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Hajiesmaeili M, Nooraei N, Alamdari NM, Bidgoli BF, Jame SZB, Moghaddam NM, Fathi M. Clinical phenotypes of patients with acute stroke: a secondary analysis. ROMANIAN JOURNAL OF INTERNAL MEDICINE = REVUE ROUMAINE DE MEDECINE INTERNE 2024; 62:168-177. [PMID: 38299606 DOI: 10.2478/rjim-2024-0003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/05/2023] [Indexed: 02/02/2024]
Abstract
INTRODUCTION Stroke is a leading cause of mortality worldwide and a major cause of disability having a high burden on patients, society, and caregiving systems. This study was conducted to investigate the presence of clusters of in-hospital patients with acute stroke based on demographic and clinical data. Cluster analysis reveals patterns in patient characteristics without requiring knowledge of a predefined patient category or assumptions about likely groupings within the data. METHODS We performed a secondary analysis of open-access anonymized data from patients with acute stroke admitted to a hospital between December 2019 to June 2021. In total, 216 patients (78; 36.1% men) were included in the analytical dataset with a mean (SD) age of 60.3 (14.4). Many demographic and clinical features were included in the analysis and the Barthel Index on discharge was used for comparing the functional recovery of the identified clusters. RESULTS Hierarchical clustering based on the principal components identified two clusters of 109 and 107 patients. The clusters were different in the Barthel Index scores on discharge with the mean (SD) of 39.3 (29.3) versus 62.6 (29.4); t (213.87) = -5.818, P <0.001, Cohen's d (95%CI) = -0.80 (-1.07, -0.52). A logistic model showed that age, systolic blood pressure, pulse rate, D-dimer blood level, low-density lipoprotein, hemoglobin, creatinine concentration, the National Institute of Health Stroke Scale value, and the Barthel Index scores on admission were significant predictors of cluster profiles (all P ≤0.029). CONCLUSION There are two clusters in hospitalized patients with acute stroke with significantly different functional recovery. This allows prognostic grouping of hospitalized acute stroke patients for prioritization of care or resource allocation. The clusters can be recognized using easily measured demographic and clinical features.
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Affiliation(s)
- Mohammadreza Hajiesmaeili
- 1Critical Care Quality Improvement Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Navid Nooraei
- 2Critical Care Quality Improvement Research Center, Shahid Modarres Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Nasser Malekpour Alamdari
- 2Critical Care Quality Improvement Research Center, Shahid Modarres Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Behruz Farzanegan Bidgoli
- 3Critical Care Quality Improvement Research Center, Dr. Masih Daneshvari Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sanaz Zargar Balaye Jame
- 4Department of Health Management and Economics, Faculty of Medicine, Aja University of Medical Sciences, Tehran, Iran
| | - Nader Markazi Moghaddam
- 2Critical Care Quality Improvement Research Center, Shahid Modarres Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- 4Department of Health Management and Economics, Faculty of Medicine, Aja University of Medical Sciences, Tehran, Iran
| | - Mohammad Fathi
- 2Critical Care Quality Improvement Research Center, Shahid Modarres Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Tonyan ZN, Nasykhova YA, Danilova MM, Glotov AS. Genetics of macrovascular complications in type 2 diabetes. World J Diabetes 2021; 12:1200-1219. [PMID: 34512887 PMCID: PMC8394234 DOI: 10.4239/wjd.v12.i8.1200] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 05/04/2021] [Accepted: 07/09/2021] [Indexed: 02/06/2023] Open
Abstract
Type 2 diabetes mellitus (T2DM) is a metabolic disorder that currently affects more than 400 million worldwide and is projected to cause 552 million cases by the year 2030. Long-term vascular complications, such as coronary artery disease, myocardial infarction, stroke, are the leading causes of morbidity and mortality among diabetic patients. The recent advances in genome-wide technologies have given a powerful impetus to the study of risk markers for multifactorial diseases. To date, the role of genetic and epigenetic factors in modulating susceptibility to T2DM and its vascular complications is being successfully studied that provides the accumulation of genomic knowledge. In the future, this will provide an opportunity to reveal the pathogenetic pathways in the development of the disease and allow to predict the macrovascular complications in T2DM patients. This review is focused on the evidence of the role of genetic variants and epigenetic changes in the development of macrovascular pathology in diabetic patients.
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Affiliation(s)
- Ziravard N Tonyan
- Department of Genomic Medicine, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, Saint-Petersburg 199034, Russia
| | - Yulia A Nasykhova
- Department of Genomic Medicine, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, Saint-Petersburg 199034, Russia
- Laboratory of Biobanking and Genomic Medicine of Institute of Translation Biomedicine, St. Petersburg State University, Saint-Petersburg 199034, Russia
| | - Maria M Danilova
- Department of Genomic Medicine, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, Saint-Petersburg 199034, Russia
| | - Andrey S Glotov
- Department of Genomic Medicine, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, Saint-Petersburg 199034, Russia
- Laboratory of Biobanking and Genomic Medicine of Institute of Translation Biomedicine, St. Petersburg State University, Saint-Petersburg 199034, Russia
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Abdosh T, Weldegebreal F, Teklemariam Z, Mitiku H. Cardiovascular diseases risk factors among adult diabetic patients in eastern Ethiopia. JRSM Cardiovasc Dis 2019; 8:2048004019874989. [PMID: 31523424 PMCID: PMC6727089 DOI: 10.1177/2048004019874989] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2018] [Revised: 08/17/2019] [Accepted: 08/19/2019] [Indexed: 01/22/2023] Open
Abstract
Objective The aim of this study was to determine the magnitude of cardiovascular disease risk factors among adult diabetic patients at Hiwot Fana Specialized University Hospital and Jugal Hospital, eastern Ethiopia. Methods An institutional based cross sectional study was conducted on a total of 416 study participants (age ≥18 years) from February to March 2017. Data were collected using: structured questionnaires, measurements of weight, height, and blood pressure, and laboratory examination of blood lipids (total cholesterol, triglycerides, low-density lipoprotein, and high-density lipoprotein cholesterol) and fasting blood glucose. Data were analyzed using SPSS version 16.0 software packages. The association of cardiovascular disease risk factors with diabetes type, age, and sex was assessed by chi-square test. Result The mean age of study participants was 52 years and 44% were male. Dyslipidemia (90.6%), physical inactivity (76%), and hypertension (62.7%) were the most common cardiovascular disease risks factors identified among diabetic patients. It was also observed that 68.5% of the study participants had uncontrolled blood glucose level. Hypertension was significant in patients over 65 compared to those ≤65 years of age (p < 0.023). Females were considered to be significantly physically inactive compared to males (p < 0.001). Conclusion Dyslipidemia is the most common risk factor of CVD in individuals with Types 1 and 2 diabetes mellitus. Identification and treatment of lipid abnormalities is very important. Controlling hypertension among older patients and lifestyle modification among female diabetic patients are also recommended.
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Affiliation(s)
- Tekabe Abdosh
- School of Medicine, Haramaya University, College of Health and Medical Sciences, Harar, Ethiopia
| | - Fitsum Weldegebreal
- Department of Medical Laboratory Sciences, Haramaya University, College of Health and Medical Sciences, Harar, Ethiopia
| | - Zelalem Teklemariam
- Department of Medical Laboratory Sciences, Haramaya University, College of Health and Medical Sciences, Harar, Ethiopia
| | - Habtamu Mitiku
- Department of Medical Laboratory Sciences, Haramaya University, College of Health and Medical Sciences, Harar, Ethiopia
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Blockade of Acid-Sensing Ion Channels Attenuates Recurrent Hypoglycemia-Induced Potentiation of Ischemic Brain Damage in Treated Diabetic Rats. Neuromolecular Med 2019; 21:454-466. [PMID: 31134484 DOI: 10.1007/s12017-019-08546-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2019] [Accepted: 05/17/2019] [Indexed: 12/18/2022]
Abstract
Diabetes is a chronic metabolic disease and cerebral ischemia is a serious complication of diabetes. Anti-diabetic therapy mitigates this complication but increases the risk of exposure to recurrent hypoglycemia (RH). We showed previously that RH exposure increases ischemic brain damage in insulin-treated diabetic (ITD) rats. The present study evaluated the hypothesis that increased intra-ischemic acidosis in RH-exposed ITD rats leads to pronounced post-ischemic hypoperfusion via activation of acid-sensing (proton-gated) ion channels (ASICs). Streptozotocin-diabetic rats treated with insulin were considered ITD rats. ITD rats were exposed to RH for 5 days and were randomized into Psalmotoxin1 (PcTx1, ASIC1a inhibitor), APETx2 (ASIC3 inhibitor), or vehicle groups. Transient global cerebral ischemia was induced overnight after RH. Cerebral blood flow was measured using laser Doppler flowmetry. Ischemic brain injury in hippocampus was evaluated using histopathology. Post-ischemic hypoperfusion in RH-exposed rats was of greater extent than that in control rats. Inhibition of ASICs prevented RH-induced increase in the extent of post-ischemic hypoperfusion and ischemic brain injury. Since ASIC activation-induced store-operated calcium entry (SOCE) plays a role in vascular tone, next we tested if acidosis activates SOCE via activating ASICs in vascular smooth muscle cells (VSMCs). We observed that SOCE in VSMCs at lower pH is ASIC3 dependent. The results show the role of ASIC in post-ischemic hypoperfusion and increased ischemic damage in RH-exposed ITD rats. Understanding the pathways mediating exacerbated ischemic brain injury in RH-exposed ITD rats may help lower diabetic aggravation of ischemic brain damage.
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5
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Shukla V, Fuchs P, Liu A, Cohan CH, Dong C, Wright CB, Perez-Pinzon MA, Dave KR. Recurrent Hypoglycemia Exacerbates Cerebral Ischemic Damage in Diabetic Rats via Enhanced Post-Ischemic Mitochondrial Dysfunction. Transl Stroke Res 2018; 10:78-90. [PMID: 29569040 DOI: 10.1007/s12975-018-0622-2] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2018] [Revised: 03/06/2018] [Accepted: 03/08/2018] [Indexed: 12/17/2022]
Abstract
Diabetes significantly increases the risk of stroke and post-stroke mortality. Recurrent hypoglycemia (RH) is common among diabetes patients owing to glucose-lowering therapies. Earlier, we showed that RH in a rat model of insulin-dependent diabetes exacerbates cerebral ischemic damage. Impaired mitochondrial function has been implicated as a central player in the development of cerebral ischemic damage. Hypoglycemia is also known to affect mitochondrial functioning. The present study tested the hypothesis that prior exposure of insulin-treated diabetic (ITD) rats to RH exacerbates brain damage via enhanced post-ischemic mitochondrial dysfunction. In a rat model of streptozotocin-induced diabetes, we evaluated post-ischemic mitochondrial function in RH-exposed ITD rats. Rats were exposed to five episodes of moderate hypoglycemia prior to the induction of cerebral ischemia. We also evaluated the impact of RH, both alone and in combination with cerebral ischemia, on cognitive function using the Barnes circular platform maze test. We observed that RH exposure to ITD rats leads to increased cerebral ischemic damage and decreased mitochondrial complex I activity. Exposure of ITD rats to RH impaired spatial learning and memory. Our results demonstrate that RH exposure to ITD rats potentially increases post-ischemic damage via enhanced post-ischemic mitochondrial dysfunction.
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Affiliation(s)
- Vibha Shukla
- Cerebral Vascular Disease Research Laboratories, University of Miami School of Medicine, 1420 NW 9th Ave, NRB/203E, Miami, FL, 33136, USA.,Department of Neurology, University of Miami School of Medicine, Miami, FL, 33136, USA
| | - Perry Fuchs
- Cerebral Vascular Disease Research Laboratories, University of Miami School of Medicine, 1420 NW 9th Ave, NRB/203E, Miami, FL, 33136, USA.,Department of Neurology, University of Miami School of Medicine, Miami, FL, 33136, USA
| | - Allen Liu
- Cerebral Vascular Disease Research Laboratories, University of Miami School of Medicine, 1420 NW 9th Ave, NRB/203E, Miami, FL, 33136, USA.,Department of Neurology, University of Miami School of Medicine, Miami, FL, 33136, USA
| | - Charles H Cohan
- Cerebral Vascular Disease Research Laboratories, University of Miami School of Medicine, 1420 NW 9th Ave, NRB/203E, Miami, FL, 33136, USA.,Department of Neurology, University of Miami School of Medicine, Miami, FL, 33136, USA.,Evelyn F. McKnight Brain Institute, University of Miami School of Medicine, Miami, FL, 33136, USA
| | - Chuanhui Dong
- Department of Neurology, University of Miami School of Medicine, Miami, FL, 33136, USA.,Evelyn F. McKnight Brain Institute, University of Miami School of Medicine, Miami, FL, 33136, USA
| | - Clinton B Wright
- Department of Neurology, University of Miami School of Medicine, Miami, FL, 33136, USA.,Evelyn F. McKnight Brain Institute, University of Miami School of Medicine, Miami, FL, 33136, USA.,Neuroscience Program, University of Miami School of Medicine, Miami, FL, 33136, USA
| | - Miguel A Perez-Pinzon
- Cerebral Vascular Disease Research Laboratories, University of Miami School of Medicine, 1420 NW 9th Ave, NRB/203E, Miami, FL, 33136, USA.,Department of Neurology, University of Miami School of Medicine, Miami, FL, 33136, USA.,Evelyn F. McKnight Brain Institute, University of Miami School of Medicine, Miami, FL, 33136, USA.,Neuroscience Program, University of Miami School of Medicine, Miami, FL, 33136, USA
| | - Kunjan R Dave
- Cerebral Vascular Disease Research Laboratories, University of Miami School of Medicine, 1420 NW 9th Ave, NRB/203E, Miami, FL, 33136, USA. .,Department of Neurology, University of Miami School of Medicine, Miami, FL, 33136, USA. .,Evelyn F. McKnight Brain Institute, University of Miami School of Medicine, Miami, FL, 33136, USA. .,Neuroscience Program, University of Miami School of Medicine, Miami, FL, 33136, USA.
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6
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Rehni AK, Liu A, Perez-Pinzon MA, Dave KR. Diabetic aggravation of stroke and animal models. Exp Neurol 2017; 292:63-79. [PMID: 28274862 PMCID: PMC5400679 DOI: 10.1016/j.expneurol.2017.03.004] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2016] [Revised: 02/03/2017] [Accepted: 03/03/2017] [Indexed: 12/16/2022]
Abstract
Cerebral ischemia in diabetics results in severe brain damage. Different animal models of cerebral ischemia have been used to study the aggravation of ischemic brain damage in the diabetic condition. Since different disease conditions such as diabetes differently affect outcome following cerebral ischemia, the Stroke Therapy Academic Industry Roundtable (STAIR) guidelines recommends use of diseased animals for evaluating neuroprotective therapies targeted to reduce cerebral ischemic damage. The goal of this review is to discuss the technicalities and pros/cons of various animal models of cerebral ischemia currently being employed to study diabetes-related ischemic brain damage. The rational use of such animal systems in studying the disease condition may better help evaluate novel therapeutic approaches for diabetes related exacerbation of ischemic brain damage.
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Affiliation(s)
- Ashish K Rehni
- Cerebral Vascular Disease Research Laboratories, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Department of Neurology, University of Miami Miller School of Medicine, Miami, FL 33136, USA
| | - Allen Liu
- Cerebral Vascular Disease Research Laboratories, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Department of Neurology, University of Miami Miller School of Medicine, Miami, FL 33136, USA
| | - Miguel A Perez-Pinzon
- Cerebral Vascular Disease Research Laboratories, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Department of Neurology, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Neuroscience Program, University of Miami Miller School of Medicine, Miami, FL 33136, USA
| | - Kunjan R Dave
- Cerebral Vascular Disease Research Laboratories, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Department of Neurology, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Neuroscience Program, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
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Shukla V, Shakya AK, Perez-Pinzon MA, Dave KR. Cerebral ischemic damage in diabetes: an inflammatory perspective. J Neuroinflammation 2017; 14:21. [PMID: 28115020 PMCID: PMC5260103 DOI: 10.1186/s12974-016-0774-5] [Citation(s) in RCA: 123] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2016] [Accepted: 12/07/2016] [Indexed: 12/16/2022] Open
Abstract
Stroke is one of the leading causes of death worldwide. A strong inflammatory response characterized by activation and release of cytokines, chemokines, adhesion molecules, and proteolytic enzymes contributes to brain damage following stroke. Stroke outcomes are worse among diabetics, resulting in increased mortality and disabilities. Diabetes involves chronic inflammation manifested by reactive oxygen species generation, expression of proinflammatory cytokines, and activation/expression of other inflammatory mediators. It appears that increased proinflammatory processes due to diabetes are further accelerated after cerebral ischemia, leading to increased ischemic damage. Hypoglycemia is an intrinsic side effect owing to glucose-lowering therapy in diabetics, and is known to induce proinflammatory changes as well as exacerbate cerebral damage in experimental stroke. Here, we present a review of available literature on the contribution of neuroinflammation to increased cerebral ischemic damage in diabetics. We also describe the role of hypoglycemia in neuroinflammation and cerebral ischemic damage in diabetics. Understanding the role of neuroinflammatory mechanisms in worsening stroke outcome in diabetics may help limit ischemic brain injury and improve clinical outcomes.
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Affiliation(s)
- Vibha Shukla
- Cerebral Vascular Disease Research Laboratories, University of Miami School of Medicine, Miami, FL, 33136, USA.,Department of Neurology (D4-5), University of Miami Miller School of Medicine, 1420 NW 9th Ave, NRB/203E, Miami, FL, 33136, USA
| | - Akhalesh Kumar Shakya
- Present address: Department of Microbiology and Immunology, and Center for Molecular and Tumor Virology, Louisiana State University Health Sciences Center, Shreveport, LA, 71130, USA
| | - Miguel A Perez-Pinzon
- Cerebral Vascular Disease Research Laboratories, University of Miami School of Medicine, Miami, FL, 33136, USA.,Department of Neurology (D4-5), University of Miami Miller School of Medicine, 1420 NW 9th Ave, NRB/203E, Miami, FL, 33136, USA.,Neuroscience Program, University of Miami School of Medicine, Miami, FL, 33136, USA
| | - Kunjan R Dave
- Cerebral Vascular Disease Research Laboratories, University of Miami School of Medicine, Miami, FL, 33136, USA. .,Department of Neurology (D4-5), University of Miami Miller School of Medicine, 1420 NW 9th Ave, NRB/203E, Miami, FL, 33136, USA. .,Neuroscience Program, University of Miami School of Medicine, Miami, FL, 33136, USA.
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Meta-analysis of telemonitoring to improve HbA1c levels: promise for stroke survivors. J Clin Neurosci 2015; 22:807-11. [PMID: 25791996 DOI: 10.1016/j.jocn.2014.11.009] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2014] [Accepted: 11/29/2014] [Indexed: 02/08/2023]
Abstract
Monitoring glycemic control is useful not only in the primary prevention of stroke in diabetics, but also in the rehabilitation from and secondary prevention of stroke. In an often functionally and neurocognitively impaired population, however, poor compliance with treatment regimens is a major problem. Wireless, telemonitoring glucometers - often integrated into the patient's healthcare system - offer a solution to the compliance issue. We sought to evaluate the effectiveness of telemonitoring technologies in improving long-term glycemic control. A search on www.clinicaltrials.gov, using keywords such as "telemonitoring" and "self-care device" was performed, and five trials were identified that compared hemoglobin A1c (HbA1c) levels of a group receiving standard care (controls) to a group receiving a telemonitoring intervention. Four of the five studies showed a greater reduction in HbA1c in the intervention group compared to controls at 6 months, although only one was statistically significant. There was considerable heterogeneity between studies (I(2)=69.5%, p=0.02), and the random effects model estimated the aggregate effect size for mean difference in reduction of HbA1c levels to be 0.08% (95% confidence interval -0.12% to 0.28%), which was not statistically significant (p=0.42). The varying results may be due to specific factors in the trials that contributed to their large heterogeneity, and further trials are needed to support the role of telemonitoring in improving diabetes management in this population. Nonetheless, in the future telemonitoring may substantially help patients at risk of ischemic stroke and those who require close glucose monitoring.
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Sickmann HM, Waagepetersen HS. Effects of diabetes on brain metabolism--is brain glycogen a significant player? Metab Brain Dis 2015; 30:335-43. [PMID: 24771109 DOI: 10.1007/s11011-014-9546-z] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2014] [Accepted: 04/10/2014] [Indexed: 10/25/2022]
Abstract
Brain glycogen, being an intracellular glucose reservoir, contributes to maintain energy and neurotransmitter homeostasis under physiological as well as pathological conditions. Under conditions with a disturbance in systemic glucose metabolism such as in diabetes, the supply of glucose to the brain may be affected and have important impacts on brain metabolism and neurotransmission. This also implies that brain glycogen may serve an essential role in the diabetic state to sustain appropriate brain function. There are two main types of diabetes; type 1 and type 2 diabetes and both types may be associated with brain impairments e.g. cognitive decline and dementia. It is however, not clear how these impairments on brain function are linked to alterations in brain energy and neurotransmitter metabolism. In this review, we will illuminate how rodent diabetes models have contributed to a better understanding of how brain energy and neurotransmitter metabolism is affected in diabetes. There will be a particular focus on the role of brain glycogen to support glycolytic and TCA cycle activity as well as glutamate-glutamine cycle in type 1 and type 2 diabetes.
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Affiliation(s)
- Helle M Sickmann
- Dept. of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Jagtvej 160, 2100, Copenhagen, Denmark,
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Associations Between Estimated Glomerular Filtration Rate and Stroke Outcomes in Diabetic Versus Nondiabetic Patients. Stroke 2014; 45:2887-93. [DOI: 10.1161/strokeaha.114.005380] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
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Khoury JC, Kleindorfer D, Alwell K, Moomaw CJ, Woo D, Adeoye O, Flaherty ML, Khatri P, Ferioli S, Broderick JP, Kissela BM. Diabetes mellitus: a risk factor for ischemic stroke in a large biracial population. Stroke 2013; 44:1500-4. [PMID: 23619130 PMCID: PMC3746032 DOI: 10.1161/strokeaha.113.001318] [Citation(s) in RCA: 113] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2013] [Accepted: 03/07/2013] [Indexed: 11/16/2022]
Abstract
BACKGROUND AND PURPOSE We previously reported increased incidence of ischemic stroke among both blacks and whites with diabetes mellitus, especially in those aged <55 years. With rising prevalence of diabetes mellitus in the past decade, we revisit the impact of diabetes mellitus on stroke incidence in the same population (≈1.3 million) 5 and 10 years later. METHODS This is a population-based study. First ischemic strokes among black and white residents of the 5-county Greater Cincinnati/Northern Kentucky region, aged ≥ 20 years, for periods 7/1993 to 6/1994, 1999, and 2005, were included in this analysis. Incidence rates were adjusted for sex, race, and age, as appropriate, to the 2000 US population. RESULTS History of diabetes mellitus among first ischemic strokes was reported for 493/1709 (28%) in 1993/1994, 522/1778 (29%) in 1999, and 544/1680 (33%) in 2005. Risk ratios (95% confidence interval) for rates of stroke in those with versus without diabetes mellitus for blacks reduced significantly from 5.6 in 1993/1994 to 3.2 in 2005; for whites the risk ratio remained stable at 3.8 in 1993/1994 and 2005. However, risk ratios varied with age, with an overall 5- to 14-fold increased risk observed in those aged 20 to 65 years. CONCLUSIONS Those with diabetes mellitus remain at greatly increased risk for stroke at all ages, especially <65 years, regardless of race. The rates and risk ratios for 1999 and 2005, although similar to those previously reported for the mid-1990s, take on increased significance, given the epidemic of diabetes mellitus and metabolic syndrome throughout the US and the world.
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Affiliation(s)
- Jane C Khoury
- Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, 3333 Burnett Av, MLC 5041, Cincinnati, OH 45229, USA.
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Li G, Xu X, Wang D, Wang J, Wang Y, Yu J. Microglial activation during acute cerebral infarction in the presence of diabetes mellitus. Neurol Sci 2011; 32:1075-9. [PMID: 21607752 DOI: 10.1007/s10072-011-0632-2] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2010] [Accepted: 05/13/2011] [Indexed: 11/28/2022]
Abstract
The patients suffering from acute cerebral infarction in the presence of diabetes mellitus (DMCI) often have poor clinical outcomes when compared with those in the absence of diabetes mellitus (non-DMCI), but the corresponding differences in pathology still remain elusive. Here, we investigated the proliferation of microglia in DMCI and non-DMCI. Patients who came to autopsy involved four DMCI cases and four non-DMCI cases. The peri-infarct region and the equivalent non-lesional region in the contralateral hemisphere were removed and analyzed. The hematoxylin-eosin staining and immunohistochemistry staining with anti-ferritin were used for evaluating the microglial activation. We found a more evident microglial proliferation in the peri-infarct region (P < 0.01) and in the non-lesional hemisphere (P < 0.05) in DMCI than in non-DMCI patients. In addition, neuronophagia was observed in peri-infarct region of DMCI. Future studies are warranted to further clarify the influence of microglial activation in DMCI.
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Affiliation(s)
- Gang Li
- Department of Neurology, East Hospital, Tongji University, Jimo Road, No. 150, Shanghai 200210, China
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Giacconi R, Muti E, Malavolta M, Cipriano C, Costarelli L, Bernardini G, Gasparini N, Mariani E, Saba V, Boccoli G, Mocchegiani E. The +838 C/G MT2A polymorphism, metals, and the inflammatory/immune response in carotid artery stenosis in elderly people. Mol Med 2007. [PMID: 17622311 DOI: 10.2119/2007-00045.giacconi] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Carotid artery stenosis (CS) is a well-established risk factor for stroke. Increased proinflammatory chemokines, enhanced metallothionein (MT), and altered metal homeostasis may play roles in atherosclerosis progression and plaque destabilization. MT may sequester zinc during chronic inflammation, provoke zinc deficiency, and modulate NK cell cytotoxicity. A recent investigation of older patients with diabetes and atherosclerosis showed an association between the -209 A/G MT2A polymorphism, CS, and zinc status. In this study, we evaluated the relationship between two MT2A polymorphisms (-209 and + 838 locus), metal status, and inflammatory/immune response in older patients with CS only (the CS1 group) or with CS and previous cerebrovascular episodes (transient ischemic attack or stroke) (the CS2 group). A total of 506 individuals (188 CS1, 100 CS2, and 218 healthy controls) were studied. Atherosclerotic patients (CS1 and CS2) showed increased levels of MT, MCP-1, and RANTES, reduced NK cell cytotoxicity, and altered trace element concentrations (zinc, copper, magnesium, iron). The +838 C/G MT2A polymorphism was differently distributed in CS1 and CS2 patients, who displayed the GG genotype (C-) with significantly higher frequency than elderly controls. C- carriers showed increased MCP-1 and decreased NK cell cytotoxicity, CD56+ cells, and intracellular zinc availability along with decreased zinc, copper, and magnesium content in erythrocytes and increased iron in plasma. C- carriers also showed a major incidence of soft carotid plaques. In conclusion, the +838 C/G MT2A polymorphism seems to influence inflammatory markers, zinc availability, NK cell cytotoxicity, and trace element status, all of which may promote CS development.
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Affiliation(s)
- Robertina Giacconi
- Immunology Center (Section of Nutrition, Immunity, and Ageing), Research Department INRCA, Ancona, Italy
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Giacconi R, Muti E, Malavolta M, Cipriano C, Costarelli L, Bernardini G, Gasparini N, Mariani E, Saba V, Boccoli G, Mocchegiani E. The +838 C/G MT2A polymorphism, metals, and the inflammatory/immune response in carotid artery stenosis in elderly people. MOLECULAR MEDICINE (CAMBRIDGE, MASS.) 2007; 13:388-95. [PMID: 17622311 PMCID: PMC1952672 DOI: 10.2119/2007–00045.giacconi] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Subscribe] [Scholar Register] [Received: 04/23/2007] [Accepted: 05/02/2007] [Indexed: 11/06/2022]
Abstract
Carotid artery stenosis (CS) is a well-established risk factor for stroke. Increased proinflammatory chemokines, enhanced metallothionein (MT), and altered metal homeostasis may play roles in atherosclerosis progression and plaque destabilization. MT may sequester zinc during chronic inflammation, provoke zinc deficiency, and modulate NK cell cytotoxicity. A recent investigation of older patients with diabetes and atherosclerosis showed an association between the -209 A/G MT2A polymorphism, CS, and zinc status. In this study, we evaluated the relationship between two MT2A polymorphisms (-209 and + 838 locus), metal status, and inflammatory/immune response in older patients with CS only (the CS1 group) or with CS and previous cerebrovascular episodes (transient ischemic attack or stroke) (the CS2 group). A total of 506 individuals (188 CS1, 100 CS2, and 218 healthy controls) were studied. Atherosclerotic patients (CS1 and CS2) showed increased levels of MT, MCP-1, and RANTES, reduced NK cell cytotoxicity, and altered trace element concentrations (zinc, copper, magnesium, iron). The +838 C/G MT2A polymorphism was differently distributed in CS1 and CS2 patients, who displayed the GG genotype (C-) with significantly higher frequency than elderly controls. C- carriers showed increased MCP-1 and decreased NK cell cytotoxicity, CD56+ cells, and intracellular zinc availability along with decreased zinc, copper, and magnesium content in erythrocytes and increased iron in plasma. C- carriers also showed a major incidence of soft carotid plaques. In conclusion, the +838 C/G MT2A polymorphism seems to influence inflammatory markers, zinc availability, NK cell cytotoxicity, and trace element status, all of which may promote CS development.
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Affiliation(s)
- Robertina Giacconi
- Immunology Center (Section of Nutrition, Immunity, and Ageing), Research Department INRCA, Ancona, Italy
| | - Elisa Muti
- Immunology Center (Section of Nutrition, Immunity, and Ageing), Research Department INRCA, Ancona, Italy
| | - Marco Malavolta
- Immunology Center (Section of Nutrition, Immunity, and Ageing), Research Department INRCA, Ancona, Italy
| | - Catia Cipriano
- Immunology Center (Section of Nutrition, Immunity, and Ageing), Research Department INRCA, Ancona, Italy
| | - Laura Costarelli
- Immunology Center (Section of Nutrition, Immunity, and Ageing), Research Department INRCA, Ancona, Italy
| | - Gianni Bernardini
- Immunology Center (Section of Nutrition, Immunity, and Ageing), Research Department INRCA, Ancona, Italy
| | - Nazzarena Gasparini
- Immunology Center (Section of Nutrition, Immunity, and Ageing), Research Department INRCA, Ancona, Italy
| | - Erminia Mariani
- Laboratorio di Immunologia e Genetica, Istituto di Ricerca Codivilla Putti, IOR, Bologna, Italy
- Dipartimento di Medicina Interna e Gastroentrologia, Università di Bologna, Italy
| | | | | | - Eugenio Mocchegiani
- Immunology Center (Section of Nutrition, Immunity, and Ageing), Research Department INRCA, Ancona, Italy
- Address Correspondence and Reprint Requests to Eugenio Mocchegiani, Immunology Center (Section Nutrition, Immunity and Ageing), Research Department INRCA, Via Birarelli 8, 60121 Ancona, Italy, Phone: + 39-071-8004216; Fax: + 39-071-206791; E-mail:
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Sobesky J, Frackowiak M, Zaro Weber O, Hahn M, Möller-Hartmann W, Rudolf J, Neveling M, Grond M, Schmulling S, Jacobs A, Heiss WD. The Cologne Stroke Experience: Safety and Outcome in 450 Patients Treated with Intravenous Thrombolysis. Cerebrovasc Dis 2007; 24:56-65. [PMID: 17519545 DOI: 10.1159/000103117] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2006] [Accepted: 12/20/2006] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Predictors of outcome and safety in intravenous thrombolysis within 3 h in clinical routine is a matter of ongoing debate. Available reports contain small patient numbers or summarize heterogeneous multicenter data. METHODS Four hundred and fifty patients received intravenous thrombolysis within 3 h after stroke. Pretreatment NIHSS score and detailed medical history were analyzed. Noncontrast CT was performed before thrombolysis, 24-36 h later and in case of clinical deterioration. Symptomatic intracranial hemorrhage (SICH; any bleeding with an NIHSS increase of > or =4 points) and clinical outcome (modified Rankin Scale, mRS) after 3 months were recorded. Logistic regression identified parameters predictive of independence (mRS 0-2) and SICH. RESULTS Median onset to admission, door to needle and onset to treatment time was 75, 50 and 135 min, respectively. Direct presentation by emergency service (64%) was the fastest way of referral. Median pretreatment NIHSS was 11 points. Independence (mRS 0-2) was reached by 53%. Mortality was 11% (7% intracerebral, 4% extracerebral complications). Logistic regression identified low NIHSS, low age and absent diabetes as predictors of independence. Overall hemorrhagic complications and SICH were found in 18 and 4% of the patients, respectively. Extracerebral bleeding complications and allergic reactions were found in 3 and 1%, respectively. CONCLUSION This largest single center report presents a sample in the range of the 3 h rt-PA cohort of all randomized controlled trials. Outcome was comparable to randomized studies with a higher rate of independence and a lower rate of mortality and SICH.
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Affiliation(s)
- Jan Sobesky
- Max Planck Institute for Neurological Research, University of Cologne, Cologne, Germany.
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