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

ABSTRACT Background 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. Objective We hypothesized that a lower intake of BC...

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Vydáno v:The American journal of clinical nutrition Ročník 110; číslo 5; s. 1098 - 1107
Hlavní autoři: Karusheva, Yanislava, Koessler, Theresa, Strassburger, Klaus, Markgraf, Daniel, Mastrototaro, Lucia, Jelenik, Tomas, Simon, Marie-Christine, Pesta, Dominik, Zaharia, Oana-Patricia, Bódis, Kálmán, Bärenz, Felix, Schmoll, Dieter, Wolkersdorfer, Martin, Tura, Andrea, Pacini, Giovanni, Burkart, Volker, Müssig, Karsten, Szendroedi, Julia, Roden, Michael
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States Oxford University Press 01.11.2019
Témata:
Adipose Tissue, White - metabolism
Amino Acids, Branched-Chain - administration & dosage
Cross-Over Studies
Diabetes Mellitus, Type 2 - microbiology
Double-Blind Method
Female
Gastrointestinal Microbiome
Humans
Insulin Secretion
Male
Meals
Middle Aged
Mitochondria - physiology
Muscle, Skeletal - metabolism
insulin sensitivity
mitochondrial function
gut microbiome
patients with type 2 diabetes
diet
insulin secretion
branched-chain amino acids
ISSN:0002-9165, 1938-3207, 1938-3207
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Shrnutí:ABSTRACT Background 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. Objective We hypothesized that a lower intake of BCAAs improves tissue-specific insulin sensitivity. Methods 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. Results 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. Conclusions 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.
Bibliografie:ObjectType-Article-1
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ISSN:0002-9165
1938-3207
1938-3207
DOI:10.1093/ajcn/nqz191