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Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."
Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011
Dr. Shankar P.R.
"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."
Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011 Anuradha
Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.
Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020
Original article / research
Full Version
Endothelial Dysfunction in Type 2 Diabetes Patients and its Association with Microvascular Complications: A Cross-sectional Study
Correspondence Address :
Dr. Siva Ranganathan Green,
1C, Type-I Staff Quarters, MGMCRI Campus, Pillaiyarkuppam, Puducherry-607402, India.
E-mail: srgreen@mgmcri.ac.in
Introduction: The prevalence of Type 2 Diabetes Mellitus (T2DM) is increasing worldwide. Microangiopathic and macroangiopathic complications are the main causes of morbidity and mortality in diabetes. Endothelial dysfunction is important in the early pathophysiology of vascular complications. Screening is very important in order to prevent these complications.
Aim: To investigate endothelial dysfunction, as measured by Flow Mediated Vasodilation (FMD) of the brachial artery, in diabetic individuals. It also aims to explore the correlation between FMD and Glycated Haemoglobin (HbA1c), as well as the association between FMD and microvascular complications such as diabetic neuropathy, diabetic retinopathy, and albuminuria.
Materials and Methods: This cross-sectional study was conducted at Mahatma Gandhi Medical College and Research Institute, Puducherry, India, between 2020 and 2021 on 160 patients. All patients diagnosed with T2DM, attending the Outpatient Department (OPD) or admitted to the ward, were enrolled in the study using consecutive sampling. FMD was measured for each patient, and Urine Albumin Creatinine Ratio (UACR) was also assessed. Diabetic retinopathy was evaluated through fundus examination, and diabetic neuropathy was screened using the monofilament test. Statistical analysis was performed using Statistical Package for Social Sciences (SPSS) version 27.0 to determine the correlation between FMD and these variables.
Results: A total of 160 patients were enrolled in this study, including 104 (65%) males and 56 (35%) females. The median age was 52 years, and the participants had a median Body Mass Index (BMI) of 29.5 kg/m2. The median HbA1c was 8.7%. The median Fasting Blood Sugar (FBS) and Postprandial Blood Sugar (PPBS) levels were 145 mg/dL and 242 mg/dL, respectively. The median FMD among all patients was 5.6%, with an Interquartile Range (IQR) of 4.9% to 6.6%. There was an inverse correlation between HbA1C and FMD values, with a correlation coefficient of -0.718 (p-value <0.01), indicating a strong and significant inverse correlation. Patients with significant macroalbuminuria had a lower median FMD compared to non albuminuric patients, and this difference was statistically significant. The median FMD was also lower in patients with diabetic neuropathy and retinopathy.
Conclusion: The study findings suggest that endothelial dysfunction, as measured by FMD, is significantly impaired in patients with elevated HbA1c and microvascular complications of diabetes mellitus.
Endothelium, Hyperglycaemia, Nitric oxide, Vasodilation
Diabetes mellitus is a chronic metabolic disorder resulting from improper intermediary metabolism due to an absolute or relative deficiency of insulin, leading to hyperglycaemia. The initial phase of hyperglycaemia, which is commonly asymptomatic, accounts for the majority of long-term complications (1). Endothelial dysfunction is considered the initial step in the progression of atherosclerosis and microvascular complications of diabetes mellitus (2). The endothelium, which lines the intimal surface of blood vessels, forms the largest endocrine organ in the human body (3). It plays a crucial role in regulating vascular smooth muscle tone, thrombosis, platelet aggregation, and blood vessel permeability. The endothelium releases vasoactive substances such as prostacyclin, endothelin, endothelial growth factors, interleukins, plasminogen inhibitors, and Nitric Oxide (NO) (4). Altered endothelial function plays a central role in the pathogenesis of vascular complications. The term “endothelial dysfunction” refers to an impairment of the endothelium’s ability to maintain vascular homeostasis properly. NO serves as an important marker of endothelial dysfunction. It is considered the initial step in the progression of atherosclerosis (5).
The endothelial cells sense the laminar stress on the endothelium caused by hyperemia, leading to increased activity of endothelial Nitric Oxide Synthase (eNOS). This, in turn, converts L-arginine to NO. NO activates guanylate cyclase, which stimulates the conversion of guanosine triphosphate to monophosphate. Consequently, this causes smooth muscle relaxation, leading to vasodilation. FMD reflects endothelial function (3). The most widely used non invasive technique for assessing endothelial function is called “FMD”. FMD measures the dilation or widening of a blood vessel in response to increased blood flow, which is a normal response of healthy endothelial cells. This non invasive method is based on the principle that physiological increases in blood flow and endothelial shear stress induce vasodilation, which is mediated by the release of endothelial NO (6). However, FMD is currently classified as class III evidence and is not routinely recommended for screening cardiovascular risk (7),(8). Screening is crucial for preventing chronic complications. FMD can be performed using ultrasound equipment, which is commonly available in most tertiary care hospitals in India (7),(9).
Only a few recent studies in India have combined all these parameters (10),(11). In a study by Ravikumar R et al., conducted on 50 diabetic and non diabetic individuals in the Chennai Urban Population study, it was found that FMD was impaired in diabetic subjects compared to non diabetics (10). Another study by Bhargava K et al., showed that the mean FMD in patients with diabetes only was 5.51% compared to 7.03% in the non diabetic group. Thus, the presence of endothelial dysfunction is considered an early risk factor for coronary artery disease as well (11). The present study aims to correlate endothelial dysfunction, as measured by FMD, in T2DM patients with glycaemic control measured by HbA1c, and to study its association with microvascular complications such as diabetic retinopathy, neuropathy, and albuminuria.
This cross-sectional study was conducted at a tertiary care institute in Puducherry, India, from March 2020 to March 2021. The approval of the Institutional Human Ethics Committee was obtained (letter no MGMCRI/Res/01/2019/41/IHEC/088).
Inclusion criteria: All patients diagnosed with T2DM who attended the OPD and were admitted to the ward were included in the study.
Exclusion criteria: Patients who were on Angiotensin Converting Enzyme Inhibitors (ACEI), had known cases of type 1 diabetes mellitus, end-stage renal disease, chronic liver disease, thyroid disorders, any proven case of peripheral neuropathy other than diabetic neuropathy, stroke, and pregnant or lactating women were excluded from the study.
Sample size: The study population consisted of 160 individuals selected from patients attending the OPD and inpatients using consecutive random sampling. The prevalence of diabetes mellitus was taken as 10.3% based on a previous study (12). The required sample size (n) was calculated using the formula:
d=0.05
Formula:
Z1-α/2=1.96 for a 95% of confidence level with α=0.05
p=10.3%=0.103 (from previous study)
1-p=0.897
d=5%=0.05 (absolute precision)
n1=(1.962×(0.103)(0.897)/(0.05)2
n1=141.9?142
Considering a 10% attrition rate, the final sample size was calculated as follows:
n=n1+n1*10%=142+14.2=156.2
n?160
Procedure
After obtaining written informed consent, demographic details and previous clinical and medical history regarding other co-morbid conditions were recorded. The recent (within two months) HbA1c value was also recorded. Patients were instructed to visit the clinic after an overnight fast, abstaining from smoking, drinking coffee, or taking antioxidant vitamins for atleast 12 hours prior to testing. They were examined in the supine position, following 15 minutes of rest in a dark, quiet, air-conditioned room. Brachial artery FMD was measured during the examination. The right arm was cuffed with a standard blood pressure cuff positioned 5 cm below the antecubital fossa, and the artery was imaged 5 to 9 cm above the antecubital fossa. The cuff was inflated to 50 mmHg above the systolic blood pressure for five minutes. Imaging of the artery was performed before cuff inflation (baseline) and for 1.5 minutes after cuff deflation (5). Normal FMD was considered to be in the range of 7.1-10% (13). Microalbuminuria was diagnosed from concentrations in a spot sample using ACR (Albumin-to-Creatinine Ratio). Microalbuminuria is defined as concentrations ranging from 30 to 299 mg/g (14). Diabetic neuropathy was screened using the monofilament test (15),(16). For the detection of diabetic retinopathy, participants underwent a fundus examination conducted by an ophthalmologist.
Statistical Analysis
The distribution of variables was initially analysed using SPSS version 27.0, and the data was found to have a non normal distribution based on the Kolmogorov-Smirnov test. Therefore, non parametric tests, specifically the Mann-Whitney U test, were used to make comparisons between two groups. To compare two quantitative variables, correlation coefficient was utilised.
The median age of the patients was 52 years (IQR 45-61), indicating that the majority of subjects belonged to the age group of 45 to 61 years. Of the enrolled subjects, 104 were males and 56 were females. The median BMI was 29.5 kg/m2. The median HbA1c was 8.7%, while the median FBS and PPBS were 145 mg/dL and 242 mg/dL, respectively. The median ACR was 21.6 mg/g (Table/Fig 1). The median systolic and diastolic blood pressure was 128 mmHg and 84.6 mmHg, respectively. Diabetic retinopathy and neuropathy were observed in 63 (39.37%) and 53 (33.12%) individuals, respectively. A total of 58 patients had albuminuria (Table/Fig 2).
The median FMD among all patients was 5.6%. Females had a slightly higher FMD compared to males (5.8% vs 5.5%), but this difference was not statistically significant (p-value=0.537). There was an inverse correlation between HbA1c and FMD values, with a correlation coefficient of -0.718 and a p-value of <0.01, indicating a strong and significant inverse correlation (Table/Fig 3).
The median FMD was lower in patients with diabetic neuropathy compared to those without neuropathy, and this difference was statistically significant. In this study, the median FMD in patients with diabetic retinopathy was 5.1% compared to those without diabetic retinopathy, who had a median FMD of 6.0%. Patients with significant macroalbuminuria, as defined by the above ACR cut-off, had a lower median FMD compared to non albuminuric patients, and this difference was statistically significant (Table/Fig 4).
Global literature has provided valuable data on FMD and the correlation between microvascular and macrovascular complications in diabetes mellitus. Most of the data available is from foreign studies, with only a few studies conducted in the Indian population (10),(11),(17),(18). This cross-sectional study was conducted in Puducherry, India aimed to contribute sufficient data on the effect of impaired FMD on the development of chronic complications in patients with T2DM. In this study, the population had a median FMD of 5.6%, which was lower than the normal values reported in recent studies (7.1% to 9%) (13). This suggests that endothelial function, as measured by FMD, was altered in patients with T2DM. The median FMD in males and females was 5.5% and 5.8%, respectively, indicating that FMD was less impaired in females compared to males in present study population, although this difference was not statistically significant (p-value=0.537). There was a significant inverse correlation between FMD and HbA1c. This indicates that endothelial function was affected by poor glycaemic control, resulting in impaired FMD in these individuals. Other studies have also concluded that poor glycaemic control is associated with impaired FMD (17),(18). This can be attributed to vascular endothelial injury caused by increased formation of advanced glycation end products, activation of protein C kinase, and increased flux through the polyol pathway due to hyperglycaemia. These factors lead to increased oxidative stress and reduced levels of NO and eNOS, ultimately resulting in endothelial dysfunction (19),(20),(21).
In the study population, 63 (39.37%) patients had diabetic retinopathy. It was found that patients with diabetic retinopathy had lower FMD values, and this difference was statistically significant (p-value <0.001). Chronic hyperglycaemia leads to the formation of advanced glycation end products and activation of protein C kinase, causing endothelial dysfunction in retinal vessels. This results in altered retinal vascular permeability, damage to pericytes, and ultimately, retinal ischaemia. Similar studies have also concluded that impaired FMD, indicating endothelial dysfunction, is associated with diabetic retinopathy in patients with poor glycaemic control (22),(23). Patients with macroalbuminuria and microalbuminuria had a median FMD values of 4.5% and 5.1%, respectively, indicating that FMD was lower in patients with macroalbuminuria compared to those with microalbuminuria. Yokoyama H et al., conducted a study in 158 diabetics in Japan to assess the relationship between FMD and microalbuminuria, independent of cardiovascular risk factors. They demonstrated that impaired FMD was associated with increased age, albuminuria, BMI, and decreased eGFR. Similar findings were reported in studies conducted by Ito H et al., and Stehouwer CDA et al., (22),(24),(25). These studies suggest that patients with albuminuria have endothelial dysfunction. Initially, there is a stage of hyperfiltration due to hyperglycaemia, followed by vascular endothelial injury caused by increased formation of advanced glycation end products, activation of protein C kinase, and increased flux through the polyol pathway due to hyperglycaemia, which ultimately leads to nephropathy (25),(26).
Among the 160 patients, 53 (33.12%) had diabetic neuropathy. Individuals with diabetic neuropathy had a median FMD of 5.0%, which was significantly lower compared to patients without diabetic neuropathy, who had a median FMD of 5.8% (p-value <0.001). Additionally, a similar cross-sectional study conducted by Roustit M et al., found that endothelial dysfunction is strongly associated with Diabetic Peripheral Neuropathy (DPN) and may serve as a potential mediator between cardiovascular risk factors and DPN. FMD of the brachial artery, a measure of endothelial function, was significantly associated with DPN. These findings suggest that early endothelial dysfunction may contribute to the development of DPN in individuals with diabetes (27).
Limitation(s)
This study did not consider the duration of diabetes and the effect of dyslipidaemia on FMD, both of which are observed in patients with diabetes. Therefore, further studies should be conducted to investigate the impact of diabetes duration and dyslipidaemia on FMD. Additionally, it is important to note that this was a cross-sectional study, and further follow-up studies are needed to establish a correlation between improvements in FMD and better glycaemic control.
Patients with T2DM exhibit endothelial dysfunction, as evidenced by impaired FMD. Endothelial dysfunction increases the risk of microvascular complications of diabetes, such as diabetic retinopathy, neuropathy, and albuminuria. Therefore, achieving good glycaemic control and implementing lifestyle changes are crucial in preventing these complications. Consequently, FMD holds prognostic significance and can be utilised to assess the response to interventions.
DOI: 10.7860/JCDR/2024/61444.18899
Date of Submission: Nov 13, 2022
Date of Peer Review: Mar 02, 2023
Date of Acceptance: Nov 20, 2023
Date of Publishing: Jan 01, 2024
AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. Yes
PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Nov 15, 2022
• Manual Googling: Apr 19, 2023
• iThenticate Software: Nov 17, 2023 (8%)
ETYMOLOGY: Author Origin
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