William P. Beetham Eye and John Cook Renal Units, Joslin Diabetes Center, Boston, MA, USA.
Metabolism. 2010 Oct;59(10):1429-34. doi: 10.1016/j.metabol.2010.01.004. Epub 2010 Mar 1.
Many hormones are secreted in a pulsatile fashion that is more efficient than continuous secretion when tested in vivo. A trial of multiple daily insulin doses with or without the addition of weekly pulsatile insulin infusion therapy was designed to determine if deterioration of renal and retinal function could be blunted. Sixty-five study subjects were evaluated prospectively in 7 centers. Thirty-six patients were randomly allocated to the infusion group and 29 to the standard therapy group. Mean serum creatinine was 1.6 mg/dL in both groups. Subjects were excluded if clearance was less than 30 mL/min. There were no significant differences between the groups with respect to age, duration of diabetes, sex distribution, glycohemoglobin, blood pressure, angiotensin-converting enzyme inhibitor use, proteinuria, or baseline diabetic retinopathy (DR) severity level (all eyes exhibited DR; 8 were deemed technically not amenable to evaluation). Progression of DR was noted in 31.6% of 57 patients (32.3% treated, 30.8% control; P = 1.0) with both eyes evaluable. For patients with 12 or more months of follow-up, 27.9% of 43 patients demonstrated progression of DR (32.0% treated, 22.2% control; P = .57). There were no significant differences between study groups with respect to progression or marked progression, nor was there any influence of duration of follow-up. Progression of DR was noted in 18.8% of 122 eyes that could be adequately evaluated (17.9% of 67 treated, 20% of 55 controls; P = .39). Serum creatinine increased to 1.7 mg/dL in the treatment group and to 1.9 mg/dL in the control group (P = .03). Statistically significant preservation of renal function by pulsatile insulin infusion was not matched by a statistically significant prevention of DR progression compared with standard diabetes care. Inadequate statistical power or duration of the study, or lack of further benefit of pulsatile insulin infusion on the retina in the presence of angiotensin-converting enzyme inhibition may be responsible.
许多激素以脉冲方式分泌，在体内测试时比连续分泌更有效。设计了多次每日胰岛素剂量的试验，以及是否添加每周脉冲胰岛素输注治疗，以确定肾功能和视网膜功能的恶化是否可以减轻。65 名研究对象在 7 个中心进行了前瞻性评估。36 名患者被随机分配到输注组，29 名患者被分配到标准治疗组。两组的平均血清肌酐均为 1.6mg/dL。如果清除率低于 30ml/min，则将患者排除在外。两组在年龄、糖尿病持续时间、性别分布、糖化血红蛋白、血压、血管紧张素转换酶抑制剂使用、蛋白尿或基线糖尿病视网膜病变（所有眼睛均存在 DR；8 只眼睛因技术原因而无法进行评估）严重程度水平方面无显著差异（所有眼睛均存在 DR；8 只眼睛因技术原因而无法进行评估）。在可评估的 57 名患者中（32.3%治疗组，30.8%对照组；P=1.0）中有 31.6%的患者出现了 DR 进展。对于随访时间为 12 个月或更长时间的患者，43 名患者中有 27.9%的患者出现了 DR 进展（32.0%治疗组，22.2%对照组；P=0.57）。两组在进展或明显进展方面无显著差异，随访时间也无影响。在可充分评估的 122 只眼中，有 18.8%的眼睛出现了 DR 进展（67 只治疗眼中有 17.9%，55 只对照眼中有 20%；P=0.39）。治疗组的血清肌酐升高至 1.7mg/dL，对照组升高至 1.9mg/dL（P=0.03）。与标准糖尿病护理相比，脉冲胰岛素输注并没有显著改善肾功能，也没有显著预防 DR 进展。这可能是由于统计学上没有充分的效力或研究持续时间，或者在使用血管紧张素转换酶抑制剂的情况下，脉冲胰岛素输注对视网膜没有进一步的益处。
