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.
Of 18 AIDS patients with Pneumocystis carinii pneumonia treated with pentamidine mesylate parenterally, four developed serious to severe hypoglycaemia, three hypoglycaemia followed by insulin-requiring diabetes, and two others diabetes alone. Hypoglycaemia (blood glucose 2.1 +/- 0.2 (+/- SE) mmol l-1) occurred 9 (2-22) days after starting treatment, and diabetes (initial blood glucose 30 +/- 6 mmol l-1) after 60 (20-90) days. The other patients remained euglycaemic. The dysglycaemic patients (hypo- and hyper-glycaemic) had a higher pentamidine dosage (p less than 0.01), and higher serum creatinine levels at end of treatment (p less than 0.001), consistent with drug accumulation and dose-dependent toxicity. Plasma C-peptide levels were low in the diabetic patients, in the basal state (0.25-0.28 nmol l-1) and following stimulation by IV glucagon (0.35-0.40 nmol l-1), vs 0.80 +/- 0.06 nmol l-1 (basal) and 1.83 +/- 0.16 nmol l-1 (stimulated) in 23 healthy control subjects (mean +/- SE). Islet cell or insulin antibodies were not detected. Serum amylase levels rose abnormally in the dysglycaemic group, and pancreatitis was proved in one, and suspected in another patient. None of 28 similar AIDS patients whose P. carinii pneumonia was treated with cotrimoxazole showed blood glucose disturbance.
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