Laboratory of Cell Therapy for Diabetes, Institute of Regenerative Medicine and Biotherapy, University Hospital of Montpellier, Saint Eloi Hospital, Montpellier, France.
Institut National de la Santé et de la Recherche Médicale U1191, Institute of Functional Genomics, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5203, Montpellier University, Montpellier, France.
J Clin Endocrinol Metab. 2018 Apr 1;103(4):1310-1319. doi: 10.1210/jc.2017-01342.
Islet transplantation (IT) can treat patients with severely unstable type 1 diabetes. Prehepatic kinetics of insulin secretion (ISec) in two phases can be calculated by C-peptide levels during meal tests. We proposed to describe the ISec profile after a mixed-meal tolerance test (MMTT) in IT recipients and to determine whether the calculated ISec indexes can predict graft outcome.
We analyzed 34 MMTT among 11 patients who underwent IT between 2011 and 2016 and compared them with healthy controls and patients with type 2 diabetes (T2D). ISec indexes and insulin sensitivity were calculated from models of Van Cauter, Breda, and Mari after MMTT. Graft success was defined by total insulin independence without any criteria for diabetes.
In patients with successful IT, the first- and second-phase ISec indexes were lower than those of controls (P < 0.001) and did not differ from those of the T2D group. Nevertheless, insulin sensitivity of IT recipients was similar to that of the control group and higher than that of the T2D group. The index of the second phase of ISec ɸS was correlated with total infused islet equivalents (IEQs), was a good predictor of diabetes (re)occurrence, and allowed us to calculate 9500 IEQ/kg as the minimum needed to reach insulin independence.
We showed that indexes from the first and second phases of ISec are altered in insulin-independent IT recipients. Higher sensitivity distinguishes them from patients with T2D. Even in insulin-independent patients, IT remains a marginal mass model. Moreover, ɸS can estimate transplanted islet mass and predict IT recipient outcomes.
胰岛移植（IT）可治疗严重不稳定 1 型糖尿病患者。通过餐试期间 C 肽水平可计算出两时相的胰岛素分泌前肝动力学（ISec）。我们提出描述 IT 受者混合餐耐量试验（MMTT）后的 ISec 谱，并确定计算的 ISec 指标是否可预测移植物结局。
我们分析了 2011 年至 2016 年间 11 例 IT 患者的 34 次 MMTT，并与健康对照者和 2 型糖尿病（T2D）患者进行了比较。MMTT 后通过 Van Cauter、Breda 和 Mari 模型计算 ISec 指数和胰岛素敏感性。成功的 IT 定义为无任何糖尿病标准的完全胰岛素独立性。
在成功的 IT 患者中，第一和第二时相 ISec 指数低于对照组（P < 0.001），与 T2D 组无差异。然而，IT 受者的胰岛素敏感性与对照组相似，高于 T2D 组。ISec 第二时相指数 ɸS 与总输注胰岛当量（IEQ）相关，是糖尿病（再）发生的良好预测指标，并可计算出 9500IEQ/kg 作为达到胰岛素独立性所需的最小量。
我们表明，ISec 第一和第二时相的指数在胰岛素非依赖性 IT 受者中发生改变。更高的敏感性将其与 T2D 患者区分开来。即使在胰岛素非依赖性患者中，IT 仍然是一种边缘质量模型。此外，ɸS 可估计移植胰岛的质量并预测 IT 受者的结局。
