1. Facts and Fiction about Type 2 Diabetes Michael L. Parchman, MD Department of Family & Community Medicine September 2004

2. Complications from Type 2 Diabetes Microvascular Microvascular  Retinopathy  Neuropathy  Nephropathy  Autonomic: gastroparesis, blood pressure Macrovascular Macrovascular  MI  CVA  Claudication/PVD

3. Preventing Complications from Type 2 Diabetes Glucose Glucose Blood Pressure Blood Pressure Lipids Lipids What is the Evidence? What is the Evidence?

4. UKPDS The only large study of patients with Type 2 DM of new onset The only large study of patients with Type 2 DM of new onset 20 year study conducted in 23 centers in the U.K. 20 year study conducted in 23 centers in the U.K. More than 5,000 patients enrolled More than 5,000 patients enrolled Primary Aim: determine the effect of intensive control of glucose on 21 predetermined end- points. Primary Aim: determine the effect of intensive control of glucose on 21 predetermined end- points. Added a secondary arm to study the effect of blood pressure and lipid control. Added a secondary arm to study the effect of blood pressure and lipid control.

5. Glucose: Fact or Fiction? Tight control of blood glucose improves mortality. Tight control of blood glucose improves mortality. FACT: Tight control of blood glucose did not prevent premature mortality FACT: Tight control of blood glucose did not prevent premature mortality

6. Glucose: Fact or Fiction? All patients with type 2 diabetes benefit from treatment with metformin. All patients with type 2 diabetes benefit from treatment with metformin. FACT: In overweight patients, metformin decreased mortality related to diabetes or other cause (13.5 v. 20.6 events per 1000 pt yrs, NNT per year=141) AND diabetes related complications (29.8 v. 43.3 events/1000 pt yrs) FACT: In overweight patients, metformin decreased mortality related to diabetes or other cause (13.5 v. 20.6 events per 1000 pt yrs, NNT per year=141) AND diabetes related complications (29.8 v. 43.3 events/1000 pt yrs) “Overweight patients with type 2 DM seem to benefit not so much from the overall control of glucose but rather from taking metformin.” “Overweight patients with type 2 DM seem to benefit not so much from the overall control of glucose but rather from taking metformin.”

7. Glucose: Fact or Fiction? Tight control of blood glucose prevents the onset of microvascular and macrovascular complications. Tight control of blood glucose prevents the onset of microvascular and macrovascular complications. FACT: Changes in HbA1c produced by intensive drug treatment did not correlate with microvascular or macrovascular outcomes. FACT: Changes in HbA1c produced by intensive drug treatment did not correlate with microvascular or macrovascular outcomes. FACT: In overweight patients, treatment with insulin or sulfonylureas had no effect on individual or aggregate microvascular or macrovascular outcomes. FACT: In overweight patients, treatment with insulin or sulfonylureas had no effect on individual or aggregate microvascular or macrovascular outcomes.

8. BP: Fact or Fiction Tight blood pressure control prevents macrovascular but not microvascular complications Tight blood pressure control prevents macrovascular but not microvascular complications FACT: Tight control of blood pressure decreased likelihood of ALL 21 different endpoints, microvascular, macrovascular and mortality. FACT: Tight control of blood pressure decreased likelihood of ALL 21 different endpoints, microvascular, macrovascular and mortality. Control of BP had greater effect on complications than glucose control (24% v. 12% decreased risk in diabetes related complications Control of BP had greater effect on complications than glucose control (24% v. 12% decreased risk in diabetes related complications

9. BP: Fact or Fiction Diastolic blood pressure is a more important risk factor for MI and stroke than systolic Diastolic blood pressure is a more important risk factor for MI and stroke than systolic FACT: Systolic BP is a more important risk factor for MI and stroke than diasolic. FACT: Systolic BP is a more important risk factor for MI and stroke than diasolic. FACT: Each 10mm Hg reduction in systolic BP associated with 12% reduction in risk for ANY complication of diabetes FACT: Each 10mm Hg reduction in systolic BP associated with 12% reduction in risk for ANY complication of diabetes FACT: No lower threshold for any complication below which risk no longer decreased. FACT: No lower threshold for any complication below which risk no longer decreased.

10. Systolic BP and Incidence Rate of Any DM Complication

11. How Do We Get This Low? UKPDS: Over 60% of patients in “tight” BP control group requires 3 or more drugs 2 (“tight” = mean BP 144/82) UKPDS: Over 60% of patients in “tight” BP control group requires 3 or more drugs 2 (“tight” = mean BP 144/82)

12. Lipids: Fact or Fiction Patients with type 2 diabetes and no history of CVD should have an LDL level of <130 Patients with type 2 diabetes and no history of CVD should have an LDL level of <130 FACT: Heart Protection Study* FACT: Heart Protection Study*  T2DM over age 40  Total Cholesterol over 135  LDL reduction of 30% associated with 25% reduction in first major coronary event, regardless of baseline LDL level

13. How Low Can We Go? Grundy et al. Circulation 2004;110:227. July 13, 2004

14. Adult Treatment Panel III Guidelines as of July 13, 2004 Diabetes AND CHD Diabetes AND CHD LDL goal of less than 70 mg/dl Diabetes Without CHD Diabetes Without CHD LDL goal of less than 100 mg/dl Grundy et al. Circulation 2004;110:227. July 13, 2004

15. Heart Protection Study* “…statin therapy should now be considered routinely for all diabetic patients at sufficiently high risk for such major vascular events, irrespective of their initial cholesterol concentrations.” “…statin therapy should now be considered routinely for all diabetic patients at sufficiently high risk for such major vascular events, irrespective of their initial cholesterol concentrations.” *Lancet 2003;361:2005-2016

16. Evidence: Know your “A,B,Cs” “A”: A1c “A”: A1c  less than 7.0 “B”: Blood Pressure “B”: Blood Pressure  less than 130/80 “C”: Cholesterol: “C”: Cholesterol:  LDL less than 100 mg/dl;  OR 30% reduction in LDL with a statin if over age 40 & total cholesterol>135 mg/dl

17. The “5-minute” Diabetes Visit Pressure Pressure Lipids Lipids Aspirin Aspirin Glucose Glucose Urine protein Urine protein Eyes Eyes Feet Feet

18. ADA Target: BP < 130/80 P: Blood Pressure

19. L: Lipid Control LDL < 100 LDL < 100 TG < 150 TG < 150 HDL > 40 men; HDL > 40 men; >50 women If over 40, and total Cholesterol >135: If over 40, and total Cholesterol >135:  Use statin to reduce LDL by 30% regardless of baseline LDL level

20. A: Aspirin, 75-162 mg/day Recommended for all patients with T2DM Recommended for all patients with T2DM US Physician’s Health Study US Physician’s Health Study  a reduction in myocardial infarction from 10.1% (placebo) to 4.0% (aspirin), Early Treatment Diabetic Retinopathy Study Early Treatment Diabetic Retinopathy Study  For those on ASA: relative risk 0.72 for myocardial infarction in the first 5 years Hypertension Optimal Treatment (HOT) Trial Hypertension Optimal Treatment (HOT) Trial  Aspirin significantly reduced cardiovascular events by 15% and myocardial infarction by 36%

21. G: Glucose Testing If < 7.0: A1c testing twice each year, at least 3 months apart If < 7.0: A1c testing twice each year, at least 3 months apart If > 7.0; every 3 months If > 7.0; every 3 months

22. ADA Target: A1c < 7.0%

23. U: Urine Protein Annual screening urine micro-albumin Detection of nephropathy Begin ACEI to slow progression of nepthropathy

24. E: Eyes Annual dilated eye exam or at frequency recommended by eye specialist after initial exam Annual dilated eye exam or at frequency recommended by eye specialist after initial exam

25. Screening for Retinopathy: Vijan S, et al JAMA 2000;238:889-896 Risk Group Risk of Any Retinopathy No Screening Annual Screening High (age 45y; A1c 11% 86.122.410.1 Moderate (age 65 y; A1c 9% 49.42.71.2 Low (age 75y; Ac1 7% 35.60.80.3 Risk of Blindness, %

26. F: Feet Visual inspection at every visit Visual inspection at every visit Comprehensive exam once each year with monofilament, tuning fork, palpation and visual examination Comprehensive exam once each year with monofilament, tuning fork, palpation and visual examination