Target Area	Treatment Goals (for the patient with diabetes)
Preprandial plasma glucose (fasting)	90–130 mg/dL
Postprandial plasma glucose (after meals)	<180 mg/dL
Glycosylated hemoglobin (HbA1c)	<7%
Blood pressure	<130/80 mmHg
Lipid levels LDL cholesterol HDL cholesterol Triglycerides

<100 mg/dL

>40 mg/dL (men); >50 mg/dL (women)

<150 mg/dL

Based on the American Diabetes Association guidelines. Individual treatment goals may vary slightly from these guidelines based on personal medical history.

E. Treatment

1. Diet

2. Exercise

3. Type 1: insulin therapy, pramlintide (Symlin)

4. Type 2: oral agents and/or insulin, pramlintide (Symlin), exenatide (Byetta)

F. Insulin

2. Types of insulin

b) Intermediate-acting

(1) Used for basal control

(2) Dosed twice daily for optimal control; may also be dosed once daily at bedtime for patients with type 2 diabetes who also take oral medications to suppress overnight hepatic gluconeogenesis

(3) Example

(a) Isophane insulin, NPH (Humulin N)

c) Long-acting

(1) Like intermediate-acting are used for basal control

(2) Usually dosed once daily

(3) Should not be mixed with any other insulin

(4) Examples

(a) Insulin glargine (Lantus)

(b) Insulin detemir (Levemir)

d) Combination products

(1) Humulin 70/30 (70% NPH, 30% regular)

(2) Humulin 50/50 (50% NPH, 50% regular)

(3) Humalog mix 50/50 (50% insulin lispro protamine suspension, 50% lispro)

(4) Humalog mix 75/25 (75% insulin lispro protamine suspension, 25% lispro)

(5) NovoLog mix 70/30 (70% insulin aspart protamine suspension, 30% aspart)

3. Cautions

a) Causes hypoglycemia at high doses

b) Lispro has more rapid onset than regular and should not be interchanged with it

c) Patients with type 1 DM should not use once-daily dosing of insulin initially

d) Changes in insulin should only be made under supervision of medical personnel

e) Caution is warranted when switching from animal (either pork or bovine) to purified porcine insulin or biosynthetic human insulin due to increased potentcy or bioavailability and increased risk of hypoglycemia.

f) Injection needles should not be reused

g) Insulin should not be used during hypoglycemia

h) Insulin should still be used when ill (may need more insulin when ill)

i) Use of lispro has not been studied in pregnancy, fetal abnormalities occurred in two infants

j) Contraindication: hypersensitivity to the medications

k) Insulin dosing and use requires constant patient education and monitoring

4. Interactions

a) Medications affecting glucose: may increase or decrease effect of insulin

b) Pork and human insulin should not be mixed or used together

5. Toxicity and side effects

a) Hypoglycemia

b) Lipodystrophy

c) Weight gain

d) Patients may develop resistance to insulin treatment

e) Patients may develop sensitivity to animal insulin

7. Injection technique

a) Use abdomen, arm, leg, or buttocks

b) Clean the injection area first with alcohol

c) Examine bottle and roll gently in hands

d) Inject air into vial, draw up desired dose

e) Pinch the skin with one hand, and insert the needle at an angle of 45°–90°

f) Dispose of the syringe properly

g) Rotate the injection site

8. Adjusting insulin dose

a) Adjustments are made based on glucose monitoring and HbA1c as well as pattern of response

b) Adjust basic insulin dose 1–2 units at a time; 2–4 units or more for extreme cases

c) For every unit of rapid-acting insulin, glucose may be reduced by 25–50 mg/dL

d) Long-acting insulin should be adjusted based on fasting glucose

Insulin Calculations

Starting Insulin: Staged Diabetes Management Guideline (SDM)

From Staged Diabetes Management, ed 4 © 2005, International Diabetes Center at Park Nicollet, Minneapolis, MN. All rights reserved. Reprinted with permission (+1)800-637-2675; and Pearson J, Powers M: Systematically Initiating Insulin: The Staged Diabetes Management Approach, The Diabetes Educator 32(Suppl)(1):23s–25s, 2006.

Guideline for starting and titrating background insulin: Background insulin + oral agent(s) insulin glargine or insulin detemir

<70 mg/dL	Decrease 1–2 U
140–250 mg/dL	Increase 2–4 U
>250 mg/dL	Increase 4–8 U

0.1 U/kg body weight if A1c levels are <9% (long acting insulin)

0.2 U/kg body weight if A1c levels are ≥9%

Adjustments are made weekly based on fasting blood glucose.

It is common to start insulin therapy by using only insulin glargine (Lantus) at bedtime in combination with oral agents. The use of background insulin with oral antidiabetic agents is a common approach to initiate insulin therapy. The average dose that was effective in the Treat-to-Target study was 0.4 to 0.5 U/kg at bedtime. Continue to escalate dose if goal is not reached. If the dose surpasses 0.7 U/kg, transition return to background insulin. Mealtime regimen is recommended for tighter control.

Guideline for starting and titrating premixed insulin: Premixed insulin Aspart 70/30 or Lispro premix 75/25

Blood Glucose Adjust Insulin*

Prebreakfast

<70 mg/dL	Decrease pm 1–2 U
140–250 mg/dL	Increase pm 1–2 U
>250 mg/dL	Increase pm 2–4 U

Presupper

<70 mg/dL	Decrease am 1–2 U
140–250 mg/dL	Increase am 1–2 U
>250 mg/dL	Increase am 2–4 U

Start

0.1 U/kg in morning and evening if A1c <9%

0.2 U/kg in morning and evening if A1c ≥9%

Total daily units

0.2–0.4 U/kg

Adjust weekly based on am or pm blood glucose

Guidelines for starting and titrating background/mealtime insulin: Long-acting insulin (insulin glargine or insulin detemir) + rapid-acting insulin with meals

Blood Glucose	Adjust Insulin^†
Prebreakfast	Long-acting (detemir or glargine)
Prelunch am	Rapid acting
Presupper lunch	Rapid acting
Prebedtime supper	Rapid acting
Start	If A1c <9%:
	• 0.1 U/kg long-acting insulin • 0.1 U/kg rapid-acting insulin divided between meals

If A1c ≥9%:

• 0.2 U/kg long-acting insulin

• 0.2 U/kg rapid-acting insulin divided between meals

Total units 0.2–0.4 U/kg Adjust Minimum weekly

^* Stop secretagogue; consider continuing insulin sensitizer(s).

^† Adjust insulin by 1–2 U based on blood glucose pattern. Review insulin-to-carbohydrate ratios and activity. Stop secretagogue; consider continuing insulin sensitizer(s).

G. Synthetic amylin analog, pramlintide acetate (Symlin)

1. Mechanism of action: synthetic analog of human amylin

a) Amylin, like insulin, is located in pancreatic beta cells. It is secreted with insulin in response to food intake.

b) Reduces postprandial glucose

c) Slows gastric emptying

d) Decreases food intake

e) Increases satiety

2. Indications

a) Type 1 and type 2 diabetes as an adjunct to mealtime insulin

3. Usual adult dosage

a) Type 1 diabetes: initially, 15 mcg SC before meals; may titrate up at 15 mcg increments (without nausea for 3 days); maintenance: 30–60 mcg SC before meals

b) Type 2 diabetes: initially, 60 mcg SC before meals; may increase dose to 120 mcg SC before meals (without nausea for three days)

4. Adverse effects

a) Nausea

b) Hypoglycemia

5. Contraindications and considerations

a) Avoid in gastroparesis and hypoglycemia unawareness

b) Potential for drug interactions due to delayed gastric emptying

c) Reduce premeal insulin by 50% when initiating pramlintide

H. Incretin mimetic agent, exenatide (Byetta)

1. Mechanism of action

a) Stimulates the body’s ability to produce insulin in response to elevated concentrations of blood glucose

b) Inhibits the release of glucagon after meals

c) Slows the rate of gastric emptying

d) Reduces food intake

2. Indications

a) Treatment of type 2 diabetes (adjunct to metformin, sulfonylurea, or thiazolidinedione)

3. Usual adult dosage

a) Initially, 5 mcg SC bid given within 60 minutes before morning and evening meal

b) May increase dose to 10 mcg SC bid after one month

c) Available in prefilled pens (must refrigerate)

4. Adverse effects

a) Hypoglycemia (more likely when combined with a sulfonylurea)

b) Nausea

5. Contraindications and considerations

a) Hypersensitivity to exenatide

b) Potential for drug interactions due to delayed gastric emptying

c) Has not been studied for use with insulin

d) Pancreatitis

I. Oral agents for diabetes

1. Sulfonylureas

a) Mechanism of action

(1) Stimulates insulin release from pancreatic beta cells; increases peripheral sensitivity

(2) Inhibits hepatic glucose production; enhances glucose uptake in muscle

(3) Insulin secretagogues

b) First generation versus second generation-

(1) Fewer adverse effects with second generation agents (e.g., glyburide, glipizide), although patient is still at risk for hypoglycemia

(2) Second generation (e.g., glyburide, glipizide, glimepiride) more potent

(3) Comparable efficacy

c) Indications: management of type 2 diabetes as monotherapy; also combined with other antidiabetic medications if needed (e.g., metformin, insulin)

d) Usual adult dosage

Comparable Efficacy

	Generic (Brand)	Adult Daily Dose Range
First generation	Acetohexamide (Dymelor)	250–1500 mg
	Tolbutamide (Orinase)	500–3000 mg
	Tolazamide (Tolinase)	100–1000 mg
	Chlorpropamide (Diabinese)	100–500 mg
Second generation	Glipizide: Glucotrol Glucotrol XL

Glyburide:

Glimepiride (Amaryl) 1–4 mg

(6) Hematologic reactions

f) Contraindications and considerations

(1) Hypersensitivity

(2) Type 1 diabetes

(3) Avoid alcohol

2. Biguanides: Metformin (Glucophage, Glucophage XR, Fortamet, Glumetza, Riomet)

a) Mechanism of action

(1) Inhibit gluconeogenesis and glycogenolysis

(2) Improve insulin sensitivity

(3) Does not stimulate insulin secretion; insulin sensitizers

b) Indications

(1) Management of type 2 diabetes as monotherapy or in combination with sulfonylurea

c) Usual adult dosage

(1) Initially, 500 mg daily for 7–10 days.

(2) Standard dose 500 mg bid with meals

(3) May increase at 1- or 2-week intervals by 500 mg if needed

(4) Maximum dose: 2550 mg/day for younger adults; pediatric and elderly patients should receive lower maximum daily doses.

d) Adverse effects

(1) Metallic taste

(2) Abdominal discomfort/cramping

(3) Diarrhea

(4) Nausea/vomiting

(5) Decrease vitamin B₁₂ levels

(6) Lactic acidosis

e) Contraindications

(1) Avoid in patients with renal dysfunction (SCr >1.5 mg/dL for men and >1.4 for women)

(2) Hypersensitivity

(3) History of lactic acidosis

(4) Pharmacologically treated heart failure

(5) Radiologic contrast procedures (use of contrast increases risk for renal dysfunction and lactic acidosis). Discontinue metformin 48 hours before and after procedure.

(6) Alcoholism (especially frequent binge drinking)

3. Thiazolidinediones, pioglitazone (Actos), rosiglitazone (Avandia)

a) Mechanism of action

(1) Increases peripheral glucose utilization

(2) Decreases hepatic glucose production

(3) Insulin sensitizer and consequently reduces insulin secretion

b) Indications

(1) Management of type 2 diabetes as monotherapy or in combination with sulfonylurea, metformin, or insulin

c) Usual adult dosage

(1) Pioglitazone: initially, 15 or 30 mg daily; may increase at 8- or 12-week intervals; maximum 45 mg daily

(2) Rosiglitazone: initially, 4 mg daily or in divided doses; may increase at 8- or 12-week intervals; maximum 8 mg daily

e) Contraindications and considerations

(1) Avoid in patients with congestive heart failure (CHF) or liver disease

4. Meglitinides, repaglinide (Prandin), nateglinide (Starlix)

a) Mechanism of action

(1) Similar to sulfonylureas

(2) Stimulates insulin release from beta cells in a glucose-dependent manner

(3) Insulin secretagogues

b) Indications

(1) Management of type 2 diabetes as monotherapy or in combination with metformin or thiazolidinedione

c) Usual adult dosage

(1) Repaglinide: If patients have HbA1c <8% or are naïve: 0.5 mg before meals. If they have been previously treated with HbA1c >8%, 1–2 mg before meals may be used. Maximum dose 16 mg daily

(2) Nateglinide: Initially, 120 mg tid before meals; maintenance 120 mg tid before meals; patients near goal HbA1c may use 60 mg tid

(3) For both: Doses should be skipped if a meal is skipped

(5) Flu-like symptoms

e) Contraindications and considerations

(1) Type 1 diabetes or for the treatment of diabetic ketoacidosis (DKA)

J. Complications of diabetes

2. Microvascular complications

a) Diabetic neuropathy (nerve damage caused by prolonged hyperglycemia, often occurring in feet and legs)

(1) Peripheral neuropathy

(2) Autonomic neuropathy

b) Diabetic retinopathy (a leading cause of blindness in the United States)

c) Diabetic nephropathy (kidney damage, nephrons lose filtering capacity, may lead to kidney failure and need for dialysis or transplant

3. Macrovascular complications

a) Hyperlipidemia

b) Hypertension

c) Cardiovascular disease, atherosclerosis

d) Stroke

4. Other complications

a) Increased risk for skin and skin structure infection (e.g., diabetic foot ulcer)

b) Gum disease; oral health complications

II. Thyroid Disorders

Thyroid disorders are among the most common medical endocrine conditions but, because their symptoms often appear gradually over time, they are commonly misdiagnosed. There are two main types of thyroid disease: hyperthyroidism, or too much thyroid hormone, and hypothyroidism, or too little thyroid hormone.

The thyroid produces hormones, called thyroxine (T₄) and triiodothyronine (T₃), which affect the body’s metabolism and energy level. T₃ is the short-acting and more potent of the two hormones. Thyroid hormone is also produced in response to thyroid stimulating hormone (TSH, also known as thyrotropin) secreted by the pituitary gland.

A. Hypothyroidism occurs when the thyroid gland does not produce enough thyroid hormone.

1. Hashimoto thyroiditis

a) Most common type

b) Inflammation of thyroid gland (not caused by infection)

c) Occurs when the individual’s immune system attacks the thyroid gland, causing low levels of thyroid hormone

d) Exhibits low plasma free T₄ and elevated TSH levels

2. Signs and symptoms

a) Thyroid replacement hormones

(1) Levothyroxine (T₄) (Synthroid, Levothroid, Levoxyl, others)

(a) Typical adult maintenance dose after titration: 100–120 mcg PO daily as a single dose 30 minutes before breakfast, given with plenty of plain water

(i) Adjust dose in the elderly and in patients with coronary artery disease

(ii) Initial dose in elderly 25 mcg per day versus the initial dose for younger adults, which is typically 50 mcg per day

(iii) Those with cardiac disease also start at 25 mcg daily

(b) Highly protein bound

(i) Long-term use has been associated with increased bone reabsorption and decreased bone density

(d) Drug interactions

(i) Antacids, calcium, or iron supplements should not be taken within four hours of levothyroxine dose; may decrease T₄ absorption

(ii) Warfarin effects are enhanced by levothyroxine

(iii) Digoxin levels may be reduced by levothyroxine

(2) Liothyronine (T₃) (Cytomel, Triostat)

(a) Adult dose: 25 mcg PO qd

(3) Liotrix (T₄ and T₃, 4:1 ratio) (Thyrolar)

(a) Adult dose: 60–120 mg PO qd

(4) Desiccated thyroid, variable T₄ and T₃ content due to animal gland sourcing (Armour Thyroid, Naturethroid, Westhyroid)

(a) Adult dose: 60–120 mg PO qd

B. Hyperthyroidism (thyrotoxicosis): occurs when the thyroid gland produces too much thyroxine. As a result, the individual’s metabolism increases dramatically, leading to weight loss and irregular heartbeat.

PATIENT PROFILE

Allergies: No known drug allergies (NKDA)

Chief Complaint:

CC is a 22-year-old woman with a history of gestational diabetes; she has one child, now 2 years old. She presents to the pharmacist clinic service for the first time because her family doctor has just told her that she now has type 2 diabetes. “My blood sugars were high on two tests,” she explains, “but I feel great, and I am young. Why do I have to take medications? Can’t I just exercise and lose some weight?”

Social History:

Tobacco use: None

Alcohol use: A few glasses of wine per week, usually with dinner

Exercise: Began walking program last week with her mother, who also has type 2 diabetes and is overweight

Medications:

Multivitamin once daily

New prescription: Metformin 500 mg PO twice daily

Other: Wears eyeglasses for reading

Laboratory:

Blood glucose: 220 mg/dL, nonfasting

Blood glucose: 140 mg/dL, fasting

Hemoglobin A1c (HbA1c): 8.6%

PATIENT PROFILE QUESTIONS

1. After discussion with the patient, it is clear that CC has little understanding of her new diagnosis and will need extensive diabetic education. When discussing blood sugar and HbA1c tests, which of the following would a pharmacist state as CC’s HbA1c treatment goal?

Answer: d. Based on well-known studies such as the Diabetes Control and Complications Trial (DCCT), a goal HbA1c of less than 7% reduces the risk of microvascular complications, such as diabetes-related nephropathy and retinopathy. Higher HbA1c levels increase the risk of chronic complications of diabetes. Some organizations recommend more aggressive goals (e.g., HbA1c <6.5%), but aggressive goals expose a patient to a greater risk of severe hypoglycemia.

2. The pharmacist encourages CC’s new exercise routine and weight loss goals. These plans are endorsed by her family doctor. Exercise may improve insulin sensitivity, promote weight reduction, and improve overall health. Weight reduction can lower the need for medications in some patients. In addition to exercise, what other preventative options should be recommended for CC at this time?

I. Checking with her doctor regarding her cholesterol levels

II. Taking a “baby aspirin” (aspirin 81 mg) daily to prevent heart disease

III. Performing daily foot self-examinations

IV. Keeping regularly scheduled ophthalmic exams

Answer: c. All patients with diabetes should be screened for lipid disorders because early management can help prevent macrovascular complications, such as myocardial infarction (MI). Current evidence suggests that aspirin is ONLY recommended for patients with diabetes with known heart disease and as primary prevention ONLY in patients with diabetes older than 30 years old with heart disease risk factors. CC is 22 years of age and is in an age bracket where insufficient benefit and risk information is available regarding preventative aspirin therapy. Daily self-examinations of the feet for cracks, callus formation, ulcers, and other issues will help avoid serious foot problems. Routine eye exams are recommended for any patient with diabetes with known visual difficulty; how often they are performed depends on age and known visual problems. Annual eye exams are recommended for those older than 30 years of age without any current visual difficulties. Younger patients should have routine exams at least every 5 years or more frequently if they already have visual impairment or changes.

3. CC will begin the metformin prescription as prescribed. During discussion with CC, the pharmacist should include which of the following in the counseling about the new prescription?

I. Metformin is often a drug of choice when type 2 diabetes is first diagnosed. It is effective at lowering blood sugar, does not cause weight gain, and does not cause low blood sugar when used alone.

II. Common side effects that usually decrease in a few weeks include nausea or reduced appetite.

III. CC should avoid binge drinking of alcohol to avoid lactic acidosis, a serious but rare side effect that can harm the kidneys.

IV. If CC follows her recommended diet and exercise plan, maintains a recommended body weight, and takes the metformin as prescribed, she can expect her HbA1c to drop about 1.5% with the medication.

Answer: d. Diabetes treatment guidelines place metformin monotherapy as first-line treatment for healthy, adults newly diagnosed with type 2 diabetes who have no other contraindications to metformin use. Common side effects are nausea, diarrhea, reduced appetite, and sometimes a metallic-like taste. These usually go away in a few weeks. Binge drinking of alcohol can be a risk factor for lactic acidosis and is often an important counseling point in a young patient with an active social life. Metformin will reduce HbA1c, will not cause weight gain, and can help CC reach her optimal health goals. If she is educated and adherent, she may avoid the need for additional medications.

REVIEW QUESTIONS

(Answers and Rationales on page 356.)

1. Lipohypertrophy in patients with diabetes is due to which of the following?

a. Repeated injections into the same site

b. Injections into fat-rich tissue

c. Too-rapid insulin injection

d. Hypersensitivity to insulin

e. Hypersensitivity to insulin vehicle

2. Which of the following is true of insulin?

a. It is secreted by pancreatic alpha cells

b. It promotes peripheral glucose uptake and utilization

c. It inhibits hepatic gluconeogenesis

d. a and b

e. b and c

3. Which of the following insulin preparations is available as a recombinant human analog?

4. Which of the following steroids have the longest duration of action?

5. Which of the following conditions increases the risk of amputations in diabetics?

a. Peripheral Neuropathy

b. Peripheral Vascular Disease

c. Erythema

d. All of the above

e. None of the above

6. Which of the following is used for treatment of thyroid storm:

I. levothyroxine

II. hydrocortisone

III. propylthiouracil

7. Which of the following classes of drugs requires periodic monitoring of liver function?

e. None of these drugs requires monitoring of liver function

8. Which of the following should be monitored in patients with diabetes treated with ACE inhibitors?

a. Serum creatinine, blood urea nitrogen, potassium, and sodium

b. Serum creatinine and blood urea nitrogen

c. Urine protein and sodium

d. Urine protein, sodium, and glucose

e. Urine protein, sodium, glucose, and potassium

9. Of the following patients, which is most likely to experience an adverse drug reaction?

a. 30-year-old man taking chlorpropamide and atenolol

b. 40-year-old woman taking pioglitazone with a serum BUN of 17 mg/dL

c. 30-year-old woman taking acarbose with an ALT of 80 IU/L and AST of 90 IU/L

d. 40-year-old man taking lisinopril and pioglitazone

e. 40-year-old woman taking lisinopril with an ALT of 30 IU/L and AST of 30 IU/L

10. Androgens are associated with which of the following adverse effects?

11. Sulfonylureas are associated with which of the following adverse effects?

12. Which of the following statements about insulin is true?

a. It is secreted by pancreatic alpha cells,

b. It promotes peripheral glucose uptake and utilization,

c. It inhibits hepatic gluconeogenesis,

d. a and b

e. b and c

13. Which of the following is a useful feature to differentiate cholinestase inhibitor overdose with myasthenia gravis exacerbation?

14. Which of the following agents can cause the syndrome of inappropriate secretion of antidiuretic hormone (SIADH)?

15. Which of the following is TRUE about sulfonylureas?

a. Tolazamide is a second generation agent

b. Chlorpropamide is a first generation agent

c. Safe to use during pregnancy

d. a and b

e. b and c

16. What is the standard daily dose of glyburide?

17. Patients taking chlorpropamide should be counseled to avoid which of the following?

18. Which of the following are responsible for inhibiting insulin release?

19. Which of the following drugs increase pancreatic insulin secretion?

21. Which of the following is/are the active ingredient(s) of Avandamet?

22. CO is a taking Precose (acarbose) 100 mg PO tid. Which of the following should be monitored?

23. Glyset is a drug that inhibits:

a. alpha glucosidase

b. angiotensin-converting enzyme (ACE)

c. protease

d. acetylcholinesterase

e. topoisomerase

24. Which of the following is NOT an appropriate treatment for hyperthyroidism?

25. Which of the following is a side effect of biosynthetic growth hormone?

a. Hepatitis B

b. Antibody formation

c. Creutzfeldt-Jakob disease

d. HIV transmission

e. Hypoglycemia

26. Which of the following statements about insulin is true?

a. It is reabsorbed in the renal tubules.

b. It is metabolized in the liver.

c. It has a half-life of less than 10 minutes.

d. a and b

e. a, b, and c

27. Which of the following causes increased insulin activity after glucose consumption?

a. Gastrin

b. Secretin

c. Gastric inhibitory polypeptide (GIP)

d. a and b

e. a, b, and c

28. Which of the following is an effect of insulin?

a. Inhibition of hormone sensitive lipase

b. Increased glycogenolysis

c. Increased CNS glucose uptake

d. a and b

e. a and c

29. Insulin ultralente:

a. has an onset of action in 1–2 hours.

b. has peak activity at 4–6 hours.

c. has a duration of action of 18–24 hours.

d. All of the above

e. None of the above

30. Which of the following is NOT a side effect of chlorpropamide?

a. Hypoglycemia

b. Rash

c. Lactic acidosis

d. Syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH)

e. Disulfiram-type reaction

31. Which of the following is an effect of sulfonylureas?

a. Decreased hepatic gluconeogenesis

b. Increased peripheral tissue insulin sensitivity

c. Increased insulin-receptor binding

d. a and b

e. a, b, and c

32. Which of the following may cause SIADH?

33. Which of the following statements about oral hypoglycemic agents is true?

a. Second-generation agents have less affinity for albumin.

b. First-generation agents are more potent due to larger R substituents.

c. First- and second-generation hypoglycemic agents are sulfonylureas.

d. a and b

e. a and c

34. Which of the following is NOT a mechanism of oral sulfonylureas?

a. Regeneration of pancreatic beta cells

b. Correction of post receptor defects

c. Increased tissue insulin sensitivity

d. Decreased hepatic gluconeogenesis

e. All of the above are mechanisms of sulfonylureas

35. Which of the following is the correct insulin: onset of action pair?

a. Insulin Lispro: 1–3 hrs

b. Regular: 10–15 min

c. Insulin glargine: 0.5–1 hr

d. All of the above.

e. None of the above.

36. Effects of insulin include:

a. increased glycogenolysis.

b. increased glycosuria.

c. increased conversion of protein to glucose.

d. increased transport of glucose into the central nervous system.

e. inhibition of hormone sensitive lipase.

37. Which of the following statements is correct?

a. Lente insulin has an initial onset of 1–2 hours, a peak at 6–14 hours, and a duration of 24 or more hours.

b. Regular insulin has an initial onset of 30 minutes to 1 hour, a peak at 2–4 hours, and a duration of 5–7 hours.

c. NPH insulin has an initial onset at 10–15 minutes, a peak at 2–4 hours, and a duration of 3–5 hours.

d. a and b

e. a and c

38. Which of the following may occur with methimazole?

a. Pruritus

b. Neutropenia

c. Decreases peroxidase activity

d. a and c

e. a, b, and c

39. What is the standard recommended dose range of glyburide?

40. Patients taking chlorpropamide should avoid products containing:

41. Which of the following pregnant patients does NOT need to undergo a 50 g glucose screening test during weeks 24–28 of pregnancy?

a. 30-year-old Latin woman with a negative screen at 15 weeks

b. 30-year-old Pacific Island woman who has a body mass index of 30 and no family history of diabetes

c. 20-year-old African American woman with a body mass index of 22 and no family history of diabetes

d. 20-year-old Caucasian woman with normal body weight

e. 20-year-old Latin woman with a body mass index of 30 and no family history of diabetes

42. A 22-year-old patient is admitted to the hospital with diabetic ketoacidosis (DKA). What is the most appropriate treatment to decrease cerebral edema in this patient?

a. Sodium bicarbonate

b. Insulin

c. Methylprednisolone

d. Mannitol

e. None of the above

43. Normal blood glucose for a fasting patient is between:

Read the following case study and answer the questions that follow.

A 55-year-old man goes to the physician for his annual check-up. He has a medical history significant for obesity, hypertension, gout, and hypercholesterolemia. He reports that 1 week earlier, he attended a free health clinic at his place of work where his random blood glucose was found to be 220 mg/dL. On examination, he has decreased hair growth over the lower legs, decreased sensation over the feet and ankles, and flame hemorrhages on opthalmoscopic examination. Laboratory diagnosis on a fasting blood sample shows a blood glucose of 175 mg/dL. His physician diagnoses DM.

44. Which of the following is NOT a risk factor for DM type 2?

e. Sedentary lifestyle

45. Which of the following is the most appropriate dosage and medication for the initial treatment of DM type 2?

a. Pioglitazone, 500 mg once per day

b. Metformin, 500 mg twice per day

c. Insulin glargine, 15 units once per day

d. Glipizide, 5 mg once per day

e. Repaglinide, 5 mg before each meal

46. Metformin:

a. may cause diarrhea.

b. is safe to use in diabetic ketoacidosis.

c. decreases gluconeogenesis.

d. a and b

e. a and c

47. Glipizide:

a. enhances insulin release.

b. enhances peripheral insulin sensitivity.

c. inhibits hepatic glucose production.

d. a and b

e. a, b, and c

48. True or False: Pioglitazone does not require dose adjustments for renal impairment.

a. True

b. False

49. Pioglitazone:

a. may cause myalgia.

b. should be taken on an empty stomach.

c. is poorly protein bound in circulation.

d. is excreted predominately (>90%) in the urine.

e. All of the above

52. Avandia:

I. Improves insulin secretion

II. Improves insulin sensitivity

III. Inhibits hepatic glucose production

a. Has a rapid onset of action

b. Should be administered subcutaneously

c. Should be given within 15 minutes of a meal

d. Is insulin Lispro

e. All of the above

54. Which of the following is a rare but serious side effect of Glucophage?

a. Pulmonary fibrosis

b. Neurotoxicity

c. Lactic acidosis

d. Pulmonary embolism

e. Infertility

55. Which of the following insulin preparations has a prolonged duration of action?

^* When mixing regular and NPH, regular should be drawn up first or the protamine in NPH will cause the regular insulin in the vial to become cloudy (the same applies to mixing regular with any other insulin).

[/level-membership-for-basic-science-category][not-level-membership-for-basic-science-category]

CHAPTER 12 Common Endocrinologic Disorders

I. Diabetes Mellitus

A. Classification

4. Prediabetes is the increased risk of developing DM.

a) Impaired fasting glucose (IFG): fasting glucose 100–125 mg/dL

b) Impaired glucose tolerance (IGT): Two-hour glucose 140–199 mg/dL during oral glucose tolerance test (OGTT)

B. Signs and symptoms

1. The 3 Ps: polyuria, polydipsia, polyphagia

2. Blurred vision

3. Fatigue

4. Dry, itchy skin

5. Slow wound healing

6. Weight loss (type 1 diabetes)

C. Diagnosis

1. Random plasma glucose > 200 mg/dL plus signs and symptoms of diabetes OR

2. Fasting plasma glucose > 126 mg/dL OR

3. Two-hour postprandial glucose > 200 mg/dL during OGTT

4. Confirm the above.

5. Hemoglobin A1c testing (HbA1c): HbA1c is not used to diagnose DM, but is used for long-term monitoring.

D. Goals of therapy

Goals of Therapy

Target Area	Treatment Goals (for the patient with diabetes)
Preprandial plasma glucose (fasting)	90–130 mg/dL
Postprandial plasma glucose (after meals)	<180 mg/dL
Glycosylated hemoglobin (HbA1c)	<7%
Blood pressure	<130/80 mmHg
Lipid levels LDL cholesterol HDL cholesterol Triglycerides

<100 mg/dL

>40 mg/dL (men); >50 mg/dL (women)

<150 mg/dL

Based on the American Diabetes Association guidelines. Individual treatment goals may vary slightly from these guidelines based on personal medical history.

E. Treatment

1. Diet

2. Exercise

3. Type 1: insulin therapy, pramlintide (Symlin)

4. Type 2: oral agents and/or insulin, pramlintide (Symlin), exenatide (Byetta)

F. Insulin

2. Types of insulin

b) Intermediate-acting

(1) Used for basal control

(2) Dosed twice daily for optimal control; may also be dosed once daily at bedtime for patients with type 2 diabetes who also take oral medications to suppress overnight hepatic gluconeogenesis

(3) Example

(a) Isophane insulin, NPH (Humulin N)

c) Long-acting

(1) Like intermediate-acting are used for basal control

(2) Usually dosed once daily

(3) Should not be mixed with any other insulin

(4) Examples

(a) Insulin glargine (Lantus)

(b) Insulin detemir (Levemir)

d) Combination products

(1) Humulin 70/30 (70% NPH, 30% regular)

(2) Humulin 50/50 (50% NPH, 50% regular)

(3) Humalog mix 50/50 (50% insulin lispro protamine suspension, 50% lispro)

(4) Humalog mix 75/25 (75% insulin lispro protamine suspension, 25% lispro)

(5) NovoLog mix 70/30 (70% insulin aspart protamine suspension, 30% aspart)

3. Cautions

a) Causes hypoglycemia at high doses

b) Lispro has more rapid onset than regular and should not be interchanged with it

c) Patients with type 1 DM should not use once-daily dosing of insulin initially

d) Changes in insulin should only be made under supervision of medical personnel

f) Injection needles should not be reused

g) Insulin should not be used during hypoglycemia

h) Insulin should still be used when ill (may need more insulin when ill)

i) Use of lispro has not been studied in pregnancy, fetal abnormalities occurred in two infants

j) Contraindication: hypersensitivity to the medications

k) Insulin dosing and use requires constant patient education and monitoring

4. Interactions

a) Medications affecting glucose: may increase or decrease effect of insulin

b) Pork and human insulin should not be mixed or used together

5. Toxicity and side effects

a) Hypoglycemia

b) Lipodystrophy

c) Weight gain

d) Patients may develop resistance to insulin treatment

e) Patients may develop sensitivity to animal insulin

7. Injection technique

a) Use abdomen, arm, leg, or buttocks

b) Clean the injection area first with alcohol

c) Examine bottle and roll gently in hands

d) Inject air into vial, draw up desired dose

e) Pinch the skin with one hand, and insert the needle at an angle of 45°–90°

f) Dispose of the syringe properly

g) Rotate the injection site

8. Adjusting insulin dose

a) Adjustments are made based on glucose monitoring and HbA1c as well as pattern of response

b) Adjust basic insulin dose 1–2 units at a time; 2–4 units or more for extreme cases

c) For every unit of rapid-acting insulin, glucose may be reduced by 25–50 mg/dL

d) Long-acting insulin should be adjusted based on fasting glucose

Insulin Calculations

Starting Insulin: Staged Diabetes Management Guideline (SDM)

Guideline for starting and titrating background insulin: Background insulin + oral agent(s) insulin glargine or insulin detemir

<70 mg/dL	Decrease 1–2 U
140–250 mg/dL	Increase 2–4 U
>250 mg/dL	Increase 4–8 U

0.1 U/kg body weight if A1c levels are <9% (long acting insulin)

0.2 U/kg body weight if A1c levels are ≥9%

Adjustments are made weekly based on fasting blood glucose.

Guideline for starting and titrating premixed insulin: Premixed insulin Aspart 70/30 or Lispro premix 75/25

Blood Glucose Adjust Insulin*

Prebreakfast

<70 mg/dL	Decrease pm 1–2 U
140–250 mg/dL	Increase pm 1–2 U
>250 mg/dL	Increase pm 2–4 U

Presupper

<70 mg/dL	Decrease am 1–2 U
140–250 mg/dL	Increase am 1–2 U
>250 mg/dL	Increase am 2–4 U

Start

0.1 U/kg in morning and evening if A1c <9%

0.2 U/kg in morning and evening if A1c ≥9%

Total daily units

0.2–0.4 U/kg

Adjust weekly based on am or pm blood glucose

Guidelines for starting and titrating background/mealtime insulin: Long-acting insulin (insulin glargine or insulin detemir) + rapid-acting insulin with meals

Blood Glucose	Adjust Insulin^†
Prebreakfast	Long-acting (detemir or glargine)
Prelunch am	Rapid acting
Presupper lunch	Rapid acting
Prebedtime supper	Rapid acting
Start	If A1c <9%:
	• 0.1 U/kg long-acting insulin • 0.1 U/kg rapid-acting insulin divided between meals

If A1c ≥9%:

• 0.2 U/kg long-acting insulin

• 0.2 U/kg rapid-acting insulin divided between meals

Total units 0.2–0.4 U/kg Adjust Minimum weekly

^* Stop secretagogue; consider continuing insulin sensitizer(s).

^† Adjust insulin by 1–2 U based on blood glucose pattern. Review insulin-to-carbohydrate ratios and activity. Stop secretagogue; consider continuing insulin sensitizer(s).

G. Synthetic amylin analog, pramlintide acetate (Symlin)

1. Mechanism of action: synthetic analog of human amylin

a) Amylin, like insulin, is located in pancreatic beta cells. It is secreted with insulin in response to food intake.

b) Reduces postprandial glucose

c) Slows gastric emptying

d) Decreases food intake

e) Increases satiety

2. Indications

a) Type 1 and type 2 diabetes as an adjunct to mealtime insulin

3. Usual adult dosage

a) Type 1 diabetes: initially, 15 mcg SC before meals; may titrate up at 15 mcg increments (without nausea for 3 days); maintenance: 30–60 mcg SC before meals

b) Type 2 diabetes: initially, 60 mcg SC before meals; may increase dose to 120 mcg SC before meals (without nausea for three days)

4. Adverse effects

a) Nausea

b) Hypoglycemia

5. Contraindications and considerations

a) Avoid in gastroparesis and hypoglycemia unawareness

b) Potential for drug interactions due to delayed gastric emptying

c) Reduce premeal insulin by 50% when initiating pramlintide

H. Incretin mimetic agent, exenatide (Byetta)

1. Mechanism of action

a) Stimulates the body’s ability to produce insulin in response to elevated concentrations of blood glucose

b) Inhibits the release of glucagon after meals

c) Slows the rate of gastric emptying

d) Reduces food intake

2. Indications

a) Treatment of type 2 diabetes (adjunct to metformin, sulfonylurea, or thiazolidinedione)

3. Usual adult dosage

a) Initially, 5 mcg SC bid given within 60 minutes before morning and evening meal

b) May increase dose to 10 mcg SC bid after one month

c) Available in prefilled pens (must refrigerate)

4. Adverse effects

a) Hypoglycemia (more likely when combined with a sulfonylurea)

b) Nausea

5. Contraindications and considerations

a) Hypersensitivity to exenatide

b) Potential for drug interactions due to delayed gastric emptying

c) Has not been studied for use with insulin

d) Pancreatitis

I. Oral agents for diabetes

1. Sulfonylureas

a) Mechanism of action

(1) Stimulates insulin release from pancreatic beta cells; increases peripheral sensitivity

(2) Inhibits hepatic glucose production; enhances glucose uptake in muscle

(3) Insulin secretagogues

b) First generation versus second generation-

(1) Fewer adverse effects with second generation agents (e.g., glyburide, glipizide), although patient is still at risk for hypoglycemia

(2) Second generation (e.g., glyburide, glipizide, glimepiride) more potent

(3) Comparable efficacy

c) Indications: management of type 2 diabetes as monotherapy; also combined with other antidiabetic medications if needed (e.g., metformin, insulin)

d) Usual adult dosage

Comparable Efficacy

	Generic (Brand)	Adult Daily Dose Range
First generation	Acetohexamide (Dymelor)	250–1500 mg
	Tolbutamide (Orinase)	500–3000 mg
	Tolazamide (Tolinase)	100–1000 mg
	Chlorpropamide (Diabinese)	100–500 mg
Second generation	Glipizide: Glucotrol Glucotrol XL