title: Pentamidine-induced derangements of glucose homeostasis. Determinant roles of renal failure and drug accumulation. A study of 128 patients.
abstract: 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.
authors.affiliation: Service de Diabétologie, Hôpital Bichat, Paris, France.
authors.forename: R
authors.initials: R
authors.lastname: Assan
authors.forename: C
authors.initials: C
authors.lastname: Perronne
authors.forename: D
authors.initials: D
authors.lastname: Assan
authors.forename: L
authors.initials: L
authors.lastname: Chotard
authors.forename: C
authors.initials: C
authors.lastname: Mayaud
authors.forename: S
authors.initials: S
authors.lastname: Matheron
authors.forename: D
authors.initials: D
authors.lastname: Zucman
mesh_terms: 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*
chemical_list: D010419:Pentamidine; D015662:Trimethoprim, Sulfamethoxazole Drug Combination