As previously mentioned, protease inhibitors (PIs) can increase the risk of type 2 diabetes. Here are some findings from several reasearch teams. Readers should note that although some of this work focuses on the PI indinavir, it is likely that all PIs have similar effects.
In one experiment, researchers in San Francisco gave a single dose of indinavir 1,200 mg or fake indinavir (placebo) to six healthy, HIV negative male subjects. The researchers found that indinavir significantly impaired the ablility of insulin to help move glucose into cells, likely by reducing its effect on glucose transporters.
Impairing the work of glucose transporters may not be the only way that PIs cause sugar problems. German researchers have found that even when glucose is able to get inside a cell, HAART-users have difficulty breaking it down to release energy.
Doctors are testing a number of drugs, singly and in combination, to help increase the body's sensitivity to insulin. Examples of these drugs include the anti-diabetic drugs metformin (Glucophage) and the glitazones — pioglitazone (Actos) and rosiglitazone (Avandia). The glitazones may also help to slow down or stop the fat redistribution that can occur in PHAs with lipodystrophy.
REFERENCES
1. Murata H, Hruz P and Mueckler M. Inhibition of cellular glucose uptake by indinavir. Abstract 1 - 3rd International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV, 23-26 October 2001, Athens, Greece.
2. Hruz PW, Murata H, Qiu H and Mueckler M. Indinavir induces acute and reversible insulin resistance in rats. Abstract 2 - 3rd International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV, 23-26 October 2001, Athens, Greece.
3. Noor MA, Seneviratne T, Aweeka FT, et al. The HIV protease inhibitor indianvir acutely inhibits insulin-stimulated glucose disposal: a randomized, placebo-controlled study. Abstract 3 - 3rd International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV, 23-26 October 2001, Athens, Greece.
4. Behrens GMN, Weber K, Boerner A-R, et al. Impaired glucose transport and phosphorylatin in skeletal muscle assessed by [18F] fluorodesoxy-glucose positron emission tomography in HIV-patients on highly active antiretroviral therapy. Abstract 4 - 3rd International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV, 23-26 October 2001, Athens, Greece.
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Copyright © 2001 - TreatmentUpdate. Reproduced with permission. Reproduction of this article (other than one copy for personal reference) must be cleared through the Editor, The Canadian AIDS Treatment Information Exchange, 555 Richmond St. West, Suite 505, Box 1104, Toronto, ON, M5V 3B1 • Phone: 416-203-7122 • Toll Free: 1-800-263-1638 • Fax: 416-203-8284 http://www.catie.ca.
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