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Exacerbated hyperglycemia associated with nelfinavirTO THE EDITOR: Protease inhibitors (nelfinavir, saquinavir, indinavir, ritonavir) have emerged as potentially useful antiviral agents in the management of HIV infection. The product information of each of the protease inhibitors includes hypoglycemia as an uncommonly observed adverse effect in association with their use. In contrast, only three recent reports 1-3 of hyperglycemia associated with protease inhibitor use have been published in peer-reviewed journals. We report a case of frank diabetes mellitus 4 occurring shortly after introduction of nelfinavir therapy.Case Report. A 58-year-old white man, who was found to be infected with HIV 7 years earlier, began a regimen consisting of nelfinavir 750 mg q8h, stavudine 40 mg q12h, and zidovudine 300 mg q12h because of poor clinical response and adverse effects from a previous regimen that did not contain a protease inhibitor (Table 1). The patient was also receiving dapsone as prophylaxis against Pneumocystis carinii infection. There was no history of opportunistic infection or neoplastic disease associated with the HIV infection and he retained good nutritional status (weight 68 kg). He had not been acutely ill and had no history of chronic liver disease. His medical history also included urate nephropathy, hypertension, hyperlipidemia, and anxiety. Prior to beginning the new regimen, the patient had mild hyperglycemia (glucose 120-140 mg/dL) with nonfasting blood testing using an automated glucose oxidase method (CX7, Beckman, Brea, CA). He had no symptoms of diabetes mellitus such as polyuria, polydipsia, or weight loss, and there was no family history of diabetes mellitus.Two months after starting the new regimen, the patient developed lethargy, polyuria, polydipsia, and weight loss (3.6 kg) and had marked hyperglycemia (313 mg/dL) on nonfasting blood samples. Repeat nonfasting blood glucose testing the same month again showed marked hyperglycemia (365 mg/dL). Dietary modifications and glyburide (7.5 mg/d) were initiated, with resultant improvement in the hyperglycemia and its associated symptoms.Discussion. Although diabetes mellitus can be a primary disease process, it can also be caused or exacerbated by a number of secondary processes such as exposure to certain pharmaceutical agents (e.g., corticosteroids) or chemicals, chronic pancreatitis, hormonal abnormalities (e.g., acromegaly, Cushing's syndrome), and genetic syndromes (e.g., lipodystrophies). 4 It is possible that this patient's symptomatic hyperglycemia was attributable solely to the natural progression of underlying impaired glucose tolerance. However, the temporal association between the introduction of nelfinavir and the development of marked and symptomatic hyperglycemia suggests a possible causal relationship between nelfinavir and diabetes mellitus, as defined by Jones' algorithm. 5 The patient was also taking nicotinic acid, an agent known to produce hyperglycemia, 6 but had been receiving this drug for at least 3 years without any notic...
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