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Finding novel targets for the treatment and reversal of type 2 diabetes mellitus and obesity

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submitted on 2023-05-11, 06:17 and posted on 2023-05-17, 11:54 authored by Imran Ramzan, Moira Taylor, Dan Wilkinson, Kenneth Smith, Philip Atherton, Iskandar Idris

Poster by Imran Ramzan, Moira Taylor, Kenneth Smith, Dan Wilkinson, Philip Atherton, and Iskandar Idris (University of Nottingham)

Background: Recent studies have identified branched chain amino acids (BCAAs; isoleucine, leucine and valine) as potential biomarkers of, and being involved in, the pathogenesis of type 2 diabetes mellitus (T2DM), insulin resistance (IR) and obesity. Reducing circulatory BCAAs by dietary restriction was suggested to mitigate these risks in rodent models, but this is a challenging paradigm to deliver in humans.

Objective: We aimed to design and assess the feasibility of a diet aimed at reducing circulating BCAA concentrations in humans, while maintaining energy balance and overall energy/protein intake. 

Methods: Twelve healthy individuals were assigned to either a 7-day BCAA-restricted diet or a 7-day control diet. Diets were iso-nitrogenous and iso-caloric, with only BCAA levels differing between the two.

Results: The BCAA-restricted diet significantly reduced circulating BCAA concentrations by ~50% i.e., baseline 437 ± 60 to 217 ± 40 µmol/L (p < 0.005). Individually, both valine (245 ± 33 to 105 ± 23 µmol/L; p < 0.0001), and leucine (130 ± 20 to 75 ± 13 µmol/L; p < 0.05), decreased significantly in response to the BCAA-restricted diet. The BCAA-restricted diet marginally lowered Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) levels: baseline 1.5 ± 0.2 to 1.0 ± 0.1; (p = 0.096).

Conclusion: We successfully lowered circulating BCAAs by 50% while maintaining iso-nitrogenous, iso-caloric dietary intakes, and while meeting the recommended daily allowances (RDA) for protein requirements. The present pilot study represents a novel dietary means by which to reduce BCAA, and as such, provides a blueprint for a potential dietary therapeutic in obesity/diabetes.

History

Language

  • English

Publication Year

  • 2023

Institution affiliated with

  • Hamad Bin Khalifa University
  • Qatar Biomedical Research Institute

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