膳食n-3多不饱和脂肪酸对中国2型糖尿病患者血糖和胰岛素抵抗的影响及机理研究

Type 2 diabetes (T2D) was one of the most common chronic diseases in the world. Dietary n-3 polyunsaturated fatty acids (n-3 PUFA) might decrease risk of T2D in Asians, and plasma phospholipids n-3PUFA were positively associated with insulin sensitivity in Chinese T2D patients. However, there were no randomized clinical trials examining the relationships between n-3 PUFA supplementation and glucose and insulin resistance in Chinese T2D patients. This study is a double-blinded randomized placebo-controlled clinical trial, we will recruit 240 Chinese T2D patients and all of them will be randomized into three groups: tuna oil (n = 80, 3g/d/head), flaxseed oil (n = 80, 3g/d/head) and corn oil (n = 80, 3g/d/head). The intervention will last for 180 days. The primary aim of this study is to examine the effects of n-3 PUFA on glucose and insulin resistance in Chinese T2D patients. The interaction of n-3 PUFA with genetic variants of key genes in the Insulin/IGF-1 signalling pathways on glucose and insulin resistance will be explored. Finally, rat model and cell culture experiments will be used to further explore the effects of n-3 PUFA on the mRNA and protein expressions of key genes in Insulin/IGF-1 pathways. This study is important for the advancement of personalized nutritional therapy for Chinese T2D patients.

血浆磷脂n-3多不饱和脂肪酸（n-3 PUFA）与中国2型糖尿病患者的胰岛素敏感性呈显著正相关，但目前尚无随机对照试验研究膳食n-3 PUFA对中国2型糖尿病患者血糖和胰岛素抵抗的影响。本项目采用双盲随机对照方法，拟征集240名2型糖尿病患者，随机分为金枪鱼油（n=80, 3g/日/人）、亚麻籽油（n=80, 3g/日/人）和玉米油（n=80，3g/日/人）三个组干预180天。主要研究n-3 PUFA对中国2型糖尿病患者血糖和胰岛素抵抗的影响；探索n-3 PUFA与Insulin/IGF-1信号通路中关键基因的多态性产生的交互作用。同时，利用大鼠实验和细胞实验进一步研究n-3 PUFA对该通路关键酶活性和关键基因mRNA表达和蛋白表达的影响。本研究对于推动中国2型糖尿病患者的个性化营养治疗具有重要意义。

海洋n-3多不饱和脂肪酸对中国2型糖尿病患者血糖代谢和胰岛素抵抗的影响及相关机理并不明确。本研究的目的是通过双盲随机对照试验探索n-3多不饱和脂肪酸对中国2型糖尿病患者血糖代谢和胰岛素抵抗的影响，并通过代谢组学和动物模型探索相关机理。首先，本研究通过双盲随机对照试验，发现在中国2型糖尿病患者中，深海鱼油相对于玉米油对照能够显著降低空腹糖化血红蛋白的浓度（P=0.037），从而起到调节血糖代谢的作用；同时，代谢组学分析显示，呋喃代谢物CMPF是深海鱼油干预的最强生物标志物。大鼠实验表明，深海鱼油能够通过调节胰岛素通路上的关键基因mRNA表达来调节胰岛素敏感性水平。本项研究结果对于中国2型糖尿病患者的营养治疗具有重要意义。