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Diabetes And Stroke Pathophysiology

Role Of Prediabetes In Stroke

Role Of Prediabetes In Stroke

1Neurology Clinic, Clinical Center of Serbia, School of Medicine University of Belgrade, 2Department of Neurosurgery, Clinical Hospital Center Zemun, Belgrade, 3Department of Neurology, General Hospital Valjevo, Valjevo, Serbia; 4Department of Neurology, Tel-Aviv Sourasky Medical Center, Tel-Aviv University, Tel-Aviv, 5Shaare Zedek Medical Center, Jerusalem, Israel *These authors contributed equally to this work Abstract: Stroke is one of the leading causes of death and probably the greatest cause of adult disability worldwide. Diabetes mellitus (DM) is a state of accelerated aging of blood vessels. Patients with diabetes have increased risk of stroke. Hyperglycemia represents a risk factor for poor outcome following stroke, and probably is just a marker of poor outcome rather than a cause. Lowering of blood glucose levels has not been shown to improve prognosis. Also, prevention of stroke risk among patients with DM is not improved with therapy for reduction of glucose levels. On the other hand, prediabetes, a metabolic state between normal glucose metabolism and diabetes, is a risk factor for the development of DM type 2 and subsequently for stroke. Several methods are known to identify prediabetes patients, including fasting plasma glucose levels, 2-hour post load glucose levels, and glycosylated hemoglobin levels. In this text, we tried to summarize known data about diagnosis, epidemiology, risk factors, pathophysiology, and prevention of prediabetes in relation to DM and stroke. Keywords: diabetes mellitus, insulin, metabolic syndrome, prediabetes, risk factors, stroke Introduction A comprehensive review of available evidence and data sources on diagnosis, epidemiology, risk factors, pathophysiology, and prevention of prediabetes in relation to diabetes mellitus (D Continue reading >>

Diabetes Insipidus Pathophysiology

Diabetes Insipidus Pathophysiology

Diabetes insipidus is caused by abnormality in the functioning or levels of antidiuretic hormone (ADH), also known of as vasopressin. Manufactured in the hypothalamus and stored in the pituitary gland, ADH helps to regulate the amount of fluid in the body. In healthy individuals, when the bodily fluids are depleted, ADH is released from the pituitary gland which prevents the excretion of fluids from the body in the form of urine. ADH acts on the kidneys to increase water permeability in the collecting duct and distal convoluted tubule. Specifically, ADH acts on transmembrane protein channels called aquaporins that open up to allow water into the collecting duct. Once the permeability rises, the water is re-absorbed into the blood, reducing urine volume and increasing its concentration. The two forms of diabetes insipidus In central (cranial) diabetes insipidus, the production or release of ADH is too low to stop the kidneys from passing dilute urine, which results in an increased loss of water and therefore more thirst. People with nephrogenic diabetes insipidus, however, have adequate amounts of ADH in the body but the kidneys fail to respond it, and again the urine is still not concentrated. Causes of diabetes insipidus Some of the causes of cranial diabetes insipidus include: Genetic inheritance of a mutation in the vasopressin gene, AVP-NPII. The pattern of inheritance is autosomal. Brain tumors such as pituitary adenoma and craniopharyngiomas Head injury causing damage to the pituitary gland or hypothalamus. Injury may also result after brain surgery. Meningitis and encephalitis or brain infections may also affect the pituitary gland and the hypothalamus. Sheehan's syndrome, deposition of iron (haemochromotosis) in pituitary/hypothalamic tissue, Langerhans' cell hi Continue reading >>

Pathophysiology And Etiology

Pathophysiology And Etiology

Definitions Stroke A stroke (apoplexy) is the sudden onset of weakness, numbness, paralysis, slurred speech, aphasia, problems with vision and other manifestations of a sudden interruption of blood flow to a particular area of the brain. The ischemic area involved determines the type of focal deficit that is seen in the patient. Transient Ischemic Attack (TIA) A TIA is similar to a stroke, but the interruption of blood flow is temporary. The clot resolves sporadically. The symptoms are relatively the same as a stroke but last less than 24 hours, whereas stroke symptoms persist for greater than 24 hours. Causes of Stroke The primary pathophysiology of stoke is an underlying heart or blood vessel disease. The secondary manifestations in the brain are the result of one or more of these underlying diseases or risk factors. The primary pathologies include hypertension, atherosclerosis leading to coronary artery disease, dyslipidemia, heart disease, and hyperlipidemia. The two types of stroke that result from these disease states are ischemic and hemorrhagic strokes. Non-reducable Risk Factors The possibilities of a stroke occurring increases with age. For every decade (10 years) over the age of 55, the possibility of a stroke occurring doubles. A patient that is 75 years of age has four times the risk of having a stroke compared to someone who is 55 years old. Of all strokes that occur in people, approximately 65% occur in those who are over the age of 65. Those who have had a stroke or TIA are more likely to have another stroke or transient ischemic attack. Approximately 60% of strokes occur in patients who have had a previous TIA. Strokes generally occur more often in males than females, until the age of 55; after age 55 the risk is the same for both men and women. The occ Continue reading >>

Stroke: Highlights On Pathophysiology, Clinical Presentation, Acute Treatment And Prevention

Stroke: Highlights On Pathophysiology, Clinical Presentation, Acute Treatment And Prevention

Lama Al-Khoury, MD Clinical Assistant Professor Neurology UCI Medical Center Stroke Epidemiology Incidence of stroke in USA is 795,000/ year in the United States of America Incidence of Non-fatal strokes is 15 million/year in the world Stroke: 4rd killer in USA (used to be third) 2nd killer in world Secondary disability is present in one third of stroke survivors Stroke Stroke is Acute brain injury caused by: Ischemic stroke: Reduced blood supply to a region of the brain resulting in brain ischemic and neuronal death (87%) Hemorrhagic stroke: Primary brain hemorrhage resulting in compression of normal brain tissue (13%) Anterior and Posterior Cerebral Arterial Circulation Internal carotid arteries and their branches: supply the anterior circulation Vertebral arteries and the basilar artery (and their branches): supply the posterior cerebral circulation Mechanism of Ischemic Stroke and Transient Ischemic Attacks Atherosclerotic cerebrovascular disease (20%): Extracranial carotid or vertebral artery disease Intracranial cerbrovascular disease Penetrating small arterial disease (25%) Cardiogenic source (33%): Atrial fibrillation & other arrythmias Myocardial infarction Valvular disease Ventricular thrombi Aortic plaque Unusual causes (<5%): dissection, migraine, illicit drugs, vasculitis, venous strokes, hypercoagulability,… Cryptogenic source (no mechanism identified) Transient Ischemic attack (TIA) Definition: duration of transient neurologic symptoms lasting less than 1 hour Transient reduction of blood flow to a region in brain in the absence of evidence of infarction on brain imaging Mechanisms for TIA similar as for ischemic stroke Reconstitution of flow to the hypoperfused region hence the resolution of symptoms Significance of TIAs is increased risk of stroke Continue reading >>

Stroke In Diabetic Patients: Is It Really A Macrovascular Complication?

Stroke In Diabetic Patients: Is It Really A Macrovascular Complication?

We have read with interest the article by Wilcox et al,1 in which they demonstrated the positive effect of pioglitazone on stroke recurrence in patients with type 2 diabetes mellitus (DM). However, we would like to stress a particular concern regarding a basic concept in the difficult question of DM and stroke. In this study, as in other previous studies, stroke is considered a macrovascular event in diabetic patients, but is this statement true? Traditionally, retinopathy, neuropathy, and nephropathy have been designated microvascular complications of DM, and stroke, myocardial infarction and gangrene are termed macrovascular complications.2 However, we think it is time to change this commonly accepted concept. The pathophysiology of cerebrovascular disease in patients with DM is not fully characterized, but both large and small blood vessels seem to be affected. Thus, the etiology of strokes in diabetics is frequently microvascular disease from fibrinoid necrosis, which causes small subcortical infarcts or lacunar strokes.3 Different studies have suggested that, though there is no doubt that diabetes is an important risk factor for ischemic stroke overall, the increase in relative risk must be similar for all subtypes of ischemic strokes. Most of the previous population-based studies have not suggested any hint of a particular association between DM and any subtype of ischemic stroke. Similar results have been obtained in a systematic review of all relevant hospital-based and population-based studies.3,4 Furthermore, in the Atherosclerosis Risk in Communities Study,5 a prospective study of 14 448 men and women, even the authors observed a positive association between lacunar strokes and diabetes, with a population-attributable fraction for DM of 26.3% for lacunar vers Continue reading >>

2. Learning Objectives

2. Learning Objectives

4.1. Diabetic Ketoacidosis (DKA) Diabetic ketoacidosis results from lack of insulin and it is considered a medical emergency as it has a mortality rate of approximately 5 percent, mostly because of late recognition and frequently suboptimal management. Diabetic ketoacidosis can be the first manifestation of type 1 diabetes in a previously undiagnosed patient or can occur in a patient with type 1 diabetes when insulin requirements rise during medical stress. Noncompliance with insulin administration is another common cause of DKA. Although DKA is much more common in type 1 diabetes, it can also occur in patients with type 2 diabetes who have a predominant insulin secretory defect under severe medical stress. 4.1.1. Pathophysiology Diabetes is often referred to as "starvation in the midst of plenty" and the progression of events that results from acute insulin deficiency holds this concept to be valid. Insulin deficiency leads to impaired peripheral glucose uptake. In the presence of inadequate insulin, energy stores in fat and muscle are rapidly broken down into fatty acids and amino acids, which are then transported to the liver for conversion to glucose and ketones (beta-hydroxybutyrate and acetoacetate). Counter-regulatory hormones such as glucagon, catecholamines, cortisol and growth hormone rise in an attempt to correct the perceived low glucose levels, further contributing to hyperglycemia and ketonemia. The combination of increased production of glucose and ketones with decreased utilization (due to insulin deficiency) results in high levels of these substances. Hyperglycemia causes osmotic diuresis with an ensuing reduction of intravascular volume, which in turn causes an impairment of renal blood flow and an inability to excrete glucose which worsens the hypergl Continue reading >>

Diabetes And Stroke: Part One—risk Factors And Pathophysiology

Diabetes And Stroke: Part One—risk Factors And Pathophysiology

Abstract Diabetes is a major risk factor for stroke and is associated with an increase in overall stroke mortality. The metabolic syndrome associated with insulin resistance is also a significant risk factor for stroke. The etiology of stroke in diabetics is frequently microvascular disease from fibrinoid necrosis, which causes small subcortical infarcts designated as lacunar strokes. Diabetics also have an increased incidence of large vessel intracranial vascular disease. Although strict control of blood sugar has not been shown to reduce the overall incidence of stroke in diabetics, careful management of other associated risk factors, particularly hypercholesterolemia and hypertension, are imperative for the prevention of stroke in diabetic patients. Continue reading >>

Cardiovascular Disease & Diabetes

Cardiovascular Disease & Diabetes

The following statistics speak loud and clear that there is a strong correlation between cardiovascular disease (CVD) and diabetes. At least 68 percent of people age 65 or older with diabetes die from some form of heart disease; and 16% die of stroke. Adults with diabetes are two to four times more likely to die from heart disease than adults without diabetes. The American Heart Association considers diabetes to be one of the seven major controllable risk factors for cardiovascular disease. Why are people with diabetes at increased risk for CVD? Diabetes is treatable, but even when glucose levels are under control it greatly increases the risk of heart disease and stroke. That's because people with diabetes, particularly type 2 diabetes, may have the following conditions that contribute to their risk for developing cardiovascular disease. High blood pressure (hypertension) High blood pressure has long been recognized as a major risk factor for cardiovascular disease. Studies report a positive association between hypertension and insulin resistance. When patients have both hypertension and diabetes, which is a common combination, their risk for cardiovascular disease doubles. Abnormal cholesterol and high triglycerides Patients with diabetes often have unhealthy cholesterol levels including high LDL ("bad") cholesterol, low HDL ("good") cholesterol, and high triglycerides. This triad of poor lipid counts often occurs in patients with premature coronary heart disease. It is also characteristic of a lipid disorder associated with insulin resistance called atherogenic dyslipidemia, or diabetic dyslipidemia in those patients with diabetes. Learn more about cholesterol abnormalities as they relate to diabetes. Obesity Obesity is a major risk factor for cardiovascular disease Continue reading >>

Hypertension And Diabetes Mellitus

Hypertension And Diabetes Mellitus

Login or register to view PDF. Order reprints There has been an increase in the prevalence of diabetes mellitus over the past 40 years, both in the US and worldwide. The worldwide prevalence of diabetes in 2000 was approximately 2.8% and is estimated to grow to 4.4% by 2030. This translates to a projected rise of diabetes from 171 million in 2000 to well over 350 million in 2030. 1 The epidemic of diabetes will continue to rise as there is growing prevalence of obesity in children, which predisposes to diabetes.2 There is considerable evidence for an increased prevalence of hypertension in diabetic persons.3 In a large prospective cohort study that included 12,550 adults, the development of type 2 diabetes was almost 2.5 times as likely in persons with hypertension than in their normotensive counterparts.3,4 Similarly, evidence points to increased prevalence of hypertension in diabetic persons.3,5 Moreover, each pathophysiological disease entity serves to exacerbate the other.3,6 Both hypertension and diabetes predisposes to the development of cardiovascular disease (CVD) and renal disease.7,8 Subjects with diabetes are at about 60% increased risk of early mortality.8,9 The age-adjusted relative risk of death due to cardiovascular events in persons with type 2 diabetes is three-fold higher than in the general population. The presence of hypertension in diabetic patients substantially increases the risks of coronary heart disease, stroke, nephropathy and retinopathy.5,10,11 Indeed, when hypertension coexists with diabetes, the risk of CVD is increased by 75%, which further contributes to the overall morbidity and mortality of an already high-risk population.5,12 Generally, hypertension in type 2 diabetic persons clusters with other CVD risk factors such as microalbuminur Continue reading >>

Stroke

Stroke

Definition and Etiology A stroke is defined as an acute loss of neurological function due to an abnormal perfusion of brain tissue. Most strokes are ischemic (87%) in nature and commonly result from an arterial obstruction by a thrombus or embolus. Hemorrhagic strokes (13%) are caused by rupture or leak of a blood vessel either within the primary brain tissue or subarachnoid space. This chapter provides a clinical approach to the evaluation and management of stroke, with a focus on ischemic stroke. Prevalence and Risk Factors Because stroke is the leading cause of morbidity and the fourth-leading cause of death in the United States today, optimal reduction of risk factors is paramount in preventing and managing stroke. Modifiable and nonmodifiable stroke risk factors are listed in Table 1. In 2005, the prevalence of stroke in noninstitutionalized adults was 5.8 million in the United States alone. Based on American Stroke Association data, the estimated direct and indirect cost of stroke for 2008 was $65.5 billion, with an estimated lifetime cost of $140,000 per patient. Table 1: Cerebrovascular Disease Risk Factors Disease Modifiable Not Modifiable Ischemic stroke Hypertension Diabetes Atrial fibrillation Smoking Hyperlipidemia Carotid stenosis Lack of physical activity Age >55 Male gender Black race Family history of stroke Personal history of stroke Sickle Cell Disease Intraparenchymal hemorrhage Hypertension Antithrombotic use Thrombolytic use Coagulopathy Illicit Drug Use Vascular malformation Amyloid angiopathy Neoplasm Trauma Acute ischemic stroke Subarachnoid hemorrhage Hypertension Smoking Alcohol Abuse Aneurysm Family history of aneurysm or connective tissue disease Black or Hispanic Race Other vascular malformation Trauma Female gender Pathophysiology and Natu Continue reading >>

Cerebral Ischemic Damage In Diabetes: An Inflammatory Perspective

Cerebral Ischemic Damage In Diabetes: An Inflammatory Perspective

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. Keywords InflammationStrokeHypoglycemiaHyperglycemiaCell deathDiabetic brainCytokinesChemokinesImmune cells Background Diabetes is one of the most important metabolic disorders for public health owing to the increased prevalence of diabetes cases worldwide. According to the International Diabetes Federation, there are 382 million people living with diabetes worldwide [1]. The World Health Organization estimates that in 2030, diabetes will be the seventh leading cause of death [2]. Diabetes occu Continue reading >>

What Can I Do To Maintain My Blood Glucose And Prevent It From Increasing From The Normal Range?

What Can I Do To Maintain My Blood Glucose And Prevent It From Increasing From The Normal Range?

According to our present day knowledge, having type 2 diabetes you need both metformin, dosed as high as you can tolerate (up to three times 1,000 mgr during meals, limited by diarrhea and abdominal cramps as a side effect), and insuline as much as needed to have your diabetes well controlled. At present metformin by lowering one's insulin resistance is the only antidiabetic med that helps you prevent having a myocardial infarction (heart attack): Metformin From Arquivos Brasileiros de Endocrinologia & Metabologia From Targeting the Underlying Pathophysiology of Type 2 Diabetes So stopping metformin certainly wasn't such a good move, metformine by lowering insulin resistance can have your diabetes better regulated on the same amount or less insulin. You evidently haven't had any education on this, look around if there is a diabetes association who can help you with that, and teach you how to best deal with your diabetes. You'll also need a doctor well versed in dealing with diabetes, which is more than just blood sugar control, but needs controlling blood pressure (to avoid strokes, end stage kidney disease and such catastrophic events) and serum lipids (to prevent heart attacks) too. Strict blood sugar control is also very important in preventing diabetic retinopathy which if unrecognized (so see an eye doctor every 2 years if all is well, otherwise more often as prescribed by that doc) can lead to irreversible blindness. At present, if metformin plus twice daily an insulin mix (usually half long acting insulin e.g. NPH insulin plus regular insulin. both not ideal) doesn't control your diabetes well (that is blood sugar levels of around 125 mg/deciliter before meals, and not higher than 200 mg/deciliters one hour after meals, over the day and night not lower than aroun Continue reading >>

Diabetes And Stroke: Part One--risk Factors And Pathophysiology.

Diabetes And Stroke: Part One--risk Factors And Pathophysiology.

Abstract Diabetes is a major risk factor for stroke and is associated with an increase in overall stroke mortality. The metabolic syndrome associated with insulin resistance is also a significant risk factor for stroke. The etiology of stroke in diabetics is frequently microvascular disease from fibrinoid necrosis, which causes small subcortical infarcts designated as lacunar strokes. Diabetics also have an increased incidence of large vessel intracranial vascular disease. Although strict control of blood sugar has not been shown to reduce the overall incidence of stroke in diabetics, careful management of other associated risk factors, particularly hypercholesterolemia and hypertension, are imperative for the prevention of stroke in diabetic patients. Continue reading >>

Diabetes, The Metabolic Syndrome, And Ischemic Stroke

Diabetes, The Metabolic Syndrome, And Ischemic Stroke

Epidemiology and possible mechanisms Stroke affects more than 700,000 individuals each year; it is the third largest cause of death and the largest cause of adult disability in the U.S. Diabetes is a major risk factor for the development of stroke, yet this risk is not realized or understood by patients with diabetes. This likely reflects a lack of understanding within the medical community of how diabetes confers this risk. We will explore the potential underlying mechanisms that lead to increased incidence of stroke among diabetic patients. Beyond diabetes itself, the metabolic syndrome and its components will also be discussed. The impact of diabetes and hyperglycemia on stroke outcomes and a discussion of current approaches to reduce stroke in this high-risk population are included. Because type 2 diabetes affects the vast majority of those diagnosed with diabetes, it will be the primary focus of this discussion. DEFINING THE PROBLEM— It has been well documented that diabetes confers a significantly increased risk of stroke, as well as increased mortality following stroke (1–7). Stroke is a preventable disease with high personal and societal cost. While great progress has been made in understanding the link between diabetes and coronary heart disease (CHD), the literature on diabetes and stroke has been less enlightening. CHD is a larger problem that accounts for 40–50% of mortality in diabetes. Because of the overwhelming impact of CHD, the impact of stroke has been relatively underappreciated. Thus, physicians, diabetes educators, and nurses are less equipped to educate patients. We therefore review the relationship between diabetes and stroke. Given that more than one million people are diagnosed with diabetes yearly, a figure that is expected to rise, the Continue reading >>

Relationship Between Risk Factors And Activities Of Daily Living Using Modified Shah Barthel Index In Stroke Patients

Relationship Between Risk Factors And Activities Of Daily Living Using Modified Shah Barthel Index In Stroke Patients

Hypertension and diabetes mellitus are the most common risk factors of stroke. The study aimed to determine the relationship between hypertension and diabetes mellitus risk factors and dependence on assistance with activities of daily living in chronic stroke patients. The study used an analytical observational cross-sectional design. The study's sample included 44 stroke patients selected using the quota sampling method. The relationship between the variables was analyzed using the bivariate chi-squared test and multivariate logistic regression. Based on the chi-squared test, the relationship between the Modified Shah Barthel Index (MSBI) score and hypertension and diabetes mellitus as stroke risk factors, were p = 0.122 and p = 0.002, respectively. The logistic regression results suggest that hypertension and diabetes mellitus are stroke risk factors related to the MSBI score: p = 0.076 (OR 4.076; CI 95% 0.861-19.297) and p = 0.007 (OR 22.690; CI 95% 2.332-220.722), respectively. Diabetes mellitus is the most prominent risk factor of severe dependency on assistance with activities of daily living in chronic stroke patients. Content from this work may be used under the terms of the Creative Commons Attribution 3.0 licence. Any further distribution of this work must maintain attribution to the author(s) and the title of the work, journal citation and DOI. References Continue reading >>

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