Idiopathic neuropathy patients are at high risk for metabolic syndrome

BACKGROUND: Idiopathic neuropathy patients are at high risk of impaired glucose tolerance (IGT). Hyperglycemia, low high density lipoprotein (HDL), elevated triglycerides (TRG), hypertension and central obesity co-associate and constitute the metabolic syndrome. Patients with hyperglycemia are at high risk of having the syndrome and each of its features. Our null hypothesis was that patients with neuropathy and IGT would have a higher prevalence of other metabolic syndrome features than those without hyperglycemia. The primary objective was to determine if metabolic syndrome features other than hyperglycemia increase neuropathy risk. METHODS: The prevalence of metabolic syndrome features was determined among 219 sequential patients with idiopathic peripheral neuropathy. Subjects were classified as having IGT or normoglycemia. The prevalence of metabolic syndrome was compared to published population prevalence data. To compensate for potential referral bias, data were also compared for175 diabetic subjects without neuropathy, given the well-recognized risk of metabolic syndrome among diabetic individuals. RESULTS: Contrary to our hypothesis, neuropathy patients with normoglycemia and IGT shared a similarly elevated prevalence of metabolic syndrome features compared to published normal populations. Compared to diabetic subjects without neuropathy, the normoglycemic neuropathy patients had significantly higher total and LDL cholesterol, and a higher prevalence of abnormal HDL and triglycerides. The prevalence of obesity and hypertension was similar among patient groups. Normoglycemic neuropathy subjects had significantly more features of metabolic syndrome (other than hyperglycemia) than diabetics. CONCLUSIONS: These findings demonstrate an association between neuropathy and metabolic syndrome features other than hyperglycemia. Lipid abnormalities are particularly prevalent among neuropathy subjects.     

Impaired glucose tolerance and metabolic syndrome in idiopathic neuropathy

Idiopathic neuropathy is one of the most common clinical problems encountered in general medical and neurological practices, accounting for up to 40% of all neuropathies in referral series. Several groups have reported an elevated prevalence of impaired glucose tolerance (IGT) in idiopathic neuropathy subjects, although the only carefully conducted case-control study suggested hypertriglyceridemia was a more important risk factor. The nature of the relationship between IGT and neuropathy is a subject of active debate. An evolving literature suggests metabolic syndrome, particularly dyslipidemia and obesity, are potent neuropathy risk factors for both idiopathic and diabetic neuropathy patients. Once established, diabetic neuropathy is likely to be very difficult to reverse. IGT-associated neuropathy, however, may be more amenable to therapy and could represent an ideal population in which to examine potential therapies for diabetes and obesity related neuropathies. Further research is needed to better define the epidemiological relation between IGT, metabolic syndrome, and neuropathy, its underlying pathophysiology, and to develop appropriate surrogate measures and clinical trials strategies.     

Association of Metabolic Syndrome and C-reactive Protein Levels with Intracranial Atherosclerotic Stroke

Background

The risk factors for intracranial atherosclerosis are unclear but may differ from those for other stroke subtypes. Here, we investigated whether metabolic syndrome, an emerging risk factor for cardiovascular disease, is associated with intracranial atherosclerotic stroke.

Methods

Using the Adults Treatment Panel III criteria, we evaluated the components of metabolic syndrome in 439 patients with ischemic stroke or transient ischemic attacks. The prevalence of metabolic syndrome within each stroke subtype was determined, and the association between intracranial atherosclerosis and metabolic syndrome was evaluated.

Results

Metabolic syndrome was observed more frequently in patients with intracranial atherosclerosis than in those with other types of stroke (P=0.003). In a multiple regression analysis, metabolic syndrome, but not conventional risk factors, was independently associated with intracranial atherosclerosis (P=0.016). By contrast, the serum level of C-reactive protein was correlated negatively with the presence of intracranial atherosclerosis. Intracranial atherosclerosis was most prevalent in patients with metabolic syndrome and low levels of C-reactive protein (P=0.024).

Conclusions

Our results indicate that metabolic syndrome is a strong independent risk factor for intracranial atherosclerotic stroke. Therefore, treatment of metabolic abnormalities may be an important prevention strategy for intracranial atherosclerotic stroke.     

Autoantibodies to cytosolic 5′‐nucleotidase 1A in inclusion body myositis

The metabolic syndrome and neuropathy are common conditions, especially in the elderly, that are associated with significant morbidity. Furthermore, the metabolic syndrome is reaching epidemic proportions across the world. Current evidence supports the association of the metabolic syndrome and its individual components with neuropathy. Several clinical trials have demonstrated that treating hyperglycemia, a component of the metabolic syndrome, has a significant effect on reducing the incidence of neuropathy in those with type 1 diabetes. However, glucose control has only a marginal effect on preventing neuropathy in those with type 2 diabetes, suggesting that other factors may be driving nerve injury in these patients. Emerging evidence supports the metabolic syndrome as including risk factors for neuropathy. Interventions exist for treatment of all of the metabolic syndrome components, but only glucose control has strong evidence to support its use and is widely employed. Our understanding of the biology of metabolic nerve injury has rapidly expanded over the past several years. Mechanisms of injury include fatty deposition in nerves, extracellular protein glycation, mitochondrial dysfunction, and oxidative stress. Additionally, the activation of counter‐regulatory signaling pathways leads to chronic metabolic inflammation. Medications that target these signaling pathways are being used for a variety of diseases and are intriguing therapeutic agents for future neuropathy clinical trials. As we move forward, we need to expand our understanding of the association between the metabolic syndrome and neuropathy by addressing limitations of previous studies. Just as importantly, we must continue to investigate the pathophysiology of metabolically induced nerve injury. Ann Neurol 2013;74:397–403     

Current understanding of multiple risk factors as the metabolic syndrome: distillation or deconstruction

The "metabolic syndrome" is a new term that defines the clustering of vascular risk factors, such as hyperlipidemia, obesity, elevated blood pressure, and elevated blood glucose. Controversy exists regarding the use of the term, which raises the question of whether the unique grouping of vascular risk factors adds more clinical risk then the additive effect of multiple risk factors viewed as separate but important entities. Whatever the answer, the metabolic syndrome constitutes a major public health problem with over 47 million persons in the United States meeting criteria for the metabolic syndrome. Although studies have demonstrated that the metabolic syndrome is a risk factor for overall mortality as well as cardiovascular events, the relationship between the metabolic syndrome and ischemic stroke has not been well characterized. Two large cross-sectional studies report an association between metabolic syndrome and increased risk of a history of stroke. One large multiethnic prospective study found the metabolic syndrome to be significantly associated with an increased risk of ischemic stroke after adjustment for sociodemographics and other cardiovascular risk factors. This study estimated that the metabolic syndrome may account for 19% of ischemic strokes including 30% of stroke in women and over 40% of stroke in Hispanics. Despite debate about the utility of its definition, there is evidence to suggest that the metabolic syndrome is an important risk factor for ischemic stroke, with differential effects by gender and race-ethnicity. Further, the metabolic syndrome has important clinical and public health implications by helping to easily identify individuals at greatest risk of vascular events.     

Diabetic neuropathy: clinical manifestations and current treatments

Diabetic peripheral neuropathy is a prevalent, disabling disorder. The most common manifestation is distal symmetrical polyneuropathy (DSP), but many patterns of nerve injury can occur. Currently, the only effective treatments are glucose control and pain management. While glucose control substantially decreases the development of neuropathy in those with type 1 diabetes, the effect is probably much smaller in those with type 2 diabetes. Evidence supports the use of specific anticonvulsants and antidepressants for pain management in patients with diabetic peripheral neuropathy. However, the lack of disease-modifying therapies for diabetic DSP makes the identification of new modifiable risk factors essential. Growing evidence supports an association between components of the metabolic syndrome, including prediabetes, and neuropathy. Studies are needed to further explore this association, which has implications for the development of new treatments for this common disorder.     

从糖尿病前期到糖尿病高危:糖调节异常与脑卒中研究最新进展

新近流行病学研究表明,由于生活方式的迅速改变,糖尿病已经成为我国的主要公共健康问题。糖尿病能够增加卒中风险2～5倍。空腹血糖受损(impaired fasting glucose,IFG)和糖耐量异常(impaired glucose tolerance,IGT)合称糖尿病前期、糖调节异常或中间型高血糖,也增加卒中风险。胰岛素抵抗,血脂代谢紊乱,凝血和纤溶异常,慢性炎症和血管内皮功能损害是可能机制。在美国糖尿病协会(American Diabetes Association)2010年指南中,"糖尿病高危"代替了"糖尿病前期"的概念,并涵盖了糖化血红蛋白(Hemoglobin A_1c)在5.7%～6.4%之间的患者。随机对照试验证实,对糖尿病高危患者进行干预能够减少糖尿病发病率。同时有研究表明治疗IGT能够减少心血管事件和高血压的发病,这需要进一步研究证实。应该对卒中患者进行筛检,发现糖尿病高危患者并进行干预。     

POEMS syndrome with prominent acute axonal lesions

Polyneuropathy is a common presenting component of POEMS syndrome whose symptoms are attributed to an overproduction of vascular endothelial growth factor (VEGF). We report two female patients with POEMS syndrome presenting as a severe predominantly axonal neuropathy. A nerve biopsy was performed for these patients; pathological data confirmed unusual numerous acute axonal lesions associated with other classical signs of POEMS syndrome. POEMS syndrome is usually associated with demyelinating neuropathy (and secondary axonal loss); however, prominent axonal neuropathy (with acute axonal lesions on nerve biopsy) can also be observed in this disease. These observations illustrate the heterogeneity of peripheral nervous system involvement in POEMS syndrome.     

Insulin resistance and risk for stroke

BACKGROUND AND PURPOSE: Resistance to insulin-mediated glucose uptake by peripheral tissues is a cardinal defect in type 2 diabetes mellitus. Insulin resistance is also common among nondiabetic individuals, and may be an important risk factor for stroke in both populations. The authors review the definition, epidemiology, and treatment of insulin resistance. METHODS: The authors searched Medline (1977-2001) and reviewed bibliographies to identify pertinent English-language publications. RESULTS: Insulin resistance is present in most patients with type 2 diabetes. It is also common among elderly persons, certain ethnic groups, and persons with hypertension, obesity, physical deconditioning, and vascular disease. The principal pathophysiologic defect is impaired intracellular signaling in muscle tissue leading to defective glycogen synthesis. Insulin resistance is associated with numerous metabolic, hematologic, and cellular events that promote atherosclerosis and coagulation. The association between insulin resistance and risk for stroke has been examined in four case-control studies and five prospective observational cohort studies. Six of the nine studies are methodologically sound and provide evidence that insulin resistance is associated with risk for stroke. CONCLUSION: Insulin resistance may be a prevalent risk factor for stroke. New drugs can safely reduce insulin resistance and may have a role in stroke prevention.     

Epidermal nerve innervation in impaired glucose tolerance and diabetes-associated neuropathy.

The authors describe skin biopsy findings in patients with peripheral neuropathy associated with diabetes and impaired glucose tolerance (IGT). Six patients with IGT, eight with early diabetes-associated neuropathy, and five controls were recruited. Most subjects underwent nerve conduction studies (NCS) and quantitative sensory tests (QST). Skin biopsy was abnormal in all neuropathy subjects and correlated poorly with NCS. Neuropathy associated with IGT primarily affects small fibers and is similar to early diabetes-associated neuropathy.     

Treatment of Risk Factors to Prevent Stroke

Much of the decline in stroke incidence and mortality for the past several decades in Western countries has been attributed to better treatment of risk factors. Many epidemiological studies and clinical trials confirmed the importance of managing hypertension. Comparative trials of anti-hypertensive drugs or drug classes have not yielded clear results, but blood pressure variability may play an important role beyond the absolute value of blood pressure. Diabetes therapy remains a conundrum. Although diabetes is clearly a risk factor for ischemic stroke, treatment trials targeting different glycemic goals have not indicated that glucose lowering results in stroke prevention. Trials focused on insulin resistance are ongoing and they may be able to help establish the management of diabetes/impaired glucose tolerance. Evidence for treatment of dyslipidemia has contrasted science to diabetes mellitus. Dyslipidemia has not been strongly or consistently linked to ischemic stroke but the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial showed the impact of statin treatment in stroke prevention. The results of clinical trials investigating dabigatran and rivaroxaban clearly indicate alternative strategies to vitamin K antagonists in stroke prevention for persons with atrial fibrillation. Evidence for stroke prevention by life style modification, treating metabolic syndrome, sleep disordered breathing, lipoprotein (a), hyperhomocysteinemia, and coagulation disorders are also discussed.     

Unfairness and the social gradient of metabolic syndrome in the Whitehall II Study

OBJECTIVES: Little work has investigated the relationship between unfairness and risk factors for heart disease. We examine the role of unfairness in predicting the metabolic syndrome and explaining the social gradient of the metabolic syndrome. METHODS: The design is a prospective study with an average follow-up of 5.8 years. Participants were 4128 males and 1715 females of 20 civil service departments in London (Whitehall II study). Sociodemographics, unfairness, employment grade, behavioral risk factors, and other psychosocial factors were measured at baseline (Phase 3, 1991-1993). Waist circumference, triglycerides, high-density lipoprotein (HDL) cholesterol, fasting glucose, and hypertension were used to define metabolic syndrome at follow-up (Phase 5, 1997-2000), according to the National Cholesterol Education Program/Adult Treatment Panel III guidelines. RESULTS: Unfairness is positively associated with waist circumference, hypertension, triglycerides, and fasting glucose and negatively associated with serum HDL cholesterol. High levels of unfairness are also associated with the metabolic syndrome [odds ratio (OR)=1.72, 95% CI=1.31-2.25], after adjustment for age and gender. After additional adjustment for employment grade, behavioral risk factors, and other psychosocial factors, the relationship between high unfairness and metabolic syndrome weakened but remained significant (OR=1.37, 95% CI=1.00-1.93). When adjusting for unfairness, the social gradient of metabolic syndrome was reduced by approximately 10%. CONCLUSION: Unfairness may be a risk factor for the metabolic syndrome and its components. Future research is needed to study the biological mechanisms linking unfairness and the metabolic syndrome.     

Evaluation and treatment of painful peripheral polyneuropathy

Pain is a common component of sensory peripheral polyneuropathy and occurs primarily as a consequence of injury to small, unmyelinated C-fiber nerve axons. This class of fibers is particularly vulnerable to metabolic injury, and the neuropathy manifests in a length-dependent pattern. Diabetes mellitus, prediabetes associated with insulin resistance, toxins, and drugs are common causes of painful neuropathy, but a substantial percentage are idiopathic. Pathogenesis of neuropathic pain involves loss of peripheral axons and inappropriate peripheral and central adaptation of neuronal signaling to this loss. Treatment of painful neuropathy should be directed at removing the offending metabolic injury, if possible. Antiepileptic drugs, tricyclic antidepressants, opiates, and other treatments have shown efficacy in clinical trials for symptomatic relief of neuropathic pain.     

Metabolic syndrome and three of its components as risk factors for recurrent ischaemic stroke presenting as large-vessel infarction

Background and purpose:  Although a clear protocol for reduction of recurrent ischaemic stroke (RIS) has been established, few studies have compared the stroke subtype distribution and risk factors between RIS and first-ever stroke (FES).
Methods:  This one-year hospital-based study enrolled 587 FES and 475 RIS patients. Patients were categorized into four stroke subtypes according to a modified TOAST stroke subtype classification system. Risk factor profiles were compared between the two major stroke groups and between the corresponding four subtypes to discriminate the significant risk factors for RIS.
Results:  A multivariate regression analysis identified hypertension (OR, 1.87; 95% CI, 1.34–2.62), diabetes mellitus (DM) (OR, 1.57; 95% CI, 1.22–2.02), low high-density lipoprotein (LHDL) (OR, 1.43; 95% CI, 1.08–1.88) and older age as significant RIS risk factors. The significance of the former three RIS factors was further recognized in its large-vessel subtype. Moreover, metabolic syndrome was significantly more common in the recurrent stroke group ( P  = 0.01), including its large-vessel subtype ( P  = 0.04). Progressively increasing odds ratios from 1.49 to 2.02, in accordance with increased number of diagnostic components of metabolic syndrome for recurrent large-vessel ischaemic stroke, were noted.
Conclusions:  Metabolic syndrome likely plays a crucial role in the development of RIS, including large-vessel infarction in modern-day Taiwan.     

Sleeping over a sleep disorder - Awareness of obstructive sleep apnoea as a modifiable risk factor for hypertension and stroke: A survey among health care professionals and medical students

Background:

Obstructive sleep apnoea (OSA) syndrome is an established and modifiable but under recognized risk factor for common disorders like stroke and hypertension.

Objective:

To assess awareness level of health care practitioners and medical students about OSA as a risk factor for stroke and hypertension.

Methods:

Questionnaire based survey with multiple response type and fill in the blanks type questions. The data was compiled and analyzed using SPSS version 19.

Results:

180 participants completed the survey questionnaire. Only 24 (13.3%) identified OSA as a reversible risk factor for ischemic stroke. 11 (6%) participants only could answer OSA as an identified risk factor for hypertension as per Seventh Joint National Committee report.

Conclusion:

This study reveals dismal level of awareness, among health professionals and medical students, about OSA being an established and modifiable risk factor for hypertension and ischemic stroke.     

Idiopathic neuropathy, prediabetes and the metabolic syndrome

Peripheral neuropathy is a common problem encountered by neurologists and primary care physicians. While there are many causes for peripheral neuropathy, none can be identified in a large percentage of patients ("idiopathic neuropathy"). Despite its high prevalence, idiopathic neuropathy is poorly studied and understood. There is evolving evidence that impaired glucose tolerance (prediabetes) is associated with idiopathic neuropathy. Preliminary data from a multicenter study of diet and exercise in prediabetes (the Impaired Glucose Tolerance Neuropathy Study) suggests a diet and exercise counseling regimen based on the Diabetes Prevention Program results in improved metabolic measures and small fiber function. Prediabetes is part of the Metabolic Syndrome, which also includes hypertension, hyperlipidemia and obesity. Individual aspects of the Metabolic Syndrome influence risk and progression of diabetic neuropathy and may play a causative role in neuropathy both for those with prediabetes, and those with otherwise idiopathic neuropathy. Thus, a multifactorial treatment approach to individual components of Metabolic Syndrome may slow prediabetic neuropathy progression or result in improvement.     

Vascular aspects of cognitive impairment and dementia

Hypertension and stroke are highly prevalent risk factors for cognitive impairment and dementia. Alzheimer''s disease (AD) and vascular dementia (VaD) are the most common forms of dementia, and both conditions are preceded by a stage of cognitive impairment. Stroke is a major risk factor for the development of vascular cognitive impairment (VCI) and VaD; however, stroke may also predispose to AD. Hypertension is a major risk factor for stroke, thus linking hypertension to VCI and VaD, but hypertension is also an important risk factor for AD. Reducing these two major, but modifiable, risk factors—hypertension and stroke—could be a successful strategy for reducing the public health burden of cognitive impairment and dementia. Intake of long-chain omega-3 polyunsaturated fatty acids (LC-n3-FA) and the manipulation of factors involved in the renin–angiotensin system (e.g. angiotensin II or angiotensin-converting enzyme) have been shown to reduce the risk of developing hypertension and stroke, thereby reducing dementia risk. This paper will review the research conducted on the relationship between hypertension, stroke, and dementia and also on the impact of LC-n3-FA or antihypertensive treatments on risk factors for VCI, VaD, and AD.     

Inflammation and ischaemic stroke

PURPOSE OF REVIEW: Inflammation is implicated in ischaemic stroke as a general cardiovascular risk factor, a possible immediate trigger, a component (and possible exacerbating factor) of the response to tissue injury, a marker of future risk, and as a therapeutic target. Each aspect is reviewed. RECENT FINDINGS: Evidence of epidemiological association of inflammatory markers, particularly C-reactive protein, has accrued, but the independence of inflammation from more conventional risk indicators is under question. Other inflammatory markers are associated with intermediate phenotypes such as hypertension. Tissue inflammation in atherosclerotic plaque is of probable relevance in identifying recently symptomatic carotid disease. Both humoral and cellular inflammation are evident following stroke, with evidence that these responses may exacerbate tissue injury. Blockade of interleukin-1, or of neutrophil chemotaxis, has reduced infarct volume in models of stroke but has yet to show benefit in clinical trials. Other anti-inflammatory strategies are promising. SUMMARY: Inflammation is implicated in several aspects of acute ischaemic stroke. It remains to be established whether the inflammatory response is a truly independent risk factor in general, or whether specific anti-inflammatory interventions are beneficial either in prevention or acute treatment.     

POEMS syndrome associated with ischemic stroke

BACKGROUND: A syndrome variously combining peripheral neuropathy, visceromegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS syndrome) is a rare variant of plasma cell dyscrasia with multisystemic manifestations. Acute ischemic strokes in patients with POEMS syndrome have rarely been reported, and the pathophysiologic mechanism of this disease is unknown. Fibrinogen is reported to be an independent risk factor for cerebrovascular disease and is correlated with the interleukin 6 level in the plasma. The serum level of interleukin 6 is high in the active stage of POEMS syndrome. OBJECTIVE: To describe the neuroimaging findings and fibrinogen levels in patients with POEMS syndrome. DESIGN: Case series. SETTING: The neurology department of a tertiary referral center. METHODS: Three patients with an acute cerebral infarction associated with POEMS syndrome underwent magnetic resonance imaging, diffusion-weighted imaging, magnetic resonance angiography, transcranial Doppler ultrasonography, and serum fibrinogen level and serum C-reactive protein level analysis. The serum fibrinogen level before the stroke was collected retrospectively from the hospital medical records. RESULTS: There was an elevated fibrinogen level in all of the patients. In 2 patients, unilateral or bilateral end artery border-zone infarcts were observed on the brain magnetic resonance imaging scan. The serum fibrinogen level was high before the stroke in 2 patients. CONCLUSIONS: The POEMS syndrome can be associated with stroke, particularly end artery border-zone infarctions. We suggest that an elevated fibrinogen level might play a role in the pathogenesis of stroke.