Association between fat free mass and glucose homeostasis: Common knowledge revisited

•The impact of fat-free mass on glucose homeostasis in human is revisited.•A greater fat-free mass seems to be associated with insulin resistance.•Gains in fat-free mass do not necessarily improve insulin sensitivity status.•This deleterious association is observed in various populations.AbstractFat free mass (FFM), which is majorly composed of skeletal muscle tissues, is generally associated with health and well-being. Given that under normal circumstances FFM is the preferred site for glucose uptake in the body, scientific literature has proposed for the past decades that higher FFM could be beneficial for the metabolic profile and, more particularly, for glucose homeostasis. However, it seems that the relation is markedly more complex and recent results from our study group led us to re-examine the association between FFM and glucose homeostasis. While some studies support that higher FFM or FFM index could be associated with desirable metabolic parameters, a growing number of evidence reveal conflicting results. In fact, the negative association between FFM and glucose homeostasis has been reported in multiple populations, with different study designs and from independent research groups; thus rejecting the fortuitous relation hypothesis. Although the mechanisms leading to this association are still poorly understood, the discrepancies between studies may be partly due to the use of different relative indices to quantify FFM: some of them are likely to strongly correlate with body fatness and therefore could distort the relationship between muscle mass and metabolic health. The aim of this narrative review is to raise scientific awareness about the “modern” face of FFM in the context of the increasing prevalence of obesity; and its role with regards to glucose homeostasis.