Pentamidine-induced derangements of glucose homeostasis. Determinant roles of renal failure and drug accumulation. A study of 128 patients.
OBJECTIVE
To assess the prevalence, presentation, and risk factors of pentamidine-induced dysglycemia.


METHODS
Blood glucose values were screened in 244 consecutive immunocompromised patients with Pneumocystis carinii pneumonia: 116 being treated with cotrimoxazole 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: hypoglycemia in 7, hypoglycemia and then diabetes in 18, and diabetes alone in 23 (P < 0.001 vs. the cotrimoxazole group). Hypoglycemia was early, sudden, often recurrent, and life-threatening, associated with inappropriately high insulin levels in plasma; the B-cell response to stimuli 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, insulin antibodies, and insulitis were not detected. The pentamidine-treated 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 pentamidine aerosols.


CONCLUSIONS
Pentamidine-induced dysglycemic accidents are primarily due to inappropriate insulin release and toxicity to the islet B-cells. Drug accumulation due to excessive doses, iterative courses, and/or renal impairment is the determining risk factor.
Assan
R
R
Service de Diabétologie, Hôpital Bichat, Paris, France.
Perronne
C
C
Assan
D
D
Chotard
L
L
Mayaud
C
C
Matheron
S
S
Zucman
D
D
D017088:AIDS-Related Opportunistic Infections / Q000150:complications / Q000188:drug therapy; D000328:Adult; D003920:Diabetes Mellitus / Q000139:chemically induced*; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000139:chemically induced*; D007003:Hypoglycemia / Q000139:chemically induced*; D007262:Infusions, Intravenous; D008297:Male; D010419:Pentamidine / Q000009:adverse effects*; D011020:Pneumonia, Pneumocystis / Q000150:complications / Q000188:drug therapy; D011863:Radioimmunoassay; D012189:Retrospective Studies; D012307:Risk Factors; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000009:adverse effects*
D010419:Pentamidine; D015662:Trimethoprim, Sulfamethoxazole Drug Combination