments. METHODS We conducted a comprehensive literature review together with a review of unpublished data from the Ministry of Health and a public health insurer (Askes). Studies presenting evidence on prevalence, incidence, mortality, costs, complications and cost of complications, treatment, and outcomes were included in the analysis. RESULTS A limited number of international, national and local studies on the burden and cost of diabetes in Indonesia were identified. National survey data suggests that in 2007 the prevalence of diabetes was 5.7%, of which more than 70% of cases were undiagnosed. This estimate hides large intracountry variation. There was very limited data available on direct costs and no data on indirect costs. The most commonly-identified complication was diabetic neuropathy. DISCUSSION There were a number of limitations in the data retrieved including the paucity of data representative at the national level, lack of a clear reference date, lack of data from primary care, and lack of data from certain regions of the country. CONCLUSIONS If left unaddressed, the growing prevalence of diabetes in the country will pose a tremendous challenge to the Indonesian healthcare system, particularly in view of the Government's 2010 mandate to achieve universal health coverage by 2014. Essential steps to address this issue would include: placing diabetes and non-communicable diseases high on the Government agenda and creating a national plan; identifying disparities and priority areas for Indonesia; developing a framework for coordinated actions between all relevant stakeholders.
Collapse
Affiliation(s)
- Pradana Soewondo
- Division of Metabolism and Endocrinology, Department of Internal Medicine, Faculty of Medicine University of Indonesia, Dr, Cipto Mangunkusumo Hospital, Jakarta, Indonesia.
| | | | | |
Collapse
|
|
20
|
Soewondo P, Ferrario A, Tahapary DL. Challenges in diabetes management in Indonesia: a literature review. Global Health 2013; 9:63. [PMID: 24299164 PMCID: PMC3901560 DOI: 10.1186/1744-8603-9-63] [Citation(s) in RCA: 78] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2013] [Accepted: 11/11/2013] [Indexed: 01/18/2023] Open
Abstract
Background and objectives The expanding diabetes epidemic worldwide could have potentially devastating effects on the development of healthcare systems and economies in emerging countries, both in terms of direct health care costs and loss of working time and disability. This study aims to review evidence on the burden, expenditure, complications, treatment, and outcomes of diabetes in Indonesia and its implications on the current health system developments. Methods We conducted a comprehensive literature review together with a review of unpublished data from the Ministry of Health and a public health insurer (Askes). Studies presenting evidence on prevalence, incidence, mortality, costs, complications and cost of complications, treatment, and outcomes were included in the analysis. Results A limited number of international, national and local studies on the burden and cost of diabetes in Indonesia were identified. National survey data suggests that in 2007 the prevalence of diabetes was 5.7%, of which more than 70% of cases were undiagnosed. This estimate hides large intracountry variation. There was very limited data available on direct costs and no data on indirect costs. The most commonly-identified complication was diabetic neuropathy. Discussion There were a number of limitations in the data retrieved including the paucity of data representative at the national level, lack of a clear reference date, lack of data from primary care, and lack of data from certain regions of the country. Conclusions If left unaddressed, the growing prevalence of diabetes in the country will pose a tremendous challenge to the Indonesian healthcare system, particularly in view of the Government’s 2010 mandate to achieve universal health coverage by 2014. Essential steps to address this issue would include: placing diabetes and non-communicable diseases high on the Government agenda and creating a national plan; identifying disparities and priority areas for Indonesia; developing a framework for coordinated actions between all relevant stakeholders.
Collapse
Affiliation(s)
- Pradana Soewondo
- Division of Metabolism and Endocrinology, Department of Internal Medicine, Faculty of Medicine University of Indonesia, Dr, Cipto Mangunkusumo Hospital, Jakarta, Indonesia.
| | | | | |
Collapse
|
|
21
|
Kovács G, Buday B, Fék A, Literáti-Nagy B, Pauer J, Pach P, Vitai M, Péterfai É, Korányi L. Metabolic differences in healthy first-degree female relatives of type 2 diabetic patients. Orv Hetil 2013; 154:1747-53. [DOI: 10.1556/oh.2013.29737] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Introduction: Today the prevalence of type 2 diabetes reached an epidemic level. It is known that type 2 diabetes could only be prevented before the manifestation, during the “prediabetic” state, urging the development of diagnostic tests to recognize the group at risk in time. Aim: The authors explored metabolic differences between healthy, normal glucose tolerant, normal insulin resistant females having first degree relatives with and without type 2 diabetes. Method: Healthy, normal insulin sensitive females without (n = 26) and with (n = 18) type 2 diabetic relatives were investigated. Results: Healthy females with first degree diabetic relatives had lower low density lipoproteins and higher high density lipoproteins as well as higher glucose and insulin levels at the 120 min of oral glucose test as compared to those without first degree diabetic relatives. Conclusions: These results suggest that the appearance of insulin resistance is preceded by hepatic insulin resistance and impaired lipid metabolism in the symptom-free prediabetic period of genetically suceptible females. Orv. Hetil., 154 (44), 1747–1753.
Collapse
Affiliation(s)
- Györgyi Kovács
- Budapesti Műszaki és Gazdaságtudományi Egyetem Vegyészmérnöki és Biomérnöki Kar Budapest
| | - Barbara Buday
- DRC Gyógyszervizsgáló Központ Kft. Balatonfüred Ady E. u. 12. 8230
| | - Attila Fék
- Therapiezentrum Wolkersdorf Schwabach Németország
| | | | - József Pauer
- DRC Gyógyszervizsgáló Központ Kft. Balatonfüred Ady E. u. 12. 8230
| | - Péter Pach
- Bay Zoltán Alkalmazott Kutatási Közhasznú Nonprofit Kft. Budapest
| | - Márta Vitai
- DRC Gyógyszervizsgáló Központ Kft. Balatonfüred Ady E. u. 12. 8230
| | - Éva Péterfai
- DRC Gyógyszervizsgáló Központ Kft. Balatonfüred Ady E. u. 12. 8230
| | - László Korányi
- DRC Gyógyszervizsgáló Központ Kft. Balatonfüred Ady E. u. 12. 8230
| |
Collapse
|
|
22
|
Faghihimani E, Aminorroaya A, Rezvanian H, Adibi P, Ismail-Beigi F, Amini M. Salsalate improves glycemic control in patients with newly diagnosed type 2 diabetes. Acta Diabetol 2013; 50:537-43. [PMID: 21938543 DOI: 10.1007/s00592-011-0329-2] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2011] [Accepted: 09/08/2011] [Indexed: 02/06/2023]
Abstract
Chronic inflammation contributes to insulin resistance and type 2 diabetes mellitus (T2DM). We investigated whether treatment with salsalate, an anti-inflammatory medication, improves glycemia in a group of newly diagnosed drug-naïve patients with T2DM. The study was a randomized, double-blind, placebo-controlled trial. Diagnosis of T2DM was made within 2 months of enrollment, and participants had not received any anti-glycemic agent. Sixty adults were randomized to receive salsalate (3 g/day) or placebo for 12 weeks. Fasting plasma glucose and insulin, glucose 2 h after 75 g oral glucose, HbA1C, lipid profile, HOMA-IR, and HOMA-B were determined before and after treatment. Salsalate reduced fasting glucose from 6.3 ± 0.2 mmol/l to 5.4 ± 0.2 mmol/l (P < 0.01) and TG from 1.9 ± 0.2 mmol/l to 1.5 ± 0.2 mmol/l (P < 0.03). Fasting insulin levels were increased in the salsalate group from 18.8 ± 1.6 to 21.6 ± 3.9, while they decreased in the placebo group. HbA1c rose in the placebo group from 6.2% ± 0.2 to 7.9% ± 1.1 mmol/mol, but decreased in the intervention group from 6.1% ± 0.5 to 5.6% ± 0.2 mmol/mol (P < 0.04 for between-group comparison). HOMA-IR did not change but HOMA-B increased ~1.7-fold (P = 0.06) in the salsalate group. The results show that salsalate is effective in improving glycemic control in newly diagnosed naïve patients with T2DM. The optimal duration of treatment with salsalate and sustainability of its effect requires further study (IRCT138709011465N1).
Collapse
Affiliation(s)
- Elham Faghihimani
- Isfahan Endocrinology and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran,
| | | | | | | | | | | |
Collapse
|
|
23
|
Lee MC, Lee CH, Shu CC, Pong WB, Lan CC, Wang JY, Lee LN, Chao KM. The impact of diabetes mellitus and its control on the development of tuberculosis: a nationwide longitudinal study in Taiwan. Pharmacoepidemiol Drug Saf 2013. [DOI: 10.1002/pds.3491] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Affiliation(s)
- Ming-Chia Lee
- Department of Pharmacy; Buddhist Tzu Chi General Hospital; Taipei Branch Taiwan
| | - Chih-Hsin Lee
- Graduate Institute of Biomedical Electronics and Bioinformatics; National Taiwan University; Taipei Taiwan
- Department of Internal Medicine; Buddhist Tzu Chi General Hospital; Taipei Branch Taiwan
- School of Medicine; Tzu Chi University; Hualien Taiwan
| | - Chin-Chung Shu
- Department of Traumatology; National Taiwan University Hospital; Taipei Taiwan
| | - Wei-Bang Pong
- Department of Internal Medicine; Buddhist Tzu Chi General Hospital; Taipei Branch Taiwan
| | - Chou-Chin Lan
- Department of Internal Medicine; Buddhist Tzu Chi General Hospital; Taipei Branch Taiwan
- School of Medicine; Tzu Chi University; Hualien Taiwan
| | - Jann-Yuan Wang
- Department of Internal Medicine; National Taiwan University Hospital; Taipei Taiwan
| | - Li-Na Lee
- Department of Laboratory Medicine; National Taiwan University Hospital; Taipei Taiwan
| | - Kun-Mao Chao
- Graduate Institute of Biomedical Electronics and Bioinformatics; National Taiwan University; Taipei Taiwan
| |
Collapse
|
|
24
|
Pauer J, Fék A, Buday B, Literáti-Nagy B, Pach P, Vitai M, Péterfai E, Korányi L. [Metabolic alteration in healthy men with first degree type 2 diabetic relatives]. Orv Hetil 2013; 154:178-86. [PMID: 23395743 DOI: 10.1556/oh.2013.29538] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
INTRODUCTION The recognition of prediabetic patients with the genetic risk of type 2 diabetes is very important as prediabetes is the last stage when manifestation of diabetes could be prevented by life style modification or drug intervention. This suggests the need for diagnostic processes to trace the risk of patients in time. AIMS The authors looked for metabolic differences between age and BMI in adjusted healthy men with or without first degree type 2 diabetic relatives. METHODS The study included 73 healthy men (21 with and 52 without) first-degree relatives with type 2 diabetes. RESULTS Total body and muscle tissue glucose utilization, glucose tolerance did not differ between the two groups, but free fatty acid levels were not suppressed by glucose load in subjects with diabetic relatives. In addition the body fat content, leptin and IL-6 levels were higher, while adiponectin and the free fatty acid/adiponectin ratio were significantly lover in healthy men with diabetic relatives. In this group HDL cholesterol, and the large buoyant LDL fraction were lower whereas the high density LDL - small molecular lipid fraction was higher than those measured in subjects without diabetic relatives. CONCLUSIONS These data suggest that deteriorations of insulin sensitivity and glucose tolerance is preceded by disturbances of fatty acid metabolism. The observed alteration in free fatty acid/adiponectin ratio, and/or the absence of free fatty acid suppression during glucose tolerance tests could be a screening tool for diabetes risk among men.
Collapse
Affiliation(s)
- József Pauer
- DRC Gyógyszervizsgáló Központ Kft. Balatonfüred Ady Endre u. 12. 8230.
| | | | | | | | | | | | | | | |
Collapse
|
|
25
|
Moresco RN, Sangoi MB, De Carvalho JAM, Tatsch E, Bochi GV. Diabetic nephropathy: traditional to proteomic markers. Clin Chim Acta 2013; 421:17-30. [PMID: 23485645 DOI: 10.1016/j.cca.2013.02.019] [Citation(s) in RCA: 72] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2012] [Revised: 02/06/2013] [Accepted: 02/09/2013] [Indexed: 01/11/2023]
Abstract
Diabetic nephropathy (DN) is one of the major microvascular complications of diabetes and it is defined as a rise in the urinary albumin excretion (UAE) rate and abnormal renal function. Currently, changes in albuminuria are considered a hallmark of onset or progression of DN. However, some patients with diabetes have advanced renal pathological changes and progressive kidney function decline even if urinary albumin levels are in the normal range, indicating that albuminuria is not the perfect marker for the early detection of DN. The present article provides an overview of the literature reporting some relevant biomarkers that have been found to be associated with DN and that potentially may be used to predict the onset and/or monitor the progression of nephropathy. In particular, biomarkers of renal damage, inflammation, and oxidative stress may be useful tools for detection at an early stage or prediction of DN. Proteomic-based biomarker discovery represents a novel strategy to improve diagnosis, prognosis and treatment of DN; however, proteomics-based approaches are not yet available in most of the clinical chemistry laboratories. The use of a panel with a combination of biomarkers instead of urinary albumin alone seems to be an interesting approach for early detection of DN, including markers of glomerular damage (e.g., albumin), tubular damage (e.g., NAG and KIM-1), inflammation (e.g., TNF-α) and oxidative stress (e.g., 8-OHdG) because these mechanisms contribute to the development and outcomes of this disease.
Collapse
Affiliation(s)
- Rafael N Moresco
- Laboratório de Pesquisa em Bioquímica Clínica, Departamento de Análises Clínicas e Toxicológicas, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
| | | | | | | | | |
Collapse
|
|
26
|
Kidney proximal tubular epithelial-specific overexpression of netrin-1 suppresses inflammation and albuminuria through suppression of COX-2-mediated PGE2 production in streptozotocin-induced diabetic mice. THE AMERICAN JOURNAL OF PATHOLOGY 2012; 181:1991-2002. [PMID: 23041393 DOI: 10.1016/j.ajpath.2012.08.014] [Citation(s) in RCA: 60] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/02/2012] [Revised: 07/25/2012] [Accepted: 08/15/2012] [Indexed: 01/15/2023]
Abstract
Inflammation plays a key role in the development and progression of diabetic kidney disease; however, the role of the anti-inflammatory molecule netrin-1 in diabetic kidney disease is unknown. We examined the role of netrin-1 in diabetes-induced kidney inflammation and injury using tubule-specific netrin-1 transgenic mice. Diabetes was induced using streptozotocin in wild-type and netrin-1 transgenic animals. Kidney function, fibrosis, glucose excretion, albuminuria, and inflammation were evaluated. The mechanism of netrin-1-induced suppression of inflammation was studied in vitro using a proximal tubular epithelial cell line. Diabetes was associated with increased infiltration of neutrophils and macrophages, chemokine expression, and tubular epithelial cell apoptosis in kidney. These changes were minimal in kidney of netrin-1 transgenic mice. In addition, diabetes induced a large increase in the excretion of prostaglandin E2 (PGE2) in urine, which was suppressed in netrin-1 transgenic mice. Netrin-1-induced suppression of PGE2 production was mediated through suppression of NFκB-mediated cyclooxygenase-2 (COX-2) in renal tubular epithelial cells. Furthermore, netrin-1 also increased albumin uptake by proximal tubular epithelial cells through the PI3K and ERK pathways without increasing glucose uptake. These findings suggest that netrin-1 is a major regulator of inflammation and apoptosis in diabetic nephropathy and may be a useful therapeutic molecule for treating chronic kidney diseases such as diabetic nephropathy.
Collapse
|
|
27
|
Aydogdu A, Tasci I, Tapan S, Basaran Y, Aydogan U, Meric C, Sonmez A, Aydogdu S, Akbulut H, Taslipinar A, Uckaya G, Azal O. High plasma level of long Pentraxin 3 is associated with insulin resistance in women with polycystic ovary syndrome. Gynecol Endocrinol 2012; 28:722-5. [PMID: 22304663 DOI: 10.3109/09513590.2011.652719] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
OBJECTIVES Polycystic ovary syndrome (PCOS) is characterized by insulin resistance. Chronic low-grade inflammation has been anticipated to play role in the pathogenesis of both insulin resistance and atherosclerosis. Pentraxin 3 (PTX3) is an inflammatory mediator synthesized in a variety of cells and tissues including heart, vascular endothelial cells, macrophages and adipocytes. In the present study, serum PTX3 level and its relationship with insulin resistance were investigated in patients with PCOS. MATERIALS AND METHODS Forty patients with PCOS and 40 age- and body mass index (BMI)-matched healthy controls were enrolled in the study. PTX3 and high-sensitivity C-reactive protein (hs-CRP) levels were determined by enzyme immunoassay (EIA). Insulin resistance was calculated by the homeostasis model assessment of insulin resistance (HOMA-IR) formula. RESULTS Plasma levels of PTX3, hs-CRP and HOMA-IR scores were all significantly higher (p = 0.021, p = 0.002 and p = 0.0001, respectively) in women with PCOS compared with healthy controls. Blood PTX3 level correlated positively with hs-CRP, BMI, waist-to-hip ratio (WHR), HOMA-IR and negatively with high-density lipoprotein cholesterol level (p < 0.05, for all). After adjustment for age and BMI, PTX3, total testosterone levels and BMI remained as independent predictors of HOMA-IR scores (p < 0.05, for all). CONCLUSION PTX3 level is increased in patients with PCOS in concordance with insulin resistance.
Collapse
Affiliation(s)
- Aydogan Aydogdu
- Department of Endocrinology and Metabolism, Gulhane School of Medicine, Etlik, Ankara, Turkey.
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
28
|
Xing LJ, Zhang L, Liu T, Hua YQ, Zheng PY, Ji G. Berberine reducing insulin resistance by up-regulating IRS-2 mRNA expression in nonalcoholic fatty liver disease (NAFLD) rat liver. Eur J Pharmacol 2011; 668:467-471. [PMID: 21839075 DOI: 10.1016/j.ejphar.2011.07.036] [Citation(s) in RCA: 68] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2011] [Revised: 06/29/2011] [Accepted: 07/24/2011] [Indexed: 01/28/2023]
Abstract
This study was performed to investigate the molecular mechanism and the therapeutic effect of berberine on nonalcoholic fatty liver disease (NAFLD). Rat models were given a high-fat diet (42% kcal) until they developed NAFLD, then were given normal saline (n=10), berberine (n-=10) at 187.5mg/kg/day, or pioglitazone (n=10) at 10.0mg/kg/day intragastrically for 4 weeks, respectively, and evaluated by hyperinsulinemic euglycemic clamping for insulin sensitivity. Serum biochemical markers and liver triglyceride (TG) were analyzed, real-time RT-PCR for mRNA expression and western blotting for protein expression of insulin receptor (IR) and insulin receptor substrate-2 (IRS-2) in liver tissues were performed, and hepatic histopathology in the rat models with NAFLD at the end of treatment was compared with normal controls (n=10). The NAFLD rats developed insulin resistance, showing increased fasting blood glucose and insulin levels, decreased glucose infusion rate, increased weight of epididymal fat (g/100g body weight), obvious hepatic steatosis and inflammation, and down-regulated IRS-2 mRNA and protein levels compared with normal controls (all P<0.05). In comparison with those treated with saline, model rats treated with berberine or pioglitazone underwent significant recovery, including up-regulated IRS-2 mRNA and protein (all P<0.05). Our results indicate that berberine may improve insulin resistance of NAFLD by up-regulating mRNA and protein levels of IRS-2, a key molecule in the insulin signaling pathway, suggesting that berberine may be used to treat NAFLD.
Collapse
Affiliation(s)
- Lian-Jun Xing
- Institute of Digestive Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, China
| | | | | | | | | | | |
Collapse
|
|
29
|
Højbjerre L, Sonne MP, Alibegovic AC, Nielsen NB, Dela F, Vaag A, Bruun JM, Stallknecht B. Impact of physical inactivity on adipose tissue low-grade inflammation in first-degree relatives of type 2 diabetic patients. Diabetes Care 2011; 34:2265-72. [PMID: 21836102 PMCID: PMC3177724 DOI: 10.2337/dc11-0631] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE First-degree relatives (FDRs) of patients with type 2 diabetes may exhibit a disproportionately elevated risk of developing insulin resistance, obesity, and type 2 diabetes when exposed to physical inactivity, which to some unknown extent may involve low-grade inflammation. We investigated whether subjects who are nonobese FDRs show signs of low-grade inflammation before or after exposure to short-term physical inactivity. RESEARCH DESIGN AND METHODS We studied 13 healthy FDR subjects and 20 control (CON) subjects matched for age, sex, and BMI before and after 10 days of bed rest (BR). Insulin sensitivity was measured by the hyperinsulinemic euglycemic clamp. Key low-grade inflammation mediators were measured in arterial blood and microdialysate from subcutaneous abdominal (SCAAT) and femoral adipose tissue. Adipokine mRNA expression was determined in SCAAT. RESULTS Before BR, FDR subjects displayed insulin resistance, elevated plasma C-reactive protein, leptin, and monocyte chemoattractant protein (MCP)-1, high interleukin (IL)-6, and MCP-1 expressions, as well as low adiponectin and leptin expressions. FDR subjects responded to BR by decreasing plasma adiponectin and IL-10 expression and increasing plasma expression of IL-10 and tumor necrosis factor-α. In contrast, CON subjects responded to BR by increasing plasma adiponectin and adiponectin expression and by decreasing SCAAT microdialysate leptin. CONCLUSIONS Young and nonobese FDR of patients with type 2 diabetes exhibit low-grade inflammation, which is further and disproportionately aggravated when exposed to physical inactivity. The study provides support for the notion that people at increased risk of type 2 diabetes should avoid even short periods of physical inactivity.
Collapse
Affiliation(s)
- Lise Højbjerre
- Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
| | | | | | | | | | | | | | | |
Collapse
|
|
30
|
Mediators of inflammation in polycystic ovary syndrome in relation to adiposity. Mediators Inflamm 2010; 2010:758656. [PMID: 20396393 PMCID: PMC2852606 DOI: 10.1155/2010/758656] [Citation(s) in RCA: 58] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2009] [Accepted: 03/18/2010] [Indexed: 11/25/2022] Open
Abstract
Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age group and is associated with a higher cardiovascular risk. Obesity, mainly visceral adiposity, is prevalent in patients with PCOS. Obesity is associated with low-grade inflammation and raised inflammatory cytokines, both of which are also described in patients with PCOS. In this paper, the potential relationships between fat distribution, adipocyte dysfunction and, altered inflammatory markers in patients with PCOS have been discussed.
Collapse
|
|
31
|
Dooley KE, Chaisson RE. Tuberculosis and diabetes mellitus: convergence of two epidemics. THE LANCET. INFECTIOUS DISEASES 2009; 9:737-46. [PMID: 19926034 PMCID: PMC2945809 DOI: 10.1016/s1473-3099(09)70282-8] [Citation(s) in RCA: 560] [Impact Index Per Article: 35.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
The link between diabetes mellitus and tuberculosis has been recognised for centuries. In recent decades, tuberculosis incidence has declined in high-income countries, but incidence remains high in countries that have high rates of infection with HIV, high prevalence of malnutrition and crowded living conditions, or poor tuberculosis control infrastructure. At the same time, diabetes mellitus prevalence is soaring globally, fuelled by obesity. There is growing evidence that diabetes mellitus is an important risk factor for tuberculosis and might affect disease presentation and treatment response. Furthermore, tuberculosis might induce glucose intolerance and worsen glycaemic control in people with diabetes. We review the epidemiology of the tuberculosis and diabetes epidemics, and provide a synopsis of the evidence for the role of diabetes mellitus in susceptibility to, clinical presentation of, and response to treatment for tuberculosis. In addition, we review potential mechanisms by which diabetes mellitus can cause tuberculosis, the effects of tuberculosis on diabetic control, and pharmacokinetic issues related to the co-management of diabetes and tuberculosis.
Collapse
Affiliation(s)
- Kelly E Dooley
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
| | | |
Collapse
|
|
32
|
Kim MS, Merke DP. Cardiovascular disease risk in adult women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Semin Reprod Med 2009; 27:316-21. [PMID: 19530065 DOI: 10.1055/s-0029-1225259] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a common autosomal recessive disorder characterized by impaired cortisol biosynthesis, with or without aldosterone deficiency, and androgen excess. Patients with the classic (severe) form also have epinephrine deficiency. Patients with CAH have an increased prevalence of risk factors for cardiovascular disease including obesity, hypertension, and insulin resistance. Androgen excess in women appears to be an additional risk factor for cardiovascular disease. Carotid intima-media thickness, a measure of subclinical atherosclerosis, also has been found to be increased in adults with CAH. The multiple hormonal imbalances present in the adult woman with CAH, in combination with chronic glucocorticoid therapy, contribute to cardiovascular disease risk. Further investigation of the predisposition to cardiovascular disease in women with CAH is warranted. Longitudinal studies are needed, and interventions targeting obesity, insulin resistance, hypertension, and hyperandrogenism may offer improved outcome.
Collapse
Affiliation(s)
- Mimi S Kim
- Reproductive Biology and Medicine Branch, The Eunice Kennedy Shriver National Institute of Child Health and Human Development, and The National Institutes of Health Clinical Center, Bethesda, MD 20892-1932, USA
| | | |
Collapse
|
|
33
|
Navarro-González JF, Mora-Fernández C. The role of inflammatory cytokines in diabetic nephropathy. J Am Soc Nephrol 2008; 19:433-42. [PMID: 18256353 DOI: 10.1681/asn.2007091048] [Citation(s) in RCA: 658] [Impact Index Per Article: 38.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Cytokines act as pleiotropic polypeptides regulating inflammatory and immune responses through actions on cells. They provide important signals in the pathophysiology of a range of diseases, including diabetes mellitus. Chronic low-grade inflammation and activation of the innate immune system are closely involved in the pathogenesis of diabetes and its microvascular complications. Inflammatory cytokines, mainly IL-1, IL-6, and IL-18, as well as TNF-alpha, are involved in the development and progression of diabetic nephropathy. In this context, cytokine genetics is of special interest to combinatorial polymorphisms among cytokine genes, their functional variations, and general susceptibility to diabetic nephropathy. Finally, the recognition of these molecules as significant pathogenic mediators in diabetic nephropathy leaves open the possibility of new potential therapeutic targets.
Collapse
Affiliation(s)
- Juan F Navarro-González
- Servicio de Nefrología, Hospital Universitario Nuestra Señora de Candelaria, Carretera del Rosario, 145, 38010 Santa Cruz de Tenerife, Spain.
| | | |
Collapse
|
|
34
|
Rana JS, Nieuwdorp M, Jukema JW, Kastelein JJP. Cardiovascular metabolic syndrome - an interplay of, obesity, inflammation, diabetes and coronary heart disease. Diabetes Obes Metab 2007; 9:218-32. [PMID: 17391148 DOI: 10.1111/j.1463-1326.2006.00594.x] [Citation(s) in RCA: 121] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
Cardiovascular disease is currently one of the biggest causes of morbidity and mortality facing humanity. Such a paradigm shift of disease pattern over the last century has only worsened due to the alarming global prevalence of obesity and type 2 diabetes. In recent years there is increasing focus on inflammation as one of the key players in the patho-physiology of these disorders. In addition to these overt risk factors new research is unraveling the significance of a constellation of early metabolic abnormalities that include weight gain, insulin resistance, prehypertension and a specific pattern of dyslipidaemia. There exists a complex interrelationship of these various metabolic disorders and their effect on cardiovascular system. Simplified explanation can be that inflammation increases insulin resistance, which in turn leads to obesity while perpetuating diabetes, high blood pressure, prothrombotic state and dyslipidaemia. While inflammation and insulin resistance have direct adverse effects on cardiac muscle, these metabolic abnormalities as a whole cause causes cardiovascular complications; warranting a multi pronged therapeutic and preventive approach for the 'Cardiovascular Metabolic Syndrome' as an entity.
Collapse
Affiliation(s)
- J S Rana
- Department of Vascular Medicine, Academic Medical Center Amsterdam, The Netherlands
| | | | | | | |
Collapse
|
|
35
|
Alexandraki K, Piperi C, Kalofoutis C, Singh J, Alaveras A, Kalofoutis A. Inflammatory process in type 2 diabetes: The role of cytokines. Ann N Y Acad Sci 2007; 1084:89-117. [PMID: 17151295 DOI: 10.1196/annals.1372.039] [Citation(s) in RCA: 211] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Population-based studies have shown strong relationship between inflammatory markers and metabolic disturbances, obesity, and atherosclerosis, whereas inflammation has been considered as a "common soil" between these clinical entities and type 2 diabetes (T2D). The accumulation of macrophages in adipose tissue (AT), the common origin of macrophages and adipocytes, the prevalent presence of peripheral mononuclear cells, and apoptotic beta cells by themselves seem to be the sources of inflammation present in T2D, since they generate the mediators of the inflammatory processes, namely cytokines. The main cytokines involved in the pathogenesis of T2D are interleukin-1beta (IL-1beta), with an action similar to the one present in type 1 diabetes, tumor necrosis factor-alpha (TNF-alpha), and IL-6, considered as the main regulators of inflammation, leptin, more recently introduced, and several others, such as monocyte chemoattractant protein-1, resistin, adiponectin, with either deleterious or beneficial effects in diabetic pathogenesis. The characterization of these molecules targeted diabetes treatment beyond the classical interventions with lifestyle changes and pharmaceutical agents, and toward the determination of specific molecular pathways that lead to low grade chronic inflammatory state mainly due to an immune system's unbalance.
Collapse
Affiliation(s)
- Krystallenia Alexandraki
- Laboratory of Biological Chemistry, University of Athens Medical School, M. Asias 75, Goudi 11527, Athens, Greece
| | | | | | | | | | | |
Collapse
|
|
36
|
Gambineri A, Pasquali R. Resistencia a la insulina, obesidad y síndrome metabólico en el síndrome del ovario poliquístico. ACTA ACUST UNITED AC 2006. [DOI: 10.1016/s1575-0922(06)71168-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
|
|
37
|
Orio F, Palomba S, Colao A. Cardiovascular risk in women with polycystic ovary syndrome. Fertil Steril 2006; 86 Suppl 1:S20-1. [PMID: 16798279 DOI: 10.1016/j.fertnstert.2006.03.003] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2006] [Revised: 03/09/2006] [Accepted: 03/09/2006] [Indexed: 11/29/2022]
Abstract
Polycystic ovary syndrome (PCOS) is not only a reproductive problem but a complex, endocrine, multifaceted disease with several health complications. Cardiovascular abnormalities represent important long-term sequelae of PCOS.
Collapse
Affiliation(s)
- Francesco Orio
- Department of Molecular and Clinical Endocrinology & Oncology, University of Naples Federico II, Naples, Italy.
| | | | | |
Collapse
|
|
38
|
Lin J, Lee D, Chase JG, Shaw GM, Hann CE, Lotz T, Wong J. Stochastic modelling of insulin sensitivity variability in critical care. Biomed Signal Process Control 2006. [DOI: 10.1016/j.bspc.2006.09.003] [Citation(s) in RCA: 66] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
|
|
39
|
Phillips LS, Langer RD. Postmenopausal hormone therapy: Critical reappraisal and a unified hypothesis. Fertil Steril 2005; 83:558-66. [PMID: 15749481 DOI: 10.1016/j.fertnstert.2004.11.012] [Citation(s) in RCA: 73] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2004] [Revised: 11/09/2004] [Accepted: 11/09/2004] [Indexed: 12/30/2022]
Abstract
OBJECTIVE To reconcile apparently conflicting evidence regarding the use of hormone therapy as a health-preserving strategy in postmenopausal women in light of that fact that findings from animal studies, human observation studies, and human clinical trials are consistent for outcomes such as fracture and breast cancer but differ for coronary heart disease (CHD). DESIGN Literature review and generation of a unified hypothesis consistent with all of the data. SETTING Animal trials, human observational studies, human studies of biologic intermediates, and human clinical trials. PATIENT(S) Premenopausal and postmenopausal women with or without antecedent CHD. MAIN OUTCOME MEASURE(S) Coronary heart disease events, proxies, risk factors, and related mechanisms. RESULT(S) The complex CHD responses to hormone therapy in recent human trials likely reflect a combination of [1] early erosion/rupture of "vulnerable" coronary plaque, which is made worse by hormone therapy, [2] long-term reduction in plaque formation, which is improved by hormone therapy, and [3] modulation of the vasculoprotective actions of estrogens by systemic progestogens. CONCLUSION(S) The unified hypothesis predicts that hormone therapy initiated at the time of menopause should produce a decrease in CHD over time. In contrast, hormone therapy begun years after menopause should produce an increase in CHD events shortly after therapy is begun, followed later by benefit. In women who require progestogens for endometrial protection, there should be greater CHD benefit from use of progestogens with less systemic activity. The unified hypothesis is consistent both with plausible biologic mechanisms and with evidence from animal studies, human observational studies, and human clinical trials such as the Women's Health Initiative. In the absence of evidence from human trials that specifically involve initiation of hormone therapy in perimenopausal women, practitioners and patients can use the unified hypothesis as a rational tool to guide decisions about clinical management.
Collapse
Affiliation(s)
- Lawrence S Phillips
- General Clinical Research Center, Emory University Hospital, Division of Endocrinology and Metabolism, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
| | | |
Collapse
|
|
40
|
Chase JG, Shaw GM, Lin J, Doran CV, Hann C, Robertson MB, Browne PM, Lotz T, Wake GC, Broughton B. Adaptive bolus-based targeted glucose regulation of hyperglycaemia in critical care. Med Eng Phys 2005; 27:1-11. [PMID: 15603999 DOI: 10.1016/j.medengphy.2004.08.006] [Citation(s) in RCA: 57] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2004] [Revised: 07/23/2004] [Accepted: 08/16/2004] [Indexed: 01/08/2023]
Abstract
Tight regulation of blood glucose can significantly reduce mortality in critical illness. Critically ill patients are extremely diverse in the dynamics of their hyperglycaemia. Hence, responses can vary significantly, due to variations in insulin levels, effective insulin utilization, glucose absorption and other factors. Consequently, fixed protocols and sliding scales can result in error, given this large variation in patient dynamics. A two-compartment glucose-insulin system model that accounts for time-varying insulin sensitivity and endogenous glucose removal, along with two different saturation kinetics, is developed and tested in preliminary proof-of-concept clinical trials for adaptive control of blood glucose levels. The adaptive control algorithm developed in this research monitors the physiological status of a critically ill patient, allowing real-time, tight glycaemic regulation. The bolus-based insulin administration provides a safe approach to glucose level management. The ability to track changing physiological status and account for insulin transport and effect saturation enabled targeted stepwise reduction in glycaemic levels in three test cases.
Collapse
Affiliation(s)
- J Geoffrey Chase
- Department of Mechanical Engineering, Centre for Bio-Engineering, University of Canterbury, Private Bag 4800, Christchurch, New Zealand.
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
41
|
Abstract
The metabolic syndrome is a condition associated with obesity, insulin resistance, hypertension, dyslipidemia, hypercoagulability, and chronic inflammation, all of which increase the risk of cardiovascular disease (CVD). The Third National Cholesterol Education Program Adult Treatment Panel extensively discussed the metabolic syndrome because it is a major health issue in the United States due to the national epidemic of obesity. Statins cause significant CVD risk reduction in patients with the metabolic syndrome by alterations in lipid levels and possibly by decreasing inflammation. Because of the increased CVD risk associated with the metabolic syndrome and extensive clinical trial evidence documenting reduction of CVD risk with statin treatment, all patients with the metabolic syndrome should be evaluated as candidates for statin treatment as part of a multidisciplinary approach to reduce CVD risk.
Collapse
|
|
42
|
Orio F, Palomba S, Cascella T, Di Biase S, Manguso F, Tauchmanovà L, Nardo LG, Labella D, Savastano S, Russo T, Zullo F, Colao A, Lombardi G. The increase of leukocytes as a new putative marker of low-grade chronic inflammation and early cardiovascular risk in polycystic ovary syndrome. J Clin Endocrinol Metab 2005; 90:2-5. [PMID: 15483098 DOI: 10.1210/jc.2004-0628] [Citation(s) in RCA: 153] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
White blood cell (WBC) count is a known risk factor for atherosclerotic vascular disease in adult women. Polycystic ovary syndrome (PCOS) is potentially a risk factor for atherosclerosis and cardiovascular disease. The aim of the present study was to investigate leukocyte count in PCOS. One hundred and fifty PCOS women matched for age and body mass index with 150 healthy women were enrolled. WBC count, C-reactive protein, and a complete anthropometrical, metabolic, and hormonal evaluation were performed in both groups. Serum insulin, glucose level, and lipid profile were also measured in each subject. WBC count was significantly higher (P < 0.0001) in PCOS with (interquartile range in parentheses) 7260 (393) cells/mm(3), compared with controls with 5220 (210) cells/mm(3). C-reactive protein levels were significantly increased (P < 0.0001) in PCOS with 2 (1) mg/liter compared with healthy women with 0.7 (0.8) mg/liter. In both groups, there was a significant (P < 0.0001) linear correlation between WBC count and homeostasis model assessment score (PCOS, r = 0.94; controls, r = 0.91). Multiple linear regression analysis showed that other hormone levels are not predictors of leukocyte count both in PCOS and control women. In conclusion, our data demonstrate that PCOS women have an increased WBC count that correlates with homeostasis model assessment values.
Collapse
Affiliation(s)
- Francesco Orio
- Department of Molecular and Clinical Endocrinology, University Federico II, Naples, Italy.
| | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
43
|
Doran CV, Chase JG, Shaw GM, Moorhead KT, Hudson NH. Automated insulin infusion trials in the intensive care unit. Diabetes Technol Ther 2004; 6:155-65. [PMID: 15117582 DOI: 10.1089/152091504773731348] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
The objective is to demonstrate the effectiveness of a simple automated insulin infusion for controlling the rise and duration of blood glucose excursion following a glucose challenge in critically ill patients with impaired glucose tolerance. A two-compartment model of the glucose regulatory system was developed for intravenous infusion control design. On two subsequent days a critically ill patient with impaired glucose tolerance was given a 75 g oral glucose tolerance test (OGTT), and the glucose level was measured every 15 min. The first day's data were used to design a heavy-derivative insulin infusion controller for the second day. Ethics approval was granted for this test. Five patients were studied. In four patients, the magnitude and duration of blood glucose excursion were reduced over 50%. Fasting level was reduced 15%, from an average of 7.2 mmol/L to 6.1 mmol/L. The fifth patient's results showed a diminished response due to the antagonistic effects of hydrocortisone on insulin, a data point not provided prior to testing. Modeling to account for this effect yielded better correlation with the test. The automated algorithm provided rapid, effective control of the blood glucose rise in response to an OGTT input. These results highlight the effectiveness of automated infusions for regulating blood glucose rise and excursions, and the potential of this approach for non-hospitalized individuals.
Collapse
Affiliation(s)
- Carmen V Doran
- Department of Mechanical Engineering, University of Canterbury, Christchurch, New Zealand.
| | | | | | | | | |
Collapse
|
|
44
|
|