Role of slowly digestible starch in diabetes risk factors in pre-diabetic people

描述(申请人提供)：在这项双盲随机对照试验中，80名糖尿病前期(IGT/IFG)患者(35-65岁)将接受含有慢速可消化淀粉(直链淀粉；N=40)或“对照”淀粉(支链淀粉；N=40)的饮食，为期3个月。我们在啮齿动物身上的数据(得到其他人的支持)表明，慢速可消化淀粉的摄入：a)增强肠道微生物谱；b)减少代谢内毒素血症；c)增加丁酸盐和丙酸的发酵和产生；d)增加有益的肠道激素，如GLP-1和PYY；e)降低血糖负荷；f)抑制食欲。因此，我们建议喂食慢速消化淀粉，以同时针对已知的几种在血糖动态平衡中重要的机制，重点是胰岛素敏感性、脂肪氧化和异位脂肪。我们将测试这样一个假设，即IGT和/或IFG患者在3个月内每天摄入45g直链淀粉，肠道微生物群的组成将反过来改善T2 DM的危险因素，如：a)胰岛素敏感性增强(FSIGTT；Aim1)；b)减少食欲和食物摄入量(AIM2)；c)减少异位脂肪储存(1H-MRS；Aim1)；d)减少炎症(血清标志物；Aim1)；以及；e)以代谢有利的方式修改大肠微生物群的组成(Aim3)。这种饮食干预方法(在酸奶中添加可缓慢消化的淀粉)可能比每日热量限制和运动更耐受，因此更适用于T2 DM的治疗。 公共卫生相关性：糖耐量受损(IGT)的人患有胰岛素抵抗和低级别炎症，并处于发展为2型糖尿病的高危状态。密集的生活方式改变(减少能量摄入和增加体力活动)降低了IGT患者的糖尿病发病率。然而，这种生活方式的改变很难长期保持，大多数减肥的人在接下来的几年里又会恢复过来。确定一种非药物干预措施来改善个体的胰岛素敏感性，可能会对日益肥胖的人群产生重大影响。因此，我们建议研究为期3个月的饮食补充45g慢消化淀粉对糖尿病前期(IGT)患者发生2型糖尿病的危险因素的影响。初步数据表明，这些淀粉可能会影响肠道微生物的种类，进而可能会增强胰岛素敏感性，预防糖尿病的发展。

DESCRIPTION (provided by applicant): In this double-blind randomized controlled trial, 80 individuals (35-65y) with pre-diabetes (IGT/IFG) will receive either a diet containing slow digestible starch (amylose; N=40) or "control" starch (amylopectin; N=40) for 3 months. Our data in rodents (supported by others) have shown that the ingestion of slow digestible starch: a) enhances the gut microbial profile; b) reduces metabolic endotoxemia; c) increases fermentation and production of butyrate & propionate; d) increases beneficial gut hormones such as GLP-1 and PYY; e) lowers the glycemic load and; f) suppresses appetite Therefore, we propose to feed a slowly digestible starch to simultaneously target several mechanisms known to be important in glucose homeostasis with emphasis on insulin sensitivity, fat oxidation and ectopic fat. We will test the hypothesis that improved composition of the gut microbiota with a daily intake of 45 g of amylose for 3 months in individuals with IGT and/or IFG will in turn improve risk factors for the development of T2DM such as: a) enhancement of insulin sensitivity (FSIGTT; Aim1); b) decrease appetite and food intake (Aim2); c) decrease ectopic fat depots (1H-MRS; Aim1); d) decrease inflammation (serum markers; Aim1) and; e) modify the composition of large intestine microbiota in a metabolically favorable way (Aim3). This dietary intervention approach (addition of slowly digestible starch in yogurts) may prove more tolerable than daily caloric restriction and exercise and therefore more practically applicable for the treatment of T2DM. PUBLIC HEALTH RELEVANCE: People with impaired glucose tolerance (IGT) suffer from insulin resistance and low grade inflammation and are at high risk of developing type 2 diabetes. Intensive lifestyle changes (reduced energy intake and increased physical activity) decrease the incidence of diabetes in people with IGT. However such lifestyle changes are difficult to maintain over the long-term and most people who lose weight regain it over subsequent years. The identification of a non-pharmacological intervention to improve insulin sensitivity in individuals could have a significant impact in an increasingly obese population. We therefore propose to study the effect of 3- month of dietary supplementation with 45-g of slowly digestible starch on risk factors for the development of type 2 diabetes in people with pre-diabetes (IGT). Preliminary data indicate that these starches may influence the gut microbial species which in turn may enhance insulin sensitivity and protect against the development of diabetes.