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Peripheral vascular disease or peripheral arterial disease presents as diminished

or absent foot pulses, intermittent claudication, skin ulcers, gangrene, or amputation.

People with diabetes are 2 to 10 times more likely to experience symptoms of

peripheral arterial disease than those without diabetes, and half of all nontraumatic

amputations in the United States are performed in patients with diabetes. In one study

that followed Type 2 patients for 7 years, 5.5% had an amputation. The prevalence of

this condition increases with age, duration of diabetes, and the presence of risk

factors such as hypertension or smoking.

293,297

Signs and symptoms of peripheral arterial disease include leg pain, which is

relieved by rest; cold feet; nocturnal leg pain, which is relieved by dangling the feet

over the bed or walking; absent pulses; loss of hair on the foot and toes; and

gangrene. Treatment of this condition includes elimination and treatment of risk

factors such as smoking, dyslipidemia, hypertension, and hyperglycemia; antiplatelet

therapy; exercise, which is the mainstay of therapy; and revascularization surgery.

297

H.D. should be thoroughly educated regarding proper foot care, perform daily selffoot examinations, and receive regular care by a podiatrist.

298

DRUG-INDUCED ALTERATIONS IN GLUCOSE

HOMEOSTASIS

Persons with diabetes are likely to take more drugs in their lifetime than any other

group of patients. Patients with Type 2 diabetes present with a constellation of

chronic conditions, including hypertension, dyslipidemia, and CVD, all of which will

likely require drug therapy. Drugs to manage depression, intermittent infections, and

neurologic and ophthalmologic conditions also are commonly prescribed. Because

we know that the actions of drugs are complex and that for every desired effect there

are several other unwanted effects, each time a drug is added to the regimen of

someone with diabetes it is important to assess the patient’s situation to determine

whether a potential exists for a drug–drug or drug–disease interaction or whether the

benefit of the newly prescribed drug is likely to outweigh its risks. With the

availability of online drug information databases to assist in assessment of drug–drug

and drug–disease interactions, a detailed listing of drugs that can exacerbate

hyperglycemia and hypoglycemia is not provided. Below, a few case examples are

illustrated. Some medications that can have significant hyperglycemic effects include

atypical antipsychotics, protease inhibitors, corticosteroids, immunosuppressants

(e.g., tacrolimus, cyclosporine), niacin (higher doses), gonadotropin-releasing

hormone agonists (used in men for prostate cancer), and pentamidine (can also cause

hypoglycemia).

299,300 Patients should be monitored closely for a medication’s

possible effect on the BG levels.

Drug-Induced Hyperglycemia

CORTICOSTEROIDS

CASE 53-20

QUESTION 1: A.L., a 37-year-old obese woman with systemic lupus erythematosus, has been taking 60

mg/day of prednisone for 6 months. During this period, her weight has increased by 30 lb and she has

experienced glycosuria (no ketones). Her primary provider asked her to start SMBG. She was referred to the

diabetes clinic, where her predinner and bedtime BG values were found to be 140 to 160 mg/dL and FBG

values were 80 to 105 mg/dL. Physical examination shows a 5 feet 2 inch, 150-lb, depressed woman with

truncal obesity and an acneiform rash. Her mother and one sister have Type 2 diabetes. How do corticosteroids

contribute to diabetes mellitus? How should A.L. be treated?

The term steroid diabetes was first used to describe the hyperglycemia and

glycosuria seen in patients with Cushing syndrome. Now, it is associated more

commonly with exogenously administered glucocorticoids and has been a side effect

of parenteral, oral, and even topical therapy. Corticosteroids are one of the most

common drug groups that unmask latent diabetes or aggravate preexisting disease,

and they may produce hyperglycemia and overt diabetes in individuals who are not

otherwise predisposed.

Corticosteroids increase hepatic gluconeogenesis, suppress insulin secretion, and

decrease tissue responsiveness to insulin.

300 The primary effect is impaired glucose

disposal after meals, resulting in daytime hyperglycemia, and by morning, the glucose

levels normalize. Although steroid-induced diabetes generally is mild and rarely

associated with ketonemia, a wide spectrum of severity may be encountered—from

asymptomatic, abnormal glucose tolerance tests to difficult-to-control, insulinrequiring disease. The onset of glucose tolerance can occur within hours to days or

after months to years of chronic therapy. The effect generally is considered dose-

dependent and usually is reversible on discontinuation of the drug.

A.L. exhibits many symptoms that can be attributed to supraphysiologic doses of

corticosteroids: truncal obesity, depression, acneiform rash, and diabetes. Mildly

elevated glucose levels in obese individuals, as in A.L.’s case, sometimes can be

controlled by diet, but may require treatment with a short-acting insulin secretagogue

or rapid-acting insulin before meals.

300 A person with diabetes whose BG is

increased by use of a glucocorticoid should modify treatment appropriately to restore

glycemic control. It is important to anticipate the need to modify insulin or other

antidiabetic therapy because corticosteroid doses are increased or decreased.

SYMPATHOMIMETICS

CASE 53-21

QUESTION 1: R.C., a 41-year-old man with Type 1 diabetes, is well controlled on a basal-bolus insulin

regimen and has been taking pseudoephedrine 30 mg QID for 7 days and Robitussin DM 10 mL QID (which

contains 2.92 g of sugar/5 mL) for a cold. Recently, glucose concentrations have been higher than usual. Can

pseudoephedrine or the cough preparation be the cause of his poor glycemic control? Discuss the use of

sympathomimetics and cough preparations in patients with diabetes.

Over-the-counter drug products, such as decongestants and diet aids, which

contain sympathomimetics, carry warning labels that caution against their use in

patients with diabetes. Standard sugar- and ethanol-containing cough preparations

also carry such warning labels. However, clinically significant drug-induced glucose

intolerance probably is very infrequent. It is well established that parenterally

administered epinephrine increases BG concentrations secondary to increased

glycogenolysis and gluconeogenesis. Other sympathomimetics generally do not have

as potent an effect on BG as epinephrine, and their use usually does not pose a

practical problem in diabetic patients. Furthermore, the effects of sympathomimetics

on BP must be considered in many patients with diabetes. Therefore, antihistamines

or occasional use of nasal sprays for severe congestion may be needed.

In summary, pseudoephedrine or the cough preparation may be aggravating R.C.’s

glycemic control, although at these low-to-normal therapeutic doses, it is quite

unlikely. The stress related to R.C.’s underlying cold is more likely to be impairing

his glucose tolerance than these low doses of sympathomimetic agents or the small

amounts of sugar contained in the cough syrup.

p. 1146

p. 1147

Drug-Induced Hypoglycemia

ETHANOL

CASE 53-22

QUESTION 1: C.F., a 22-year-old woman with newly diagnosed Type 1 diabetes, enjoys a glass or two of

wine with her evening meal. What effect does alcohol have on a patient with diabetes, particularly one using

insulin? Is alcohol contraindicated in C.F. or any person with diabetes?

Clinicians often are reluctant to permit the use of alcoholic beverages in patients

with diabetes. However, barring contraindications that are similar in the nondiabetic

and diabetic patient alike (e.g., alcoholism, hypertriglyceridemia, gastritis,

pancreatitis, pregnancy), a person with diabetes can safely enjoy a moderate alcohol

intake as long as certain precautions are taken. For an in-depth discussion, the reader

is referred to two comprehensive reviews of alcohol and diabetes,

301,302 parts of

which are summarized in the following list:

Drink in moderation. The ADA defines this as a daily intake of one drink for adult

women and two drinks for adult men (one drink is defined as 5 ounces of wine,

12 ounces of beer, or 1.5 ounces of distilled liquor). The patient should be aware

of his/her own sensitivity to the intoxicating effects of ethanol and adjust

consumption downward, if needed. This is particularly important for insulindependent patients. When having a drink, be sure to have it with a carbohydratecontaining meal.

Avoid drinks that contain large amounts of sugar, such as liqueurs, sweet wines, and

sugar-containing mixes. Instead, consider dry wines, light beers, and distilled

spirits. Not only does the simple sugar content add an additional source of

glucose and calories to the diet, but ethanol ingested with simple sugar-containing

mixers enhances reactive hyperglycemia.

Remember to count the calories in alcohol (calories = [0.8] × [proof] × [ounces]);

substitute 1 ounce of alcohol for two fat exchanges.

Be aware that the symptoms of alcohol intoxication and hypoglycemia are similar. If

hypoglycemia is mistaken for intoxication by others, appropriate and potentially

life-saving treatment can be delayed.

Be aware of alcohol–sulfonylurea drug interactions, specifically the alcoholinduced enzyme induction of tolbutamide metabolism and the chlorpropamide–

alcohol flush reaction.

ACKNOWLEDGMENT

The authors acknowledge Lisa A. Kroon and Craig Williams for their contributions

to this chapter in earlier editions.

KEY REFERENCES AND WEBSITES

A full list of references for this chapter can be found at

http://thepoint.lww.com/AT11e. Below are the key references and websites for this

chapter, with the corresponding reference number in this chapter found in parentheses

after the reference.

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Key Websites

American Diabetes Association. http://www.diabetes.org.

The American Association of Clinical Endocrinologists. https://www.aace.com/

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