Diabetes Health Maintenance

1. Diabetes Health Maintenance Author: Laura Leigh Fitzpatrick, MD, MPH Editor: Amy Shaheen, MD, Assistant Professor of Clinical Medicine Duke University Medical Center

2. Cardiovascular Considerations: Hypertension • Diabetes increases the risk of coronary events (2x in men; 4x in women).1 • Associated CV risk factors such as HTN, dyslipidemia are partly responsible for the increase in risk. • Measure BP at every routine diabetes visit.1 • The ADA recommends a target BP goal of <130/80 in pts with diabetes; This is consistent with JNC VII recommendations, and supported by K/DOQI and HOT trial. 1, 2, 3

3. Cardiovascular Considerations: Hypertension (2) • There is evidence to suggest moderate Na dietary restriction, physical activity and weight reduction improves BP control. 1 • Patients with sbp of 130-139 mm Hg and dbp 80-89 mm Hg can have lifestyle/ behavioral therapy alone for up to 3 months, then pharmacologic therapy if targets are not achieved. 1 • Patients with DM and HTN should be treated with an agent shown to decrease CVD events. (ACE-I’s, ARB’s, beta-blockers, diuretics, CCB’s)1 • ACE-I’s/ ARB’s should be considered in patients with evidence of proteinuria.

4. Cardiovascular Considerations: Dyslipidemia • The most common pattern of lipid elevation in patients with diabetes is low HDL and high TG. LDL among pts with DM is not markedly different than among patients without diabetes. 4 • Primary therapy should be directed at LDL-c lowering. • The ADA recommends “testing for lipid disorders at least annually and more often if needed to achieve goals.” If lipid values are low-risk, can test every 2 years. 4 • Goal LDL-c for pts with diabetes as recommended by current ATP-III guidelines is 100. 5

5. Cardiovascular Considerations: Dyslipidemia (2) • -Several studies have suggested benefits to further lowering among high-risk individuals: • PROVE IT (2004) – randomized 4000 pts with ACS in the prior 10 days to pravastatin 40 mg vs. atorvastatin 80 mg. LDL’s achieved were 95 (pravastatin group), and 62 (atorvastatin group). Primary endpoints of death, MI, revascularization were significantly reduced at 2 years. 6

6. Cardiovascular Considerations: Dyslipidemia (3) • Heart Protection Study (2002)- Randomized about 20,000 pts with CAD, other arterial disease, and/or diabetes to simvastatin 40 mg vs. placebo. Simvastatin group had significant reductions in all-cause mortality, MI, CVA and revascularization. Similar reductions in relative risk occurred in groups regardless of baseline LDL-c level. Those with LDL-c >135, <116 or <100 achieved the similar benefits. Those subgroups with combined CVD and diabetes had the greatest risk reduction in outcomes. 7 • Until further data, controlling LDL-c to <100 in pts with diabetes is firmly recommended. Strong consideration should be given to placing pts on a statin to achieve LDL-c to < 70.

7. Cardiovascular Considerations: Smoking Click here for an enlarged .pdf file of this table Table from “Smoking and Diabetes 8

8. Cardiovascular Considerations: Aspirin • Primary Prevention – • Subset of patients with diabetes from the Physicians’ Health Study showed a reduction in MI from 10% to 4% with low-dose aspirin therapy. 9 • The Early Treatment Diabetic Retinopathy Study (ETDRS) included pts with diabetes (both with and without CVD) randomized to ASA vs. placebo. Those receiving aspirin had a significantly lower relative risk of MI in 5 years of 0.72. 10 • The Hypertension Outcomes Treatment trial (HOT) randomized patients with HTN to aspirin 75 mg vs. placebo and found a 15% decrease in CV events and a 36% decrease in MI among those tx with aspirin. 7

9. Cardiovascular Considerations: Aspirin (2) • Secondary Prevention – • The Antiplatelet Trial was a meta-analysis examining patients with prior CVD, CVA/TIA or other vascular disease (both diabetics and nondiabetics). There were about 25% fewer incidents among those treated with aspirin. 11

10. Nephropathy • Diabetes is the single most common cause of ESRD in the U.S. • 20-30% of patients with type 1 or type 2 diabetes develop nephropathy • a smaller proportion of those with type 2 progress to ESRD. • Native Americans, Hispanics and African Americans at increased risk. • The earliest evidence of nephropathy is microalbuminuria. This progresses into clinical albuminuria and overt nephropathy. ESRD develops in 50% of those with type 1 DM with overt nephropathy over 10 yrs. The rate of this progression among type 2 DM is slower, with only 20% having overt nephropathy progressing to ESRD over 20 yrs. 13

11. Nephropathy (2) • Recommendations: • Optimize glucose control (both the DCCT and UKPDS support this in reduction of microvascular complications) 13, 14, 15 • Optimize blood pressure control. 13 • Perform an annual test for microalbuminuria in patients with type 1 DM with disease >5 yrs, and in type 2 DM patients starting at diagnosis. 13

12. Nephropathy (3) • Consider an ACE-I/ ARB among those with microalbuminuria: • 1.) Lewis et al. (1993) randomized pts with type 1 DM and urinary protein excretion >500 mg/ day to captopril vs. placebo. The rate of doubling of serum Cr was significantly lower in the captopril group. Captopril treatment was also associated with reduction in combined death, dialysis and transplantation. 16 • 2.) Lewis et al. (2001) randomized 1715 pts with hypertension and nephropathy (defined as urinary protein excretion > 900 mg/ 24 hours and serum Cr between 1-3) to amlodipine 10 mg vs. irbesartan 300 mg vs. placebo. Composite end-point was doubling of baseline Cr, development or ESRD or death from any cause. Risk of this endpoint was lowest among those on irbesartan. This effect was independent of BP reduction. 17

13. Nephropathy (4) • Withthe onset of overt nephropathy, initiate protein restrictionto: • 0.8 g · kg-1 body wt · day-1 (10% of dailycalories). 13 • Consider referralto a nephrologistwhen: • either the GFR has fallen to <60ml · min-1 ·1.73 m-2 or difficulties have occurredin the management ofhypertension or hyperkalemia.13 • If ACE-I’s or ARB’s used, monitor for development of hyperkalemia.

14. Retinopathy • Diabetic retinopathy is the most common cause of new blindness among adults between 20-74 years. 18 • Laser photocoagulation surgery can reduce severe visual loss from PDR. 19 • Progression of diabetic retinopathy from non-proliferative (NPDR) to proliferative diabetic retinopathy (PDR) to progressive visual loss and ultimately, blindness.

15. Retinopathy (2) • Recommendations 18: • Refer for comprehensive dilated eye exam among type 1 patients within 3-5 yrs after onset of diabetes. Refer type 2 pts at diagnosis of DM. • Following initial exam, repeat exam annually, less frequently (q 2-3 yrs) with advice from eye professional in the setting of normal exams. More frequent exams may be required if retinopathy is progressing. • Follow pregnant women with diabetes (not gestational) closely with regard to eye examination. Have comprehensive exam in 1st trimester and closely follow throughout remainder of pregnancy. • As always, tightly control blood pressure and glucose.

16. Foot care • Foot ulcers and amputations are a major cause of morbidity and disability in patients with diabetes. • Risk factors for amputation include 20: • peripheral neuropathy with loss of protective sensation • altered biomechanics (in the presence of neuropathy) • evidence of increased pressure (erythema, bleeding) • bony deformity • peripheral vascular disease • history of ulcers or amputation • severe nail pathology • additional risk factors include presence of diabetes>10 yrs, male gender, poor glucose control, existing CV/ retinal/renal complications.

17. Foot care (2) • Recommendations 20: • annual foot exam, including assessment of sensation, foot structure, pulses and skin integrity. • Evaluate those with >=1 high-risk foot conditions more frequently • People with neuropathy should have a visual inspection of their feet at each visit. • Evaluation of sensation should be performed with the Semmes-Weinstein 10-g monofilament. • Patient education about risk factors and foot management.

18. Foot care (3) • Here are some things to suggest to patients: • check your feet every night for lesions (use a hand mirror if necessary) • consider moisturizing lotion for dry skin • do not go barefoot/ sockfoot • appropriate foot wear (avoid sandals without socks) • do not trim calluses/ be careful with toenail cutting • alert your doctor should you develop a lesion

19. Immunizations • Annually provide an influenza vaccine. 21 • Provide at least one lifetimepneumococcal vaccine. A one-time revaccinationis recommended for individuals>64 years of age previouslyimmunized when they were <65years of age if the vaccinewas administered >5 years ago.Other indications for repeatvaccination include nephrotic syndrome,chronic renal disease,and other immunocompromised states.21

20. Clinical Vignette A 54 y.o. white female with history of GERD, fibromyalgia and hypertension presents to your clinic complaining of fatigue, malaise for 3 months. She denies myalgias or arthralgias. She does not smoke or drink alcohol. Her medications include amitryptiline 50 mg qhs, HCTZ 25 mg qd, amlodipine 10 mg qd, and pantoprazole 40 mg qd. She reports unusual thirst and blurred vision. She denies family history of diabetes, and states her mother had an MI at age 43. BP- 154/ 92, P- 80, regular, calculated BMI- 34. On exam, she is well-appearing and anxious. Exam is otherwise unremarkable. A fasting blood sugar is 278, and you regretfully inform her she has a diagnosis of diabetes. Chem7 panel and CBC is WNL, U/A shows 1+ protein with a SG of 1.012 but is otherwise negative. A1c is pending.  What is the patient’s goal blood pressure? (see next slide for answer)

21. Clinical Vignette (2) • Answer: • 130/80 mmHg according to JNC VII guidelines • 125/75 if her proteinuria totals over 1g per day Vignette continued on the next slide

22. Clinical Vignette (3) You correctly decide she needs better blood pressure control. Should you start another medicine or ask her to try lifestyle modification (diet and exercise)? (see next slide for answer)

23. Clinical Vignette (4) • Answer: • With her bp of 154/ 92, you should start another medicine, or increase the dose of an existing medication (although this pt is on essentially maximal doses of her bp meds. With a blood pressures between 130-139/ 80-89, it is appropriate to recommend lifestyle changes up to 3 months, then if not successful add a bp agent. What class of antihypertensives should you strongly consider using in this pt? (see next slide for answer)

24. Clinical Vignette (5) • Answer: • Given proteinuria, start an ACE-I. What other medication would you strongly consider in this patient to reduce her risk of CV events and why? (see next slide for answer)

25. Clinical Vignette (5) • Answer: • ASA 75mg – 162 mg daily, because she has other risk factors for CV disease. What other labwork do you need to more definitely outline her CV risk? (see next slide for answer)

26. Clinical Vignette (5) • Answer: • A fasting lipid panel, with strong consideration of placing her on a statin if LDL > 70. What other medication would you strongly consider in this patient to reduce her risk of CV events and why? (see next slide for answer)

27. Please remember to complete the Course Evaluation here. A link to this evaluation is also included in the Content Tree

28. References 1 “Hypertension management in adults with diabetes”. Position Statements, American Diabetes Association. Diabetes Care 2004;27 S65-S67. 2 Chobanian et al. “Seventh report of the joint national committee on prevention, detection, and treatment of high blood pressure”. Hypertension 2003; 42: 1206-1252.  3 Hansson et al. “Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomized trial”. Lancet 1998 Jun 13;351(9118):1755-62   4 “Dyslipidemia management in adults with diabetes”. Position Statements, American Diabetes Association. Diabetes Care 2004;27 S68-71.  5 Third report of the National Cholesterol Education Program (NCEP) Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). Circulation 2002; 106:3143.  6 Cannon et al. N Engl J Med 2004 Apr 8;350(15):1495-504.  7 Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomized placebo-controlled trial. Lancet 2002 Jul 6;360(9326):7-22.  8 “Smoking and diabetes”. Position Statements, American Diabetes Association. Diabetes Care 2004;27 S74-75.  9 Final report on the aspirin component of the ongoing Physicians’ Health Study Research Group. N Engl J Med 321:129–135, 1989.  10 The ETDRS Investigators: Aspirin effects on mortality and morbidity in patients with diabetes mellitus: Early Treatment Diabetic Retinopathy Study report 14, JAMA 268:1292–1300, 1992. 

29. References (2) 11 “Collaborative overview of randomized trials of antiplatelet therapy-I: prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. Antiplatelet Trialists’ Collaboration.” BMJ 308:81–106, 1994. 12 “Aspirin therapy and diabetes”. Position Statements, American Diabetes Association. Diabetes Care 2004;27 S72-73. 13 “Nephropathy in diabetes”. Position Statements, American Diabetes Association. Diabetes Care 2004;27 S79-83. 14 DCCT 15 UK Prospective Diabetes Study Group: Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ 317: 708–713, 1998 16 Lewis EJ, Hunsicker LG, Bain RP, and Rohde RD. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N Engl J Med 329:1456–1462, 1993. 17 Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, Lewis JB, Ritz E, Atkins RC, Rohde BS, Raz I: Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Eng J Med 345:851–860, 2001. 18 Fong et al. “Nephropathy in diabetes”. Position Statements, American Diabetes Association. Diabetes Care 2004;27 S84-87. 19 Photocoagulation treatment of proliferative diabetic retinopathy. Clinical application of Diabetic Retinopathy Study (DRS) findings, DRS Report Number 8. The Diabetic Retinopathy Study Research Group. Ophthalmology 1981 Jul;88(7):583-600.

30. References (3) 20 “Preventive foot care in diabetes”. Position Statements, American Diabetes Association. Diabetes Care 2004;27 S63-64. 21 “Influenza and pneumococcal immunization in diabetes”. Position Statements, American Diabetes Association. Diabetes Care 2004;27 S111-113.