SUBCUTANEOUS INSULIN AND RHIGF IN INSULIN DEPENDENT DIABETES MELLITUS

在IDDM患者中，短期皮下联合治疗(SC) 重组人胰岛素样生长因子-I和胰岛素改善血糖控制，降低胰岛素 生长激素轴参数的要求和标准化。这个 目前的研究是为了评估更长期的、 多剂量重组人胰岛素样生长因子-I治疗2型糖尿病224例(年龄11~66岁) 在这16周的研究中(治疗2周，治疗12周，2周 后续行动)，PTS。以双盲方式随机接受 每日两次注射胰岛素和安慰剂(n=53)，或胰岛素和 重组人IGF-I剂量：a)80：60(5g/kg AM：PM，n=56)；b)80：40 57例；或c)40：40(n=54)。家庭血糖(BG)监测 每日4次，各组均为PTS。被指示调整 同时给予胰岛素剂量以优化血糖水平(即，达到DCCT目标 BGS)。在PT方面，所有组均具有可比性。人口统计数据， 糖化血红蛋白和治疗前空腹血糖。与重组人胰岛素样生长因子联合治疗- I/胰岛素治疗12周后，基线HgbA1c值降低1.2%(40：40)， 与强化胰岛素治疗相比，0.9%(80：40)和1.0%(80：60) 单独(0.6%)。重组人IGF-I 40：40剂量组的初步数据为 下面显示了与安慰剂(均值+扫描电子显微镜)的比较。(*=p&lt；.01用于 基线与第12周；#=p&lt；0.01第12周成对比较， 胰岛素/安慰剂与胰岛素/重组人胰岛素样生长因子-I) 胰岛素/安慰剂胰岛素/重组人胰岛素样生长因子-I 基线第12周基线第12周 HgbA1c(%)9.24+.18 8.65+.18*9.21+.17 8.05+.13*# 胰岛素剂量(单位/天)53+4 59+4 52+3 42+3*# 游离IGF-I(ng/ml)0.2+0.1 0.7+0.4 0.1+0.1 0.8+0.2 体重在两组中都没有显著变化。此外， 尽管血糖控制较好，但报告的低血糖事件没有 在接受胰岛素/重组人IGF-I 40：40(45)治疗的受试者中更常见 与单独使用胰岛素相比(42次，p=0.65)。人胰岛素样生长因子- I40：40剂量也耐受性良好。较高剂量的重组人IGF-I 与不良事件的不可接受的发生率有关，例如 周围性浮肿、颌痛和视盘肿胀。这些结果 证明重组人胰岛素样生长因子-I/胰岛素联合治疗改善了糖尿病患者的血糖控制 PTS。对于IDDM，超过了强化胰岛素所能达到的效果 仅限于管理层，并建议需要更长期的试验来 评价重组人胰岛素样生长因子-I作为一种新的治疗方法的安全性和有效性 改善IDDM患者的代谢控制。 根据这项研究的结果，基因泰克公司现在正在发起 一项为期一年的多中心多剂量联合效应研究 胰岛素和重组人胰岛素样生长因子-I对IDDM患者血糖控制的影响。这项研究将 在全国范围内招募约1400名患者，提供约100项医疗保健服务 设施。

In patients with IDDM, short-term co-therapy with subcutaneous (SC) rhIGF-I and insulin improves glycemic control, reduces insulin requirements and normalizes parameters of the somatotropin axis. The present study was undertaken to assess the effects of longer-term, multidose rhIGF-I treatment in 224 patients with IDDM (ages 11-66 yrs.). During this 16 week study (2 wks pretreatment, 12 wks treatment, 2 wks follow-up), pts. were randomized in a double-blind fashion to receive twice daily SQ injections of insulin and placebo (n=53), or insulin and rhIGF-I at an rhIGF-I dose of: a) 80:60 (5g/kg am:pm, n=56); b) 80:40 (n=57); or c) 40:40 (n=54). Home blood glucose (BG) monitoring was performed 4 times daily and in all groups pts. were instructed to adjust concurrent insulin doses to optimize BG levels (i.e., toward DCCT target BGs). All groups were comparable with respect to pt. demographics, HgbA1c and fasting BG prior to treatment. Co-therapy with rhIGF- I/insulin for 12 weeks reduced baseline HgbA1c values by 1.2% (40:40), 0.9% (80:40) and 1.0% (80:60), compared with intensified insulin therapy alone (0.6%). Preliminary data for the rhIGF-I 40:40 dose group is shown below compared with placebo (mean + SEM). (* = p < .01 for Baseline vs. Week 12; # = p < 0.01 for pairwise week 12 comparisons, Insulin/Placebo vs. Insulin/rhIGF-I) Insulin/Placebo Insulin/rhIGF-I Baseline Week 12 Baseline Week 12 HgbA1c (%) 9.24 + .18 8.65 +.18* 9.21+.17 8.05 + .13*# Insulin Dose(units/d) 53 + 4 59 + 4 52 + 3 42 + 3*# Free IGF-I (ng/ml) 0.2 + 0.1 0.7 + 0.4 0.1 + 0.1 0.8 + 0.2 Body weight did not change significantly in either group. Moreover, despite better glycemic control, reported hypoglycemic events were no more frequent in subjects treated with insulin/rhIGF-I 40:40 (45 episodes) compared with insulin alone (42 episodes, p=0.65). The rhIGF- I 40:40 dose was also well tolerated. Higher rhIGF-I doses were associated with an unacceptable incidence of adverse events such as peripheral edema, jaw pain and optic disc swelling. These results demonstrate that rhIGF-I/insulin co-therapy improves glycemic control in pts. with IDDM, beyond that achievable with intensified insulin management alone, and suggest that longer-term trials are needed to evaluate the safety and efficacy of rhIGF-I as a new therapy for improving metabolic control in IDDM. Based upon the results of this study, Genentech Inc. is now initiating a year-long, multicenter, multidose study of the combined effects of Insulin and rhIGF-I on glycemic control in IDDM. This study will enroll approximately 1400 patients nationally, at about 100 health care facilities.