1. Getting to Goal: ‘Practical Tricks of the trade‘ How to Achieve the ABCs Robert Gabbay MD, PhD Director Penn State Hershey Diabetes Institute Penn State College of Medicine rgabbay@psu.edu

2. The ‘ABCs’ A 1C B P < 130/80 C holesterol (LDL<100, if CAD <70)

3. Evidence based interventions that reduce morbidly and mortality HbA1C < 7 BP < 130/80 LDL cholesterol < 100 (or <70 if CAD) Aspirin age > 50 men, 60 women with 1 risk factor ACE -age >55 Statin use- age >40 Yearly screen for nephropathy, feet, and eye exams

4. Current Diabetes Care in US 71 % < 1 A1c measurements per year –18 % A1C > 9.5 –½ A1C > 7 ~64% blood pressure above goal 89 % LDL > 100 37 % no dilated eye exam 45 % no yearly foot exam

5. How Low to Go?

6. What’s the Problem? Not Bad Patients or Bad Doctors It’s the System Acute Care vs. Chronic Care – Self-management Clinical Inertia

7. A1C < 7 Why? How?

8. 7.9 UKPDS: Hemoglobin A 1C (HbA 1C ) Median HbA 1C (%) 7.0

9. % Risk Reduction UKPDS: Risk Reductions Any Diabetes- related Endpoint Microvascular Endpoints Laser Rx Cataract Albuminuria

10. But I thought it was Bad to Lower A1C too Much All recent studies aimed at A1C = 6.5 or lower No evidence that A1C = 7 is bad Data says to reduce CVD- its not so much about Glucose It’s the Blood Pressure and Cholesterol

11. Really really important points: 1.Aggressive control early prevents complications. 2.Because of the log-linear relationship between control and complications, absolute benefits are greatest at high HbA1c values. 3.Pushing patients with advanced disease (particularly macrovascular complications) to ‘tight’ control that they cannot achieve probably increases mortality attention to hypoglycemia and particularly nocturnal hypoglycemia

12. Sites of Drug ActionCarbohydrate DIGESTIVE ENZYMES Glucose Defective -cell secretion  -cell secretion Excessglucoseproduction Resistance to the action of insulin Reduced glucose uptake Excessivelipolysis Dinneen SF. Diabet Med. 1997; 14 (Suppl 3): S19-24. Sulfonlyureas Meglitinides Incretins Insulin Alpha-glucosidase Inhibitors, Incretins Metformin TZD Incretins TZD, Metformin

13. How to choose? Pathophysiology – I resist or I secretion? Cost Rapid onset- avoid TZD Co-morbidities – Renal – no metformin – Liver –no TZD – CHF – no TZD – CAD? – avoid TZD? – Weight- favor metformin, incretins – Concern hypo- avoid SU

14. Points to remember Each oral agent lower A1C 1-2 If A1C >9, start two agents Follow SMBG, A1C, and Titrate!!!!!

15. T2DM treatment strategies revisited 7 9 HbA 1c (%) 8 Diagnosis Target-driven therapy* Adapted from Riddle M. Endo Metab Clin NA 1997;26:659―77. Riddle M. Am J Med 2004;116:35 ―95. *Individualise STEP 1 STEP 2 STEP 4 OHA monotherapy OHA combinations STEP 3 Lifestyle modification Basal insulin Basal plus prandial

16.  20  10 0102030 Natural History of Type 2 Diabetes Adapted from International Diabetes Center (IDC). Minneapolis, Minnesota. Years of Diabetes Relative  -Cell Function Plasma Glucose Insulin resistance Insulin secretion 126 mg/dL Fasting glucose Postmeal glucose 6-6

17. TYPE 2 DIABETES... A PROGRESSIVE DISEASE Over time, most patients will need insulin to control glucose 6-7

18. Correcting Fasting Hyperglycemia… 100 200 300 Normal A1C 5%–6% PG (mg/dL) 0800120018000800 Time of Day Uncontrolled A1C ~9% A1C ~6% Is Usually the First Task!! …then, Tackle Postprandial Hyperglycemia if A1C still >7%! “Controlled” A1C <7% Adapted with permission from Cefalu WT. In: Leahy J, Cefalu W, eds. Insulin Therapy. New York: Marcel Dekker; 2002:1 2003 Aventis Pharmaceuticals Inc

19. Titrating Glargine or Detemir 2 units q 3 days until FPG < 100 Its that easy and it works!

20. 50 4:00 25 75 8:0012:0016:0020:0024:004:00 BreakfastLunchDinner Plasma Insulin ( U/mL) Insulin ( µU/mL) Time 8:00 Physiologic Serum Insulin Secretion Profile

21. Blood Pressure <130/80 Why? How?

22. Benefits of tight vs less tight BP control Risk Reduction (%) Any Diabetes- related Endpoint Diabetes- related Death RetinopathyStrokeHF  24 P=.0046  32 P=.019  34 P=.0038  44 P=.013  56 P=.0043 -70 -20 0 -10 -50 -60 -30 -40 UKPDS: Effect of Intensive BP Lowering on Risk of Micro- and Macrovascular Complications MI  21 P=.13 Renal Failure  42 P=.29  47 P=.0036 Vision Deterioration UKPDS 36. BMJ. 2000;321:412-419. UKPDS 38. BMJ. 1998;317:703-713. UKPDS (United Kingdom Prospective Diabetes Study) was a randomized, prospective trial in which 1,148 hypertensive patients with type 2 diabetes were allocated to tight (<150/<85 mm Hg, n=758) or less tight (<180/<105 mm Hg, n=390) BP control and followed for a median of 8.4 years. Microvascular endpoints included retionpathy requiring photocoagulation, vitreous hemorrhage, and fatal or nonfatal renal failure.

23. Consistency Across Guidelines on BP Goal in Patients With Diabetes JNC 7: ADA: BP Goal Is <130/80 mm Hg NKF: Adapted from American Diabetes Association. Diabetes Care. 2003;26(suppl 1):S33-S50; NHBPEPCC. JNC 7 Express. 2003. NIH Publication No. 03-5233; NKF. Available at: www.kidney.org/general/news/diabetic.cfm?id=64. Accessed March 9, 2004.

24. ABCD 2,3 (132 mm Hg) AASK 1 (134 mm Hg) High-Risk Hypertensive Patients Require Multiple Agents to Achieve Goal 1 Wright JT et al. JAMA. 2002;288:2421-2431. 2 Bakris GL. J Clin Hypertens. 1999;1:141-147. 3 Estacio RO et al. N Engl J Med. 1998;338:645-652. 4 The ALLHAT Officers and Coordinators. JAMA. 2002;288:2981-2997. 5 Hansson L et al. Lancet. 1998;351:1755-1762. 6 Lewis EJ et al. N Engl J Med. 2001;345:851-860. 7 Bakris GL et al. Arch Intern Med. 2003;163:1555-1565. 8 UK Prospective Diabetes Study Group. BMJ. 1998;317:703-713. Number of BP Medications ALLHAT 4 (135 mm Hg) RENAAL 7 (140 mm Hg) IDNT 6 (140 mm Hg) UKPDS 2,8 (144 mm Hg) HOT 2,5 (141 mm Hg) Achieved Systolic BP

25. Evidence Based Guidelines < 130/80 (you will report <140/90) How about LOWER??? ACCORD looked at lower (120)- no better What is the first line medication? – Who cares?

26. 20 01234567 Cumulative Event Rate (%) 0 4 8 12 16 Chlorthalidone Amlodipine Lisinopril ALLHAT (The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack) participants were randomly assigned to receive chlorthalidone, 12.5 to 25 mg/d (n=15,255); amlodipine, 2.5 to 10 mg/d (n=9,048); or lisinopril, 10 to 40 mg/d (n=9,054) for planned follow-up of approximately 4 to 8 years, mean follow-up 4.9 years. ALLHAT Collaborative Research Group. JAMA. 2002;288:2981-2997. ALLHAT: Cumulative Event Rates for Fatal CHD or Nonfatal MI by Treatment Years to Event Number at Risk: Chlorthalidone 15,25514,47713,82013,10211,3626,3402,956209 Amlodipine 9,048 8,576 8,218 7,843 6,8243,8701,878215 Lisinopril 9,054 8,535 8,123 7,711 6,6623,8321,770195

27. Medication Treatment Algorithm? Start with ACE or ARB and/or HCTZ – Either one - best might be early combo since all will likely need it Third agent based on co-morbidity – Beta blocker and/or Ca channel Add the 4 th and hopefully you’ve reached goal- if not call an expert +/- alpha blocker?

28. Tashko and Gabbay, Integrated Blood Pressure Control (2010)

29. Practical: What can I do on when I get back to work? Track BP Don’t miss an opportunity to escalate Shared goals Standing Orders?

30. Cholesterol LDL control <100 If CVD <70

31. LDL Treat the water supply?

32. % Follow-up (years) Placebo Simvastatin Benefit/1,0001334475158 P<0.0001 0123456 0 5 10 15 20 25 30 HPS Collaborative Group. Lancet. 2003;361:2005-2016. HPS Substudy: First Major Vascular Event in Patients With Diabetes 22 %

33. Follow-up (yr) Cumulative incidence (%) 0 1 2 3 4 0.00.51.01.52.02.53.03.5 Atorvastatin 10 mg Placebo Number of events: 100 Number of events: 154 HR=0.64 (0.50-0.83)P=0.0005 36% reduction Nonfatal MI (including silent MI) and fatal CHD. Sever PS et al. Lancet. 2003;361:1149-1158. ASCOT-LLA: Primary End Point

34. Statins for DM The question is: Who do we NOT treat?

35. Putting it All together

36. The Chronic Care Model 36 Informed, Activated Patient Productive Interactions Prepared, Proactive Practice Team Delivery System Design Decision Support Clinical Info Systems Self- Management Support Health System Resources and Policies Community Health Care Organization Improved Outcomes

37. Self-management support Increase adherence Education but most important SUPPORT Use handouts, share goals Combo Rx for pill burden – Who else on the team can help? – Use Diabetes Educators where available

38. Delivery System Design Distribute tasks amongst team – It takes a TEAM to manage a Chronic disease Care management of high risk – Stratifying your population Regular f/u by team Planned Visits Dealing with CLINICLA INERTIA

39. The Chronic Care Model 39 Informed, Activated Patient Productive Interactions Prepared, Proactive Practice Team Delivery System Design Decision Support Clinical Info Systems Self- Management Support Health System Resources and Policies Community Health Care Organization Improved Outcomes

40. Decision support – Evidence based guidelines (ADA) – SHARE WITH YOUR PATIENTS

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43. Clinical Information systems Registry!!!! Track outcomes and ID those not at goal with a plan for intensification

44. Evidence based interventions that reduce morbidly and mortality HbA1C < 7 BP < 130/80 LDL cholesterol < 100 (or <70 if CAD) Aspirin age > 50 men, 60 women with 1 risk factor ACE -age >55 Statin use- age >40 Yearly screen for nephropathy, feet, and eye exams

45. QUESTIONS?