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Diabetic neuropathy
Classification and external resources
ICD-10 E10. The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The International Statistical Classification of Diseases and Related Health Problems 10th Revision ( ICD -10) is a coding of diseases and signs symptoms abnormal findings 4, E11. 4, E12. 4, E13. 4, E14. 4
ICD-9 250.6

Diabetic neuropathies are neuropathic disorders that are associated with diabetes mellitus. The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. Neuropathy is a medical term usually short for Peripheral neuropathy. Diabetes mellitus (ˌdaɪəˈbiːtiːz or /ˌdaɪəˈbiːtəs/ /məˈlaɪtəs/ or /ˈmɛlətəs/ often referred to simply as diabetes ( Ancient Greek: grc These conditions are thought to result from diabetic microvascular injury involving small blood vessels that supply nerves (vasa nervorum). The blood vessels are part of the Circulatory system and function to transport Blood throughout the body Vasa nervorum are small arteries that provide blood supply to peripheral nerves Relatively common conditions which may be associated with diabetic neuropathy include third nerve palsy; mononeuropathy; mononeuropathy multiplex; diabetic amyotrophy; a painful polyneuropathy; autonomic neuropathy; and thoracoabdominal neuropathy. Oculomotor nerve palsy is an eye condition resulting from damage to the third cranial nerve or a branch thereof Mononeuropathy (or "mono Neuritis " is a type of Neuropathy that only affects a single Nerve. Amyotrophy is progressive wasting of Muscle tissues Muscle pain is also a symptom Pain, in the sense of physical pain, is a typical sensory experience that may be described as the unpleasant awareness of a noxious stimulus or bodily harm

Contents

Epidemiology

Diabetes mellitus
Types of Diabetes
Diabetes mellitus type 1
Diabetes mellitus type 2
Gestational diabetes

Pre-diabetes:
Impaired fasting glycaemia
Impaired glucose tolerance
Disease Management
Diabetes management:
•Diabetic diet
•Anti-diabetic drugs
•Conventional insulinotherapy
•Intensive insulinotherapy
Other Concerns
Cardiovascular disease

Diabetic comas:
•Diabetic hypoglycemia
•Diabetic ketoacidosis
•Nonketotic hyperosmolar

Diabetic myonecrosis
Diabetic nephropathy
Diabetic neuropathy
Diabetic retinopathy

Diabetes and pregnancy
Blood tests
Blood sugar
Fructosamine
Glucose tolerance test
Glycosylated hemoglobin

Diabetes is the leading known* cause of neuropathy in developed countries, and neuropathy is the most common complication and greatest source of morbidity and mortality in diabetes patients. Diabetes mellitus (ˌdaɪəˈbiːtiːz or /ˌdaɪəˈbiːtəs/ /məˈlaɪtəs/ or /ˈmɛlətəs/ often referred to simply as diabetes ( Ancient Greek: grc Diabetes mellitus type 1 (Type 1 diabetes Type I diabetes T1D T1DM IDDM juvenile diabetes is a form of Diabetes mellitus. Diabetes mellitus type 2 or Type 2 Diabetes (formerly called non - Insulin -dependent Diabetes mellitus (NIDDM or adult-onset diabetes is a metabolic Gestational diabetes (or gestational diabetes mellitus, GDM) is a condition in which women without previously diagnosed diabetes exhibit high blood Impaired fasting glycaemia (IFG is a pre-diabetic state of dysglycemia associated with insulin resistance and increased risk of cardiovascular pathology although of lesser risk than Impaired Glucose Tolerance (IGT is a pre- Diabetic state of dysglycemia that is associated with Insulin resistance and increased risk of cardiovascular pathology Diabetes is a Chronic disease with no cure As of 2008. It is associated with an impaired Glucose cycle, altering Metabolism. The diet most often recommended for people who suffer from Diabetes mellitus is high in Dietary fiber, especially soluble fiber but low in fat (especially Saturated fat Anti-diabetic drugs treat Diabetes mellitus by lowering Glucose levels in the blood Conventional insulinotherapy is a therapeutic regimen for treatment of Diabetes mellitus which contrasts with the newer Intensive insulinotherapy. Intensive insulinotherapy is a therapeutic regimen for Diabetes mellitus treatment Cardiovascular disease or cardiovascular diseases refers to the class of diseases that involve the Heart or Blood vessels ( arteries and Diabetic coma is a Medical emergency in which a person with Diabetes mellitus is Comatose (unconscious because of one of the acute complications Diabetic hypoglycemia describes a low blood glucose level occurring in a person with Diabetes mellitus. Diabetic ketoacidosis (DKA is a life-threatening complication in patients with diabetes mellitus Nonketotic hyperosmolar coma (nonketotic Hyperglycaemia) is a type of Diabetic coma associated with a high mortality seen in Diabetes mellitus type 2. Diabetic myonecrosis is a rare complication of Diabetes. It is caused by Infarcted Muscle tissue usually in the thigh Diabetic nephropathy ( nephropatia diabetica) also known as Kimmelstiel-Wilson syndrome and intercapillary glomerulonephritis, is a progressive Kidney Diabetic retinopathy is Retinopathy (damage to the Retina) caused by complications of Diabetes mellitus, which can eventually lead to Blindness For women with Diabetes mellitus, Pregnancy can present some particular challenges for both mother and child Blood sugar, used in a physiological context is a misnomer and misleading Fructosamine is a compound that can be considered the result of a reaction between Fructose and Ammonia or an Amine (with a molecule of water being released A glucose tolerance test in medical practice is the administration of Glucose to determine how quickly it is cleared from the blood Glycosylated (or glycated hemoglobin ( hemoglobin A1c Hb1c, or HbA1c) is a form of Hemoglobin used primarily to identify the average In Medicine, Epidemiology and Actuarial science, the term morbidity can refer to the state of poor health (from Latin Death is the termination of the biological functions that define living Organisms It refers both to a specific It is estimated that the prevalence of neuropathy in diabetes patients is approximately 20%. In Epidemiology, the prevalence of a Disease in a Statistical population is defined as the total number of cases of the disease in the population at a given Diabetic neuropathy is implicated in 50-75% of nontraumatic amputations. Amputation is the removal of a body extremity by trauma or Surgery.

The main risk factor for diabetic neuropathy is hyperglycemia. Hyperglycemia, hyperglycaemia, or high blood sugar is a condition in which an excessive amount of Glucose circulates in the Blood plasma It is important to note that people with diabetes are more likely to develop symptoms relating to peripheral neuropathy as the excess glucose in the blood results in a condition known as Glucojasinogen. This condition is affiliated with erectile dysfunction and epigastric tenderness which in turn results in lack of blood flow to the peripheral intrapectine nerves which govern the movement of the arms and legs. In the DCCT (Diabetes Control and Complications Trial, 1995) study, the annual incidence of neuropathy was 2% per year, but dropped to 0. 56% with intensive treatment of Type 1 diabetics. The progression of neuropathy is dependent on the degree of glycemic control in both Type 1 and Type 2 diabetes. Duration of diabetes, age, cigarette smoking, hypertension, height and hyperlipidemia are also risk factors for diabetic neuropathy. Senescence refers to the biological processes of a living Organism approaching an advanced age (i A cigarette ( French "small Cigar " from cigar + -ette) is a product consumed through Smoking and manufactured Hypertension, also referred to as high blood pressure, HTN or HPN, is a medical condition in which the Blood pressure is chronically elevated Hyperlipidemia, hyperlipoproteinemia or dyslipidemia is the presence of raised or abnormal levels of Lipids and/or Lipoproteins in the

 *The largest group of neuropathy patients are of unknown cause, referred to as idiopathic in origin. Idiopathic is an Adjective used primarily in Medicine meaning arising spontaneously or from an obscure or unknown cause. Of the roughly 100 known causes, diabetes is by far the largest. Other known causes include genetic factors, damaging chemical agents such as chemotherapy drugs, and HIV.

Pathology and pathogenesis

There are four factors thought to be involved in the development of diabetic neuropathy:

  1. Microvascular disease,
  2. Advanced Glycation Endproduct,
  3. Protein kinase C, and the
  4. Polyol pathway. Protein kinase C ('PKC') is a family of protein kinases consisting of ~10 Isozymes. Also called the Sorbitol -aldose reductase pathway, the Polyol pathway appears to be implicated in diabetic complications especially in microvascular damage to the

Microvascular disease

Vascular and neural diseases are closely related and intertwined. Blood vessels depend on normal nerve function, and nerves depend on adequate blood flow. The blood vessels are part of the Circulatory system and function to transport Blood throughout the body Blood flow is the flow of Blood in the Cardiovascular system. The first pathological change in the microvasculature is vasoconstriction. Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels particularly the large Arteries, Arterioles As the disease progresses, neuronal dysfunction correlates closely with the development of vascular abnormalities, such as capillary basement membrane thickening and endothelial hyperplasia, which contribute to diminished oxygen tension and hypoxia. Chronic Hypoxia is a pathological condition in which the body as a whole ( generalized hypoxia) or region of the body ( tissue hypoxia) is deprived of adequate Neuronal ischemia is a well-established characteristic of diabetic neuropathy. Vasodilator agents (e. g. , ACE inhibitors, α1-antagonists) can lead to substantial improvements in neuronal blood flow, with corresponding improvements in nerve conduction velocities. ACE inhibitors, or inhibitors of '''A'''ngiotensin-'''C'''onverting '''E'''nzyme, are a group of Pharmaceuticals that are used primarily in treatment of Hypertension Blood flow is the flow of Blood in the Cardiovascular system. A nerve conduction study (NCS is a test commonly used to evaluate the function especially the ability of Electrical conduction, of the motor and Sensory nerves Thus, microvascular dysfunction occurs early in diabetes, parallels the progression of neural dysfunction, and may be sufficient to support the severity of structural, functional, and clinical changes observed in diabetic neuropathy.

Advanced glycated end products

Elevated intracellular levels of glucose cause a non-enzymatic covalent bonding with proteins, which alters their structure and destroys their function. Glucose (Glc a Monosaccharide (or simple Sugar) also known as grape sugar, is an important Carbohydrate in Biology. Proteins are large Organic compounds made of Amino acids arranged in a linear chain and joined together by Peptide bonds between the Carboxyl Some of these glycosylated proteins have been implicated in the pathology of diabetic neuropathy and other long term complications of diabetes.

Protein kinase C (PKC)

PKC is implicated in the pathology of diabetic neuropathy. Increased levels of glucose cause an increase in intracellular diacylglycerol, which activates PKC. A diglyceride, or a diacylglycerol (DAG is a Glyceride consisting of two Fatty acid chains covalently bonded to a Glycerol PKC inhibitors in animal models will increase nerve conduction velocity by increasing neuronal blood flow. An animal model is a non-human Animal that has a Disease or injury that is similar to a human condition

Polyol pathway

Also called the Sorbitol/Aldose Reductase Pathway, the Polyol Pathway may be implicated in diabetic complications that result in microvascular damage to nervous tissue, and also to the retina and kidney. Also called the Sorbitol -aldose reductase pathway, the Polyol pathway appears to be implicated in diabetic complications especially in microvascular damage to the

Glucose is a highly reactive compound, and it must be metabolized or it will find tissues in the body to react with. Increased glucose levels, like those seen in diabetes, activates this alternative biochemical pathway, which in turn causes a decrease in glutathione and an increase in reactive oxygen radicals. In Biochemistry, a metabolic pathway is a series of chemical reactions occurring within a cell. Glutathione ( GSH) is a Tripeptide. It contains an unusual Peptide linkage between the amine group of Cysteine and the Carboxyl In Chemistry, radicals (often referred to as free radicals) are atoms molecules or ions with Unpaired electrons on an otherwise Open shell The pathway is dependent on the enzyme aldose reductase. Aldose reductase (or aldehyde reductase) is an Enzyme in Carbohydrate metabolism that converts an Aldose to a Sugar alcohol, using Inhibitors of this enzyme have demonstrated efficacy in animal models in preventing the development of neuropathy.

While most body cells require the action of insulin for glucose to gain entry into the cell, the cells of the retina, kidney and nervous tissues are insulin-independent. Therefore there is a free interchange of glucose from inside to outside of the cell, regardless of the action of insulin, in the eye, kidney and neurons. The cells will use glucose for energy as normal, and any glucose not used for energy will enter the polyol pathway and be converted into sorbitol. Under normal blood glucose levels, this interchange will cause no problems, as aldose reductase has a low affinity for glucose at normal concentrations.

However, in a hyperglycemic state, the affinity of aldose reductase for glucose rises, meaning much higher levels of sorbitol and much lower levels of NADPH, a compound used up when this pathway is activated. The sorbitol can not cross cell membranes, and when it accumulates, it produces osmotic stresses on cells by drawing water into the cell. Fructose does essentially the same thing, and it is created even further on in the chemical pathway.

The NADPH, used up when the pathway is activated, acts to promote nitric oxide and glutathione production, and its conversion during the pathway leads to reactive oxygen molecules. Glutathione deficiencies can lead to hemolysis caused by oxidative stress, and we already know that nitric oxide is one of the important vasodilators in blood vessels. NAD+, which is also used up, is necessary to keep reactive oxygen species from forming and damaging cells.

Furthermore, the high levels of sorbitol are believed to reduce the cellular uptake of another alcohol, myoinsitol, decreasing the activity of the plasma membrane Na+/K+ ATPase pump required for nerve function, further contributing to the neuropathy.

In summary, excessive activation of the Polyol pathway leads to increased levels of sorbitol and reactive oxygen molecules and decreased levels of nitric oxide and glutathione, as well as increased osmotic stresses on the cell membrane. Any one of these elements alone can promote cell damage, but here we have several acting together.

Experimental evidence has yet to confirm that the polyol pathway actually is responsible for microvasculature damage in the retina, kidney and/or neurons of the body. However, physiologists are fairly certain that it plays some role in neuropathy.

Clinical manifestations

Diabetic neuropathy affects all peripheral nerves: pain fibers, motor neurons, autonomic nerves. It therefore necessarily can affect all organs and systems since 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. Symptoms vary depending on the nerve(s) affected and may include symptoms other than those listed. A symptom' (from Greek σύμπτωμα, "accident misfortune that which befalls" from συμπίπτω, "I befall" from Symptoms usually develop gradually over years.

Usual symptoms may be:

Sensorimotor polyneuropathy

Longer nerve fibers are affected to a greater degree than shorter ones, because nerve conduction velocity is slowed in proportion to a nerve's length. Dysesthesia is defined as an unpleasant abnormal sensation It is caused by lesions of the nervous system peripheral or central and it involves abnormal sensations whether spontaneous In Medicine, diarrhea, also spelled diarrhoea (see spelling differences) is frequent loose or liquid Bowel movements Acute diarrhea Urinary incontinence ( UI) is any involuntary leakage of Urine. Many different terms are often used to describe what is collectively known as dizziness. Dysphagia should not be confused with the similarly pronounced Dysphasia, a language disorder Speech refers to the processes associated with the production and perception of Sounds used in Spoken language. A fasciculation (or "muscle Twitch " is a small local involuntary Muscle contraction (twitching visible under the skin arising from the spontaneous discharge Anorgasmia (often related to Delayed ejaculation in males is a form of Sexual dysfunction sometimes classified as a Psychiatric disorder in which the patient In this syndrome, decreased sensation and loss of reflexes occurs first in the toes bilaterally, then extends upward. It is usually described as glove-stocking distribution of numbness, sensory loss, dysesthesia and night time pain. Dysesthesia is defined as an unpleasant abnormal sensation It is caused by lesions of the nervous system peripheral or central and it involves abnormal sensations whether spontaneous The pain can feel like burning, pricking sensation, achy or dull. Pins and needles sensation is common. Loss of proprioception, the sense of where a limb is in space, is affected early. Proprioception (ˌproʊpriːəˈsɛpʃən PRO -pree-o-SEP-shun from Latin proprius, meaning "one's own" and perception is the Sense These patients cannot feel when they are stepping on a foreign body, like a splinter, or when they are developing a callous from an ill-fitting shoe. Consequently, they are at risk for developing ulcers and infections on the feet and legs, which can lead to amputation. Ulcers are healing wounds that develop on the skin mucous membranes or eye Amputation is the removal of a body extremity by trauma or Surgery. Similarly, these patients can get multiple fractures of the knee, ankle or foot, and develop a Charcot joint. Neuropathic osteoarthropathy refers to progressive degeneration of a Weight bearing Joint, a process marked by bony destruction Bone resorption, and Loss of motor function results in dorsiflexion, contractures of the toes, loss of the interosseous muscle function and leads to contraction of the digits, so called hammer toes. A muscle contracture is a permanent shortening of a Muscle or Tendon in the Human body in response to continued Hypertonic stress exerted on A hammer toe is a Deformity of the middle joint of the second third or fourth Toe causing it to be permanently bent resembling a Hammer. These contractures occur not only in the foot but also in the hand where the loss of the musculature makes the hand appear gaunt and skeletal. The loss of muscular function is progressive.

Autonomic neuropathy

The autonomic nervous system is composed of nerves serving the heart, gastrointestinal system and Genitourinary system. &trade The autonomic nervous system ( ANS) (or visceral nervous system) is the part of the Peripheral nervous system that acts as a Control The heart is a muscular organ in all Vertebrates responsible for pumping Blood through the Blood vessels by repeated rhythmic In Anatomy, the genitourinary system is the Organ system of all the Reproductive organs and the Urinary system. Autonomic neuropathy can affect any of these organ systems. Autonomic Neuropathy (also called visceral neuropathy) is a disease of the non-voluntary non-sensory Nervous system (i The most commonly recognized autonomic dysfunction in diabetics is orthostatic hypotension, or the uncomfortable sensation of fainting when a patient stands up. In Physiology and Medicine, hypotension refers to an abnormally low Blood pressure. In the case of diabetic autonomic neuropathy, it is due to the failure of the heart and arteries to appropriately adjust heart rate and vascular tone to keep blood continually and fully flowing to the brain[failure of the sensitivity of the baroreceptors]. The brain is the center of the Nervous system in animals All Vertebrates and the majority of Invertebrates have a brain This symptom is usually accompanied by a loss of sinus respiratory variation, that is, the usual change in heart rate seen with normal breathing. When these 2 findings are present, cardiac autonomic neuropathy is present.

GI tract manifestations include delayed gastric emptying, gastroparesis, nausea, bloating, and diarrhea. Gastroparesis, also called delayed gastric emptying is a medical condition consisting of a Paresis (partial Paralysis) of the Stomach ("gastro-" Nausea ( Latin: Nausea, Greek:, " Sea-sickness " also called wamble) is the sensation of unease and discomfort Bloating is any abnormal general Swelling, or increase in diameter of the abdominal area In Medicine, diarrhea, also spelled diarrhoea (see spelling differences) is frequent loose or liquid Bowel movements Acute diarrhea Because many diabetics take oral medication for their diabetes, absorption of these medicines is greatly affected by the delayed gastric emptying. This can lead to hypoglycemia when an oral diabetic agent is taken before a meal and does not get absorbed until hours, or sometimes days later, when there is normal or low blood sugar already. Hypoglycemia or hypoglycaemia is the medical term for a pathologic state produced by a lower than normal level of Glucose ( sugar) in the blood Sluggish movement of the small instestine can cause bacterial overgrowth, made worse by the presence of hyperglycemia. The Bacteria ( singular: bacterium) are a large group of unicellular Microorganisms Typically a few Micrometres in length bacteria have Hyperglycemia, hyperglycaemia, or high blood sugar is a condition in which an excessive amount of Glucose circulates in the Blood plasma This leads to bloating, gas and diarrhea. Bloating is any abnormal general Swelling, or increase in diameter of the abdominal area In Medicine, diarrhea, also spelled diarrhoea (see spelling differences) is frequent loose or liquid Bowel movements Acute diarrhea

Urinary symptoms include urinary frequency, urgency, incontinence and retention. Urinary incontinence ( UI) is any involuntary leakage of Urine. Again, because of the retention of urine, urinary tract infections are frequent. Urine is a liquid waste product of the body secreted by the Kidneys by a process of filtration from Blood and Excreted through the Urethra. A urinary tract infection ( UTI) is a bacterial Infection that affects any part of the Urinary tract. Urinary retention can lead to bladder diverticula, stones, reflux nephropathy. Reflux nephropathy, RN is a term applied when small and scarred kidneys (chronic Pyelonephritis, CPN are associated with Vesico-ureteric reflux (VUR

Cranial neuropathy

When cranial nerves are affected, oculomotor (3rd) neuropathies are most common. Cranial nerves are Nerves that emerge directly from the Brain stem in contrast to Spinal nerves which emerge from segments of the Spinal cord. The oculomotor nerve controls all of the muscles that move the eye with the exception of the lateral rectus and superior oblique muscles. The oculomotor nerve is the third of twelve paired Cranial nerves. Eyes are organs that detect Light, and send signals along the Optic nerve to the visual areas of the brain For the muscle of the neck see Rectus capitis lateralis muscle The lateral rectus muscle is a Muscle in the orbit. For the abdominal muscle see External oblique muscle The superior oblique muscle, or obliquus oculi superior, is a fusiform Muscle in the It also serves to constrict the pupil and open the eyelid. The pupil is the hole that is located in the center of the iris of the eye and that controls the amount of light that enters the Eye. The onset of a diabetic third nerve palsy is usually abrupt, beginning with frontal or periorbital pain and then diplopia. Diplopia, commonly known as double vision, is the simultaneous Perception of two images of a single object All of the oculomotor muscles innervated by the third nerve may be affected, except for those that control pupil size. This is because pupillary function within CNIII is found on the periphery of the nerve (in terms of a cross sectional view), which makes it less susceptible to ischemic damage (as it is closer to the vascular supply). The sixth nerve, the abducens nerve, which innervates the lateral rectus muscle of the eye (moves the eye laterally), is also commonly affected but fourth nerve, the trochlear nerve, (innervates the superior oblique muscle, which moves the eye downward) involvement is unusual. The abducens nerve (the sixth cranial nerve, also called the sixth nerve or simply VI) is a “somatic efferent” nerve that controls the movement of a The trochlear nerve (the fourth cranial nerve, also called the fourth nerve or simply IV) is a motor nerve (a “somatic efferent” nerve that innervates Mononeuropathies of the thoracic or lumbar spinal nerves can occur and lead to painful syndromes that mimic myocardial infarction, cholecystitis or appendicitis. The term spinal nerve generally refers to the mixed spinal Nerve, which is formed from the dorsal and ventral roots that come out of the Spinal cord. Myocardial infarction ( MI or AMI for acute myocardial infarction) also known as a heart attack, occurs when the blood supply Cholecystitis is Inflammation of the Gall bladder. Causes and pathology Cholecystitis is often caused by Cholelithiasis (the presence of Appendicitis (or epityphlitis) is a condition characterized by Inflammation of the appendix. Diabetics have a higher incidence of entrapment neuropathies, such as carpal tunnel syndrome. Carpal tunnel syndrome (CTS or median neuropathy at the wrist is a medical condition in which the Median nerve is compressed at the Wrist, leading

Treatment

Despite advances in the understanding of the metabolic causes of neuropathy, treatments aimed at interrupting these pathological processes have been limited by side effects and lack of efficacy. Thus, with the exception of tight glucose control, treatments are for reducing pain and other symptoms and do not address the underlying problems.

Agents for pain control include tricyclic antidepressants (TCAs), serotonin reuptake inhibitors (SSRIs) and antiepileptic drugs (AEDs). Tricyclic antidepressants (abbreviation TCAs) are a class of Antidepressant drugs first used in the 1950s Selective serotonin reuptake inhibitors ( SSRIs) are a class of Antidepressants used in the treatment of depression, Anxiety disorders A systematic review concluded that "tricyclic antidepressants and traditional anticonvulsants are better for short term pain relief than newer generation anticonvulsants. A systematic review is a Literature review focused on a single question which tries to identify appraise select and synthesize all high quality research evidence relevant to Tricyclic antidepressants (abbreviation TCAs) are a class of Antidepressant drugs first used in the 1950s The anticonvulsants, also called antiepileptic drugs (abbreviated "AEDs" are a diverse group of pharmaceuticals used in the treatment of epileptic "[1]

Tight glucose control

Treatment of early manifestations of sensorimotor polyneuropathy involves improving glycemic control. [2] Tight control of blood glucose can reverse the changes of diabetic neuropathy, but only if the neuropathy and diabetes is recent in onset. Conversely, painful symptoms of neuropathy in uncontrolled diabetics tend to subside as the disease and numbness progress. Of course, these uncontrolled patients are at great risk for diabetic foot ulcers and amputation because of neuropathy.

Tricyclic antidepressants

TCAs include imipramine, amitriptyline, desipramine and nortriptyline. Imipramine (sold as Antideprin, Deprenil, Deprimin, Deprinol, Depsonil, Dynaprin, Eupramin, Imipramil Amitriptyline (or Amitryptyline) hydrochloride (sold as Elavil Tryptanol Endep Elatrol Tryptizol Trepiline Laroxyl Saroten is a Tricyclic antidepressant Desipramine is a Tricyclic antidepressant (TCA that inhibits the reuptake of Norepinephrine. Nortriptyline is a second generation Tricyclic antidepressant marketed as the Hydrochloride under the trade names Sensoval, Aventyl, Pamelor These drugs are effective at decreasing painful symptoms but suffer from multiple side effects that are dosage dependent. One notable side effect is cardiac toxicity, which can lead to fatal arrhythmias. Dysrhythmia redirects here For the American band see Dysrhythmia (band. At low dosages used for neuropathy, toxicity is rare, but if symptoms warrant higher doses, complications are more common. Toxicity is the degree to which a substance is able to damage an exposed organism Among the TCAs, amitriptyline is most widely used for this condition, but desipramine and nortriptyline have fewer side effects. In Medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as Chemotherapy or Surgery.

Serotonin reuptake inhibitor

SSRIs include fluoxetine, paroxetine, sertraline and citalopram. Selective serotonin reuptake inhibitors ( SSRIs) are a class of Antidepressants used in the treatment of depression, Anxiety disorders Paroxetine (trade names Seroxat, Paxil, Parotin, Aropax, Xetanor, ParoMerck, Rexetin) is a Selective serotonin Citalopram is an Antidepressant drug used to treat major depression associated with Mood disorders It is also used on occasion in the treatment They are less effective than TCAs in relieving pain but are better tolerated. Side effects are rarely serious, and do not cause any permanent disabilities. They cause sedation and weight gain, which can worsen a diabetic's glycemic control. They can be used at dosages that also relieve the symptoms of depression, a common concommitent of diabetic neuropathy. Major depressive disorder, also known as major depression, unipolar depression, unipolar disorder, clinical depression, or simply depression

The SSNRI duloxetine (Cymbalta) is approved for diabetic neuropathy. Serotonin-norepinephrine reuptake inhibitors (SNRIs are a class of Antidepressant used in the treatment of major depression and other mood disorders Duloxetine (brand names Cymbalta, Yentreve) is a Serotonin-norepinephrine reuptake inhibitor (SNRI used for Major depressive disorder (MDD By targeting both serotonin and norepinephrine, it targets the painful symptoms of diabetic neuropathy, and also treats depression if it exists. Typical dosages are between 60 mg and 120 mg.

Antiepileptic drugs

AEDs, especially gabapentin and the related pregabalin, are emerging as first line treatment for painful neuropathy. The anticonvulsants, also called antiepileptic drugs (abbreviated "AEDs" are a diverse group of pharmaceuticals used in the treatment of epileptic Gabapentin (brand name Neurontin) is a medication originally developed for the treatment of Epilepsy. Pregabalin ( INN) (prɨˈgæbəlɨn is an Anticonvulsant drug used for Neuropathic pain and as an adjunct therapy for Partial seizures with or Gabapentin compares favorably with amitriptyline in terms of efficacy, and is clearly safer. Its main side effect is sedation, which does not diminish over time and may in fact worsen. It needs to be taken three times a day, and it sometimes causes weight gain, which can worsen glycemic control in diabetics. Carbamazepine (Tegretol) is effective but not necessarily safe for diabetic neuropathy. Carbamazepine ("CBZ" is an Anticonvulsant and mood stabilizing drug used primarily in the treatment of Epilepsy and Bipolar disorder Its first metabolite, oxcarbazepine, is both safe and effective in other neuropathic disorders, but has not been studied in diabetic neuropathy. Topiramate has not been studied in diabetic neuropathy, but has the beneficial side effect of causing mild anorexia and weight loss, and is anecdotally beneficial. Topiramate (brand name Topamax) is an Anticonvulsant drug produced by Ortho-McNeil Neurologics and Noramco Inc Anorexia (deriving from the Greek "α(ν-" ( a(n-, a prefix that denotes absence + "όρεξη (orexe = appetite is the decreased sensation Weight loss, in the context of Medicine or Health or Physical fitness, is a reduction of the total Body weight, due to a mean loss of fluid

Other treatments

α-lipoic acid, an anti-oxidant that is a non-prescription dietary supplement has shown benefit in a randomized controlled trial that compared once-daily oral doses of 600 mg to 1800 mg compared to placebo, although nausea occurred in the higher doses. An antioxidant is a Molecule capable of slowing or preventing the oxidation of other molecules A randomized controlled trial (RCT is a type of scientific Experiment most commonly used in testing the Efficacy or Effectiveness of Healthcare Placebo is a substance or procedure a patient accepts as medicine or therapy but which has no specific therapeutic activity [3]

In addition to pharmacological treatment there are several other modalities that help some cases. While lacking double blind trials, these have shown to reduce pain and improve patient quality of life particularly for chronic neuropathic pain: Interferential Stimulation; Acupuncture; Meditation; Cognitive Therapy; and prescribed exercise. In more recent years, Photo Energy Therapy devices are becoming more widely used to treat neuropathic symptoms. Photo Energy Therapy devices emit near infrared light typically at a wavelength of 890 nm. This wavelength is believed to stimulate the release of Nitric Oxide, an Endothelium-derived relaxing factor into the bloodstream, thus vasodilating the capilaries and venuoles in the microcirculatory system. Nitric oxide or nitrogen monoxide is a Chemical compound with Chemical formula N[[Oxygen O]] This article is about the biological functions of Nitric oxide. This increase in circulation has been shown effective in various clinical studies to decrease pain and improve sensation in diabetic and non-diabetic patients. Photo Energy Therapy devices seem to address the underlying problem of neuropathies, poor microcirculation, which leads to pain and numbness in the extremities4, 5. The microcirculation is the Blood flow through Blood vessels smaller than 100 µm (i

While it is quite true that recognized treatment modalities backed up by double blind trials do not address the underlying causality of diabetic neuropathy, two other programs have had substantial although still anecdotal results. The first involves a program of nutritional supplements put forth in an Internet article researched and published by diabetic neuropathy patients themselves (although heavily referencing peer-reviewed research articles). This article is entitled "A Multidisciplinary Approach to Diabetic Neuropathy Treatment" and its treatment regimen has been instrumental in substantial reversal in individuals throughout the world. [4]

The second method involves a combination of a vegan diet combined with moderate walking exercise. It has been used over several decades to affect both Type II diabetes as well as diabetic peripheral neuropathy.

Though not yet commercially available, C-peptide has shown promising results in treatment of diabetic complications, including neuropathies. C-peptide is a Peptide which is made when Proinsulin is split into Insulin and C-peptide Once thought to be a useless bi-product of insulin production, it helps to ameliorate and reverse the major symptoms of diabetes[5].

Epalrestat: Long-term treatment with epalrestat is well tolerated and can effectively delay the progression of diabetic neuropathy and ameliorate the associated symptoms of the disease, particularly in subjects with good glycemic control and limited microangiopathy.

Prognosis

The mechanisms of diabetic neuropathy are poorly understood. At present, treatment alleviates pain and can control some associated symptoms, but the process is generally progressive.

As a complication, there is an increased risk of injury to the feet because of loss of sensation (see diabetic foot). Diabetic foot is an umbrella term for foot problems in patients with Diabetes mellitus. Small infections can progress to ulceration (skin and soft tissue breakdown) and this may require amputation. An infection is the detrimental Colonization of a host Organism by a foreign Species. Ulcers are healing wounds that develop on the skin mucous membranes or eye The skin is the outer covering of living tissue of an animal (or plant Amputation is the removal of a body extremity by trauma or Surgery. In addition, motor nerve damage can lead to psychotic breakdown and imbalance. [6]

See also

References

  1. ^ Wong MC, Chung JW, Wong TK (2007). Diabetes mellitus (ˌdaɪəˈbiːtiːz or /ˌdaɪəˈbiːtəs/ /məˈlaɪtəs/ or /ˈmɛlətəs/ often referred to simply as diabetes ( Ancient Greek: grc The National Diabetes Information Clearinghouse (NDIC is an information dissemination service of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK Neuropathy is a medical term usually short for Peripheral neuropathy. "Effects of treatments for symptoms of painful diabetic neuropathy: systematic review". BMJ 335 (7610): 87. doi:10.1136/bmj.39213.565972.AE. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 17562735.  
  2. ^ "The effect of intensive diabetes therapy on the development and progression of neuropathy. The Diabetes Control and Complications Trial Research Group" (1995). Ann. Intern. Med. 122 (8): 561-8. PMID 7887548.  
  3. ^ Ziegler D, Ametov A, Barinov A, et al (2006). "Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: the SYDNEY 2 trial". Diabetes Care 29 (11): 2365-70. doi:10.2337/dc06-1216. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 17065669.  
  4. ^ A MULTIDISCIPLINARY APPROACH TO DIABETIC NEUROPATHY TREATMENT. Retrieved on 2007-07-25. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 285 - Diocletian appoints Maximian as Caesar, co-ruler
  5. ^ Cotter, M. A. , Ekberg, K. , Wahren, J. , & Cameron, N. E. 2003. Effects of Proinsulin C-Peptide in Experimental Diabetic Neuropathy: Vascular Actions and Modulation by Nitric Oxide Synthase Inhibition. Diabetes 52:1812-1817, 2003. The American Diabetes Association, Inc.
  6. ^ Need Citation

External links

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