On July 19, 2024, a thorough search was conducted on the Web of Science Core Collection (WoSCC) using the following search terms: TS=(“mitochondria”OR “mitochondrial contraction”OR”mitochondrial property”)AND TS=(“Type 2 Diabetes Mellitus*” OR”Type 2 Diabetes*”). The search was limited to articles and reviews written in English, excluding conference abstracts, preemptive experience articles, editorial materials, letters, collections, thesis collections, news projects, book chapters, hardware reviews, and withdrawn publications. The retrieval period spans from January 1st, 2003 to December 31st, 2023, encompassing a total of 2732 articles. This selection comprises 2029 articles and 703 reviews. A comprehensive extraction was conducted for each publication, including the title, year of publication, country or region, institution, author, journal, references, and key words. For further insights into the literature extraction process, refer to Figure 1 .

For bibliometric and knowledge mapping analysis, we utilized CiteSpace 6.3r1, vosviewer 1.6.18, bibliometrix in RStudio (v.4.4.1), and Microsoft Excel 2021.

CiteSpace is a software designed by Professor Chao Mei Chen from Drexel University in Philadelphia, Pennsylvania, USA, specifically to provide a visual representation of knowledge domains (22, 23). Please adjust the time parameter to span from 2003 to 2023, and configure the parameter threshold as 1. Additionally, Top N (N=25),LRF=2.5,LBY=5,e=1.0. In this paper, we examine the operations of countries, institutions, jointly cited references, reference bursts, keywords, and keyword bursts.

The dataset underwent basic statistical analysis utilizing RStudio (v.4.4.1). The data were organized in the bibliometrix format, while the biblioshiny package facilitated the extraction of various features pertaining to research literature spanning from 2003 to 20223 (24). It comprises the primary information, the foremost pertinent authors, their production over time, and the globally most-cited literature for quantitative analysis.

Vosviewer, which was developed by Eck and Waltman from the Leiden scientific and technological research center in the Netherlands, is a software designed for mapping scientific knowledge. This software has the capability to construct and visualize the relationships between network data, revealing the structure, evolution, and cooperation within the knowledge field. Its standout features include a graphical display and powerful large-scale data analysis abilities. In this article, we explore the implementation of various elements such as the author, co-cited author, journal, and co-cited journal.

This article utilizes Microsoft Excel 2021 to examine yearly publication patterns while simultaneously searching for the impact index of magazines and periodicals in 2023 on Web of Science.

The objective of this study is to examine 2732 pieces of literature spanning from January 1, 2003, to December 31, 2023, and utilize the collected data to establish the evolving trend of the correlation between mitochondria and T2DM. As illustrated in Figure 2A , the number of research articles on this topic steadily rose from 2003 to 2011. Subsequently, from 2011 to 2023, there was a significant surge in publications, reflecting a growing fascination with relevant research on this subject during this timeframe. It is noteworthy that the peak production of 252 articles occurred in 2021. To gain a deeper understanding of the publication trend, a linear trend line for annual publications was created. The resulting equation is y=10.121x-20243, where y denotes annual publications and x represents the year. The model’s coefficient of determination (R²) is 0.9304. Figure 2B presents an overview of the analyzed articles, which comprise a total of 128,401 references. The average publication year stands at 8.15. Furthermore, each article has garnered an average of 57.27 citations, and the annual publishing growth rate has been recorded at 8%.

A total of 493 countries were involved in this study. Figure 3 illustrates the co-occurrence of countries, with nodes denoting individual countries and the size of each node reflecting the national circulation. Notably, the United States is represented by the largest circle, highlighting its significant influence in the region. The purple segment of the circle symbolizes the center, and the prominent position of the United States suggests frequent collaboration with other nations. Referring to Table 1 , the top 11 countries with the highest citation frequencies are listed. The United States leads with 988 citations, followed by China with 464 citations, and Italy with 157 citations. In terms of centrality, the United States tops the list with a centrality score of 0.33, Italy ranks second with 0.3, and Germany comes in third with 0.13.

A total of 2897 institutions contributed to the research on this subject. The network pruning analysis ( Figure 4 ) revealed 475 nodes and 1843 connections in total. Table 2 presents the top 10 institutions based on their literature output. Notably, the University of California system tops the list with 91 publications, followed by the Institut National de la Santé et de la Recherche Médicale with 81 publications, and the US Department of Veterans Affairs with 67 publications. It is evident from the table that six out of the top 10 institutions hail from the United States, highlighting the country’s profound exploration of this topic and its strong scientific research footing. Furthermore, it’s worth mentioning that the Institut National de la Santé et de la Recherche Médicale demonstrated a higher h-index, signifying its significant impact in publishing scholarly articles.

A total of 15,379 authors contributed to the study of this topic, with 29 authors publishing 10 or more articles. Table 3 highlights the top 10 most prolific authors. Notably, Rocha Milagros,Victor Victor M led the pack, each with 24 articles. Roden Michael (n=18) and Schrauwen Patrick (n=17) closely followed. Figure 5A illustrates the co-occurrence of authors, displaying 25 clusters. Within one particular cluster, cooperation is notably more pronounced, However, among the authors actively engaged in this topic, only Rocha Milagros and Banuls Celiaform a distinct cluster. Simultaneously, Roden Michael,Schrauwen Patrick form a closely knit cluster while the remaining authors exhibit less cooperation.

Out of the 78,634 co-cited authors, 48 were co-cited over 100 times, as illustrated in Figure 5B . This figure displays them in a density map format, effectively highlighting the high-frequency co-cited authors. The brightness of the color corresponds to the number of citations; the brighter the color, the more citations. Based on Table 3 , Figure 5B , Petersen KF, Kelley De, Patti ME share the most frequent citations.

A total of 757 journals have published literature pertaining to this topic. Table 4 , Figure 6A present the top 10 journals with the highest number of published papers. Collectively, these top 10 journals published 540 papers, which constitute 31.17% of the overall published literature. The majority of the papers were published in the DIABETES (n = 80). AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM,DIABETOLOGIA tied for second place with 72 publications each. Notably, DIABETOLOGIA boasts the highest impact factor of 8.4, while the JOURNAL OF BIOLOGICAL CHEMISTRY leads with the highest h-index of 477.

A total of 8232 journals were cited in research on this topic. Out of these, 31 journals had over 1000 citations each (refer to Figure 6B ). According to Table 5 , Diabetes tops the list with the highest number of citations (n=10566), closely followed by JOURNAL OF BIOLOGICAL CHEMISTRY (n=8882) and PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA(n=4838). Within the top 10 co-cited journals, NATURE boasts the highest impact factor at 50.5, preceded by CELL at 45.5 and Cell Metabolism at 27.7. Notably, eight out of the top 10 frequently cited journals are positioned in Q1 of JCR, while the remaining two are in Q2.

We utilized CiteSpace to assess the influence of highly-cited literature in this research domain. We segmented the data spanning from 2003 to 2023 and extracted the co-cited reference network, which comprises 1312 references and 4447 connections. Figure 7A ’s left side displays the co-occurrence diagram of co-cited references, where each node signifies a document. The circle’s size indicates the frequency of the journal’s citations, while a purple halo denotes journals with stronger centrality (>0.1). The linkage between nodes signifies collaboration between two journals within a thematic cluster for this research. Table 6 presents the top 10 co-cited references. Based on the citation count, the most highly ranked reference is “Important mitochondrial activity in the insulin resistant offspring of patients with type 2 diabetes” (25), garnering 64 citations. The second most cited reference is “Mitochondrial dysfunction and type 2 diabetes” (26), with 55 citations, followed by “Deficiency of subsarcolemmal mitochondria in obesity and type 2 diabetes” (27) with 54 citations, rounding out the top three. To obtain the reference clustering analysis diagram ( Figure 7B ), please follow these steps: first, adjust the scale factor by increasing or decreasing it to k=12. Next, select “Pathfinder” to prune the merged network. After that, click on “find cluster,” then select “K,” and finally “LLR.” Through this analysis, 22 clusters are identified, and the modular value (Q value) is determined to be 0.807. This Q value suggests that each cluster possesses distinct and clearly defined characteristics. The average contour value of 0.9214 suggests that the literature exhibits a remarkable homogeneity, which underscores the scholars’ profound exploration and focused concentration in the research domain of this subject matter. The cluster number is marked in the form of increasing from 0. The smaller the number is, the more literatures are included in the corresponding cluster. Among them, “#0 empagliffozin”is the most important cluster, indicating that a large number of studies on “empagliffozin”cite the literatures in the cluster.

CiteSpace has identified the top 25 references experiencing the most significant citation bursts, as illustrated in Figure 7C . Notably, the majority of citation outbreaks took place in 2007(4/25,16%), closely followed by 2003(3/25,12%),2005(3/25,12%)and 2008(3/25,12%). Furthermore, it’s remarkable that the citation explosion persisted until 2023 for 4 references(16%).Among these, the article authored by Mootha, VK (28) exhibited the strongest citation burst, with an intensity of 24.66, spanning from 2004 to 2008.

We employed CiteSpace to create a visual representation of the frequently occurring keywords in the literature pertaining to our study topic. The resulting visualization, depicted in Figure 8A , illustrates that the size of the circle corresponds to the frequency of the associated keyword in the literature; a larger circle indicates a higher frequency. Specifically, 209 keywords occurred more than 10 times, while 29 keywords surfaced over 100 times. Table 7 presents the top ten most popular keywords ranked by their frequency of occurrence. Notably, “oxidative stress”, “insulin resistance”, and “type 2 diabetes”emerge as the highest-ranked keywords. Although high-frequency keywords may be prevalent, not all of them exhibit high centrality. Consequently, solely relying on such keywords may not precisely pinpoint research hotspots. Within the CiteSpace software, keywords boasting a centrality of 0.01 or greater stand out as inflection points on the keyword frequency knowledge map, thereby serving as indicators of research hotspots in the respective field. From the centrality perspective, “energy metabolism”holds a centrality of 0.06, while “apoptosis”and “insulin sensitivity”both possess a centrality of 0.05. These factors serve as the backbone of our research and occupy a supporting position within the network. Figure 8B offers a chronological description of keyword clustering analysis, presenting a timeline perspective. The various clusters are represented by brightly colored horizontal lines on the right, and each cluster corresponds to a specific set of keywords. The nodes positioned along these horizontal lines symbolize the keywords themselves. Notably, the spatial distribution of these nodes along the horizontal axis signifies the year in which the respective keywords first emerged in academic literature, ultimately forming a comprehensive temporal portrayal of the evolution of keyword clusters. “0#skeletal muscle”is the largest, followed by “#1diabetes mellitus”, “#2insulin secretion”, “#3prevalence”, “#4alzheimers disease” and”#5 diabetic cardiomyopathy”.

The term “keyword burst”denotes the abrupt surge of specific keywords within associated domains during a particular timeframe. Figure 8C illustrates the top 25 keywords experiencing the most significant citation explosions. Among them, “human skeletal muscle”exhibits the highest outbreak intensity, closely followed by “uncoupling protein 2” and “physical activity”. It is noteworthy that “mitochondrial dynamics”, “homeostasis”, “injury”, “tissue”, “mouse model”, and “hydroperoxide”were all in a state of explosion until 2023, with “uncoupling protein 2” emerging as the most prominent factor.

In this study, a scientometric analysis was conducted on the scientific literature pertaining to mitochondria and T2DM in the Web of Science (WOS) database, spanning from 2003 to 2023. The analysis was carried out using CiteSpace, VOSviewer, and Bibliometrix, with the aim of exploring the relationship between mitochondria and T2DM in the scientific literature.

From 2003 to 2023, a total of 2732 articles were included. The publication trends of these articles over time reflect the evolving interest in this research field. Initially, from 2003 to 2011, the number of papers grew gradually, but there was a significant surge in publications from 2011 to 2023, indicating a marked increase in attention and interest in this topic.The distribution of papers across different countries reveals each nation’s scientific impact in this field. Notably, the United States, China, and Italy are leading contributors, collectively accounting for 58.89% of all published papers. The United States stands out with the highest centrality in this research area, demonstrating extensive collaboration with other countries. This suggests that the US has conducted substantial and influential research in this domain.Given this, research teams from Asian countries might consider enhancing their international collaboration, particularly with European and American counterparts, to broaden their impact. It’s worth noting that among the top 10 institutions contributing to this field, 60% are American, and all belong to developed countries. This underscores the depth and thoroughness of research in these nations compared to developing countries, which have a later start and need to enhance their research outputs. While most institutions prefer domestic collaborations, international cooperation remains relatively limited.

Following a thorough examination of the author network, I have identified Rocha Milagros, Victor Victor m, Roden Michael, Schrauwen Patrick, and Moreira Paula as ranking within the top five based on the total number of publications. Therefore, researchers and teams engaged in pertinent studies should prioritize collaborating and communicating with these individuals for future research endeavors. It is noteworthy that Rocha milagros and Victor Victor m published a review in 2017 (29) that delved into the molecular pathways of mitochondrial dynamics, their damage caused by T2DM, and the pathophysiological importance of compromised mitochondrial dynamics in T2DM. This review has been cited 221 times. Petersen KF, Kelley De, Patti ME, Efronzo RA, and Mootha VK are ranked within the top 5 based on the number of co-authors. This suggests that these individuals have established themselves as cornerstone figures in this research field and have made substantial contributions to the advancement of the topic.

The analysis of journals and co-cited journals revealed that Diabetes had published the highest number of studies on mitochondria and T2DM, and had garnered the most co-citations. The AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, PLoS One, and JOURNAL OF BIOLOGICAL CHEMISTRY are ranked among the top 10 published journals, as well as being the top 10 co-cited journals. This underscores their significant role in the research of this subject matter. If journals like CELL, CELL Metabolism, and Nature are ranked among the top 10, the papers they publish can offer a solid theoretical foundation for future research.

The Co-citations references can demonstrate the research foundation pertaining to this subject and offer substantial reference value for future investigations on this topic. In our study, we employed CiteSpace to examine the Co-citations references, and the top 10 most frequently cited works are listed below.

In 2003, the New England Journal of Medicine published the highly cited research (25), co-authored by KITT Falk Petersen and five other esteemed scholars. This study compared the age, height, weight, and physical activity of the offspring of healthy, young, thin individuals with those of offspring from patients with insulin-resistant T2DM and IR control subjects. Through an assessment of liver and muscle insulin sensitivity, intramuscular lipid and triglyceride content in muscle cells, whole-body and subcutaneous lipolysis incidence, as well as mitochondrial oxidative phosphorylation activity in muscle, it was determined that a genetic defect in mitochondrial oxidative phosphorylation among T2DM patients results in dysregulation of skeletal muscle IR and intramuscular fatty acid metabolism in the offspring with IR. Additionally, this study underscores mitochondrial oxidative phosphorylation as a promising target for the prevention and treatment of T2DM.

The second most frequently co-citations references study is the one published by Bradford B Lowell in Science in 2005, titled “mitochondrial dysfunction and type 2 diabetes” (26). The maintenance of normal blood glucose levels relies on a complex interplay between the insulin responsiveness of skeletal muscle and liver, and the insulin secreted by pancreatic β cells upon glucose stimulation. Defects in the former lead to IR, while impairments in the latter result in the progression to hyperglycemia. Our study verifies that mitochondrial dysfunction underlies these two distinct characteristics of T2DM.

The third co-citations references is a study published in diabetes by Vladimir B Ritov et al. in 2005 (27). This study aimed to explore the correlation between the subcellular distribution of mitochondria in human skeletal muscle and IR in T2DM and obesity. To achieve this, mitochondrial components of myofibrils were observed after conducting a percutaneous biopsy of the vastus lateralis muscle. The subjects included 11 T2DM patients, 12 age-, gender-, and weight-matched obese sedentary nondiabetic volunteers, and 8 healthy volunteers.

In 2003, vamsi K Mootha and his team published their fourth research in NAT Genet, which was co- citations as reference (28). In this study, gene set enrichment analysis was employed to pinpoint a cluster of genes linked to oxidative phosphorylation. Notably, the expression of these genes is uniformly downregulated in human diabetic muscle. Conversely, their expression is elevated at the site where insulin facilitates glucose disposal, a process activated by PGC-1 α and correlated with overall aerobic capacity.

The fifth most frequently co-citations references is a study collaboratively conducted by Timothy R Koves and his team, which was published in Cell Metabolism in 2008 (30). Utilizing targeted metabolomics, this article verifies that obesity-associated IR in skeletal muscle is marked by excessive β-oxidation, compromised conversion to carbohydrate substrates during the fasting-to-eating transition, and concurrent depletion of organic acid intermediates within the tricarboxylic acid cycle. These findings underscore a profound connection between skeletal muscle IR and lipid-induced mitochondrial stress.

“Patients with type 2 diabetes have normal mitochondrial function in skeletal muscle” (31), authored by R Boushel et al. and published in Diabetologia in 2007, ranks as the sixth most frequently cited reference. In this study, a high-resolution breath assay was employed to measure the oxidative phosphorylation and electron transport capacity of permeabilized muscle fibers from biopsy samples of the quadriceps femoris muscle taken from both healthy subjects and patients with T2DM. The aim was to verify whether the mitochondrial function of T2DM patients was unaffected, and to ascertain if the coupled and uncoupled respiratory retardation observed could be attributed to a reduced mitochondrial content.

The seventh article is a study on diabetes, authored by Martin Mogensen and his team, and published in a renowned publication (32). This study evaluated 3-hydroxyacyl-CoA-dehydrogenase and citrate synthase activities, uncoupling protein content, oxidative stress (measured by 4-hydroxy-2-nonenal), fiber type distribution, and mitochondrial respiration in muscle biopsies obtained from T2DM patients and non-diabetic male subjects. The findings revealed mitochondrial respiratory dysfunction and an elevated number of 2x type fibers in the muscles of T2DM patients.

In 2003, Mary Elizabeth Patti and her team published a study in Proceedings of the National Academy of Sciences of the United States of America (33). This study analyzed skeletal muscle gene expression in both diabetic and non-diabetic patients, demonstrating the presence of PGC1 α and β, as well as multiple oxidative metabolism genes, in high-risk non-diabetic subjects with diabetes mellitus and a family history of diabetes.

The ninth article, authored by Charlotte Bonnard et al. and published in J Clin Invest in 2008, is an experimental study (34). After prolonged dietary intervention with a high-fat, high-sucrose diet, mice developed a diabetic state. In this condition, alterations in mitochondrial biogenesis, structure, and function were noticed in the mouse muscle tissue. This confirms that mitochondrial dysfunction is not an early occurrence in the progression of IR in diabetic mice, but rather a consequence of reactive oxygen species production in skeletal muscle triggered by hyperglycemia and hyperlipidemia.

The tenth co-citations references, authored by KITT Falk Petersen (35) and his team, was published in Science in 2003. This study has verified that IR in elderly individuals is linked to an elevation of fatty acid metabolites in muscle cells, potentially stemming from the age-related decline in mitochondrial oxidation and phosphorylation activity.

In summary, the initial ten co-citations references collectively emphasize the clinical investigation and data gathering contrasting T2DM patients with non-T2DM patients, particularly exploring mitochondrial function, skeletal muscle mitochondria, and their correlation with T2DM. Liver mitochondrial dysfunction is characterised by disturbances in energy metabolism, fat accumulation and oxidative stress, while skeletal muscle mitochondrial dysfunction is characterised by insulin resistance, abnormal lipid metabolism and reduced exercise capacity. Together, hepatic and skeletal muscle mitochondrial dysfunction contributes to the metabolic imbalance in T2DM. Hepatic mitochondrial dysfunction increases glucose output, whereas skeletal muscle mitochondrial dysfunction decreases glucose uptake, both of which together lead to increased hyperglycaemia and insulin resistance. Meanwhile, abnormal fatty acid metabolism interacts in liver and skeletal muscle. Decreased hepatic mitochondrial fatty acid oxidation capacity increases plasma levels of free fatty acids, which are transported to skeletal muscle, further affecting insulin signalling and energy metabolism in muscle. It is noteworthy that the top ten co-cited references have more discussion around skeletal muscle mitochondrial function.This establishes a groundwork for the ensuing discussion on the connection between T2DM and mitochondria.

In Bibliometrics, the co-occurrence of keywords can indicate the prevalent topics in an academic field, while bursts in keywords and reference citations can reveal emerging topics within a discipline. This study aims to identify the trending topics and cutting-edge research areas by examining reference clustering, bursts in references and keywords, as well as conducting timeline mapping of keyword clustering.

According to the clustering network diagram of co-citations references, the publication time of #18 proteomics, #11 fatty acid transporters, #12 pyruvate, #3 uncoupling protein, #19 ipla (2) beta, #16 glucose uptake, #8 cardiac efficiency, #13 mitofusin, #1 myotubes is generally far from now, These early research papers are primarily located on the left side of the network. For instance, Nishikawa and colleagues (36) investigated three distinct biochemical pathways involved in vascular endothelial cell injury caused by hyperglycemia. They discovered that specific inhibitors targeting these pathways could restore mitochondrial reactive oxygen species levels to normal, thereby preventing hyperglycemic damage. The publication time of the clustered literatures on the right side of the co-citation network is closer now. Further combining the time characteristics of the co-citation relationship and the average time of various literatures, it can be concluded that the current research fields of mitochondria and T2DM are mainly #4 mitochondrial-associated er membranes, #5 inflammasome, #6 adipocyte, #7 metformin. Ana Paula Arruda and her colleagues (37) discovered that obesity results in a significant reorganization of the mitochondria-associated endoplasmic reticulum in the liver. This reorganization causes mitochondrial calcium overload, diminishes mitochondrial oxidative capacity, and increases oxidative stress. Research frontiers and emerging trends are primarily concentrated in clustering #0 empagliflozin, #9 transmission electron microscope, These studies primarily examined the association between mitochondrial dysfunction and both T2DM and IR (38, 39).

References experiencing significant citation explosions can also be identified by the emergence of new themes within a specific field. Out of the top 25 references burst, 4 studies are currently undergoing a citation explosion. These articles reflect the newest and most prominent research topics related to this subject and indicate potential avenues for future exploration,Examples include mitochondrial dynamics, mitochondrial dysfunction, and diabetes prevalence (29, 38–40). Among the remaining 21 references, 11 studies primarily focused on detailing the role of mitochondria in skeletal muscle and its association with T2DM and IR (27, 28, 30–32, 34, 41–45); Six studies were focused on exploring the impact of mitochondrial dysfunction on T2DM and IR (25, 26, 33, 35, 46, 47); Four studies specifically examined the role of mitochondria in T2DM and IR (48–51).

The keyword analysis reveals a close association between mitochondria and T2DM. Additionally, skeletal muscle mechanisms such as mitochondrial dysfunction, oxidative stress, and energy metabolism, along with other factors, are intricately linked to T2DM and its pathological manifestations like obesity, IR, and insulin sensitivity. The keyword analysis aligns with the results obtained from the sudden analysis of Co-citations references. Furthermore, the timeline graph analysis of keywords provides a detailed illustration of the time span of each cluster and the connections under various labels. In this field, the time span of #0,#1 is relatively large. It shows that the research on skeletal muscle mitochondria in diabetes has been paid attention by relevant researchers.

Emergent words refer to terms whose frequency of usage experiences a sudden surge within a specific timeframe, serving as a distinct indicator of shifting research priorities. Over the past two decades, investigations into this subject matter can be broadly categorized into two primary phases. Between 2003 and 2015, research efforts were predominantly centered around clinical applications. However, since 2015, there has been a notable shift towards terms like mitochondrial dynamics, organization, and mouse models, reflecting a current research emphasis on deeper explorations of underlying mechanisms.

According to the above analysis, we have summarized the following three aspects: