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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
Serum Homocysteine and C-reactive Protein Levels in Diabetic Patients with Nerve Conduction Velocity Proven Neuropathy: A Cross-sectional Study
Correspondence Address :
Vijayashree Gokhale,
Professor, Department of General Medicine, Dr. D.Y. Patil Medical College, Hospital and Research Centre, Dr. D.Y. Patil Vidyapeeth, Pune-411018, Maharashtra, India.
E-mail: vijayashree.gokhale@dpu.edu.in
Introduction: Diabetic Neuropathy (DN) is a well known difficult to treat microvascular complication of diabetes. Based on Nerve Conduction Velocity (NCV) studies, DN has been classified into various types. Many possible aetiologies have been proposed. C-Reactive Protein (CRP) plays a role in the development of diabetic microvascular complications, while Homocysteine (Hcys) can harm the endothelium by inducing excessive sulfation of connective tissue.
Aim: To study the levels of Hcys and CRP in NCV-proven patients with DN and to associate these levels with the type of DN.
Materials and Methods: This was a cross-sectional study conducted at a semi-urban medical college hospital in Western Maharashtra, India, between February 2022 and May 2024. The study included 70 patients over 18 years of age with NCV-proven DN in Type 2 Diabetes Mellitus (DM), in whom serum Hcys and CRP levels were evaluated. Data collected were analysed using Statistical Package for Social Sciences (SPSS) software version 26.0.
Results: A total of 32 female participants (45.7%) and 38 male participants (54.3%). Among the study participants, 23 (32.9%) had a duration of diabetes of 5-10 years, and 47 (67.1%) had a mixed type of neuropathy. Elevated Hcys levels were observed in 18 (25.7%) participants, while 49 (70%) showed elevated CRP levels. CRP levels were raised in the mixed type of neuropathy, with 35 (71.4%) affected, while elevated Hcys levels were observed among the sensory neuropathies in 6 (33.3%) participants.
Conclusion: No significant association was found between elevated Hcys and CRP levels and the type of neuropathy.
Hyperhomocysteinemia, Mixed neuropathy, Neurodegeneration
Diabetes is a persistent metabolic disorder characterised by increased levels of blood glucose, commonly referred to as blood sugar (1). DN is a medical condition that occurs when the peripheral and autonomic nerve systems are damaged, leading to a variety of clinical symptoms. It is the most common type of neuropathy. Neuropathy, also known as nerve injury, can manifest with various symptoms that may occur throughout the body or in localised regions. The pathogenesis of this condition is primarily defined by metabolic and inflammatory damage that specifically affects the peripheral nerves responsible for transmitting motor and sensory signals. Diabetic Peripheral Neuropathy (DPN) significantly increases the risk of developing ulcers and amputations in the lower extremities, ultimately leading to disability (2),(3).
Risk factors associated with the onset and progression of Diabetic Sensory Polyneuropathy (DSP) include an HbA1c level greater than 7%, male gender, insulin therapy, being ethnically non-Hispanic Black, advanced age, longer duration of DM, dyslipidemias, albuminuria, and a history of Systemic Hypertension (SH) (4).
Progressive DN is characterised by the retraction and degeneration of sensory axons in the peripheral nervous system, while the cell bodies remain relatively intact. The pattern of involvement in DN, known as the “stocking and glove” pattern, indicates that damage primarily affects the longest sensory axons. This means that the loss of distal leg epidermal axons occurs before the loss in more proximal limbs. Due to this characteristic, DN is classified as a length-dependent neuropathy. While DN is not primarily classified as a demyelinating neuropathy, it does affect Schwann cells. In more severe cases of DN, individuals may exhibit signs of demyelination (5).
The C-reactive Protein is a biomarker that indicates inflammation in the body. CRP is a member of the pentraxin family, and the liver is the main organ responsible for synthesising this acute phase reactant. High concentrations of CRP in the blood result from trauma, inflammatory conditions, and acute infections (6). There is evidence suggesting that CRP plays a role in the development of diabetic microvascular problems, including retinopathy, nephropathy, and neuropathy. High levels of glucose can lead to changes in small blood vessels and an increase in the production of inflammatory substances such as TNF-α, IL-6, and CRP (7).
Homocysteine (Hcys) is a sulfur-containing amino acid generated from methionine, and it is known to be toxic and non proteinogenic. It occupies a junction where several metabolic pathways intersect and is synthesised from methionine through several transmethylation processes (8),(9). Prior research has indicated that Hcys can harm the endothelium by inducing excessive sulfation of connective tissue (8),(9).
Thus, DN is a common and debilitating complication of diabetes, leading to significant morbidity. Early identification of biomarkers that correlate with the type and severity of neuropathy can aid in better management and prognosis. Therefore, the present study was undertaken to understand how homocysteine (Hcys) and CRP levels relate to different types of DN, which could provide valuable insights for personalised treatment strategies and help identify patients at higher risk for more severe forms of neuropathy.
To study Hcys and CRP levels in NCV-proven patients with DN and to associate serum Hcys and CRP levels with the type of DN.
This cross-sectional study was conducted at a semi-urban medical college hospital in Western Maharashtra, India, from February 2022 to May 2024. The study targeted known cases of Type 2 Diabetes with NCV-proven neuropathy. Participants were recruited from the general medicine wards, the Diabetes Outpatient Department (OPD), and among those admitted to the wards. The study protocol received approval from the Institutional Ethics Committee (IESC/PGS/260/2022).
Inclusion criteria: Patients aged 18-80 years with Type 2 DM and NCV-proven neuropathy were included.
Exclusion criteria: patients with Neuropathy due to other causes and patients on vitamin B12 supplements were excluded from the study.
Sample size calculation: Considering the prevalence of DN at 18.84% in the study “Prevalence and Risk Factors for Severity of DN in Type 2 DM” by Rani PK et al., with a 95% confidence interval and an acceptable difference of 9.8%, the calculated sample size was 62 (10). The software used for this calculation was WinPepi. Therefore, selecting a sample size of 70 aligns with established research norms and ensures comparability with existing literature. Informed written consent was obtained from all patients. Purposive sampling was employed, selecting all consecutive cases of NCV-proven DN that met the inclusion criteria until the desired sample size was achieved.
Study Procedure
Clinical histories were recorded, the duration of diabetes was noted, and clinical examinations were conducted. Blood samples were drawn randomly under aseptic conditions to measure serum Hcys and CRP. The samples were centrifuged to separate serum and plasma. Serum Hcys levels were measured using the chemiluminescence immunoassay method (laboratory normal range: 5.08-15.39 micromol/liter), and serum CRP levels were measured using the nephelometry method (laboratory normal range: up to 5.0 mg/L).
Statistical Analysis
Data were collected using pre-formed data collection and case record forms. Data entry was performed in Microsoft excel and analysed using Statistical Package for Social Sciences (SPSS) software version 26.0. Categorical variables were expressed in terms of frequency and percentage, while continuous variables were expressed in terms of mean and SD. The association between various study parameters was analysed using the Chi-square test or Fisher’s exact test, with p-value≤0.05 considered significant.
The mean age of study participants was 57.6±10.71 years (range: 18-80 years). Out of 70 participants, the majority were in the age group of 51-60 years (22, 31.4%) and 61-70 years (22, 31.4%). Of the participants, 38 (54.3%) were male and 32 (45.7%) were female, resulting in a male-to-female ratio of 1.2:1. Additionally, 23 (32.9%) patients had diabetes for a duration of 5-10 years. The mean duration of diabetes among participants was 12.0±7.06 years (range: 1-32 years) (Table/Fig 1).
Out of the 70 participants, 47 (67.1%) had mixed neuropathy, 12 (17.1%) had pure sensory neuropathy, 7 (10%) had carpal tunnel syndrome, 3 (4.3%) had pure motor neuropathy, and 1 (1.4%) had polyneuropathy (Table/Fig 2).
Normal serum Hcys levels were found in 52 (74.3%) participants, while 18 (25.7%) patients had raised serum Hcys levels (Table/Fig 3). A total of 49 (70%) patients had raised CRP levels (Table/Fig 4).
(Table/Fig 5) shows the relationship between the type of DN and Hcys values. Upon analysing the study findings using the Chi-square test, there was no significant association between raised Hcys levels and the type of DN (p-value=0.307). Similarly, there was no significant association between raised serum CRP levels and the type of DN among the study participants (p-value=0.426) (Table/Fig 6).
The present study aimed to investigate Hcys and CRP levels in NCV-proven patients with DN and to associate serum Hcys and CRP levels with the type of DN. The study found no significant association between raised Hcys and CRP levels and the type of DN. This study revealed that most of the participants, i.e., 47 (67.1%), had mixed neuropathy, 12 (17.1%) had pure sensory neuropathy, 7 (10%) participants had carpal tunnel syndrome, 3 (4.3%) participants had pure motor neuropathy, and 1 (1.4%) participant had polyneuropathy. A study conducted by Papanas N and Ziegler D observed that patients with Distal Sensorimeter Polyneuropathy (DSPN) frequently suffer from Diabetic Autonomic Neuropathy (DAN) (11). A study conducted by Fahmy E et al., found that 57.69% of patients had distal sensory polyneuropathy, 23.08% had both distal sensory polyneuropathy and lower motor facial palsy, and 19.23% had distal sensory-motor polyneuropathy (12). The ankle reflex was absent in 18 individuals, accounting for 69.23% of the total, and reduced in eight patients, representing 30.77%. Twelve individuals (46.15%) exhibited a deficit in deep sensation.
In the present study, the mean duration of diabetes among participants was 12.0±7.06 years (range: 1-32 years). A study conducted by Rujaswini T et al., revealed that the mean duration of diabetes was 3.18±1.6 years in participants without neuropathy and 5.71±1.8 years in participants with neuropathy (13). A study conducted by Lin XY et al., observed that the mean duration of diabetes in patients with DN was 8.82±4.75 years (14). Another study conducted by Doupis J et al., reported that the mean duration of diabetes among study participants was 20±13 years (15).
This study revealed raised serum Hcys levels in only 18 (25.7%) participants. Hcys plays a role in the progression of DN in individuals with type 2 diabetes, and high levels of Hcys are likely linked to DN (16). A study conducted by Rujaswini T et al., revealed that the mean serum Hcys level without DN was 6.8±2.9, while the serum Hcys level with DN was 21.6±0.29, with a p-value of 0.0017 (13). The association between serum Hcys and DN was found to be statistically significant (p-value=0.001). A study conducted by Ambrosch A et al., showed that the frequency of hyperhomocysteinemia was significantly greater in patients with DN compared to those without neuropathy (17). This suggests that Hcys is independently associated with the prevalence of DN in a group of type 2 diabetic patients. Cohen JA et al., found a significant correlation between total Hcys (tHcy) and DAN (18). However, there was no correlation between tHcy and Diabetic Sensorimotor Peripheral Neuropathy (DSPN). Their conclusion suggests that hyperhomocysteinemia may be a risk factor for DAN, but not for diabetic Sensorimotor Polyneuropathy (DSPN). This may be associated with unequal damage to small nerve fibers.
A case-control study conducted by Fahmy E et al., examined 42 participants, including 26 diabetic individuals and 16 healthy individuals (12). The study found that diabetic patients had significantly higher plasma levels of Hcys compared to the control group (p-value=0.001). Furthermore, elevated serum Hcys levels were found to be associated with the presence of DN in type 2 diabetic patients. A study conducted by Guo H et al., showed that patients with DN exhibited higher levels of serum Hcys compared to those without DN (16). Additionally, there was a strong correlation between hyperhomocysteinemia and an elevated risk of DPN in individuals diagnosed with type 2 diabetes. Hcys serves as a biomarker for DN and shows potential for use in preventing or treating this condition.
In this study, 70% of the patients had raised CRP levels; however, no significant association was found between the type of neuropathy and raised CRP levels. A study conducted by Banait T et al., revealed a significant correlation between elevated blood CRP levels and an increased risk of developing type 2 DM and neurodegenerative disorders (19). A study conducted by Kang ES et al., found that there were no differences between the mean serum high-sensitivity CRP (hsCRP) levels of those with and without neuropathy (p-value>0.05) (20). Najafi L et al., observed a significant difference in serum hsCRP levels between patients with nephropathy and those without nephropathy (p-value=0.003) (21). Hassaan A et al., found that CRP levels were non-significantly higher in diabetic patients with microvascular complications compared to those without complications (p-value=0.35) (22). Aslam M and Chandrasekhara P discovered a significant positive correlation between hsCRP levels and microvascular complications (p-value<0.0001) (23).
Previous studies by Hassaan A et al., and Aslam M suggested that Hcys may damage the endothelium through excessive sulfation of connective tissues (22),(23), while vascular risk factors have been linked to DN. Therefore, Hassaan A et al., and Aslam M and Chandrasekhara P hypothesised that the status of Hcys is associated with the risk and progression of neuropathy in type 2 diabetes (22),(23). In addition to increased levels of Hcys, high levels of CRP have also been found to be associated with diabetic polyneuropathy and some neuropathic deficits. The treatment of DN has always been challenging and has never been completely successful. Various aetiologies have been proposed. In this study, comparing Hcys levels and CRP levels among the various types of DN revealed that mixed types of diabetic neuropathies had higher serum CRP levels, indicating inflammation possibly due to end glycation products, while sensory DN showed higher serum Hcys levels. Thus, B12 supplementation may yield better results in this context.
Limitation(s)
The cross-sectional nature of this study design limits the inference of a causal relationship between the correlates and DPN. Therefore, the present findings need to be confirmed in prospective studies with larger sample sizes.
A total of 25.7% of the participants showed raised Hcys levels, and 70% showed raised CRP levels. No significant association was found between raised Hcys and CRP levels and the type of neuropathy. However, mixed-type DN had elevated CRP levels, indicating a possible inflammatory process. These findings highlight the need for further research with larger sample sizes to validate these associations and enhance treatment approaches.
The authors would like to thank the Department of Neurology for the NCV studies and the Department of Biochemistry for conducting the serum Hcys and CRP tests.
DOI: 10.7860/JCDR/2024/73825.20235
Date of Submission: Jun 25, 2024
Date of Peer Review: Jul 26, 2024
Date of Acceptance: Aug 20, 2024
Date of Publishing: Nov 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:
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ETYMOLOGY: Author Origin
EMENDATIONS: 7
- Emerging Sources Citation Index (Web of Science, thomsonreuters)
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