As a global epidemic, the incidence of obesity has been steadily increasing in recent years. At present, more than 2.1 billion people in the world are overweight or obese (1). Scientific studies have confirmed that obesity is the starting point of various metabolic related diseases such as T2DM, Polycystic Ovary Syndrome (PCOS), and cardiovascular diseases (2, 3). Data shows that about 60% of type 2 diabetic patients were obese (BMI>30kg/m²) and combined with insulin resistance (4). Obesity could lead to T2DM through insulin resistance, which in turn could aggravate obesity and increase blood sugar (4, 5). Obesity and T2DM are cause-and-effect to each other, resulting in a vicious cycle that ultimately increases the incidence of diabetes complications and increases the social and economic burden. Therefore, the method of treating obesity and T2DM is urgent.

In recent years, domestic and foreign studies have found asprosin, a new discovered fasting-induced glucogenic adipokine, was significantly elevated in the patients with obesity and T2DM (including newly diagnosed and existing patients) (6–13). As clinical studies suggested that asprosin may be an early indicator of glucose, lipid impairment and insulin resistance. It can be used as a factor to predict the risk of T2DM and obesity (14). Furthermore, animal research indicated asprosin antibody can reduce blood sugar and appetite, suggesting that it can be used as a therapeutic target for T2DM and obesity. However, this adipokine has not been studied in people with T2DM and obesity at the same time. The purpose of this study was to explore the role of asprosin in patients with T2DM combined with obesity, and to provide new ideas for therapeutic targets for these patients.

In our cross-sectional study, comprehensive clinical data of patients diagnosed with T2DM were retrospectively collected from a community health care center (Zhuoma Community Care Station and Chengbei West Street Community Care Service Center in Changzhi City of Shanxi Province) in southeastern Shanxi Province from November 2019 to July 2021. Patients who met the WHO diagnostic criteria for T2DM in 1999 (15) and had available clinical and asprosin data were included, while those with type 1 diabetes mellitus, diabetic ketoacidosis and diabetic hypertonic coma, severe liver and kidney dysfunction, serious infection, malignant tumors, communication disorders such as mental diseases or inability to cooperate with researchers, or diabetes caused by other endocrine diseases were excluded. A total of 491 subjects with T2DM were categorized into three groups based on BMI (normal weight group: BMI 19-23.9 kg/m2; overweight group: BMI 24-27.9kg/m2; obesity group: BMI≥28 kg/m2) (16), 60.1% were men(295/491). The research protocol is applicable by the ethics committee of the First Hospital of Shanxi Medical University (No. 2019 [K056]). All study participants provided informed written consent. The study kept patient data confidential and complied with the Declaration of Helsinki. There is no conflict of interests among all authors.

With the escalating prevalence of obesity, the incidence of obesity-related disorders such as diabetes increased concurrently, resulting in serious outcomes. Thus, to investigate the pathogenesis of obesity would be a great help to prevent and treat the chronic disease. Studies confirmed that adipose tissue is served as an energy storage organ and regulate various aspects of human metabolism including glucose and lipid homeostasis, insulin sensitivity and inflammatory response by secreting a variety of adipokines (14). Imbalances between pro-inflammatory and anti-inflammatory adipokines can result in metabolic dysfunctions associated with obesity, such as type 2 diabetes mellitus (T2DM) and subsequent cardiovascular diseases (17). Consequently, understanding the mechanisms underlying adipokine activity and restoring their balance may provide therapeutic avenues for addressing obesity and its related complications.

Asprosin is a recently discovered adiponectin factor secreted by white adipose tissue. As a pro-inflammatory adipocytokine, asprosin could lead to the inflammation, dysfunction and apoptosis of islet βcell through TLR4/JNK-mediated signaling in animal studies (18). It could further promote β cell apoptosis by inhibiting the autophagy of β-cell via AMPK-mTOR pathway (19). Besides, clinical trials suggested that pathological elevated asprosin levels were observed in some metabolic diseases, such as obesity, T2DM, diabetes complications, and PCOS (14).

Pre-clinical and clinical research has indicated that asprosin may serve as an independent risk factor for patients with obesity and T2DM (10, 20–22). However, prior studies have primarily concentrated on isolated cases of T2DM or simple obesity, neglecting the examination of serum asprosin levels in patients who present with both conditions. In clinical practice, T2DM and obesity frequently coexist rather than manifest independently; they often exacerbate one another. Consequently, our objective is to investigate the relationship between asprosin levels and individuals suffering from both T2DM and obesity. This study aims to provide convenient and accurate predictors for this specific population while establishing a foundation for targeted therapeutic interventions.

This study confirmed that in type 2 diabetic patients, the circulating levels of asprosin were significantly higher in the obese group compared to both the normal weight and overweight groups (P < 0.05) ( Figure 1 ). Furthermore, a statistically significant difference was observed in serum asprosin levels between the overweight and obese groups, with asprosin concentrations increasing alongside body weight. Additionally, serum asprosin levels exhibited positive correlations with BMI and waist circumference (r=0.428, P<0.05; r=0.356, P<0.05), which aligns with previous research on adult obesity (6–9). In contrast, studies focusing on children with obesity have produced differing conclusions. Corica (23) and Long (24) reported lower blood asprosin concentrations in obese children when compared to normal controls, noting gender differences among participants. Wang et al. (7) found no significant variation in asprosin concentration across mild, moderate, and severe obesity categories. These discrepancies may be attributed to variations in age among the child subjects studied. Thus, it is hypothesized that asprosin may serve not only as a predictor of obesity but also for assessing its severity.

Furthermore, asprosin has been confirmed to be associated with lipid metabolism (25). This study demonstrated that, compared to the normal weight group, both TG levels increased in the overweight and obesity groups as body weight rose (P < 0.05) ( Table 1 ), while HDL-C levels decreased (P < 0.05) ( Table 1 ). Correspondingly, an increase in asprosin was also associated with a rise in TG levels (P < 0.05), which aligns with findings from most studies (17, 20, 25–28). The results indicated that asprosin is positively correlated with TG and negatively correlated with HDL-C; however, it showed no significant relationship with LDL-C. Nevertheless, some researchers have presented differing viewpoints. Li (13) posited that serum asprosin is positively correlated with LDL-C in females, while Ugur (6) suggested that both serum and salivary asprosin are positively correlated with LDL-C. These contrasting conclusions may be attributed to gender differences and the relatively limited number of subjects involved. Similarly, another study conducted on children reported no correlation between asprosin and TC, LDL-C, or HDL-C (24), potentially due to the age factor of the participants.

Other metabolic markers were also observed in this study. According to the tertiles of serum asprosin levels, patients in the high asprosin subgroup exhibited higher SUA levels compared to those in the overweight and obese groups (p<0.05). This finding has not been previously reported, suggesting that under obese conditions, asprosin may contribute to an increased incidence of hyperuricemia in patients with T2DM through an unknown mechanism. Furthermore, our results indicated a positive correlation between asprosin and SBP, while no significant relationship was found with DBP, which aligns with conclusions drawn from other research conducted by Xu et al. (29). Regarding hepatic enzymes, our study suggested that there was no significant correlation between asprosin and ALT or AST as body weight increased. In contrast, studies by Long (24) and Liu (30) confirmed a negative relationship between asprosin and AST. The discrepancy may be attributed to the fact that subjects recruited for their research were exclusively children.

In terms of blood glucose, numerous studies have confirmed that fasting blood levels of asprosin are significantly elevated in patients with T2DM, newly diagnosed T2DM, and those with abnormal glucose tolerance when compared to individuals with normal glucose tolerance (10–13, 21). These findings suggest that asprosin exhibits a notable response to fluctuations in glucose levels among type 2 diabetic patients and may play a crucial role in both the early stages and progression of T2DM through the mechanism of insulin resistance. A study conducted on an Iraqi population (31) reported elevated blood levels of asprosin in individuals with long-standing T2DM but not in those who were newly diagnosed; this discrepancy may be attributed to racial differences. Nevertheless, our research indicated no significant correlation between asprosin levels and FPG or HbA1c, which contrasts with previous studies (10, 13, 20, 21). This difference may arise from the fact that prior investigations primarily focused on individuals with uncomplicated T2DM without obesity. Furthermore, studies examining childhood obesity revealed that unlike adults, asprosin was not correlated with insulin resistance (26).

Asprosin has emerged as a focal point in the study of diabetes and obesity. Recent research indicates that several antidiabetic medications, including metformin, acarbose, liraglutide (a GLP-1 receptor agonist), and dapagliflozin, have been shown to lower blood glucose levels while concurrently reducing asprosin levels in patients with diabetes (32–35). Furthermore, the administration of asprosin antibodies has demonstrated efficacy in decreasing serum asprosin levels and lipid profiles, along with reductions in food intake and body weight in diet-induced obese mice. This intervention exhibits relatively reliable long-term efficacy and safety (36). Consequently, asprosin may represent a promising therapeutic target; thus, investigating the relationship between asprosin and obesity concerning T2DM is essential. However, it is noteworthy that all previous investigations were conducted exclusively on individuals with either uncomplicated T2DM or simple obesity; none included subjects affected by both T2DM and obesity simultaneously. Our research concluded that serum asprosin levels are positively correlated with BMI among individuals suffering from both T2DM and obesity. Therefore, serum asprosin could serve as a potential predictor for assessing the risk and severity of obesity within this population.

However, this research has certain limitations. It is a cross-sectional study with a small sample size, and the potential causal relationship between serum asprosin and obesity in patients with type 2 diabetes requires further validation through future prospective studies, as well as animal and cellular investigations.

Serum asprosin levels were found to be correlated with obesity in community-based patients with T2DM in Changzhi, Shanxi Province, China. Furthermore, the risk of obesity significantly increased with rising asprosin levels. Therefore, we propose that serum asprosin may serve as a potential risk predictor for obesity in individuals with T2DM.