The prevention of frailty is an important strategy to address related comorbidities such as falls, cardiovascular events, cognitive impairment, and mortality. [36, 37] The cycle of frailty consists of four main components: reduced resting metabolic rate, decreased total energy expenditure, chronic undernutrition, and sarcopenia. [38] Of these, sarcopenia is of particular importance for enabling the activities of daily living, preventing falls, and reducing various metabolic diseases.37,38 Therefore, methods for the early detection and prevention of sarcopenia would be of clinical and societal value.
In this study, adults of both sexes who had higher a TyG index were more likely to have LSMI, even after adjusting for age and other confounding factors. These findings were based on data from a representative, nationwide, cross-sectional survey. The exact mechanism by which TyG index is positively associated with LSMI is not known, but we hypothesize that insulin resistance and chronic inflammation may be the major link between elevated TyG index and increased risk of sarcopenia. The pathogenesis of sarcopenia has been suggested to be closely related to chronic inflammation, [20] which consequently increases insulin resistance [39] and may be reflected as an increased TyG index. The TyG index is thought to represent insulin resistance because it is calculated on the basis of two metabolic parameters: serum triglycerides and fasting glucose. Although we could not directly investigate the association between TyG index and insulin resistance indices due to lack of insulin data in the 2008–2011 KNHANES, we did find that the TyG index was related to the severity of metabolic syndrome, which is closely associated with insulin resistance. [24, 40] In addition, we found that a higher TyG index was associated with higher blood leukocyte count, a marker of chronic inflammation [41].
Sarcopenia is accompanied by muscle fat accumulation and an increase in pro-inflammatory cytokines, such as interleukin-6 (IL-6) and tissue necrosis factor alpha (TNF-α) within myocytes, [42], [43] which contribute to subsequent decreases in muscle mass and strength. [44, 45] IL-6 downregulates glucose transporter 4 expression and insulin receptor substrate-1 (IRS-1), resulting in reduced transport of glucose into cells (including myocytes), and aggravating insulin resistance. [46] TNF-α initiates a wide range of downstream signalling cascades, such as the activation of nuclear factor kappa B (NF-κB) and c-Jun N-terminal kinase (JNK). [47, 48] In turn, NF-κB and JNK lead to the impairment of IRS-1 and aggravation of insulin resistance. [47] Moreover, upregulated NF-κB caused by pro-inflammatory cascades causes ubiquitination of muscle proteins and dissociation of actin and myosin filaments, which consequently leads to further loss of skeletal muscle. [49, 50]
In the subgroup analysis, although adults under 65 years had higher odds of LSMI with increasing higher TyG tertile, there was no relationship between TyG index and LSMI in adults over 65 years of age. We believe that adults over 65 years may be less affected by the TyG index than the younger group because of the dominant influence of other factors, such as aging, chronic diseases, physical activity, and nutrition, which could each exert a stronger effect on LSMI than the TyG index. [51] Although adults who regularly exercised did not have significantly increased odds of LSMI as a function of increasing TyG tertile, adults who did not regularly exercise did. Although the IPAQ does not provide information about the timing of exercise and or type/duration of physical activity, the negative effects caused by insulin resistance and chronic inflammatory reactions might be offset by the protective and anabolic signalling due to regular exercise. [52, 53] The relationship between the TyG index and LSMI was only significant in the subgroup of adults that did not drink more than 30 g alcohol per day. Prior evidence has suggested that heavy alcohol drinking may accelerate sarcopenia, [54] so we think that alcohol use may interfere with the relationship between TyG index and LSMI. Similarly, smoking causes oxidative stress and chronic inflammation,56 and we only observed a significant relationship between TyG index and LSMI among the non-smoker group. One notable result in our subgroup study was that, in the low protein-intake group, the adjusted OR of LSMI in T3 compared to T1 was 1.456 (1.071–1.981). Supplementation with protein and amino acids may stimulate the synthesis of muscle protein, [55–57] eventually leading to gains in muscle mass. These results support a target consumption of at least 1.5 g protein per kg weight per day, especially in patients at high risk of sarcopenia.
This study had several limitations. First, we only had access to muscle mass information and could not obtain muscle strength or performance data, precluding a direct diagnosis of sarcopenia among the adults in this study. Second, we could not compare TyG indices with an insulin resistance index such as HOMA-IR. Finally, due to the cross-sectional study design, we could not assess causality between TyG index and LSMI. However, this is the first study to confirm the relationship between TyG index and muscle mass through the use of DXA and a representative, nationwide dataset from Korean adults.
In conclusion, we found that the TyG index was independently and negatively associated with muscle mass in Korean adults over 19 years old. Because the TyG index can be easily measured in the clinical setting, this may serve as a helpful method for the early detection of sarcopenia and related comorbidities, thus enabling timely initiation of treatment. Longitudinal cohort studies and experimental studies are needed to confirm the relationship between TyG and sarcopenia.