Haugaard Steen B, Andersen Ove, Halsall Ian, Iversen Johan, Hales Charles Nicholas, Madsbad Stein
Clinical Research Unit, Hvidovre University Hospital, DK-2650 Hvidore, Copenhagen, Denmark.
Metabolism. 2007 Jul;56(7):939-46. doi: 10.1016/j.metabol.2007.02.007.
The beta-cell function of HIV-infected patients on highly active antiretroviral therapy who display lipodystrophy may be impaired. An early defect in beta-cell function may be characterized by an increase in secretion of 32-33 split proinsulin (SP) and intact proinsulin (IP). To address this issue, the secretion patterns of SP and IP of 16 HIV-infected men with lipodystrophy (LIPO) and 15 HIV-infected men without lipodystrophy (NONLIPO) were studied during an oral glucose tolerance test (OGTT). All patients received highly active antiretroviral therapy. Insulin secretion rates were determined by deconvolution of plasma C-peptide concentrations. More LIPO than NONLIPO patients displayed diabetes mellitus and impaired glucose tolerance than normal glucose tolerance (LIPO 2/8/6 vs NONLIPO 1/2/12, P = .05). LIPO patients had increased fasting levels of SP and IP, ratio of SP/IP, and area under the curve of SP and IP during the early phase (0, 10, and 20 minutes) and during the late phase (45, 75, and 105 minutes) of the OGTT compared with NONLIPO patients (Ps < .05). LIPO patients exhibited significantly increased fasting SP/IP ratio, fasting SP/insulin ratio, and total proinsulin to C-peptide ratio during the OGTT. LIPO patients displayed increased incremental secretion of IP during the first 10 minutes of the OGTT (P < .05), although the incremental insulin secretion during this period did not differ between LIPO and NONLIPO patients. These data suggest that HIV-infected patients with lipodystrophy display major perturbations of proinsulin secretion in the fasting state and during an OGTT, which is compatible with the notion of a beta-cell dysfunction of such patients.
接受高效抗逆转录病毒治疗且出现脂肪代谢障碍的HIV感染患者，其β细胞功能可能受损。β细胞功能的早期缺陷可能表现为32-33裂解胰岛素原（SP）和完整胰岛素原（IP）分泌增加。为解决这一问题，我们研究了16例有脂肪代谢障碍的HIV感染男性（LIPO组）和15例无脂肪代谢障碍的HIV感染男性（NONLIPO组）在口服葡萄糖耐量试验（OGTT）期间SP和IP的分泌模式。所有患者均接受高效抗逆转录病毒治疗。通过血浆C肽浓度反卷积法测定胰岛素分泌率。与正常糖耐量相比，LIPO组患者中糖尿病和糖耐量受损的比例高于NONLIPO组（LIPO组为2/8/6，NONLIPO组为1/2/12，P = 0.05）。与NONLIPO组患者相比，LIPO组患者在OGTT早期（0、10和20分钟）和晚期（45、75和105分钟）的空腹SP和IP水平、SP/IP比值以及SP和IP的曲线下面积均升高（P值均<0.05）。LIPO组患者在OGTT期间的空腹SP/IP比值、空腹SP/胰岛素比值以及总胰岛素原与C肽比值显著升高。LIPO组患者在OGTT的前10分钟IP的增量分泌增加（P < 0.05），尽管在此期间LIPO组和NONLIPO组患者的胰岛素增量分泌无差异。这些数据表明，有脂肪代谢障碍的HIV感染患者在空腹状态和OGTT期间胰岛素原分泌存在重大紊乱，这与这类患者β细胞功能障碍的观点相符。
