Diabetes & Its Relevance to Retinopathy Screening Dr John Doig Consultant 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

Osmotic Symptoms & Fatigue Weight loss / gain Infection 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 = IFG 2 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 33

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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 regimen Intensified High insulin doses Impaired awareness of hypoglycaemia Acute (Preceding hypoglycaemic episodes) Chronic (Central autonomic failure) Long duration of diabetes Increasing age of patient Sleep, Excessive alcohol consumption 36

Morbidity of hypoglycaemia CNS Coma and Convulsions Transient motor deficits Permanent brain damage Cerebral Oedema CVS Arrhythmia Myocardial ischaemia Stroke Fractures, Vitreous haemorrhage 37

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. 38

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 5 10 15 20 1 2 3 4 4.75 Placebo 189 events Atorvastatin 134 events Cumulative Hazard (%) Years Placebo 1410 1334 1275 992 621 287 Atorva 1428 1372 1337 1040 663 306

Updated mean systolic blood pressure All Cause Mortality 12% decrease per 10 mm Hg decrement in BP p<0.0001 . 5 1 2 3 4 6 7 Updated mean systolic blood pressure Hazard ratio UKPDS 36. BMJ 2000; 321: 412-19

HOT: Events in relation to target blood pressure. Diabetic patients

All Cause Mortality p<0.0001 Hazard ratio 14% decrease per 1% decrement in HbA1c p<0.0001 . 5 1 6 7 8 9 Updated mean HbA1c Hazard 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 yrs rare 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 %

UKPDS Blood Pressure Control Study 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=0.0046 diabetes-related deaths 32% p=0.019 stroke 44% p=0.013 heart failure 56% p=0.0043 microvascular disease 37% p=0.0092 retinopathy progression 34% p=0.0038 deterioration of vision 47% p=0.0036

Microvascular Endpoints . 5 1 6 7 8 9 37% decrease per 1% decrement in HbA1c p<0.0001 Updated mean HbA1c Hazard 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