Short-term dietary reduction of branched-chain amino acids reduces meal-induced insulin secretion and modifies microbiome composition in type 2 diabetes: a randomized controlled crossover trial

• DOI: 10.1093/ajcn/nqz191
• Publication Date: 2019-07-25T19:10:43Z
• Authors: Yanislava Karusheva; Theresa Koessler; Klaus Strassburger; Daniel Markgraf; Lucia Mastrototaro; Tomas Jelenik; Marie-Christine S...; Dominik Pesta; Oana-Patricia Zah...; Kálmán Bódis; Felix Bärenz; Dieter Schmoll; Martin Wolkersdorfer; Andrea Tura; Giovanni Pacini; Volker Burkart; Karsten Müssig; Julia Szendroedi; Michael Roden
• Keywords: Crossover study

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 a lower intake of BCAAs improves tissue-specific sensitivity. 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% an AA mixture either containing all AAs lacking BCAAs. The intervention ensured sufficient BCAA supply above the recommended minimum daily intake. underwent mixed meal tolerance test (MMT), hyperinsulinemic-euglycemic clamps (HECs), skeletal muscle white adipose tissue biopsies to assess signaling. After BCAA− diet, reduced 17% during fasting (P < 0.001), 13% HEC 0.01), 62% MMT 0.001). Under clamp conditions, whole-body hepatic sensitivity did not differ between diets. however, oral glucose index was 24% 0.01) fibroblast-growth factor 21 21% higher 0.05), whereas meal-derived secretion 28% 0.05). Adipose expression mechanistic target rapamycin lower, mitochondrial respiratory control ratio 1.7-fold (both P fecal microbiome enriched in Bacteroidetes but depleted Firmicutes. Short-term reduction decreases postprandial gut composition. Longer-term will be needed evaluate safety metabolic efficacy patients. registered at clinicaltrials.gov as NCT03261362.