Protective role of skeletal muscle mass against progression from metabolically healthy to unhealthy phenotype

Abstract

Objective: Metabolically healthy individuals are known to be resistant to cardiovascular disease development. However, a considerable fraction of those individuals shows deteriorated metabolic health over time. Although skeletal muscle is the primary insulin-responsive target organ, a longitudinal investigation of the skeletal muscle mass in relation to the development of metabolically unhealthy phenotype has not been performed. We aimed to evaluate whether greater skeletal muscle mass is an independent protective factor for the development of metabolically unhealthy phenotype. Design, Participants and Measurements:We conducted a retrospective cohort study with 9033 metabolically healthy volunteers who underwent routine health examinations in 2012 and a follow-up examination in 2016. Obesity was defined as Asian-Pacific body mass index criterion ≥25 kg/m 2 . Subjects with fewer than two risk factors (elevated blood pressure, triglyceride, glucose, high-sensitivity C-reactive protein, insulin resistance and decreased high-density lipoprotein cholesterol levels)were characterized as metabolically healthy using Wildman criteria.Results: At the 4-year follow-up, approximately one-fourth of the nonobese participants and half of the participants with obesity showed metabolic deterioration. In nonobese men and women, higher appendicular skeletal muscle mass (ASM)/weight at baseline was significantly associated with decreased risk of metabolic deterioration. Compared to the lowest quartile of ASM/weight, the adjusted odds ratios (95% confidence intervals) of the highest quartile were 0.68 (0.52-0.89) in nonobese men and 0.64 (0.46-0.90) in nonobese women. However, this association was not observed in obese subjects. Conclusions:Greater skeletal muscle mass at baseline is significantly associated with maintenance of metabolically healthy status, especially in nonobese individuals. K E Y W O R D Scardiovascular diseases, insulin resistance, obesity phenotypes, sarcopenia | 103 LEE Et aL.

The way fat‐free mass is reported may change the conclusions regarding its protective effect on metabolic health

“…The main result reported by the authors is that a greater muscle mass at baseline is associated with a decreased risk of progressing to a metabolically unhealthy phenotype at a 4‐year follow‐up. We refer readers to the original article for the full definition of ‘unhealthy phenotype’. In this letter, we would like to discuss the way FFM is expressed and how this may alter the outcomes.…”

“…Although exact mechanisms have never been pinpointed, it is commonly accepted in the scientific and clinical communities that a greater FFM would play a protective role in glucose homoeostasis and metabolic health. Longitudinal studies investigating the role of FFM on metabolic syndrome (MetS) are scarce considering the importance of the issue, and it is thus with interest that we read the article from Lee et al (2019) titled ‘Protective Role of Skeletal Muscle Mass against Progression from Metabolically Healthy to Unhealthy Phenotype’. The main result reported by the authors is that a greater muscle mass at baseline is associated with a decreased risk of progressing to a metabolically unhealthy phenotype at a 4‐year follow‐up.…”

The Authors' Reply: ‘The way fat‐free mass is reported may change the conclusions regarding its protective effect on metabolic health.’ by Legace et al.

“…1 These results suggested that the harmful effects of excess fat in individuals with obesity may override the beneficial effects of muscle mass, as previously mentioned. 1 However, previous studies have suggested that the relative dis- for women]. 3 We adjusted WC as an indicator of accumulation of fat in the upper body (abdominal region) in our original analysis, and the protective effect of high ASM/weight for progression to a metabolically unhealthy phenotype still remained significant.…”

“…In our article, we reported that a higher appendicular skeletal muscle mass (ASM) at baseline was significantly associated with a decreased risk of metabolic deterioration in nonobese individuals. 1 However, this association was not observed in obese subjects. 1 These results suggested that the harmful effects of excess fat in individuals with obesity may override the beneficial effects of muscle mass, as previously mentioned.…”

“…1 However, this association was not observed in obese subjects. 1 These results suggested that the harmful effects of excess fat in individuals with obesity may override the beneficial effects of muscle mass, as previously mentioned. 1 However, previous studies have suggested that the relative dis- for women].…”