Open AccessEffects of Totum-63 on glucose homeostasis and postprandial glycemia: a translational study
Author(s) -
Vivien Chavanelle,
Yolanda F. Otero,
Florian Le Joubioux,
Doriane Ripoche,
Maxime Bargetto,
Aurore Vluggens,
Christophe Montaurier,
Gisèle Pickering,
Gilles Ducheix,
Claude Dubray,
Christian Dualé,
Sylvia Boulliau,
Nicolas Macian,
Geoffroy Marceau,
Vincent Sapin,
Frédéric Dutheil,
Bruno Guigas,
Thierry Maugard,
Nathalie Boisseau,
Murielle Cazaubiel,
Sébastien Peltier,
Pascal Sirvent
Publication year - 2021
Publication title -
endocrinology and metabolism/american journal of physiology: endocrinology and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.507
H-Index - 201
eISSN - 1522-1555
pISSN - 0193-1849
DOI - 10.1152/ajpendo.00629.2020
Subject(s) - medicine , endocrinology , glucose homeostasis , postprandial , insulin , steatosis , type 2 diabetes , overweight , triglyceride , carbohydrate metabolism , biology , diabetes mellitus , insulin resistance , body mass index , cholesterol
Global prevalence of type 2 diabetes (T2D) is rising and may affect 700 million people by 2045. Totum-63 is a polyphenol-rich natural composition developed to reduce the risk of T2D. We first investigated the effects of Totum-63 supplementation in high-fat diet (HFD)-fed mice for up to 16 wk and thereafter assessed its safety and efficacy (2.5 g or 5 g per day) in 14 overweight men [mean age 51.5 yr, body mass index (BMI) 27.6 kg·m -2 ] for 4 wk. In HFD-fed mice, Totum-63 reduced body weight and fat mass gain, whereas lean mass was unchanged. Moreover, fecal energy excretion was higher in Totum-63-supplemented mice, suggesting a reduction of calorie absorption in the digestive tract. In the gut, metagenomic analyses of fecal microbiota revealed a partial restoration of HFD-induced microbial imbalance, as shown by principal coordinate analysis of microbiota composition. HFD-induced increase in HOMA-IR score was delayed in supplemented mice, and insulin response to an oral glucose tolerance test was significantly reduced, suggesting that Totum-63 may prevent HFD-related impairments in glucose homeostasis. Interestingly, these improvements could be linked to restored insulin signaling in subcutaneous adipose tissue and soleus muscle. In the liver, HFD-induced steatosis was reduced by 40% (as shown by triglyceride content). In the subsequent study in men, Totum-63 (5 g·day -1 ) improved glucose and insulin responses to a high-carbohydrate breakfast test (84% kcal carbohydrates). It was well tolerated, with no clinically significant adverse events reported. Collectively, these data suggest that Totum-63 could improve glucose homeostasis in both HFD-fed mice and overweight individuals, presumably through a multitargeted action on different metabolic organs. NEW & NOTEWORTHY Totum-63 is a novel polyphenol-rich natural composition developed to reduce the risk of T2D. Totum-63 showed beneficial effects on glucose homeostasis in HFD-fed mice, presumably through a multitargeted action on different metabolic organs. Totum-63 was well tolerated in humans and improved postprandial glucose and insulin responses to a high-carbohydrate breakfast test.