Leth Henrik, Andersen Kristian K, Frystyk Jan, Tarnow Lise, Rossing Peter, Parving Hans-Henrik, Flyvbjerg Allan
The Medical Research Laboratories, Clinical Institute, Aarhus University Hospital, Nørrebrogade 44, DK-8000 Aarhus C, Denmark.
J Clin Endocrinol Metab. 2008 Aug;93(8):3186-91. doi: 10.1210/jc.2008-0360. Epub 2008 May 27.
Several studies have shown that type 1 diabetic patients have elevated total levels of the adipocyte-derived adipocytokine adiponectin. However, adiponectin circulates in three different subforms, and the high-molecular-weight (HMW) subform is believed to be the primary biologically active form. The effects of the medium-molecular-weight (MMW) subform and the low-molecular-weight (LMW) subform are still unresolved.
The objective of the study was to investigate the distribution of the three molecular subforms of adiponectin in well-characterized groups of type 1 diabetics with varying degrees of nephropathy as well as in healthy control subjects.
Two hundred seven individuals were included: 58 type 1 diabetics with normoalbuminuria, 46 with microalbuminuria, 46 with macroalbuminuria, and 57 matched controls.
The HMW, MMW, and LMW subforms were measured using a validated in-house time-resolved immunoflourometric assay after separation by fast protein liquid chromatography.
The absolute concentrations of total adiponectin and all subforms were higher in type 1 diabetic patients than healthy controls. However, the relative HMW fraction was up-regulated in type 1 diabetes (P < 0.001), whereas the MMW (P < 0.001) and LMW fractions (P < 0.05) were down-regulated, compared with controls. Accordingly, the increase in concentration of total adiponectin was primarily caused by a major increase of the HMW subform. Levels of total adiponectin and the HMW subform (absolute and relative) were generally unaffected by nephropathy status defined by urinary albumin excretion rate.
Type 1 diabetes per se is associated with higher adiponectin levels than healthy subjects. This increase is mainly explained by an elevation in the HMW subform. The elevation is unaffected by gender and diabetic kidney disease.
多项研究表明，1型糖尿病患者脂肪细胞源性脂肪因子脂联素的总水平升高。然而，脂联素以三种不同的亚形式循环，高分子量（HMW）亚形式被认为是主要的生物活性形式。中分子量（MMW）亚形式和低分子量（LMW）亚形式的作用仍未明确。
本研究的目的是调查脂联素的三种分子亚形式在具有不同程度肾病的1型糖尿病特征明确的群体以及健康对照受试者中的分布情况。
纳入了207名个体：58名正常白蛋白尿的1型糖尿病患者、46名微量白蛋白尿患者、46名大量白蛋白尿患者以及57名匹配的对照。
通过快速蛋白质液相色谱分离后，使用经过验证的内部时间分辨免疫荧光测定法测量HMW、MMW和LMW亚形式。
1型糖尿病患者中脂联素总量和所有亚形式的绝对浓度均高于健康对照。然而，与对照组相比，1型糖尿病中HMW组分上调（P < 0.001），而MMW（P < 0.001）和LMW组分（P < 0.05）下调。因此，脂联素总量浓度的增加主要是由HMW亚形式的大幅增加引起的。脂联素总量和HMW亚形式的水平（绝对和相对）通常不受尿白蛋白排泄率定义的肾病状态的影响。
1型糖尿病本身与高于健康受试者的脂联素水平相关。这种增加主要是由HMW亚形式的升高所解释。这种升高不受性别和糖尿病肾病的影响。
