Johansson B L, Borg K, Fernqvist-Forbes E, Kernell A, Odergren T, Wahren J
Department of Surgical Sciences, Karolinska Hospital, Stockholm, Sweden.
Diabet Med. 2000 Mar;17(3):181-9. doi: 10.1046/j.1464-5491.2000.00274.x.
Recent studies have indicated that proinsulin C-peptide shows specific binding to cell membrane binding sites and may exert biological effects when administered to patients with Type 1 diabetes mellitus. This study was undertaken to determine if combined treatment with C-peptide and insulin might reduce the level of microalbuminuria in patients with Type 1 diabetes and incipient nephropathy.
Twenty-one normotensive patients with microalbuminuria were studied for 6 months in a double-blind, randomized, cross-over design. The patients received s.c. injections of either human C-peptide (600 nmol/24 h) or placebo plus their regular insulin regimen for 3 months.
Glycaemic control improved slightly during the study and to a similar extent in both treatment groups. Blood pressure was unaltered throughout the study. During the C-peptide treatment period, urinary albumin excretion decreased progressively on average from 58 microg/min (basal) to 34 microg/min (3 months, P < 0.01) and it tended to increase, but not significantly so, during the placebo period. The difference between the two treatment periods was statistically significant (P < 0.01). In the 12 patients with signs of autonomic neuropathy prior to the study, respiratory heart rate variability increased by 21 +/- 9% (P < 0.05) during treatment with C-peptide but was unaltered during placebo. Thermal thresholds were significantly improved during C-peptide treatment in comparison to placebo (n = 6, P < 0.05).
These results indicate that combined treatment with C-peptide and insulin for 3 months may improve renal function by diminishing urinary albumin excretion and ameliorate autonomic and sensory nerve dysfunction in patients with Type 1 diabetes mellitus.
近期研究表明,胰岛素原C肽可与细胞膜结合位点特异性结合,且在应用于1型糖尿病患者时可能发挥生物学效应。本研究旨在确定C肽与胰岛素联合治疗是否能降低1型糖尿病初发肾病患者的微量白蛋白尿水平。
采用双盲、随机、交叉设计,对21例血压正常的微量白蛋白尿患者进行了6个月的研究。患者皮下注射人C肽(600 nmol/24小时)或安慰剂,并采用常规胰岛素治疗方案,为期3个月。
在研究期间,血糖控制略有改善,两个治疗组的改善程度相似。在整个研究过程中,血压未发生变化。在C肽治疗期间,尿白蛋白排泄量平均从58微克/分钟(基础值)逐渐降至34微克/分钟(3个月,P<0.01),而在安慰剂治疗期间则有升高趋势,但无显著升高。两个治疗期之间的差异具有统计学意义(P<0.01)。在研究前有自主神经病变体征的12例患者中,C肽治疗期间呼吸心率变异性增加了21±9%(P<0.05),而在安慰剂治疗期间未发生变化。与安慰剂相比,C肽治疗期间热阈值显著改善(n = 6,P<0.05)。
这些结果表明,C肽与胰岛素联合治疗3个月可能通过减少尿白蛋白排泄来改善肾功能,并改善1型糖尿病患者的自主神经和感觉神经功能障碍。