Does high dietary protein intake contribute to the increased risk of developing prediabetes and type 2 diabetes?

Oana Ancu, Monika Mickute, Nicola D. Guess, Nicholas M. Hurren, Nicholas A. Burd, Richard W. Mackenzie

Research output: Contribution to journalReview articlepeer-review


Insulin resistance is a complex metabolic disorder implicated in the development of many chronic diseases. While it is generally accepted that body mass loss should be the primary approach for the management of insulin resistance-related disorders in overweight and obese individuals, there is no consensus among researchers regarding optimal protein intake during dietary restriction. Recently, it has been suggested that increased plasma branched-chain amino acids concentrations are associated with the development of insulin resistance and type 2 diabetes. The exact mechanism by which excessive amino acid availability may contribute to insulin resistance has not been fully investigated. However, it has been hypothesised that mammalian target of rapamycin (mTOR) complex 1 hyperactivation in the presence of amino acid overload contributes to reduced insulin-stimulated glucose uptake because of insulin receptor substrate (IRS) degradation and reduced Akt-AS160 activity. In addition, the long-term effects of high-protein diets on insulin sensitivity during both weight-stable and weight-loss conditions require more research. This review focusses on the effects of high-protein diets on insulin sensitivity and discusses the potential mechanisms by which dietary amino acids can affect insulin signalling. Novelty: Excess amino acids may over-activate mTOR, resulting in desensitisation of IRS-1 and reduced insulin-mediated glucose uptake.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalApplied Physiology, Nutrition and Metabolism
Issue number1
StatePublished - Jan 2021


  • Branched-chain amino acids
  • High-protein diet
  • Insulin resistance
  • MTOR/S6K1
  • Type 2 diabetes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Nutrition and Dietetics
  • Physiology (medical)


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