Pancreatic beta cell function persists in many patients with chronic type 1 diabetes, but is not dramatically improved by prolonged immunosuppression and euglycaemia from a beta cell allograft
Pancreatic beta cell function persists in many patients with chronic type 1 diabetes, but is not dramatically improved by prolonged immunosuppression and euglycaemia from a beta cell allograft
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DOI：
10.1007/s00125-009-1342-7
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发表时间：
2009-07-01
期刊：
影响因子：
8.2
通讯作者：
Harlan, D. M.
中科院分区：
文献类型：
--
作者：
Liu, E. H.;Digon, B. J., III;Harlan, D. M.
我们测定了54例(38%)慢性1型糖尿病患者的血清C-肽(至少0.167 nmol/L)，并寻找可能区分可检测到的C-肽和不能检测到C-肽的因素。没有发现差异，鉴于这类患者持续的抗β细胞自身免疫，我们推测1型糖尿病移植治疗中伴随的免疫抑制(以减弱自身免疫攻击)和正常血糖可能促进自然胰腺β细胞功能的恢复。我们对3例胰岛移植和4例全胰腺移植的受者进行了精氨酸刺激试验，并在选定的静脉取样点测定了刺激的C-肽。根据每个采样点的C-肽浓度和动力学，我们区分了个体天然的胰岛β细胞和同种异体移植的胰岛细胞分泌的胰岛素。选择性静脉采样表明，尽管长期存在1型糖尿病，但所有七个异基因胰岛细胞移植受者都有证据表明他们的天然胰腺分泌C-肽。然而，即使慢性免疫抑制加上接近正常的血糖确实改善了天然胰腺C-肽的产生，其影响的幅度也相当小。在大多数1型糖尿病患者发病数年后，一些天然的胰腺β细胞功能仍然存在。然而，如果长期的正常血糖加抗排斥免疫抑制治疗改善了自然胰腺胰岛素的产生，对我们的参与者的影响很小。我们可能低估了胰腺的再生能力，因为我们只研究了有限数量的参与者，或者创造了损害β细胞功能的条件(例如循环中胰岛素浓度高或对β细胞有毒的免疫抑制剂)。
We measured serum C-peptide (at least 0.167 nmol/l) in 54 of 141 (38%) patients with chronic type 1 diabetes and sought factors that might differentiate those with detectable C-peptide from those without it. Finding no differences, and in view of the persistent anti-beta cell autoimmunity in such patients, we speculated that the immunosuppression (to weaken autoimmune attack) and euglycaemia accompanying transplant-based treatments of type 1 diabetes might promote recovery of native pancreatic beta cell function.We performed arginine stimulation tests in three islet transplant and four whole-pancreas transplant recipients, and measured stimulated C-peptide in select venous sampling sites. On the basis of each sampling site's C-peptide concentration and kinetics, we differentiated insulin secreted from the individual's native pancreatic beta cells and that secreted from allografted beta cells.Selective venous sampling demonstrated that despite long-standing type 1 diabetes, all seven beta cell allograft recipients displayed evidence that their native pancreas secreted C-peptide. Yet even if chronic immunosuppression coupled with near normal glycaemia did improve native pancreatic C-peptide production, the magnitude of the effect was quite small.Some native pancreatic beta cell function persists even years after disease onset in most type 1 diabetic patients. However, if prolonged euglycaemia plus anti-rejection immunosuppressive therapy improves native pancreatic insulin production, the effect in our participants was small. We may have underestimated pancreatic regenerative capacity by studying only a limited number of participants or by creating conditions (e.g. high circulating insulin concentrations or immunosuppressive agents toxic to beta cells) that impair beta cell function.ClinicalTrials.gov NCT00246844 and NCT00006505.