INTRODUCTION:

Diabetic neuropathy is commonest complication of DM with varied clinical presentation and significant morbidity. The aetiopathogenesis, treatment and relation with glycemic control is always controversial and challenge to physicians. Various new treatment protocols are on trial.

It was described by Rollo about 200 years ago. In 1864 Michael de Calvi proposed that neuropathy is due to Diabetes. In 1945 Rundles first gave the comprehensive description.

There are 3 proposed stages of neuropathy giving emphasis on early diagnosis and treatment. They are a) Functional neuropathy- reversible biochemical alteration in nerves b) Structural neuropathy – structural damage to nerve cells but reversible c) Nerve death - Irreversible.

PHYSIOLOGY & METABOLISM OF NERVE CELLS

Normally the production and utilization of energy depending on the rate of production and utilization of adenosine triphsophate (ATP) is a balanced state in the cells. Whenever the ATP production is restricted the cells adopt by either decreasing energy requirement for biological activities, increasing glycolysis for ATP production or using phosphocreatine stores for ATP production.

Endoneurium glucose is the major substrate for energy production in peripheral nerves, which is independent of Insulin. In ischemic conditions there is reduced oxygen supply, glucose supply for glycolysis and ATP production resulting in lactate accumulation and acidosis which effects the structure and function of neuronal tissues.

AETIOPATHOGENESIS
The mechanism of multifactorial. They are vascular and metabolic. The various factors responsible are hyperglycemia, increased polyol pathway activity, myoinositol depletion, Na/K ATpase activity, endoneural hypoxia due to micro vascular disease and vasonervorum involvement.

Metabolic Theory:
a. Polyol Pathway: Normally 1% glucose is metabolized through this which is independent of insulin. Hyperglycemia leads to intracellular glucose accumulation which is converted to sorbitol by enzyme aldose reductase. Some sorbitol is fructose by sorbitol dehydrogenase. Sorbitol and Fructose damage the Schwann cell by more osmolarity and effect nerve conduction.
b. Myoinositol Pathway: Myoinositol, a cyclic hexitol is normally found in plasma and mammalian cells and major constituent of phospholipids and cell membrane. Higher levels are found in peripheral nerve. The tissue level is maintained by synthesis from glucose 6-phosphate and recovery from phosphinositol hydrolysis.
Increased polyol activity leads to depletion of myoinositol concetration by unknown mechanism, which inhibits Na+/K+ ATPase activity leading to reduced myoinosital uptake.
c. Lipids – Myelin synthesis is reduced due to reduction of membrane cholesterol, cerebroside, sphingomyelin and phosphatidyl serine – phosphatidyl inositol.

Vascular Theory:
Chronic hypoxia causing structural damage to nerves is due to reduced endoneural blood flow. In diabetes the normal vascular autoregulations is lost. Endoneural hypoxia with reduced Na+/ K+ ATpase reduce nerve conduction velocity and cause axonal atrophy. In diabetes there is multifocal loss of proximal fibres and diffuse loss of distal fibre. However both metabolic and vascular mechanisms are overlapped. Changes occur in endoneuroal and perineural blood vessels in the form of endothelial proliferation with luminal narrowing, pericyte basement membrane hyperplasia, perivascular space thickening and closed capillaries.

In general metabolic, vascular factors along with glycosylation of protein, hyperaggregation of platelets and altered haematology combindly responsible for neuropathy. Hyperglycaemia reduce pain threshold. Increased blood flow to extremities with hyperglycaemia, loss of vascular tone produce pain.

PATHOLOGY:
Peripheral nerve is classified as motor, sensory, autonomic and small or large and degree of lyelination and each with a distinct function.

Both large and small fibres are involved and on biopsy show axonal degeneration, segmental demyelination, intraneural vascular thrombi, loss of myelin due to Schwann cell damage.

ELECTROPHYSIOLOGICAL CHANGES:
The nerve conuction are more helpful than clinical and histological studies. In majority cases – axonopathy – reduced evoked motor response and sensory action potential with preservation of conduction velocity. Focal nerve entrapments: Carpal tunnel, cubital tunnel, common peroneal tunnel etc., Presence of mononeuropathy simplex/multiplex are detected.
Newer techniques like: Motor unit counting, near nerve action potential and refractory period, Needle electromyography – (recent, sophisticated), Sensory action potential and autonomic function test are sensitive.

Sequential EMG changes ranging from reduced recruitment of motor unit potentials, presence of fibrillation potential, polyphasic high amplitude long duration motor unit potential, absent of F waves occur at various stages of axonal damage.

CLINICAL CLASSIFICATION:
On the basis of clinical presentation the arbitrary classification for better understanding is accepted.
1. Gradual onset type: Distal symmetrical polyneuropathy: Usually mixed or Predominantly sensory with autonomic neuropathy
2. Acute onset type: Painful symmetric polyneuropathy, Diabetic amyotrophy (plexopathy), Mononeuropathies (Cranial, truncal, isolated, multiple mononeuropathies)., Radiculopathies, Neuropathic cachexia,
3. Autonomic neuropathy are Sympathetic and Parasympathetic

CLINICAL JUDGEMENT OF SEVERITY

By using UK screening test the severity can be graded.
Part – 1
 What is the sensation felt? – burning numbness or tingling in the feet (2 points) fatigue, cramping or arching (1 point). Maximum is 2 points.
 What is the location of symptoms? Feet (2 points) calves (1 Point): elsewhere (no points) maximum is 2 points.
 Have the symptoms ever woken you at night? yes (1 point)
 What is the timing of symptoms? Worse at night (2 points) present day and night (1 point): Present only during the day (no point) maximum is 2 points.
 How are symptoms relieved: walking around (2 points) standing (1 points); sitting or lying or no relief (no points) maximum 2 points.
 The total symptom score can then be determined: 0 to 2 – normal, 3-4 – mild neuropathy, 5-6 – moderate neuropathy & 7-9 – severe neuropathy.

Part - 2
A similar quantitative score can be made for the physical findings:
 What is the Achilles tendon reflex? - Absent (2 points for each foot); present with reinforcement (1 point for each foot).
 What is vibration sense? Absent or reduced (1 point for each foot)
 What is pin prick sensation? – Absent or reduced (1 point for each foot)
 What is temperature sensation? ( reduced ( 1 point for each foot)
The neurologic signs score can then be determined. 0-2 normal, 3-5 mild neuropathy, 6-8 moderate neuropathy and 9-10 sever neuropathy

Peripheral neuropathy is considered to be present if there are moderate or sever signs (6 points) even in the absence of symptoms or if there are at least mild signs (3 point) in the presence of moderate symptoms ( 5 points). A neurologic sign score or 8 or more indicates that the patient’s feet are at high risk for ulceration.

CLINICAL PRESENTATION
I. GRADUAL ONSET TYPE
Distal symmetrical polyneuropathy
Commonest presentation, developing over few years, detected on routine examination by absent ankle jerk. Though all somatic nerve fibres are effected, the distal parts of limbs (feet > hands) are more effected, giving rise to typical “glove and stocking” presentation. The symptoms are often symmetrical and exacerbate at night.

The symptoms and signs vary depending on predominant small or large fibre involvement.
 Small sensory neuropathy – undetected trauma to extremities specially to feet inform of scald by hot water or ulcer, infection with minor injury. May have absent or diminished sensation (cold or numb) May present as parasthesia or dysthesias in form of “tingling” or “pin and needle” sensation in extremities. Many complain severe burning or pain described as tearing , gnawing , aching or deep seated.
 Large fibre involvement: May have loss of vibration sensation followed by touch and position sense, producing sensory ataxia, unsteady gait and positive Romberg’s sign. Involvement of afferent fibres of stretch receptors lead to loss of reflexes.
 Due to loss of touch and pain sensation there may be neuropathic arthropathy or perforating ulcer in feet , associated with diminished muscle strength and vascular dysfunction.
 Diabetic neuroarthropathy involves small joints of foot and ankle. In initial phase the foot is swollen, painless and red without fever or leucocytosis (differ from infective arthropathy). The condition resembling tabes dorsalis so called “Diabetic pseudotabes”.
 In a classical presentation neurogenic atrophy of small muscle of plantar arch leads to flat foot and chronic flexion of the metatarsophalangeal joints producing callus over metatarsal heads and ulceration. The foot is warm with palpable dorsalis pedis and intact veins. Neuropathic ulcers are seen at other contact points of feet like ill fitted shoes.
 Distal symmetric polyneuropathy may show motor involvement although masked by sensory component. In Some predominant motor involvement shows flexor and extensor of foot which may be atrophied later. Involvement of small muscles of hand and feet lead to claw hand, claw foot or pescavus deformity. Predominant motor neuropathy though rare is associated with insulinoma induced repeated hypoglycaemia.
 Distal symmetrical polyneuropathy is usually associated with autonomic neuropathy.

II. ACUTE ONSET TYPE
A. Painful symmetric polyneuropathy :
o Commonest acute onset painful neuropathy. It is very painful with nocturnal exacerbation. It tends to develops 3 weeks after stressful conditions like surgery, ketosis, infection etc., May develop after insulin initiation under rapid and repeated hypoglycemia. Seen in severe diet restriction with undernourishment. This neuropathy remains for 6-18 months and disappears.
o Motor involvement is common and severe than gradual onset type.
B. Diabetic amytrophy (Plexopathy)
o Seen in elderly diabetes of short duration. It is painful and associated with stress. Typically there is painful weakness and atrophy of pelvic girdle and thigh muscles involving ileo-psoas, quadriceps relative sparing of hip extensors and hamstrings. Occasionally the peroneal and tibial muscles are effected.
o Sensory sign and symptoms may occur like pain, paraesthesia of anterior thigh and anteromedial leg radiating to dorsum of foot or pain from sacroiliac region radiating to back . The knee jerk is absent.
o The plexopathy is usually unilateral at onset but other side is somewhat involved. Shoulder girdle plexopathy is rare.
C. Mononeuropathies:
i. Cranial nerve involvement: Isolated or multiple nerve involvement may be seen without any sign of peripheral neuropathy. The III and VI are commonly involved and IV th is rarely alone. The diplopia is acute onset with pain behind and above the affected eye ( may be due to involvement of 1st and 2nd part of Vth nerve). The pupil is spared. Symptoms resolve after 6-12 weeks. The VIIth Cranial nerve may be affected rarely where the prognosis is less favorable than III and VI cranial nerve. Other upper cranial nerves may be rarely involved while the lower cranial nerves are never effected.
ii. Isolated peripheral nerve lesion. Relatively more common. The cause may be due to vascular, trauma or entrapment to superficial nerves. Any major nerve may be involved. When several nerves are affected simultaneously it is called “mononeuritis multiplex”. The nerves commonly involved are median, ulnar, radial, femoral, sciatica and peroneal , lateral cutaneous nerve of thigh. The sign and symptoms dpends on the nerve involved. The onset is usually acute painful but rarely indiduous.
iii. Radiculopathy: Relatively uncommon but correct diagnosis is necessary for unnecessary intervention. Root involvement at different segmental levels mimic different emergency conditions like constructive chest pain, pain abdomen. The cause of involvement though not definitive , may be ischaemia. EMG of involved muscles and recovery after some period without residual damage is helpful.
iv. Diabetic neuropathic cachexia: Recognized as a separate entity, where painful , acute onset symmetrical neuropathy associated with much weightloss. The nerve involvement usually disappears within 6-12 months.

III. AUTONOMIC NEUROPATHY
Usually associated with gradual onset type. It varies from mild involvement to severe masking other presentations. But mild involvement may produce significant incapacity.
A. Cardiovascular
 Postural hypotension : Commonest manifestation when postural drop occurs more than 20 mm of Hg. In some the postural drop occurs after insulin therapy greatest effect being 1 to 3 hours after injection.
 Cardiac denervation: May show partial or complete denervation with a fixed P/R of 80/90 which does not change with stress, exercises or sleep. There also occurs adnergic supersensitivity. These two factors lead to greater incidence of coronary artery spasm, painless MI, and sudden death.
 Exercise intolerance: Besides cardiac involvement changes in the autonomic tone may prevent an adequate rerouting of the blood flow after exercise. Pre-exercise evaluation is required for diabetic before advising exercise therapy.
B. Gastrointestinal tract
 Oesophageal dysmotility: May cause dysphagia, regurgitation due to low tone of LES and sense of retrosternal fullness and discomfort.
 Gastroparesis diabeticorum – In 50% of cases of diabetes due to impaired gastric acid secretion and motility produce early satiety, anorexia, nausea, vomiting, epigastric discomfort and bloating . Usually associated with bezoars. Interference of nutrient delivery to small intestine disrupts glucose absorption and exogenous insulin administration resulting a state of apparent “brittle diabetes” state.
 Diarrhoea: Common disturbing manifestation preceded by abdominal discomfort having nocturnal frequency may have faecal incontinence. The stool is usually watery but may be steatorrhic, with a frequency of 25-30 times /day. The attack may be intermittent with interval of normality or constipation. The cause of diarrhoea may be due to hypermotility by decreased sympathetic tone, bacterial over growth, pancreatic insufficiency, diabetic sprue and bile salt malabsorption.
 Constipation is a common symptoms in some studies.
 Gastric and colonic atony and enlarged gall bladder are common.
C. Genitourinary System:
 Bladder dysfunction is common. Initially may have diminished frequency with nocturia and later there may be incontinence , over flow dribbling, residual urine leading to infection.
 Impotency in form of erectile dysfunction found in more than 50% of male. Retrograde ejaculation may be seen. Neurogenic sexual dysfunction occur in 25-30% of females. Loss of testicular sensations in few studies reported.
D. Pseudomotor function
 Sweating disturbances manifest as abnormal and bizarre pattern commonly absence of sweating over distal parts of lower limb (like distal symmetrical neuropathy) with compensatory hyperhydrosis of trunk and face. Patient shows heat intolerance and there occurs nocturnal sweating. Facial sweating during meal is rare. It is more with cheese and tyramine containing foods and starts after chewing. Starting from forehead it spreads to face , scalp, back and upper chest. Anticholinergic drugs are less helpful
E. Pupillary Changes: Pupil may be constricted and that may be Argyll – Robertson type pupil. It reflects duration of diabetes, metabolic factors and other associated complications.
F. Metabolic: Hypoglycemia associated autonomic dysfunction – As glucagons and adrenal medulla depend on functional integrity of ANS, the signs and symptoms of hypoglycemia are diminished.
G. Respiratory system: Respiratory arrest may rarely occur
H. Vasomotor: Changes like loss of skinvasomotor response, peripheral vascular changes, osteopathy and charcot’s arthropathy and dependant oedema may occur.

MANAGEMENT
The protocol consists of management of hyperglycemia , metabolic abnormality , painful neuropathy and autonomic neuropathies.
I. Treatment of hyperglycemia
By assessing the glycaemic status drugs are tried to maintain good and sustained glycaemic control. In Type 2 DM diet control and oral drugs may be enough. Insulin maybe tried as its membrane stabilizing effect. In some poorly controlled diabetes pain may be aggravated when tight sugar control is done by insulin which subside after stabilization. Stable glucose control relieves pain and slow the progress of neuropathy.
II. Treatment metabolic abnormalities:
i. Aldose reductase inhibitors (ARI) – Alrestatin and Sorbinil are two drugs.
- Alrestatin – Not used due to average side effect
- Sorbinil – In dose of 250mg/day improves peroneal, median and sensory conduction velocity in 2 months, reduction of sciatic nerve sorbitol content and restoration of myoinositol is achieved. Side effects of hypersensitivity causing fever, rash , lymphadenopathy has restricted its use.
ii. Gangliosides – Facilitates neural sprouting of regenerating nerves producing subjective and objective improvement. Myoinositol is another trial drug. Seafood and vegetables like drumstick are myoinositol rich foods.
iii. Protein kinase C inhibitors (PKC) – Its role in preventing neuropathy is under trial.
iv. Gamma linoleic Acid (GLA) – GLA , an essential fatty acid is required for arachadonic acid derivatives like prostaglandin production, helpful in diabetic neuropathy.
v. Antioxidants – Several drugs have shown good results. Alpha lipoic acid, a potent hydrophilic antioxidant improves nerve blood flow, nerve glucose uptake, myoinosital content and sensory nerve conduction velocity.
vi. Neurotrophins – A group of soluble proteins like NGF, BTNT, NT3, NT4, NT5 affecting growth , differentiation, maturation , function and survival of particular set of neurons are under trial.
vii. Mecobalamin – It is an active coenzyme form of Vit B12. It is a cofactor in the methionine synthetase which functions for methyl transfer of methionine from homocysteine. It is related to folate metabolism which is responsible for purin and pyramidines of DNA. It acts as a methyl donor for synthesis of lecithin, a component of myelin sheath. Mecobalamin is better transported than cyanocobalamin into nerve cells prompting nucleic acid regeneration and protein synthesis. It promotes axonal transport and regeneration. Mecobalamin promotes myelination (phospholipid synthesis ) and lecithin synthesis of lipid sheath and inceases meylination of neurons. In a dose of 500 gm I/M or I/V thrice in a week or orally 500 to 1000gm/ daily in effective.
viii. Nandrolone – a nonsteroidal anabolic drug in a dose of 25 mg weekly for two months.

III. Treatment of painful neuropathy

Many drugs have been tried to relieve this painful condition with various degree of relief.
a. NSAID and Analgesics:
- Tramadol a non-narcotic centrally acting analgesic in a dose of 50 mg daily increasing by 50 mg daily to maximum 400mg/day is commonly used at bed time.
- Analgesics like propoxyphene and acetaminophen given in evening before bed reduces pain. Use of NSAID are to be carefully considered due to GI and Renal complications. They may be used as short term adjuvant therapy.
- Few cases may require opiods like oxycodone where regimen is to be considered on individual basis.
b. Antidepressants
i. Tricyclic compounds (modulate alpha receptor activity): - Though used frequently potential side effects and cardiotoxicity has limited its use.
a. Amitryptiline – Started at 25 mg bed time and increasing upto 150mg depending on response. The adverse affects are anticholinergic (constipation, dry mouth, blurring vision, tachycardia, weight gain, orthostatic hypotension) and sedation.
b. Nortryptiline – Preferable in elderly diabetic due to less anticholinergic effect.
TCA are contraindicated in arrythmias, II0 and III0 heart block , MI, liver diseases , and to be used with caution in closed angle glaucoma, BHP, Constipation, urinary retention, cardiovascular and liver diseases.TCA are to be tappered over 2-4 weeks to avoid withdrawal symptoms
c. Other TCA drugs like imipramine 50-150mg/daily , desipramine 25-150mg/daily , Mianserine 30-90mg/daily may be used.
ii. Serotonin –nonepinephrine reuptake inhibitors (SNRI)
Duloxetine
- An antidepressant has been recently used with good result.
- Dose is 60mg/day. May be given upto 120mg /day. No adjustment is required in renal dysfunction but contraindication in hepatic diseases.
- Side effect - Commonly nausea, constipation, dry mouth and fatigue are seen. As it raise BP, causes tachycardia should be used with caution in cardiovascular disorders. It may cause sexual dysfunction.
Venlafaxine
- Venlafaxine or Venlafaxine ER is effective with minimal adverse events. The dose is 75mg 225 mg daily.
c. Anticonvulsants
These drugs depress abnormal discharge and raise threshold for neuronal propagation. It is effective in more than 50% patients.
i. 2- Ligands
Gabapentin
 This anticonvulsant is now first line drug. It decreases pain, sleep interference, positive effect on mood and quality of life.
 Dose- Start – 100mg 1st day, 200mg BID 2nd and 300mg TID on 3rd day. Then increase by 100mg every three days depending on response and side effect until a maximum of 3600 mg/daily. Dose is to be titred in Renal impairment.
 Side effects: Commonly dizziness and somnolence which subside by 10 days. Less common side effects are nystagmus, tremour, diplopia, ataxia, fatigue, weight gain.

Pregabalin
 This anticonvulsant drug is similar to Gabapentin.
 Dose – Start with 75 mg twice daily. Increase to 150mg twice daily after one week depending on response upto maximum 600mg daily. Dose is to be adjusted in renal dysfunction.
 Side effects are like Gabapentin but drowsiness is common. Its better absorption and rapid onset of action than Gabapentin makes it a better choice.
 The mechanism though unclear they may reduce excitatory neurotransmitter release by binding to a2 -  protein subunits of voltage gated calcium channels.
ii. other drugs
 Carbamazepine: (200- 800mg/daily) works by slowing the recovery rate of voltage gate Na+ channel from depolarization.
 Phynytoin though have similar effect itself produce neuropathy.
 Valporic acid increases GABA level by decreasing degradation
 Newer anticonvulsant drugs like Oxcarbamazepine, Toporamate, Tamotrigine and others are better tolerated and safe. But the choice of drugs differ in different patients.
 Lamotrigine: An anticonvulsant having antidepressant properties acts by stabilization of neural membrane through voltage-gated sodium channel and inhibition of presynaptic release of glutamate. The dose is 200 – 400 mg/daily. Side effect are nausea, epigastric pain, headache , drowsiness, dizziness.
d. Local and other therapies
 Capsaicin ointment (0.075%) may be useful in painful neuropathy. It is to be applied 3-4 times daily in bulk amount. It produces burning sensation locally which gradually diminishes. The side effects are cough, sneezing, irritation and rash.
 Isosorbide dinitrate spray – Local spray before bedtime reduces pain and burning. Glyceryl nitrate patch is an alternate. The mechanism is not known.
 Several local anaesthetic cream though tried no consistent benefits achieved. Example – Lidocaine patch (5%).
 Lignocaine intravenous infusion or normal saline infusion for 6-7 days have been tried.
 Acupuncture – With minimal risk some analgesic efficacy is seen. It relieves pain and reduce analgesic need.
 Other trial drugs: Bupropion – 150- 300mg/daily, Citalopam – 40mg/daily, Methadone – 10-20mg/daily, Dextromethorphan – 400mg/daily, Paroxetine –40 mg/daily, Topiramate – 400mg/daily have been used.
 Other modalities – No good result achieved. Transcutaneous electrical nerve stimulation or magnetic insole spinal cord stimulation and frequency modulated electromagnetic stimulation
IV. Treatment of autonomic neuropathy
A. Postural hypotension
 Supportive garments like elastic stocking causing increased venous return. Gradual assumption of upright posture after getting up.
 Drugs like plasma and ECF expanders may be tried.
- High sodium intake
- Fludrocortisone – start with 0.1mg tablet daily and increase to 0.5 mg/daily.
- Vasoconstrictors like – vasopression, Levodopa and Pindolol. Indomethacin (Increase endogenous nonadrenalin and angiotensin II). Dihydroergotamine have been tried.
- Midodrine – Peripherally acting selective  agnosist in a dose of 2.5 to 10 mg thrice daily.
B. Gastroenteropathy
 Diet – small , multiple feeding with less fat and less fibres to avoid bezoars.
 Prokinetics drugs: Metoclopramide – 10mg, orally , ½ hour before meal and bed time accelerates gastric emptying time, Domperidone – 10-20 mg 4 times daily and Mosapride are effective. Cisapride – Not used due to side effects.
 Oral erythmycin – 250mg thrice daily improves gastric emptying time.
 For diabetic diarrhoea – Loperamide , codeine , antibiotics like tetracycline, metronidazole and preprobiotics may be effective. Diphenoxylate with atropine may help.
 If medication fails jejunostomy to normal bowel may be done.
C. Bladder dysfunction
 If difficulty in initiation Credes maneuver (massage or pressure over lower abdomen above pubis) every 4 hourly to improve bladder emptying is tried. Parasympathomimetic like Bethanechol (10-30 mg thrice daily) may be helpful. Extended sphincter relaxation is achieved by 1- blocker – prazosin, doxazosin. Self catheterization maybe useful.
 Rarely bladder neck surgery is required.
D. Erectile dysfunction in males - 5 phosphodiesterase (PDE-5) inhibitors like sidenafil, tadalafil and Vardenafil are options which are rarely used due to side effect and will be obsolete soon. Papaverine injection (40-80mg) directly to corpus cavernosum may restore impotency. Penile prosthetic implants like semirigid or malleable or inflatable devices may be useful. Recently “Erect aid systems” with vaccum fitting devices has been well accepted.
E. Female sexual dysfunction – though not well studied vaginal dryness and dryspareuria respond to water based lubricants. The effect of PDE-5 may provide some benefit in absence of contraindications.
F. Hyperhydrosis – If severe anticholinergics like trihexyphenidyl or scopolamine in high doses may be used. But side effects limits their use.

SUMMARY

Diabetic neuropathy, the complication of long standing uncontrolled diabetes is common. The aetiopathogenesis is multifactorial and poorly understood. It is classified on clinical basis. The severity may be graded by UK screening test. Distal symmetrical polyneuropathy and painful symmetric polyneuropathy are common clinical presentation. Autonomic neuropathy leads to significant incapacitating situations. Sustained glycemic control and metabolic correction are first line of treatment . For painful neuropathy newer anti-depressants and anticonvulsants are quite effective. For autonomic neuropathies the treatment is supportive and symptomatic.

CONCLUSION

In the present scenario, diabetic neuropathy having multifacorial, aetiology, varied clinical neurological presentation is a challenge to the patient and physicians. Various therapies to minimize the pain and other morbid situations have been tries without 100% benefit. Many drugs are on trial phase. However the basic theme is early diagnosis, sustained glycemic control for prevention of this complication.

CLINICAL FOCUS:

 Diabetic neuropathy is commonest complication with morbidity.
 Various metabolic alterations and vascular changes lead to functional and structural damage to nerves.
 Distal symmetrical polyneuropathy and acute painful symmetric polyneuropathy are commonest among the presentations.
 The severity is graded by UK screening test.
 Silent MI and sudden death is common in diabetic autonomic neuropathy .
 Gastrointestinal and genitourinary , other autonomic complications lead to much physical and mental stress.
 Erectile dysfunction in male and inpotency is a major social problem.
 Persistent glycemic control and metabolic management are basic management.
 For painful neuropathy though various drugs have been tried the newer antidepressants and anticonvulsants are effective.
 For management of autonomic neuropathy the treatment is supportive and symptomatic.