Heliyon 10 (2024) e31405

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Heliyon
journal homepage: www.cell.com/heliyon

Research article

Bibliometric and visual analysis of ACE2/Ang 1–7/MasR axis in

diabetes and its microvascular complications from 2000 to 2023
Weiwen Hu , Jian Tan , Yeting Lin , Yulin Tao , Qiong Zhou *
Department of Ophthalmology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi Province,
People’s Republic of China

A R T I C L E I N F O A B S T R A C T

Keywords: Background: The pathogenesis of diabetes and its microvascular complications are intimately
Diabetes associated with renin angiotensin system dysregulation. Evidence suggests the angiotensin con­
Diabetic microvascular complications verting enzyme 2 (ACE2)/angiotensin 1-7 (Ang 1–7)/Mas receptor (MasR) axis regulates meta­
Angiotensin-converting enzyme 2
bolic imbalances, inflammatory responses, reduces oxidative stress, and sustains microvascular
Angiotensin 1-7
integrity, thereby strengthening defences against diabetic conditions. This study aims to conduct
Mas receptor
Bibliometric analysis a comprehensive analysis of the ACE2/Ang 1–7/MasR axis in diabetes and its microvascular
complications over the past two decades, focusing on key contributors, research hotspots, and
thematic trends.
Methods: This cross-sectional bibliometric analysis of 349 English-language publications was
performed using HistCite, VOSviewer, CiteSpace, and Bibliometrix R for visualization and metric
analysis. Primary analytical metrics included publication count and keyword trend dynamics.
Results: The United States, contributing 105 articles, emerged as the most productive country,
with the University of Florida leading institutions with 18 publications. Benter IF was the most
prolific author with 14 publications, and Clinical Science was the leading journal with 13 articles.
A total of 151 of the 527 author’s keywords with two or more occurrences clustered into four
major clusters: diabetic microvascular pathogenesis, metabolic systems, type 2 diabetes, and
coronavirus infections. Keywords such as “SARS”, “ACE2”, “coronavirus”, “receptor” and
“infection” displayed the strongest citation bursts. The thematic evolution in this field expanded
from focusing on the renin angiotensin system (2002–2009) to incorporating ACE2 and diabetes
metabolism (2010–2016). The latter period (2017–2023) witnessed a significant surge in diabetes
research, reflecting the impact of COVID-19 and associated conditions such as diabetic retinop­
athy and cardiomyopathy.
Conclusions: This scientometric study offers a detailed analysis of the ACE2/Ang 1–7/MasR axis in
diabetes and its microvascular complications, providing valuable insights for future research
directions.

1. Introduction

According to the 10th edition of the International Diabetes Federation Diabetes Atlas, an estimated 536.6 million individuals aged

* Corresponding author.
E-mail addresses: [email protected] (W. Hu), [email protected] (J. Tan), [email protected] (Y. Lin), [email protected] (Y. Tao),
[email protected] (Q. Zhou).

https://doi.org/10.1016/j.heliyon.2024.e31405
Received 19 January 2024; Received in revised form 15 May 2024; Accepted 15 May 2024
Available online 16 May 2024
2405-8440/© 2024 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).
W. Hu et al. Heliyon 10 (2024) e31405

20–79 were living with diabetes globally in 2021, with projections suggesting a rise to 783.2 million by 2045 [1]. In the modern era,
diabetes has become a leading chronic metabolic disorder, significantly endangering individual health and placing considerable
pressure on worldwide healthcare systems and economies. Diabetics are at increased risk of microvascular complications, such as
diabetic retinopathy, nephropathy, and neuropathy—which contribute to higher mortality rates, blindness, kidney failure, and a
diminished quality of life [2]. Despite significant progress, the exact mechanisms underlying diabetes and its microvascular compli­
cations are still not fully understood. Therefore, keeping abreast of current trends and developments in this filed is crucial to elucidate
the precise pathogenesis of these conditions.
The renin angiotensin system, a critical endocrine regulator of haemodynamics, body fluid balance, neuroendocrine functions,
inflammation, oxidative stress and tissue fibrosis, is modulated globally by classical circulating elements and locally through tissue
specific mechanisms [3]. Activation of the angiotensin converting enzyme/angiotensin II axis and its type 1 receptor forms the classical
pathway of renin angiotensin system, implicated in the pathogenesis of several diseases, including diabetes and its microvascular
complications. Angiotensin converting enzyme 2 (ACE2), a homolog of angiotensin-converting enzyme and a carboxypeptidase, plays
a pivotal role in local and systemic hemodynamics, primarily by lowering blood pressure [4]. The enzyme’s primary product,
angiotensin 1-7 (Ang 1–7), engages the Mas receptor (MasR), promoting vasodilation, antioxidative effects, anti-inflammation, pro­
liferation inhibition, enhanced glucose tolerance, and improving insulin sensitivity. The ACE2/Ang 1–7/MasR pathway functions as a
counter-regulatory mechanism against the angiotensin converting enzyme/angiotensin II axis and its type 1 receptor pathway in
various pathological conditions [5]. Although considered the protective arm of the renin angiotensin system, the precise mechanisms
underpinning these effects remain poorly understood [6]. Extensive research is currently underway on the ACE2/Ang 1–7/MasR axis
in metabolic disorders, including diabetes, which shows great potential as a therapeutic target for managing diabetes and its related
microvascular complications [6].
Bibliometrics is a methodological approach that quantifies and analyzes the quantity, quality, and impact of scientific literature,
playing a crucial role in assessing research outcomes and academic contributions [7]. Compared to traditional review articles, bib­
liometrics offers researchers an objective and quantifiable perspective, enabling a more thorough understanding and evaluation of
academic research achievements, hotspots, and trends within a specific field or disease, thus establishing a foundation for future
research endeavors [8]. However, bibliometric studies on the ACE2/Ang 1–7/MasR axis related to diabetes and its microvascular
complications are scarce. Consequently, this study utilizes bibliometric analysis to thoroughly examine academic publications con­
cerning the ACE2/Ang 1–7/MasR axis in diabetes and its microvascular complications. The primary aim of this research is to elucidate
potential directions and trajectories for clinical researchers and practitioners.

2. Methods

2.1. Data sources and search strategy

Data were retrieved from the Web of Science Core Collection (WoSCC, https://webofscience.clarivate.cn/wos/alldb/basic-search)
between January 1, 2000, and December 20, 2023, comprising full records and cited references. The search utilised the terms “diabetes
and its microvascular complications” AND “ACE2/Ang 1–7/MasR axis” (full search terms listed in the appendix). Searches were
completed in a single day (December 22, 2023) to circumvent potential errors from daily database updates. For this study, the inclusion
criteria limited to English and excluded specific document types: meeting abstracts (n = 20), editorial materials (n = 3), proceeding
papers (n = 5), book chapters (n = 1) and letter (n = 5). Only articles (n = 243) and review articles (n = 106) were included, as other
types generally bypass peer review and thus, were excluded from the bibliometric analysis (Fig. S1).

2.2. Data analysis and visualization

HistCite Pro 2.1 was used to calculate the total local citation score (TLCS) and total global citation score (TGCS) for publications,
authors, institutions, journals and countries/regions, highlighting citation frequencies within local datasets (finally determined 349
publications) and broader recognition across the Web of Science database, respectively. TLCS values were noted to be significantly
lower than TGCS values [8]. Biblioshiny R (version 4.1.4) was utilised to analysis authors’ h-index, g-index, m quotient, production
over time, adherence to Lotka’s law, and journals’ compliance with Bradford’s law [8,9]. The m-index is determined by calculating the
median number of citations that the papers in a scientist’s h-core receive, with the h-core being defined by the h-index. The q2 index of
√̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅
the author was derived manually using the specified formula: q2 = (h − index) × (m − index) [10]. The calculation and definitions
of the h-index, g-index, m-index, m quotient, and q2-index are listed in Table S1. Core authors were identified in accordance with
√̅̅̅̅̅̅̅̅̅̅̅
Price’s Law, M = 0.749 Nmax (M represents a threshold for defining core authors’ publication output, with Nmax representing the most
productive author’s paper count) [11]. Microsoft Excel 2019 facilitated the statistical compilation of publication data. VOSviewer
(version 1.6.19) enabled the visualization of collaborations and co-occurrences at various levels, including countries/regions, insti­
tutional, and authorial, as well as journals and keywords [12]. Three-field plot and theme evolution were performed using Biblioshiny
R. CiteSpace (version 6.2.R5) was used to generate keyword bursts and ridge plots [13] (Fig. S1).

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3. Results

3.1. Annual publications and citations

Our study identified 349 publications on the ACE2/Ang 1–7/MasR axis related to diabetes and its microvascular complications
indexed in the WoSCC, including 243 articles (69.6 %) and 106 review articles (30.4 %). Curve fitting analysis revealed that since
2002, the cumulative number of publications has shown a consistent upward trend, with an averge annual growth rate of 11.03 %. The
fitted curve is described by the equation: y = 0.9824x2-10.717x+26.969 (R2 = 0.9835) (Fig. 1A). Between 2000 and 2011, fewer than
10 publications per year were published in this field, however, since then, the annual output has consistently exceeded 10 publications.
Notably, in the past four years, there has been a rapid increase in the number of published articles (Table S2). As of the latest search,
these publications have accrued 16504 citations, with an average of 47.29 per publication. The year 2020 recorded the highest TGCS at
5243, signifying substantial research excellence during this period. Other years with notably high citation counts include 2013 (TGCS
= 1207), 2014 (TGCS = 1254) and 2021 (TGCS = 1925). Given their proximity to the search date, the citations frequencies for 2022
and 2023 were lower than those of earlier years (Fig. 1B). The continuous increase in annual publications and citations mirrors the
rapid advancement in the field.

3.2. Analysis of countries/regions

A total of 52 countries/regions contributed to this research field (Fig. 2A). As shown in Table 1, the United States is the most
productive country (n = 105), followed by China (n = 67), and Canada (n = 31). Publications from the United States rank first in both
TLCS (424) and TGCS (5953). Although Kuwait, Spain and South Korea are not among top 10 in terms of publications, but their citation
score of publications is still considerable. Each circle represents a country/region, with its size indicated the total link strength from
that specific location. The thickness of the connecting lines the reflects the intensity of cooperation, and the same color signifies
relatively closer collaboration (Fig. 2B). Evidently, the United States, the United Kingdom, Canada, China, Germany and Brazil are
prominent in this research field, with closest cooperation observed between the United States and Canada. Some countries/regions do
not have academic exchange within this research field, such as Pakistan, Mexico and Ghana. Fig. 2C shows that Kuwait and Brazil were

Fig. 1. Analysis of publication outputs and citations. (A) Cumulative number of publications. (B) Annual global citations. TGCS: total global
citation score.

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Fig. 2. Visualization analysis of countries/regions involved in research on the ACE2/Ang 1–7/MasR axis in diabetes and its microvascular com­
plications. (A) Global distribution of publications using Biblioshiny R. (B) Network visualization using VOSviewer (minimum number of publica­
tions of a country/region is five), the size of each circle represents the total link strength of a country, with more cooperation producing larger
circles. The line between the two points in the figure represents those two countries/regions had established a similar relationship. The thicker the
line, the closer the link between the two countries/regions. (C) Overlay visualization using VOSviewer (minimum number of publications of a
country/region is five), the occurrence of the blue words took place in the early stages, whereas the yellow words emerged more recently. The
weights and normalization method for the visual analysis of VOSviewer were set to total link strength and LinLog/modularity, respectively. (For
interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Table 1
The top 10 countries/regions with the most publications or total citation score.
Rank Publication Country/region Rank TLCS Country/region Rank TGCS Country/region

1 105 USA 1 424 USA 1 5953 USA

2 67 China 2 213 Canada 2 3775 China
3 31 Canada 3 205 China 3 3416 Canada
4 30 Brazil 4 99 Kuwait 4 2568 UK
5 19 India 5 95 Brazil 5 1531 Brazil
6 19 UK 6 87 UK 6 1108 Germany
7 17 Germany 7 81 Japan 7 1050 Italy
8 17 Italy 8 71 Australia 8 817 Japan
9 15 Japan 9 63 Germany 9 710 South Korea
10 14 Australia 10 57 Spain 10 660 Kuwait

TLCS: total local citation score. TGCS: total global citation score.

the first to begin study in this field, while Iran, Egypt, and the United Arab Emirates were relatively late. The corresponding authors of
publications in this field are spread across all five continents, indicating that every region is actively exploring this field of study. In
Asia, 22.7 %, Europe 31.7 %, Africa 50 %, Oceania 40 %, North America 27.4 %, and South America 36.7 % of the publications are the
result of international collaborations by the corresponding authors (Table S3).

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Table 2
The top 10 institutions with the most publications or total citation score.
Rank Publication Institution Country/region Rank TLCS Institution Country/region Rank TGCS Institution Country/region

1 18 Univ Florida USA 1 110 Capital Med Univ China 1 2112 Capital Med Univ China
2 13 Capital Med Univ China 2 101 Univ Florida USA 2 1915 Univ Florida USA
3 13 Kuwait Univ Kuwait 3 99 Kuwait Univ Kuwait 3 1804 Univ Leeds UK
4 13 Univ Fed Minas Gerais Brazil 4 85 Univ Toronto Canada 4 1574 Univ Alberta Canada
5

5 10 Univ Sao Paulo Brazil 5 83 Univ Fed Minas Gerais Brazil 5 1311 Univ Alabama Birmingham USA
6 8 Univ Ottawa Canada 6 76 Univ Alberta Canada 6 803 Univ Toronto Canada
7 7 Univ Alberta Canada 7 70 Austrian Acad Sci Austria 7 770 IRCCS Tradate VA Italy
8 7 Univ Toronto Canada 8 66 Wake Forest Univ USA 8 770 Univ Insubria Italy
9 7 Wake Forest Univ USA 9 56 Northwestern Univ USA 9 770 Osped S Maria Misericordia Italy
10 6 Univ Alabama Birmingham USA 10 47 Louisiana State Univ USA 10 677 Univ Fed Minas Gerais Brazil

TLCS: total local citation score. TGCS: total global citation score.

Heliyon 10 (2024) e31405

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3.3. Analysis of institutions

A total of 554 institution collectives conducted studies on the ACE2/Ang 1–7/MasR axis in diabetes and its microvascular com­
plications. Table 2 shows the top 10 institution collectives (minimum number of documents of a institution: 6) with the most published
papers. Among them, the University of Florida (n = 18) had the highest output, followed by Capital Medical University (n = 13) and
Kuwait University (n = 13). The 10 most productive institution collectives were located in the United States (n = 3), Canada (n = 3),
Brazil (n = 2), China (n = 1) and Kuwait (n = 1). The top 3 institution collectives with the highest local cited were the Capital Medical
University (TLCS = 110), University of Florida (TLCS = 101) and Kuwait University (TLCS = 99). The top 3 institution collectives with
the highest global cited were the Capital Medical University (TGCS = 2112), University of Florida (TGCS = 1915) and University of
Leeds (TGCS = 1804). Moreover, only 520 out of 554 institutional collectives have established academic external exchanges. Fig. 3A
shows the collaboration network of institutional collectives with two or more publications, and there is close cooperation between
most of them. Kuwait University, University of Sao Paulo and Universidade Federal de Minas Geraiswere the earliest to start this
research field (Fig. 3B).

3.4. Analysis of authors

A total of 1820 authors engaged in research and published articles in this field. Of these authors, 87.7 percent published only one
paper, and 12.3 percent published multiple papers, fitting with Lotka’s law (Fig. S2). In order to identify the core authors among these
more precisely, Price’s law was used. After calculating the number of papers published by the core authors, the threshold value was
2.803 papers, and this resulted in 85 core authors. The top 10 core authors (minimum number of documents of a author: 7) were shown
in Table 3 and author rankings based on the h-index, g-index and m quotient were listed in Table S4. Among the ten most productive
authors, Benter IF (n = 14) published the most articles, while Oudit GY (TLCS = 145, TGCS = 1971) was the most cited author. Benter
IF had the highest h-index (12) and g-index (14), Pascual J and Riera M had the highest m-quotient (both 0.7) and Oudit GY had the
highest q2-index of 32.496. In addition, potential relationships between top 10 authors and institutions-countries/regions were
visualized (Fig. S3). Fig. 4A presents the network of collaboration of authors who published two and more papers, and it is possible to
observe multiple author collaborations, such as Raizada MK, Grant MB and Oudit GY, Benter IF and Yousif MHM, Pascual J, Riera M
and Gimeno J, Scholey JW and Oudit GY. Among the top 10 most productive authors, both Benter IF, Oudit GY and Yang JK were
pioneers in this field and continue to achieve notable advancements in their research over the last 5 years. Moreover, Grant MB,
Raizada MK and Oudit GY have shown enhanced activity in this research area over the last 5 years (Fig. 4B and C).

3.5. Analysis of journals

The analysis resulted in 349 publications from 202 journals. Table 4 displays the top 10 most productive or cited journals based on
statistical analysis, highlighting their Impact Factor (IF) and ranked in the category quartile of the Journal Citation Reports 2022. The

Fig. 3. Visualization analysis of institution collectives involved in research on the ACE2/Ang 1–7/MasR axis in diabetes and its microvascular
complications. (A) Network visualization using VOSviewer (minimum number of publications of a institution collective is two), the size of each
circle represents the total link strength of a country, with more cooperation producing larger circles. The line between the two points in the figure
represents those two institution collectives had established a similar relationship. The thicker the line, the closer the link between the two institution
collectives. (B) Overlay visualization using VOSviewer (minimum number of publications of a institution collective is two), the occurrence of the
blue words took place in the early stages, whereas the yellow words emerged more recently. The weights and normalization method for the visual
analysis of VOSviewer were set to total link strength and LinLog/modularity, respectively. (For interpretation of the references to color in this figure
legend, the reader is referred to the Web version of this article.)

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Table 3
The top 10 authors with the most publications or total citation score.
Rank Publications Author h-indexa g-indexa m quotienta m-indexa q2-indexa

1 14 Benter IF 12 14 0.667 37.5 21.213

2 10 Akhtar S 9 10 0.6 25 15.000
3 10 Raizada MK 9 10 0.692 65 24.187
4 9 Soler MJ 8 9 0.615 43 18.547
5 9 Yousif MHM 9 9 0.5 47 20.567
6 8 Oudit GY 8 8 0.444 132 32.496
7 8 Santos SHS 8 8 0.533 61 22.091
8 8 Yang JK 8 8 0.471 31.5 15.875
9 7b Burns KD 7 7 0.538 41 16.941
10 7b Grant MB 6 7 0.462 75 21.213

Rank TLCS Author h-indexa g-indexa m quotienta m-indexa q2-indexa

1 145 Oudit GY 8 8 0.444 132 32.496

2 100 Benter IF 12 14 0.667 37.5 21.213
3 98 Yousif MHM 9 9 0.5 47 20.567
4 86 Yang JK 8 8 0.471 31.5 15.875
5 78 Scholey JW 5 5 0.278 71 18.841
6 75 Raizada MK 9 10 0.692 65 24.187
7 73 Grant MB 6 7 0.462 75 21.213
8 70 Penninger JM 3 3 0.13 189 23.812
9 69 Herzenberg AM 2 2 0.111 198.5 19.925
10 67 Santos SHS 8 8 0.533 61 22.091

Rank TGCS Author h-indexa g-indexa m quotienta m-indexa q2-indexa

1 1971 Oudit GY 8 8 0.444 132 32.496

2 1804 Turner AJ 4 4 0.19 260 32.249
3 1584 Raizada MK 9 10 0.692 65 24.187
4 1500 Grant MB 6 7 0.462 75 21.213
5 1308 Zhong JC 3 3 0.231 124 19.287
6 1176 Gheblawi M 1 1 0.2 1176 34.293
7 1176 Nguyen Q 1 1 0.2 1176 34.293
8 1176 Viveiros A 1 1 0.2 1176 34.293
9 1176 Wang KM 1 1 0.2 1176 34.293
10 921 Yang JK 8 8 0.471 31.5 15.875

TLCS: total local citation score. TGCS: total global citation score.
a
The calculation of the h-index, g-index, m quotient, m-index and q2-index was based on the literature data collected in this study, and not on all
scientific publications of a particular scholar.
b
Seven authors each have a publication tally of seven, including Burns KD, Grant MB, Li QH, Pascual J, Riera M, Santos RAS, and Wang Y. Based on
the alphabetical ordering of the authors’ surnames, only Burns KD and Grant MB are listed in the table.

highest publication counts were in Clinical Science (n = 13, 2022IF = 6, Q1), Peptides (n = 11, 2022IF = 3, Q3), and American Journal of
Physiology-Renal Physiology (n = 9, 2022IF = 4.2, Q1). Notably, the most cited journals were Circulation Research (TGCS = 1300,
2022IF = 20.1, Q1), European Journal of Internal Medicine (TGCS = 710, 2022IF = 8, Q1), and Acta Diabetologica (TGCS = 707, 2022IF
= 3.8, Q2). The core journals of this research field by Bradford’s Law [9] was also analyzed (Fig. S4). The top 59 most productive
journals (minimum number of documents of a journal: 2) were visualized in Fig. 5A. 349 publications have cited 15,278 references
from 2820 journals. The most cited reference journals include Hypertension, Diabetes, The New England Journal of Medicine, Circulation
Research, Nature, and The Journal of Biological Chemistry. Fig. 5B presents a network visualization of journals cited 20 and above times.

3.6. Keywords co-occurrence and clustering analysis

Keywords serve as concise descriptors used in indexing or cataloguing to provide a brief and precise summary of an article. In this
study, a total of 527 author’s keywords were identified across 349 documents, with 151 satisfied the criterion (minimum number of
occurrences of a keyword: 2). Through co-occurrence visualization of these keywords using VOSviewer, it was not difficult to identify
four main clusters (Fig.6A and Table S5). The cluster 1 (red) encompasses keywords such as “diabetes”, “angiotensin 1-7”, “oxidative
stress”, “apoptosis”, “diabetic nephropathy” and “diabetic retinopathy”, primarily related to the pathological mechanism of the ACE2/
Ang 1–7/MasR axis in diabetic microvascular complications. The cluster 2 (blue) predominantly studies the targets and pathways of
the renin angiotensin system in the metabolism system associated with diabetes, with keywords such as “insulin”, “glucose”, “adipose
tissue”, “lipid metabolism” and “hypertension”. The cluster 3 (green), including “type 2 diabetes”, “chronic kidney disease”, “SGLT2
inhibitor”, “biomarkers”, “olmesartan”, and “metformin”, represents the relationship between this axis and type 2 diabetes. The cluster
4 (yellow) includes terms like “ACE2”, “COVID-19”, “SARS-COV-2”, “lung”, and “ARDS”, focusing on the role of ACE2/Ang 1–7/MasR
axis in diabetes and coronavirus interaction. VOSviewer also color-coded the keywords according to the average appearing year
(Fig. 6B), where blue represents earlier appearances and yellow signifies more recent ones. These keywords were published
sequentially from 2014 to 2022 in this field.

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Fig. 4. Visualization analysis of authors involved in research on the ACE2/Ang 1–7/MasR axis in diabetes and its microvascular complications. (A)
Network visualization using VOSviewer (minimum number of publications of a author is two), the size of each circle represents the total link
strength of a country, with more cooperation producing larger circles. The line between the two points in the figure represents those two authors had
established a similar relationship. The thicker the line, the closer the link between the two authors. (B) Overlay visualization using VOSviewer
(minimum number of publications of a author is two), the occurrence of the blue words took place in the early stages, whereas the yellow words
emerged more recently. The weights and normalization method for the visual analysis of VOSviewer were set to total link strength and LinLog/
modularity, respectively. (C) The top 10 authors’ production overtime using Biblioshiny R. (For interpretation of the references to color in this figure
legend, the reader is referred to the Web version of this article.)

3.7. Keyword burst detection and theme evolution

Compared to analyzing high-frequency keywords, identifying burst keywords (i.e., frequently cited keywords within a defined
period) until December 20, 2023 offers deeper insight into cutting-edge themes and developing trends. The top 55 keywords were
selected based on their burst intensity and arranged chronologically according to their burst time, as illustrated in Fig. 7A. The results
indicated that “SARS”, “ACE2”, “coronavirus”, “receptor” and “infection” were the top five keywords with the strongest citation bursts.
The earliest burst keywords of ACE2/Ang 1–7/MasR axis in diabetes and its microvascular complications include “renin angiotensin”,
“carboxypeptidase”, “diabetes”, “homolog” and “angiotensin II type 1 receptor”. Moreover, fourteen keywords burst continue to last
until the end of 2023, including “obesity”, “inflammation”, “receptor”, “infection”, “COVID-19”, “mortality”, “spike protein”, “risk”,
“pathogenesis”, “cells”, “axis”, “dipeptidyl peptidase 4”, “tmprss2”, “type 2 diabetes”. In the analyzed period from 2002 to 2023,
research themes transitioned from the renin-angiotensin system (RAS) to emerging intersections between diabetes, its complications,
and COVID-19. The thematic evolution in this field expanded from focusing on the renin angiotensin system (2002–2009) to incor­
porating ACE2 and diabetes metabolism (2010–2016). The latter period (2017–2023) witnessed a significant surge in diabetes
research, reflecting the impact of COVID-19 and associated conditions such as diabetic retinopathy and cardiomyopathy (Fig. 7B).
Additionally, we utilised CiteSpace to further explore research topics of persistent interest, those with fluctuating attention, as well as
emerging or declining themes (Fig. 7C).

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Table 4
The top 10 most productive or cited journals.
Rank Most productive journals Publication TLCS TGCS Quartile (Q) 2022IF

1 Clinical Science 13 49 462 Q1 6

2 Peptides 11 35 364 Q3 3
3 American Journal of Physiology-Renal Physiology 9 68 433 Q1 4.2
4 European Journal of Pharmacology 7 21 174 Q1 5
5 Frontiers in Endocrinology 7 0 78 Q1 5.2
6 Plos One 7 0 250 Q2 3.7
7 Diabetes 6 99 427 Q1 7.7
8 Endocrinology 6 19 443 Q2 4.9
9 Kidney International 6 88 499 Q1 19.6
10 American Journal of Physiology-Endocrinology and Metabolism 5 27 148 Q2 5.1

Rank Most cited journals Publication TLCS TGCS Quartile (Q) 2022IF

1 Circulation Research 2 44 1300 Q1 20.1

2 European Journal of Internal Medicine 1 11 710 Q1 8
3 Acta Diabetologica 2 32 707 Q2 3.8
4 Nature Reviews Endocrinology 1 5 520 Q1 40.5
5 Kidney International 6 88 499 Q1 19.6
6 Clinical Science 13 49 462 Q1 6
7 Endocrinology 6 19 443 Q2 4.9
8 American Journal of Physiology-Renal Physiology 9 68 433 Q1 4.2
9 Diabetes 6 99 427 Q1 7.7
10 Cell Metabolism 3 3 403 Q1 29

TLCS: total local citation score. TGCS: total global citation score. Q: a journal that is ranked in the quartile of the Journal Citation Reports. IF: impact
factor.

Fig. 5. Analysis of journals from publications and references using VOSviewer. (A) Network visualization (minimum number of publications of a
journal is two), the size of each circle represents the number publication of a journal, with more production producing larger circles. The weights
and normalization method for the visual analysis of VOSviewer were set to documents and LinLog/modularity, respectively. (B) Network visual­
ization (minimum number of cited of a journal is twenty), the size of each circle represents the number publication of a journal, with more citation
producing larger circles. The weights and normalization method for the visual analysis of VOSviewer were set to citations and LinLog/modularity,
respectively. The line between the two points in the figure represents those two journals had established a similar relationship. The thicker the line,
the closer the link between the two journals.

3.8. Analysis of co-cited publications and co-cited references

We performed a statistical analysis of 349 publications and found that 37 documents had more than 100 citations. The top 10 most
global cited publications were shown in Table 5. The most cited publication was a review written by Gheblawi, M et al. [3] in Cir­
culation Research titled Angiotensin-Converting Enzyme 2: SARS-CoV-2 Receptor and Regulator of the Renin-Angiotensin System
(TGCS = 1176), followed by Verdecchia P (TGCS = 710) and Yang JK (TGCS = 688). The top 11 most co-cited references was listed in
Table 6, and the results illustrated that the document published by Donoghue M [4] had the highest record of co-cited references
followed by Tipnis SR [14] and Santos RAS [15].

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Fig. 6. Visual analysis of author keywords co-occurrence on the ACE2/Ang 1–7/MasR axis in diabetes and its microvascular complications research
using VOSviewer. (A) Network visualization, each node represents a keyword, and more frequent keywords occurrence, the larger the node. The line
between nodes represents the extent of keywords co-occurrence. (B) Overlay visualization, the occurrence of the blue words took place in the early
stages, whereas the yellow words emerged more recently. The weights and normalization method for the visual analysis of VOSviewer were set to
occurrences and LinLog/modularity, respectively. The minimum cluster size set at 20. (For interpretation of the references to color in this figure
legend, the reader is referred to the Web version of this article.)

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Fig. 7. Keyword burst detection and theme evolution on the ACE2/Ang 1–7/MasR axis in diabetes and its microvascular complications research. (A)
Detect the top 55 keywords with the strongest citation bursts using CiteSpace. (B) Visualization of theme evolution using Biblioshiny R, analysis field
set as all author’s keyword, weight index set as inclusion index weighted by word occurrences, time slices set as 2 cutting points (2009 and 2016).
(C) Ridge plot of theme using CiteSpace, timespan set as 2002–2023 (slice length = 1), selection criteria set as top 50 per slice, LRF = 3.0, L/N = 10,
LBY = 5, e = 1.0.

Table 5
The top 10 most cited publications in research of ACE2/Ang 1–7/MasR axis in diabetes and its microvascular complications from 2000 to 2023.
Rank Publication Title (*review and #article) Corresponding Year Journal TGCS DOI
author

1 Angiotensin-Converting Enzyme 2: SARS-CoV-2 Gavin Y. Oudit 2020 Circulation Research 1176 10.1161/
Receptor and Regulator ofthe Renin-Angiotensin circresaha.120.317015
System Celebrating the 20th Anniversary of the
Discovery of ACE2*
2 The pivotal link between ACE2 deficiency and Paolo Verdecchia 2020 European Journal of 710 10.1016/j.
SARS-CoV-2 infection* Internal Medicine ejim.2020.04.037
3 Binding of SARS coronavirus to its receptor Jin-Kui Yang 2010 Acta Diabetologica 688 10.1007/s00592-009-
damages islets and causes acute diabetes# 0109-4
4 COVID-19 and diabetes mellitus: from Michael A. 2020 Nature Reviews 520 10.1038/s41574-020-
pathophysiology to clinical management* Nauck Endocrinology 00435-4
5 ACE2: from vasopeptidase to SARS virus receptor# Anthony J. 2004 Trends in Pharmacological 391 10.1016/j.
Turner Sciences tips.2004.04.001
6 COVID-19: angiotensin-converting enzyme 2 Érika Bevilaqua 2021 European Journal of Clinical 322 10.1007/s10096-020-
(ACE2) expression and tissue susceptibility to Rangel Microbiology & Infectious 04138-6
SARS-CoV-2 infection* Diseases
7 Organ-specific manifestations of COVID-19 Meletios A. 2020 Clinical and Experimental 284 10.1007/s10238-020-
infection* Dimopoulos Medicine 00648-x
8 Angiotensin-converting enzyme 2 and angiotensin Cheng Zhang 2014 Nature Reviews Cardiology 278 10.1038/
1-7: novel therapeutic targets* nrcardio.2014.59
9 Organ-protective effect of angiotensin-converting Gui-Qiang Wang 2020 Journal of Medical Virology 274 10.1002/jmv.25785
enzyme 2 and its effect on the prognosis of COVID-
19*
10 Coronavirus Infections and Type 2 Diabetes-Shared Daniel J. Drucker 2020 Endocrine Reviews 272 10.1210/endrev/
Pathways with Therapeutic Implications* bnaa011

TGCS: total global citation score.

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W. Hu et al. Heliyon 10 (2024) e31405

Table 6
The top 11 most co-cited references in research of ACE2/Ang 1–7/MasR axis in diabetes and its microvascular complications from 2000 to 2023.
Rank Reference Title (*review and #article) Corresponding Year Journal Citations DOI
author

1 A novel angiotensin-converting enzyme-related Susan Acton 2000 Circulation Research 89 10.1161/01.

carboxypeptidase (ACE2) converts angiotensin I to res.87.5.e1
angiotensin 1-9#
2 A human homolog of angiotensin-converting Sarah R. Tipnis 2000 The Journal of Biological 88 10.1074/jbc.
enzyme. Cloning and functional expression as a Chemistry M002615200
captopril-insensitive carboxypeptidase#
3 Angiotensin-(1–7) is an endogenous ligand for the G Thomas Walther 2003 Proceedings of The National 69 10.1073/
protein-coupled receptor Mas# Academy of Sciences of The pnas.1432869100
United States of America
4 SARS-CoV-2 Cell Entry Depends on ACE2 and Stefan Pӧhlmann 2020 Cell 68 10.1016/j.
TMPRSS2 and Is Blocked by a Clinically Proven cell.2020.02.052
Protease Inhibitor#
5 Angiotensin-converting enzyme 2 is an essential Josef M. 2002 Nature 62 10.1038/
regulator of heart function# Penninger nature00786
6 Hydrolysis of biological peptides by human Peter Tummino 2002 The Journal of Biological 52 10.1074/jbc.
angiotensin-converting enzyme-related Chemistry M200581200
carboxypeptidase#
7 Human recombinant ACE2 reduces the progression Gavin Y. Oudit 2010 Diabetes 46 10.2337/db09-
of diabetic nephropathy# 1218
8 Glomerular localization and expression of Daniel Batlle 2006 Journal of The American 46 10.1681/
Angiotensin-converting enzyme 2 and Angiotensin- Society of Nephrology ASN.2006050423
converting enzyme: implications for albuminuria in
diabetes#
9 Tissue distribution of ACE2 protein, the functional W Timens 2004 Journal of Pathology 43 10.1002/path.1570
receptor for SARS coronavirus. A first step in
understanding SARS pathogenesis#
10 Angiotensin I-converting enzyme type 2 (ACE2) Eric Lazartigues 2010 Diabetes 42 10.2337/db09-
gene therapy improves glycemic control in diabetic 0782
mice#
11 Decreased glomerular and tubular expression of Andrew M. 2008 Kidney International 42 10.1038/
ACE2 in patients with type 2 diabetes and kidney Herzenberg ki.2008.497
disease#

4. Discussion

This study represents the first global bibliometric analysis focus on the ACE2/Ang 1–7/MasR axis in diabetes and its related
microvascular complications, where invaluable insights are provided. Through bibliometric assessments and network visualizations,
research trends over the last two decades have been explored, with significant engagement from journals, contributions by author,
collaborations between institutions, involvement across countries/regions, and keywords dynamics. A notable increase in publications
and TGCS was observed in 2020 and 2021, likely attributed to the heightened interest in ACE2 as a potential receptor for severe acute
respiratory syndrome coronavirus during the COVID-19 pandemic [3,16]. An ongoing increase in both publications and citations
annually has been recorded, reflecting a growing interest in this research filed, thereby suggesting its sustained importance and the
potential for further studies. Notably, the highest citation papers are predominantly review articles, while research articles are most
frequently cited references, indicating the field’s substantial potential for further research advancements.
Research within this domain is globally dispersed, with publication output and citation metrics predominantly led by the United
States, China, Canada and Brazil. Contributions are notably made by their respective institutions such as the University of Florida,
Wake Forest University, and the University of Alabama at Birmingham in the United States; the University of Ottawa, the University of
Alberta, and the University of Toronto in Canada; and Capital Medical University in China. Despite Kuwait not ranking within the top
ten for publication volume, significant impact is imparts by their research, as evidenced by the meticulous scholarship of Professors
Benter IF, Akhtar S, and Yousif MHM. At the core of the collaboration network, countries such as the United States, Italy, Germany, the
United Kingdom, Canada, Brazil, China, and India are seen, each having collaborated on publications with at least six other countries/
regions, thereby underscoring their considerable influence in this field. Collaborative relationship have been established by the United
States with 22 countries/regions, most frequently with Canada (12 times), followed by Brazil (6 times), China (5 times), and Kuwait (4
times). European countries like Germany and Italy have also engaged in cross-continental collaborations, notably with Argentina,
South Africa, and Australia respectively. Moreover, Egypt, located on the African continent, has been involved in collaborations with
India, Portugal, Saudi Arabia and Iraq [17,18]. These findings highlight the establishment of an initial collaborative network across the
five continents within this research field.
The analysis of authors demonstrated that significant progress in this research field has been driven by a select few, consistent with
Lotka’s law [11]. As per Price’s law, those with more than two publications have been identified as core authors. In the collaboration
network analysis of the ten most productive authors, it was found that various relationships exist, notably excluding Yang JK. These
include links among Benter IF, Akhtar S and Yousif MHM; Raizada MK, Oudit GY, Grant MB and Santos SHS; as well as Soler MJ and

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W. Hu et al. Heliyon 10 (2024) e31405

Burns KD. This indicates that these prolific authors recognise and collaborate with each other to further the field. The h-index, g-index,
m quotient, m-index, and q2 index are widely accepted indicators used to assess author productivity [10]. Benter IF, with the highest
h-index, g-index, and the fourth highest m quotient, is characterised by a substantial publication volume and extensive citation reach,
demonstrating the profound impact and quality of his research. The pathological and pharmacological mechanisms of Ang 1–7 in
diabetic cardiovascular and erectile dysfunction have been extensively investigated by Benter IF et al. [19–30]. Raizada MK and Akhtar
S, with g-index exceeding their h-index, highlight the significant citation of key papers, despite fewer publications. Yousif MHM
consistently deliver balanced research output and paper quality. Pascual J and Riera M, with lower h-index and g-index but highest m
quotient, produce high-quality, impactful work within shorter academic careers. In collaboration with Soler MJ, Pascual J and Riera M
have extensively studied ACE2 and ADAM17’s role in diabetic kidney disease [31–33]. Additionally, Raizada MK, ranked second in m
quotient, has actively collaborated with Grant MB and Oudit GY in recent research, garnering significant attention. Furthermore, the
author with the highest citation count, Oudit GY, possesses a significantly high m-index and q2 index, indicating that his papers garner
above-average citations, thus exerting a greater impact compared to those of his peers. Collaborating with Reich HN, Patel VB, and
Grant MB, Oudit GY investigated the effects of ACE2 gene intervention on diabetic nephropathy, retinopathy, and cardiovascular
complications [34–40].
In the sphere of core journals within this field, minimal variation is observed in the publications they publish, highlighting the
significant influence these journals have in their domain. A distinct preference for papers focusing on the journals focusing on the
ACE2/Ang 1–7/MasR axis is demonstrated by journals specializing in diabetes, endocrinology, and broader interdisciplinary research.
This axis is acknowledged as a critical protective factor in the development of diabetes and its microvascular complications [41]. It is
anticipated that such journals will maintain a focus on research concerning advancements related to the ACE2/Ang 1–7/MasR axis,
especially regarding diabetes and its microvascular complications.
Publications garnering the most citations typically represent the most pivotal research outcomes within a research field, serving to
identify the hotspots or key developments therein. Among the top 10 screened publications, the highest global citation count is
attributed to a review authored by Gheblawi M et al. [3], published in 2020 in Circulation Research, elucidating ACE2’s role. Marking
the 20th anniversary of ACE2’s discovery, this review extensively discusses its discovery, biochemical actions, and essential role in
cardiovascular disease, including its recent identification as the receptor for SARS-CoV-2. Remarkably, nine of the top 10 cited
publications explore the link between coronavirus receptors and diabetes [3,16,42–48].
In identifying the most cited references, researchers are enabled to swiftly establish the theoretical background and empirical
analysis of their papers. This study has identified the top 10 references, with the two most cited being seminal original articles. The
first, “A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9” was pub­
lished by Donoghue M et al. [4] in Circulation Research in 2000. The second, “A human homolog of angiotensin-converting enzyme.
Cloning and functional expression as a captopril-insensitive carboxypeptidase” published by Tipnis SR et al. [14] in The Journal of
Biological Chemistry in the same year. These studies have been pivotal in elucidating the organismal characterization of ACE2 and have
laid a crucial foundation for further research into the ACE2/Ang 1–7/MasR axis, particularly regarding diabetes and its microvascular
complications.
Keyword co-occurrence analysis is employed to discern the principal themes and trends within a research field by examining how
frequently keywords co-appear in the literature. When two or more keywords are often found together in one or several documents, a
potential relationship or dependency between these themes is indicated. VOSviewer is used to automatically categorize keywords into
clusters, guided by the strength and frequency of their co-occurrences. Each cluster’s keywords are shown to co-occur frequently,
suggesting their association with similar or interconnected research topics. In this study, VOSviewer analyzed author keywords
appearing more than once, revealing four primary aspects of this research: the pathomechanisms of diabetic microvascular compli­
cations, the metabolic system, type 2 diabetes, and coronavirus infections.
To further explore the hotspots and trends in ACE2/Ang1-7/MasR axis research in diabetes and its microvascular complications,
keyword bursts and theme evolution were analyzed. From 2002 to 2009, research literature frequently mentioned the renin-
angiotensin system and Ang 1–7, especially in cardiovascular protection, were highlighted. Between 2010 and 2016, a marked in­
crease in attention to ACE2 was observed, indicating a deeper understanding of its role in diabetes, particularly its critical function in
generating Ang 1–7. The actions of angiotensin II, exploring its role in diabetes-related cardiovascular pathologies, were also exten­
sively studied, signifying a refined focus from the overall renin-angiotensin system system to specific components. From 2017 to 2023,
literature focus broadened to encompsss diabetes as a critical global healh issue. The emergence of COVID-19 during this period was
link with diabetes research themes, examining the pandemic’s impact on diabetic patients. Furthermore, there was a rise in studies on
diabetic complications, notably retinopathy and cardiomyopathy, suggesting a growing interest in the disease’s deeper mechanistic
studies. The bibliometric analysis reveals an evolution in ACE2/Ang 1–7/MasR axis research, from initial broad discussions on an­
giotensins and the renin system to detailed investigations of ACE2 and Ang 1–7, and now to studies connecting it with diabetic
complications and COVID-19. This evolution not only highlights a deepening scientific understanding but also reflects shifts in
research interests and foci in response to global health changes.
Ridges plot of research themes can clearly show dynamic changes in thematic research over time, as illustrated by the 14 thematic
clusters presented in Fig. 7C. Continued interest in Islet cell function (cluster#4) and insulin resistance (cluster#7), pivotal pathogenic
mechanisms in diabetic microvascular complications, has been well documented. It has been shown that activation of the ACE2/Ang
1–7 axis enhances glucose metabolism and ameliorates insulin resistance [49–51]. Compared to wild type mice, ACE2-knockout mice
exhibit greater vulnerability to pancreatic β-cell dysfunction induced by high-fat diets [52]. Furthermore, the ACE2/Ang 1–7/MasR
axis contributes to improved glucose tolerance and insulin sensitivity by safeguarding pancreatic β cells, augmenting insulin secretion,
optimizing glucose metabolism in adipose tissue, facilitating glucose uptake in skeletal muscle, and reducing hepatic gluconeogenesis

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[6]. The expression (cluster#8) of ACE2/Ang 1–7/MasR axis components was frequently highlighted, underscoring the need for
enhanced mechanistic studies in diabetes. Utilizing a variety of complementary techniques, the presence of ACE2, Ang 1–7, and MasR
in both human and animal retinas has been established, primarily localizing in the retinal ganglion cell layer, inner plexiform layer,
inner nuclear layer, and photoreceptor outer segments [53–56]. In individuals diagnosed with type 2 diabetes, an increase in ACE2
expression in the pancreas, liver, and adipose tissue has been observed [57]. Additionally, clinical and experimental studies have
indicated that diminished ACE2 expression may contribute to the progression of diabetic renal injury [39,58,59]. Diabetic ne­
phropathy (cluster#0), commonly leading to severe end-stage renal disease, is influenced by oxidative stress and pro-inflammatory
pathways within the angiotensin II and its type 1 receptor axis. Research in the diabetic Akita mouse indicates that human recom­
binant ACE2 administration mitigates kidney injury, lowers blood pressure, and decreases NADPH oxidase activity. In vitro studies
show human recombinant ACE2 enhances Ang 1–7 signaling, reducing angiotensin II levels [60]. Resistance training alters the renal
renin-angiotensin system in diabetes, reducing inflammatory markers such as interleukins and cytokine-induced neutrophil
chemoattractant-1 [51]. Olmesartan treatment in type 2 diabetes patients decreased urinary albumin excretion, linked to increased
serum Ang 1–7 and ACE2 levels, suggesting their therapeutic potential in diabetic nephropathy [61]. However, Ang 1–7’s short plasma
half-life limits its clinical application, leading to the exploration of the lanthionine-stabilized Ang 1–7 (cyclic Ang 1–7) in experimental
studies [62]. Cyclic Ang 1–7, used with lisinopril, shows superior antiproteinuric effects, reduces glomerular fibrosis and inflamma­
tion, and enhanced capillary density compared to lisinopril alone [62]. Retinopathy (cluster#6), a severe microvascular complication
of diabetes leading to blindness, remains a significant concern. It has been shown that activating the ACE2/Ang 1–7/MasR axis may
decrease the risk of retinopathy in diabetic patients [63]. Intravitreal injections of adeno-associated virus-ACE2 or Ang 1–7 have
reduced retinal vascular leakage and inflammation triggered by diabetes, effectively preventing retinopathy [64]. Additionally,
diabetes-induced gut bacterial dysregulation increases the synthesis of microbial peptides, which enter the bloodstream, reach the
retina, and damage retinal vascular endothelial cells via the Toll-like receptor 2-mediated MyD88-ARNO-ARF6 signalling pathway,
thereby exacerbating diabetic retinopathy [36]. ACE2, abundantly expressed in the gut and crucial for maintaining gut barrier
integrity, has been the foucus of recent studies. Elevating enteral ACE2 to enhance gut barrier integrity has been shown to prevent
retinopathy in type 1 diabetes [65]. Furthermore, O-GlcNAcylation modifications regulated by the ACE2/Ang1-7/MasR axis are
believed to ameliorate diabetic retinopathy [66]. Bone marrow (cluster#12) dysfunction significantly influences diabetic retionpathy
pathogenesis by impairing hematopoietic stem/progenitor cells, marked by increased proinflammatory cytokines secretion and
reduced vascular reparative and circulating angiogenic cells (CD34+ cells) populations [36]. Treating diabetic CD34+ cells with
Ang1-7 activates the renin-angiotensin system’s protective mechanism, restoring their functionality through enhance nitric oxide
levels, reduced reactive oxygen species, and improved mobility, thereby aiding retinal vascular repair [40,63]. A recent study has
reported, intrathecal administration of Ang 1–7 attenuates streptozotocin-induced diabetic neuropathic pain, and this occurs through a
mechanism involving spinal MasR and the inhibition of p38 MAPK phosphorylation [67].
ACE2 was identified in 2003 as a critical receptor for severe acute respiratory syndrome coronavirus [68]. With the emergence of
the COVID-19 pandemic, interest in ACE2, especially its pivotal role in viral cell entry, was reignited (cluster#2). This receptor’s
significance is particularly notable in diabetic individuals, who are believed to have increased vulnerability to the virus. Research
efforts have predominantly been directed towards adjusting the ACE2/Ang 1–7 axis to reduce cardiovascular risk in diabetic patients
post-infection. Noteworthy is the surge in studies within the fields of diabetic nephropathy, diabetic cardiomyopathy (cluster#1 and
#3), the adrenergic-angiotensin system (cluster#11), and hydponatraemia (cluster#14), highlighting the escalated awareness of these
complications. Moreover, pandemic-era research has elucidated the intricate interactions between chronic conditions and disease
challenges. These studies collectively enhance our understanding of the interplay between diabetes and coronaviruses, forming a solid
foundation for the formulation of comprehensive public health strategies.
Several limitations inherent in this study must be acknowledged. Firstly, as a bibliometric analysis, the collection and processing of
data heavily depended on software. Although not a substitute for systematic reviews, this approach offers valuable insights through
syntheis of extensive data and visual perspectives. Secondly, the study focused exclusively on English-language publication from
WoSCC database, potentially omitting valuable research. Given WoSCC’s extensive coverage, this oversight is unlikely to significantly
affect the overall trends. Lastly, due to the time lag in citation impact, some recent high-quality studies might be underestimated in
their influence, necessitating future tracking and updates.

5. Conclusion

To summarize, this study highlights the growing importance of the ACE2/Ang 1–7/MasR axis in diabetes and its microvascular
complications through comprehensive bibliometric analysis. It emphasizes the superiority of bibliometric technigues over traditional
reviews and underscores the need for more advanced software tools for deeper and more accurate visual investigations. Ongoing
research in this research field is crucial for furthering our understanding and driving scientific progress.

Declarations

Ethical statement

As there are no animal or human studies presented in this manuscript, including any potentially identifiable human images or data,
ethical approval for this work is not required.

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W. Hu et al. Heliyon 10 (2024) e31405

Funding

This work was supported by grants from the National Natural Science Foundation of China (No.: 82260211, Qiong Zhou and
81460092, Qiong Zhou), the Central Government Guides Local Science and Technology DevelopmentFoundation (No.:
20211ZDG02003, Qiong Zhou), the Key research and development project in Jiangxi Province (No.: 20203BBG73058, Qiong Zhou and
20192BBGL70033, Qiong Zhou), the Chinese medicine science and technology project in Jiangxi province (No.: 2020A0166, Qiong
Zhou). The funding sources: National Natural Science Foundation of China; Ministry of Science and Technology of the People’s Re­
public of China; Science and Technology Department of Jiangxi Province, People’s Republic of China.

Data availability statement

All data generated or analyzed during this study are included in this published article and its supplementary information files.

CRediT authorship contribution statement

Weiwen Hu: Writing – review & editing, Writing – original draft, Visualization, Validation, Software, Methodology, Investigation,
Formal analysis, Data curation, Conceptualization. Jian Tan: Validation, Formal analysis, Data curation. Yeting Lin: Validation,
Formal analysis, Data curation. Yulin Tao: Validation, Formal analysis, Data curation. Qiong Zhou: Writing – review & editing,
Writing – original draft, Validation, Supervision, Methodology, Funding acquisition, Conceptualization.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to
influence the work reported in this paper.

Acknowledgements

We would like to acknowledge all the authors of the research articles uesd for the analysis.

Appendix A. Supplementary data

Supplementary data to this article can be found online at https://doi.org/10.1016/j.heliyon.2024.e31405.

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Abbreviations

ACE2: Angiotensin-converting enzyme 2

Ang 1–7: Angiotensin 1-7
MasR: Mas receptor
TLCS: Total local citation score
TGCS: Total global citation score
IF: Impact factor
WoSCC: Web of science core collection
COVID-19: Corona virus disease 2019
SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2

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