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LETTER

New-Onset Diabetes Mellitus Associated with Use of Protease Inhibitor

John A. Eastone, MD, and Catherine F. Decker, MD

15 November 1997 | Volume 127 Issue 10 | Page 948

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TO THE EDITOR:

The use of protease inhibitors has revolutionized the treatment of HIV infection through the ability of these drugs to decrease viral load [1]. Although these agents are fairly well tolerated, previously unrecognized adverse reactions will become more evident as the availability of the drugs improves and use becomes more widespread. New-onset diabetes mellitus has been described with several agents commonly used to manage HIV disease [2-4]. We noted a strong temporal relation between the onset of hyperglycemia and the initiation or change in protease inhibitor therapy in five HIV-infected patients.

The Table 1 shows the characteristics of these patients. All were known to have had HIV infection for more than 5 years, and all experienced disease progression despite extensive use of nucleoside analogues. Before protease inhibitor therapy began, the mean CD4⁺ count was 87 cells/mm³, and viral loads ranged from 7000 to 355 000 copies/mL. None of the patients had risk factors for diabetes, although one had had elevated random blood glucose levels before treatment. None of the patients had received pentamidine or megestrol. At the time of hyperglycemia onset, the mean CD4⁺ count had increased to 224 cells/mm³ and the mean decrease in viral load was 128 000 copies/mL.

View this table: [in this window] [in a new window]   Table 1. Characteristics of Patients Receiving Protease Inhibitor Therapy Who Developed Hyperglycemia

 

Hyperglycemia was controlled without difficulty through either oral hypoglycemic agents or diet modification and did not necessitate discontinuation of therapy with the protease inhibitor. None of the patients developed diabetic ketoacidosis, and only one patient required hospitalization for glycemic control. In one case, withdrawal of protease inhibitor therapy resulted in correction of hyperglycemia; subsequent rechallenge caused recurrence.

The mechanism by which hyperglycemia occurs in association with protease inhibitor use is unclear. Discontinuation of therapy with the drug, which may promote viral resistance [5], is not necessary for glycemic control. Until more data are available, clinicians who treat HIV-infected patients must be aware that protease inhibitors can cause hyperglycemia in patients with or without a history of glucose intolerance.

Author and Article Information

Top Author & Article Info References

National Naval Medical Center; Bethesda, MD 20889

References

Top Author & Article Info References

1. Bartlett J. Protease inhibitors for HIV infection. Am J Med. 1996; 124:1086-8.

2. Nasti G, Zanette G, Inchiostro S, Donadon V, Tirelli U. Diabetes mellitus following intravenous pentamidine administration in a patient with HIV infection. Arch Intern Med. 1995; 155:645-6.

3. Henry K, Rathgaber S, Sullivan C, McCabe K. Diabetes mellitus induced by megestrol acetate in a patient with AIDS and cachexia. Ann Intern Med. 1992; 116:53-4.

4. Albrecht H, Stellbrink HJ, Arastéh K. Didanosine-induced disorders of glucose intolerance. Ann Intern Med. 1993;119:1050.

5. Mellors JW, McMahon DK, Chodakewitz JA, Schleif WA, Emini EA, Condra IH. Correlation between genotypic evidence of HIV-1 resistance to the protease inhibitor MK-639 and loss of antiretroviral effect in treated patients [Abstract]. In: Program and Abstracts of the Fourth International Workshop on HIV Drug Resistance, 6-9 July 1995, Sardinia, Italy.

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