1. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Duke Internal Medicine Residency Curriculum Diabetes: A Brief Summary on Diagnosis and Screening Jason Goebel, MD

2. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Learning Objectives Realize the economic impact and health care burden of diabetes Understand epidemiological characteristics of diabetes Describe both screening and definitive diagnosis of diabetes Be able to describe testing for gestational diabetes Recall the intervals and indications for screening for other co- morbidities associated with diabetes Apply current ADA standards to your patient care involving foot care, eye exams, ASA therapy, and screening for CAD, HTN, and HL Encourage all smokers to stop smoking Understand currently vaccination guidelines for diabetics Be able to apply ADA guidelines to hypothetical patient scenarios

3. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Overview The following presentation will briefly review the epidemiology, economic impact, current shortcomings in care, and diagnosis of diabetes. In addition, it will give a more in depth summary of screening and health maintenance recommendations as outlined by the American Diabetes Association.

4. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Epidemiology >7% of people in the US are known to have diabetes Health care costs account for approximately 20% of the US Gross Domestic Product 1 DM accounts for 14% of US health care expenditures –Mostly from vascular complications Myocardial infarction Strokes ESRD Retinopathy Foot ulcers –Costs in 2002 were estimated at 132 billion US dollars 2 –This figure grossly underestimates current burden on health care expenditures

5. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Current Compliance to Practice Guidelines Despite well-published guidelines supported by sound data most diabetics are not receiving recommended levels of healthcare 3 In academic centers rates of testing for risk factors are quite high (>90%). However, rates of medication adjustment were much lower (6-40%) 4,5 NHANES III (US National Health and Nutritional Examination Survey) demonstrated inadequacy of obtaining treatment goals: 6 –18% had A1C >9.5 –34% had BP > 140/90 (previous treatment goal) –58% had LDL >130 (previous treatment goal) –37% had no annual eye exam –45% had no dedicated foot exam Lower compliance has been demonstrated in uninsured populations 6 Screening for other health issues is suboptimal in diabetic patients 7 Data comparing compliance to practice guidelines by diabetic specialists versus primary care physicians has been equivocal 8 Outcomes are improved by implementing organized screening programs 9

6. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Classification of Diabetes 10 Type 1 Diabetes –Results from beta-cell destruction and insulin deficiency Type 2 Diabetes –Progressive insulin secretory defect in addition to insulin resistance Gestational Diabetes (GDM) –Diagnosed during pregancy Other types or acquired diabetes Impaired Fasting Glucose

7. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Diagnosis 11 Oral Gucose Tolerance Test (OGTT) –Baseline fasting glucose followed by 75g oral glucose load with measurement of serum glucose 1 and 2 hours later –More sensitive and specific than fasting plasma glucose (FPG) –More difficult and time consuming for patients and more costly Fasting Plasma Glucose (preferred method) –Glucose measured 8 hours after fasting overnight

8. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Diagnosis Hemoglobin A1C –Measure of average blood glucose over past 90 days –Results variable depending on transfusions, acute illness, and other factors –Most patient who meet diagnostic criteria for diabetes by OGTT but not FPG will have an A1C < 7 –Not an acceptable measure to diagnose diabetes

9. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Diagnosis Symptoms of diabetes plus a random plasma glucose concentration >/=200 mg/dL Classic symptoms of diabetes such as unexplained weight loss, polydipsia, polyuria, or blurred vision -OR- Fasting plasma glucose concentration >/=126 mg/dL No caloric intake for 8 hours -OR- 2-hr plasma glucose concentraion >/= 200 mg/dL on a OGTT If symptoms are not present values should be confirmed on repeat examination

10. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Gestational Diabetes-Diagnosis Gestational Diabetes –Initial screening involves measurement of BG 1 hour after 50g oral glucose load If BG is greater than 140 one of two OGTT below should be performed and if any value exceeds maximal concentration below diagnosis of GDM is obtained –100g glucose load (can be initial test if high pre-test probability) TimeFasting1hr2hrs3hrs Plasma glucose (mg/dL)95180155140 –75g glucose load (not as well validated) TimeFasting1hr2hrs3hrs Plasma glucose (mg/dL)95180155

11. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Diagnosis Impaired fasting glucose (IPG) 100-125 mg/dL Impaired glucose tolerance (IGT) 2 hr glucose 140-199 mg/dL IPG and IGT have been termed "pre-diabetes" and are risk factors for future diabetes and cardiovascular disease

12. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Blood Glucose Screening Screening to detect IGT, IFG, or DM should be considered in individuals >/= 45 years of age especially if BMI is >/= 25 Perform screening on younger individuals if they exhibit other risk factors of diabetes Repeat screening every three years In confirmed diabetics hemoglobin A1C should be measured every 6 months in well controlled populations and quarterly in those not at goal or undergoing changes in medication regimens

13. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Diabetic Retinopathy By 20 years, retinopathy is present in almost all patients with DM1 and 50-80% in DM2 12 Following retinopathy treatment and screening guidelines would result in 169,000 person-years of sight and 325 million US dollars annually 13 Screening is performed by dilated opthalmoscopy by well- trained personnel or seven-field stereoscopic fundus photography –Both are well validated, cost-effective, comparable, and the former easier to perform 14 –Opthalmoscopy performed by primary care physicians is of less sensitivity and specificity 15

14. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Diabetic Retinopathy Patients with DM1 should undergo opthalmoscopy five years after diagnosis diabetes or after puberty and annually thereafter –Trials have shown that in type 1 diabetics of less than 5 year duration, none had proliferative retinopathy requiring laser treatment and only 0.4% had preproliferative retinopathy 15 Type 2 diabetics should undergo screening at the time of diagnosis and annually thereafter Patients with macular edema, severe nonproliferative retinopathy, or proliferative retinopathy should be followed closely by an experienced opthalmologist

15. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Diabetic Retinopathy The degree of protection from retinopathy is greatest in those with early stages of the disease and directly correlates with the degree of glycemic control 16 Management of HTN controls progression to retinopathy and reduces risk of vitreous hemorrhage Diastolic BP appears to be a better predictor of progression than systolic 17 UKPDS showed therapy with atenolol or captopril and resultant decreases of BP to 144/87 and 154/87, respectively, resulted in 47%reduction in deterioration of retinopathy and visual acuity 18 Lisinopril has been shown to decrease events in a similar fashion 19 No conclusive study has shown aspirin to reduce development or progression of opthalmic complications of diabetes 20

16. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Routine Foot Examination Foot complications due to peripheral neuropathy and PVD are a major cause of morbidity and mortality in diabetics Diabetics should undergo a comprehensive annual foot exam and visual inspection of feet at each visit –Comprehensive foot exam performed with Semmes-Weinstein 5.07 (10g) monofilament –Screen for PVD by taking are careful history regarding claudication and checking peripheral pulses. The presence of pulses may be misleading since stiff diabetic vessels may transmit pulses despite minimal flow –Check capillary refill and dependent rugor –Evaluate skin for ulcers, calouses, fungus, or wounds –Neurologic exam should include monofilament testing, proprioception, light touch, and vibration

17. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Routine Foot Examination Diabetics should undergo a comprehensive annual foot exam and visual inspection of feet at each visit –Shoes should be checked to ensure proper fit –High heels should be avoided as shoes should have a deep toe box to allow adequate circulation and avoid excess pressure –Patients' family members should be trained in foot self- assessment –Patients with any sign of diabetic complications in the foot should be referred to a qualified podiatrist for further management and/or orthotics –Lifestyle modification and management of blood pressure and glucose are of equal importance in maintaining good foot care

18. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Diabetic Nephropathy Nearly one third of diabetic patients will develop nephropathy and more type 1 diabetics will progress to ESRD Increased urinary protein excretion is the earliest clinical finding of diabetic nephropathy and not detectible by urine dipstick until levels are greater than 300 mg/dL Normal levels are less than 20mg/day and levels between 20 and 300 mg/dL are termed microalbuminuria and indicative of nephropathy 21 Values can be obtained by 24 hour urine collection or spot morning assessment of protein/creatinine ratio –Spot values >30 mg/g are indicative of nephropathy but should be confirmed by repeat measurement on at least two separate occasions to prevent false positives 22 Albuminuria (>300mg/dL) is associated with a 4-8 fold increase of CAD in diabetics

19. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Diabetic Nephropathy Screening for microalbuminuria should begin at diagnosis in DM2, patients with GDM, and after 5 years in DM1 and repeated annually It is less clear if annual testing is of benefit in patients already diagnosed with microalbuminuria –Expert opinion suggests that normalizing micoalbuminuria to normal range can improve renal and cardiovascular prognosis Febrile illness, hematuria, glycosuria, heavy exercise and UTI can all cause proteinuria in normal persons Patients to be educated to decrease dietary protein to less than 0.8 g/kg body weight daily 26 Several large clinical trials have proven that nephropathy can be prevented with tight BG 23, 24 and BP control 25 with ACE-I and ARBs Early referral to nephrologist is cost-effective, maintains renal function, and improve quality of care 27

20. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Diabetic Nephropathy ACE-I and ARBs should be used in micro- and macroalbuminuria unless patient is pregnant Role of ACE-I and ARB are unproven in normotensive patients with abnormal proteinuria but recommended by expert opinion In DM1 with HTN and albuminuria ACE-I have been shown to delay the progression of nephropathy In DM2 with HTN and microalbuminuria ACE-I have been shown to delay the progression to macroalbuminuria In DM2 with HTN, macroalbuminuria and creatinine >1.5 ARBs have been shown to delay progression of nephropathy Some evidence suggests ARBs have a smaller rise in serum potassium than ACE-I 28

21. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Cardiovascular Disease Cardiovascular disease is a major cause of morbidity and mortality in diabetics Diabetics often have metabolic syndrome and other comorbidities which substantially increase CAD risk 29 UKPDS identified modifiable risk factors for CAD in diabetics that should be managed appropriately 30 LDL in upper third tertile (Hazard Ratio 2.3) HDL in upper third tertile – beneficial (HR 0.6) Elevated Hemoglobin A1C (HR 1.5) Systolic Blood Pressure (HR 1.8) Smoking (HR 1.4) The ADA recommends that cardiovascular risk factors be assessed annually and as follows: Cardiac stress testing in patients with a history of peripheral or carotid occlusive disease, sedentary lifestyle, age >35 year, prior to beginning an aggressive exercise program, or two or more CHD risk factors

22. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Smoking Cessation Cigarette smoking contributes to 1 in 5 deaths in the US and is the most modifiable cause of premature death 33 A large survey found that the prevalence of cigarette smoking was greater in diabetics than nondiabetic subjects 32 All smokers should be advised to stop smoking at every clinic visit Several large RCTs have demonstrated the efficacy and cost-effectiveness of smoking cessation counseling 30,31

23. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Aspirin Therapy A large meta-analysis has demonstrated that the greatest benefit from ASA is in patients over 65 and those with DM and diastolic HTN The US Physicians Health Survey demonstrated a non- significant increased trend in hemorrhagic stroke and GI bleed. However, the risk is far outweighed by the benefit in most diabetics. 35 Current ASA use in appropriate diabetics is very low 74% in secondary prevention 38% in primary prevention The ADA has made the following recommendations: –ASA 75-162 mg/day for secondary prevention in diabetics with a history of MI, PVD, CVA or TIA, claudication, or angina. –ASA 75-162 mg/day for primary prevention in diabetics with a history of one additional CHD risk factor unless <21 years old

24. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Hypertension BP should be checked at every diabetic visit Cardiovascular complications in diabetics are reduced with diastolic BP down as low as 85 mm/Hg. 37 Similar benefit is seen with SBP below 120 mm/Hg. 38 Blood pressure for most diabetics should be 130/80 Target BP for Diabetics with CKD and nephrotic range proteinuria is 120/75 mm/Hg 39 ALLHAT found that high risk patients including diabetics have better outcomes with thiazide diuretics than ACE-I 40 Diabetics with HTN should be initiated on a thiazide or ACE-I unless they have other compelling indications (nephropathy, microalbuminuria, retinopathy- all indicating ACE-I) ARBs should be substituted in patients intolerant of ACE-I because of cough or other minor side effects.

25. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Hyperlipidemia Patients with diabetes should be screened for hyperlipidemia at least annually if higher risk and biannually for those with favorable lipid profiles Diabetes is considered a CAD equivalent and therapy should be directed at lowering LDL below 100 mg/dL Particular attention should be given to the metabolic syndrome often associated with diabetics

26. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Vaccinations Observational studies have shown that diabetics have higher in- hospital morbidity and mortality from influenza than matched cohorts 41 The influenza vaccine has been shown to reduce hospital related admission for influenza by 79% 42 Patients with diabetes also have an increased risk of the bacteremic form of nosocomial pneumonia and a higher mortality (>50%) than non-diabetics 41 All diabetics should receive annual influenza vaccinations Provide at least one lifetime pneumococcal vaccine to adults with diabetes –One-time revaccination is recommended for individuals >64 years of age if immunized before age 60 (>5 yrs prior) –Repeat vaccination indicated in patients with nephrotic syndrome, CKD, and other immunocompromised states

27. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Summary Diabetes accounts for a substantial portion of US health care expenditures US health care providers grossly under-diagnose diabetes Diabetics often have multiple co-morbidities which can be medically managed and reduce overall complications Multiple medical problems make it more difficult for health care providers to meet standards of care in managing diabetes Practitioners must be cognizant of screening guidelines in order to improve quality of care and outcomes in diabetics It is imperative to refer patients to the appropriate subspecialist when they demonstrate certain complications of diabetes

28. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Case #1 Stacy G. is a 29 y/o male with a hx of heavy smoking who presents to your PM clinic as a new patient. He has a multitude of complaints but most concerning to you (and him for different reasons) is polyuria for several months as well as weight loss. You think he has diabetes, which of the following is appropriate to diagnose diabetes? A. check a hemoglobin A1C and tell him he has diabetes when it returns at 7.4 B. check a chem 7 which reveals a BG of 218 mg/dL C. give him a 50g OGTT test D. wait until the following morning and check a fasting glucose and if >125 mg/dL have the test repeated at a later time. E. Don't do any testing because you know he will be noncompliant on his medications and will continue to eat Krispy Kreme doughnuts

29. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Case #2 Andy "Toughguy" W. is a 30 y/o male who you see for routine follow up of his diabetes which has been complicated by severe retinopathy w/ 20/400 vision in both eyes. He has missed several appointments and has not seen his opthalmologist. On exam you note his BP is 138/86 after being repeated on several occasions. He asks you if he should be treated for his BP and if so with what drug? A.Yes, start lisinopril 10mg po daily B.Yes, start long-acting metoprolol 25mg po daily C.Yes, start chlorthalidone 10mg po daily D.Yes, start amlodipine 2.5mg po daily E.No, his blood pressure is at goal of <140/90

30. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Case #3 Sascha T. is a 75 y/o patient with diet controlled diabetes, HTN, HL, PVD, and smoking. He comes to clinic with a list of things he wants you to "fix". However, he said his wife told him he can't multi-task with anything in life and wants to know what one thing will give him the best chance of living to 100. Which of the following measures will result in the greatest mortality benefit. A. Send him for his annual eye exam B. Tell him to stop smoking C. Increase his atorvastatin to get his LDL below 100 D. Take off his shoes, examine his feet, and suggest that he cut his 2" fungus laden toenails E. Tell him to eat a steak and baked potato with every meal

31. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Case #4 You have just finished your rotation on diabetes management when you see one of seven patients with diabetes scheduled to see you in continuity clinic. You feel a little guilty because you have been content with A1C's in the 8-9 range. Now you pull out your ADA guidelines on screening and management for diabetes. Which of these would meet standard of care as established by the ADA? A.Ordering your long-time 65 y/o diabetic patient their first pneumococcal vaccine B.Testing for microalbuminuria in patient with a random glucose of 400 mg/dL C.Checking A1C every six months on your diabetic patient who has been <7 for 3 years D.Performing a brief foot exam once a year on a diabetic who sees you every 2 months in clinic. E.Telling the patient to try the Ultimate Double Gravy Biscuit at Biscuitville so you can utilize "shock & awe" when he sees his blood sugar surpass your SAT score

32. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Final Question Which of the following is true of diabetics? a.They have similar rates of smoking than nondiabetic counterparts b.All diabetics should have a dilated eye exam at the time of diagnosis c.Daily aspirin is recommended for all diabetics for primary prevention d.They are less likely to have an annual mammogram performed if indicated e.When seen at Academic centers like Duke, the majority (>50%) of the time their diabetic medications are titrated appropriately

33. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum References 1.Mokdad, AH, Ford, ES, Bowman, BA, et al. Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. JAMA 2003; 289:76. 2.Hogan, P, Dall, T, Nikolov, P. Economic costs of diabetes in the US in 2002. Diabetes Care 2003; 26:917. 3.Kenny, SJ, Smith, PL, Goldschmid, MG, et al. Survey of physician practice behaviors related to diabetes mellitus in the U.S. Diabetes Care 1993; 16:1507. 4.Grant, RW, Buse, JB, Meigs, JB. Quality of diabetes care in U.S. academic medical centers: low rates of medical regimen change. Diabetes Care 2005; 28:337. 5.Wexler, DJ, Grant, RW, Meigs, JB, et al. Sex disparities in treatment of cardiac risk factors in patients with type 2 diabetes. Diabetes Care 2005; 28:514. 6.Saaddine, JB, Engelgau, MM, Beckles, GL, et al. A diabetes report card for the United States: quality of care in the 1990s. Ann Intern Med 2002; 136:565. 7.Beckman, TJ, Cuddihy, RM, Scheitel, SM, Naessens, JM. Screening mammogram utilization in women with diabetes. Diabetes Care 2001; 24:2049. 8.Greenfield, S, Rogers, W, Mangotich, M, et al. Outcomes of patients with hypertension and non- insulin-dependent diabetes mellitus treated by different systems and specialties. Results from the Medical Outcomes Study. JAMA 1995; 274:1436. 9.Hayes, TM, Harries, J. Randomized controlled trial of routine hospital care versus routine general practice care for type II diabetics. BMJ 1984; 289:728. 10.Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 1997; 20:1183. 11.Genuth, S, Alberti, KG, Bennett, P, et al. Follow-up report on the diagnosis of diabetes mellitus. Diabetes Care 2003; 26:3160. 12.Javitt, JC, Aiello, LP, Chiang, Y, et al. Preventive eye care in people with diabetes is cost saving to the federal government. Diabetes Care 1994; 17:909.

34. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum References Continued 13.Moss, SE, Klein, R, Kessler, SD, Richie, KA. Comparison between ophthalmoscopy and fundus photography in determining severity of diabetic retinopathy. Ophthalmology 1985; 92:62. 14.O'Hare, JP, Hopper, A, Madhaven, C, et al. Adding retinal photography to screening for diabetic retinopathy. A prospective study in primary care. Br Med J 1996; 312:679. 15.Ramsay, RC, Goetz, FC, Sutherland, DE, et al. Progression of diabetic retinopathy after pancreas transplantation for insulin-dependent diabetes mellitus. N Engl J Med 1988; 318:208. 16.Javitt, JC, Canner, JK, Frank, RG, et al. Detecting and treating retinopathy in patients with type 1 diabetes mellitus. Ophthalmology 1990; 97:483. 18.Cohen, RA, Hennekens, CH, Christen, WG, et al. Determinants of retinopathy progression in type 1 diabetes mellitus. Am J Med 1999; 107:45. 19.Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group. BMJ 1998; 317:703. 20Chaturvedi, N, Sjolie, AK, Stephenson, JM, et al. Effect of lisinopril on progression of retinopathy in normotensive people with type 1 diabetes. Lancet 1998; 351:28. 21.Effects of aspirin treatment on diabetic retinopathy. ETDRS report number 8. Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology 1991; 98:757. 22. Mogensen, CE. Prediction of clinical diabetic nephropathy in IDDM patients. Alternatives to microalbuminuria? Diabetes 1990; 39:761. 23.Mogensen, CE, Vestbo, E, Poulsen, PL, et al. Microalbuminuria and potential confounders. A review and some observations on variability of urinary albumin excretion. Diabetes Care 1995; 18:572. 24.Reichard, P, Nilsson BY, Rosenqvist U: The effect of long-term intensified insulin treatment on the development of microvascular complications of diabetes mellitus. N Engl J Med 1993; 329:304.

35. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum References Continued 25.Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998; 352:837. 26.Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group. BMJ 1998; 317:703. 27.Andersen, S, Tarnow, L, Rossing, P, et al. Renoprotective effects of angiotensin II receptor blockade in type 1 diabetic patients with diabetic nephropathy. Kidney Int 2000; 57:601. 28.Molitch, ME, DeFronzo, RA, Franz, MJ, et al. Nephropathy in diabetes. Diabetes Care 2004; 27 Suppl 1:S79. 29.Pepine, CJ, Handberg EM, Cooper-DeHoff RM, Marks RG, Kowey P, Messerli FH, Mancia G, Cangiano JL, Garcia- Barreto D, Keltai M, Erdine S, Bristol HA, Kolb HR, Bakris GL, Cohen JD, Parmley WW: A calcium antagonist vs a non-calcium antagonist hypertension treatment strategy for patients with coronary artery disease: the International Verapamil-Trandolapril study (INVEST): a randomized controlled trial. JAMA 2003; 290:2805. 30.Stamler, J, Vaccaro, O, Neaton, JD, Wentworth, D. Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial. Diabetes Care 1993; 16:434. 31.U.S. Preventive Services Task Force: Counseling to prevent tobacco use. In Guide to Clinical Preventive Services. 2nd ed. Williams Wilkins, Baltimore MD 1996. p.597. 32.Fiore, M, Bailey W, Cohen S: Smoking Cessation: Clinical Practice Guideline Number 18. Rockville, MD, U.S. Department of Health and Human Services, Public Health Service, Agency for Health Care Policy and Research, 1996. 33.Ford, ES, Malarcher, AM, Herman, WH, Aubert, RE. Diabetes mellitus and cigarette smoking: findings from the 1989 National Health Interview Survey. Diabetes Care 1994; 17:688. 34.Yudkin, JS. How can we best prolong life? Benefits of coronary risk factor reduction in non-diabetic and diabetic subjects. BMJ 1993; 306:1313.

36. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum References Continued 35.Collaborative overview of randomised 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 1994; 308:81. 36.Final report on the aspirin component of the ongoing Physicians' Health Study. Steering Committee of the Physicians' Health Study Research Group. N Engl J Med 1989; 321:129. 37.Persell, SD, Baker, DW. Aspirin use among adults with diabetes: recent trends and emerging sex disparities. Arch Intern Med 2004; 164:2492. 38.Hansson, L, Zanchetti, A, Carruthers, SG, et al, for the HOT Study Group. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: Principal results of the Hypertension Optimal Treatment (HOT) randomised trial. Lancet 1998; 351:1755. 39.Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group. BMJ 1998; 317:703. 40.Adler, AI, Stratton, IM, Neil, HA, et al. Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): prospective observational study. BMJ 2000; 321:412. 41.Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 2002; 288:2981. 42.Bridges, CB, Fukuda K, Uyeki TM, Cox NJ, Singleton JA: Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2002; 51:1. 43.Colquhoun, AJ, Nicholson KG, Botha JL, Raymond NT: Effectiveness of influenza vaccine in reducing hospital admissions in people with diabetes. Epidemiol Infect 1997; 119:335.

37. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Answers Case #1 Stacy G. is a 29 y/o male with a hx of heavy smoking who presents to your PM clinic as a new patient. He has a multitude of complaints but most concerning to you (and him for different reasons) is polyuria for several months as well as weight loss. You think he has diabetes, which of the following is appropriate to diagnose diabetes? A. Incorrect. According to the ADA an A1C should never be used to diagnose diabetes. B. Correct. Diabetes can be diagnosed with a one time measurement of random plasma glucose if two conditions are met: BG should be greater than 200 mg/dL – and- the patient has to be demonstrating classic symptoms of diabetes at that time. C. Incorrect. A 50g OGTT is indicated only for screening in pregnancy. In GDM, if the initial 50g OGTT is >140 at one hour then a confirmatory test should be performed using a 100g load OGTT. Note that in the patient above a 75g OGTT would be used since he is not being screened for GDM. The 100g OGTT is not recommended in non- pregnant adults. D.Incorrect. Though this is a correct way to diagnose diabetes, the patient has active classic symptoms and a random BG>200 will secure the diagnosis without further testing.. E. Incorrect. Though this may be true of the patient it is not c/w the ADA guidelines and innapropriate.

38. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Answers Case #2 Andy "Toughguy" W. is a 30 y/o male who you see for routine follow up of his diabetes which has been complicated by severe retinopathy w/ 20/400 vision in both eyes. He has missed several appointments and has not seen his opthalmologist. On exam you note his BP is 138/86 after being repeated on several occasions. He asks you if he should be treated for his BP and if so with what drug? A.Correct. The patient has confirmed diabetic retinopathy. Both lisinopril and captopril have been shown in RCTs to slow the progression of diabetic retinopathy. Other anti-hypertensives have not. In addition, since the patient has severe retinopathy, he likely has some early diabetic nephropathy which would be another indication for ACE-I (or ARB). B.Incorrect. There is good data for beta blocker therapy in diabetics even without CAD. No data supports BB use to curtail diabetic retinopathy. C.Incorrect. Though ALLHAT showed substantial mortality benefit and primary endpoint reduction with thiazides, no trial has examined the relationship between thiazide use and the progression of diabetic retinopathy. JNC VII would classify diabetes as a compelling indication to initiate ACE-I as first line therapy for HTN in diabetics. ADA guidelines would support HCTZ or chlorthalidone as first line therapy if the patient has uncomplicated diabetes. D.Incorrect. Large RCTs have not shown non-dihydropyridine CCBs to prevent progression of retinopathy (or CAD, nephropathy, or PVD). E.Incorrect. His blood pressure goal is 130/80. If his diabetes was complicated by nephrotic range proteinuria his goal would be 120/75

39. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Answers to Case #3 Sascha T. is a 75 y/o patient with diet controlled diabetes, HTN, HL, PVD, and smoking. He comes to clinic with a list of things he wants you to "fix". However, he said his wife told him he can't multi-task with anything in life and wants to know what one thing will give him the best chance of living to 100 years of age. Which of the following measures will result in the greatest mortality benefit. A. Incorrect. Though patient needs annual eye exam, there is little short term mortality benefit when compared to other options listed below. B. Correct. This is the number one modifiable cause of death in the US and all patients who smoke should be encouraged to quit at every visit. C. Incorrect. If the patient is already on a statin increasing the dose to get his LDL <100 is standard of care. NHANES III found that only 42% of diabetics had LDL <130. This was prior to ATP III recommended a goal of <100. We can assume that the numbers are likely no better today- and perhaps worse. D. Incorrect. Though this may be true, and the patient needs to have his feet examined at every diabetic visit- this answer just is not right! E. Incorrect. The starch in the potato will make his BG elavated. If he has proteinuria, there is some evidence to support protein restriction to 0.8g/kg/day. A large steak can easily have a daily allowance of protein in this setting.

40. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Answers to Case #4 You have just finished your rotation on diabetes management when you see one of seven patients with diabetes scheduled to see you in continuity clinic. You feel a little guilty because you have been content with A1C's in the 8-9 range. Now you pull out your ADA guidelines on screening and management for diabetes. Which of these would meet standard of care as established by the ADA? A.Incorrect. All diabetics should receive annual influenza vaccinations. You should rovide at least one lifetime pneumococcal vaccine to adults with diabetes. One-time revaccination is recommended for individuals >64 years of age if immunized before age 60 (>5 yrs prior). Repeat vaccination indicated in patients with nephrotic syndrome, CKD, and other immunocompromised states B.Incorrect. Spot microalbuminuria should be confirmed by repeat testing over a 6 month period. In addition, febrile illness, hematuria, glycosuria, heavy exercise and UTI can all cause proteinuria in normal persons C.Correct. The ADA recommends checking hemoglobin A1C twice yearly in pharmacologically stable patients with A1Cs at goal. They recommend checking quarterly in those with elevated A1Cs of those undergoing medication changes. D.Incorrect. The feet should be examined at every diabetic clinic visit and a complete and thourough foot exam should be performed annually. E.Incorrect. Though Biscuitville gravy biscuits taste great (and they are really good when you are post-call) but they should be off limits to your diabetics. You know they have already had a few anyway.

41. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Answer Question #5 Which of the following is true of diabetics? A. False. They have higher rates of smoking than nondiabetic counterparts B. False. Type 2 diabetics should have a dilated eye exam at the time of diagnosis. However, type 1 diabetics should have a dilated eye exam 5 years after diagnosis. C.False. Aspirin (75-162 mg/day) is recommended for all diabetics for secondary prevention. It should be used for primary prevention in adults 21 or older with one additional CHD risk factor. D.True. They are less likely to have an annual mammogram performed if indicated. Diabetic women have trends towards increased rates of breast cancer. Ironically, studies have shown that they are less likely than non-diabetics to receive mammograms and other routine health maintenance. E.False. When seen at Academic centers like Duke, less than half of the time diabetic medications are titrated appropriately. However, we do a good job at checking for other comorbidities (>90% screening for HTN and HL).