Sarcopenia is an age-related clinical condition characterized by progressive loss of skeletal muscle mass with reduced muscle strength and physical performance (1). The problems of the elderly are attracting greater attention largely because the global population is steadily growing older as the proportion of its aged members increases. In 2019, the Chinese population constituted 18% of the world population, with 164.5 million Chinese citizens aged 65 and above (65+) (2). A study, according to the Asian Working Group on Sarcopenia (AWGS), reported that the prevalence rate of sarcopenia in the Chinese population over 60 years old was 10.5% (3). Age, physical inactivity, insulin resistance, endocrine factors, and low-grade chronic inflammation are the main mechanisms underlying sarcopenia (4).

Sarcopenia is associated with an increased risk of adverse outcomes and is reported to have approximately two‐ to four‐fold higher risk of mortality and functional disability irrespective of differences in the measurement and criteria of sarcopenia (5, 6). The prevalence of sarcopenia increases with age; however, it can be treated and even cured (7). Early diagnosis and intervention are extremely important to arrest the disability cascade that accompanies a clinical condition with this potential prevalence and well-known negative outcomes (8).

Several studies have reported laboratory biomarkers for the diagnosis of sarcopenia. One study reported that low alanine aminotransferase (ALT) levels predict low muscle strength in older patients with diabetes (9). ALT is a transaminase enzyme found in the liver and muscle tissue (10), while aspartate aminotransferase (AST) is expressed in the liver, heart, skeletal muscle, etc. Generally, high ALT or AST values (>40 IU/L) are considered pathological and reflect liver damage, caused by hepatitis, etc. (11). Another study also reported that low ALT activity in the peripheral blood is a surrogate marker for low general body muscle mass and sarcopenia (12). The aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio has been reported to be associated with mortality and disability in chronic liver disease, which is an age-related disease characterized by chronic low-grade inflammation (13). So, its role as a possible diagnostic biomarker for sarcopenia with the same pathogenesis of chronic low-grade inflammation was evaluated.

Prealbumin (PA), another biomarker, has been reported that its levels were inverse with sarcopenia incidence in hospitalized patients over 60 years old (14) or in older men with type 2 diabetes mellitus (15). PA is an indicator of protein metabolic balance in a non-acutely infected individual, which has a short half-life and can reflect drastic changes in nutritional status (16). Meanwhile, insulin plays a major role in protein metabolism by stimulating and enhancing protein synthesis and inhibiting proteolysis (17). A number of studies have reported that hyperinsulinemia can increase muscle protein synthesis (18). We used fasting insulin*prealbumin (INS*PA) to amplify the difference between sarcopenia and non-sarcopenia groups and to evaluate its potential as a diagnostic biomarker for sarcopenia. To our knowledge, this is the first study to report the effectiveness of the INS*PA product in the diagnosis of sarcopenia.

The serological method is cheap and simple for the diagnosis of sarcopenia, and there is no universal diagnostic standard for sarcopenia. Through this study, we hope to find the calculated value of some combination of biomarkers to amplify the difference between the sarcopenia group and the non-sarcopenia group, so as to better assist in the prediction of sarcopenia. The aim of this study was to evaluate the relationship between AST/ALT, INS*PA, and sarcopenia among elderly Chinese participants from the West China Health and Aging Trend (WCHAT) study under the background of China’s aging population. Moreover, we evaluate whether it is confounded by other metabolic factors in older participants. In addition, we calculate the usefulness of AST/ALT and INS*PA in predicting sarcopenia among all participants, male participants, and female participants, respectively.

With the advancement of the global aging process, age-related diseases are becoming a growing concern for the medical community. Generally, this study was conducted to evaluate the relationship between sarcopenia and high serum AST/ALT ratio and low serum INS*PA product levels among elderly Chinese participants from the WCHAT study under the background of China’s aging population. The independent risk factors for sarcopenia were serum AST/ALT >1.14, INS*PA <1,833 μU/ml*g/L, FT3 <4.48 pmol/L, VitD <18.5 ng/ml (in male participants), PTC >336 nmol/L, and DBP <81 mmHg (in female participants). INS*PA and AST/ALT have better diagnostic efficacy for sarcopenia, with AUC of 0.705 and 0.680 and with cutoff values of ≤1,500.16 μU/ml*g/L and >1.35, respectively. After the combination of the two indicators, the AUC for diagnosing sarcopenia could reach 0.727, with a cutoff value of >7.75, and the sensitivity and specificity were 68.0 and 66.7, respectively.

The AWGS modified their diagnostic criteria in 2019 to determine whether subjects have low muscle strength, such as handgrip strength, or low physical performance, using the 6-m walk test. Meanwhile, dual-energy X-ray absorptiometry or bioimpedance was used to assess muscle mass (20). The AWGS diagnostic criteria require hospitals to be equipped with specific instruments that are complex and costly and are not available in all community or primary care hospitals. Therefore, combinations of clinical and serum indicators are needed to predict and assess the risk of sarcopenia, which are measured worldwide as part of regular medical checkups because they can be rapidly, inexpensively, and reproducibly assayed. To our knowledge, this is the first study to predict the risk of sarcopenia using AST/ALT ratio and INS*PA product.

Sarcopenia results in structural or functional defects in skeletal muscles (21). Skeletal muscles are known to contain isozymes of AST, which may be released into the bloodstream following muscle necrosis (22). AST is a clinically accepted biomarker of liver and skeletal muscle injury (23). We found that serum AST activity was higher in patients with sarcopenia, but the difference was not statistically significant compared with those without sarcopenia. Perhaps because AST is widely distributed, the results are influenced by other target organs. Several studies have shown that low serum ALT is associated with lower muscle mass (24) and sarcopenia (25). The results of our research are consistent with the results of other studies. High AST, accompanied by low ALT, predominantly reflects mild-to-moderate skeletal muscle pathology (22, 26), which might imply the presence of incipient sarcopenia. We found a higher AST/ALT in the sarcopenia group, which was a risk factor and a diagnostic marker of sarcopenia. This may explain why an elevated AST/ALT ratio in the sarcopenia group was observed.

Insulin resistance causes loss of muscle tissue, which in turn decreases insulin sensitivity if the glucose supply remains constant and, thus, may lead to a vicious circle and the onset of sarcopenia (27–29). Insulin is involved in the maintenance of muscle mass via the p38MAPK and the mTOR/p70S6 kinase pathways, thus suppressing proteolysis (30–32). Insulin deprivation elevates protein breakdown, whereas insulin elevation increases protein synthesis in the setting of amino acid repletion (33). The above may explain why we observed a decrease in median INS levels in the sarcopenia group.

ALB is an indicator of protein metabolic balance in a non-acutely infected individual; however, a half-life of 18 to 21 days does not reflect drastic changes in nutritional status. In a meta-analysis, a significant association was found between low ALB levels and sarcopenia in adults 60 years of age and older (34). PA has a shorter half-life than ALB (16), so its role as a possible biomarker for sarcopenia was evaluated. There are few reports on PA in sarcopenia patients. We found that the sarcopenia group had lower ALB and PA levels. Due to the half-life advantage of PA, we used INS*PA to amplify the difference between the sarcopenia and non-sarcopenia groups and to evaluate its potential as a diagnostic biomarker for sarcopenia. Thus, we observed lower INS*PA levels in the sarcopenia group.

Metabolic syndrome includes hypertension, obesity, hypertriglyceridemia, and diabetes mellitus. Metabolic syndrome causes changes in the concentrations of indicators. To investigate whether AST/ALT and INS*PA are affected by metabolic factors, we obtained from Figure 1 that they were not and had reversed trends in median levels and prevalence. In addition, there was no statistical significance between AST/ALT and hypertension prevalence; all the others were statistically different. It has been reported that obesity, hypertriglyceridemia, and diabetes mellitus are associated with insulin resistance in adipocytes and hepatocytes, but hypertension is associated with insulin resistance in the vascular endothelium (35), which is why the prevalence of hypertension is not associated with AST/ALT but has to do with INS*PA (9). Lower AST/ALT and higher INS*PA were also able to predict obesity, hypertriglyceridemia, and diabetes mellitus in older subjects.

FT3 stimulates myogenesis and muscle contraction and regulates the metabolism of skeletal muscle cells that decrease with age (36). Mechanistically, VitD directly affected various aspects of muscle function, including myofibrillar protein degradation and impaired calcium transmission in the mitochondria (37). It has been reported that VitD is associated with sarcopenia (38). Nutritional supplementation with VitD attenuates the progression of chronic low-grade inflammatory profile in older sarcopenic persons with mobility limitations (39).

Exposure to excess cortisol plays a negative effect on muscle performance, strength, and muscle quality, which persists even many years after its resolution (40, 41). Glucocorticoids induce atrogin-1 and MuRF-1 in the ubiquitin–proteasome system, thus causing protein degradation of skeletal muscle (42, 43). In our study, higher PTC concentration was observed in the sarcopenia group, but the diagnostic efficacy was limited. The relationship between PTC and sarcopenia needs further study.

We found significant reductions in UA levels in patients with sarcopenia. UA was positively correlated with grip strength and nutritional score (44). In the sarcopenic group, HDL levels increased, while TG and VLDL levels decreased. An inverse relationship was observed between TG and mortality (45). Lower TG levels may be a consequence of poor health status associated with sarcopenia (46). HDL has multiple cardiovascular protective properties, such as anti-inflammatory effects (47). Sarcopenia involves chronic low-grade inflammation, and future research is necessary to validate the relationship between HDL and sarcopenia via a cohort study approach. One study in older women reported that appendicular fat-free mass was positively correlated with DBP, which is consistent with our findings (48). We found a higher NPR and a lower LPR in the sarcopenic group than in the non-sarcopenic group.

In conclusion, the current study shows that the independent risk factors for sarcopenia in middle-aged and older patients are serum AST/ALT >1.14, INS*PA <1,833 μU/ml*g/L, FT3 <4.48 pmol/L, VitD <18.5 ng/ml (in male participants), PTC >336 nmol/L, and DBP <81 mmHg (in female participants). Among these risk factors, serum AST/ALT ratio and INS*PA product have stronger effects on sarcopenia. High AST/ALT and low INS*PA are simple biomarkers that can diagnose sarcopenia in older patients, independent of the accompanying metabolic disorders.

The present study had several limitations. For one, our measures of smoking/drinking history, activity of daily living, and chronic diseases were based on questionnaires and should thus be interpreted with caution. Second, we used a single measurement of serum. Larger prospective studies are needed to confirm our findings. However, this is the first large-scale study based on a large sample population-based study in West China with complete information on sociodemographics, health conditions, physical examination, anthropometric measurement, and blood sample test, focusing on the general population. We provided potential calculated markers that were cheap and easily accessed for sarcopenia in the clinical setting. More attention should be paid to the levels of AST/ALT and INS*PA in the geriatric population with sarcopenia.

The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding authors.

The studies involving human participants were reviewed and approved by the Ethics Committee of the West China Hospital of Sichuan University (reference: 2017-445). The patients/participants provided their written informed consent to participate in this study.

All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.

This study was supported by the National Key R&D Program of China (2020YFC2005600 and 2020YFC2005603) and Sichuan Science and Technology Agency of Sichuan Province (2021YFS0148, 2020YFS0185, and 2019YFS0277).

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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