Inflammation and endothelial activation is evident at birth in offspring of mothers with type 1 diabetes
Inflammation and endothelial activation is evident at birth in offspring of mothers with type 1 diabetes
复制标题
DOI：
10.2337/db07-0662
复制
发表时间：
2007-11-01
期刊：
影响因子：
7.7
通讯作者：
Lindsay, Robert S.
中科院分区：
文献类型：
--
作者：
Nelson, Scott M.;Sattar, Naveed;Lindsay, Robert S.
糖尿病母亲的后代在以后的生活中有肥胖和葡萄糖耐受不良的风险。在成人中，亚临床炎症标志物（C-反应蛋白[CRP]和白细胞介素[IL]-6）和内皮活化（细胞内粘附分子[ICAM]-1）与肥胖和2型糖尿病发病风险较高相关。研究设计和方法-在139名OT 1DM和48名对照后代中测量脐带血浆CRP、IL-6和ICAM-1，与胎儿脂质和激素轴相关的分析。（四分位距）CRP（OT 1DM 0.17 mg/l [0.13- 0.22]对比对照受试者0.14 mg/l [0.12-0.17]，P < 0.001）和ICAM-1（OT 1DM 180 ng/ml [151-202] vs对照受试者166 ng/ml [145-187]，P = 0.047）。在对分娩方式进行必要的调整后，IL-6无差异。出生体重与炎症指标无关，而瘦素与CRP（对照组r = 0.33，P = 0.02; OT 1DM组r = 0.41，P < 0.001）、11，6（r = 0.23，P < 0.01）和ICAM-1（r = 0.29，P < 0.001）相关。在OT 1DM中，CRP与母体血糖控制相关（35-40周时的A1 C; r = 0.28，P = 0.01）。多因素分析显示瘦素是OT 1DM患者CRP（P < 0.001）、ICAM-1（P = 0.003）和11.6（P = 0.02）的决定因素。炎症指标显示OT 1DM（CRP、IL-6和ICAM-1 P < 0.05）和对照受试者（ICAM-1 P = 0.001）与甘油三酯呈正相关。亚临床炎症是糖尿病子宫内环境的一个新的组成部分，应被认为是子宫内疾病编程的潜在病因学机制。
OBJECTIVE-Offspring of mothers with diabetes are at risk of obesity and glucose intolerance in later life. In adults, markers of subclinical inflammation (C-reactive protein [CRP] and interleukin [IL]-6) and endothelial activation (intracellular adhesion molecule [ICAM]-1) are associated with obesity and higher risk for incident type 2 diabetes. We examined whether these biomarkers were elevated at birth in offspring of type 1 diabetic mothers (OT1DM).RESEARCH DESIGN AND METHODS-Umbilical cord plasma CRP, IL-6, and ICAM-1 were measured in 139 OT1DM and 48 control offspring, with analysis relative to fetal lipids and hormonal axes.RESULTS-OT1DM had higher median (interquartile range) CRP (OT1DM 0.17 mg/l [0.13- 0.22] vs. control subjects 0.14 mg/l [0.12-0.17], P < 0.001) and ICAM-1 (OT1DM 180 ng/ml [151-202] vs. control subjects 166 ng/ml [145-187], P = 0.047). IL-6 was not different after necessary adjustment for mode of delivery. Birth weight was unrelated to inflammatory indexes; however, leptin was correlated with CRP (control subjects r = 0.33, P = 0.02; OT1DM r = 0.41, P < 0.001) and with 11,6 (r = 0.23, P < 0.01) and ICAM-1 (r = 0.29, P < 0.001) in OT1DM. In OT1DM, CRP correlated with maternal glycemic control (A1C at 35-40 weeks; r = 0.28, P = 0.01). In multivariate analysis, leptin was a determinant of CRP (P < 0.001), ICAM-1 (P = 0.003), and 11,6 (P = 0.02) in OT1DM. Inflammatory measures demonstrated positive relationships with triglycerides in OT1DM (CRP, IL-6, and ICAM-1 P < 0.05) and control subjects (ICAM-1 P = 0.001).CONCLUSIONS-Inflammatory markers are increased in OT1DM and are related to measures of fetal adiposity, particularly leptin, and maternal glycemia. Subclinical inflammation is a novel component of the diabetic intrauterine environment and should be considered a potential etiological mechanism for in utero programming of disease.