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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
A Cross-sectional Study to Assess Neutrophil Lymphocyte Ratio as a Predictor of Microvascular Complications in Type 2 Diabetes Mellitus Patients
Correspondence Address :
Himanshu Verma,
Associate Professor and Head, Department of Nephrology, VMMC and Safdarjung
Hospital, Delhi, India.
E-mail: himanshu.verma16@gmail.com
Introduction: Neutrophil Lymphocyte Ratio (NLR) is a novel marker of chronic inflammation that exhibits a balance of two interdependent components of the immune system and can be used to predict microvascular complications in diabetes.
Aim: To study the NLR in type 2 diabetes patients and its association with microvascular complications in these patients.
Materials and Methods: This was a cross-sectional study conducted over 18 months at Safdarjung Hospital, New Delhi. Eighty patients of type 2 Diabetes Mellitus (DM) were selected for the study. Detailed history was taken including duration of DM, symptoms suggestive of any complications or co-morbidity and treatment history. Physical examination (height and weight) and systemic examination was performed to check for presence of any diabetic complications. NLR was obtained from the complete blood counts by dividing the absolute number of neutrophils to the absolute number of lymphocytes. Data recorded were analysed using Statistical Package for Social Sciences (SPSS) software version 21.0 Logistic regression analysis and Receiver Operating Curve (ROC) curve were used.
Results: Total 38.7% (31) of the patients had high NLR, with mean±Standard Deviation (SD) of NLR being 3.29±1.49. There was a statistically significant association between poorly controlled diabetes HbA1C >7%, high-sensitivity C-Reactive Protein (hs-CRP) levels and NLR. NLR was found to be the best predictor of diabetic neuropathy and diabetic nephropathy. NLR was also significantly higher in DM patient having more than one microvascular complication.
Conclusion: NLR can be used as a simple parameter to predict presence of diabetic microvascular complications. Thus, an early diagnosis and subsequently targeting inflammatory pathways could possibly be a component of the strategies to prevent and control diabetes related complications.
Inflammation, Nephropathy, Neuropathy
India is home to 69.1 million people with DM and is estimated to have the second highest number of cases of DM in the world after China (1). Type 2 DM due to insulin resistance and an inadequate compensatory insulin secretion, accounts for 90% of all the diabetic cases globally (2). The microvascular complications of diabetes are retinopathy, nephropathy and neuropathy. Although chronic hyperglycaemia is an important etiological factor leading to complications of DM, the mechanism by which it leads to such diverse cellular and organ dysfunction is still unknown (3). Glycated proteins cause damage to cells and impair their function, which induces the production of inflammatory cytokines like CRP, Tumour Necrosis Factor-alpha (TNF-α), Interleukin-6 (IL-6) and free radicals. Activation of inflammatory processes appear to be one of the major mechanisms responsible for vascular damage leading to clinically well recognised complications of DM (4).
Number of leukocytes in the circulation change during the inflammatory response; neutrophilia is associated with relative lymphopenia (5). An index has thus been subsequently generated to reflect both neutrophilia, which accompanies the acute state of inflammation, and lymphopenia, which is a response to physiological stress. This index, which is the NLR, has been demonstrated to be a reliable indicator of the inflammatory status (6). NLR is a novel marker of chronic inflammation that exhibits a balance of two interdependent components of the immune system; neutrophils, which mediate the first line of inflammatory defense, whereas lymphocytes are the regulatory and protective component of inflammation (7). NLR has proven its usefulness in the stratification of mortality in major cardiac events and as a strong prognostic factor in several types of cancers (8),(9).
Recent studies have shown that NLR was significantly higher in type 2 DM patients with microvascular complications as compared to those without these complications (10),(11),(12). Thus, due to its easy availability and inexpensive method of determination, NLR is emerging as a simple parameter to assess inflammatory status of a patient as compared to estimation of IL-1, IL-6, TNF-α, etc., which are expensive and cumbersome. Most of the studies have shown NLR association with individual microvascular complications in diabetes and also have not taken into account the cumulative effect of all the three microvascular complications. Thus, this study has been undertaken to evaluate NLR and its correclation with microvascular complications in type 2 diabetic patients.
This cross-sectional study was conducted over a period of 18 months from November 2017 to April 2019 at Safdarjung Hospital, New Delhi, India. Eighty patients of type 2 DM who fulfilled the inclusion criteria were selected for the study.
Consent was taken from the patients after mentioning both verbally and in writing the purpose of the study, the study procedure, maintaining their confidentiality and their right to refuse participation and/or withdrawal from the study at any stage. Institutional Ethics Committee clearance was also obtained (IEC No.- 2017-099).
Sample size calculation: Relation of NLR to microvascular complications of DM was studied by Srinivas B et al., (13). The study observed the sensitivity and specificity of NLR for assessment of microvascular complication to be 71.43% and 78.95%, respectively and out of 40 cases, 21 cases had microvascular complications. Taking these values as reference, the minimum required sample size with desired precision of 15% and 5% level of significance was 67 patients. To reduce margin of error, total sample size taken was 80.
Inclusion criteria: Patients with type 2 DM, both male and female, above the age of 30 years were selected for the study.
Exclusion criteria: Type 2 DM patients with any of the following conditions: history of any infectious disease within the past one week; any non infectious immunological disease; significant smoking history; Body Mass Index (BMI) >30 kg/m2; coronary artery disease; heart failure; malignancy; pregnancy were excluded from the study.
Study Procedure
Detailed history was taken including duration of DM, symptoms suggestive of any complications or co-morbidity and complete treatment history. Complete physical examination was done including measurement of height, weight, BMI and detailed systemic examination was performed for the presence of any diabetic complications. Criteria for diagnosing DM in the study was Fasting Plasma Glucose of ≥7 mmol/L (126 mg/dL) or two hour post prandial blood glucose ≥11.1 mmol/L (200 mg/dL) or Glycosylated haemoglobin (HbA1c) ≥6.5% (3). In these patients, a random spot urine test with protein creatinine ratio of more than 30 unit on two or more occasions three months apart was defined as diabetic nephropathy (3). For suspected diabetic neuropathy, 10 gm monofilament test was performed to check for sensation and any abnormality was confirmed with Nerve Conduction Velocity (NCV) test (14). Diabetic retinopathy was screened by fundus examination after dilation with a mydriatic and classified into Non Proliferative Diabetic Retinopathy (NPDR), Proliferative Diabetic Retinopathy (PDR) and macular oedema (15). Data were recorded in a proforma designed for the study. Routine investigations were performed for these patients - fasting blood sugar levels, postprandial blood sugar levels, HbA1c was measured using A1C Now+®, kidney function tests, liver function tests, serum lipid profile, highly sensitive C-Reactive Protein (Hs-CRP), urine routine and microscopy, urinary albumin excretion was determined using MICRAL-TEST®, fundus examination, electrocardiogram, chest X-ray, NCV (whenever indicated).
Complete blood count with Erythrocyte Sedimentation Rate (ESR), including haemoglobin, total leukocyte count, Differential Leukocyte Count (DLC) and platelet count were measured using automated analyser Sysmex XT-2000i.
The NLR was obtained from the complete blood counts by dividing the absolute number of neutrophils to the absolute number of lymphocytes. A cut-off NLR value of more than 3.53 was considered to be high (16).
Statistical Analysis
The data was entered in Microsoft excel spreadsheet and analysis was done using Statistical Package for Social Sciences (SPSS) version 21.0. Categorical variables were presented as number and percentage (%) and continuous variables were presented as mean±SD and median. Normality of data was tested by Kolmogorov-Smirnov test. The normality was rejected and non parametric tests were used. Quantitative variables were compared using Independent t-test/Mann-Whitney Test between the two groups. Qualitative variables were correclated using Chi-Square test/Fisher’s-Exact test. Spearman rank correlation coefficient was used to assess the association of various parameters with NLR. Receiver operating characteristic curve was used to find out cut-off point of parameters for predicting various microvascular complications. A p-value of ≤0.05 was considered statistically significant.
Amongst 80 patients, 47 (58.8%) were male and 33 (41.2%) were female. Minimum age of study population was 37 years and maximum was 84 years. Mean age (SD) was 59.89 (10.9) years. Mean (SD) duration of diabetes was 8.62 (5.33) years, 54 (67.5%) patients had poor glycaemic control (HbA1c >7%), mean (SD) HbA1c was 7.1% (1.1%). Total 45% patients had high hs-CRP >3 mg/L indicating high state of inflammation. The mean (SD) hs-CRP value was 5.135 mg/L (4.46 mg/L).
Microvascular complications were found in 68.75% of patients (Table/Fig 1). Distribution of microvascular complications in study subjects is demonstrated in (Table/Fig 2). Out of 39 patients having nephropathy, 30 had microalbuminuria and 9 had macroalbuminuria. NPDR was present in 15 patients, 9 patients had NPDR with macular oedema, while 8 patients had PDR. Out of 23 patients with diabetic neuropathy, 5 had autonomic neuropathy while the rest had polyneuropathy. A total of 38.7% patients had high NLR (Table/Fig 3). Mean NLR was 3.29±1.49. There was a statistically significant association between poorly controlled diabetes HbA1C >7% and high NLR (p-value of 0.012). A significant positive correlation was also found between high NLR levels and high HsCRP levels (p-value 0.01). There was no correlation between high NLR with age of these patients and duration of diabetes. High NLR was significantly associated with diabetic nephropathy (Table/Fig 4) and neuropathy (Table/Fig 5), but was not associated with retinopathy (Table/Fig 6). There was a statistically significant association of high NLR with the presence of all three microvascular complications together in these diabetic patients (Table/Fig 7).
Logistic regression analysis revealed NLR to be the best predictor of diabetic neuropathy followed by diabetic nephropathy (Table/Fig 8). The values of area under curve derived from ROC curve for, diabetic nephropathy (Table/Fig 9), diabetic retinopathy (Table/Fig 10), and diabetic neuropathy (Table/Fig 11) were 0.668 (95% CI of 0.554 to 0.769, p-value 0.0062), 0.578 (95% CI: 0.462 to 0.687, p-value 0.2475) and 0.718 (95% CI: 0.606 to 0.813, p-value 0.0019), respectively. Thus, it can be seen that the strongest association was seen between NLR and diabetic neuropathy.
Hyperglycaemia in diabetes leads to generation of glycated proteins which damage the cells in various ways, including impaired cellular function, and subsequently induces the production of inflammatory cytokines like CRP, TNF-α, IL-6, etc., (3). This inflammation contributes to development of microvascular complications. NLR is an inexpensive and easily available marker to assess the inflammatory status in these patients. This study was conducted to assess NLR in diabetic patients and its correlation with age, duration of diabetes, HbA1c and microvascular complications. The statistically significant association found between high NLR and high HbA1c could be corroborated with the fact that maintaining a good HbA1c can help in reducing inflammation in diabetes and subsequent microvascular complications.
In this study, out of 39 patients with nephropathy, 53.84% had a high NLR and this correlation was found to be statistically significant. A study by Zhang J et al., found increased NLR to be associated with worsening renal function and corresponded with increased severity of histological lesions in patients with diabetic nephropathy (17). Indian studies by Khandare SA et al., and Chittawar S et al., also found high NLR values to be significantly associated with diabetic nephropathy. Inflammatory and oxidative pathways lead to intraglomerular haemodynamic abnormalities, alteration of extracellular matrix and glomerular basement membrane ultimately leading to development of diabetic nephropathy (12),(18).
Amongst 32 patients with diabetic retinopathy 50% had a high NLR. No statistically significant association was found between diabetic retinopathy and high NLR in the study. Similarly, a study conducted by Ciray H et al., also showed no significant association of high NLR between diabetics having retinopathy and those without retinopathy (19). In contrast Ulu SM et al., demonstrated NLR to be a quick and reliable prognostic marker for diabetic retinopathy and its severity (20). The exact reason behind the contrasting findings in these studies are not known but may be due to variations in baseline glycaemic status of the study population.
In this study, out of 23 diabetics with neuropathy, 65.21% had a high NLR. A highly significant correlation was found between high NLR and diabetic neuropathy. Moursy EY et al., also found a significant association between high NLR and diabetic neuropathy (10). A study by Xu T et al., showed that diabetic peripheral neuropathy was significantly associated with high NLR (21). Ischemic reperfusion injury induced inflammatory response in diabetic nerves is believed to be responsible for the pathogenesis of diabetic neuropathy (12). In diabetics having all the three microvascular complications, 77.77% of 9 patients had a high NLR and this association was also found to be statistically significant. From regression analysis, high NLR was found to be the best predictor for diabetic neuropathy followed by diabetic nephropathy.
Limitation(s)
This study is limited by the fact that it was cross-sectional without any follow-up of the study subjects.
It is clear that high NLR was associated with microvascular complications in type 2 DM patients and can be used as a reliable predictor. It can be a cheaper and simpler alternative to IL-6, TNF-α and Hs-CRP for assessing inflammation in diabetic patients. To the best of our knowledge this is the first Indian study to find NLR as an independent predictor of diabetic neuropathy and also to study the correlation of NLR in diabetics having more than one microvascular complications.
Based on the findings of this study, NLR offers a relatively simpler tool for predicting future development of microvascular complications in diabetes patients. Such patients can be screened more extensively and frequently. Early diagnosis and subsequently targeting inflammatory pathways could possibly be a component of the strategies to prevent and control diabetes related complications.
10.7860/JCDR/2021/47046.15266
Date of Submission: Oct 13, 2020
Date of Peer Review: Dec 07, 2020
Date of Acceptance: Apr 19, 2021
Date of Publishing: Aug 01, 2021
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. NA
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