妊娠期糖尿病患者高分子量脂联素水平降低：对2型糖尿病病理生理学的影响

Decreased high-molecular-weight adiponectin in gestational diabetes: implications for the pathophysiology of Type 2 diabetes.

作者信息

Retnakaran R, Connelly P W, Maguire G, Sermer M, Zinman B, Hanley A J G

机构信息

Division of Endocrinology, University of Toronto, Toronto, Canada.

出版信息

Diabet Med. 2007 Mar;24(3):245-52. doi: 10.1111/j.1464-5491.2007.02077.x.

DOI:10.1111/j.1464-5491.2007.02077.x

PMID:17305786

Abstract

AIMS

Low serum concentrations of the insulin-sensitizing protein adiponectin predict the development of incident Type 2 diabetes (T2DM). It has recently emerged that the anti-diabetic activity of adiponectin may be mediated by its high-molecular-weight (HMW) isoform, circulating levels of which are decreased in T2DM. The relevance of decreased HMW adiponectin to incident T2DM, however, has not been assessed. Since gestational diabetes (GDM) identifies a population of young women at high risk of future T2DM (i.e. representing an early stage in the natural history of the disease), we sought to determine if decreased HMW adiponectin is a feature of GDM.

METHODS

HMW and total adiponectin were measured in 121 women at the time of oral glucose tolerance testing (OGTT) in late pregnancy, following an abnormal glucose challenge test. Based on the OGTT, there were 41 women with and 80 without GDM.

RESULTS

Median HMW adiponectin concentration was lower in women with GDM (3.5 microg/ml) than in those without GDM (5.5 microg/ml) (P < 0.0001). After full adjustment for covariates, mean HMW adiponectin remained significantly lower in women with GDM compared with their peers (3.6 vs. 5.3 microg/ml, P = 0.0035). HMW adiponectin was positively associated with insulin sensitivity (IS(OGTT)) (r = 0.38, P < 0.0001) and pancreatic B-cell function [insulin secretion-sensitivity index (ISSI)] (r = 0.33, P = 0.0002) and inversely related to blood glucose levels, including area-under-the-glucose-curve during the OGTT (AUC(glucose)) (r = -0.31, P = 0.0007). On separate multiple linear regression analyses, HMW adiponectin emerged as an independent determinant of AUC(glucose), IS(OGTT) and ISSI, respectively, mirroring the relationships of total adiponectin.

CONCLUSIONS

HMW adiponectin is significantly decreased in women with GDM. Deficiency of HMW adiponectin may be an early event in the natural history of T2DM.

摘要

目的

血清中胰岛素增敏蛋白脂联素浓度较低预示着2型糖尿病（T2DM）的发生。最近发现，脂联素的抗糖尿病活性可能由其高分子量（HMW）亚型介导，而T2DM患者循环中该亚型的水平会降低。然而，HMW脂联素降低与新发T2DM的相关性尚未得到评估。由于妊娠期糖尿病（GDM）可识别出未来发生T2DM风险较高的年轻女性群体（即代表疾病自然史的早期阶段），我们试图确定HMW脂联素降低是否为GDM的一个特征。

方法

在妊娠晚期进行口服葡萄糖耐量试验（OGTT）时，对121名葡萄糖耐量试验异常的女性测定了HMW和总脂联素水平。根据OGTT结果，41名女性患有GDM，80名女性未患GDM。

结果

GDM女性的HMW脂联素浓度中位数（3.5微克/毫升）低于未患GDM的女性（5.5微克/毫升）（P<0.0001）。在对协变量进行全面调整后，GDM女性的平均HMW脂联素水平仍显著低于同龄人（3.6对5.3微克/毫升，P = 0.0035）。HMW脂联素与胰岛素敏感性（IS(OGTT)）呈正相关（r = 0.38，P<0.0001），与胰腺B细胞功能[胰岛素分泌敏感性指数（ISSI）]呈正相关（r = 0.33，P = 0.0002），与血糖水平呈负相关，包括OGTT期间的葡萄糖曲线下面积（AUC(glucose)）（r = -0.31，P = 0.0007）。在单独的多元线性回归分析中，HMW脂联素分别成为AUC(glucose)、IS(OGTT)和ISSI的独立决定因素，这与总脂联素的关系相似。