84-1

84
TYPE 2 DIABETES MELLITUS: EXISTING DISEASE
Establishing Optimal Control . . . . . . . . . . . . . Level II
Antoinette B. Coe, PharmD Sharon B.S. Gatewood, PharmD

CASE SUMMARY
A 45 yo woman come to the pharmacy for an education class about diabetes taught by the pharmacist. She was diagnosed with diabetes 6 months ago and started on therapy along with lifestyle modications. The patients blood glucose levels and A1C have worsened, and the patient is not maintaining her lifestyle modications. Her drug regimen for diabetes and lifestyle modications will need to be changed. Because of her diabetes and obesity, her cholesterol and blood pressure are uncontrolled. The reader will have to create a treatment plan that optimizes control of the patients hypertension and dyslipidemia as well.

CHAPTER 84
Type 2 Diabetes Mellitus: Existing Disease

INSTRUCTORS GUIDE TO CHANGES IN THIS EDITION

New coauthor (Dr Coe). CASEBOOK Patient Presentation New patient (slightly older) with different HPI, FH, SH, medications (specically, the patient in this case is receiving metformin vs. glyburide in the previous case), allergies, vital signs, laboratory ndings, and initial assessment. At initial assessment, diabetes control was attempted with metformin, lifestyle, and dietary modication. INSTRUCTORS GUIDE Problem Identication Revised based on this patients medical history and current drug regimen. Therapeutic Alternatives Nonpharmacologic therapies have been modied based on this patients history. New information added regarding the role of saxagliptin and liraglutide as treatment options. Optimal Plan The optimal plan in this case is to add basal insulin therapy to metformin monotherapy (vs. changing glyburide to metformin in the previous case) along with lifestyle modifications to hopefully gain better control of the patients diabetes. Outcome Evaluation Adverse effect parameters for insulin added. Patient Education General information was added regarding patient education and adverse effects for insulin glargine. Follow-Up Question Answer revised based on initial therapy with metformin in this case. References Updated to include two new references.

QUESTIONS
Problem Identication
1.a. What are this patients drug therapy problems? Type 2 DM is uncontrolled on current drug therapy and lifestyle modications. Hypertension is uncontrolled on the current dose of an ACE inhibitor. Dyslipidemia is uncontrolled on the current statin therapy. Bipolar condition seems to be controlled on the current drug regimen (although it should be noted that the patients atypical antipsychotic medication may have an impact on her glycemic control). Atypical antipsychotic class of drugs could possibly precipitate diabetes. Obesity is uncontrolled and contributes to the instability of the patients diabetes, hypertension, and dyslipidemia. 1.b. What ndings indicate poorly controlled diabetes in this patient? Self-monitored blood glucose levels range from 215 to 280mg/dL. Self-monitored fasting blood glucose levels average 200mg/dL. A random blood glucose is 243 mg/dL. The A1C is 10.0%. Signs and symptoms of hyperglycemia in this patient include polydipsia, polyuria, and nocturia.

Desired Outcome
2.a. What are the goals of treatment for type 2 diabetes in this patient? Control of blood glucose levels as close to normal as possible. Preprandial plasma glucose: 70130 mg/dL. Peak postprandial plasma glucose: <180 mg/dL (measurements should be made 12 hours after the beginning of the meal). A1C of <7%.1 Short-term goals for diabetes are to prevent and relieve acute complications. Long-term goals for diabetes are to prevent and maintain any microvascular and macrovascular complications and improve patient quality of life.

Copyright 2011 by The McGraw-Hill Companies, Inc. All rights reserved.

84-2 Maintain blood pressure with a goal of <130/80 mm Hg.1,2 The goals for dyslipidemia are total cholesterol <200 mg/dL, HDL >40 mg/dL (for women, it has been suggested that this goal be increased by 10 mg/dL), LDL <100 mg/dL (the goal of <70 mg/dL should be considered in patients who are very high risk and have overt CVD), and triglycerides <150 mg/dL. Also because the patients triglycerides are >200 mg/dL, the non-HDL cholesterol should be considered with a goal 130 mg/dL.1,3,4 The long-term goals for treating hypertension, dyslipidemia, and obesity are to reduce the risk factors for developing cardiovascular disease, thereby preventing the development or progression of the complications of target organ disease (including nephropathy and retinopathy in the case of both diabetes and hypertension). Management and goals of therapy are determined in part by the stage or severity of the disease and the presence of various risk factors. Initial goal for obesity is a 10% weight reduction from baseline within a 6-month time period. The rate of weight loss should be no more than 12 lb per week to maintain the loss.5 2.b. What individual patient characteristics should be considered in determining the treatment goals? Setting individual goals should be based on the patients ability to understand and carry out the treatment regimen, her risk for severe hypoglycemia, and other factors such as age and comorbidities that may increase risks or decrease benets. Although the Zyprexa could have precipitated the diabetes and caused weight gain, this drug plays an important role in the treatment of the bipolar disorder.6 Therefore, the goal is to achieve the goals of the other comorbidities while maintaining the drug regimen for this patients seemingly well-controlled bipolar disorder.

Dyslipidemia:
Work with dietitian to incorporate the therapeutic lifestyle change (TLC) approach, which includes keeping saturated fats to <7% of total calorie intake and cholesterol intake to <200 mg per day, incorporating 2 g per day of plant stanols/ sterols, and increasing ber to 1025 g per day.1,3,4 This should be combined with a decreased total daily caloric intake to help decrease weight. Encourage weight reduction with diet and exercise. An exercise plan for this patient should be cleared with her physician prior to starting.

SECTION 8
Endocrinologic Disorders

Obesity:
Initiate a low-calorie diet (LCD) that includes 8001,500 kcal per day under the guidance of a dietitian.5 The LCD should employ the principles of the TLC for helping to control cholesterol. Exercise initially for 3045 minutes at least three times per week including some type of cardio activity (e.g., rapid walking). Maintenance exercise should consist of 30 minutes or more for most days of the week to maintain weight loss. An exercise plan for this patient should be cleared with her physician prior to starting.

Bipolar disorder:
Continue psychotherapy. Initiate an exercise program that will help to relieve stress and depression. An exercise plan for this patient should be cleared with her physician prior to starting. Encourage alcohol avoidance. If the patient continues to consume alcohol, encourage her to have no more than one to two drinks per week. 3.b. What pharmacologic interventions could be considered for this patients drug therapy problems?

Therapeutic Alternatives
3.a. What nonpharmacologic interventions should be recommended for this patients drug therapy problems?

Diabetes mellitus:
Metformin plus insulin is a reasonable option. Insulin therapy is being initiated earlier in the management of type 2 diabetes to be more aggressive in obtaining goals for blood glucose and A1C. Patients may be started on a bedtime intermediateacting insulin or a morning long-acting insulin (can initiate with 10 Units or 0.2 Units/kg).7 Depending on the pattern of the blood glucose levels, an intermediate- or long-acting basal insulin and rapid- or short-acting insulin may be necessary to treat the patient to target. Any combination of these insulins may be necessary depending on the patients blood glucose trends, work, and meal schedule. Insulin is the most effective diabetes medication to lower blood glucose, with no maximum dose or effect, and will help the patient to reach her goal A1C.7 Insulin glargine is considered a peakless insulin with a duration of action from 20 to 24 hours and may be an appropriate addition. Metformin is very effective in obese patients who are starting oral agents, is considered rst-line therapy along with lifestyle modications, and should be continued in this patient with insulin therapy. It improves glycemic control by decreasing hepatic glucose production, thereby decreasing blood glucose levels. It decreases intestinal absorption of glucose and improves peripheral glucose uptake and utilization, thereby improving insulin sensitivity and decreasing the risk of hypoglycemia (relative to secretagogues, such as sulfonylureas, or insulin therapy), and may aid in weight loss. When used alone, metformin decreases the fasting blood glucose by about 6070 mg/dL and A1C by 1.52%.8 Metformin can also have a positive effect on the LDL, TG, and weight.

Diabetes mellitus:
Have the patient begin testing her blood glucose at least twice a day (preferably one fasting, one preprandial, and one 2-hour postprandial per day) and recording her results in a blood glucose diary. Have the patient test her blood glucose at different times of the day to get a more complete picture of her blood glucose levels. Improve lifestyle modications and exercise. Reduce or avoid alcohol consumption. Encourage weight reduction with diet and exercise. Refer to a dietitian for medical nutrition therapy. Receive diabetes self-management education according to national standards.

Hypertension:
Decrease salt intake to <2.4 g of sodium per day. Recommend the DASH dieta diet rich in vegetables, low-fat dairy products, and fruits, along with a dietary reduction in total and saturated fat intake.2 Work with dietitian to maintain adequate potassium, calcium, and magnesium. Encourage weight reduction with diet and exercise.
Copyright 2011 by The McGraw-Hill Companies, Inc. All rights reserved.

84-3 Metformin plus sulfonylurea (e.g., glyburide) dual combination therapy may result in improved glycemic control initially and is relatively cost-effective, but the magnitude of benet over monotherapy with metformin may be small. Maximum effective doses of sulfonylureas are lower than those previously assumed, and continued exposure to high concentrations may downregulate -cell sensitivity.8 It would also increase the risk of adverse effects including hypoglycemia, hyperinsulinemia, and weight gain. However, this combination would be an option if the patient was not willing to start insulin therapy. Metformin plus thiazolidinedione (rosiglitazone or pioglitazone) is an option. Thiazolidinediones represent a therapeutic approach for this patient that addresses insulin resistance as its primary mechanism of action by insulin sensitivity of muscle and adipose tissue.8 This regimen may improve glycemic control through improved glucose utilization without increasing (and by possibly decreasing) insulin requirements. However, these medications are costly and require intensive monitoring of liver enzymes prior to and during therapy. Thiazolidinediones will not achieve the necessary lowering of the patients A1C to goal. Also, thiazolidinediones commonly cause weight gain, and for this reason, it may be prudent to avoid their use in this patient at this time. Metformin plus sulfonylurea plus thiazolidinedione (triple-drug therapy) is becoming a common strategy to treat type 2 DM. However, this approach is more expensive than the other options available for this patient. It could be considered if the patient does not respond to changes in other double combination oral therapy and is resistant to starting insulin therapy. If the triple-drug therapy is needed, a combination drug can be used to decrease the total number of drugs that the patient is taking. Metformin plus an -glucosidase inhibitor (acarbose or miglitol). -Glucosidase inhibitors are unlikely to produce a satisfactory response because they decrease postprandial blood glucose levels with minimal effect on fasting levels. These agents, when used in combination with other diabetes medications, are generally unacceptable due to additive GI adverse effects, poor adherence prospects, and additional costs. Metformin plus a meglitinide derivative (repaglinide or nateglinide) is a reasonable option. Meglitinide derivatives are nonsulfonylureas that stimulate phase I insulin secretion. They have a rapid onset and short duration of action, which allows for exible adjustable dosing given two, three, or four times a day, with each meal. Repaglinide is approved for use as monotherapy or in combination with metformin. Its rapid elimination may lessen the risks of prolonged hypoglycemia and downregulation of -cell sensitivity.8 Adjustable dosing schedules may allow for more exible and individualized drug therapy management plans for patients on oral agents. Nateglinide is a phenylalanine derivative that works similarly but may be more dependent on and responsive to glucose levels. Patients inadequately controlled with glyburide or other insulin secretagogues should not be switched to these agents, nor should they be added to the regimen. Metformin plus dipeptidyl peptidase-4 (DPP-4) inhibitor (sitagliptin or saxagliptin) has a complimentary effect when taken together. Sitagliptin and saxagliptin have been approved as monotherapy or for use in combination therapy (e.g., with metformin, thiazolidinediones, or sulfonylureas). In combination with either metformin or a thiazolidinedione, the three key defects can be addressed: insulin resistance, -cell dysfunction, and -cell dysfunction. The DPP-4 inhibitors work by inhibiting the DPP-4 enzyme that is responsible for the breakdown of glucagonlike peptide-1 (GLP-1). GLP-1 functions in the body include promoting satiety and reducing appetite, slowing gastric emptying, decreasing postprandial glucagon secretion by its action in the pancreatic -cells (which further reduces hepatic glucose output), and increasing glucose-dependent insulin secretion by its action in the pancreas -cells. Kidney function must be assessed before starting either of these medications with a required dose adjustment before initiation. A combination product with metformin and sitagliptin is available if this option is chosen to decrease the amount of medications taken by the patient. Incretin mimetic therapy (exenatide or liraglutide) plus metformin is a reasonable option. These injectable medications have been approved for monotherapy use or in combination therapy for the management of type 2 diabetes. Drugs in this class are analogs of incretin (GLP-1), a substance which increases the secretion of insulin, increases -cell growth, slows gastric emptying, and possibly decreases food intake. These medications can also be used in combination with thiazolidinediones and sulfonylureas. Pramlintide is a synthetic version of the natural hormone amylin. Amylin is released from the pancreas -cells at the same time as insulin in response to food. It primarily affects postprandial blood sugars by delaying gastric emptying, stops glucagon production, and promotes satiety. It can be an adjunct medication for type 2 diabetes patients on metformin, sulfonylureas, or insulin. It is an injectable medication that must be given with a meal. BIDS therapy (bedtime insulin/daytime sulfonylurea) has been increasingly successful when initiated before titration to maximum doses of sulfonylureas and while there is still sufcient -cell function intact. It provides for a period of interim insulin use with only one daily injection. Bedtime administration of insulin enhances the suppression of nocturnal hepatic glucose production that occurs in the fasting state. It does pose increased risks for weight gain, hypoglycemia, and hyperinsulinemia. Increased frequency of self-monitoring of blood glucose (SMBG) and patient acceptance may be limiting factors. Pioglitazone and metformin are also approved for use in combination with insulin. Though not an approved indication, an interesting regimen to consider might be bedtime insulin to suppress fasting glucose levels plus nateglinide to stimulate phase 1 insulin secretion and control postprandial glucose levels.

CHAPTER 84
Type 2 Diabetes Mellitus: Existing Disease

Hypertension:
Increase dose of lisinopril by 5 mg per day in 1- to 2-week intervals up to a maximum of 40 mg per day given as a single daily dose or divided dose. In patients with type 2 diabetes, hypertension, and microalbuminuria, ACE inhibitors have been shown to delay the progression to macroalbuminuria and nephropathy.1,2 Addition of a thiazide diuretic such as hydrochlorothiazide 12.5 mg per day. Combination therapy at low doses will minimize the potential adverse effects of either agent when used alone at higher doses. A low dose of hydrochlorothiazide will have minimal adverse effects on glycemic control. Many studies have shown a reduction in morbidity and mortality with the use of diuretics. The current lisinopril dose should be sufcient to delay the progression to macroalbuminuria. If a patient with diabetes needs combination therapy to control
Copyright 2011 by The McGraw-Hill Companies, Inc. All rights reserved.

84-4 blood pressure, the combination of an ACE inhibitor and thiazide diuretic is rst-line therapy. In addition, this would be the most cost-effective option and can be made available in one pill for once-a-day dosing. Addition of a -blocker to lisinopril may be considered. -Blockers are effective in signicantly reducing cardiovascular morbidity and mortality. However, -blockers may mask hypoglycemia symptoms (e.g., tachycardia) in patients with diabetes. Addition of an angiotensin II receptor blocker (ARB) to lisinopril 10 mg may be considered. ARBs should usually be reserved for patients who are unable to tolerate ACE inhibitors. However, some research suggests that these agents may be added to ACE inhibitors for a synergistic effect regarding renal protection. Data regarding the cardiovascular benet of the synergistic effect of ACE inhibitors and ARBs are still conicting. ARBs have also been shown to delay the progression of microalbuminuria to macroalbuminuria.1 However, data are lacking in the important comparison between ARBs and an ACE inhibitor or diuretic. Addition of a nondihydropyridine calcium channel blocker (diltiazem, verapamil) to lisinopril 10 mg may also be considered.9 Calcium channel blockers should be considered third-line therapy due to benet of the other antihypertensive class of drugs toward diabetes. no brate trial has demonstrated a reduction in all-cause mortality. The patient and her physician need to be made aware that with this combination there is an increased risk of rhabdomyolysis. Addition of niacin could be considered; however, the patients HDL is already at goal. Prompt-release niacin has more favorable effects on HDL and triglycerides than slow-release preparations.4 Niacin is the most effective drug for raising HDL but can signicantly increase blood glucose at high doses.1

SECTION 8
Endocrinologic Disorders

Obesity:
Because the patient has not maintained the current lifestyle modications, they will be reinitiated. No drug therapy will be started for this patient at this time because of uncontrolled hypertension. Most of the weight loss medications contain some form of stimulant that could aggravate the patients hypertension. OTC orlistat could be an option for weight loss for this patient. However, it is not a practical option for this patient due to her binge eating to self-treat her mood swings. As such, this patient may potentially suffer from the adverse gastrointestinal effects that are associated with this medication.

Dyslipidemia:
The patients LDL cholesterol is uncontrolled (141 mg/dL) on current statin therapy. A goal LDL of <100 mg/dL is recommended, and in high-risk patients (i.e., those with overt CVD), treatment to an LDL of <70 mg/dL should be considered.1,3 An approximate deduction of 29% is needed to get the patients LDL to goal. Additionally, triglycerides are elevated (225 mg/dL) and the HDL level is good (58 mg/dL). Treatment goals are triglycerides <150 mg/dL and HDL above 50 mg/dL.1,3,4 The primary treatment goal for a patient with diabetes is to reduce the LDL level to goal, unless severe hypertriglyceridemia (e.g., >500 mg/dL) exists.1 Options for the treatment of this patients dyslipidemia include: Do not adjust pharmacologic therapy for cholesterol in this patient until diabetes is under control. Continued exercise will help raise HDL-C, and decreasing the intake of saturated fats will help lower triglycerides. Also as the patients glucose begins to decrease, the triglycerides will follow. Change the current therapy by increasing the pravastatin to 80 mg once daily, or change the therapy to atorvastatin 20 mg once daily. An increase in the statin dose is necessary to achieve target LDL levels. The statin therapy can decrease the risk of cardiovascular events including stroke; therefore, it is an important part of this patients drug regimen.10,11 Also, atorvastatin has been shown to have a greater effect of the lipid prole than pravastatin, and therefore this may prove to be a better choice for this patient. Addition of bric acid derivatives (gembrozil, fenobrate) could be considered if lifestyle modications are insufcient to achieve the target triglyceride and HDL levels. Fibric acid derivatives are the drugs of choice for patients with diabetes who have elevated triglycerides or mixed dyslipidemia. They decrease triglycerides and increase HDL but have little effect on lowering LDL. Lowering triglycerides and increasing HDL cholesterol with a brate are associated with a reduction in cardiovascular events in patients with clinical CVD, low HDL, and near-normal levels of LDL.1 However,
Copyright 2011 by The McGraw-Hill Companies, Inc. All rights reserved.

Optimal Plan
4. What pharmacotherapeutic regimen would you recommend for each of the patients drug therapy problems? This patient is currently being treated with metformin 1,000 mg BID with meals along with lifestyle modications, which is consistent with ADA guideline recommendations. Metformin is the drug of choice in patients who are obese because it has been shown to reduce weight and improve the lipid prole and glycemic control. However, the patient has not reached her therapeutic target (A1C <7%) on metformin monotherapy, and an additional agent is therefore needed. The patient should be started on 10 Units insulin glargine subcutaneously daily (either at bedtime or in the morning, as long as the time of day is consistent) and continued on her current dose of metformin 1,000 mg BID with meals. The patient should be instructed to test her fasting blood sugar daily to see if this dose is adequate to achieve target fasting blood glucose levels (70130 mg/dL). If the fasting blood glucose is outside of this range, a reasonable titration would be to increase the insulin glargine dose by an additional 2 Units every 3 days as needed to achieve the goal fasting blood glucose.7 Education should be provided to the patient on subcutaneous insulin injection technique including the patient demonstrating proper injection technique. Education on the appropriate treatment and management of hypoglycemic episodes should be provided. Emphasis on appropriate SMBG, lifestyle modications, and exercise should be discussed with the patient.

Diabetes mellitus:

Hypertension:
Hydrochlorothiazide 12.5 mg should be added to the ACE inhibitor, lisinopril. These two classes of drugs in combination will have a synergistic effect on control of the hypertension. The ACE inhibitor will be continued at the current dosage. Strong consideration should be given to the use of ACE inhibitors in all patients with diabetes, not only for control of hypertension and renal protection but also for cardiovascular risk reduction. The

84-5 need for cardiovascular risk reduction is present in all patients with diabetes, regardless of whether hypertension exists as a comorbid problem. If the patient wishes to not take an additional medication, a lisinopril/HCTZ combination product is available for a convenient one tablet daily dosing in various strengths. 2 Units. Continue dose titration and follow up schedule until the patient is in target fasting blood glucose range.
7

CHAPTER 84

Educate patient about what to do if she becomes hypoglycemic. Measure the A1C every 3 months until stable. Then measure twice a year for maintenance. Adverse effect monitoring (insulin glargine): The most common adverse effects of insulin glargine are hypoglycemia, injection site reactions, allergic reactions, weight gain, pruritis, lipodystrophy, and rash. Counsel the patient to make sure that she uses proper insulin injection technique, rotates her injection site daily, and knows the proper treatment of a hypoglycemic episode. Baseline renal and hepatic function tests should be done prior to starting insulin therapy and then at least yearly during course of therapy. Adverse effect monitoring (metformin): The most common adverse effects of metformin are GI in nature (nausea, vomiting, epigastric fullness, diarrhea, or constipation). Ask the patient if she is experiencing these symptoms and to what extent they are occurring. Counsel the patient to take her metformin with food. These side effects are common within the rst 23 weeks and then should subside. Lactic acidosis is a rare but potentially severe consequence of metformin therapy. The drug is contraindicated in patients with disorders that increase the risk of lactic acidosis. These include acute heart failure, renal impairment (SC 1.5 mg/dL in males or 1.4 mg/dL in females), chronic or acute metabolic acidosis, liver failure or hepatic disease, chronic or excessive ethanol use, dehydration, and hypoxemic states (including respiratory failure). Renal and liver function must be monitored throughout the course of therapy. Baseline renal function tests should be performed prior to initiation of therapy and then at least yearly. Therapy should be discontinued if serum creatinine is 1.5 mg/dL in men or 1.4 mg/dL in women. Baseline liver function tests (ALT) should be performed before initiation of therapy. Tests should also be obtained if the patient develops nausea, vomiting, abdominal pain, fatigue, anorexia, dark urine, or jaundice. If the ALT is moderately elevated ALT (>12.5 times normal) at any time during therapy, patients should be evaluated to determine the cause, and more frequent monitoring should occur. If the ALT increases to >3 times the upper limit at any time, the test should be repeated as soon as possible. If it remains elevated at >3 times the upper limit of normal (ULN), the drug should be discontinued.

Dyslipidemia:
Pravastatin 40 mg should be changed to atorvastatin 20 mg once daily to increase LDL-lowering effect. Once the diabetes goals are achieved, the goal for the triglycerides will probably be reached. The LDL will still need some improving to reach the goal of less than 100 mg/dL, given that diabetes is considered a coronary heart disease risk equivalent. A fasting lipid panel should be drawn in 6 weeks to check the LDL, triglycerides, and liver function. If patient is not improving toward the goal, the dose of the atorvastatin may need to be increased to 40 mg.

Type 2 Diabetes Mellitus: Existing Disease

Obesity:
Because the patient has not maintained the current lifestyle modications, they will be reinitiated. No drug therapy should be started for the patient at this time because of uncontrolled hypertension. Most of the weight loss medications contain some form of stimulant that could aggravate the patients hypertension. OTC orlistat could be an option for weight loss for this patient. However, it may not be well tolerated if the patient continues her dietary habits of binge eating to self-treat her mood swings.

Bipolar disorder:
No change will be made to the drug regimen treating the bipolar disorder at this time. The patients bipolar disorder is currently stable on the current medication regimen. Although there is a chance that the Zyprexa may be contributing to the diabetes progression and increased weight gain, the benets of this drug may outweigh the risk of losing adequate control of the patients bipolar symptoms.6 The atypical antipsychotics tend to be better tolerated by patients with fewer side effects than the typical antipsychotics. Two atypical antipsychotics, aripiprazole and ziprasidone, have been shown to have a lower incidence of weight gain than olanzapine if a future change in therapy is needed.12 At this time, the typical antipsychotics are not a good option for this patient.

Outcome Evaluation
5. What parameters should be monitored to evaluate the efcacy and possible adverse effects associated with the optimal regimens you selected?

Diabetes mellitus:
Efcacy monitoring: Increase the frequency of SMBG to include fasting, postprandial, and bedtime measurements, and monitor for the occurrence of signs and symptoms of hypoglycemia or hyperglycemia until the patients goals are reached. Have the patient record her results in a log book and share them with you and her physician at every visit. Follow up with the patient in 3 days after initiation of basal insulin therapy to assess fasting blood glucose measurements. If patients fasting blood glucose is elevated and not in the target range (70130 mg/dL), increase dose by

Hypertension:
Efcacy monitoring: Blood pressure needs to be monitored once a week until patient reaches goal of <130/80 mm Hg. Adverse effect monitoring: For lisinopril, monitor the patients blood pressure for hypotension and evaluate the patient for hypotensive symptoms (e.g., fatigue, dizziness, headache, fainting). Ask the patient about the presence of cough, skin rash, and taste disturbances. Monitor serum creatinine and potassium at baseline, approximately 1 week after initiation of therapy or dosage titration, and then periodically. Although rare,
Copyright 2011 by The McGraw-Hill Companies, Inc. All rights reserved.

84-6 patients should be aware of signs and symptoms of angioedema; this may present as facial swelling (lips and around eyes) and swelling in the extremities (legs and arms). This is a very serious reaction and patients should be made aware of the severity of it and instructed on what to do if these symptoms occur. Hydrochlorothiazide can cause hypotension, uid and electrolyte disturbances, and sensitivity to sunlight. Monitor BP and for symptoms of hypotension, low potassium (aching muscles, leg cramps), and gout. Serum creatinine, potassium, lipids, glucose, and uric acid levels should be measured periodically. Serum potassium and uric acid should be measured within 26 weeks after initiation of therapy. the blood into the muscles. In type 1 diabetes, the pancreas does not produce any insulin, so insulin injections are needed. In type 2 diabetes, the pancreas does not produce enough insulin or the body cannot use the insulin it produces properly. Many people with type 2 diabetes also need to use insulin. You can control your blood glucose levels by following a treatment plan designed for you that includes meal planning to t your needs and preferences, regular exercise, and medication. The amount of glucose in your blood depends on the amount and types of food you eat, the timing of your meals, the amount and timing of activity or exercise (which pulls more glucose out of the blood for energy), and the amount and timing of your medication. High or low blood glucose levels can result if all of these actions are not coordinated appropriately. Maintaining your blood glucose levels as close to normal as possible may prevent or delay complications such as blindness, kidney disease, nerve damage, limb amputations, heart disease, and strokes. High blood sugar (or hyperglycemia) can cause symptoms such as increased thirst; increased hunger; increased urination, headaches, and dry, itchy skin; more frequent infections that are difcult to cure; nausea; fatigue; blurry vision; and numbness or tingling in the ngers or toes. If untreated, it can lead to coma and death. It is important to increase the frequency of your blood glucose monitoring while we adjust your insulin and until you reach your goals. A schedule of testing before and after meals, fasting, and at bedtime should be negotiated with the patient. Would you show me how you check your blood glucose so we can make sure everything is accurate and still working properly? Ideally, your fasting blood glucose should stay between 70 and 130 mg/dL, and your blood glucose 2 hours after a meal should be <180 mg/dL. Check your blood glucose more often if you are sick or under any other physical or emotional stress that could cause your levels to elevate. Always ask for advice if any of these problems occur and before taking any nonprescription medicines. You can also get low blood sugar (or hypoglycemia) due to delayed or missed meals, increased activity or exercise, alcohol consumption on an empty stomach, or taking too much diabetes medicine, especially insulin. The warning signs of hypoglycemia include increased heart rate, weakness, dizziness, headache, shakiness, sweating, numbness or tingling around the mouth, irritability, drowsiness, coldness, and unconsciousness, which can progress to seizures, coma, and death. It is important for you to know your symptoms of a low blood sugar in order to recognize hypoglycemia so that you can treat it appropriately. When any symptoms of low blood sugar occur, check your blood glucose, if possible. If it is low, treat it immediately with a quick-acting source of sugar such as cup of juice or regular soda, three to four glucose tablets, glucose gel, or one cup of milk. You want to ideally ingest 15 g of fast-acting carbohydrates. Check your blood glucose again in 15 minutes and repeat the treatment if necessary; then follow with a snack if a meal is not planned within 0.51 hour. Some people do not experience any symptoms when their blood glucose is low. Always carry some form of quick-acting sugar with you and wear a medical alert bracelet or necklace. Glucagon injections may be needed to treat low blood sugar if you cannot swallow or if you are unconscious. A Glucagon Emergency Kit contains a vial containing 1 mg of powder

SECTION 8
Endocrinologic Disorders

Dyslipidemia:
Efcacy monitoring: Check a fasting lipid prole in 68 weeks. Repeat a fasting lipid panel approximately every 6 weeks, until goals are met. Then check yearly thereafter. Adverse effect monitoring: Monitor the risk for hepatotoxicity by checking the ALT and AST at baseline and then again at 12 weeks. Repeat LFTs also with each escalation in dose, and then periodically throughout therapy. If AST or ALT increases to > 3 ULN, either reduce the dosage or discontinue atorvastatin. Educate patient on the signs and symptoms of rhabdomyolysis (e.g., intense muscle pain, tea-colored urine) and instruct the patient regarding what to do if symptoms occur.

Bipolar disorder:
Efcacy monitoring: Have patient continue with her psychotherapy and monitor efcacy by talking with the patient when she picks up her Zyprexa rell. Adverse effect monitoring: Monitor the patients blood sugar closely since she will remain on the Zyprexa for the bipolar disorder. The patient should also be monitored for the following adverse effects while taking Zyprexa: somnolence, weight gain/increased appetite, constipation, dizziness, akathisia, asthenia, and dry mouth. Although many of the extrapyramidal symptoms are more common with the rst-generation antipsychotics, these adverse effects can still occur with the atypical antipsychotics and need to be monitored.

Patient Education
6. What information should be given to the patient regarding diabetes mellitus, hypertension, dyslipidemia, bipolar disorder, obesity, and her treatment plan to increase adherence, minimize adverse effects, and improve outcomes?

General information:
Note: Patient education regarding diabetes mellitus should be comprehensive and delivered over a series of visits. Determine what the patient knows and what information other members of the health care team are providing. Diabetes is a condition in which your body cannot properly use glucose or sugar from digested food. It builds up in the blood and does not get into the muscles and other organs that need it as a source of energy. Insulin allows the glucose to move from
Copyright 2011 by The McGraw-Hill Companies, Inc. All rights reserved.

84-7 with 1 mL of liquid contained in a disposable syringe with needle. The liquid in the syringe should be injected into the vial and mixed. Then the entire solution should be drawn back into the syringe and injected. Although any site can be used, injecting into the abdomen at a 4590 angle will work most quickly. Glucagon may cause nausea and possibly vomiting. A response usually occurs in 520 minutes and should be followed with liquids containing sugar. Check blood glucose levels every 15 minutes and follow with a recommended quick-acting sugar until levels rise to normal. Follow with a snack to replace the body stores of energy to prevent repeated hypoglycemia. Check blood glucose levels every 24 hours for 1224 hours. Someone else should be instructed on how to give this injection. If you do not recover sufciently, call emergency personnel. While waiting, a second dose may be given. Always notify your physician when a severe reaction occurs. It is also important to check your feet daily since simple irritations, calluses, or infections can progress quickly to ulcers and infections that do not heal well. Apply lotion to the calluses on your feet every day, avoiding in between your toes, and wear socks and shoes that t properly. If any redness or discomfort develops, or the condition worsens, consult a podiatrist. Good oral hygiene is important to prevent periodontal disease. Poor glucose control can make infections very difcult to cure. It is important to see a dentist at least yearly. It is very important to control all of your risk factors for developing complications, especially your blood pressure and cholesterol. Your blood pressure should be maintained below 130/80 and your LDL cholesterol below 100 mg/dL. We will check your blood pressure and cholesterol regularly. To help control your blood pressure and cholesterol: Decrease salt intake to <2.4 g of sodium per day and get adequate amounts of dietary potassium, calcium, and magnesium. Follow a healthy diet that limits saturated fats to <7% of total calorie intake and cholesterol intake to <200 mg per day, incorporating 2 g per day of plant stanols/sterols and increased viscous (soluble ber) 1025 g per day. Try to increase the amount of vegetables, fruit, and low-fat dairy products in your diet. Always get regular exercise, keep a healthy weight, and drink alcohol in moderation (if at all). It is important to ask for advice if any problems arise, or if you have any questions, because it is possible to control your diabetes if everyone works together to help you learn how to manage it. You should have an annual dilated eye exam to check for eye damage (retinopathy), a yearly urine test for microalbuminuria to check for kidney disease (nephropathy), and a yearly foot exam to check for any signs of nerve damage (peripheral neuropathy). Get an inuenza shot each year and a pneumococcal vaccine once if you have never received one. You will need a one-time revaccination of the pneumococcal vaccine when you turn 65 years old. Inuenza and pneumonia are common preventable infectious diseases associated with high mortality and morbidity in people with chronic diseases, such as diabetes. (under the skin) injection. It helps your body to move the sugar in your blood into your cells for energy. This type of insulin is what is called a basal insulin (or a background insulin) and is made to keep a constant amount, or peakless amount, of insulin in your body. This should decrease your blood sugar levels. To start you will inject 10 Units of insulin glargine subcutaneously once daily. Is there a time that works best for you to take the insulin at the same time each day? Can you show me how you would draw up this dose and inject the insulin? It is possible to have low blood sugars when you are on any kind of insulin. Signs of a low blood sugar include shakiness, anxiousness, fast heartbeat, sweating, and confusion. It is important that you always carry a fast-acting type of sugar, such as glucose tablets, with you at all times. Keeping a blood sugar and food diary will help you and your health care providers see how the insulin glargine dose is working to control your diabetes. It is important to bring your blood sugar monitor, diaries, and medications to all of your physician visits and visits with the pharmacist to get a better picture of how you are doing with your diabetes care. Notify your physician if you have any low blood sugar reactions, as he or she may need to adjust your insulin dose.

CHAPTER 84
Type 2 Diabetes Mellitus: Existing Disease

Metformin:
Metformin (also known as Glucophage) is a medication used to treat your diabetes. It works by allowing your body to become more sensitive to the insulin your body is producing and stops your liver from releasing extra sugar. This should decrease your blood sugar levels. Continue taking metformin 1,000 mg in the morning and 1,000 mg in the evening with food. You may experience some stomach or intestinal side effects such as nausea, vomiting, diarrhea, or constipation. It is best to take this medication with food to lessen some of these symptoms. These symptoms should subside in 23 weeks. If these symptoms persist longer than 3 weeks or become severe or intolerable, contact your physician. Your doctor will want you to have blood tests done to check your kidneys and liver every 2 months for the rst year of therapy with metformin. Let the physician know if you have any signs of tiredness, muscle pain, and difculty breathing; they may be signs of a severe adverse effect known as lactic acidosis. It is best not to drink alcohol while on metformin.

Lisinopril:
Lisinopril (also known as Prinivil or Zestril) is a medication used to treat high blood pressure. It works by blocking an enzyme in the body that is necessary to produce a substance that causes vessels to tighten, so it relaxes blood vessels. This lowers blood pressure. Lisinopril is also useful in preventing or delaying damage to your kidneys caused by diabetes. You will take one 20-mg tablet each morning. This medicine sometimes causes dizziness or lightheadedness, cough, skin rash, or diarrhea. Notify your physician if you have any signs of facial (swelling of lips or around the eyes) or extremity (legs or arms) swelling and/or difculty swallowing or breathing. This is a serious side effect of lisinopril. If this occurs, you must discontinue the medication and report to your physician immediately. It is important to stay well hydrated while taking these blood pressure medications. If you become too dehydrated, your blood pressure may drop too low.
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Insulin glargine:
Insulin glargine (also known as Lantus) is a long-acting form of insulin to treat your diabetes. It is a once-daily subcutaneous

84-8 Do not take any nonprescription medications, including herbal products and dietary supplements, unless you have checked with your physician or pharmacist. glucose diary. The insulin glargine dose should be adjusted approximately every 3 days until the fasting blood glucose level falls into the target range consistently. If the patient is still not her target A1C, her blood glucose pattern should be evaluated to see if she experiences high postprandial blood glucose numbers at certain times during the day. Prandial insulin may need to be added to the patients drug regimen. For example, if the patient consistently has high blood glucose results after dinner, a mealtime rapid-acting insulin dose with dinner should be added. Patient-specic factors must be addressed. Other approaches, including those that are least likely to cause hypoglycemia, would be to add a thiazolidinedione or DPP-4 inhibitor to the current drug therapy.1 Lifestyle modications, such as diet and exercise, should be evaluated for areas of improvement and are part of any diabetes treatment regimen.

SECTION 8
Endocrinologic Disorders

Hydrochlorothiazide:
Hydrochlorothiazide is a medication used to treat high blood pressure. It causes your body to lose water and salt. You will need to urinate more frequently, especially at rst. This medicine will be used with the lisinopril. Your physician will check your blood pressure regularly to see how effective the combination is working for your blood pressure. You will take one 12.5-mg tablet each morning. Do not take the medication at bedtime to avoid having to get up to use the bathroom during the night. There is a possibility that this medication may need to be increased to 25 mg in a couple of weeks if your blood pressure is still not under control. Hydrochlorothiazide may cause your skin to be more sensitive to sunlight or ultraviolet light than it is normally. Exposure to sunlight may cause skin rash, itching, redness, or other skin discoloration. Apply a sunblock with at least an SPF 15 and wear protective clothing, including a hat. It is very important that you have blood tests prior to starting your medication and then periodically. Hydrochlorothiazide may cause you to lose potassium in the urine. Your health care provider may have you take a potassium supplement or you may be asked to eat more food with potassium. Do not change your diet without the advice of your health care provider. The following foods contain high amounts of potassium: bananas, coconuts, peaches, orange juice, dates, gs, and apricots. If you experience muscle pain, weakness, or cramps, notify your physician.

REFERENCES
1. American Diabetes Association. Standards of medical care in diabetes. Diabetes Care 2010;33(Suppl 1):S11S61. 2. Joint National Committee on Prevention, Detection, Evaluation, Treatment of High Blood Pressure. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, Treatment of High Blood Pressure. Arch Intern Med 2003;42:12061252. 3. Grundy SM, Cleeman JI, Merz CN, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004;110:227239. 4. Expert Panel on Detection, Evaluation, Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:24862497. 5. NHLBI Obesity Education Initiative Expert Panel on the Identication, Evaluation, and Treatment of Overweight and Obesity in Adults. NIH Publication No. 98-4083. National Institutes of Health, September 1998. 6. Haupt DW. Differential metabolic effects of antipsychotic treatments. Eur Neuropsychopharmacol 2006;16:S149S155. 7. American Diabetes Association. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. Diabetes Care 2009;32(1):193203. 8. Koski RR. Practical review of oral antihyperglycemic agents for type 2 diabetes mellitus. Diabetes Educ 2006;32(2):869876. 9. Pepine CJ, Handberg EM, Cooper-DeHoff RM. A calcium antagonist vs a noncalcium antagonist hypertension treatment strategy for patients with coronary artery disease: the International VerapamilTrandolapril Study (INVEST): a randomized control trial. JAMA 2003;290: 28052816. 10. Colhoun HM, Betteridge DJ, Durrington PN, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet 2004;364:685696. 11. Collins R, Armitage J. Heart Protection Study Collaborative Group: MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet 2003;361:20052016. 12. Edwards SJ, Smith CJ. Tolerability of atypical antipsychotics in the treatment of adults with schizophrenia or bipolar disorder: a mixed treatment comparison of randomized controlled trials. Clin Ther 2009;31:13451359.

Atorvastatin:
Atorvastatin 20 mg will replace your pravastatin 40 mg. This medication is similar to the pravastatin, but more effective in lowering cholesterol. The physician will check your cholesterol panel in 6 weeks and the liver function tests in 3 months. If you notice any unusual muscle aches once this medication has been started, you need to contact your physician immediately. This medication should be taken once a day, preferably at bedtime because cholesterol that is made by the body is mainly produced at night. However, because atorvastatin is a verylong-acting medication, it is not necessary to take this medication at bedtime like the other medications in this class.

m FOLLOW-UP QUESTION
1. What alternative therapies might be appropriate if the initial plan for diabetes treatment fails? The patient is on the recommended daily dose of metformin and has started on basal insulin therapy with insulin glargine. According to the ADA guidelines, the most effective approach would be to intensify insulin therapy.7 The patient should be testing her blood glucose and recording the results in her blood

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