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Impaired Glucose Tolerance and Protease Inhibitors
- Ravi Walli, MD;
- Frank D. Goebel, MD; and
- Thomas Demant, MD
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TO THE EDITOR:
Protease inhibitors are a crucial component of highly active antiretroviral therapy for HIV infection. However, the use of these drugs is associated with hyperglycemia, hyperlipidemia, and lipodystrophy [1-3]. The underlying mechanisms leading to these metabolic alterations are unknown. We evaluated peripheral insulin sensitivity in 24 HIV-positive patients treated with protease inhibitors, 8 therapy-naive HIV-positive patients, and 18 HIV-negative controls (Figure 1) using an intravenous insulin tolerance test [4].
Patients treated with protease inhibitors had a significantly lower median insulin sensitivity (67 µmol/L per minute) than did untreated patients (156 µmol/L per minute; P < 0.001) and controls (177 µmol/L per minute; P < 0.001). Untreated patients did not differ significantly from controls (P > 0.2). With stratification according to oral glucose tolerance, insulin sensitivity was significantly higher in the treated patients with normal glucose tolerance (121 µmol/L per minute; n = 11) than in those with impaired or diabetic glucose tolerance (55 µmol/L per minute; n = 13). We used the mean insulin sensitivity of the HIV-negative controls − 2 SDs (92 µmol/L per minute) to distinguish between normal and abnormal insulin sensitivity. All controls and untreated patients had normal insulin sensitivity. All treated patients with impaired (n = 4) or diabetic (n = 9) oral glucose tolerance had abnormal insulin sensitivity. Of note, in the treated patients with normal oral glucose tolerance, both normal (n = 5) and abnormal (n = 6) insulin sensitivity was seen.
These data suggest that treatment with protease inhibitors can lead to abnormal insulin sensitivity. In some patients, this can result in impaired or even diabetic oral glucose tolerance. A possible explanations for the reported peripheral insulin resistance is interference with insulin receptors or glucose transporters. Other factors, such as perturbance of insulin secretion or alterations of anti-insulinergic factors, may also be involved. Abnormal insulin sensitivity was seen in patients treated with all currently available protease inhibitors (indinavir, nelfinavir, ritonavir, and saquinavir).
Ravi Walli, MD
Frank D. Goebel, MD
Medizinische Poliklinik; Munich, Germany
The Editors welcome submissions for possible publication in the Letters section. Authors of letters should:
•Include no more than 300 words of text, three authors, and five references
•Type with double-spacing
•Send three copies of the letter, an authors' form signed by all authors, and a cover letter describing any conflicts of interest related to the contents of the letter.
Letters commenting on an Annals article will be considered if they are received within 6 weeks of the time the article was published. Only some of the letters received can be published. Published letters are edited and may be shortened; tables and figures are included only selectively. Authors will be notified that the letter has been received. If the letter is selected for publication, the author will be notified about 3 weeks before the publication date. Unpublished letters cannot be returned.
Annals welcomes electronically submitted letters.
- Copyright ©2004 by the American College of Physicians
