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低脂联素血症与肾移植术后胰岛素抵抗和葡萄糖耐量异常相关:免疫抑制和抗高血压药物治疗的影响

Hypoadiponectinemia is associated with insulin resistance and glucose intolerance after renal transplantation: impact of immunosuppressive and antihypertensive drug therapy.

作者信息

Hjelmesaeth Jøran, Flyvbjerg Allan, Jenssen Trond, Frystyk Jan, Ueland Thor, Hagen Monica, Hartmann Anders

机构信息

Department of Medicine, Rikshospitalet University Hospital, Oslo, Norway.

出版信息

Clin J Am Soc Nephrol. 2006 May;1(3):575-82. doi: 10.2215/CJN.01471005. Epub 2006 Mar 22.

Abstract

The objectives of this analysis were (1) to assess whether low serum adiponectin concentrations are associated with insulin resistance, metabolic syndrome, and new-onset posttransplantation diabetes mellitus (PTDM) and (2) to examine the possible effects of immunosuppressive and antihypertensive therapies on circulating adiponectin levels after renal transplantation. A total of 172 consecutive previously nondiabetic renal transplant recipients were examined 3 mo after transplantation, the majority (n = 167) with an oral glucose tolerance test. Serum adiponectin was measured by an in-house time-resolved immunofluorometric assay. Insulin secretion and insulin sensitivity were estimated by previously validated oral glucose tolerance test-derived indexes. One- and 6-yr follow-up data were available in subgroups of patients. Lower adiponectin levels were significantly associated with insulin resistance but not with insulinopenia. Patients with low adiponectin levels (first quartile) had significantly higher odds of PTDM (odds ratio [OR] 3.6; 95% confidence interval [CI] 1.1 to 12.7; P = 0.049) and metabolic syndrome (OR 3.9; 95% CI 1.6 to 9.5; P = 0.003) than patients in the upper (fourth) quartile. The increased risk for PTDM in patients with low adiponectin levels remained significant after adjustment for age, steroid dose, and family history of diabetes. Treatment with beta blockers was independently associated with lower serum adiponectin levels, and total steroid dose was associated with higher serum adiponectin levels. Low baseline adiponectin levels were also associated with significantly higher odds of PTDM at 6 yr (OR 6.9; 95% CI = 1.1 to 41.8; P = 0.037). Serum adiponectin levels correlate with posttransplantation insulin sensitivity and glucose tolerance. Glucocorticoids and beta blockers seem to have opposite effects on circulating adiponectin levels.

摘要

本分析的目的是

(1)评估血清脂联素浓度低是否与胰岛素抵抗、代谢综合征及移植后新发糖尿病(PTDM)相关;(2)研究免疫抑制和抗高血压治疗对肾移植后循环脂联素水平的可能影响。共对172例连续的既往无糖尿病的肾移植受者在移植后3个月进行检查,大多数(n = 167)接受了口服葡萄糖耐量试验。采用内部时间分辨免疫荧光分析法测定血清脂联素。通过先前验证的源自口服葡萄糖耐量试验的指标评估胰岛素分泌和胰岛素敏感性。部分患者亚组有1年和6年的随访数据。脂联素水平较低与胰岛素抵抗显著相关,但与胰岛素缺乏无关。脂联素水平低(第一四分位数)的患者发生PTDM(比值比[OR] 3.6;95%置信区间[CI] 1.1至12.7;P = 0.049)和代谢综合征(OR 3.9;95% CI 1.6至9.5;P = 0.003)的几率显著高于处于上(第四)四分位数的患者。在调整年龄、类固醇剂量和糖尿病家族史后,脂联素水平低的患者发生PTDM的风险增加仍具有显著性。使用β受体阻滞剂治疗与血清脂联素水平较低独立相关,而类固醇总剂量与血清脂联素水平较高相关。低基线脂联素水平也与6年时发生PTDM几率显著更高相关(OR 6.9;95% CI = 1.1至41.8;P = 0.037)。血清脂联素水平与移植后胰岛素敏感性和糖耐量相关。糖皮质激素和β受体阻滞剂似乎对循环脂联素水平有相反的影响。

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