Introduction
Diabetes is a chronic metabolic disease caused by the progressive loss of β-cell mass and/or function due to various genetic and environmental factors, resulting in hyperglycemia [
1]. Latest evidence shows that the number of individuals with diabetes is 537 million worldwide and 141 million in China, and this number is rapidly increasing, thus making diabetes, which is closely associated with disability and death, a major public health concern of the 21st century [
2].
Sarcopenia is a skeletal muscle disorder characterized by progressive and generalized loss of muscle mass and strength, which is usually associated with age [
3]. With the aging of the Chinese population, the prevalence of sarcopenia is rapidly increasing and has become a new research hotspot [
3]. The diagnostic criteria for “sarcopenia” have not yet been standardized worldwide. To the best of our knowledge, all diagnostic criteria consider muscle mass, muscle strength, and physical performance, which are associated with poor health [
4‐
7]. Access to reliable equipment to measure muscle mass in community settings remains a challenge; therefore, the Asian Working Group for Sarcopenia (AWGS) 2019 consensus introduced the concept of “possible sarcopenia” to allow the early identification of individuals at risk for sarcopenia and their timely intervention [
6]. Possible sarcopenia refers to reduced muscle strength or poor physical performance that can be measured using simple and affordable methods in community screening and clinical practice [
6]. This concept was developed to help better manage the risk of sarcopenia and improve the quality of life of patients.
Recent studies have shown that sarcopenia and type 2 diabetes mellitus (T2DM) have a bidirectional association [
8]. T2DM can lead to the development of sarcopenia [
9], which in turn can exacerbate diabetes [
10], through possible mechanisms, including impaired glucose metabolism, insulin resistance, mitochondrial dysfunction, inflammation, and antioxidant stress response [
8,
11]. Although several cross-sectional studies have reported that sarcopenia increases the risk of new-onset T2DM [
12‐
14], it remains unclear whether possible sarcopenia increases the risk of new-onset T2DM. The concept of “possible sarcopenia” is relatively new, and its diagnostic criteria are not as strict as those of sarcopenia. The introduction of “possible sarcopenia” to explore its association with new-onset T2DM may help older adults prevent and manage the risk of the disease in a more timely manner.
Therefore, based on nationally representative data from the China Health and Retirement Longitudinal Study (CHARLS), we aimed to investigate the longitudinal relationship between possible sarcopenia and new-onset T2DM, as defined by the AWGS 2019 criteria, among community-dwelling older adults aged ≥ 60 years in China. This study may further improve the understanding of the relationship between possible sarcopenia and new-onset T2DM and provide a basis for better prevention of T2DM.
Discussion
In this study, we revealed that possible sarcopenia was associated with an increased risk of new-onset T2DM during the 7-year follow-up. This association was independent of sex, age group, BMI classification, central obesity, residence, marital status, educational level, and smoking and drinking statuses and remained significant after adjustment for fasting plasma glucose and several chronic diseases (e.g., hypertension and hyperlipidemia). In subgroup analysis, we observed a significant association between possible sarcopenia and T2DM in individuals younger than 75 years and with a BMI below 24. These results suggest that possible sarcopenia is a risk factor for T2DM. However, our study failed to determine a significant association between low muscle strength or reduced physical performance and increased risk of new-onset T2DM.
With the rapid aging of the population, possible sarcopenia has become a significant issue. The concept of possible sarcopenia has been proposed in several guidelines worldwide, including AWGS and the European Working Group on Sarcopenia in Older People. Moreover, numerous studies have investigated the epidemiology of possible sarcopenia [
21‐
24]. Our findings revealed that the prevalence of possible sarcopenia was 45.1% in the older adult nondiabetic population in China, indicating that possible sarcopenia is a relatively common disorder, which is consistent with the findings of previous studies reporting a 46% prevalence of possible sarcopenia in community-dwelling older adults aged ≥ 60 years in China [
22]. However, multiple factors, including age, genetic factors, lifestyle, nutritional status, socioeconomic status, and different research methods and criteria influence muscle strength and physical performance; therefore, the prevalence of possible sarcopenia varies across age groups, countries, and regions [
9,
21]. For example, the prevalence of possible sarcopenia is 5.3% in individuals aged 40–70 years in the United Kingdom [
21], approximately 25% in individuals aged ≥ 75 years in Switzerland [
24], and 46.5% in individuals aged ≥ 60 years in Colombia [
23].
Previous studies have shown a relationship between sarcopenia and new-onset T2DM [
12‐
14]. These studies were cross-sectional; however, longitudinal studies can monitor changes in the same cohort and observe the evolution of the group or participants, with more convincing results. In our 7-year follow-up of 3,707 older adults in a Chinese community, we noted that the probability of developing T2DM in patients with possible sarcopenia was 17.3%, whereas that in participants without possible sarcopenia was 14%. After adjusting for as many confounders as possible (e.g., sex, age group, BMI classification, central obesity, residence, smoking and drinking statuses, fasting plasma glucose, and some chronic diseases), individuals with possible sarcopenia had an approximately 27% higher risk of developing T2DM than those without possible sarcopenia, indicating that possible sarcopenia is a risk factor for T2DM. This study was conducted using a large, nationally representative sample of Chinese individuals, indicating that the findings can be generalized to the Chinese older adult population. Our findings have significant public health implications because screening for possible sarcopenia is easy and inexpensive; thus, it can be easily extended to community health screening and routine clinical practice, which may help identify individuals at increased risk of developing T2DM who would benefit from early intervention.
Our study uncovered significant findings regarding the association between possible sarcopenia and incident T2DM across different age and BMI groups. Specifically, we observed a notable correlation between possible sarcopenia and T2DM among individuals with a BMI below 24 kg/m
2, while this relationship was not significant among those with a BMI of 24 kg/m
2 or higher, aligning with previous research indicating an increased risk of T2DM in non-obese individuals with sarcopenia [
13]. Interestingly, we also found a clear association between possible sarcopenia and T2DM in individuals younger than 75 years, but this association was not evident among those aged ≥ 75 years. These results contradict previous cross-sectional studies conducted in a Korean population [
12]. The discrepancies in findings may stem from differences in study design, population characteristics, and the adjustments made for confounding factors. Longitudinal studies like ours, which assess temporal associations, provide more robust evidence. Additionally, variations in lifestyle patterns and environmental factors could also contribute to the observed differences [
25]. The complex relationship between possible sarcopenia, age, BMI, and T2DM likely involves various underlying mechanisms, such as age-related muscle changes, adipose tissue distribution, metabolic alterations, and inflammation [
26]. Further research is needed to delve into these mechanisms and gain a better understanding of how age and BMI influence the association between possible sarcopenia and T2DM risk.
Possible sarcopenia is diagnosed based on physical performance and muscle strength [
6]. Reduced physical performance is reported to be associated with T2DM development [
27,
28]; however, the existence of a relationship between low muscle strength and T2DM development remains controversial [
27,
29‐
31]. Some studies have suggested that low muscle strength contributes to the occurrence of T2DM [
27,
29], whereas other studies have proposed that there is no association between muscle strength and the onset of T2DM [
30,
31]. In the present study, we defined low muscle strength or reduced physical performance according to the AWGS 2019 criteria and followed up 3,707 older adults for 7 years. The results showed that low muscle strength or reduced physical performance alone was not statistically significantly associated with the risk of developing T2DM; however, an increasing trend was observed. This finding was inconsistent with the primary results of this study, which may be because the number of participants with low muscle strength or reduced physical performance was smaller than that of participants with possible sarcopenia; consequently, the effects of these factors on the risk of developing T2DM may be masked. Future studies should increase the sample size to explore the relationship between low muscle strength or reduced physical performance and the risk of new-onset T2DM. However, our study result was not entirely consistent with previous findings [
27‐
31], and a relevant explanation for these inconsistent findings is the different definitions of low muscle strength and reduced physical performance [
32,
33]. Our study defined low muscle strength and reduced physical performance based on the AWGS 2019 criteria; however, no previous studies have adopted this definition. Therefore, caution is needed when comparing these findings. Moreover, other possible factors, including genetics, diet, and exercise, should be considered [
9,
34]. Therefore, further studies are warranted to better understand the relationship between muscle strength or physical performance and new-onset T2DM.
The mechanism by which possible sarcopenia increases the risk of incident diabetes remains unclear. The skeletal muscle is the primary site of glucose disposal, and approximately 80% of glucose is metabolized in the muscle in the postprandial state [
35]. Therefore, muscle wasting may weaken the ability to maintain glucose homeostasis, particularly in the postprandial state [
3]. Furthermore, sarcopenia is associated with insulin resistance [
36], which is considered to be the main defect in T2DM development [
37]. Furthermore, oxidative stress, inflammation, and physical inactivity may link sarcopenia to T2DM [
38]. Finally, our regression analysis suggested that BMI, hypertension, and hyperlipidemia were all associated with an increased risk of T2DM. Increased BMI may lead to the development of obesity and insulin resistance, which may increase the risk of T2DM [
39]. Hypertension and hyperlipidemia may contribute to the development of conditions, such as atherosclerosis and cardiovascular disease, which were also associated with T2DM development [
40]. Patients with sarcopenia were more likely to have metabolic abnormalities, such as high BMI, hypertension, and hyperlipidemia, than those without sarcopenia [
41]. Thus, high BMI, hypertension, and hyperlipidemia may be involved in the mechanisms by which possible sarcopenia leads to T2DM and together contribute to the development of new-onset T2DM. Future studies are warranted to elucidate the mechanisms underlying the association between possible sarcopenia and T2DM.
This study has several limitations. First, this was an observational study, and the established relationships between possible sarcopenia and incident diabetes may be biased by confounding factors. To overcome this problem, we analyzed the association by testing multiple models that included different correction factors. Additionally, we used the multiple imputation method and sensitivity analysis to minimize the offset. However, it is important to note that certain confounding factors, such as family history of diabetes, physical activity, and a fat-rich diet, were not available and could not be included in our analyses for correction. Second, there may be some bias in the diagnosis of T2DM. Medical records were not included in CHARLS, and T2DM was diagnosed using blood examinations (e.g., blood glucose and HbA1c) and structured questionnaires (e.g., self-reported physician diagnosis or current use of diabetes medication). Moreover, as blood samples were only available during baseline survey and CHARLS 2015, a higher number of new-onset T2DM cases were diagnosed in 2015 than in other years during the follow-up. To validate the reliability of T2DM diagnosis in this study, we carefully searched for studies on T2DM epidemiology in China and compared them with the present study. According to the 2010 and 2013 diabetes censuses in China, the prevalence of diabetes in individuals aged ≥ 60 years was approximately 20% [
42]. However, its prevalence in 2011 in the current study was 14.4%, suggesting that the prevalence of T2DM may have been underestimated during the baseline survey. However, the rate of prevalence per 1,000 person-years during the 7-year follow-up period was approximately 23.8, which is consistent with the rate of 24.5 per 1,000 person-years reported in previous studies among urban older adults in China [
43]. Although this study may have underestimated the prevalence of T2DM in older Chinese adults during baseline survey, the incidence of T2DM during follow-up was generally consistent with that of previous reports [
43]; therefore, it can be considered relatively reliable for exploring the possible relationship between possible sarcopenia and new-onset T2DM. Finally, some participants with missing data on T2DM and possible sarcopenia during baseline survey were excluded from this study, which may result in a bias. Future studies are warranted to answer these important questions. Despite these limitations, this study highlights the metabolic importance of possible sarcopenia.
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