Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany.
German Center for Diabetes Research, München-Neuherberg, Germany.
Am J Clin Nutr. 2019 Nov 1;110(5):1098-1107. doi: 10.1093/ajcn/nqz191.
Epidemiological studies have shown that increased circulating branched-chain amino acids (BCAAs) are associated with insulin resistance and type 2 diabetes (T2D). This may result from altered energy metabolism or dietary habits.
We hypothesized that a lower intake of BCAAs improves tissue-specific insulin sensitivity.
This randomized, placebo-controlled, double-blinded, crossover trial examined well-controlled T2D patients receiving isocaloric diets (protein: 1 g/kg body weight) for 4 wk. Protein requirements were covered by commercially available food supplemented ≤60% by an AA mixture either containing all AAs or lacking BCAAs. The dietary intervention ensured sufficient BCAA supply above the recommended minimum daily intake. The patients underwent the mixed meal tolerance test (MMT), hyperinsulinemic-euglycemic clamps (HECs), and skeletal muscle and white adipose tissue biopsies to assess insulin signaling.
After the BCAA- diet, BCAAs were reduced by 17% during fasting (P < 0.001), by 13% during HEC (P < 0.01), and by 62% during the MMT (P < 0.001). Under clamp conditions, whole-body and hepatic insulin sensitivity did not differ between diets. After the BCAA- diet, however, the oral glucose sensitivity index was 24% (P < 0.01) and circulating fibroblast-growth factor 21 was 21% higher (P < 0.05), whereas meal-derived insulin secretion was 28% lower (P < 0.05). Adipose tissue expression of the mechanistic target of rapamycin was 13% lower, whereas the mitochondrial respiratory control ratio was 1.7-fold higher (both P < 0.05). The fecal microbiome was enriched in Bacteroidetes but depleted of Firmicutes.
Short-term dietary reduction of BCAAs decreases postprandial insulin secretion and improves white adipose tissue metabolism and gut microbiome composition. Longer-term studies will be needed to evaluate the safety and metabolic efficacy in diabetes patients.This trial was registered at clinicaltrials.gov as NCT03261362.
流行病学研究表明，循环支链氨基酸（BCAAs）水平升高与胰岛素抵抗和 2 型糖尿病（T2D）有关。这可能是由于能量代谢或饮食习惯的改变。
我们假设摄入较低水平的 BCAAs 可改善组织特异性胰岛素敏感性。
这是一项随机、安慰剂对照、双盲、交叉试验，研究了接受等热量饮食（蛋白质：1g/kg 体重）4 周的血糖控制良好的 T2D 患者。蛋白质需求由市售食品补充，补充的必需氨基酸混合物（AA 混合物）仅占 60%，该混合物包含所有必需氨基酸或缺乏必需氨基酸。饮食干预确保了 BCAA 的供应充足，超过了推荐的最低每日摄入量。患者接受混合餐耐量试验（MMT）、高胰岛素-正常血糖钳夹（HEC）和骨骼肌和白色脂肪组织活检，以评估胰岛素信号。
在补充 BCAA 的饮食后，空腹时 BCAAs 降低了 17%（P<0.001），HEC 时降低了 13%（P<0.01），MMT 时降低了 62%（P<0.001）。在钳夹条件下，两种饮食之间的全身和肝胰岛素敏感性没有差异。然而，在补充 BCAA 的饮食后，口服葡萄糖敏感指数增加了 24%（P<0.01），循环成纤维细胞生长因子 21 增加了 21%（P<0.05），而餐后胰岛素分泌降低了 28%（P<0.05）。脂肪组织中雷帕霉素靶蛋白的表达降低了 13%，而线粒体呼吸控制比增加了 1.7 倍（均 P<0.05）。粪便微生物组中拟杆菌门增加，厚壁菌门减少。
短期饮食中 BCAAs 的减少可降低餐后胰岛素分泌，并改善白色脂肪组织代谢和肠道微生物组组成。需要进行更长时间的研究来评估糖尿病患者的安全性和代谢疗效。本试验在 clinicaltrials.gov 上注册为 NCT03261362。
