Effects of aerosolized pentamidine on glucose homeostasis and insulin secretion in HIV-positive patients: a controlled study.
OBJECTIVE
Intravenous pentamidine induces hypo- and hyperglycaemia (dose-dependent toxicity on islet beta cells), pancreatitis and nephrotoxicity. Conversely, aerosolized pentamidine (AP) is usually devoid of systemic side-effects: few reports of hypo- or hyperglycaemia have been published. Our study aimed to assess the influence on glucose homeostasis and insulin secretion of long-term exposure to AP used for prophylaxis of Pneumocystis carinii pneumonia in HIV-positive patients, and to compare the impact on insulin secretion of AP, whether administered for the first time or after prolonged monthly exposure.


METHODS
Retrospective cross-sectional controlled study (main objective) and non-randomized prospective controlled study.


METHODS
We compared glucose homeostasis and C peptide response to 1 mg intravenous glucagon in patients who had previously inhaled > or = 10 prophylactic aerosols (group 1, n = 21) and in HIV-positive controls (groups 2 and 3, n = 28) who had received none. Both groups were comparable for age and body-mass index, but CD4 T-lymphocyte counts and Karnofsky scores were both significantly higher in the control group.


RESULTS
Fasting (T0) blood glucose, fructosamine and response to the first glucagon test were similar in both groups, but postprandial glucose, glycated haemoglobin and fasting C peptide were significantly higher (P < 0.05) in the pentamidine group. A second glucagon test was performed on the same day, 3 h (T3) after AP inhalation in 35 patients (in 21 after > or = 10 aerosols, group 1; in 14 after the first, group 2) and in 14 HIV-positive controls (group 3). The only significant difference between the three groups in C peptide response to this second test was a lower peak T3/peak T0 ratio in group 1. Plasma amylase and creatinine were not altered by the aerosol.


CONCLUSIONS
Long-term prophylactic exposure to AP had minor but significant effects on glucose homeostasis and insulin secretion but did not modify pancreatic and renal function. The detrimental effects induced by long-term exposure to AP found in our study are probably not clinically relevant, but a more prolonged exposure to AP might conceivably induce more severe alterations.
Uzzan
B
B
Department of Pharmacology-Hormonology, Avicenne Hospital, CHU Paris-Nord, Bobigny, France.
Bentata
M
M
Campos
J
J
Mosnier
A
A
Krivitzky
A
A
Perret
G Y
GY
Modigliani
E
E
D017088:AIDS-Related Opportunistic Infections / Q000517:prevention & control; D000280:Administration, Inhalation; D000328:Adult; D000336:Aerosols; D002096:C-Peptide / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D005947:Glucose / Q000378:metabolism*; D015658:HIV Infections / Q000188:drug therapy* / Q000503:physiopathology; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D010419:Pentamidine / Q000008:administration & dosage* / Q000009:adverse effects*; D011020:Pneumonia, Pneumocystis / Q000517:prevention & control; D011446:Prospective Studies; D012189:Retrospective Studies; D013997:Time Factors
D000336:Aerosols; D002096:C-Peptide; D007328:Insulin; D010419:Pentamidine; D005947:Glucose