抗胰岛素抗体对胰岛移植结果的影响：GRAGIL 网络的数据。

Impact of anti-insulin antibodies on islet transplantation outcome: data from the GRAGIL Network.

机构信息

1 Department of Endocrinology, Pôle DigiDune, Grenoble University Hospital, Joseph Fourier University, Grenoble, France. 2 Centre Hospitalier Universitaire Jean Minjoz, Service d'Endocrinologie-Métabolisme et Diabétologie-Nutrition, Besançon, France. 3 Hospices Civils de Lyon, Service de Néphrologie Médecine de la Transplantation et Immunologie clinique, Lyon, France. 4 Department of Nephrology, Pôle DigiDune, Grenoble University Hospital, Joseph Fourier University, Grenoble, France. 5 Hospices Civils de Lyon, Service d'Urologie et de Chirurgie de la Transplantation, Pôle Chirurgie, Lyon, France. 6 Hospices Civils de Lyon, Service d'Endocrinologie Diabète Nutrition, Lyon, France. 7 Centre Hospitalier de Montpellier, Pôle Rein Hypertension Métabolisme, Service d'Endocrinologie, Montpellier, France. 8 Centre Hospitalier Universitaire de Nancy, Service de Néphrologie, Nancy, France. 9 Hôpitaux Universitaires de Strasbourg, Service d'Endocrinologie Diabète et Maladies Métaboliques, Pôle NUDE, Strasbourg, France. 10 Hospices Civils de Lyon, Pôle Information Médicale Evaluation Recherche, Lyon, France. 11 Lyon University, EA Santé-Individu-Société, Lyon, France. 12 Address correspondence to: Sandrine Lablanche, Department of Endocrinology, CHU de Grenoble, BP217X, 38043 Grenoble, France.

出版信息

Transplantation. 2014 Aug 27;98(4):475-82. doi: 10.1097/TP.0000000000000081.

DOI:10.1097/TP.0000000000000081

PMID:24837539

Abstract

BACKGROUND

In patients with type 1 diabetes, insulin antibodies (IA), altering the pharmacokinetics of circulating insulin, might be associated with high glucose concentration, prolonged hypoglycemia, and higher insulin requirement. The impact of IA on islet transplantation has never been explored. Our aim was to evaluate islet transplantation results at 1 year according to the presence of IA.

METHODS

Our work is a retrospective, case-control study, comparing IA-negative and IA-positive patients among the cohort of patients with type 1 diabetes transplanted within the Swiss-French GRAGIL network between 2003 and 2010.

RESULTS

Data about IA were available for 17 patients. Before islet transplantation, 10 patients (59%) were screened positive for IA. At 12 months after transplantation, IA-positive patients reached insulin independence less frequently than IA-negative patients (cumulative incidence of insulin independence, 22.2% vs. 71.4%; P=0.02); β score was ≥7 in 43% of IA-negative patients versus 0% in IA-positive patients (P=0.022). When comparing IA-positive patients with IA-negative patients, insulin dose was 0.15 U/kg (0.10-0.18 U/kg) versus 0.01 U/kg (0-0.09 U/kg) (P=0.2); HbA1c was 6.1% (5.8%-6.3%) versus 6.1% (5.9%-6.8%) (P=0.16); basal C-peptide level was 460 ρmol/L (350-510 ρmol/L) versus 265 ρmol/L (177-405 ρmol/L) (P=0.28); occurrence of hypoglycemia was 12.5% versus 16.5% (P=0.9); and homeostatic model assessment insulin resistance was 1.25 (1-2.4) versus 0.7 (0.52-0.92) (P=0.01).

CONCLUSION

After islet transplantation, IA-positive patients achieved insulin independence less frequently, exhibiting lower β score and higher homeostatic model assessment insulin resistance compared with IA-negative patients. However, in both groups, islet transplantation restored good glycemic control and drastically reduced hypoglycemia and insulin requirements.

摘要

背景

在 1 型糖尿病患者中，改变循环胰岛素药代动力学的胰岛素抗体（IA）可能与高血糖浓度、延长的低血糖和更高的胰岛素需求有关。IA 对胰岛移植的影响从未被探索过。我们的目的是根据 IA 的存在来评估 1 年后的胰岛移植结果。

方法

我们的工作是一项回顾性病例对照研究，比较了 2003 年至 2010 年间在瑞士-法国 GRAGIL 网络内接受胰岛移植的 1 型糖尿病患者队列中 IA 阴性和 IA 阳性患者。

结果

17 名患者有关于 IA 的数据。在胰岛移植前，有 10 名患者（59%）IA 检测呈阳性。在移植后 12 个月时，IA 阳性患者达到胰岛素独立性的频率低于 IA 阴性患者（胰岛素独立性累积发生率，22.2%对 71.4%；P=0.02）；IA 阴性患者的β评分≥7 的比例为 43%，而 IA 阳性患者为 0%（P=0.022）。IA 阳性患者与 IA 阴性患者相比，胰岛素剂量为 0.15 U/kg（0.10-0.18 U/kg）对 0.01 U/kg（0-0.09 U/kg）（P=0.2）；HbA1c 为 6.1%（5.8%-6.3%）对 6.1%（5.9%-6.8%）（P=0.16）；基础 C 肽水平为 460 ρmol/L（350-510 ρmol/L）对 265 ρmol/L（177-405 ρmol/L）（P=0.28）；低血糖发生率为 12.5%对 16.5%（P=0.9）；稳态模型评估胰岛素抵抗为 1.25（1-2.4）对 0.7（0.52-0.92）（P=0.01）。