Diabetes Care：胰岛素分泌降低可能是肾移植术后新发糖尿病的潜在病理机制

为了确定移植术后新发糖尿病(NODAT)的发病率、危险因素、表型和病理生理机制，以产生针对 NODAT患者高血糖的最佳药物治疗策略，来自奥地利维也纳大学医学院肾内科的Manfred Hecking博士等人进行了一些研究，研究发现，肾移植受试者与非移植对照者的血糖代谢有很大的不同，胰岛素分泌降低(而非胰岛素抵抗)可能是肾移植术后新发糖尿病的主要原因。研究结果在线发表于2013年5月8日美国的《糖尿病治疗》(Diabetes Care)杂志上。

这是一项回顾性队列研究，研究人员对肾移植受试者和非肾移植人群的人口统计学特征、实验室生化数据和口服葡萄糖耐量试验(OGTT)代谢参数进行了比较。

结果显示，在1,064名稳定期肾移植受试者(移植术后≥6个月)中，113名(11%)有NODAT病史，132名(12%)患有移植前糖尿病。剩余的患者随机分配进行OGTTs，结果显示，血糖代谢异常发病率升高(11%为糖尿病，32%为空腹血糖受损、葡萄糖耐量受损或两者兼有)，主要出现在以他克莫司作为主要免疫抑制剂的老年患者中。经OGTT 2h后血糖三分位分组(<140, 140-199, ≥200mg/dL)，每一分位组中稳定期肾移植受试者与1,357名非肾移植受试者比较，基线血糖值降低、糖化血红蛋白升高、胰岛素分泌降低，胰岛素敏感性升高。这些研究发现在胰岛素分泌和敏感度的线性样条内插组合模型和另一个线性回归模型中进一步得到增强(P值均<0.001)，在线性回归模型中，尽管经年龄、性别和BMI调整后，肾移植受试者估算的口服葡萄糖胰岛素敏感性指数较非移植受试者仍大大升高(79-112mL/min m2)。

研究发现，肾移植受试者与非移植对照者的血糖代谢有很大的不同。由于胰岛素分泌受损可能是肾移植术后主要的病理生理特征，作者认为具有保护、维持和改善β细胞功能的早期干预治疗对这类人群具有潜在的益处。

Glucose Metabolism After Renal Transplantation.
Abstract
OBJECTIVEWe determined prevalence, risk factors, phenotype, and pathophysiological mechanism of new-onset diabetes after transplantation (NODAT) to generate strategies for optimal pharmacological management of hyperglycemia in NODAT patients.RESEARCH DESIGN AND METHODSRetrospective cohort study comparing demographics, laboratory data, and oral glucose tolerance test (OGTT)-derived metabolic parameters from kidney transplant recipients versus subjects not receiving transplants.RESULTSAmong 1,064 stable kidney transplant recipients (≥6 months posttransplantation), 113 (11%) had a history of NODAT and 132 (12%) had pretransplant diabetes. In the remaining patients, randomly assigned OGTTs showed a high prevalence of abnormal glucose metabolism (11% diabetes; 32% impaired fasting glucose, impaired glucose tolerance, or both), predominantly in older patients who received tacrolimus as the primary immunosuppressant. Compared with 1,357 nontransplant subjects, stable kidney transplant recipients had lower basal glucose, higher glycated hemoglobin, lower insulin secretion, and greater insulin sensitivity in each of the three subgroups, defined by OGTT 2-h glucose (<140, 140-199, ≥200 mg/dL). These findings were reinforced in linear spline interpolation models of insulin secretion and sensitivity (all P < 0.001) and in another regression model in which the estimated oral glucose insulin sensitivity index was substantially higher (by 79-112 mL/min m2) for transplant versus nontransplant subjects despite adjustments for age, sex, and BMI (all P < 0.001).CONCLUSIONSGlucose metabolism differs substantially between kidney transplant recipients and nontransplant controls. Because impaired insulin secretion appears to be the predominant pathophysiological feature after renal transplantation, early therapeutic interventions that preserve, maintain, or improve β-cell function are potentially beneficial in this population.