4. 50% of newly presenting patients with type 2 diabetes already have one or more complications at diagnosis . Retinopathy: 21% Hypertension: 35% Stroke or TIA: 1% Absent foot pulses: 13% Intermittent claudication: 3% Ischaemic skin changes to feet: 6% Erectile dysfunction: 20% Plasma creatinine >120 mol/l: 3% Myocardial Infarction: 1% Abnormal ECG: 18% UKPDS Group. Diabetes Research 1990;13:1–11. Complications at diagnosis in the UKPDS
5. Goodkin G. Journal of Occupational Medicine 1975;17(11): 716–721. Donnelly R, et al. British Medical Journal 2000; 320: 1062–1066. Life expectancy and diabetes 40 45 50 55 60 65 70 75 80 85 15-19 20-29 30-39 40-49 50-59 60-70 Life expectancy (yrs) Diabetics Non Diabetics Age at diagnosis (yrs)
6. Diabetes in the UK Indo - Asian community Asian European Men Women Age groups 20–39 40–59 60–79 20–39 40–59 60–79 30% 25% 20% 15% 10% 5% 0%
7. U.K. economic costs Diabetes UK. May 2000. Year 2000 projected NHS diabetes expenditure ( 9% ) : £4,878,000,000 Equivalent to: per week £93,807,692 per day £13,401,098 per hour £ 558,379 per minute £ 9,306 per second £ 155 50% of Costs are due to premature complications
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9. GMS Contract NICE National Service Framework Guidelines Increasing prevalence Evidence base User expectations
11. “ Excellence requires that important, simple things are done right all the time . ” National Service Framework for Coronary Heart Disease
12. Patel V, Morrissey J The Alphabet Strategy British Journal of Diabetes & Vascular Disease, 2002: 2: 1: 58-59
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18. Prevention of progression of IGT to diabetes Finnish Diabetes Prevention Study Intensive lifestyle intervention reduced progression to diabetes by 58%. Diabetes Prevention Program Intensive lifestyle management reduced diabetes by 58%. Standard lifestyle advice plus metformin reduced diabetes by 31% Incidence of diabetes was 11, 7.8 and 4.8 cases per 100 person years with placebo, metformin and intensive lifestyle intervention respectively.
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20. UKPDS design Adapted from UK Prospective Diabetes Study (UKPDS) Group Lancet 1998;352:837-853; Turner R et al Ann Intern Med 1996;124(1 pt 2):136-145. Aim To determine whether intensified blood glucose control , with either sulphonylurea or insulin , reduces the risk of macrovascular or microvascular complications in type 2 diabetes. To determine the effect of aggressive blood pressure control . Study Population 3867 newly diagnosed type 2 diabetic patients who were asymptomatic after 3 months of diet ; fasting glucose 6.1–15 mmol/l (110–270 mg/dl) ; treat for 10 years .
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22. UKPDS : diabetes-related deaths 0% 5% 10% 15% 20% 0 3 6 9 % of patients with events Years from randomisation Tight blood pressure control (758) Less tight blood pressure control (390) Risk reduction 32% ( p=0.019 )
23. UKPDS : microvascular endpoints Risk reduction 37% ( p=0.0092 ) 0% 5% 10% 15% 20% 25% 0 3 6 9 % patients with event Years from randomisation Tight Blood Pressure Control (758) Less Tight Blood Pressure Control (390)
24. UKPDS blood pressure control study In 1148 type 2 diabetic patients a tight blood pressure control policy which achieved blood pressure of 144 / 82 mm Hg gave reduced risk for : Any diabetes-related endpoint 24% p=0.0046 Diabetes-related deaths 32% p=0.019 Stroke 44% p=0.013 Microvascular disease 37% p=0.0092 Heart failure 56% p=0.0043 Retinopathy progression 34% p=0.0038 Deterioration of vision 47% p=0.0036
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28. SIMVASTATIN: CAUSE-SPECIFIC MORTALITY Risk ratio and 95% CI STATIN PLACEBO Cause of death (10269) (10267) STATIN better STATIN worse CHD 577 701 Other vascular 214 242 ALL VASCULAR 791 943 (7.7%) (9.2%) 17% SE 4.4 reduction (2P<0.0002) Neoplastic 352 337 Respiratory 93 111 Other medical 76 91 Non-medical 16 21 ALL NON-VASCULAR 537 560 (5.2%) (5.5%) 5% SE 5.9 reduction ALL CAUSES 1328 1503 (12.9%) (14.6%) 12% SE 3.5 reduction (2P<0.001) 0.4 0.6 0.8 1.0 1.2 1.4
29. SIMVASTATIN: MAJOR VASCULAR EVENTS Risk ratio and 95% CI STATIN PLACEBO Vascular event (10269) (10267) STATIN better STATIN worse Total CHD 914 1234 Total stroke 456 613 Revascularisation 926 1185 ANY OF ABOVE 2042 2606 (19.9%) (25.4%) 24% SE 2.6 reduction (2P<0.00001) 0.4 0.6 0.8 1.0 1.2 1.4
30. SIMVASTATIN: VASCULAR EVENT by PRIOR DISEASE STATIN worse Risk ratio and 95% CI STATIN PLACEBO Baseline feature (10269) (10267) STATIN better STATIN worse Previous MI 1007 1255 Other CHD (not MI) 452 597 No prior CHD CVD 182 215 PVD 332 427 Diabetes 279 369 ALL PATIENTS 2042 2606 (19.9%) (25.4%) 24% SE 2.6 reduction (2P<0.00001) 0.4 0.6 0.8 1.0 1.2 1.4
33. CARDS Collaborative Atorvastatin Diabetes Study Helen Colhoun, John Betteridge, Paul Durrington, Graham Hitman, Andrew Neil, Shona Livingstone, Margaret Thomason, Michael Mackness, Valentine Menys, John Fuller on behalf of the CARDS Investigators Presented at ADA 2004
34. Primary prevention diabetes patients with one other risk factor (hypertension, smoker, micro-albuminuria, retinopathy) CARDS Design Placebo Atorvastatin 10mg Placebo 2838 patients
35. Treatment effect on the primary endpoint 21 (1.5%) 24 (1.7%) 51 (3.6%) 83 (5.8%) Atorva* 48% (11- 69) 39 (2.8%) Stroke 31% (16- 59) 34 (2.4%) Coronary revascularisation 36% (9- 55) 77 (5.5%) Acute coronary events 37% (17- 52) p=0.001 127 (9.0%) Primary endpoint ** Hazard Ratio Risk Reduction (CI) Placebo* Event * N (% randomised) .2 .4 .6 .8 1 1.2 Favours Atorvastatin Favours Placebo ** Fatal MI, other acute CHD death , n on fatal MI , u nstable angina , CABG , f atal stroke , n on fatal stroke
37. CHD prevention trials with statins in diabetes : CHD Endpoints: † HPS = first major vascular event; †† CARE = absolute risk of coronary events; ** CARDS: Acute Coronary Events ‡ 4S = major CHD events; ‡‡ 4S reanalysis = major coronary events. Cohorts: *HPS = risk reduction for the entire cohort (nondiabetics and patients with diabetes). Footnote: NS = results not statistically significant. 1. HPS Collaborative Group. Lancet. 2002;360:7-22. 2. Goldberg RB, Mellies MJ, Sacks FM, et al. Circulation. 1998;98:2513-2519. 3. Py ö r ä l ä K, Pedersen TR, Kjekshus J, et al. Diabetes Care. 1997;20:614-620. 4. Haffner SM, Alexander CM, Cook TJ, et al. Arch Intern Med. 1999;159:2661-2667. CARDS Study ADA 2004. GREACE Study Secondary Prevention Primary Prevention 12% NS 24%* 3051 Simvastatin HPS 1 42% 32% 483 Simvastatin 4S reanalysis 4 ‡‡ 55% 59% 32% 202 313 Simvastatin Atorvastatin 24mg 4S 3 ‡ GREACE 25% 23% 586 Pravastatin CARE 2 †† 37%** 26 -33 % 25%* 2838 2912 Atorvastatin 10mg Simvastatin 40mg CARDS HPS 1 † CHD risk red n Diabetes CHD risk red n Nondiabetics Number of patients Drug Study
38. Cholesterol Treat all d iabetes patients with statins! (evidence if total cholesterol greater than 3.5 mmol/l) Alphabet t arget : t otal cholesterol <4 . 0 LDL <2 HDL ≥ 1.0: GMS t arget : t otal cholesterol <5 . 0
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42. UKPDS : any diabetes related endpoint 0% 20% 40% 60% 0 3 6 9 12 15 % of patients with an event Years from randomisation Intensive (2729) Conventional (1138) Risk reduction 12%
55. HOPE: Heart Outcomes Prevention Evaluation Study: Micro-HOPE sub study Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus Lancet 2000; 355: 253 - 59
56. HOPE : MI rate - ramipril vs placebo in diabetics 0.00 0.02 0.04 0.06 0.08 0.10 0.12 0.14 0.16 0 500 1000 1500 2000 Days of Follow-up Kaplan-Meier Rates ramipril Placebo RRR = 22% (6 - 36) p= 0.01
57. HOPE : stroke rate - ramipril vs placebo in diabetics 0.00 0.02 0.04 0.06 0.08 0 500 1000 1500 2000 Days of Follow-up Kaplan-Meier Rates ramipril Placebo RRR = 33% (10 - 50) p=0.0074
58. HOPE : CV death - ramipril vs placebo in diabetics 0.00 0.02 0.04 0.06 0.08 0.10 0.12 0 500 1000 1500 2000 Days of Follow-up Kaplan-Meier Rates ramipril Placebo RRR = 37% (21 - 51) p=0.0001
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60. LIFE : losartan intervention for endpoint reduction in hypertension study Lancet 2002 ; 359 : 995 - 1003
61. LIFE : total mortality – diabetes subgroup Study Month 0 6 12 18 24 30 36 42 48 54 60 66 Proportion of patients, % 24 20 16 12 8 4 0 RRR = 39%; p=0·002 Losartan Atenolol
62. LIFE : new onset diabetes by treatment group Study Month 0 6 12 18 24 30 36 42 48 54 60 66 0 2 4 6 8 10 Proportion of patients, % Atenolol Losartan
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67. POEM 400 : heart disease risk score UKPDS: T0 vs. Tfu p=NS Tadj vs. Tfu p<0.001 n=315
68. Pulling it all together : the Steno 2 Study Multifactorial intervention in high-risk individuals with type 2 diabetes Gaede P et al (2003) N Eng J Med 348:5 p383
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70. Steno-2 : objective To compare the effect of a targeted , intensified, multifactorial intervention with that of conventional treatment on modifiable risk factors for cardiovascular disease in patients with type 2 diabetes and microalbuminuria.
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72. Steno-2 vs Alphabet Strategy : targets Annually Annually F eet UKPDS risk Events H eart disease Most All ACEI / AIIA Most All G uardians : aspirin Annually Annually E yes 7.0 6.5 D iabetes Control : HbA1c% 5.0 4.5 C holesterol 140 / 80 130 / 80 (140 / 85) B lood Pressure Standard Standard A dvice Alphabet Strategy Steno-2 intensive cohort
73. Steno-2 intensive cohort : results 28 AIIA use 79 ACEI use 85 Statin use 87 Aspirin use 15 HbA1c% =< 6.5 72 Total cholesterol =< 4.5 70 Diastolic BP =< 80 54 Systolic BP =< 130 % Target
74. Steno-2 : CVD event reduction 33 events in 19 patients 85 events in 35 patients 6 12 Revascularisation for PVD 7 14 Amputations 3 20 Stroke : non-fatal 0 5 PCI 5 10 CABG 5 17 MI : non-fatal 7 7 Cardiovascular Death Intensive Conventional Event
76. Steno-2 : conclusion “ A target driven, long-term, intensified intervention aimed at multiple risk factors in patients with type 2 diabetes and microalbuminuria reduces the risk of cardiovascular and microvascular events by about 50%.”
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