PENTAMIDINE-INDUCED DERANGEMENTS OF GLUCOSE-HOMEOSTASIS - DETERMINANTROLES OF RENAL-FAILURE AND DRUG ACCUMULATION - A STUDY OF 128 PATIENTS

OBJECTIVE - To assess the prevalence, presentation, and risk factors o f pentamidine-induced dysglycemia. RESEARCH DESIGN AND METHODS - Blood glucose values were screened in 244 consecutive immunocompromised pat ients with Pneumocystis carinii pneumonia: 116 being treated with cotr imoxazole and 128 others with pentamidine. RESULTS - Two cotrimoxazole patients developed diabetes as a result of necrotizing pancreatitis ( 1.7%); the others remained euglycemic. Forty-eight pentamidine-treated patients (38.5%) developed severe glucose homeostasis disorders: hypo glycemia in 7, hypoglycemia and then diabetes in 18, and diabetes alon e in 23 (P < 0.001 vs. the cotrimoxazole group). Hypoglycemia was earl y, sudden, often recurrent, and life-threatening, associated with inap propriately high insulin levels in plasma; the B-cell response to stim uli was poor. Of the 41 diabetic patients, 26 required insulin therapy ; their plasma C-peptide levels were lower than normal, and the B-cell secretory responses to stimuli were poor. Islet cell antibodies, insu lin antibodies, and insulitis were not detected. The pentamidine-treat ed dysglycemic patients differed from their euglycemic counterparts by higher pentamidine doses (P < 0.001), higher plasma creatinine levels (P < 0.001), and more severe anoxia (P < 0.05) and shock (P < 0.001). Most of them had received pentamidine mesylate parenterally (n = 36; 75%); six others received the isethionate salt and six exclusively pen tamidine aerosols. CONCLUSIONS - Pentamidine-induced dysglycemic accid ents are primarily due to inappropriate insulin release and toxicity t o the islet B-cells. Drug accumulation due to excessive doses, iterati ve courses, and/or renal impairment is the determining risk factor.