Diabetic Neuropathy

Dr Muhammad Khurram

FCPS, FRCP

Diabetes Mellitus

• What is DM

• DM is an increasingly serious social, economicand medical threat that is not just a healthissue, but a development issue (as it hindersprogress).

DM Figure Wise

• World Total 366 + million

• Pakistan currently 7.1 + million

• % Population 7-9%

• By 2030 11.4 + million

• Death toll/year 88000

Diabetic Neuropathy

• The San Antonio Consensus Statement onDiabetic Neuropathy defined the condition asbeing a demonstrable disorder, eitherclinically evident or subclinical in the setting ofdiabetes without other causes of peripheralneuropathy.

• 50-90% of patients who have diabetes alsohas neuropathy

• 22.7% DM I, 32.1% DM II

• 11-32% of patients with Diabetic Neuropathyexperience painful symptoms

Risk Factors

• Glycaemic control• with age

– 5% 20-29 years 44.2% 70-79 years– 50% T2DM >60 years of age

• with duration of diabetes– 20.8% < 5years 36.8%>10 years

• Smoking• Microalbuminuria• Height• Nutritional factors, additional illnesses

Pathogenesis

• Increased aldose reductase activity.

• Auto oxidation of glucose

• Non enzymatic glycation of protein(AGE)

• Activation of protein kinase C

• Oxidative stress

• Decrease essential fatty acid

• Reduced serum levels of nerve growth factor

• Nerve ischemia/hypoxia.

• Axonal loss

• Focal demyelination & regeneration

• Intraneural capillary abnormalities

• conduction velocity and sensory thresholds

Classification

• Somatic

– Polyneuropathy

• Symmetrical, mainly sensory and distal

• Asymmetrical, mainly motor and proximal

– Mononeuropathy & MNM

• Visceral

– GIT, CVS, Genitourinary

– Vasomotor, sudomotor, pupillary

Clinical Features

• Alone or combination

• Occur as the disease duration increases and depend on glycemic control generally

• Acute and rapid

• Slow and progressive

Symmetrical Mainly Sensory DPN

• Asymptomatic

• Symptomatic– Paresthesia

– Pain

– Burning sensations

– Hyperaesthesia

– Gait

– Small muscle wasting

– Charcot Joint

Asymmetrical Motor DN

• Severe, progressive weakness of proximal muscles

• Predominant LL involvement

• Pain

• Neuropathic cahexia

• Upgoing planters and depressed refelexes

• Outcome

Mononeuropathy & MNM

• Peripheral/cranial nerve involvement

• Motor, sensory or both components

• Sudden and rapid onset

• Good recovery

• 3rd, 6th, Femoral/Sciatic nreves

• Truncal radiculopathies

• Entrapment neuropathies– Median, Ulnar, Lateral popliteal

– AGE of tissues and Neuropathy

Autonomic DNP

• Different- relation with glycemia control

• Sympathetic or parasympathetic predominance

• Poor outcome

• CVS– Postural hypotension, resting tachycardia, fixed heart

rate

• GIT– Dysphagia

– Nausea, vomiting, distension, bloating,

– Diarhea, incontinencnce

– Constipation

• Uinary

– Difficulty in micturation, incontinence, recurrent infection

• Sudomotor

– Sweating, Anhidrosis, Gustatory sweating

• Vasomotor

– Cold feet, Edema, Bullae

• Pupillary

– Meiosis, mydriatic resistance, reflex abnormality

• Erectile dysfunction

– Multifatorial

– Neuropathy, vascular, psychological, endocrine, Rx

How to diagnose

• History

• Clinical Examination

• Investigations

– General Investigations

– Imaging

– NCS

– Biopsy

AN Tests

• Resting heart rate

– >100/m is abnormal.

• Systolic BP response to standing

– BP measured supine. Patient stands, BP aft 2 m.

– Normal response- fall of <10 mmHg,

– Borderline - fall of 10–29 mmHg

– Abnormal - fall of >30 mmHg with symptoms

• Beat-to-beat HRV

– At rest and supine heart rate by ECG while patient

breathes at 6/m

– Difference of >15 bpm - normal, <10 bpm -

abnormal.

• Heart rate response to the Valsalva manoeuvre

– Exhales into manometer to 40 mmHg for 15 seconds

– Healthy subjects develop tachycardia & peripheral

vasoconstriction during strain & overshoot bradycardia,

rise in BP with release.

– The ratio of longest R-R to shortest R-R should be ≥1.2.

• Neurovascular flow

– Using noninvasive laser Doppler measures of

peripheral sympathetic responses to nociception.

• Radionuclide Cardiac Imaging

– MIBG

– 11-C-hydroxyephedrine

Tips

• Duration of illness

• Glycemia control

• Other complications

• Symptoms

• Clinical evaluation

Management

• Glycemia assessment and control

• Exclusion of other causes

• Risk factors modifications

• Specific measures

Exclusion of other causes/Risk factor modification

• Vitamin deficiencies

• Malignant disease (e.g., bronchogeniccarcinoma)

• Metabolic

• Toxic (e.g., alcohol)

• Infective/post infection

• Medications

Specific Measures

• Pain and paresthesias– Anticonvusants (gabapentin, pregabalin,

carbamezapine, phenytoin)

– TCA (amitryptaline, nortriptaline)

– Duloxetine

– Capsaicin

– Opiates

– Memrane stabilizers (mexilitine)

– Antioxidants

• Postural hypotension

– Compression stocking

– NSAIDS

– Fludrocortisone

• Gastroparesis

– Dopamine antagonisits

– Erythromycine

– Jejunal feeding, Pacing

• Diarrhea– Loperamide

– Abx

– Octreotide

– Clonidine

• Constipation– Laxative

• Bladder atony– Catheterisation

• Excessive sweating– Oxybutinin, propantheline

– Clonidine

– Glycopyrolate

• Erectile dysfunction– Sildenafil, verdenafil, tadalafil

– Dopamine agunsist- apomorphine SL

– PGE1- Alprostadil

– Vacuum devices, implants

– Psychosexual therapy

Take Home Message

• Diabetic neuropathy is common

• Metabolic & vascular factors cause it.

• Distal symmetrical sensorimotor polyneuropathy is commonest form

• Non DM aetiologies need exclusion

• Should be sought

• Optimal glycemic control is required

• Other DM issues should be managed

• Focused care and medications are required

THANX A LOT