Updated May 2007
Diabetes is a common disease in the United States, affecting approximately 21 million people and accounting for >224,000 deaths per year.1 HIV-infected patients are developing disorders of glucose metabolism because they are living longer and/or may be predisposed to developing diabetes. There is also evidence that hyperinsulinemia with abnormal glucose metabolism may result from the use of protease inhibitors (PIs) and possibly nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs, NtRTIs).2,3
The association between hyperinsulinemia and ARV therapy may result from direct effects of ARV drugs on cellular glucose uptake4 and lipolysis, as well as peripheral insulin resistance associated with decreased limb fat and/or increased visceral fat. Lipid abnormalities and/or body fat changes (the “lipodystrophy syndrome”) often accompany these glucose metabolism abnormalities. Clinical presentation and complications of diabetes in HIV-infected patients receiving ARV therapy are similar to those in patients not receiving ARV therapy and to those in non-HIV-infected individuals.
A. Assessment and Prevention of Diabetes
Clinicians should assess for risk factors for type 2 diabetes in HIV-infected patients at baseline and annually (see Table 1).
Clinicians should emphasize appropriate diet, weight control, and exercise as methods to avoid the development of type 2 diabetes.
Clinicians should assess fasting blood glucose before initiating HAART, 3 to 6 months after initiation, and at least annually thereafter.
Clinicians should administer 75 g of oral glucose (2-hour glucose tolerance test) to distinguish between impaired glucose tolerance (glucose level ≥140 mg/dL 2 hours after oral glucose) and diabetes (glucose level ≥200 mg/dL after oral glucose) in patients with repeated borderline fasting glucose values.
Baseline and annual assessment of risk factors for type 2 diabetes in HIV-infected individuals allows for early identification and intervention. See Table 1 for risk factors.
|Table 1: Risk Factors for Type 2 Diabetes in HIV-Infected Patients*|
|IGT, impaired glucose tolerance; IFG, impaired fasting glucose.
* Except for HIV-related risk factors (i.e., PI use, severe body fat changes, and hepatitis C), the information provided is based on criteria established by the American Diabetes Association for diabetes testing in asymptomatic non-HIV-infected adults.5
Body mass index (BMI) is a tool for assessing obesity in patients. Calculation of BMI measures amount of body mass according to height and weight (see Table 2). A BMI ≥25 kg/m2 is a risk factor for diabetes. Some clinicians find waist circumference a useful measure as well. A waist circumference >40 inches in men and >35 inches in women signifies increased risk in those who have a BMI of 25 to 34.9 kg/m2.6
|Table 2: Body Mass Index Measurement|
Fasting blood glucose should be assessed before initiating HAART and should be monitored while the patient is receiving HAART (3-6 months after starting and at least annually thereafter). Normal fasting blood glucose is <100 mg/dL. Prediabetes occurs between 100 and 125 mg/dL. If fasting blood glucose level increases to ≥126 mg/dL, a person has diabetes.
If fasting blood glucose tests are not feasible, random blood glucose values may be used as an alternative screening method. Patients with random glucose consistently <100 mg/dL do not require follow-up testing. A random glucose >140 mg/dL should prompt use of a standardized diagnostic test, such as a glucose tolerance test. A random plasma glucose ≥200 mg/dL, either repeated on a subsequent day or in the presence of unequivocal symptoms of hyperglycemia (e.g., serum glucose >400 mg/dL, lactic acidosis, small to moderate amounts of ketones, serum pH of <7.3, bicarbonate of <15 mEq/L, anion gap >12), meets the threshold for the diagnosis of diabetes.5
B. Prevention of Diabetes Disease Progression
Clinicians who lack experience in treating diabetic patients should refer patients for evaluation by clinicians experienced in managing diabetes.
When possible, clinicians should prescribe alternatives to a protease inhibitor-based HAART regimen in patients with preexisting glucose intolerance or diabetes.
Clinicians should recommend life-style interventions, including diet, exercise, weight management, and smoking cessation, for HIV-infected patients with glucose intolerance or diabetes.
When possible, HIV-infected patients with diabetes should develop and maintain a nutrition plan with a qualified nutrition counselor.
Clinicians should refer diabetic patients who are not responsive to medical intervention or who have symptoms and signs of worsening diabetes to an endocrinologist.
Appropriate management of diabetes requires not only optimal control of blood sugar but also aggressive management of blood pressure and lipids, annual eye care, annual foot examination, visual foot inspection at every visit for patients at high risk for developing foot conditions (e.g., patients with prior ulcer, amputation, or diabetic neuropathy), screening and management of microalbuminuria, and annual measurement of serum creatinine levels for glomerular filtration rate calculation.
Diabetic patients are at risk for episodic hypoglycemia. Each patient should be educated about symptoms, signs, and management of hypoglycemia. Symptoms of hypoglycemia may be masked in patients who 1) have longstanding disease and autonomic dysfunction, 2) receive ß-blocker therapy, or 3) use alcohol. Dose adjustments or changes in medications may be required in the presence of renal or hepatic disease.
First-line therapy directed at hyperglycemia includes diet and exercise. Referral for nutritional counseling and education can be a useful adjunct to medical management of diabetes. When possible, patients should develop and maintain a nutrition plan with a Registered Dietician or Certified Diabetes Educator.
Medications directed at hyperglycemia include agents to improve insulin sensitivity and to increase insulin secretion, as well as insulin itself. Special caution is warranted with the use of metformin due to its potential to cause lactic acidosis, which can also be a side effect of nucleoside/-tide reverse transcriptase inhibitors. Metformin-related lactic acidosis is increased in patients with renal insufficiency, cardiac disease, chronic pulmonary disease, dehydration, sepsis, hypoperfusion, and advanced age. For additional information regarding the management of diabetes in the setting of ARV therapy, see Long-Term Complications of Antiretroviral Therapy.
1. Centers for Disease Control and Prevention. National Diabetes Fact Sheet: General Information and National Estimates on Diabetes in the United States, 2005. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention; 2005. Available at: http://www.cdc.gov/diabetes/pubs/estimates05.htm.
2. Hadigan C, Meigs JB, Corcoran C, et al. Metabolic abnormalities and cardiovascular disease risk factors in adults with human immunodeficiency virus infection and lipodystrophy. Clin Infect Dis 2001;32:130-139.
3. Dube MP. Disorders of glucose metabolism in patients infected with human immunodeficiency virus. Clin Infect Dis 2000;31:1467-1475.
4. Murata H, Hruz PW, Mueckler M. The mechanism of insulin resistance caused by HIV protease inhibitor therapy. J Biol Chem 2000;275:20251-20254.
5. American Diabetes Association. Standards of medical care in diabetes—2007. Diabetes Care 2007;30(Suppl 1):S4-S41. Available at: http://care.diabetesjournals.org/cgi/content/full/30/suppl_1/S4.
6. The National Heart, Lung, and Blood Institute. Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults: The Evidence Report. Bethesda, MD; 1998.