Diabetic Diabetic Microvascular Microvascular ComplicationsComplications

Mathew John MD, DM, DNB

Consultant Endocrinologist

Microvascular complication

MICROVASCULAR COMPLICATIONS

Retinopathy

Neuropathy

NephropathyCardiomyopathy

Cheiroarhropathy

Dermopathy

Structure of talk

• Screening • Diagnosis • Treatment

Retinopathy Nephropathy

Neuropathy

Therapeutic failures in diabetes

• When a patient reaches end stage renal failure

• When a patient becomes blind or severely visually impaired

• When a patient has a leg or foot amputated

• When a patient suffers from MI or stroke

Magnitude of the problem

• Somewhere in the world a leg is lost to diabetes every thirty seconds

• Leading cause of new onset blindness

• 10% to 20% of people with diabetes die of renal failure

• Diabetes is the leading cause of end stage renal disease requiring dialysis

• Every 10 seconds a person dies from diabetes-related causes

UKPDS results of Intensive therapy

Risk reduction vs. conventional therapy

Risk factors for microvascular complications

• Degree of glycemic control• Duration of disease • Hypertension • Dyslipidemia • Smoking

Pathophysiology of complications

Diabetic Retinopathy

Retinopathy

• Sight threatening microvascular complication

• Changes in retinal microvascular architecture

• Leading cause of new onset blindness in the developed world

• > 90 % of vision loss resulting from proliferative retinopathy can be prevented

How common is retinopathy ?

• Type 1 diabetes : 25 % of type 1 diabetes after 5 years

: 60-80 % after 10-15 years

• Type 2 diabetes : PDR present in 25 % after 15 years

International Clinical Diabetic Retinopathy (DR) Disease Severity Scale

• No apparent DR

• Mild nonproliferative DR

• Moderate nonproliferative DR

• Severe nonproliferative DR

• Proliferative DR

Mild non proliferative retinopathy

Flame shaped hemorrhages

MicroaneursmsDot & Blot hemorrhages

Severe non proliferative retinopathy

Proliferative retinopathy

Clinically Significant Macular edema

www.retinalphysician.com/archive%5C2009%5CJan

Vitreous hemorrhage

Symptoms of diabetic retinopathy

NO SYMPTOMS

Even stages up to proliferative retinopathy can be asymptomatic

Visual loss : Macular edema Vitreous hemorrhage Retinal detachment

Screening & Diagnosis

• Dilated fundus evaluation : annually / 6 monthly • Ophthalmologist

Only 50 % of the eyes are correctly classified as to the presence of retinopathy through undilated eye examinations

Appropriate eye evaluation

Pupillary dilatationSlit lamp biomicroscopyIndirect ophthalmoscopy for retinal periphery Gonioscopy Flourescein Angiogram

Prognosis

• High risk PDR : 28 % risk of severe vision loss within 2 years

• Untreated CSME is associated with a 25 % moderate visual loss after 3 years

PDR : Proliferative diabetic retinopathy CSME : Clinically significant Macular edema ETDRS study, 1991

Effective LASER treatment

HIGH RISK PDR

• This risk is reduced to < 4 % by panretinal photocoagulation

• Reduced need for pars plana vitrectomy(PPV) by 50 %

CLINICALLY SIGNIFICANT MACULAR EDEMA

Loss of vision in CSME reduced by 50 % after focal laser photocoagulation

Metabolic management

• Glycemic control • Intensive BP control : 34 % improvement in

retinopathy outcomes after intensive BP control

• Lipid management • Anemia correction

Diabetic Nephropathy

Nephropathy

• Leading cause of chronic renal failure in the developed world 

• It is also one of the most significant long-term complications in terms of morbidity and mortality for individual patients with diabetes.  

• Diabetes is responsible for 30-40% of all end-stage renal disease (ESRD)

• Microalbuminuria is a cardiovascular risk factor

Signs & Symptoms

• None • None • None • New onset hypertension/ resistant

hypertension • Edema• Reducing insulin requirements

As diabetic nephropathy is asymptomatic, we need to screen for nephropathy in all our patients with diabetes mellitus

Laboratory investigations

• Urine microalbumin • Serum creatinine • Serum potassium • Urine routine

Urine microalbumin Measurement of the albumin-to-creatinine ratio

in a random spot collection

Preferable : early morning urine

Short-term hyperglycemia, exercise, urinary tract infections, marked hypertension, heart failure, and acute febrile illness can cause transient elevations in urinary albumin excretion

Repeat urine sample to confirm microalbuminuria

Progression of nephropathy

Normal Microalbuminuria 2% per annum

Clinical Nephropathy> 300 mg/gm

2% per annum

< 30 mg/gm 30-300 mg/gm

If microalbumin is positive

• Do urine routine

• Urine microalbumin > 300 mg/gm : do 24 hour urine protein• Creatinine, serum potassium

• Consider ultrasound abdomen

Treatment

• Intensive glycemic control 25% risk reduction (P = .0099) in microvascular end points in UKPDS

trial 33 % in RR reduction after microalbuminuria or clinical grade

nephropathy after 12 years

• Hypertension control Risk reduction in diabetic nephropathy progression with the use

of antihypertensive therapy : 29 % in UKPDS study

Treatment

• Blockage of renin-angiotensin-aldosterone( RAAS) ACE inhibitor •Ramipril : 2.5 to 10 mg/day•Perindopril : 4-8 mg/day •Enalapril : 2.5 –20mg/day•Lisinopril : 2.5-20 mg/day

Agents that block the RAAS provide additional benefit on reduction of microalbumin independent of blood pressure reduction

Prevention of nephropathy progression

• Dietary protein restriction • Blood pressure : < 130/80 mm Hg

< 120/75 mm Hg if proteinuria or renal insufficiency is present

• Blood sugars HbA1c < 7 %

• ACE inhibitor/ Angiotensin receptor blocker

• Statins for CV risk

Diabetic Neuropathy

WHO definition

A disease characterized by decline and damage of nerve function leading loss of sensation, ulceration and subsequent amputation.

Why is neuropathy important ?

• Neuropathy increases risk of amputation 1.7 fold

• Neuropathy + deformity: increases risk of amputation 12 fold

• Neuropathy + deformity + previous ulceration: increases risk by 36 fold

• Autonomic neuropathy: 25-50 % , 5 –10 year mortality

Classification

• Symmetric polyneuropathy• Polyradiculopathy• Mononeuropathy• Autonomic neuropathy

Symmetric polyneuropathy

• Most common form of diabetic neuropathy

• Affects distal lower extremities and hands (“stocking-glove” sensory loss)

• Symptoms/Signs– Pain– Paresthesia/dysesthesia– Loss of vibratory sensation

Symmetric neuropathy

Small fiber neuropathy • Involves A delta and C

fibres• Painful paraesthesias

that are burning, stabbing, crushing, aching, or cramp like, with increased severity at night

• Loss or pain & temperature sensation

• Preserved reflexes

Large fiber neuropathy• Large fiber sensory nerves

• Electric tingling or a snug bandlike sensation around ankles and feet

• Prominent ataxia

• Absent ankle jerk reflexes, prominent proprioceptive sensory impairment

• Gait instability with eyes closed

Signs of sensory neuropathy

• Dystrophic nails• Callus • Dry skin/ cracked skin ( autonomic

neuropathy)• Charcot’s feet

Signs of motor neuropathy

• Muscle wasting • Muscle weakness

Claw toe

                                                                                    

              

Diagnosis

• Clinical signs• Sensation: Vibration with tuning fork (128 Hz) Proprioception Touch/ pressure • Deep tendon reflexes : Ankle jerk Knee jerk

Simple tools

Monofilament: 5.07 Semmes-Weinstein (10-g) nylon filament test (10-g monofilament test)

Biothesiometer

• Basically an electronic tuning fork• To detect the vibration perception threshold

Picture courtesy: http://www.diabetes.usyd.edu.au/foot/Fexam1.html

>25 volts: suggestive of neuropathy

Road to ulcer

Bunions Clawed toes Abnormal toe nails

Fissure Story –Origin: Dysautonomia Autonomic neuropathy

Dry Feet

Fissuring

Infection

Abscess

Ulcer

The Callus Story- Origin: Motor Motor Neuropathy

Deformity

Abnormal pressures

Callus

Callus haematoma

Abscess

Ulcer

The Extent of Diabetic Neuropathy

Carpal Tunnel Syndrome

• Most common entrapment neuropathy in type 2 DM

• Tingling, numbness, parasthesias• Women > men • Surgical release by severing the carpal ligament

Diabetic Amyotrophy

• Acute or subacute pain, weakness, and atrophy of the pelvic girdle and thigh musculature.

• Weak hip flexion• Absent knee jerk • Initially unilateral• Weight loss

Cranial Nerve Palsy

• 3 rd nerve palsy is the common

• Diplopia, eye pain, ptosis

• Usually pupillary sparing

• Spontaneous recovery present

Treatment

• Foot care education • Foot care education • Foot care education

Effective patient education can reduce the incidence of foot ulceration and amputation by over 50 %

Boulton AJM. Lowering the risk of neuropathy, foot ulcers and amputationsDiabetic Medicine Volume 15 Issue S4, Pages S57 - S59

Basic foot care education

Washing and inspecting feet on a daily basis Selecting and using appropriate and properly

fitted footwear Using slippers indoors (i.e., no bare feet). Providing proper nail and callus care (e.g., no

bathroom surgery) Avoiding extreme temperatures Avoiding soaking feet for > 10 min Promptly reporting problems, such as infections,

ulcers, and cuts that do not heal.

Drugs for symptomatic relief

• Tricyclic antidepressants: amytryptline, imipramine

• Selective serotonin uptake inhibitors: Paroxetine, Escitalopram, Duloxetine

• Anticonvulsants : Carbamazepine, Gabapentin, Pregabalin

• Analgesics : Tramadol

Autonomic Neuropathy

• Cardiovascular • Gastrointestinal• Genitourinary • Erectile dysfunction

Key messages

• Diabetic microvascular complications are preventable

• SCREEN 1. Microalbumin to detect nephropathy 2. Neurological exam for neuropathy 3. Retina evaluation for retinopathy • TREAT 1. ACEI/ ARB for nephropathy 2. Foot care education for neuropathy 3. Good metabolic control for all

microvascular complications

Thank you

• Nishanth S, Endocrinologist • Aniyan Poulose, Registrar • Pradeep R, Podiatrist • Vani KB, Diabetes Educator

The Endocrinology & Diabetes PracticeTrivandrum www.endocrinologydiabetes.com