An Animal Model Of Diabetic Peripheral Neuropathy And The Pathophysiology Of Takotsubo Syndrome: A Proposal Of An Experiment
In-spite of >3000 published works in PubMed about Takotsubo syndrome (TTS) [1] the pathophysiology of this disease continues to elude us. A starting point traditionally is an allusion to an underlying mechanism being either an uninhibited hyperactivity of the autonomic (primarily sympathetic) nervous system [2], or an abundance of blood borne catecholamines [3], exerting their noxious influence on the cardiomyocytes. It has been hypothesized that diabetes mellitus, with its accompanied diabetic peripheral neuropathy (DPN), including autonomic nervous system (ANS) DPN, could exert an ameliorating or inhibiting effect on the emergence of TTS, and thus patients with manifest TTS would be expected to have a low prevalence of DM [4]. Continue reading >>
Diabetic Neuropathy
Go to: Abstract Diabetic neuropathy (DN) refers to symptoms and signs of neuropathy in a patient with diabetes in whom other causes of neuropathy have been excluded. Distal symmetrical neuropathy is the commonest accounting for 75% DN. Asymmetrical neuropathies may involve cranial nerves, thoracic or limb nerves; are of acute onset resulting from ischaemic infarction of vasa nervosa. Asymmetric neuropathies in diabetic patients should be investigated for entrapment neuropathy. Diabetic amyotrophy, initially considered to result from metabolic changes, and later ischaemia, is now attributed to immunological changes. For diagnosis of DN, symptoms, signs, quantitative sensory testing, nerve conduction study, and autonomic testing are used; and two of these five are recommended for clinical diagnosis. Management of DN includes control of hyperglycaemia, other cardiovascular risk factors; α lipoic acid and L carnitine. For neuropathic pain, analgesics, non‐steroidal anti‐inflammatory drugs, antidepressants, and anticonvulsants are recommended. The treatment of autonomic neuropathy is symptomatic. Keywords: neuropathy, diabetes, treatment, classification, pathophysiology Diabetic neuropathy (DN) is a common disorder and is defined as signs and symptoms of peripheral nerve dysfunction in a patient with diabetes mellitus (DM) in whom other causes of peripheral nerve dysfunction have been excluded. There is a higher prevalence of DM in India (4.3%)1 compared with the West (1%–2%).2 Probably Asian Indians are more prone for insulin resistance and cardiovascular mortality.3 The incidence of DN in India is not well known but in a study from South India 19.1% type II diabetic patients had peripheral neuropathy.4 DN is one of the commonest causes of peripheral neuropathy. It a Continue reading >>
Pathophysiology And Treatment For Diabetic Neuropathy
Diabetic neuropathy (DN) is the most frequent among peripheral neuropathies. Since its pathophysiology is so complicated, neither classification nor therapeutic management of DN has been established. Sensory/autonomic polyneuropathy (DP) is the main type of DN. Since diabetic patients occasionally have one or more subtypes of DN and/or other polyneuropathy including treatable neuropathy like CIDP, the treatment for DP has to be conducted after excluding the possibility of other conditions. Glycemic control is most essential to prevent the development of DP. However, it is practically difficult to keep HbA1c under 6.5% so that drinking and smoking better be restricted and blood pressure be properly maintained to retard the progression of DP. Aldose reductase inhibitor is only one commercially available drug for DP and its efficacy must be evaluated by nerve function tests along with subjective symptoms. More vigorous therapeutic procedure is expected by obtaining not only more potential drugs based on pathogenic mechanisms but also the technique targeting of DNA/siRNA of given peptides at dorsal root ganglion neurons. Continue reading >>
What Is The Pathophysiology Of Diabetic Neuropathy?
As per some studies, patients with impaired glucose tolerance develop neuropathy. Neuropathy is much mild in newly diagnosed diabetes and the earliest detectable sign is small nerve fiber involvement. The factors which cause neuropathy are not very well understood, but the pathophysiology behind this is due to: · Polyol Pathway: In case of hyperglycemia, there is increase in the levels of the intracellular glucose of the nerves which leads to saturation of the glycolytic pathway. The extra glucose is transferred to the polyol pathway where it is converted to fructose and sucrose by the enzymes. When the sucrose and fructose get accumulated, it leads to the reduction of the nerve myoinositol, decrease in membrane Na+/K+ -ATPase activity and the breakdown of the nerves. · Advanced glycation end products: The advanced glycation end products or AGEs are the end products of the nonenzymatic reaction of excess glucose with proteins, nucleotides, and lipids. The AGEs have an ability to disrupt the neuronal integrity. · Oxidative stress: When the increased production of free radicals has a direct damage on the blood vessels it leads to oxidative stress. This leads to neuropathic symptoms. Continue reading >>
Pathogenesis Of Painful Diabetic Neuropathy
Copyright © 2014 Amir Aslam et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract The prevalence of diabetes is rising globally and, as a result, its associated complications are also rising. Painful diabetic neuropathy (PDN) is a well-known complication of diabetes and the most common cause of all neuropathic pain. About one-third of all diabetes patients suffer from PDN. It has a huge effect on a person’s daily life, both physically and mentally. Despite huge advances in diabetes and neurology, the exact mechanism of pain causation in PDN is still not clear. The origin of pain could be in the peripheral nerves of the central nervous system. In this review, we discuss various possible mechanisms of the pathogenesis of pain in PDN. We discuss the role of hyperglycaemia in altering the physiology of peripheral nerves. We also describe central mechanisms of pain. 1. Introduction Diabetes affects 382 million people wordlwide and its prevalence is expected to increase to 592 million by the year 2035 [1]. Diabetic neuropathy, a well-known, long-term complication of diabetes, can affect almost half of the diabetic population [2] and is associated with higher morbidity and mortality [3]. Diabetic neuropathy encompasses a variety of clinical or subclinical presentations. Painful diabetic neuropathy (PDN) is a common type of diabetic neuropathy and the most common cause of neuropathic pain [4]. The reported prevalence of PDN varied from 11% in Rochester, Minnesota, USA [5], to 53.7% in the Middle East [6]. One UK study published in 2011 reported that the prevalence of PDN was 21.5% in type 2 diabetes p Continue reading >>
Class Act: Age-rage: What We Know About The Pathophysiology Of Diabetic Neuropathy.
Commentary by Regina Mysliwiec, NYU Medical Student Faculty Peer Reviewed G.L. is a 62 year-old African-American male with a six year history of Type 2 Diabetes with variable glucose control and a progressive one year history of burning pain in a unilateral T10 distribution. The pain began at his right abdomen, then spread first to his umbilicus and finally ventrodorsally to his spine. His most recent HgbA1c is 8.0. One does not have to be a medical student in New York City for very long to find a patient with tingling and numbness that started in the toes, spread up both legs, and is sometimes accompanied by sharp or burning pain. Distal symmetric polyneuropathy is common in diabetes, and diabetes is common in NYC. The patient described above may be an example of the less common diabetic thoracic radiculopathy. What he has in common with his stocking-and-gloved counterparts is poor glucose control. Several long-term clinical trials focusing on the effects of glycemic control have illustrated the correlation between hyperglycemia and what are now commonly known as the microvascular complications of diabetes – including neuropathy. We know that nerve damage happens. What remains somewhat unclear is how it is accomplished. There appear to be three main mechanisms of nerve damage in diabetics. First, excess glucose causes endothelial injury. Second, there are changes in activation of various cellular pathways that alter cell function without immediately causing cell death. And third, AGE meets RAGE; time and the accumulation of altered molecules wreak additional havoc on patients’ tissues. Endothelial damage is evidenced by the increased presence of thrombomodulin, a marker of microangiopathy in animal models of diabetes. It is assumed that microangiopathy caused by gl Continue reading >>
Spectrum Of High-resolution Mri Findings In Diabetic Neuropathy
ABSTRACT : OBJECTIVE. Diabetes is the most common cause of neuropathy. Focal diabetic neuropathy, although less common than entrapment neuropathy, clinically mimics entrapment neuropathy. This article depicts the spectrum of MR abnormalities in diabetic subjects— from abnormal T2 hyperintensity and fascicular enlargement in the acute and subacute stages to atrophic-appearing fascicles with intraepineurial fat deposition in the chronic stage—on high-resolution high-field (3-T) MRI. CONCLUSION. A spectrum of imaging abnormalities is observed in diabetic neuropathy. It is important for radiologists to understand the pathophysiology and recognize high-resolution MR appearances of these lesions and of related entities in the differential diagnosis for appropriate diagnosis and patient treatment. Continue reading >>
The Pathophysiology Of Neuropathic Pain
A discussion of the pathophysiology of neuropathic pain and an overview of the modalities used to alleviate it. Page 1 of 3 Neuropathic Pain is a complex, chronic pain state that usually is accompanied by tissue injury. Neuropathic pain is common in clinical practice and presents a challenge to patients and clinicians alike. With neuropathic pain, the nerve fibers themselves may be damaged, dysfunctional or injured. Neuropathic pain is the result of disease or injury to the peripheral or central nervous system and the lesion may occur at any point. These damaged nerve fibers send incorrect signals to other pain centers. The impact of a nerve fiber injury includes a change in nerve function—both at the site of the injury and areas around the injury.1 Clinical manifestations of neuropathic pain typically include positive sensory phenomena such as spontaneous pain, paresthesias and hyperalgesia.2 Neuropathic pain as defined by the International Association of the Study of Pain (IASP) is “pain initiated or caused by a primary lesion or dysfunction of the nervous system.”3 It can result from damage anywhere along the neuraxis: peripheral nervous system, spinal or supraspinal nervous system. Traits that differentiate neuropathic pain from other types of pain include pain and sensory symptoms lasting beyond the healing period. It is characterized in humans by spontaneous pain, allodynia (the experience of non-noxious stimuli as painful), and causalgia (constant burning pain). Spontaneous pain includes sensations of ‘pins and needles,’ shooting, burning, stabbing and paroxysmal pain (electric-shock like) often associated with dysesthesias and paresthesias.4 These sensations not only affect the patient’s sensory system, but also the patient’s well-being, mood, focu Continue reading >>
Diabetic Neuropathy
LYRICA is contraindicated in patients with known hypersensitivity to pregabalin or any of its other components. Angioedema and hypersensitivity reactions have occurred in patients receiving pregabalin therapy. There have been postmarketing reports of hypersensitivity in patients shortly after initiation of treatment with LYRICA. Adverse reactions included skin redness, blisters, hives, rash, dyspnea, and wheezing. Discontinue LYRICA immediately in patients with these symptoms. There have been postmarketing reports of angioedema in patients during initial and chronic treatment with LYRICA. Specific symptoms included swelling of the face, mouth (tongue, lips, and gums), and neck (throat and larynx). There were reports of life-threatening angioedema with respiratory compromise requiring emergency treatment. Discontinue LYRICA immediately in patients with these symptoms. Antiepileptic drugs (AEDs) including LYRICA increase the risk of suicidal thoughts or behavior in patients taking AEDs for any indication. Monitor patients treated with any AED for any indication for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Pooled analyses showed clinical trial patients taking an AED had approximately twice the risk of suicidal thoughts or behavior than placebo-treated patients. The estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one patient for every 530 patients treated with an AED. The most common adverse reactions across all LYRICA clinical trials are dizziness, somnolence, dry mouth, edema, blurred vision, weight gain, constipation, euphoric mood, balance Continue reading >>
Diabetic Neuropathy
1. DIABETICNEUROPATHYDr. Tushar Patil , M.D.Senior Resident, Dept of Neurology,King George’s Medical University, LucknowIndia 2. DEFINITIONAn internationally agreed simple definition of Diabetic neuropathy for clinical practice is“the presence of symptoms and/or signs of peripheral nerve dysfunction in people with diabetes after the exclusion of other causes” Boulton AJ et al. Diabetic neuropathies: a statement by the American Diabetes Association. Diabetes Care. 2005 Apr;28(4):956-62. 3. A more detailed definition of neuropathy was previously agreed upon at the San Antonio Consensus Conference:“diabetic neuropathy is a descriptive term meaning a demonstrable disorder, either clinically evident or subclinical, that occurs in the setting of diabetes mellitus without other causes for peripheral neuropathy. The neuropathic disorder includes manifestations in the somatic and/or autonomic parts of the peripheral nervous system”American Diabetes Association, American Academy of Neurology: Report and recommendations of the San Antonio Conference on Diabetic Neuropathy (Consensus Statement). Diabetes Care 11:592–597, 1988 4. CHRONIC COMPLICATIONS OFDIABETES MELLITUSMicrovascular Macrovascular Eye disease Coronary heart diseaseRetinopathy Peripheral arterial disease (nonproliferative/proliferative) Cerebrovascular diseaseMacular edema Other Neuropathy Gastrointestinal (gastroparesis,Sensory and motor (mono- and diarrhea) polyneuropathy) Genitourinary (uropathy/sexualAutonomic dysfunction) Nephropathy Dermatologic Infectious Cataracts Glaucoma Periodontal disease Hearing loss 5. DIABETIC NEUROPATHY:PROBLEM STATEMENT DM risen over past two decades, 30 million in 1985 to 285 million in 2010. IDF projects 438 million Continue reading >>
Diabetic Autonomic Neuropathy: Pathogenesis To Pharmacological Management
S.No. Animal model Advantage Disadvantage 1. Type 1 diabetes Hyperglycemia persists for several days Spontaneous destruction of β-cells mimics the disease pathology in humans They are suited to study diabetic autonomic neuropathy Diabetes and obesity symptoms overlaps Limited availability and expensive. Mortality due to ketosis is high in animals with brittle pancreas (db/db, ZDF rats), and it requires insulin in later stage for survival Drug-induced tissue toxicity 2. Type 2 diabetes These models mimic the pathology of humans It is likely to be as complex and heterogeneous as human condition Polyphagia and polyuria Drug Dosage Diagnostic tests Side effects Orthostatic hypotension 9-α-fluoro hydrocortisone 0.1 mg titrated to 0.5 to 2.0 mg/day Measure B.P. by active standing test and passive head up tilt testing (HUT) Measure catecholamines Ankle edema, hypokalemia, congestive heart failure Sympathomimetic agents Ephedrine 25-50 mg t.i.d. Sympathetic symptoms Pseudoephedrine 30-60 mg t.i.d. Phenylpropanolamine 12.5-25 mg t.i.d. α-agonist Midodrine (FDA approved) 2.5-10 mg t.i.d. Anxiety and tachycardia Clonidine 0.1-0.5 mg Hypotension Octreotide 0.1-0.5 μg/kg/day Injection site pain and diarrhea Supplementary therapy like cox-inhibitor, caffeine etc. can be used Diabetic Gastroparesis Metoclopramide 10 mg q.i.d. Antroduodenal manometry Breath test Magnetic response imaging Ultrasonography Gastric emptying study Electrogastrography Dystonic reactions, hyperprolactinemia, extrapyramidal symptoms Erythromycin 250 mg t.i.d. Nausea, vomiting, abdominal pain, antibiotic resistance Domperidone 10-20 mg t.i.d. Galactorrhea Bethanechol 20 mg q.i.d. Salivation, blurred vision, abdominal cramps, bladder spasm Levosulpiride 25 mg t.i.d. Galactorrhea Botulinum toxin type A ---- - Continue reading >>
Diabetic Neuropathy
Diabetic neuropathies are nerve damaging disorders associated with diabetes mellitus. These conditions are thought to result from a diabetic microvascular injury involving small blood vessels that supply nerves (vasa nervorum) in addition to macrovascular conditions that can accumulate in diabetic neuropathy. Relatively common conditions which may be associated with diabetic neuropathy include third, fourth, or sixth cranial nerve palsy[1]; mononeuropathy; mononeuropathy multiplex; diabetic amyotrophy; a painful polyneuropathy; autonomic neuropathy; and thoracoabdominal neuropathy. Signs and symptoms[edit] Illustration depicting areas affected by diabetic neuropathy Diabetic neuropathy affects all peripheral nerves including sensory neurons, motor neurons, but rarely affects the autonomic nervous system. Therefore, diabetic neuropathy can affect all organs and systems, as all are innervated. There are several distinct syndromes based on the organ systems and members affected, but these are by no means exclusive. A patient can have sensorimotor and autonomic neuropathy or any other combination. Signs and symptoms vary depending on the nerve(s) affected and may include symptoms other than those listed. Symptoms usually develop gradually over years. Symptoms may include the following: Trouble with balance Numbness and tingling of extremities Dysesthesia (abnormal sensation to a body part) Diarrhea Erectile dysfunction Urinary incontinence (loss of bladder control) Facial, mouth and eyelid drooping Vision changes Dizziness Muscle weakness Difficulty swallowing Speech impairment Fasciculation (muscle contractions) Anorgasmia Retrograde ejaculation (in males) Burning or electric pain Pathogenesis[edit] The following factors are thought to be involved in the development of dia Continue reading >>
Pathophysiology Of Nerve Conduction: Relation To Diabetic Neuropathy
Pathophysiologic and clinicopathologic aspects of diabetic nerve disease are reviewed. Abnormal modes of impulse conduction in diseased nerves include decreased conduction velocity, temporal dispersion of impulses, frequency-related and total conduction block, abnormal cross-talk, and impulse reflection. Because structural and electrophysiologic variables (such as fiber geometry, ionic channel density, and properties of the extracellular milieu) vary with diameter, it is suggested that pathophysiologic mechanisms also should vary with diameter. Topographic patterns of clinical deficit, and their pathologic basis, are reviewed; it is suggested that lesions distributed at random along the length of the entire fiber may result in dysfunction that exhibits distinct proximal-distal gradients. Continue reading >>
Pathophysiology And Treatment Of Painful Diabetic Neuropathy Of The Lower Extremity.
Abstract BACKGROUND: Symptomatic peripheral neuropathy is the most common complication of diabetes mellitus, affecting up to 62% of Americans with diabetes. METHODS: We reviewed the literature using the National Library of Medicine's MEDLINE search service. In total, we reviewed 54 articles. RESULTS: Hyperglycemia leads to increased activity in the polyol pathway in nerve cells; this ultimately results in abnormal nerve function. Numerous pharmacologic agents have been used to treat symptomatic peripheral neuropathy, but all of these drugs can be associated with adverse side effects. Recent work has indicated that subsensory electrical stimulation may be preferred to pharmacotherapy, since it is equally effective and has a more favorable safety profile. CONCLUSION: Although the pathophysiology of diabetic neuropathy is well understood, treatment of the symptoms associated with this condition can be challenging. Additional research is needed to reveal a safe and effective treatment for this debilitating sequela of diabetes mellitus. Continue reading >>
Neuropathy
Tweet Neuropathy (or diffuse neuropathy) is a nerve disorder which may be categorised as sensory neuropathy, motor neuropathy or autonomic neuropathy. Neuropathy can be caused by both type 1 and type 2 diabetes. Types of neuropathy Diabetic neuropathy may be categorised as follows: Sensory neuropathy occurs when nerves which detect touch and temperature are damaged. This form of neuropathy commonly affects the feet and hands. Motor neuropathy results from damage to the nerves affecting muscle movement. Autonomic neuropathy follows if the nerves which control involuntary actions, such as digestion or heart rate are affected. Over time, people with diabetes who do not control their condition, may develop damage to the nerves around the body. The term peripheral neuropathy may also be used and the term simply refers to nerve damage affecting any nerve outside of the brain or spinal cord. How common is diabetic neuropathy? Incidences are more common in patients with poor control, overweight, have higher levels of blood fat and blood pressure, and are over the age of 40. The longer a person has diabetes, the greater the risk of developing neuropathies. Neuropathy may affect up to 50% of people with diabetes.[1] Symptoms of neuropathy will often first manifest as numbness or pain in the hands, feet, arms or legs (distal symmetric neuropathy). However, they may also affect the organs, including the heart and sex organs. What exactly causes neuropathy amongst people with diabetes? The exact effect of glucose on the nervous system is still not known. However, prolonged exposure to higher than normal glucose levels certainly damages the nerves, causing neuropathy. High levels of triglycerides, a key blood fat which is measured during a cholesterol check, are also associated with Continue reading >>
