diabetes & its relevance to retinopathy screening dr john doig consultant diabetologist drs...
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Diabetes & Its Relevance to Retinopathy Screening
Dr John DoigConsultant Diabetologist
DRS Clinical Lead Forth Valley
Diabetes & Its Relevance to Retinopathy Screening• What is diabetes• Diagnosis• Types of Diabetes• Treatment• Complications
– Acute metabolic– Macrovascular– Microvascular
• Managing Risk Factors
What is Diabetes Mellitus• Diabetes = excessive production of urine • mellitus = honeyed
• Life-long illness associated with various complications – Blindness– Heart disease– Kidney disease– Damage to the feeling in the limbs (peripheral
neuropathy).
Diabetes Mellitus• characterised by high blood sugar levels,
disturbances of carbohydrate, fat and protein metabolism
• absolute lack or a relative deficiency in insulin action and/or insulin secretion
• Prevalence increasing– Scottish Survey 2001 = 2.1 %– Forth Valley 2006 = 4.1 %– Some practices = 5.0 %
Management of Diabetic Patient
• Main Issues– Diagnosis– Glycaemic Control– Screening
•Microvascular Complications•Macrovascular Complications
– Diabetes related issues / Education•Driving, Work, Pregnancy•Injection sites, Diet, Monitoring
Diagnosis
• Symptoms– Osmotic Symptoms & Fatigue– Weight loss / gain– Infection– Neuropathic Symptoms– Visual Upset– Cardiovascular symptoms
Diagnosis: Diagnostic Criteria
Fasting Plasma Glucose >7.0 (on 2 occasions*)
Random Plasma Glucose >11.1 (on 2 occasions*)(1 occasion if symptomatic)
Fasting Plasma Glucose 6.1 - 6.9 = IFG2 hr post 75g glucose 7.8 - 11.1 = IGT 2 hr post 75g glucose > 11.1 = DM
Type of Diabetes
• Type I– Young < 35– Thin + weight loss– Rapid onset– Ketonuria
– Autoimmune– B Cell failure– Insulin Dependent
• Type 2– Older > 35– Overweight– Onset months– Strong FH– Complications
– Insulin resistance– Late B Cell failure– Hyperinsulinaemia– Metabolic syndrome– Cardiovascular Disease
Other types of Diabetes
• Gestational• Drug induced
– Steroids, Atypical Neuroleptics• Metabolic
– Haemachromatosis, Cushings, Acromegaly• Pancreatic disease• MODY (Genetic)• Stress hyperglycaemia
Treatment• Diet
• Oral Hypoglycaemic Agents– Sulphonylureas– Biguanides– Alpha 1 glucosidase inhibitors– Thiazolidinediones(Glitazones or Insulin sensitisers)– Exenatide GLP-1 agonists – DPP4 Inhibitors Gliptins
• Insulin– Soluble, Biphasic, Intermediate / Long acting
Acute Metabolic Complications• Diabetic Ketoacidosis• Hyper Osmolor Nonketotic Coma
• Lactic Acidosis
• Hypoglycaemia
Hypoglycaemia
• Common side effect of Insulin or Sulphonylureas
• Does not occur with Metformin, Acarbose or TZD’s
• Minor hypos often go unreported (Self treated)• Severe hypos occurs in 25-30 % of patients
each year• Coma occurs in ~ 10 % of patients each year
~ 4.6 mmol/l Inhibition of insulinsecretion
~3.8 mmol/l Counter-regulatoryhormonal secretionbefore symptoms
Adrenaline, Growth hormone,Glucagon, Cortasol
~3.0 mmol/l Autonomic symptoms Sweating, Hunger, Palpitation,Shaking
2.8 mmol/l Neuroglycopenicsymptoms
Confusion, Drowsiness, Speechdifficulties, Incoordination,Atypical behaviour, Malaise,Nausea, Headache
< 1.0 mmol/l Coma / Convulsions
Death
Causes of hypoglycaemia
Management Errors
Inadequate Carbohydrate
Altered Kinetics Lipohypertrophy, Site massage, Heat, Cold, Antibodies, Renal, Exercise, Human insulin
Increased Sensitivity Addison’s disease, Hypothyroidism, Hypopituitarism, Changes in gonadal steroids, Pregnancy
Factitious
Risk factors for severe hypoglycaemia
• Insulin treatment regimenIntensified High insulin doses
• Impaired awareness of hypoglycaemiaAcute (Preceding hypoglycaemic
episodes) Chronic (Central autonomic failure)
• Long duration of diabetes• Increasing age of patient• Sleep, Excessive alcohol consumption
Morbidity of hypoglycaemia
• CNS Coma and ConvulsionsTransient motor deficitsPermanent brain damageCerebral Oedema
• CVS ArrhythmiaMyocardial ischaemiaStroke
• Fractures, Vitreous haemorrhage
Treatment of hypoglycaemia
• Treated immediately by oral glucose 10-20 g• If unable to swallow then
– Intravenous glucose 50ml 20%– Intravenous glucose 25ml 50 %– Subcutaneous glucagon 1 mg
• Patients usually recover within minutes• Failure to do so may be due to cerebral oedema
• On recovery encourage consumption of complex carbohydrate
• Identify cause & take appropriate action / patient to contact diabetes care team.
Macrovascular Complications
• Coronary Artery Disease• Peryipheral Vascular Disease• Cerebro Vascular Disease
– Hyperlipidaemia– Hypertension– Obesity
Cumulative Hazard for Any CVD Endpoint CARDS
Relative Risk = -32% (95% CI -45, -15)
p=0.001
Years
306287
663621
1040992
13371275
13721334
AtorvaPlacebo
14281410
Placebo189 events
Atorvastatin134 events
Cu
mu
lati
ve H
azar
d (
%)
0
5
10
15
20
0 1 2 3 4 4.75
12% decrease per 10 mm Hg decrement in BP
p<0.0001
0.5
1
5
110 120 130 140 150 160 170
All Cause Mortality
Updated mean systolic blood pressure
Haz
ard
ratio
UKPDS 36. BMJ 2000; 321: 412-19
HOT: Events in relation to target blood pressure. Diabetic patients
0
5
10
15
20
25
Eve
nts
/ 1
000
pat
ien
t ye
ars
MajorVascularEvents
All MIs All CVAs
<90 mmHg
<85 mmHg
<80 mmHg
p=0.11rr=2.01
p=0.005rr=2.06
p=0.34rr=1.43
All Cause Mortality
14% decrease per 1% decrement in HbA1c
p<0.0001
0.5
1
5
0 5 6 7 8 9 10 11Updated mean HbA1c
Haz
ard
ratio
UKPDS 35. BMJ 2000; 321: 405-12
Cardiovascular Disease Prevention• Improved cardiovascular risk with:
– Improved glycaemic control (Metformin)– Improved BP control (Target < 140/80)– Addition of long acting ACEI if high risk– Lipid reduction– All secondary preventative measures
•Aspirin, B Blocker
Microvascular Complications• Diabetic Retinopathy• Diabetic Nephropathy
– Microalbuminuria– Macroalbuminuria– Renal impairment
• Diabetic Neuropathy– Sensory - Ulceration, Neuroarthropathy– Motor – Foot deformity– Autonomic – GI upset, Hypotension, ED
Diabetic Eye Disease
• Diabetic eye complications major cause of visual loss.• Most important preventable cause of blindness in Europe.• Accounts for about 90 % of blindness in diabetic patients.
• St. Vincent Declaration 5 year targets 1989– Incidence of blindness due to diabetes should be
reduced by one third or more.
• Duration of diabetes is the most important predictor.
Prevalence of Retinopathy
• In young persons with duration less than 5 yrsrare
• In patients > 30 yrs with duration 5 yrs 20 %• Duration 10 yrs 40-50 %• Duration 20 yrs 90 %
• Approx 30% of diabetic population have DR
• Prevalence of visual impairment in UK ? 2-5 %?
Diabetic Retinopathy
• Approx 10-15 % of patients progress to sight threatening retinopathy– Pre proliferative retinopathy– Proliferative retinopathy– Vitreous haemorrhage– Maculopathy
• Other sight threatening disease more common in diabetes– Cataract– Macular Degeneration– Glaucoma
Risk Factors for Diabetic Retinopathy• duration of diabetes• poor glycaemic control
• raised blood pressure
• increasing number of microaneurysms• microalbuminuria and proteinuria (nephropathy)
• raised triglycerides and lowered haematocrit• pregnancy
Modifiable Risk Factors for Prevention of DR• Glycaemic Control
– 1.7 % reduction in HbA1c (8.9% vs 7.2%)– 76 % risk reduction for developing DR– 43 % risk reduction for retinopathy
progression• Blood Pressure Control
• Smoking
Evidence For Good Control• 1993 DCCT HbA1c 8.9 vs. 7.2 %
– Reduced risk of developing:• Retinopathy 76 %• Microalbuminuria 39 %• Clinical neuropathy 60 %
• 1998 UKPDS HbA1c 7.9 vs. 7.0 %– Reduced risk of:
• Retinopathy 21%• Microalbuminuria 33%• Myocardial Infarction 16 %
in 1148 Type 2 diabetic patients a tight blood pressure control policy which achieved blood pressure of 144 / 82 mmHg (vs 154/87) gave reduced risk for
any diabetes-related endpoint 24% p=0.0046diabetes-related deaths 32% p=0.019stroke 44% p=0.013heart failure56% p=0.0043
microvascular disease 37% p=0.0092
retinopathy progression 34% p=0.0038deterioration of vision 47% p=0.0036
UKPDS Blood Pressure Control Study
Microvascular Endpoints
0.5
1
10
15
0 5 6 7 8 9 10 11
37% decrease per 1% decrement in HbA1c
p<0.0001
Updated mean HbA1c
Haz
ard
ratio
UKPDS 35. BMJ 2000; 321: 405-12
Sight Threatening Retinopathy
• No visual symptoms when most amenable to treatment
• If visual symptoms present then prognosis poorer
• Potocoagulation will abolish new vessels in 80 % and prevent blindness in >50% after 10 years
• Photocoagulation will salvage vision in 50-60 %
• Vitrectomy may be effective in restoring meaningful vision > 6/36
Detection of Diabetic Retinopathy
• Retinopathy is detected in its earliest and most treatable form only by clinical examination of eyes.
• Ideally suited to screening programs• Screening must be comprehensive, of
high sensitivity (>80%) and specificity (>95%). Should include measurement of visual acuity. Clear line of referral.
• Various options:
Performance of screening
Sensitivity Specificity• General Practitioners 41 89• Hospital Physician 67 96 • Non Mydriatic Camera 67 98• Diabetologist 70 97• Ophthalmology registrar 75 97
• 2 Field retinal photographs 89 86• Combined 5 field + direct 97 95
Patients with retinopathy
• Aim for – Good glycaemic control HbA1c <
7.0%– Good BP control <130/70– Lipid control / Statin Cholesterol <4.0– Stop smoking– Correct anaemia