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Altogether, the data of Ikeda et al. indicate an additional hepatic entrainment that can be applied to chronotherapy by controlling protein-only diet in peoples with diabetes and/or circadian rhythm disorders. In some clinical setting, the augmentation of IGF-1, but not insulin, by a protein-rich diet might mediate a beneficial effect on entrainment of liver circadian rhythm. In fact, strong epidemiological evidence indicate that, independently of age, high protein intake was associated with higher IGF-1 levels and a 5-fold increase in diabetes mortality (Levine et al., 2014). However, these association studies do not shed light on the long-term mechanistic effects of protein-rich and/or low-carbohydrate diets on diabetes. In this respect, Ikeda et al. propose that the consumption of high-protein food limited to breakfast might entrain peripheral circadian rhythm and prevents obesity (Ikeda et al., 2018). This is consistent with clinical studies showing that in type 2 diabetic individuals, compared with a high-carbohydrate breakfast, the consumption of a high-protein breakfast meal attenuates the postprandial glucose response (Rabinovitz et al., 2014, Park et al., 2015). To our knowledge, no consensus exists about dietary recommendations for diabetic patients, and a wide debate about the nutrient composition in a balanced and healthy diet is still underway in the scientific community. American Diabetes Association (ADA) and National Health Service UK (NHS UK) currently recommend consumption of 50–55 g of proteins per day for all individuals – healthy or diabetics – that accounts for 15–20% of average energy intake from proteins. In agreement with Ikeda et al., both in vivo and epidemiological findings suggest the potential role of cysteine supplementation as a low-cost adjuvant therapy in the management of diabetic patients, by controlling glycemic level, lipid profile and oxidative stress (Prasenjit Manna, 2013). Further, pilot randomized controlled clinical trials testing protein- or cysteine-rich diets, and different meal timing/frequency, in individuals affected by type 1 or 2 diabetes are warranted.

Source: Protein-Rich or Amino-Acid Only Diets Entrain the Liver Clock: Time to Scrap Insulin? – EBioMedicine

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