1. Diabetes & Retinopathy Screening Dr John Doig Consultant Diabetologist DRS Clinical Lead Forth Valley

2. Diabetes & Retinopathy Screening What is diabetes Diagnosis Types of Diabetes Treatment Complications –Acute metabolic –Macrovascular –Microvascular Managing Risk Factors

3. 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).

4. 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 2007 = 4.4 % –Some practices = 5.0 %

5. 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

6. Diagnosis Symptoms –Osmotic Symptoms & Fatigue –Weight loss / gain –Infection –Neuropathic Symptoms –Visual Upset –Cardiovascular symptoms

7. 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

8. 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

9. 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

10. Other types of Diabetes Gestational Drug induced Steroids, Atypical Neuroleptics Metabolic Haemachromatosis, Cushings, Acromegaly Pancreatic disease MODY (Genetic) Stress hyperglycaemia

11. Treatment Diet Oral Hypoglycaemic Agents –Sulphonylureas (Gliclazide, Glimepiride) –Biguanides (Metformin) –Alpha 1 glucosidase inhibitors (Acarbose) –Thiazolidinediones(Rosiglitazone, Pioglitazone) –GLP-1 agonists (Exenatide, Liragutide) –DPP4 Inhibitors (Sitagliptin, Vildagliptin) Insulin –Soluble, Biphasic, Intermediate / Long acting

12. Acute Metabolic Complications Diabetic Ketoacidosis Hyper Osmolor Nonketotic Coma Lactic Acidosis Hypoglycaemia

13. Common side effect of Insulin or Sulphonylureas Does not occur with other oral treatments 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

15. Causes of hypoglycaemia Management Errors Inadequate Carbohydrate Altered KineticsLipohypertrophy, Site massage, Heat, Cold, Antibodies, Renal, Exercise, Human insulin Increased SensitivityAddison’s disease, Hypothyroidism, Hypopituitarism, Changes in gonadal steroids, Pregnancy Factitious

16. 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

17. Morbidity of hypoglycaemia CNSComa and Convulsions Transient motor deficits Permanent brain damage Cerebral Oedema CVSArrhythmia Myocardial ischaemia Stroke Fractures, Vitreous haemorrhage

18. Treatment of hypoglycaemia Treated immediately by oral glucose 10-20 g If unable to swallow / unconscious then Ensure patient safe (ABCD, Recovery position, Get help) –Intravenous glucose 50ml 20% –Intravenous glucose 25ml 50 % –Subcutaneous glucagon 1 mg Patients should 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.

19. Macrovascular Complications Coronary Artery Disease Peryipheral Vascular Disease Cerebro Vascular Disease –Hyperlipidaemia –Glycaemic control –Hypertension –Obesity / Smocking / FH Angina, MI, Heart Failure Claudication, Risk of limb ischaemia, infection, amputation TIA’s, Stroke disease

20. Cumulative Hazard for Any CVD Endpoint CARDS Relative Risk = -36% (95% CI -45, -15) p=0.001 Years 306 287 663 621 1040 992 1337 1275 1372 1334 Atorva Placebo 1428 1410 Placebo 189 events Atorvastatin 134 events Cumulative Hazard (%) 0 5 10 15 20 012344.75 NNT = 30

21. 12% decrease per 10 mm Hg decrement in BP p<0.0001 0.5 1 5 110120130140150160170 All Cause Mortality Updated mean systolic blood pressure Hazard ratio UKPDS 36. BMJ 2000; 321: 412-19

22. All Cause Mortality 14% decrease per 1% decrement in HbA1c p<0.0001 0.5 1 5 0567891011 Updated mean HbA 1c Hazard ratio UKPDS 35. BMJ 2000; 321: 405-12

23. 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

24. Microvascular Complications Diabetic Retinopathy Diabetic Nephropathy Diabetic Neuropathy Microalbuminuria Macroalbuminuria Renal impairment End Stage Renal Disease Sensory Ulceration,Neuroarthropathy Motor Foot deformity Autonomic GI upset, Hypotension, ED

25. Prevalence of Retinopathy In young persons with duration less than 5 yrsrare In patients > 30 yrs with duration 5 yrs20 % Duration 10 yrs40-50 % Duration 20 yrs90 % Approx 30% of diabetic population have DR Prevalence of visual impairment in UK ? 2-5 %?

26. 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

27. Risk Factors for Diabetic Retinopathy Duration of diabetes (age of onset) Poor glycaemic control Raised blood pressure Microalbuminuria and proteinuria (nephropathy) Raised triglycerides and lowered haematocrit Pregnancy Genetic / ethnicity Smoking

28. Modifiable Risk Factors for Prevention of Diabetic Retinopathy Glycaemic Control Blood Pressure Control Smoking?

29. Evidence For Good Control 1993 DCCT Type 1HbA1c 8.9 vs. 7.2 % –Reduced risk of developing: Retinopathy 76 % Microalbuminuria 39 % Clinical neuropathy 60 % 1998 UKPDS Type 2HbA1c 7.9 vs. 7.0 % –Reduced risk of: Retinopathy 21% Microalbuminuria 33% Myocardial Infarction 16 %

30. Complication DCCT EDIC 1982-19931994-2006 HbA1c7.2 v 9.1%7.9 v 8.1% Retinopathy 3-step change 63 72 Proliferative 47 76 Macular oedema 26* 77 Laser therapy 51 77 Nephropathy Microalbuminuria (> 28mg/min) 39 53 Clinical albuminuria (> 208mg/min) 54 82 Reduction in Risk for Microvascular Complications

31. Microvascular Endpoints 0.5 1 10 15 0567891011 37% decrease per 1% decrement in HbA1c p<0.0001 Updated mean HbA 1c Hazard ratio UKPDS 35. BMJ 2000; 321: 405-12

32. 1148 Type 2 diabetic patients tight blood pressure 144 / 82 mmHg v standard 154/87 gave reduced risk for any diabetes-related endpoint24% p=0.0046 diabetes-related deaths32%p=0.019 stroke44%p=0.013 heart failure56%p=0.0043 microvascular disease37%p=0.0092 retinopathy progression34%p=0.0038 deterioration of vision47%p=0.0036 UKPDS Blood Pressure Control Study

33. 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