Gallstone disease (GS) is a common gastrointestinal disease worldwide. Epidemiological surveys have revealed that the prevalence of GS among adults in the United States (US) and Europe is approximately 5–25% (1, 2), whereas among Asians, it is relatively low (3). The annual healthcare cost associated with GS in the US is approximately $6 billion (4), placing a significant burden on public health. Most patients with GS are asymptomatic and are diagnosed through physical examination. A small number of patients may experience abdominal pain, loss of appetite, nausea, and vomiting. In a very small number of patients, GS involving the common bile duct can lead to cholangitis and pancreatitis, which can be life-threatening in severe cases (5, 6). Previous studies have reported the potential mechanisms and risk factors for developing GS; however, validated indicators for predicting or evaluating the risk of developing GS are lacking.

The arm circumference (AC) is a simple, direct, cost-effective, and noninvasive indicator of nutritional status and risk of developing diseases. AC reflects an individual’s muscle mass and fat reserves, particularly the muscle-to-fat ratio in the upper arm area. In developing countries, AC has been utilized to evaluate the nutritional status of children and adolescents, with a small AC value indicating that a child or adolescent may be malnourished or have stunted growth (7–10). Moreover, a low AC value is linked to a higher risk of mortality in patients with cirrhosis and cardiac failure, those undergoing hemodialysis, and the elderly (11–15). Recent studies have shown that AC can be used as a novel bioindicator to assess obesity, insulin resistance (IR), metabolic syndrome (MetS), and non-alcoholic fatty liver disease (NAFLD) in adults (16–19).

Although waist circumference (WC) is an established indicator of central obesity and metabolic health, AC provides complementary information about body composition, particularly in terms of the muscle-to-fat ratio and upper extremity nutritional status. Unlike WC, which primarily reflects abdominal fat distribution, AC captures a broader physiological profile, including peripheral muscle and fat reserves. This distinction is important when exploring conditions like GS, where factors beyond central obesity may contribute to disease risk. Furthermore, there are specific clinical scenarios where accurate WC measurement may not be feasible, such as in individuals with abdominal deformities, surgical scars, or extreme obesity. In such cases, AC offers a practical and reliable alternative for assessing body composition.

However, the relationship between AC and GS remains unclear. Given that GS is, to some extent, a metabolic disorder, we hypothesized a link between AC and GS. This study aimed to evaluate the relationship between AC and the prevalence of GS in US adults, utilizing data from the National Health and Nutrition Examination Survey (NHANES) to provide evidence of AC’s potential role in adult health assessments. By focusing on AC as a less explored but complementary bioindicator, we sought to uncover novel insights into the relationship between body composition and GS, thereby contributing to a more comprehensive understanding of metabolic health.

This study is the first to comprehensively examine the relationship between AC and GS prevalence. We found a linear positive correlation between AC and GS prevalence, with an 8% increase in the prevalence of GS for every 1 cm increase in AC. After categorizing AC into tertiles, we observed a 2.43-fold increase in GS prevalence among individuals in the highest AC tertile than in those in the lowest AC tertile. The results of the subgroup analyses further indicated that AC showed a positive association with GS prevalence across nearly all populations, with only slight variations. Our results confirm the importance of AC as a predictor of the risk of developing GS.

While our findings are novel, it is essential to position AC within the broader context of established indicators of obesity, such as BMI and WC, which are well-recognized predictors of MetS and GS. BMI is the most commonly used measure of overall adiposity, while WC serves as a strong indicator of visceral fat accumulation, which is closely linked to metabolic abnormalities. In contrast, AC is a simple, practical, and noninvasive measure that simultaneously reflects body composition (including muscle and fat mass) and nutritional status. Importantly, our study demonstrated that the association between AC and GS prevalence remained significant even after adjusting for BMI, WC, and other metabolic confounders. This finding suggests that AC provides complementary information beyond BMI and WC, particularly in populations where assessing WC or BMI is not feasible or practical.

GS is prevalent globally, especially in developed countries, with 1.5 million people seeking medical care for GS in the US in 2015 alone (21). The pathogenesis of GS is complex and involves several factors. Earlier studies have indicated a higher prevalence of GS in females compared to males (22, 23), which may be because of estrogen-induced increase in the synthesis and secretion of hepatic cholesterol by increasing the expression of estrogen receptor 1 and G protein-coupled receptor 30 as well as decreased bile salt synthesis, and ultimately promoting GS development (24). Moreover, estrogen weakens the contractility of the gallbladder and prolongs the retention time of bile, thereby increasing the deposition of cholesterol crystals (24). Similarly, we found a higher prevalence of GS in females than in males. Advanced age is considered an important factor in the increased prevalence of GS (25, 26). Similarly, our study found that the mean age of individuals without GS was 50 years (ranging from 35 to 63), while for those with GS, it was 60 years (ranging from 46 to 71). With increasing age, the composition of bile changes, and the amount of cholesterol in bile may increase, whereas the amount of bile acid salts may decrease, leading to an increased risk of cholesterol crystal formation and, consequently, an increased incidence of GS (27).

Moreover, the motor function of the gallbladder may weaken, leading to a longer bile retention time, which increases the risk of developing GS (28, 29). However, recent studies have highlighted that metabolic factors, such as obesity and diabetes, significantly influence the prevalence of GS, particularly among younger populations (30, 31). Genetic factors are also important risk factors for GS, with its prevalence varying according to race. In developed countries, the prevalence of GS is significantly higher in white populations than in black populations (28). For example, an epidemiological survey found that, in the US, the prevalence of GS was 16.6% among white women compared with 13.9% among black women and 8.6% among white men, compared with 5.3% among black men (32). This may be related to the differences in dietary habits, lifestyles, and healthcare among the different races. For example, white populations have greater access to high-calorie food, which may have contributed to a higher prevalence of GS. Similarly, our study found that the prevalence of GS is highest among non-Hispanic white people compared with other populations.

Recently, a growing body of research has identified a strong correlation between the rising incidence of GS and the high prevalence of MetS (26, 33, 34). Among them, IR is a key mechanism underlying the increased incidence of GS. In hepatocytes, IR promotes cholesterol secretion by causing abnormal expression of the transcription factor forkhead box protein O1 through the action of ABCG5 and ABCG8 (35), which may explain the higher prevalence of GS among individuals with diabetes. The prevalence of GS was also higher among individuals with obesity than among those without obesity (26). The main reason for this is obesity-induced metabolic changes, such as increased bile secretion from the liver, hyperlipidemia, reduced intestinal motility, and dysfunctions in various metabolic organs, including the liver and gallbladder (36). Further, our study revealed that the mean BMI of participants in the GS group was higher than that of those in the non-GS group [31.8 (27.7–37.7) vs. 28.5 (24.6–33.3), p < 0.001]. Notably, the prevalence of GS is increasing among the younger population due to the increased intake of high-calorie foods as society develops, and economic standards increase, as well as increased physical inactivity (37).

AC is a simple and noninvasive measure of great value for evaluating the nutritional status of the body and the risk of disease development. The connection between AC, MetS, and related diseases has been thoroughly investigated (23, 26, 33, 38–40). In a cross-sectional study including 2,397 patients, Wang et al. discovered a positive association between AC and both hepatic steatosis and fibrosis and that this positive association was consistent across sex and race (Mexican Americans, other Hispanics, non-Hispanic white people, Black population, Asians, and other races) (41). Xiao et al. investigated the relationship between AC and both all-cause and cardiovascular-related mortality in patients with diabetes (20). They identified a significant negative correlation between AC and both all-cause and cardiovascular-related mortality in this population (20). In a study by Chao et al. that included 11,527 participants, AC showed a significant positive association with HOMA-IR, an indicator of IR (42).

As mentioned previously, the pathogenesis of GS is closely related to metabolic abnormalities. However, the relationship between the AC and GS has not yet been effectively explored. In this study, we examined the association between AC and GS prevalence. We discovered that AC showed a linear positive correlation with the prevalence of GS and that this relationship was maintained across different subgroups, although there were subtle differences. Our findings offer new insights into the potential utility of AC in evaluating adult health.

Our study has several strengths. First, this study is the first to clarify the relationship between AC and GS prevalence. Second, NHANES provided a representative sample of US participants who followed a meticulously designed study protocol and underwent stringent quality control and assurance, thereby ensuring the reliability of our conclusions. Third, the comprehensive demographic and metabolic data, along with detailed follow-up information, enabled us to account for potential confounders. Finally, we also performed subgroup analyses to ensure the generalizability of our results to a wider population.

Nevertheless, our study has certain limitations. First, as this was a cross-sectional study, we were unable to establish a causal relationship between AC and GS. While causal inference methods, such as propensity score matching or instrumental variable analysis, could strengthen causal interpretations, the nature of our study and data limitations restricted their application. Nonetheless, sensitivity analyses demonstrated consistent results, underscoring the robustness of our findings. Future longitudinal or Mendelian randomization studies are warranted to explore causal relationships further. Second, GS was diagnosed based on a questionnaire survey, which might have been influenced by recall bias. Third, owing to the design of the NHANES, we could only measure AC at a single time point at baseline; however, AC may change over time. Finally, although we adjusted for many possible confounders, we could not eliminate the potential impact of unmeasured confounders.

Despite these limitations, our study provides new insights into the relationship between AC and GS prevalence. Compared with BMI and WC, AC represents a practical and complementary indicator that may help assess GS risk, particularly in resource-limited or large-scale screening settings. In the future, we plan to conduct prospective cohort studies to evaluate the longitudinal relationship between AC and GS incidence, as well as comparative analyses to explore the relative predictive value of AC, WC, and BMI in identifying individuals at high risk of GS. These efforts will further clarify the utility of AC in metabolic and gallstone disease management.

Our study is the first to uncover the link between AC and GS prevalence. Specifically, there was a linear positive correlation between AC and GS prevalence, with GS prevalence increasing by 8% for each 1 cm rise in AC. While we could not establish a causal relationship between AC and GS prevalence, the result remains noteworthy.