Luzi Livio, Picena Sereni Lucia, Battezzati Alberto, Elli Attilio, Soulillou Jean-Paul, Cantarovich Diego
Department of Medicine, San Raffaele Scientific Institute, Milan, Italy.
Transplantation. 2003 Jun 27;75(12):2018-23. doi: 10.1097/01.TP.0000065177.18714.2E.
A corticosteroid (CS)-free immunosuppressive regimen may be considered less diabetogenic than treatments including CSs principally after pancreas transplantation.
To test whether a CS-free immunosuppressive treatment is metabolically superior to a regimen including CSs, we prospectively studied 19 CS-free simultaneous pancreas and kidney (SPK) transplant recipients (body mass index=22+/-1 kg/m2; cyclosporine dose=400+/-19 mg/kg/day; azathioprine dose=77+/-8 mg/day; basal plasma C-peptide=1.3+/-0.12 ng/mL) and 12 matched CS-treated SPK transplant recipients (prednisone dose=9+/-1 mg/day; basal C-peptide=2.2+/-0.2 ng/mL) by means of the 6,6-2H(2)-glucose infusion and the euglycemic insulin clamp (1 mU/kg/min, insulin infusion rate). In addition, six renal transplant recipients receiving a CS-free regimen were also studied as a control group.
In the postabsorptive state, CS-treated SPK transplant recipients demonstrated comparable plasma glucose levels but higher plasma insulin levels than CS-free SPK transplant recipients. Plasma triglyceride levels were significantly higher in CS-treated SPK patients than in CS-free SPK patients (1.16+/-0.16 mg/dL vs. 0.88+/-0.08; P<0.05). High-density lipoprotein and apoprotein A(1) levels were similar in both groups. No difference was observed in pyruvate, lactate, beta-OH-butyrate, and basal endogenous glucose production in all three groups of patients studied. During euglycemic hyperinsulinemia, the inhibition of endogenous glucose production and the stimulation of tissue glucose disposal were not statistically different among the three groups.
SPK recipients receiving chronic low-dose CS maintenance therapy do not present a lower glucose disposal than CS-free recipients. Nonetheless, this is obtained at the expense of a higher endogenous insulin secretion, which can cause an alteration of the triglyceride profile.
无皮质类固醇(CS)的免疫抑制方案可能被认为比主要包括CS的治疗方案致糖尿病作用更小,尤其是在胰腺移植后。
为了测试无CS的免疫抑制治疗在代谢方面是否优于含CS的方案,我们前瞻性地研究了19例接受无CS的同期胰肾(SPK)移植受者(体重指数=22±1kg/m²;环孢素剂量=400±19mg/kg/天;硫唑嘌呤剂量=77±8mg/天;基础血浆C肽=1.3±0.12ng/mL)和12例匹配的接受CS治疗的SPK移植受者(泼尼松剂量=9±1mg/天;基础C肽=2.2±0.2ng/mL),通过6,6-²H₂-葡萄糖输注和正常血糖胰岛素钳夹技术(胰岛素输注速率为1mU/kg/min)。此外,还研究了6例接受无CS方案的肾移植受者作为对照组。
在空腹状态下,接受CS治疗的SPK移植受者的血浆葡萄糖水平相当,但血浆胰岛素水平高于无CS的SPK移植受者。接受CS治疗的SPK患者的血浆甘油三酯水平显著高于无CS的SPK患者(1.16±0.16mg/dL对0.88±0.08;P<0.05)。两组的高密度脂蛋白和载脂蛋白A(1)水平相似。在所有三组研究患者中,丙酮酸、乳酸、β-OH-丁酸和基础内源性葡萄糖生成均未观察到差异。在正常血糖高胰岛素血症期间,三组之间内源性葡萄糖生成的抑制和组织葡萄糖处置的刺激在统计学上无差异。
接受慢性低剂量CS维持治疗的SPK受者与无CS受者相比,葡萄糖处置能力并不更低。尽管如此,这是以更高的内源性胰岛素分泌为代价的,这可能会导致甘油三酯谱的改变。