Diabetes mellitus and stroke: A clinical update
Diabetes doubles your risk of a stroke, so it's important that it's treated and controlled well if you have it. This guide explains what diabetes is. This approach has been informative, yet the relationships between diabetes, the components of the metabolic syndrome, and stroke are clearly unique. Here, we . Diabetes and stroke are both serious health conditions that affect millions of people around the world. Learn more about their possible connection, and discover.
Insulin resistance Insulin resistance plays a major role in the pathology of cardiovascular disease. In the context of excess adipose tissue, insulin is unable to suppress lipolysis activity, which results in free fatty acid FFA mobilization.
The influx of FFA inhibits insulin stimulated peripheral glucose uptake in the liver, skeletal muscle, and other organs. In the vascular endothelial cells, FFA influx leads to mitochondrial overproduction of ROS, which activates the same pathogenic processes as hyperglycaemia. Increased FFA release also results in an adverse lipid profile characterized by raised triglycerides, reduced high-density lipoprotein cholesterol, and increased levels of small dense low-density lipoprotein LDL particles that accumulate in the arterial wall.
In the context of insulin resistance, increased FFA and defective insulin signaling receptors on the macrophages contribute to macrophage apoptosis and poor clearance of LDL by phagocytosis.
Consequently, necrotic breakdown of advanced lipid-rich plaques occurs, which lead to the progression of clinically relevant atherosclerotic lesions[ 39 ]. Unfortunately, studies reviewing the use of thiazolidinediones in patients with T2DM have not consistently shown this effect[ 4546 ]. The more recent Insulin Resistance Intervention after Stroke trial reviewed the use of the thiazolidinedione pioglitazone in patients without established T2DM but with markers of insulin resistance.
In many patients, the first diagnosis of diabetes is often made in the event of an acute stroke and especially in the elderly. Numerous observational studies have shown that acute hyperglycaemia in stroke is associated with larger infarct volumes, longer in-hospital stay, poor functional recovery, and increased d mortality[ 33 ]. There is limited evidence to suggest active glucose reduction with intravenous insulin therapy improves stroke outcomes[ 4950 ].
The largest efficacy trial to date, the United Kingdom Glucose Insulin in Stroke Trial, showed no difference in mortality or functional outcomes in patients with mild to moderate blood glucose elevations median 7. Therefore, the use of insulin infusion regimens with mild to moderate hyperglycaemia is not advisable.
The evidence of glycaemic management in the following days after a stroke is less clear as enteral feeding and oral intake can cause fluctuations in post-prandial glucose excursions. No randomised, prospective intervention studies have proven insulin administration for diurnal glycaemic variability translates to clinical benefits[ 5354 ].
The use of subcutaneous or intravenous insulin or oral agents will need to be balanced with the clinical presentation and risk of hypoglycemia[ 52 ].
However, it is less clear how beneficial long-term glycaemic control is on cardiovascular outcomes including stroke[ 55 - 59 ]. This study suggested poor glycaemic control is associated with increased cardiovascular risk and intensive treatment reduces such risk in individuals with T1DM.
The increase and early risk of cardiovascular disease in T1DM has been well-documented in the literature.
Even with early institution of intensive glycaemic control, its prevention and management require target-driven optimisation of individual cardiovascular risk factors dyslipidaemia, hypertension, hypercoagulability, renal impairment.
Diabetes and ischemic stroke are common diseases that frequently occurring together. Diabetes is an important risk factor for ischemic stroke and the association between these two conditions has been analyzed by several studies. Previously the Framingham study [ 1 ] found a 2. A multicenter cohort study from Italy [ 2 ], the DIA study including In persons with no history of cardiovascular disease, the age-standardized incidence of stroke per person-years was 5. In persons with a history of cardiovascular disease, it was These results underline that the incidence rates of stroke that were observed in this study confirm the importance of this event in subjects with diabetes mellitus.
Indeed the incidence of stroke in this cohort is times higher than that observed in the populations without diabetes. In addition, authors have also found that the combined role of Hba1c, microvascular complications, low HDL cholesterol, and treatment with insulin plus oral agents highlights the importance of diabetes mellitus history and clinical background in the development of stroke. Furthermore some authors [ 4 ], with the aim to quantify the associations of diabetes mellitus and fasting glucose concentration with risk of Coronary Heart Disease CHD and major stroke subtypes, have conducted a meta-analysis of individual records of diabetes, fasting blood glucose concentration, and other risk factors in people without initial vascular disease from prospective studies including participants.
They found that diabetes confers about a two-fold excess risk for coronary heart disease, major stroke subtypes, and deaths attributed to other vascular causes, independently from other conventional risk factors.
The risk of stroke associated with diabetes is assessed predominantly in people with type 2 diabetes, because in the age group in which most strokes take place, type 2 diabetes is much more common than type 1 diabetes.Diet Linked To Heart Disease Stroke And Diabetes Death HD
The risk of stroke in patients with type 1 diabetes has been assessed in few epidemiological studies and usually with limited sample size, and the results have been inconsistent. Nevertheless with regard of this issue Janghorbani et al.
In this study authors showed that both type 1 and type 2 diabetes are associated with substantially increased risks of total and most subtypes of stroke and also that the association between stroke and type 1 diabetes was stronger and this was probably attributable to younger age at onset, longer duration of diabetes, insulin deficiency, and development of hypertension with diabetic nephropathy, disturbances of coagulationfibrinolytic parameters, increased platelet adhesiveness, or episodes of hypoglycemia.
Therefore, the results of this study as well as others [ 6 ] that enable the direct confrontation between the two types of diabetes have shown that the relative risk of stroke in people with type 1 diabetes is at least similar or perhaps even higher in subjects with type 2 diabetes.
How Diabetes Increases Your Risk of Stroke
The results of all these studies [ 1 - 4 ] confirm that subjects with diabetes mellitus have approximately twice the risk of ischemic stroke compared with those without diabetes and then underline that diabetes mellitus is an important risk factor for ischemic stroke.
Furthermore, an important concept to emphasize is that the association between ischemic stroke and diabetes is bidirectional. Moreover, acute stroke may lead to abnormalities in glucose metabolism, which in turn could influence the outcome. In addition, in the context of cerebrovascular disease, diabetes may contribute to a more insidious brain damage represented by the diseases of Small Cerebral Vessels SVD such as lacunae or White Matter Hyperintensity WMH increasing the risk of cognitive decline and dementia [ 7 ] suggesting that the relationship between impaired glucose metabolism and cerebrovascular disease is not limited to acute ischemic stroke.
Risk Factors of Stroke Associated with Diabetes Among patients with diabetes several risk factors play a role together to promote the development of ischemic stroke.
Diabetes, Heart Disease, and Stroke | NIDDK
In the analysis of these risk factors can be identified diabetes-specific factors such as hyperglycemia and vascular risk factors such as hypertension and dyslipidemia [ 8 - 10 ]. In addition to these also genetic, demographic, and lifestyle factors contribute in varying degrees to the overall risk of the subjects with diabetes mellitus [ 11 - 15 ].
Role of Chronic Hyperglycemia As is well known, prolonged hyperglycemia is associated with microvascular complications, such as retinopathy, neuropathy, and nephropathy, and with macrovascular complications such as cerebrovascular and cardiovascular events and Peripheral Arterial Disease PAD caused by atherosclerosis [ 1617 ]. Hyperglycemia contributes to the pathogenesis of macrovascular complications through several possible pathways including the generation of large amounts of Reactive Oxygen Species ROS such as superoxide anions which may lead to the endothelial dysfunction by reducing the bioavailability of endothelium-derived NO, formation of Advanced Glycosylation End Products AGEs that by binding to their receptors accelerates the atherosclerotic process by promoting LDL uptake and oxidation leading to foam cell formation and finally the diversion of glucose into the aldose reductase pathway and the activation of one or more isozymes of protein kinase C PKC [ 18 - 22 ].
These changes, in their complexity, leading to the typical diabetic milieu that is characterized by a chronic state of low-grade inflammation, endothelial dysfunction, hypercoagulability, dyslipidemia and insulin resistance.
However, although it is well known the harmful role of prolonged hyperglycemia in the development of micro and macrovascular complications of diabetes, until now there are no evidence to show that stroke prevention will be improved by intensive glucose-lowering treatment, in people with either type 1 or type 2 diabetes [ 23 ].
Role of Hyperglycemia in Acute Ischemic Stroke On the other hand, deserves a separate mention, the pathogenetic and prognostic role of hyperglycemia in the acute phase of ischemic stroke. In animal models of reversible focal brain ischemia, hyperglycemia consistently increased infarct size and several mechanisms have been identified through which hyperglycemia could aggravate cerebral damage in ischemic stroke. These include the altered recanalization that has been attributed to disorders in coagulation and in fibrinolytic pathways mediated by hyperglycemia [ 2425 ], the decreased reperfusion of the damaged brain area caused by the disturbances in metabolism of endothelium-derived nitric oxide and last but not least the increased reperfusion injury which is the result of the detrimental effects of oxidative stress and inflammation [ 26 ].
The effects of the above mentioned mechanisms alter the recovery of the ischemic penumbra that is the part of the ischemic area which may still potentially recover if proper reperfusion is restored within hours after stroke onset.
- Diabetes, Heart Disease, and Stroke
- Diabetes mellitus and stroke: A clinical update
- Stroke: Diabetes and Other Risk Factors
On this basis, some authors [ 27 ] systematically reviewed the published literature to summarize the available evidence and to estimate the strength of the association between admission hyperglycemia and both short-term mortality and functional recovery after stroke with the aim to evaluate if stress hyperglycemia may be associated with increased mortality and poor recovery in people with diabetes and in patients without diabetes after stroke.
Furthermore other studies [ 2829 ] suggest that the association between hyperglycemia and poor outcome after stroke is stronger in patients with large-vessel thromboembolic stroke than in those with lacunar stroke and this is understandable considering that hyperglycemia primarily exerts its detrimental effects at the level of the ischemic penumbra which is usually not present in lacunar subtype.
The detected relationship between hyperglycemia and poor outcome in patients with ischemic stroke arouses the question of whether the outcome may be improved by glucose-lowering treatment. In fact, although it is true that the concentrations of glucose can be reduced by several treatment regimens of insulin, one has to consider that in the early days after the onset of stroke the realization of normal blood glucose concentrations may be difficult probably because the intake of oral food causes fluctuations in the levels of glucose.
Therefore, the achievement of stable normoglycemia in the acute phase of stroke can be difficult and the possibility of hypoglycemia remains a concern, because even with intensive monitoring, many patients may experience one or more episodes of hypoglycemia [ 3031 ].
Findings of randomized controlled trials specifically targeting individuals with stroke have failed to show beneficial effects. Therefore, there is evidence suggesting that that glucose-lowering treatment improves clinical outcome in patients with acute ischemic stroke and to date uncertainty persists about the issue of whether glucose-lowering treatment for early stroke can improve clinical outcome.
Diabetes mellitus and hypertension are both common diseases and they represent two powerful independent risk factors for cardiovascular, renal and atherosclerotic disease. The pathogenesis of hypertension in diabetes type 1 and type 2 is different. Diabetic nephropathy is considered to be the main factor that contributes to the development of hypertension in patients with diabetes mellitus type 1.
In the case of type 2 diabetes mellitus, hypertension is more often essential and it is part of a plurimetabolic syndrome in a context of insulin resistance. In all cases, hypertension worsens the prognosis of patients, increasing the risk of both macrovascular and microvascular complications. Role of Dyslipidemia Dyslipidemia is one of the major risk factors for cardiovascular and cerebrovascular disease in diabetes mellitus.
The defects in the synthesis and clearance of plasma lipoproteins are among the most commonly metabolic abnormalities that accompany diabetes.
The diabetic dyslipidemia, a characteristic pattern characterized by the presence of low levels of High Density Lipoprotein HDL cholesterol, hypertriglyceridemia, and postprandial lipemia and which is observed more frequently in type 2 diabetes, is one of several factors that contribute to accelerating macrovascular disease in subjects with diabetes mellitus. Among the different factors involved in developing of diabetic dyslipidemia should be considered: The acknowledgment and treatment of dyslipidemia are therefore two important elements in the framework of a multidisciplinary approach aimed at the prevention of cerebrovascular and cardiovascular events in people with diabetes.
In this regard, several studies aimed to assess the effectiveness of statins for primary and secondary prevention of major cardiovascular events in patients with type 2 diabetes. It is based on the presence of 3 of the following components: The relationship between MetS and stroke was evaluated by several studies. On this purpose, with the aim to investigate the relation between the MetS and risk of ischemic stroke and vascular events in the urban community—based, multiethnic, prospective cohort of the Northern Manhattan Study NOMASa total of subjects were recruited and enrolled between and [ 37 ].
The authors found a significant association between the MetS and ischemic stroke risk, independent of other confounding factors including age, education, physical activity, alcohol use, and current smoking.
Although the MetS is often considered a prediabetic condition and diabetes is a major risk factor for ischemic stroke, the association of the MetS without diabetes with incident ischemic cerebrovascular events has not been studied in depth, and therefore, some authors [ 38 ] conducted a study with the aim to assess the prevalence of the MetS in a large cohort of patients with atherosclerotic cardiovascular diseases and to explore the relation of MetS versus frank diabetes with first-ever ischemic stroke or Transient Ischemic Attack TIA.
The results of this study showed that, after adjusting for stroke risk factors, patients with MetS without diabetes exhibited a 1.