Complications of Diabetes: Screening and Prevention. Dr Martin McIntyre Consultant Physician Royal Alexandra Hospital Paisley

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1 Complications of Diabetes: Screening and Prevention Dr Martin McIntyre Consultant Physician Royal Alexandra Hospital Paisley

2 Diabetic Complications Microvascular: Retinopathy Nephropathy Neuropathy Macrovascular: Coronary heart disease (CHD) Cerebrovascular disease (CVD) Peripheral vascular disease (PVD)

3 Type 2 diabetes is NOT a mild disease Diabetic Retinopathy Leading cause of blindness in working age adults 1 Diabetic Nephropathy Leading cause of end-stage renal disease 2 Stroke 2 to 4 fold increase in cardiovascular mortality and stroke 3 Cardiovascular Disease 8/10 diabetic patients die from CV events 4 Diabetic Neuropathy Leading cause of non-traumatic lower extremity amputations 5

4 Macrovascular disease at diagnosis in Type 2 diabetes Cerebrovascular disease Abnormal ECG 1% 18% 75% of all deaths in people with Type 2 diabetes are due to cardiovascular disease Hypertension 35% Absent foot pulses 13% Intermittent claudication 3% UKPDS Group. Diabetes Res 1990; 13: 1 11.

5 Type 2 diabetes the microvascular burden is already present at diagnosis Retinopathy 1 21% Nephropathy 2 18% Erectile dysfunction 1 20% Neuropathy 1 12% 1. UKPDS Group. Diabetes Res 1990; 13: The Hypertension in Diabetes Study Group. J Hypertens 1993; 11:

6 Retinopathy Specific for diabetes Type 1 and type 2 diabetes Related to duration of diabetes and control Individual risk factors (?genetic) Commonest cause of preventable blindness <65 year old Other Diabetic Eye Diseases Cataracts Glaucoma

7 Normal Retina

8 Preproliferative Retinopathy

9 Proliferative Retinopathy

10 Vitreous Haemorrhage

11 Cataract

12 Retinopathy - Prevention Good diabetes control Type 1 diabetes (DCCT, 1993) Type 2 diabetes (UKPDS, 1998) ACE inhibitors Type 1 diabetes (Lewis et al, 1993) Type 2 diabetes (HOPE, 2000) Early referral to ophthalmologist

13 DCCT - New Retinopathy Percentage of Patients Conventional P<0.001 Intensive Year of Study NEJM 1993;329:977-86

14 DCCT - Progressive Retinopathy Percentage of Patients Conventional P<0.001 Intensive Year of Study NEJM 1993;329:977-86

15 Nephropathy Specific for diabetes Type 1 and type 2 diabetes Related to duration of diabetes and control Associated with retinopathy Commonest cause of ESRD Progressive Microalbuminuria (30-300mg/24hr, albustix -ve) Albuminuria (>300mg/24hr, albustix +ve) Renal impairment (egfr <60mL/min) Dialysis (Transplantation)

16

17 Nephropathy - Prevention Good diabetes control Type 1 diabetes (DCCT, 1993) Type 2 diabetes (UKPDS, 1998) Good blood pressure control (esp. ACEi) Type 1 diabetes (Lewis et al, 1993) Type 2 diabetes (HOPE, 2000) Early referral to nephrologist

18 DCCT - New Microalbuminuria Percentage of Patients Conventional P<0.04 Intensive Year of Study NEJM 1993;329:977-86

19 Neuropathy Clinical Syndromes Chronic sensory neuropathy Acute painful neuropathy Proximal motor neuropathy (amyotrophy) Diffuse motor neuropathy Focal neuropathy Autonomic neuropathy

20 Neuropathy - Prevention Good diabetes control (DCCT, UKPDS) Neuropathy - Treatment Improve diabetes control Anti-depressants (amitriptyline, duloxetine) Anti-epileptics (gabapentin, pregabalin) Axain cream Acupuncture

21 DCCT - Neuropathy Percentage of Patients Intensive Conventional P<0.001 P=0.04 P< Neurological Examination Autonomic- Nerve Study Nerve-Conduction Study NEJM 1993;329:977-86

22 Macrovascular Disease Coronary Heart Disease (CHD) Angina Myocardial infarction PTCA CABG Cerebrovascular Disease (CVD) Stroke TIA Peripheral Vascular Disease (PVD) Intermittent claudication Ulceration Gangrene Amputation

23 Annual Incidence of CVD (per 1000) Cardiovascular Disease DM DM DM DM DM DM Males Females The Framingham Study Kannel and McGee. Circulation 1979

24 Coronary Heart Disease Fatal or non-fatal MI (%) MI +MI Non-DM -MI +MI DM Haffner SM et al. NEJM (1998) 339:

25 Glycaemic Control

26 UKPDS 3867 patients with type 2 DM randomised Conventional control Target: FPG<15mmol/l n=1138 Achieved: HbA1c 7.9% v Intensive control Target: FPG <6mmol/l Achieved: HbA1c 7.0% Sulphonylurea: n=1234 Insulin: n=1156 Lancet (1998) 352:

27 UKPDS Total deaths: 702 (18%) Cardiovascular deaths: 402 (57%) Cancer deaths: 170 (24%) Diabetes deaths: 12 (2%) Accidental deaths: 7 (1%) Other deaths: 111 (16%) Lancet (1998) 352:

28 UKPDS - Glycaemic Control Aggregate Endpoint Log-rank p Any diabetes-related endpoint Diabetes-related deaths 0.34 All-cause mortality 0.44 Myocardial infarction Stroke 0.52 Amputation or death from PVD 0.15 Microvascular Favours Favours Intensive Conventional Single Endpoints Fatal myocardial infarction 0.63 Non-fatal myocardial infarction 0.79 Lancet (1998) 352:

29 Cardiovascular Death HR 0.62 (95% CI 0.49, 0.77) p< Zinman B., Wanner C., Lachin J.M., et al. N Engl J Med 2015; 373:

30 Major Adverse Cardiovascular Events (MACE) LEADER Trial Investigators N Engl J Med 2016; 375:

31 Blood Pressure Control

32 UKPDS (HDS) 1148 hypertensive patients with type 2 DM Tight control (<150/85) v Less tight control (<180/105) BMJ (1998) 317:

33 UKPDS (HDS) Achieved blood pressure: Tight control 144/82 Less tight control 154/87 Clinical end point Any diabetes related end point Deaths related to diabetes All cause mortality Myocardial infarction Stroke Peripheral vascular disease Microvascular disease P value Favours tight control 1 10 Favours less tight control BMJ (1998) 317:

34 Hypertension Optimal Treatment (HOT) Trial 18,790 Patients 50 y.o. (8% DM = 1,501) Felodipine at baseline Adding ACEi, β-blocker, Diuretic Blood Pressure Target DBP Achieved Aspirin 75mg v placebo <90mmHg 144/85 <85mmHg 141/83 <80mmHg 139/81 Hansson et al. Lancet (1998) 351:

35 Hypertension Optimal Treatment (HOT) Trial Subgroup with Diabetes Mellitus Events/1000pt-yrs 30 51% (p=0.005) 37% (p=0.045) 67% (p=0.016) 43% (p=0.068) <90 <85<80 <90 <85<80 <90 <85<80 <90<85<80 Major CV inc Silent CV Total Events... MI Mortality Mortality Hansson et al. Lancet (1998) 351:

36 Antiplatelet Therapy

37 Aspirin in type 2 DM 2 o Prevention: Antiplatelet Trialists Collaboration Meta-analysis of 145 randomised trials in DM and non-dm Vascular Events (% of patients) % RRR p< ConαP non-dm 17% RRR p<0.002 ConαP DM BMJ (1994) 308: 71-72,

38 Hypertension Optimal Treatment (HOT) Trial Events/1000pt-yrs % (p=0.03) 36% (p=0.002) 2% (p=0.88) 7% (p=0.36) 0 P ASA P ASA P ASA P ASA Major CV Events All MI All CVA Total Mortality NB relative benefit of ASA on major CV events was about the same in patients with DM Hansson et al. Lancet (1998) 351:

39 U.S. Physicians Health Study 22,071 U.S. physicians without CV disease Aspirin 325mg v placebo 60% RRR 5yr risk of MI (%) DM DM +Asp 40% RRR o DM o DM +Asp NEJM (1989) 321:

40 Antiplatelet Therapy SIGN 116, March 2010, Updated September 2013

41 Lipid Control

42 Lipid Control in Type 2 DM 2 o Prevention 0 Diabetes RRR (%) CARE LIPID All Three VA-HIT 4S

43 Lipid control in type 2 DM Name of trial Patients No. Intervention MRC/BHF HPS CHD risk (29% DM) 20,536 Simvastatin ALLHAT HBP (35% DM) 10,362 Pravastatin ASCOT HBP (sig. DM) 9,000 Atorvastatin CARDS DM+RF ( o vasc. dis.) 2,000 Atorvastatin ASPEN DM ± vasc. dis. 2,250 Atorvastatin FIELD DM ± vasc. dis. 9,000 Fenofibrate LDS DM o vasc. dis. 5,000 Cerivastatin/ Fenofibrate

44 Lipid control in type 2 DM European Task Force (July 1998): Chol>5.0mmol/l; 10yr CHD risk >20% Joint British Societies (Dec 1998): Chol>5.0mmol/l; 10yr CHD risk >30% BHS (Sept 1999): Chol>5.0mmol/l; 10yr CHD risk >30% SIGN (Jan 2000): Chol>5.0mmol/l; 10yr CHD risk >30% SIGN (Nov 2001): Chol>5.0mmol/l; 10yr CHD risk >30% N.B. 10yr CHD risk >15% when affordable

45 Cardiovascular Risk Assessment Dundee Risk Disk Joint European Task Force Charts Joint British Societies Charts and Disk New Zealand Charts Sheffield Tables Bayer plc HeartScore Computer Programme Yudkin and Chaturvedi Charts

46 Lipid control in type 2 DM European Task Force (July 1998): Chol>5.0mmol/l; 10yr CHD risk >20% Joint British Societies (Dec 1998): Chol>5.0mmol/l; 10yr CHD risk >30% BHS (Sept 1999): Chol>5.0mmol/l; 10yr CHD risk >30% SIGN (Jan 2000): Chol>5.0mmol/l; 10yr CHD risk >30% SIGN (Nov 2001): Chol>5.0mmol/l; 10yr CHD risk >30% N.B. 10yr CHD risk >15% when affordable SIGN (March 2010): Age >40; Simva 40mg or Atorva 10mg

47 The Diabetic Foot Feet are at risk from microvascular (neuropathy) and/or macrovascular disease (PVD) Annual foot examination Skin condition (infection, ulceration) Deformity (claw toes, Charcot joint) Peripheral pulses (dorsalis pedis, posterior tibial) Fine touch (10g monofilament) Vibration (tuning fork, neurosethesiometer) Ankle reflexes

48 The Diabetic Foot

49 The Diabetic Foot

50 Foot ulcers Prevention always better than cure therefore CPR for feet. Check Protect Refer

51 Screening in Practice The following should be done annually: 1. Retinopathy screening - Diabetologist - Optometrist - Ophthalmologist - G.P. - Retinal camera 2. Foot examination - Diabetologist - Chiropodist - Practice Nurse 3. HbA1c - Aiming for <58mmol/mol

52 Screening in Practice 4. Microalbuminuria screening EMU for albumin/creatinine ratio (ACR) Repeat to confirm +/- ACEi or ARB 5. Blood pressure Aiming for <140/80 (<130/80) 6. Lipids Age >40yrs Simvastatin 40mg or Atorvastatin 10mg

53 If you have been Thank you for listening

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