Gender difference in diabetes-associated risk of first-ever and recurrent ischemic stroke

Policardo, Laura; Seghieri, Giuseppe; Francesconi, Paolo; Anichini, Roberto; Franconi, Flavia; Seghieri, Chiara; Prato, Stefano Del

doi:10.1016/j.jdiacomp.2014.12.008

Cited by 33 publications

(28 citation statements)

References 35 publications

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“…However, the exact mechanism by which diabetes induces stroke is unclear till date [16,17] . Similarly, risk of diabetes and stroke were reported to increase with advancing age [6,18] . We found that majority of diabetic AIS patients (83%) were of advanced age group (i.e.…”

Section: Discussionmentioning

confidence: 99%

“…Diabetes is one of the vital comorbidity risk factor reported to be associated with occurrence, poor outcome, and recurrence in stroke patients [3][4][5] . An increased incidence of stroke has been reported in advanced age among diabetic patients [6] . Recent report by the International Diabetes Federation suggested that diabetes is rapidly increasing worldwide, and it is estimated to reach a total of approximately 366 million by 2030 [7] .…”

Section: Prediction Of Outcome In Diabeticmentioning

confidence: 99%

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Prediction of Outcome in Diabetic Acute Ischemic Stroke Patients: A Hospital-Based Pilot Study Report

Nayak

Badar²,

Lande

et al. 2016

Ann Neurosci

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Background: Demographic and clinical characteristics are known to influence the outcome in acute ischemic stroke (AIS) patients. Purpose: This study is aimed at evaluating short- and long-term outcomes in diabetic AIS patients. In addition, the study also evaluates the impact of diabetes on the performance of indigenously reported biomarker, inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) and known biomarkers, neuron-specific enolase (NSE) and glial-derived S-100 beta beta protein (S-100ββ). Methods: This study was performed on 29 diabetes and 75 non-diabetes AIS patients. Outcome of AIS patients was analyzed by using modified Rankin scale at discharge, then at 12 and 18 months after discharge. Based on the obtained scores, patients were classified as improved group (scales 1-3) and dependent/expired group (scales 3-6). Blood samples were collected during admission and at discharge/expired time. Levels of NSE, S100ββ, and ITIH4 were analyzed in all samples. Results: On discharge, frequencies of dependent/expired outcome were 4/29 (14%) and 19/75 (17%) in diabetic and non-diabetic AIS patients. However, follow-up outcome at 12 and 18 months showed higher dependent/expired cases of 43 and 41% among diabetic AIS patients compared to 27 and 21% in non-diabetic patients. Multivariate analysis revealed that diabetes is an independent risk factor for dependent/expired outcome in AIS patients (OR 0.484 (at discharge); 1.307 (at 12 months) and 1.675 (at 18 months)). NSE, S100ββ, and ITIH4 showed a differential expression in both the outcome groups of AIS patients, irrespective of diabetes. Conclusion: Diabetes increases the risk of dependent/expired outcome in AIS patients. Also, serum NSE, S100ββ, and ITIH4 are independent biomarkers for prognosis of outcome in AIS patients, irrespective of diabetes.

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Section: Discussionmentioning

confidence: 99%

Section: Prediction Of Outcome In Diabeticmentioning

confidence: 99%

Prediction of Outcome in Diabetic Acute Ischemic Stroke Patients: A Hospital-Based Pilot Study Report

Nayak

Badar²,

Lande

et al. 2016

Ann Neurosci

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“…In a different carotid occlusion model and hyperglycemia, female sex was associated with less severe outcomes ( 52 ). Clinically there are reported differences in both stroke risk and outcomes in diabetics related to gender ( 53 , 54 ), which is complicated by different risk factors, stroke etiologies, and treatment responses but remains an important issue to address in preclinical models.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Novel Carbon Nanoparticle Antioxidant Therapy in a Severe Model of Reversible Middle Cerebral Artery Stroke in Acutely Hyperglycemic Rats

et al. 2018

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IntroductionWhile oxidative stress can be measured during transient cerebral ischemia, antioxidant therapies for ischemic stroke have been clinically unsuccessful. Many antioxidants are limited in their range and/or capacity for quenching radicals and can generate toxic intermediates overwhelming depleted endogenous protection. We developed a new antioxidant class, 40 nm × 2 nm carbon nanoparticles, hydrophilic carbon clusters, conjugated to poly(ethylene glycol) termed PEG-HCCs. These particles are high-capacity superoxide dismutase mimics, are effective against hydroxyl radical, and restore the balance between nitric oxide and superoxide in the vasculature. Here, we report the effects of PEG-HCCs administered during reperfusion after transient middle cerebral artery occlusion (tMCAO) by suture in the rat under hyperglycemic conditions. Hyperglycemia occurs in one-third of stroke patients and worsens clinical outcome. In animal models, this worsening occurs largely by accelerating elaboration of reactive oxygen species (ROS) during reperfusion.MethodsPEG-HCCs were studied for their protective ability against hydrogen peroxide in b.End3 brain endothelial cell line and E17 primary cortical neuron cultures. In vivo, hyperglycemia was induced by streptozotocin injection 2 days before tMCAO. 58 Male Sprague-Dawley rats were analyzed. They were injected IV with PBS or PEG-HCCs (4 mg/kg 2×) at the time of recanalization after either 90- or 120-min occlusion. Rats were survived for up to 3 days, and infarct volume characteristics and neurological functional outcome (modified Bederson Score) were assessed.ResultsPEG-HCCs were protective against hydrogen peroxide in both culture models. In vivo improvement was found after PEG-HCCs with 90-min ischemia with reduction in infarct size (42%), hemisphere swelling (46%), hemorrhage score (53%), and improvement in Bederson score (70%) (p = 0.068–0.001). Early high mortality in the 2-h in the PBS control group precluded detailed analysis, but a trend was found in improvement in all factors, e.g., reduction in infarct volume (48%; p = 0.034) and a 56% improvement in Bederson score (p = 0.055) with PEG-HCCs.ConclusionThis nano-antioxidant showed some improvement in several outcome measures in a severe model of tMCAO when administered at a clinically relevant time point. Long-term studies and additional models are required to assess potential for clinical use, especially for patients hyperglycemic at the time of their stroke, as these patients have the worst outcomes.

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“…The sex ratio of risk of fatal CHD or stroke showed a greater risk in women, which did not improve over time ( 273 , 274 ). An Italian register study found that diabetes increased the risk of first ever ischemic stroke by more than 50% in both men and women ( 299 ). Interestingly, this risk decreased with advancing age in both sexes but at a faster rate among men.…”

Section: Cardiovascular Complicationsmentioning

confidence: 99%

Sex and Gender Differences in Risk, Pathophysiology and Complications of Type 2 Diabetes Mellitus

2016

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The steep rise of type 2 diabetes mellitus (T2DM) and associated complications go along with mounting evidence of clinically important sex and gender differences. T2DM is more frequently diagnosed at lower age and body mass index in men; however, the most prominent risk factor, which is obesity, is more common in women. Generally, large sex-ratio differences across countries are observed. Diversities in biology, culture, lifestyle, environment, and socioeconomic status impact differences between males and females in predisposition, development, and clinical presentation. Genetic effects and epigenetic mechanisms, nutritional factors and sedentary lifestyle affect risk and complications differently in both sexes. Furthermore, sex hormones have a great impact on energy metabolism, body composition, vascular function, and inflammatory responses. Thus, endocrine imbalances relate to unfavorable cardiometabolic traits, observable in women with androgen excess or men with hypogonadism. Both biological and psychosocial factors are responsible for sex and gender differences in diabetes risk and outcome. Overall, psychosocial stress appears to have greater impact on women rather than on men. In addition, women have greater increases of cardiovascular risk, myocardial infarction, and stroke mortality than men, compared with nondiabetic subjects. However, when dialysis therapy is initiated, mortality is comparable in both males and females. Diabetes appears to attenuate the protective effect of the female sex in the development of cardiac diseases and nephropathy. Endocrine and behavioral factors are involved in gender inequalities and affect the outcome. More research regarding sex-dimorphic pathophysiological mechanisms of T2DM and its complications could contribute to more personalized diabetes care in the future and would thus promote more awareness in terms of sex- and gender-specific risk factors.

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Gender difference in diabetes-associated risk of first-ever and recurrent ischemic stroke

Cited by 33 publications

References 35 publications

Prediction of Outcome in Diabetic Acute Ischemic Stroke Patients: A Hospital-Based Pilot Study Report

Prediction of Outcome in Diabetic Acute Ischemic Stroke Patients: A Hospital-Based Pilot Study Report

Efficacy of Novel Carbon Nanoparticle Antioxidant Therapy in a Severe Model of Reversible Middle Cerebral Artery Stroke in Acutely Hyperglycemic Rats

Sex and Gender Differences in Risk, Pathophysiology and Complications of Type 2 Diabetes Mellitus

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