胰岛素不敏感患者异位脂肪的磁共振波谱特征研究

Numerous studies demonstrated that ectopic fat content and composition are closely related to insulin resistance. Our previous studies using magnetic resonance spectroscopy (MRS) found that fat content and composition in tibialis anterior muscle and liver of ob/ob mouse, a model of human obesity and Type II Diabetes Mellitus(T2DM), are statistically significant correlated to insulin resistance (NMR in Biomed, 2011 ; NMR in Biomed, 2013). To further explore this correlation in the human insulin resistance diseases, and especially in pancreas, the organ play key role in the transition from insulin resistance to T2DM, we designed this study. The answers to these questions will advance the understanding of pathogenesis, and provide a reliable evaluation tool for the development and prognosis of clinical treatment. MRS is the golden standard of non-invasive fat quantification. We intend to apply this technique in our study in a systematic way, including muscle, liver and pancreas, and assessing the ectopic fat content and composition using self-developed method, in combination with blood parameters which associated to insulin resistance or T2DM. This study will assess the feasibility of ectopic fat as the biomarker of insulin resistance, and the ability to predict the conversion from insulin resistance to T2DM in a systematic way.

大量研究发现异位脂肪与胰岛素不敏感的病理机制密切相关。申请人近期通过磁共振波谱研究发现，在模拟人类肥胖和II型糖尿病的ob/ob小鼠模型中，小腿胫骨前肌和肝脏内的脂肪含量及成分与胰岛素不敏感有显著统计学相关性(NMR in Biomed, 2011& 2013)。前期结果促使我们进一步思考这种相关性是否在人类疾病中成立，而在胰岛素不敏感期转化为II型糖尿病中起关键作用的胰腺，其脂肪变性在疾病发展中发挥怎样的作用？上述问题的解决将有助于深化对疾病发病机理的理解，并为临床治疗及预后评价提供可靠的科学依据。磁共振波谱(MRS)是无创测定体脂含量的金标准。我们拟应用此技术研究肌肉、肝脏及胰腺内的脂肪含量，采用独创的新方法分析其成分，并结合血液中与胰岛素不敏感或II型糖尿病相关的因素的变化，研究其相关性，从系统网络角度评估异位脂肪作为胰岛素不敏感的生物标记的可行性，为未来疾病转化的预判奠定基础。

本项研究采用活体磁共振氢谱(1H MRS)研究胰岛素不敏感患者异位脂肪的磁共振波谱特征。脂肪代谢在胰岛素不敏感中发挥着至关重要的作用，近几年有些学者提出跟异位脂肪的含量相比，脂肪的成分(饱和，单链不饱和和双链不饱和脂肪)起了更加直接的作用。技术上，我们通过T1/T2弛豫时间校正及运动校正，精确定量Ⅱ型糖尿病患者肝脏、肌肉和胰腺内脂肪的含量和成分，并筛选年龄BMI等相匹配的糖尿病前驱患者作为对照组，来研究脂肪和胰岛素不敏感的关系。本项目研究发现， 糖尿病前期者血液中甘油三酸脂，胆固醇，高密度脂蛋白胆固醇，丙氨酸转氨酶，与糖尿病患者没有统计学上的差异，但是非脂肪组织内，尤其肌肉内的脂肪，差异明显，肌肉细胞内脂肪与胰岛素抵抗的病程发展更加相关。