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[使用环孢素A诱导新诊断的胰岛素依赖型糖尿病缓解]

[Use of cyclosporin A for remission induction in newly-detected insulin-dependent diabetes].

作者信息

Zamaklar M, Lalić N, Djordjević P, Dragasević M, Vujosević S, Savić K, Kalimanovska V

机构信息

Institute for Endocrinology, Diabetes and Metabolic Diseases University Clinical Center, Belgrade, Yugoslavia.

出版信息

Glas Srp Akad Nauka Med. 1994(44):89-100.

PMID:7590419
Abstract

It has been postulated that some of the recent-onset insulin-dependent diabetics, after the initial use of insulin therapy, might develop the "honey moon period", i.e., a spontaneous remission of the disease, defined as the state of normal metabolic control maintained without insulin therapy. However, it has also been shown that spontaneous remission appears only in 5% of the patients treated with conventional insulin therapy and lasts, most frequently, not more than a few weeks. Different therapeutic regimens of immunosuppression and immunomodulation have been used worldwide in order to induce the remission, based on the findings that an autoimmune process underlies the pathogenesis of this type of diabetes. In this study, we have shown the results of the follow-up analysis of the effects of the treatment with cyclosporin A in 21 recent-onset insulin-dependent diabetics. In 15 of those patients insulin treatment was applied as bi-daily doses of monocomponent insulin preparations, and in 6 of them intensified insulin therapy with human insulin was used. In the first group, the remission was achieved in 46.66% and in the second group in 66.66%, which is a significantly higher incidence than in control groups treated only with insulin, without cyclosporin. Moreover, the duration of remission was longer in the patients treated with cyclosporin. The analysis of the residual beta cell secretory capacity has shown that C-peptide levels (taken as a marker for insulin secretion) were slightly higher in patients with the spontaneous remission than in those with the cyclosporin-induced remission both in basal conditions and after stimulation with 1 mg of glucagon. In the patients with cyclosporin A-induced remission we found an improved basal C-peptide secretion and, even more, we detected a significant improvement in beta cell response to the glucagon stimulation. The analysis of the first-phase insulin secretory response (the insulin response to rapidly injected glucose during the intravenous glucose tolerance test) which has been shown to be impaired very early during the development of diabetes, has demonstrated the lack of its recovery both in the spontaneous and in cyclosporin A-induced remissions. The analysis of the molar insulin/C-peptide ratio has detected the impairments of this ratio which remains decreased both in spontaneous and cyclosporin-induced remissions.

摘要

据推测,一些近期发病的胰岛素依赖型糖尿病患者在最初使用胰岛素治疗后,可能会进入“蜜月期”,即疾病的自发缓解期,定义为无需胰岛素治疗即可维持正常代谢控制的状态。然而,也有研究表明,在接受传统胰岛素治疗的患者中,只有5%会出现自发缓解,而且这种缓解最常见的持续时间不超过几周。基于自身免疫过程是这类糖尿病发病机制的基础这一发现,世界各地采用了不同的免疫抑制和免疫调节治疗方案来诱导缓解。在本研究中,我们展示了对21例近期发病的胰岛素依赖型糖尿病患者使用环孢素A治疗效果的随访分析结果。在这些患者中,15例采用每日两次的单组分胰岛素制剂进行胰岛素治疗,6例采用强化人胰岛素治疗。在第一组中,缓解率为46.66%,第二组为66.66%,这一发生率明显高于仅接受胰岛素治疗而未使用环孢素的对照组。此外,接受环孢素治疗的患者缓解期更长。对残余β细胞分泌能力的分析表明,无论是在基础状态还是在注射1毫克胰高血糖素刺激后,自发缓解患者的C肽水平(作为胰岛素分泌的标志物)略高于环孢素诱导缓解的患者。在环孢素A诱导缓解的患者中,我们发现基础C肽分泌有所改善,甚至更明显的是,我们检测到β细胞对胰高血糖素刺激的反应有显著改善。对糖尿病发病早期就已受损的第一相胰岛素分泌反应(静脉葡萄糖耐量试验期间对快速注射葡萄糖的胰岛素反应)的分析表明,在自发缓解和环孢素A诱导缓解的患者中,该反应均未恢复。对胰岛素/C肽摩尔比的分析发现,无论是自发缓解还是环孢素诱导缓解,该比值均受损且仍降低。

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