IN PATIENTS WITH TYPE 2 DIABETES, HYPERTENSION AND MICROALBUMINURIA MACROALBUMINURIA, Exams of Nursing

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1. Mr. Shields is a 42-year-old man with recently diagnosed type 2 diabetes. His initial blood pressure was 150/95 mm Hg. Despite urging from his physician the patient refuses pharmacologic therapy for hypertension, instead insisting on a trial of lifestyle modification. After 8 weeks his repeat blood pressure was 140/85 mm Hg. Which of the following statements is true? a) The observed blood pressure reduction if maintained over the long-term is associated with significant reduction in morbidity and mortality from cardiovascular conditions. b) The patient requires immediate pharmacologic therapy to lower blood pressure to JNC targets in order to appreciate significant change in deaths related to diabetes. c) The observed blood pressure reduction if maintained over the long-term is associated with a reduction in macro-vascular complications but not micro-vascular complications. d) The patient is at JNC target for blood pressure control in diabetics without evidence of end organ damage and should be followed closely to ensure he maintains this level of control. Pharmacological blood pressure lowering in persons with diabetes mellitus results in reductions in micro- and macro-vascular complications as well as in deaths related to diabetes mellitus and overall mortality. Correct answer: a
2. A 45 year old man presents with for follow-up evaluation of elevated blood pressures (noted on two previous examinations). On exam his blood pressure is again elevated at 150/90. Laboratory evaluation reveals a fasting glucose of 122. Which of the following is true in regards to antihypertensive drug therapy for this patient? a) Thiazide diuretics are contraindicated because they have been associated with an increased risk of developing diabetes mellitus. b) B-blockers are contraindicated because they have been associated with an increased risk of developing diabetes mellitus. c) ACE inhibitors and angiogenesis receptor blockers may decrease this patient’s risk of developing diabetes mellitus. d) Calcium channel blockers are contraindicated in metabolic syndrome. Both thiazides and beta-blockers have been linked to an increased risk of developing diabetes in persons initially free of diabetes who are treated with these agents over the long-term. ACE inhibitors and ARBs have been shown in several studies to reduce the risk of new diabetes cases by ~ 30%. ACE inhibitors improve insulin sensitivity and, in some studies, have been associated with increased risk of hypoglycemia, but typically do not affect fasting glucose levels. Relative to beta-blockers, angiotensin receptor blockers have a reduced risk of diabetes development in patients treated for hypertension (LIFE Study). ACE inhibitors provide their greatest protection relative to calcium antagonists and other agents in the setting of heavy proteinuria. ACE inhibitors do not appear to preserve kidney function better than calcium antagonists in diabetics without heavy proteinuria (ABCD study). Angiotensin receptor blockers protect the kidney better (proteinuria, ESRD incidence, doubling of serum creatinine) than calcium antagonist-based regimens (IDNT study). There is no evidence that calcium channel blocker adversely affect patients with the metabolic syndrome. Correct answer: c

3. JW is a 56-year-old woman with diabetes mellitus for the last 10 years. Her glycemic control has been excellent since her diagnosis. Her body mass index (BMI) is 34 kg/m2. Though she follows a diabetic diet, her sodium intake remains relatively unrestricted. Blood pressure control has been poor ranging from 158 – 196 mm Hg systolic and between 70 – 92 mm Hg diastolic. Her current BP is 160/84 mm Hg. At present she takes naproxen (an NSAID) for joint aches, hydrochlorothiazide 25 mg once daily, and quinapril (an ACEI) 40 mg/d. Her estimated glomerular filtration rate is 40 ml/min/1.73 m2. At this point you would a) Discontinue naproxen therapy. b) Discontinue naproxen therapy and increase hydrochlorothiazide to 50 milligrams once daily. c) Discontinue naproxen therapy and hydrochlorothiazide; begin furosemide 40 milligrams once daily. d) Discontinue naproxen therapy and hydrochlorothiazide and begin metolazone 5 milligrams once daily. Unrestricted dietary sodium intake antagonizes the BP lowering effect of most antihypertensive drugs, especially agents with their primary locus of action on the renin- angiotensin-system (ACE inhibitors, beta blockers, and angiotensin receptor blockers). Thus, inadequate restriction of dietary sodium is a very plausible culprit in this patient poor blood pressure control. NSAID therapy (not aspirin), including the new COX- inhibitors, can cause salt and water retention and antagonize blood pressure lowering of antihypertensive agents. Furosemide is a very short-acting diuretic and is not prescribed optimally when used once daily – bid – tid dosing is required for a sustained reduction in intravascular volume. The level of kidney function determines the most appropriate diuretic. Until the estimated GFR descends to the mid to low 40’s, thiazide diuretics are usually better choices than furosemide for BP lowering. Metolazaone, a very long-acting thiazide like diuretic, also works well in persons with reduced kidney function and has the added bonus of working well even in persons with good kidney function. Obesity has also been linked to poor BP lowering responsiveness to antihypertensive drug therapy. Therefore, it would be appropriate to discontinue the NSAID and modify the choice of diuretic. It would also be important to have the patient restrict her sodium intake. Correct answer: d
4. All of the following patients require referral to an ophthalmologist except? a) A patient with newly diagnosed Type 1 diabetes b) A patient with newly diagnosed Type 2 diabetes c) A patient with long standing Type 1 diabetes d) A patient with long standing Type 2 diabetes The ADA Clinical Practice Guidelines recommend ophthalmologic evaluation for all Type 1 diabetes who have had diabetes for at least 3 years and in all patients with Type 2 diabetes. A major difference between type 1 and type 2 diabetes mellitus is that many persons with type 2 diabetes have had the disease for many years prior to diagnosis Correct answer: a
5. Mrs. X is a 35-year-old African American woman who presents to the office with complaints of polyuria, polydipsia and intermittent blurred vision. She is overweight and states she was never able to lose the weight she gained with her pregnancy. Her son, now age 3, weighed 9 pounds 4 ounces at birth. Which of the following tests could be used to diagnose diabetes in Mrs. X?

a) Fasting glucose of 140 b) 1-hour post-prandial glucose of 190 mg/dl c) A random glucose of 165 d) Hgb A1C of 10.0% The revised criteria for diabetes mellitus include either 1) a casual glucose of

200 mg/dl repeated on a subsequent day or 2) a casual glucose of > 200 mg/dl in a patient with symptoms of diabetes (polyuria, polydipsia, and unexplained weight loss) or 3) a fasting (no caloric intake for 8 hours) glucose of > 126 mg/dl confirmed on a subsequent day. Normal fasting glucose is < 110 mg/dl. Fasting glucose of 110 – 125 mm Hg are considered impaired fasting glucose. In its early stages, diabetes is a post-prandial rather than a fasting disease. That is, fasting glucose levels will often be normal despite post- prandial elevations in glucose levels. Although hemoglobin A1C is elevated in many patients with diabetes and is used to document metabolic control, there are no diagnostic criteria available for diabetes using this measure. Thus, until the diagnosis of diabetes is made, there is no clear rationale for ordering hemoglobin A1C levels. This test provides an integrated look at glucose levels over the previous 2 – 3 months. Nevertheless, it is very likely that a hemoglobin A1C of 8.0% does actually represent poor glycemic control and clinical diabetes. A 1-hour postprandial glucose is not diagnostic of diabetes mellitus. Correct answer: a

6. Mrs. X returns to the office to discuss the results of her blood work. The fasting glucose done last visit was 140 mg/dl. Her fasting glucose today is 160 mg/dl. During your discussion of her laboratory results Mrs. X. relates trying to diet and says that she lost five pounds since her last visit. She still, however, complains of polyuria and polydipsia. After a lengthy discussion the patient elects to begin medical therapy. Which of the following hypoglycemic drugs has been associated with weight gain? a) Glargine Insulin b) Sulfonylureas c) Thiazolidinediones d) All of the above Metformin has been associated with weight loss. Both sulfonylureas and insulin have been associated with weight gain. TZDs have also been associated with weight gain and edema however, redistribution of fat has been noted away from the visceral depots to the subcutaneous region and peripheral depots. Though she has lost 5 pounds, one concern is that this may not solely reflect her dietary efforts but rather may be related to her persistently catabolic state attributable to unabated hyperglycemia. Correct answer: d
7. Mrs. Miller is a 25-year African American woman who was diagnosed to have Type 2 diabetes at her last office visit two months ago. At that time, her blood pressure was 144/86. She saw a dietician four weeks ago and began a low sodium ADA diet. Blood pressure at that time was reported to be 140/86. Today her blood pressure is 134/84. Which of the following is an appropriate treatment plan? a) This is an acceptable blood pressure; however her blood pressure should be closely monitored. b) The patient should now be started on a thiazide diuretic to achieve a target blood pressure of 130/ c) Blood pressure should now be measured next visit to confirm the diagnosis of hypertension. d) The patient should be started on an ACEI to achieve a target blood pressure of 130/

e) It is reasonable to give this patient a trial of life style modification prior to initiating pharmacologic therapy. This patient’s hypertension has been confirmed on three separate office visits thus answer c is incorrect. Before initiating any kind of treatment plan for a patient with diabetes it is important to define target goals for blood pressure control. Although 140/90 is an acceptable goal for the general population, patients with diabetes have an increased risk of adverse outcomes with even mildly elevated blood pressures. A target BP level of <130/80 mm Hg is recommended (JNC VII, ADA, and ISHIB) for patients with diabetes and no evidence of renal insufficiency or proteinuria. Appropriate treatment for blood pressures of 130-139/80-89 includes lifestyle modification such as weight reduction, reduction in dietary sodium, adopting the DASH eating plan, increasing physical activity, and moderating alcohol consumption. These interventions can decrease systolic blood pressure from 2-20 mmHg (JNC VII). Patients with blood pressures that are consistently above 130/80 mm Hg despite lifestyle modification should also be started on pharmacologic treatment. Correct answer: e

8. Which of the following medications has not been associated with potassium elevation in patients with diabetes? a) Thiazide diuretic b) NSAID c) ACE inhibitor d) ARB ACE inhibitors, angiotensin receptor blockers, and aldosterone antagonists all can increase serum potassium. There is some evidence that angiotensin receptor blockers increase potassium less than ACE inhibitors do. Both thiazide diuretic and loop diuretics may cause hypokalemia and are not known to cause hyperkalemia under normal circumstances. Calcium channel blockers are unlikely to affect potassium homeostasis. Correct answer: a
9. Mrs. Miller returns to the office to discuss her lipid profile. Her fasting LDL cholesterol is 110, HDL is 20, and triglycerides are 250. Which of the following is true? a) Triglycerides are elevated, HDL is normal, and her LDL is at goal levels. b) Triglycerides are normal, HDL is low, and her LDL is above goal levels. c) Triglycerides are elevated, HDL is low, and her LDL is above goal levels. d) Triglycerides are normal, HDL is normal, and her LDL is below goal levels. ATP III recommended aggressive lipid lowering therapy for patients with an absolute 10 year risk of clinical coronary disease of > 20%. Patients with diabetes are considered to have a “coronary heart disease equivalent.” The NCEP/ATP III recommends a target LDL cholesterol of less than 100 for all patients with diabetes whether or not clinical coronary disease is present. This is the same LDL-C goal for persons with known coronary heart disease. Triglyceride levels should be less than 150 mg/dl. Average HDL level for a middle-aged woman is ~ 55mg/dl, so her HDL is low. In addition, and an HDL level < is considered to be an independent risk factor for coronary artery disease.

Correct Answer: c

10. Which of the following medications should not be prescribed during pregnancy? a) ACE inhibitors b) Metformin c) Acarbose d) Insulin Pregnancy in diabetic patients should be planned. Discussions with patients should include planning for pregnancy and adjustment of medication to minimize risks to the fetus while maintaining the health of the mother. ACE inhibitors are category C in the first trimester (maternal benefit may outweigh fetal risk in certain situations), but category D in later pregnancy, and should be discontinued prior to pregnancy. Statins are pregnancy category X and should be discontinued prior to conception or as soon as the woman is found to be pregnant. Correct answer: a
11. Mrs. X’s HgbA1C at the time her pregnancy is diagnosed is 4.8% Which of the following statements are true? a) Mrs. X is no longer a diabetic b) Mrs. X has an increased risk for delivering a diabetic infant. c) Mrs. X’ baby has increased risk likelihood or having congenital malformations. d) Mrs. X’s baby has a no increased likelihood of having congenital malformations. The majority of pregnancies in women with diabetes are unplanned. This is very unfortunate because maternal hyperglycemia is associated with an increased rate of fetal malformations. All women with diabetes and childbearing potential should be educated about the need for good glucose control before pregnancy and instructed in effective contraception at all times unless the patient is in good metabolic control and actively trying to conceive. Hemoglobin A1C should be normal or as close to normal as possible in an individual before conception is attempted. Metformin and acarbose are pregnancy category B CATEGORY INTERPRETATION A CONTROLLED STUDIES SHOW NO RISK. Adequate, well-controlled studies in pregnant women have failed to demonstrate a risk to the fetus in any trimester of pregnancy. B NO EVIDENCE OF RISK IN HUMANS. Adequate, well-controlled studies in pregnant women have not shown increased risk of fetal abnormalities despite adverse findings in animals, or, in the absence of adequate human studies, animal studies show no fetal risk. The chance of fetal harm is remote, but remains a possibility. C RISK CANNOT BE RULED OUT. Adequate, well-controlled human studies are lacking, and animal studies have shown a risk to the fetus or are lacking as well. There is a chance of fetal harm if the drug is administered during pregnancy; but the potential benefits may outweigh the potential risks. D POSITIVE EVIDENCE OF RISK. Studies in humans, or investigational or post-

marketing data, have demonstrated fetal risk. Nevertheless, potential benefits from the use of the drug may outweigh the potential risk. For example, the drug may be acceptable if needed in a life-threatening situation or serious disease for which safer drugs cannot be used or are ineffective. X CONTRAINDICATED IN PREGNANCY. Studies in animals or humans, or investigational or post-marketing reports, have demonstrated positive evidence of fetal abnormalities or risks which clearly outweighs any possible benefit to the patient. NA = None assigned Correct answer: d

12. A 40 year old woman with diet controlled Type 2 diabetes is seen for evaluation. After completing your history and physical examination and reviewing previous records you feel confidant the patient has no evidence of end-organ damage. Laboratory studies reveal a Hgb A1c of 6.5% and LDL cholesterol to be 120. Which of the following would you recommend? a) Begin clopidogrel to prevent cardiovascular events. b) Begin 325 milligrams ASA daily to decrease cardiovascular events. c) Begin aspirin and lovastatin d) Begin lovastatin and clopidogrel to prevent cardiovascular events. Aspirin (75-325 mg/d) is recommended in all adult patients with diabetes and macrovascular disease. It should be considered in patients older than forty with diabetes and possibly as young as thirty with additional cardiovascular risk factors. Aspirin is contraindicated in patients less than 21 years of age secondary to concerns about Reyes Syndrome. Clopidogrel should be considered in patients who are aspirin intolerant. Correct answer: c
13. Mrs. X’s brother, age 50, presents to your office for an initial evaluation. She is asymptomatic. She is a large woman. Her weight is 189 and her calculated BMI is 30. Waist circumference is 38 inches. Blood pressure is 135/88 mm Hg. Fasting glucose is 112 mg/dl, triglycerides are 175 mg/dl, LDL is 130 mg/dl and HDL is 46 mg/dl. She wants to know if she has diabetes and is she at increased risk of a heart attack? At this point you would a) Initiate life style modification b) Initiate life style modification and begin ASA daily c) Start the patient on pharmacologic therapy for hypertension as her target BP is 130/ d) Diagnose the patient to have borderline Type 2 diabetes and begin an aggressive program of weight loss and exercise. This patient appears to have the “metabolic syndrome.” Factors characteristic of the metabolic syndrome include abdominal obesity (waist circumference of >40 in men and

35 in women), atherogenic dyslipidemia (triglycerides >150, low HDL <40 in men and <40 in women), elevated blood pressure (130-149/85-89), and insulin resistance (fasting glucose 110-125). Although the metabolic syndrome is not considered a coronary heart disease equivalent it is associated with an increase risk for coronary heart disease. Furthermore, this patient is at increased risk for diabetes. At this point life style modification is imperative. Exercise and weight loss have been shown to decrease the likelihood of developing diabetes mellitus. It is important to note although this patient’s

fasting glucose is in the impaired fasting glucose range and is not diagnostic of diabetes mellitus. However, after an oral glucose tolerance test, she may be found to actually have diabetes mellitus. Thus, she might have diabetes and would be an excellent candidate for oral glucose tolerance testing. Furthermore, diagnosing diabetes would modify targets for blood pressure and lipids. Correct answer: b

14. A 40 year old man with Type 2 diabetes wants to begin exercising. He has never been athletic and is interested in something easy and not too vigorous. After a thorough history and physical examination you find Mr. X to be mildly overweight (BMI 28) but otherwise healthy. His blood pressure is 128/80. HgbA1C is 6.9. At this time you would advise Mr. X to a) Start slow and gradually advance to a modest exercise program. b) Order a 12 lead EKG, stress test and echocardiogram. c) Order an exercise stress test. d) Order a cardiac calcium scan. There are no specific recommendations advocating the use of screening 12 lead EKGs in asymptomatic diabetics. The ADA Clinical Practice Guidelines states candidates for screening exercise stress testing include patients with either 1) atypical cardiac symptoms, 2) an abnormal resting ECG, 3) a history or peripheral or carotid occlusive disease, 4) sedentary lifestyle age >35 and plans to begin a vigorous exercise program or 5) those with two or more risk factors noted above. There is, however, no current evidence that exercise testing in asymptomatic patients with risk factors improves prognosis. It is advisable for sedentary patients to begin their exercise program slowly before advancing to a vigorous program. If Mr. X wanted to proceed with a vigorous program, a resting EKG and an exercise stress test are indicated. Correct answer: a
15. Mr. X started walking every night after dinner. Recently he noticed some chest heaviness after walking for 2-3 minutes. He denies frank pain but states now unable to finish his walk. At this point you would a) Schedule a exercise stress test b) Obtain a lipid profile. c) Initiate aspirin @ 325 mg per day d) Initiate aspirin @ 325 mg per day, order a lipid profile and schedule a pharmacologic stress test. Mr. X has a classic history of angina pectoris. It would be appropriate to begin aspirin if this was not already done. In addition, assessment of lipids is appropriate in all diabetics and in particular in patients with vascular disease. An exercise stress test is may not achieve a high enough degree of sensitivity if the patient cannot exercise. A pharmacological stress test would be an acceptable alternative. Correct answer: d
16. Mr. Phillips is a 65-year-old white man with a three-year history of Type 2 diabetes. He returns to the office for re-evaluation of his blood pressure. Three months ago his blood pressure was found to be 158/80. Today he is asymptomatic. He is currently following an 1800-calorie ADA

diet. He has finally achieved ideal body weight. His last HgbA1C was 7.0%. Today his blood pressure is 136/80. Which of the following is true? a) This patient likely has white coat hypertension. No additional therapy is needed b) It is likely that this patient will require at least two drugs of different classes to adequately control his blood pressure. c) This patient is doing well and should be encouraged to continue his present dietary program. Follow-up should be arranged in 3 months. d) This patient should be started on an ACE inhibitor to achieve a blood pressure of less than 130/80. Patients with diabetes are at increased risk for coronary events. Part of this risk is related to associated cardiovascular risk factors such as hypertension. Diabetics with hypertension have twice the risk of cardiovascular disease when compared with non- diabetic with hypertension. (Clinical Practice Recommendations 2005) Lifestyle modification should be recommended for all patients with diabetes and elevated blood pressure. This should include a low-sodium (< 2g/d), low-saturated fat (< 10% to total daily fat intake), low-cholesterol diet. In addition, patients should be strongly counseled to quit smoking restrict alcohol consumptions, achieve ideal body weight and participate in regular aerobic exercise. Multi-drug therapy is the rule to attain a goal blood pressure when the blood pressure is above 15/10 mmHg above the target goal blood pressure. The target blood pressure for diabetic patients is less than 130/80(JNC VII). One should not settle for suboptimal control. ACE inhibitors or angiotensin receptor blockers are the antihypertensive drugs of choice in persons with diabetes. Correct answer: d

17. Mr. Johnson has long standing diabetes. His doctor recently moved out-of-state and he presents to you for evaluation and treatment of his hypertension. Despite taking enalapril 20 mg bid and amlodipine 10 mg q day his blood pressure remains 148/90. His EGFR is 58. Which of the following would not be recommended? a) Obtain a spot urine for microalbumin b) Obtain a 24 hour urine for protein and creatinine determination c) Add a thiazide diuretic or metolazone. d) Refill all current medications and wait for blood pressure to fall below goal. Modest decreases in systolic blood pressure are associated with significant decreases in any complications related to diabetes. Decreasing systolic blood pressure in patients with Type 2 diabetes by 10 mmHg is associated with a 12% reduction for any complication related to diabetes. Achieving target goals for hypertension are important and one should not settle for near goals despite using multiple medications. Nevertheless, target goals in diabetics are different for patients with and without evidence of renal disease. The target goal for blood pressure in diabetics with proteinuria > 1 gram/24 hours (spot urine protein/ creat ratio > 0.66) is < 125/75 mm Hg. Thus testing for the presence of protinuria is indicated in this patient. However, current recommendations are to check spot urines rather than 24-hour urines to determine protein content. The urinary protein/creatinine ratio is a good test when the total urinary protein excretion is > ` 500 mg/day. Another alternative would be to measure the albumin:creatinine ratio on a spot urine. First morning void urines are the best, however, random urines are acceptable for spot albumin or protein measurements.

Most patients with diabetes and hypertension require multiple medications to control blood pressure. Diuretics are essential to the multi-drug “cocktail” when > 2 antihypertensive medications are prescribed. The correct answer is d.

18. Mrs. Jones is a 50-year-old African American woman who presents for assistance with weight loss. She has always been overweight but gained 20 pounds after her husband died 3 months ago. She states she sits at home drinking lemonade and looking at the family album. Past medical history is unremarkable. On review of systems the patient is able to walk a flight of stairs without chest pain, pressure or shortness of breath. However, she does complain of having to go to the bathroom often and also of urinary incontinence which she attributes to having children. Her largest baby was 9 pounds. She does not smoke. Family history is positive for diabetes in her two sisters and mother, hypertension and coronary artery disease. Mrs. Jones weighs 180 lbs. She is 5’4”. Blood pressure is 140/90 and pulse is 80. The remainder of the physical examination is within normal limits except for trace pedal edema. Laboratory analysis reveals a random glucose of 145 mg/dl, total cholesterol 210 mg/dl, LDL 125 mg/dl, HDL 50, mg/dl and TG 175 mg/dl. At this point you would a) Educate the patient in lifestyle modification, and reevaluate blood pressure and lipids in 6 weeks b) Measure fasting glucose, serum TSH level, electrolytes, BUN and creatinine, refer patient to a dietician c) Educate the patient in lifestyle modification, measure HgbA1c, serum TSH level, electrolytes, BUN and creatinine and arrange follow-up when labs are available. d) Educate the patient in lifestyle modification, measure fasting glucose, serum TSH level, electrolytes, BUN and creatinine and reevaluate in one month This patient very likely has Type 2 diabetes mellitus. She has polyuria and polydipsia and an elevated fasting glucose. (Normal fasting glucose < 126.) However, she does not fit the strict definition of diabetes because she does not have symptoms of diabetes and a casual glucose of >200. Furthermore, although her fasting glucose > 126 it has not been confirmed on a subsequent visit. It is important make the diagnosis of diabetes because it dictates specific target goals for both serum lipid levels and blood pressure. The diagnosis can be confirmed by repeat measurement of her fasting glucose on another day. Another potential option would be to perform oral glucose tolerance testing. According to the NCEP/ATP III guidelines, patients with elevated lipids should be evaluated for secondary causes of dyslipidemia including diabetes. Other causes of secondary dyslipidemia include hypothyroidism, chronic renal failure and obstructive liver disease. Therefore, measure of TSH and renal function would indeed be appropriate for this patient. Consultation with a dietician is recommended as part of a prescription for “therapeutic lifestyle modification.” Therapeutic lifestyle modification is appropriate for both hypertension and dyslipidemia. However, according to the NCEP/ATP III guidelines, lifestyle modification for 6 weeks is appropriate. This should be followed by reevaluation of LDL-C and either, intensification of therapeutic lifestyle changes (TLC), or initiation of medical therapy. In addition, if this patient is in fact diagnosed with diabetes (confirmation of elevated fasting glucose on a subsequent visit,) then the patient should be treated with both TLC and pharmacologic therapy to achieve a blood pressure of < 130/80 mm Hg. Lifestyle modification alone is only recommended for diabetics with blood pressure of 130-139/80-89 and only for a maximum of three months. The target

goals outlined in NCEP/ATP III and JNC VI for patients with diabetics are recommended to modify the elevated risk for cardiovascular disease associated with diabetes. Correct answer: d

19. Mr. Reynolds has longstanding type 2 diabetes. Urine for microalbuminuria demonstrated 380 micrograms per milligram of creatinine. Today his blood pressure is 166/92 and his creatinine is 1.6 mg/dl. Which of the following statements are true? a) Diuretic therapy is indicated to reduce albuminuria. b) Reduction of blood pressure is important to capture the reversible component of microalbuminuria. c) Initiation of an ARB will delay the progression of nephropathy d) Treatment with an ACE will delay the progression to microalbuminuria ACE inhibitors slow progression of diabetic nephropathy in both Type 1 and Type 2 diabetes. ACE inhibitors decrease glomerular capillary pressure by decreasing arterial pressure and selectively dilating the efferent glomerular more so than the afferent arteriole. ARBS have recently been shown to decrease progression of diabetic nephropathy in persons with type 2 diabetes mellitus. ARB's do have a stronger database that ACE inhibitors supporting their use in diabetic nephropathy, especially heavy (more than microalbuminuria) proteinuria patients. There are no long-term studies of the effect of alpha-blockers, loop diuretics or centrally acting agents on the long-term complications of diabetics. Nevertheless, the overwhelming evidence is in favor of obtaining blood pressure control as an effective means for preventing micro- and macro-vascular complications. These drugs should be used as adjunctive therapy to better studied drugs in persons with diabetes such angiotensin receptor blockers, ACE inhibitors, calcium antagonists, and thiazide diuretics. Diuretics are also important drugs when attempting to control blood pressure in complex (>2) drug regimens to combat the expansion of extracellular fluid volume that antagonizes blood pressure lowering with many antihypertensive agents. Dihydropyridine calcium blockers selectively dilate afferent arterioles and can result in increase in intraglomerular pressures. For this reason they are not favored in the management of hypertension in diabetics with severe reductions in kidney function or with proteinuria – unless there is simultaneous use of an ARB or an ACE. The RENAAL study demonstrated the safety of adding a dihydropyridine calcium antagonist to losartan, an ARB, in person with diabetic nephropathy and heavy proteinuria. There was no diminution of the effect of the ARB on preservation of kidney function when this combination was used. Though rate-lowering calcium antagonists such as verapamil and diltiazem theoretically cause less preferential dilation of the afferent arteriole, there are no long-term clinical studies showing their impact on clinical outcomes such as doubling of serum creatinine or development of ESRD. This patient already has microalbuminuria. Therefore the correct answer is Correct answer: c
20. Mr. Reynolds is a 40 year old man. He was started on hydrochlorothiazide and an ACE inhibitor three weeks ago. He returns to clinic four weeks later. At this visit his blood pressure is 150/ mm Hg (down from 160/90). He is however, complaining of some dizziness, especially early in the morning that comes and goes throughout the remainder of the day. At this point you would you would…

a) Discontinue his antihypertensive medication and reevaluate his blood pressure in one month. b) Reassure him. c) Discontinue the diuretic but continue the ACE inhibitor. d) Evaluate him for pheochromocytoma. Overall, it is often very difficult to control blood pressure in diabetics with nephropathy. It also takes 4 - 6 or sometimes 8 weeks to see the maximal blood pressure lowering effect when a drug is prescribed. He has only been on his dual therapy for a few weeks. Given the height of his BP elevation above his goal BP (<130/80 mm Hg) you can up-titrate his medication, add another drug, or watch his BP on his current dose for a few more weeks. It is very likely that he will need another second drug; yet gradually lowering blood pressure will minimize side effects as blood pressure is reduced. On the other hand, at eight weeks it is unlikely that his BP will have fallen to goal with either watching him for a few more weeks or up titrating his medication dose. This is a judgment call –however, there is no immediate payoff in lowering BP too rapidly. If it takes you three or four months to get his BP to goal, you shouldn't worry. Thus, reassuring him is fine. Patients frequently require multiple medications to achieve blood pressure targets. Generally a diuretic should be added to an ACE or ARB prior to adding a calcium blocker, except where contraindicated. Diabetic patients should always have orthostatic blood pressure changes measured given their propensity to autonomic neuropathy. There is no reason to stop his current medication or to evaluate him for pheochromocytoma. His dizziness might be related to his blood pressure elevation, to the fall in his blood pressure, or his medication. Correct answer: b

21. Mr. Santiago is a 40-year old man with a ten-year history of diabetes mellitus, hypertension and hypercholesterolemia and recently diagnosed coronary heart disease. His medications include metformin, a statin, metoprolol, chlorthalidone, and ACE inhibitor. He saw the ophthalmologist you referred him to last week and has the consultative report for you to see. According to the ophthalmologist he has “non-proliferative retinopathy” with evidence of dot and blot hemorrhages. Which of the following medications are contraindicated in Mr. Santiago? a) Aspirin b) Clopidorgrel c) Sildenafil d) None of the above The Early Treatment of Diabetic Retinopathy Study (ETDRS) investigated whether aspirin (650 mg/day) could retard the progression of retinopathy. After examining progression of retinopathy, development of vitreous hemorrhage, or duration of vitreous hemorrhage, aspirin was shown to have no effect on retinopathy. There are no ocular contraindications to the use of aspirin when required for cardiovascular disease or other medical indications. Correct answer: d
22. A 64 year old patient has Type 2 Diabetes and microalbuminuria. Which of the following interventions will reduce urinary albumin excretion? a) Increased sodium intake b) Use of an ACE inhibitor c) Reduction in potassium intake d) Enhanced fluid intake e) All of the above ACE inhibitors and ARB's reduce urinary protein excretion. However, they cannot maximally reduce urinary albumin excretion in the setting of unrestricted sodium intake. Decreased sodium intake will act with ACE and ARBS to reduce proteinuria. Increased

adiposity elevates urinary protein excretion. Decreasing adiposity will decrease urinary albumin excretion. Therefore, Glycemic control is well established as an effective strategy to reduce urinary protein excretion. Other effective strategies to reduce proteinuria include smoking cessation and lowering of blood pressure. Correct answer: b

23. A patient presents for follow-up evaluation. She is 45 years old and has long standing Type 2 diabetes, hypertension and hyperlipidemia. Her blood pressure today is 160/92 mm Hg a level that is similar to previously documented clinical visits. Her calculated BMI is 30 kg/m2. Fasting glucose is 280 mg/dl. Her hemoglobin A1C is 11.8%. Her lipid profile is: LDL cholesterol is 145 mg/dl, HDL cholesterol is 44 mg/dl and triglycerides are 300. At this point you would a) Begin lifestyle modification, and initiate treatment for diabetes with metformin. b) Begin lifestyle modification, pharmacologic treatment for hypertension, metformin, a thiazolidinedione, a statin and aspirin. c) Begin lifestyle modification, pharmacologic treatment for hypertension, sulfonyluria and a statin. d) First control her diabetes and then discuss treatment for her hypertension and hyperlipidemia. According to JNC VII, all patients with diabetes and Stage 2 hypertension should be started on pharmacologic therapy. Furthermore, although the ADA practice Guidelines recommends repeat blood pressure measurement in one month to confirm hypertension, they recommend immediate pharmacologic treatment for all patient with blood pressures >160/100 without waiting an additional month to confirm. Lifestyle modification should also be provided concurrently. The NCEP/ATP III guidelines recommend lifestyle modification for 6 weeks after which response to therapy should be evaluated. In patients with coronary heart disease (CH) or (CHD) equivalents including diabetes, intensive lifestyle therapy and maximal control of other risk factors should be started. The most recent ADA practice guidelines 2005 recommend patients over 40 with total cholesterol > 135 be started on a statin to achieve an LDL reduction of 30-40% regardless of baseline LDL. The primary goal is an LDL of < 100 When choosing treatment regimens for patients with diabetes it is important to consider the effects of treatment on weight. Sulfonylureas are associated with weight gain. In the absence of contraindications, it is therefore reasonable to start patients with BMI > 25 who have moderate hyperglycemia (fasting glucose 140 to <200) on metformin as it is not associated with significant weight gain. Finally patients with moderate to severe fasting hyperglycemia will likely require two agents to achieve euglycemia. Correct answer: b
24. Mrs. Z comes in for evaluation of her diabetes. You have not seen her for several years. She states her glucoses are very well controlled now on BID NPH insulin. Her glucose flow sheets confirm this. In fact, her glucose levels are now all under 160 mg/dl whereas chart review indicates her glucose levels in the past had always been well above 250 mg/dl. There has been no significant change in dietary intake or physical activity in the last several years. She now experiences hypoglycemic episodes 2 to 3 times per week whereas this rarely ever occurred prior to 1 year ago. PMH is remarkable for longstanding poorly controlled hypertension, hyperlipidemia and smoking. Today Mrs. Z weighs 239 pounds. (Previous weight 180). Her blood pressure is 188/100 mm Hg. Her fasting glucose is 145 mg/dl. Which of the following lab panels are likely to belong to Mrs. Z?

a) Random glucose 160, HgbA1c 7.0%, Na 138, K 5.0, Cl 100, bicarb CO2 18, creat 1. b) Random glucose 220, HgbA1c 10.0%, Na 138, K 5.0, Cl 100, bicarb CO2 18, creat 1. c) Random glucose 160, HgbA1c 7.0%, Na 138, K 5.0, Cl 104, bicarb CO2 24, creat 0. d) Random glucose 220, HgbA1c 10.0%, Na 138, K 5.0, Cl 100, bicarb CO2 18, creat. As patients develop renal insufficiency it is not uncommon to see glycemic control improve. The kidney clears insulin and therefore insulin remains in the circulation longer. Although it is possible Mrs. Z is finally following all your recommendations the fact that her weight has not decreased but rather increased suggests that insulin sensitivity is unlikely to have improved. Finally, Mrs. Z may be lying but is more likely that she is developing renal insufficiency. Persons without diabetes who have chronic kidney disease appear to have an increased risk of developing diabetes mellitus. Correct answer: a

25. In patients with Type 2 diabetes receiving statins for lipid lowering, which of the following is to be expected? a) Reduction in proteinuria b) Reduction in stroke risk c) Enhanced erectile function d) Improved glycemic control Statins reduce both coronary and stroke risk. Unfortunately they have not been shown to reduce the likelihood of erectile dysfunction in patients with established ED or to enhance erectile function. Although theoretically they might since they improve endothelial function. Also, statins might reduce urinary albumin excretion also because of their ability to improve endothelial function. One study suggested that statins lowered the risk of future diabetes but no studies have shown improved glycemic control with statins. Correct answer: b
26. Which of the following blood pressure phenotypes is most common in patients with diabetes mellitus? a) Systolic >140 and diastolic >90 with normal pulse pressure b) Systolic pressure 130-140, Diastolic <80, pulse pressure > c) Systolic > 140, diastolic blood pressure 70-90, pulse pressure > 40 d) None of the above are correct Persons with diabetes mellitus have predominantly SBP elevations compared to persons without diabetes DBP levels are either the same or slightly lower than non-diabetics. Thus, pulse pressure, the difference between SBP and DBP, is greater in persons with diabetes than in non-diabetics. Diabetes represents a premature aging of the vascular system with arterial stiffening and reduced arterial compliance that occurs years earlier than in non-diabetics. Correct answer: c
27. RR is a 47-year-old white man with fasting plasma glucose levels consistently in the 115 - 125 mg/dl range. He weighs 230 pounds and is 5' 8" tall. At this point you would a) Inform the patient he has borderline diabetes and refer him to a dietician for instruction in a 1500 calorie ADA diet. b) Inform the patient he has borderline diabetes and initiate treatment with metformin

c) Inform the patient he has borderline diabetes and initiate treatment with a sulfonylurea d) Inform the patient he has impaired glucose tolerance and advise him to begin a 1500 calorie ADFA diet. e) Inform the patient he has impaired fasting glucose and advise lifestyle modification and strongly consider referring him or an oral glucose tolerance test Correct answer: Normal fasting glucose is < 100 mg/dl, impaired fasting glucose is 100-125 and diabetes is diagnosed when glucose is persistently > 126 mg/dl. Lifestyle modifications including appropriate physical activity, weight loss, and calorie restriction should be encouraged to promote weight loss to a healthier body weight. Correct answer: e PD is a 32-year-old woman who is in her 20th^ week of pregnancy with her first child. She has not had any prenatal visits. Her fasting glucose levels, however, have been at the upper limits of normal (~ 95 mg/dl). A 75 gram oral glucose tolerance test is obtained after a 12 hour fast. Her fasting plasma glucose was 128 mg/dl and her 1-hour post-glucose load plasma glucose was 188 mg/dl and her 2- hour post-load glucose was 160 mg/dl. Prior to this pregnancy her fasting glucose values were all normal at her annual physicals.

28. How would you classify her OGTT?

a) She has normal glucose tolerance

b) She has gestational diabetes

c) She has developed type 2 diabetes mellitus

d) None of the above

Correct answer: According to the ADA 2005 guideline, “gestational diabetes mellitus (GMD) is defined as any degree of glucose intolerance with onset or first recognition during pregnancy. The definition applies regardless of whether insulin or only diet modification is used for treatment or whether the condition persists after pregnancy. It does not exclude the possible that unrecognized glucose intolerance may have antedated or begun concomitantly with the pregnancy.” Normal fasting plasma glucose is < 95 mg/dl, 1-hour post-load glucose should be < 180 mg/dl, and 2-hour post-load glucose should be < 155 mg/dl. When two or more of these values are either met or exceeded in a woman where the first evidence of impaired glucose tolerance is occurring during this pregnancy, then the diagnosis of gestational diabetes mellitus is made. Glucose tolerance typically deteriorates during the third trimester of pregnancy. Women, who are not at low-risk for GDM, should be screened at the first prenatal visit and retested at 24 - 28 weeks of gestation. Women at low risk of GDM including women who are < 25 years, are of normal body weight, have no first degree relative with DM, no history of abnormal glucose tolerance or poor obstetrical outcome and women who are not members of a racial or ethnic group with high diabetes prevalence do not require testing for gestational diabetes. Given that this patient is Hispanic, she should have been screened at her first prenatal visit. Correct answer: b

29. Which of the following is not true regarding gestational diabetes mellitus? a) GDM is a risk factor for perinatal morbidity and mortality b) GDM is a risk factor for development of diabetes mellitus later in life c) GDM is a risk factor for prolonged gestation d) GDM is a risk factor for cesarean section GDM is a risk factor for all of the above. GDM accounts for ~ 90% of the diabetes encountered during pregnancy. 6-weeks post delivery the mother should be reclassified

according to standard criteria - normal, impaired fasting glucose, impaired glucose tolerance, or diabetes mellitus. Correct answer: c

30. Which of the following patients should be screened for diabetes? a) A 35 year old Native American with BMI of 22 kg/m b) A 30 year white woman who is physically inactive with a BMI of 34 kg/m c) A 40 year old African American woman with BMI of 24 d) A 28 year old African American man who is physically active and has a BMI of 28 Testing for diabetes should be considered in all individuals at age 45 years and above, particularly in those with a BMI >25 kg/m2 and if normal should be repeated a 3 year intervals. Testing should be considered at a younger age in individuals who area overweight (BMI > 25 kg/m2 and have additional risk factors as follows:  are habitually physically inactive  have a first degree relative with diabetes  are member of a high risk group (e.g. African American, Latino, Native American, Asian American, Pacific Islander  persons with first degree relatives with diabetes  women who have delivered a baby > 9 pounds or were diagnosed with gestational diabetes mellitus  are, hypertensives (> 140/90)  have an HDL cholesterol level , 35 mg/dl or a triglyceride level. 250  have PCOS  on previous testing had IGT or IFG  Have other clinical conditions associate with insulin resistance (acnthosis nigrican)  Have history of vascular Correct answer: b
31. JC is a 55 year white old man with known chronic kidney insufficiency, presumably secondary to poorly controlled hypertension and diabetes mellitus. His primary care physician recently initiated treatment with 4 mg once daily of trandolapril, an ACE inhibitor. His current medications additionally include HCTZ 12.5 mg/d, amlodipine 10 mg/d, acetaminophen 1000 mg every 6 hours, and prn ranitidine. His estimated glomerular filtration rate is 37 ml/min/1.73 m^2 (serum creat 2 mg/dl). 6 weeks after initiating ACE inhibitor, his creatinine rises to 3.3 mg/dl. Prior to starting his ACE inhibitor, his BP had ranged between 160 -188/78 – 92 mm Hg. His BP is currently 176/84 mm Hg. He has no intercurrent illness ness to report. The least liklely explanation for his rise in serum creatinine is: a) Hyperglycemia b) Bilateral “critical” renal artery stenosis c) ranitidine d) acetominphen This man has chronic kidney insufficiency. In persons with reduced kidney mass, auto- regulation of renal blood flow and glomerular filtration rate is abnormal. That is, instead of the normal sigmoidal relationship between systemic blood pressure and GFR, there is a more linear relationship. Thus, renal perfusion pressure is more closely linked to GFR than in normal kidneys. Stated another way, the normal auto-regulation of renal blood flow and GFR are disrupted. When GFR and renal blood flow auto-regulation are abnormal, abrupt and/or sizeable drops in BP can cause reductions in GFR and therefore elevations in serum creatinine.

In chronic kidney disease the remaining nephrons also over-express COX-2. The over- expression of this enzyme leads to the production of vasodilatory prostaglandins (dilates glomerular afferent arteriole) and also augments angiotensin II synthesis (constricts glomerular efferent arteriole); this leads to increased glomerular pressure that, if maintained over the long-term, causes renal injury and loss of kidney function. In the setting of bilateral – not typically unilateral – critical renal artery stenosis, drops in BP as well as initiation of ACE inhibitor therapy can lead to global reductions in GFR and elevations in serum creat. There is, however, no evidence that this man has experienced a significant drop in BP. NSAID’s including COX-2 inhibitors can lead to reductions in global GFR, so ibuprofen is a viable suspect. Ranitidine is unlikely to have caused the deterioration in kidney function. The most likely explanation for his acute deterioration in kidney function is that the bilaterally critically stenosed renal arteries were highly dependent on vasodilatory prostaglandins and ang II to maintain GFR in the underperfused nephrons. The ACE inhibitor, maybe in conjunction with the NSAID, interrupted this compensatory set of mechanisms leading to global reductions in GFR. Overdiuresis is the most common cause of deteriorations in kidney function in persons with chronic kidney disease after initiating ACE inhibitor therapy. However, with a GFR below the mid-40’s, the low-dose thiazide he had been prescribed is not likely to have caused much, if any, diuresis. Thiazides are typically ineffective when the GFR drops much below the mid 40’s. Best answer: b

32. RA is a 48-year-old person with long-standing diabetes mellitus for the last 10 years. Over the last 3 years eight hemoglobin A1C’s have ranged between 8 – 9.9%. His blood pressure has ranged 156–190 / 78–96 mm Hg during this same time frame. He currently takes two antihypertensive medications – atenolol 50 mg once daily and doxazosin 4 mg once daily. He rarely misses taking his antihypertensive medications. A 24-hour urine recently showed 1. grams of protein. Which of the following is least likely to improve his blood pressure control? a) Encouraging dietary sodium restriction. b) Discontinuing doxazosin, and add an ACE- inhibitor along with a diuretic. c) Adding an ACE inhibitor and a diuretic. d) Discontinue doxazosin and adding an ARB and a diuretic. Diuretics enhance the blood pressure lowering effect of virtually all antihypertensive drug classes. Furthermore, when taking more than 2 antihypertensive drugs, if a diuretic was not one of the first two drugs, in most instances it must be the third drug if BP lowering is to be effective. Because of his diabetes, he is a good candidate for an ACE inhibitor or an ARB. In type 2 diabetes the data is strongest (RENAAL, IDNT trials) for angiotensin receptor blockers than ACE inhibitors for preventing progressive loss of kidney function. Nevertheless, though the database is less significant for ACEI in type 2 diabetic nephropathy; there is no physiological reason for these agents not to forestall progressive nephropathy in type 2 diabetes. In persons with type 1 diabetes mellitus, the data on forestalling progressive nephropathy belongs to the ACE inhibitors; however, there is little reason to believe that angiotensin receptor blockers wouldn’t be effective in this setting – despite the fact that the database for their use in type 1 diabetes mellitus is far less robust than for ACE inhibitors. Dietary sodium restriction will lower blood pressure. However, the major problem is getting the patient to restrict sodium. Thus of the choices available, choice ‘‘a” is the least likely to lead to improvement his blood pressure control. Best answer: a
33. TT is a 52 year old woman with long-standing diabetes mellitus. Her glycemic control has been quite good over the years. Over the past 3 years, a review of her chart documents no hemoglobin A1C’s above 7%. She experiences hypoglycemia episodes ~ twice weekly. After a recent myocardial infarction, she was placed on a beta-blocker. She read information on the

internet that has led her to be concerned about some of the potential adverse effects of beta blockers. Which of the following may occur as a consequence of taking a beta-blocker? a) Weight loss b) Absent or blunted tachycardia during hypoglycemia c) Absence of sweating with hypoglycemia d) Warm extremities Beta-blockers can cause weight gain, blunting of the tachycardic response during hypoglycemia and cool extremities. Sweating with hypoglycemia is a sympathetic cholinergic function and is thus unaffected by beta-blockers. Best answer: b

34. Which of the following is the best answer? a) The goal blood pressure level in persons with diabetes is < 140/90 mm Hg. b) If hemoglobin A1C is 6.4% during a clinic visit, intensification of diabetes drug therapy is indicated. c) In persons with diabetes, systolic blood pressure is very close to that of age- and sex- matched persons without diabetes, however, diastolic blood pressure is usually much higher in persons with diabetes compared to persons without diabetes d) Goal LDL-cholesterol in persons with diabetes mellitus is < 130 mg/dl. e) Lowering blood pressure is a proven way to reduce the need for retinal laser surgery to treat neovascularization. The goal BP according to the American Diabetes Association (ADA) is < 130/80 mm hg. According to the JNC VII report, the goal BP for persons with diabetes is < 130/80 mm Hg. Hemoglobin A1C > 7% is an indication for intensification of diabetes therapy. Compared to persons without diabetes, persons with diabetes mellitus tend to have much higher systolic blood pressure levels but similar to slightly lower diastolic blood pressures. The goal LDL-C is < 100 mg/dl in persons with diabetes. Both glycemic control and effective BP lowering are proven ways to reduce the risk of microvascular disease (e.g., nephropathy, retinopathy). Best answer: e
35. NX is a 48-year-old African American woman with a 14 year history of diabetes mellitus. She has never experienced DKA nor hyperosmolar coma. Her most recent serum creatinine was 1. mg/dl (EGFR ~ 50 ml/min/1.73 m^2 ). She has chosen you as her primary care physician. During your initial visit you note that her BP is 166/68 mm Hg. Her physical examination reveals background retinopathy, and evidence of left ventricular enlargement. She also has loss of sensation over the plantar surface of the foot. Her stool guaiac is negative. Previous BP levels and blood counts according to her old medical records are essentially unchanged. She has had repeated dipstick positive proteinuria (1+), although her urinary protein has never been quantified. Her current hemoglobin is 10.8 mg/dl (reticulocyte count 1%, MCV 84, Iron studies normal) Her current medications include verapamil SR 240 mg once daily, ASA 81 mg/d, and HCTZ 25 mg/d. Which of the following statements is correct? a) A screening colonoscopy should be ordered. b) The patient should be started in iron and folic acid. c) The patient should have three stool guaiacs performed. d) The patient hemoglobin is normal for her. Diabetes and reduced kidney function both cause anemia. Diabetes has been linked to an earlier expression of anemia at reduced, though higher GFR’s, than persons with reduced

GFR but no diabetes. The anemia of reduced kidney function, particularly in persons with diabetes, begins to be manifest at GFR’s of ~60 ml/min/1.73 m^2. Nonetheless is prudent to exclude intermittent GI bleeding. If these are positive the patient deserves a diagnostic colonoscopy. Best answer: c

36. In a patient with a strong family history of diabetes which approach for establishing the diagnosis of diabetes mellitus is most likely to confirm the diagnosis of diabetes mellitus in its earliest stages? a) Measuring hemoglobin A1C b) Fasting plasma glucose c) Oral glucose tolerance testing d) Measuring glycated hemoglobin Though hemoglobin A1C is used to follow the course of therapeutic response to diabetes therapy, no diagnostic criteria are available for using this test to diagnose diabetes mellitus. Diagnostic criteria definitely exist for fasting plasma glucose, however, in its earliest stages, diabetes mellitus is more readily detected in the post-prandial than in the fasting state. Some labs measure and report glycated hemoglobin levels (always higher than hemoglobin A1C levels), however, diagnostic criteria for diabetes mellitus do not exist for this lab test. Oral glucose tolerance testing is most likely to detect diabetes mellitus in its earliest stages. Correct answer: c
37. VB is a 58 year old overweight woman with a 15-year history of diabetes mellitus. Over the years, she has taken multiple oral hypoglycemic agents and for many years had very good control of her fasting and post-prandial glucose levels. There has been no evidence of retinopathy, although she developed microalbuminuria ~ 3 years ago. Her medical records now indicate a progressive rise in her fasting and post-prandial blood sugars. Her hemoglobin A1C levels have risen from 6.1% to 8.8% over the last 18 months with no change in diet, stable medications, and no evidence of intercurrent infections or other identifiable stressors. Her weight, diet, and physical activity levels have remained relative constant over the last 2 years. Current medications include metformin 2550 mg/d (taken in divided doses), pioglitazone 45 mg/d, enalapril 20 mg bid, amlodipine 5 mg/d, ASA 325 mg/d, and lamisil 250 mg once daily. She says that she takes her medications every day and rarely misses any doses. The most likely explanation for her deterioration in glucose tolerance is? a) Increasing insulin resistance b) Progressive insulinopenia c) The patient is not being entirely truthful d) Her antihypertensive medication The natural history of persons with Type 2 Diabetes Mellitus is progressive loss of pancreatic beta-cell insulin secretion. Some patients will clearly become insulinopenic and may even develop symptoms such of polyuria, polydipsia, polyphagia, weight loss, and visual symptoms if their hyperglycemia becomes severe enough. Insulin resistance, per se, is not a sufficient cause for diabetes mellitus – unless pancreatic insulin secretion is also abnormal. Furthermore, in this lady there is no evidence that some of the main causes of insulin resistance such as physical inactivity, high-fat diet, and weight gain have changed much over the last several years. Her antihypertensive medications have no effect (amlodipine, dihydropyridine calcium antagonist) on glucose tolerance or actually improve glucose tolerance (enalparil, an ACE inhibitor). ACE inhibitors typically do not change fasting glucose levels, however, they do improve glucose tolerance and have been implicated as contributing to the risk of hypoglycemia.

Correct answer: b

38. Which of the following drug(s) is/are contraindicated in diabetics? a) thiazide diuretics b) dilantin c) nicotinic acid d) doxazosin e) None of the above Thiazide and other potassium-wasting diuretics may precipitate diabetes or worsen glycemic control and/or glucose tolerance. Nevertheless, they are important agents in the management of hypertension in patients with diabetes. Beta-blockers can also worsen glucose tolerance and have been linked to an increased risk of developing diabetes mellitus. ACE inhibitors appear to reduce the long-term risk of developing diabetes mellitus by ~30% and improve insulin sensitivity though not fasting glucose in persons with diabetes. Virtually every authoritative body recommends an ACE inhibitor (or an ARB)in persons with diabetes. Nicotinic acid or niacin also can worsen glucose tolerance, and for these reason are cautiously used in the management of lipid abnormalities in persons with diabetes. Alpha-interferon also can cause worsening glucose tolerance. Other drugs that may worsen glucose tolerance or cause diabetes include pentamidine, glucocorticoids, and thyroid hormone. Doxazosin, an alpha adrenergic blocker, improves insulin sensitivity and glucose tolerance, and therefore has an opposite effect on glucose tolerance and levels compared to the other drugs discussed. However, none of the above drugs are “contraindicated” in diabetics. As always thgough the therapeutic benefit must out weigh the risk. Correct answer: e
39. KL is a 44-year-old woman with diabetes mellitus for the past 5 years. She once experienced diabetic ketoacidosis during a bout of pyelonephritis complicated by sepsis. KL also smoked for 50-pack years and has severe hypercholesterolemia (LDL-C 200 mg/dl), low HDL cholesterol ( mg/dl) and elevated fasting triglycerides (280 – 440 mg/dl). Three years ago she experienced an anterior wall myocardial infarction. Cardiac catheterization showed severe LAD stenosis that was amenable to angioplasty with stent placement and 40 – 70% patchy stenosis of her right coronary artery. Serial ejection fractions have ranged from 30 – 38% over the last 18 months. Her major complaint today is progressive shortness of breath. She experiences significant SOB with only minimal physical exertion. Hemoglobin A1C levels have ranged from 8.8 – 11.2% over the last 18 months. Her estimated glomerular filtration rate is 40 ml/min/1.73 m^2. Current medications include ASA 325 mg once daily, lipitor 40 mg @ HS, quinapril 40 mg bid, felodipine 10 mg once daily, glucotrol XL 10 once daily, and pioglitazone 30 mg once daily. Vitals show a BP of 150/72 in the seated position without significant orthostatic change, pulse rate of 88 beats per minute (regular), respirations of 18/minute Physical examination is normal except for a fourth heart sound, bilateral lower lung field rales that do not clear with cough extending ~ ¼ way up, mild elevation of her jugular venous pressure @ 45 degrees, bilateral femoral bruits, and 3 + lower extremity edema extending to the level of the knees. Which of the following is true? a) She has class III heart failure symptoms. b) The most logical drug to add to her diabetes treatment regimen, after reinforcing dietary counseling, is metformin. c) The drug in her current regimen that should definitely be discontinued is glucotrol. d) Her lower extremity edema is predominantly from her heart failure.

e) HCTZ/triamterene should be prescribed. She does not have heart failure symptoms at rest (class IV), however, given the appearance of he heart failure symptoms with minimal exertion, this is consistent with class III heart failure. Her glycemic control has been poor and her kidney function is significantly depressed. Both class III heart failure and reduced kidney function are contraindications to metformin – there is an increased risk in these settings of lactic acidosis. There is no compelling reason to discontinue glucotrol at this time. Her physical exam suggests that she indeed has both right and left sided heart failure. Thus, the right-sided heart failure has likely contributed to her lower extremity edema. However, assigning right sided heart failure the predominant role in her edema cannot be done with confidence. Both felodpine (a dihyrdopyridine calcium antagonist) and pioglitazone can cause edema, though the underlying mechanisms are different. Furthermore, pioglitazone is a known cause of fluid retention/volume expansion and is therfore contraindicated in class III – IV heart failure. Multiple causes of lower extremity edema can be identified. Given that her estimated GFR is below the mid 40’s, a thiazide diuretic, especially at low dose, is unlikely to be effective in initiating a diuresis or in controlling blood pressure. A higher dose diuretic (bid furosemide or metolazone, for example) would effectively diurese her and help her attain better BP control. Improved BP control might improve her cardiac performance as well. Correct answer: a

40. Mr. Khan is a 58 year man with Type 2 Diabetes and coronary heart disease. He has a strong family history of early coronary heart and sudden death. His sugars are currently well controlled on diet and an alpha glucosidase inhibitor and metformin. His LDL cholesterol is 99 on a statin. Triglycerides are 200 and his HDL cholesterol is 23. He takes ASA 325 milligrams daily. Which of the following approaches would optimize his lipid profile? a) Advise the patient to drink 4 four alcoholic beverages daily. b) Begin Niacin 250 milligrams bid and gradually titrate to 1000 milligrams per day. c) Begin a vigorous exercise program d) Start Folic acid 1 milligram daily This patient has a low HDL level. There are various ways to increase HDL. Although alcohol has been shown to increase HDL levels recommending four alcoholic beverages a day would not be advised. Niacin increases HDL cholesterol, lowers LDL cholesterol and triglycerides. Adding niacin to statins has been shown to slow the progression of atherosclerosis (Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol (ARBITER 2 Trial). Niacin can be used safely in diabetic patients. Exercise can increase HDL levels but recommending a “vigorous” exercise program in a patient with CAD would not be advisable. Niacin Correct answer: b
41. Mr. N is a 45 man who was diagnosed to have diabetes more than 12 years ago. His GFR is 40. Four months ago he underwent stent placement for occlusion of his LAD. He also has proliferative retinopathy which was treated by laser 2 years ago. He is doing well today although he mentions he is having some burning discomfort of his feet for the last two months. His glycemic control has been excellent; fasting glucoses range between 110 and 125 and post prandial glucoses are never higher than 160. At this visit you would: a) Order an ankle brachial index test b) Test sensation with a 10 g monofilament c) Order nerve conduction tests

d) Test sensation to pain and temperature, vibration, and light touch with a cotton wisp This patient’s symptoms are suggestive of peripheral neuropathy. The best initial way to evaluate this patient is to assess sensation using a 10 g monofilament. Testing for sensation to pain, temperature, vibration and light touch are appropriate but will not be as sensitive or reproducible as testing sensation with the monofilament. Nerve conduction tests will diagnoses peripheral neuropathy but are not recommended as part of a standard office evaluation. The ankle brachial index is recommended to evaluate for arterial insufficiency not neuropathy. would define might be helpful Correct answer: b

42. Mr. N’s sensation is found to be intact to all modalities. Which of the following statements is true? a) Mr. N should be instructed in use of the monofilament so that he can asses his sensation and participate in reducing his risk of ulceration and amputation b) Mr. N has had diabetes for more than 10 years and is at increased risk for amputation c) Mr. N has a normal sensory examination and is therefore not at increased risk for diabetic food ulcer d) Mr. N has a normal sensory examination and is therefore not at increased risk for risk of amputation Correct answer: b
43. Mr. U presents for a follow visit for diabetes. He takes metformin 1000 milligrams twice daily and self-monitors his blood glucose. Fasting and pre-prandial glucose are all less than 130. HgbA1c is 8%. At this point you would a) Continue the metformin and have the patient come backing in six months for another HgBA1c. b) Add a TZD. c) Repeat the HgBA1c as it is very unlikely that to have such a high value with the fasting and pre-prandial values described d) Discontinue metformin and begin a sulfonylurea to achieve a HgBA1c of <7% Metformin does not require endogenous insulin secretion to be effective Insulin secretion typically declines over time even in persons with Type 2 Diabetes Mellitus. Checking post prandial glucose is great but what this patient mostly needs is combination oral hypoglycemic therapy and/or a radical change in diet. Correct answer: b
44. Which of the following tests is not a component of an initial comprehensive evaluation in an asymptomatic 30 year old patient with newly diagnosed Type 1 diabetes? a) HgBA1c b) Fasting lipid profile c) Thyroid-stimulating hormone (TSH) d) Test for microalbuminuria Correct answer: d
45. Which of the following statement is true? e) Patients with diabetes who are older than 40 years of age should take ASA for primary prevention of myocardial infarction

f) Patients with diabetes who are older than 40 years of age should take ASA daily for primary prevention of retinopathy g) Patients with diabetes and proliferative retinopathy should not take ASA if because it increases the risk of retinal hemorrhage h) Patients with diabetes should take ASA daily to prevent microalbuminuria Correct answer: a

46. Which of the following should be performed at every routine diabetes visit? a) Comprehensive foot examination b) Measurement of capillary glucose c) Measurement of blood pressure d) Measurement of HgbA1c Correct answer: c
47. A 45 year woman with type 2 diabetes is found to have a single blood pressure measurement of 160/80. There is evidence of left atrial enlargement and left ventricular hypertrophy on EKG. At this point you would a) Arrange follow-up in one month to repeat her blood pressure b) Arrange follow-up in one week to repeat her blood pressure c) Begin chlorthalidone 25 milligrams daily d) Begin chlorthalidone 25 milligrams and lisinopril 10 milligrams daily and arrange follow-up in one month This is a tough problem. With evidence of target organ injury present it becomes easy to justify treatment after one visit. There is no evidence to support this treatment strategy. However, the ADA did adopt a recommendation to intimate immediate pharmacologic treatment for diabetic patients with a single systolic blood pressures > 160 or diastolic blood pressures >100. The blood pressures is > 20/10 over goal so two drugs are needed. The ACE inhibitor should definitely be used. Correct answer: d
48. Mrs. Z was recently diagnosed with type 2 diabetes. She completed diabetes education classes and is following a 1500 calorie ADA diet. At this point you would recommend she a) Measure capillary blood glucose twice daily b) Measure fasting and post-prandial capillary blood glucose daily c) Measure capillary blood glucose three or more times daily d) None of the above The role of SMBG in stable diet-treated patients with type 2 diabetes is not known. Daily SMBG is especially important for patients treated with insulin to monitor for and prevent asymptomatic hypoglycemia and hyperglycemia. For most patients with type 1 diabetes and pregnant women taking insulin, SMBG is recommended three or more times daily Correct answer: d
49. Which of the following statements is correct? a. A thorough foot examination should be performed annually in diabetics annually to identify high risk foot conditions b. A thorough foot examination should be performed every visit in diabetics to identify evidence of increased plantar pressure (calluses, corns etc.)

c. A thorough foot examination should be performed quarterly in diabetics to identify evidence of neuropathy d. A thorough foot examination should be performed biannually in diabetics to identify evidence of peripheral vascular disease Correct answer: a