In CiteSpace, the Authors Collaborative Network denotes the collaborative relationships among authors formed through citation connections in academic literature. CiteSpace constructs this network by examining instances where authors co-occur in the literature. When two or more authors are found in the same document, the system identifies a collaborative relationship and establishes the corresponding link in the collaborative network. This network facilitates researchers in discerning the authors who collaborate in a particular field.

Figure 3 illustrates an author collaboration network comprising 336 nodes and 264 links, clarifying collaborative relationships among prolific authors. Table 2 provides information on the top five authors based on publication volume. Most publications are attributed to Professor John P. Kirwan at Case Western Reserve University, with six relevant papers published in the past decade. Professor Kirwan’s team identified growth differentiation factor 15 (GDF15) as a signaling protein generated during skeletal muscle contraction. GDF15 enhances glucose-stimulated insulin secretion (GSIS) by activating the insulin secretion pathway in β-cell, playing a crucial role in regulating glucose metabolism during exercise (40). Professor Kirwan collaborates closely with the second-highest contributor, Professor Steven K. Malin, from the Department of Kinesiology and Health at Rutgers University. Professor Malin is dedicated to determining optimal exercise and diet prescriptions to reduce the risk of chronic diseases (22, 41, 42). His focus includes identifying how each “dose” of exercise impacts cardiovascular and metabolic insulin sensitivity in individuals at risk for diabetes (43).

The third-highest contributor in terms of publication volume is Professor Bente Klarlund Pedersen from the University of Copenhagen. Her research centers on the impact of exercise on physical health, particularly its effects on physiological processes such as metabolism, the immune system, and inflammation (44–46). Professor Pedersen has achieved noteworthy results in exercise and chronic diseases (47–49). Additionally, she advocates combining different types of exercise to enhance health and prevent chronic diseases. Her research indicates that both supervised high-intensity interval endurance training and resistance training effectively reduce cardiac fat in individuals with abdominal obesity, with resistance training specifically targeting pericardial adipose tissue (50). Furthermore, her studies demonstrate that high-intensity interval training (HIIT) can offer similar or superior benefits in physical fitness, body composition, and glycemic control compared to endurance training, making HIIT a time-efficient option for managing T2D (51).

The largest connected component showcases the collaboration network of Professor Toshinari Takamura’s team at Kanazawa University in Japan. The team rediscovered Selenoprotein P (SeP) as a hepatokine overproduced in T2D, leading to insulin and exercise resistance (52). As early as 2017, the team demonstrated that the anti-oxidative hepatokine SeP induces exercise resistance through its muscle receptor, low-density lipoprotein receptor-related protein 1 (LRP1) (53). Subsequently, the team delved further into the mechanisms of exercise resistance in individuals with T2D.

Utilizing the collaborative network established by the authors facilitates the identification of influential contributors in specific fields. It also allows for the exploration of potential research teams or collaborative partnerships. This functionality is essential for understanding the dynamics, trends, and patterns of research collaboration within the academic community. According to the results, John P. Kirwan, Steven K. Malin, Bente Klarlund Pedersen have made significant contributions to the field of exercise intervention for T2D. However, a stable core network of author collaborations has not yet been formed, the betweenness centrality among authors appears modest, suggesting restricted collaboration in this research domain and highlighting the necessity for future efforts to promote more robust and extensive collaborations.

Figure 4 depicts an institutional network graph comprising 348 nodes and 558 links, with the top ten prolific institutions marked in the graph. In addition, Table 3 presents the years of their initial related article publications spanning from 2013 to 2022, along with betweenness centrality. The top three institutions in terms of publication volume are the University of Copenhagen, Harvard Medical School, and the University of Colorado. Notably, the University of Copenhagen has the highest publication volume and demonstrates the strongest betweenness centrality among these institutions. Sustaining an annual research output, the University of Copenhagen exhibits a consistent upward trend in publication volume. As evidenced by the results, the University of Copenhagen has showcased remarkable research achievements in this field. Examining the previously discussed collaborative network, it is evident that Bente Klarlund Pedersen, affiliating with this institution, enjoys a strong reputation for her contributions to improving metabolic diseases through exercise.

The network graph for national collaboration comprises 80 nodes and 438 links. We analyzed 1,210 articles from 80 different countries. The findings revealed that the top three countries were USA (n = 382, 31.57%), China (n = 154, 12.73%), and England (n = 111, 9.17%), accounting for over 50% of the total publications, as outlined in Table 4 . Furthermore, Figure 5 illustrates collaborative relationships among countries, with node size representing the number of published documents. Interconnections between nodes signify collaborations between countries. Notably, the United States demonstrated significantly higher total link strength than other nations, indicating more substantial collaborations with other countries. The volume of publications in China ranks second only to that of the United States. However, when considering measures such as centrality in comparison with other countries, it appears relatively lower. This suggests that there is room for closer collaboration between China and international counterparts. Strengthening partnerships with institutions from other countries is essential for future endeavors.

Co-cited references denote citations found in two or more publications concurrently. The formation of a co-citation relationship occurs when a third publication references two other publications jointly (54). This interconnection positions co-cited references as a significant knowledge repository within a specific academic domain (55). The importance of a scholarly work in that field increases with the frequency of its citations (37).

The findings from the co-citation analysis applied to the cited literature are presented in this section. The co-cited references map reveals 77,107 references cited across 1,210 articles. The co-citation network of references, consisting of 580 nodes and 2,027 edges, illustrates the complex network of co-citation relationships among these references in the academic literature. This observation suggests that, within the subset of 1,210 articles, 580 references were co-cited, resulting in 2,027 instances of simultaneous co-citation. Figure 6 provides a visual representation of the co-citation network involving frequently cited references, while Table 5 presents a summary of the top 5 co-cited references.

The most extensively cited reference, authored by Bostrom et al. in 2012 and published in Nature, clarified the PGC-1α-dependent myokine irisin. It was revealed that the increased exercise-induced irisin contributes to elevated energy expenditure. Moreover, it is suggested that irisin could have therapeutic potential for human metabolic diseases and other disorders that benefit from exercise (56). Following this, the second most frequently co-cited reference, presented by Zinman et al. in 2015 and published in the New England Journal of Medicine, emphasizes the importance of a comprehensive approach to managing diabetes, encompassing pharmacotherapy and lifestyle modifications such as increased physical activity (57). Colberg’s study in 2016, published in Diabetes Care and ranking third in co-citation count, offers a clinically oriented review along with evidence-based recommendations concerning physical activity and exercise in people with T2D, highlights the significant benefits of physical activity and exercise in reducing blood glucose levels, improving insulin sensitivity, promoting weight reduction, and reveals the importance of personalized exercise programs (12). Occupying the fourth position in co-citation count is Petersen’s study from 2018, published in Physiological Reviews, which underscores the critical role of physical activity and exercise in the management and prevention of diabetes. The research explores the role of insulin and its resistance mechanisms, advocating for comprehensive health management approaches in T2D exercise interventions (58). Lastly, Wiviott’s study from 2017, published in the New England Journal of Medicine and ranking fifth in citation count, provides information on the cardiovascular safety profile of dapagliflozin in individuals with T2D (59).

Keywords in CiteSpace play a critical role in defining key terms and facilitating scientific literature’s systematic analysis and visualization of citation networks. These keywords are instrumental in discerning primary themes and pivotal points, enabling researchers to gain detailed insights into developmental trends, research hotspots, and critical contributors within a specific field. The selection of precise and comprehensive keywords ensures the accurate indexing of research articles, as evidenced by previous research (60). Clear and concise presentation of keywords reflects the fundamental themes and perspectives of a scholarly article. As elucidated in earlier studies, it establishes a vital link between diverse research domains (32, 38).

In this study, we conducted a time-slicing analysis of annually published papers. Figure 7A illustrates the top 10 keywords with high frequency, covering topics such as “type 2 diabetes,” “insulin resistance,” “physical activity,” “skeletal muscle,” “exercise,” “mechanism,” “oxidative stress,” “obesity,” “cardiovascular disease,” and “metabolic syndrome.” Furthermore, we showcased keywords with a centrality exceeding 0.1, as depicted in Figure 7B . These keywords, including “disease (0.21),” “glucagon like peptide 1 (0.18),” “cardiovascular risk factor (0.17),” “all cause mortality (0.16),” “heart failure (0.14),” “mortality (0.14),” “Alzheimer’s disease (0.13),” “exercise capacity (0.13),” “hyperglycemia (0.13),” “impact (0.13),” “C-reactive protein (0.12),” “blood pressure (0.12),” “endothelial dysfunction (0.11),” “free fatty acid (0.11),” “cancer (0.11),” “glycemic control (0.1),” “molecular mechanism (0.1),” “diet-induced obesity (0.1),” “induced insulin resistance (0.1),” and “gene (0.1)” illuminate the current research focal points and trends within the field.

T2D is characterized by a progressive decline in pancreatic β-cell function and insulin resistance (73, 74), where pancreatic β-cell plays a central role in the pathogenesis of this complex multi-organ disease. Current approaches to diabetes treatment focus on strategies aimed at enhancing β-cell signal transduction and function. Exercise has emerged as an effective intervention to improve pancreatic β-cell function (73, 75), particularly in the early stages of the disease, leading to increased insulin secretion and reduced blood glucose levels. However, the complete exploration of the impact of physical exercise on β-cell remains an ongoing focus in current research.

Various forms of exercise have been demonstrated to effectively enhance the functionality of pancreatic β-cell. A study in diabetic fatty rats indicates that a 13-week swimming training regimen effectively enhances β-cell insulin signal transduction and secretion. This improvement is associated with increased cell surface levels of GLUT2, intracellular glucose kinase, and insulin vesicles within β-cell (76). Additionally, another research showcases that a ten-week regimen of resistance exercise training in healthy mice enhances glucose-stimulated insulin secretion and improves β-cell function (77). After an 8-week period of low-volume HIIT in individuals with T2D, there was a notable improvement in overall blood glucose control and pancreatic β-cell function (78).

Numerous studies have examined two distinct exercise modalities: moderate- and vigorous-intensity exercise. Multiple research findings indicate moderate and vigorous exercise improves β-cell function, although through distinct mechanisms (79, 80). The specific mechanisms responsible for the positive impact of exercise on β-cell in T2D patients remain unclear. Future investigations should explore critical regulatory factors influencing exercise-induced enhancements in both β-cell mass and function.

Current research indicates that bioactive molecules activated by physical activity, referred to as exerkines, may play a crucial role in regulating metabolic balance, thereby reducing the risk of metabolic disorders. Exerkines are identified as signaling molecules released in response to acute or chronic exercise, exerting their effects through endocrine, paracrine, and autocrine pathways (27), with potential implications in improving cardiovascular and metabolic functions. Exerkine research primarily focuses on myokines (49), hepatokines, and adipokines (81).

Interleukin-6 (IL-6) stands as one of the earliest-discovered exerkines. In 2000, Pedersen et al. proposed that actively contracting skeletal muscles are a source of IL-6, exerting its effects in a hormone-like manner (82). Following this, IL-6 has been identified as a myokine (83, 84), demonstrating the capability to augment basal glucose uptake and facilitate the translocation of the glucose transporter GLUT4 (85). Additionally, IL-6 can induce the production of anti-inflammatory cytokines, such as interleukin-1 receptor agonist (IL-1ra) and interleukin-10 (IL-10) (86), while inhibiting the production of tumor necrosis factor-α (TNF-α) (87), thereby manifesting anti-inflammatory effects.

Various exerkines have been extensively studied, including irisin, myostatin, SeP, fetuin-A, fibroblast growth factor 21 (FGF21), interleukin-15 (IL-15), follistatin (FST), β-aminoisobutyric acid (BAIBA), angiopoietin-like 4 (ANGPTL4), chitinase 3-like protein 1 (CHI3L1), cysteine-rich angiogenic inducer 61 (CYR61), and connective tissue growth factor (CTGF) (88–93).

Consequently, these bioactive molecules may represent viable therapeutic avenues for conditions such as cardiovascular diseases, T2D, and obesity.

The concept of the “developmental origins of health and disease” (DOHaD) is based on epidemiologic observations, linking the health status and disease risk in late childhood and adulthood to early-life environmental conditions. This concept involves research on organ development and epigenetic mechanisms, suggesting that chronic non-communicable diseases result from the combined influence of genetic, environmental, and behavioral factors (94).

MicroRNAs (miRNAs), short regulatory RNAs involved in post-transcriptional gene regulation (95), play a fundamental role in the post-transcriptional regulation of gene expression, and participate in various physiopathological processes (96). The secretion of miRNAs into the blood can reveal subtle alterations in key metabolic organs. Changes in the miRNAs profile in the blood are associated with the occurrence of T2D (97). Research has found that in both healthy individuals and those with diabetes, different types of exercise training can regulate the expression of miRNAs (98, 99). Notably, some miRNAs exhibit opposite expression trends in T2D and post-exercise, such as miR-15a, miR-96, miR-192, and miR-532 (100). This suggests that exercise can improve T2D by modulating the expression of miRNAs.

A specific miRNA of interest is miR-126. Its primary involvement extends to angiogenesis, anti-inflammatory responses, and apoptosis, contributing to cardiovascular protection. Multiple clinical studies demonstrate a downregulation of circulating miR-126 levels in patients with T2D (101). Diverse forms of exercise have been identified as regulators of miRNA expression (100). Aerobic exercise has been shown to induce an elevation in circulating levels of miR-126 in mice and rats with metabolic disorders.

Hence, miRNAs can function as an early biomarker to assess the susceptibility to metabolic diseases in later life, assisting in identifying populations prone to obesity and metabolic disorders. This discovery presents new prospects for personalized, precision healthcare and exercise interventions.

Exercise interventions play a crucial role in T2D management by enhancing insulin sensitivity, optimizing blood glucose control, and mitigating the risk of complications. Previous investigations suggest that aerobic exercise, resistance exercise, and HIIT benefit individuals with T2D.

Aerobic exercises, such as brisk walking, jogging, swimming, and cycling, are deemed preferable for patients with T2D due to their substantial enhancement of cardiovascular fitness and insulin sensitivity (102–104). Resistance training, encompassing weightlifting and resistance bands, improves muscle strength, muscle mass, and insulin sensitivity. Combining aerobic exercise with resistance training has become the most common and effective intervention for T2D. Researchers are increasingly focusing on HIIT compared to these two intervention approaches. HIIT, characterized by short bursts of high-intensity exercise followed by moderate or low-intensity recovery, has demonstrated effectiveness in enhancing insulin sensitivity, glycemic control, pancreatic β-cell function, and reducing abdominal fat mass (78).

However, the precise influence of distinct exercise modalities on the pathophysiological mechanisms of T2D still needs to be clarified. Moreover, prevailing studies predominantly emphasize the short-term ramifications of exercise interventions, primarily focusing on parameters such as blood glucose regulation and insulin sensitivity. More attention should be directed towards comprehending the prolonged consequences of exercise interventions, particularly concerning the complications associated with T2D.

In summation, exercise interventions emerge as a vital component in managing T2D. Future research endeavors should formulate and implement personalized exercise intervention programs to achieve more productive disease management and prevention. Furthermore, the temporal aspects of exercise may play a pivotal role in the treatment strategy for T2D.

The keyword analysis found particular significance in the term “circadian clock.” Several critical physiological processes in the human body, including blood pressure regulation, temperature maintenance, and immune function, follow a day-night rhythm pattern (105). The biological clock plays a pivotal role in influencing essential processes such as the cell cycle, redox homeostasis, inflammation, and metabolism (106). The circadian clock comprises the central and peripheral clocks, with the skeletal muscle clock falling under the peripheral category. Notably, the skeletal muscle clock demonstrates heightened sensitivity to physical activity, resulting in varied transcriptional and metabolic outputs at different times of the day (107). A normal circadian rhythm is crucial for stabilizing internal glucose metabolism (108). Disruptions in circadian rhythm are closely linked to the onset of T2D (108, 109). Factors such as sleep, light exposure, and diet, which are regulated by the circadian rhythm, can significantly impact the development of T2D (108). This raises the question of whether exercising at different times of the day might have varying effects on improving T2D. This finding prompts consideration of whether exercise timing could be considered a viable therapeutic strategy for T2D (110). Nevertheless, there are relatively few studies on this topic, and the intervention durations are often short. A 12-week randomized controlled trial found that exercising three times per week in the morning compared to the evening did not lead to significant differences in glycemic control or alterations in circadian rhythm (111). Look AHEAD trial shows that afternoon bout-related moderate-to-vigorous physical activity (bMVPA) is associated with improved blood glucose control in adults with T2D, particularly within the initial 12 months of intervention (112). Future research should include more intervention studies focusing on exercise timing to gain a deeper understanding of its impact on the circadian rhythm in T2D. This would be crucial for developing precise exercise prescriptions.