Clinical Guide > Comorbidities and Complications > Insulin Resistance

Insulin Resistance, Hyperglycemia, and Diabetes on Antiretroviral Therapy

January 2011

Chapter Contents


Diabetes is a substantial risk factor for coronary artery disease, stroke, and peripheral vascular disease, as well as for a number of other conditions including retinopathy and kidney disease. Patients taking antiretroviral (ARV) medications, especially certain protease inhibitors (PIs) and nucleoside reverse transcriptase inhibitors (NRTIs), appear to have an increased risk of hyperglycemia and diabetes mellitus. In particular, the ARVs indinavir and stavudine (now seldom used in the United States) have been shown to induce insulin resistance in short-term studies of healthy HIV-uninfected volunteers, but other ARVs also perturb glucose homeostasis.

Disorders of glucose metabolism may present as the following:

The incidence of new-onset hyperglycemia among HIV-infected patients on ARV therapy (ART) has been reported as about 5%, on average. Even if fasting glucose levels remain normal in patients taking ARVs, up to 40% of those on a PI-containing regimen will show impaired glucose tolerance. The etiology of insulin resistance and hyperglycemia in HIV-infected patients probably is multifactorial, with varying contributions from traditional risk factors (e.g., obesity, family history), comorbid conditions (e.g., hepatitis C virus infection), and ARV-related factors (e.g., direct effects of PIs, cumulative exposure to NRTIs, hepatic steatosis, and fat redistribution).

Patients who have preexisting diabetes should be monitored closely when starting ART; some experts would consider avoiding PIs for these patients, if other options are feasible. Alternatively, PIs with favorable metabolic profiles (e.g., atazanavir) may be preferred for such patients. Patients with no history of diabetes should be advised about the warning signs of hyperglycemia (polydipsia, polyuria, and polyphagia) and the need to use diet and exercise to maintain an ideal body weight.

S: Subjective

Clinicians should consider the potential for abnormal glucose metabolism in the following types of patients:

Although most patients with hyperglycemia are asymptomatic, some (rarely) may report polydipsia, polyuria, polyphagia, or blurred vision.

When recording the patient's history, ask about the following:

O: Objective

Perform a physical examination that includes the following:

A/P: Assessment and Plan

Diagnostic Evaluation

Determine whether the patient has normal blood glucose, impaired fasting glucose, or diabetes.

Most experts recommend routine checks of fasting blood glucose levels at baseline and within 3-6 months after starting or changing ART, if baseline results are normal. For patients with normal glucose levels, recheck every 6-12 months. Monitoring should be more frequent if abnormalities are detected or if any additional risk factors exist. Patients with risk factors for diabetes must be counseled about prevention of hyperglycemia before starting ART.

The role of 2-hour postprandial glucose measurements or the 75 g oral glucose tolerance test in screening for diabetes is uncertain but may be appropriate for patients with multiple risk factors. The use of HbA1c testing to screen for diabetes has yet to be validated for the HIV-infected population. Of note, HbA1c values may underestimate glycemia in HIV-infected patients, especially in the setting of elevated red blood cell mean corpuscular volume (MCV) (e.g., owing to zidovudine) or anemia.

For patients with diabetes, monitor the following:


Patients with insulin resistance

For patients with insulin resistance who have normal blood glucose levels, current evidence is inadequate to recommend drug treatment. However, it may be possible to prevent the development of diabetes, and lifestyle modifications can be recommended, including exercise, avoidance of obesity, weight loss if indicated, and diet changes. Weight loss is strongly recommended if the patient is overweight. Refer the patient to a dietitian, if possible. Studies of insulin resistance in HIV-infected individuals are under way, and patients with access to clinical trials may be referred to these studies.

Patients with insulin resistance and hyperglycemia require treatment. A trial of lifestyle modifications may be attempted, including weight loss (if indicated), diet changes, and exercise.

For patients with diabetes and those whose lifestyle changes are not adequate to control blood glucose, specific treatment should be started.

Patients with diabetes

For further information, see the American Diabetes Association, Clinical Practice Recommendations, Diabetes Care.

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