Uzzan B, Bentata M, Campos J, Mosnier A, Krivitzky A, Perret G Y, Modigliani E
Department of Pharmacology-Hormonology, Avicenne Hospital, CHU Paris-Nord, Bobigny, France.
AIDS. 1995 Aug;9(8):901-7. doi: 10.1097/00002030-199508000-00011.
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.
Retrospective cross-sectional controlled study (main objective) and non-randomized prospective controlled study.
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.
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.
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.
静脉注射喷他脒可导致低血糖和高血糖（对胰岛β细胞有剂量依赖性毒性）、胰腺炎和肾毒性。相反，雾化喷他脒（AP）通常没有全身副作用：关于低血糖或高血糖的报道很少。我们的研究旨在评估长期接触用于预防HIV阳性患者卡氏肺孢子虫肺炎的AP对葡萄糖稳态和胰岛素分泌的影响，并比较首次使用AP和每月长期接触后对胰岛素分泌的影响。
回顾性横断面对照研究（主要目的）和非随机前瞻性对照研究。
我们比较了既往吸入≥10次预防性气雾剂的患者（第1组，n = 21）和未接受过吸入的HIV阳性对照者（第2组和第3组，n = 28）对1 mg静脉注射胰高血糖素的葡萄糖稳态和C肽反应。两组在年龄和体重指数方面具有可比性，但对照组的CD4 T淋巴细胞计数和卡诺夫斯基评分均显著更高。
两组的空腹（T0）血糖、果糖胺和对首次胰高血糖素试验的反应相似，但喷他脒组的餐后血糖、糖化血红蛋白和空腹C肽显著更高（P < 0.05）。在35例患者（21例吸入≥10次气雾剂后，第1组；14例首次吸入后，第2组）和14例HIV阳性对照者（第3组）中，在AP吸入后3小时（T3）于同一天进行了第二次胰高血糖素试验。三组对该第二次试验的C肽反应的唯一显著差异是第1组的T3峰值/T0峰值比值较低。气雾剂未改变血浆淀粉酶和肌酐水平。
长期预防性接触AP对葡萄糖稳态和胰岛素分泌有轻微但显著的影响，但未改变胰腺和肾功能。我们的研究中发现的长期接触AP所产生的有害影响可能在临床上并不相关，但更长期接触AP可能会导致更严重的改变。
