Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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Dr Mohan Z Mani

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On Sep 2018




Prof. Somashekhar Nimbalkar

"Over the last few years, we have published our research regularly in Journal of Clinical and Diagnostic Research. Having published in more than 20 high impact journals over the last five years including several high impact ones and reviewing articles for even more journals across my fields of interest, we value our published work in JCDR for their high standards in publishing scientific articles. The ease of submission, the rapid reviews in under a month, the high quality of their reviewers and keen attention to the final process of proofs and publication, ensure that there are no mistakes in the final article. We have been asked clarifications on several occasions and have been happy to provide them and it exemplifies the commitment to quality of the team at JCDR."



Prof. Somashekhar Nimbalkar
Head, Department of Pediatrics, Pramukhswami Medical College, Karamsad
Chairman, Research Group, Charutar Arogya Mandal, Karamsad
National Joint Coordinator - Advanced IAP NNF NRP Program
Ex-Member, Governing Body, National Neonatology Forum, New Delhi
Ex-President - National Neonatology Forum Gujarat State Chapter
Department of Pediatrics, Pramukhswami Medical College, Karamsad, Anand, Gujarat.
On Sep 2018




Dr. Kalyani R

"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



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Professor and Head
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Sri Devaraj Urs Medical College
Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
On Sep 2018




Dr. Saumya Navit

"As a peer-reviewed journal, the Journal of Clinical and Diagnostic Research provides an opportunity to researchers, scientists and budding professionals to explore the developments in the field of medicine and dentistry and their varied specialities, thus extending our view on biological diversities of living species in relation to medicine.
‘Knowledge is treasure of a wise man.’ The free access of this journal provides an immense scope of learning for the both the old and the young in field of medicine and dentistry as well. The multidisciplinary nature of the journal makes it a better platform to absorb all that is being researched and developed. The publication process is systematic and professional. Online submission, publication and peer reviewing makes it a user-friendly journal.
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Dr Saumya Navit
Professor and Head
Department of Pediatric Dentistry
Saraswati Dental College
Lucknow
On Sep 2018




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Their prompt and timely response to review's query and the manner in which they have set the reviewing process helps in extracting the best possible scientific writings for publication.
It's a honour and pride to be a part of the JCDR team. My very best wishes to JCDR and hope it will sparkle up above the sky as a high indexed journal in near future."



Dr. Arunava Biswas
MD, DM (Clinical Pharmacology)
Assistant Professor
Department of Pharmacology
Calcutta National Medical College & Hospital , Kolkata




Dr. C.S. Ramesh Babu
" Journal of Clinical and Diagnostic Research (JCDR) is a multi-specialty medical and dental journal publishing high quality research articles in almost all branches of medicine. The quality of printing of figures and tables is excellent and comparable to any International journal. An added advantage is nominal publication charges and monthly issue of the journal and more chances of an article being accepted for publication. Moreover being a multi-specialty journal an article concerning a particular specialty has a wider reach of readers of other related specialties also. As an author and reviewer for several years I find this Journal most suitable and highly recommend this Journal."
Best regards,
C.S. Ramesh Babu,
Associate Professor of Anatomy,
Muzaffarnagar Medical College,
Muzaffarnagar.
On Aug 2018




Dr. Arundhathi. S
"Journal of Clinical and Diagnostic Research (JCDR) is a reputed peer reviewed journal and is constantly involved in publishing high quality research articles related to medicine. Its been a great pleasure to be associated with this esteemed journal as a reviewer and as an author for a couple of years. The editorial board consists of many dedicated and reputed experts as its members and they are doing an appreciable work in guiding budding researchers. JCDR is doing a commendable job in scientific research by promoting excellent quality research & review articles and case reports & series. The reviewers provide appropriate suggestions that improve the quality of articles. I strongly recommend my fraternity to encourage JCDR by contributing their valuable research work in this widely accepted, user friendly journal. I hope my collaboration with JCDR will continue for a long time".



Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
The journal has a monthly publication and the articles are published quite fast. In time compared to other journals. The on-line first publication is also a great advantage and facility to review one's own articles before going to print. The response to any query and permission if required, is quite fast; this is quite commendable. I have a very good experience about seeking quick permission for quoting a photograph (Fig.) from a JCDR article for my chapter authored in an E book. I never thought it would be so easy. No hassles.
Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".



Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


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

Important Notice

Original article / research
Year : 2021 | Month : September | Volume : 15 | Issue : 9 | Page : BC04 - BC07 Full Version

Comparison of Serum Vitamin B12 Levels in Type 2 Diabetes Mellitus Patients with and without Diabetic Retinopathy: A Case-control Study


Published: September 1, 2021 | DOI: https://doi.org/10.7860/JCDR/2021/48346.15376
Supriya, Mangala Narayan Sirsikar

1. Assistant Professor, Department of Biochemistry, Oxford Medical College Hospital and Research Centre, Bengaluru, Karnataka, India. 2. Associate Professor, Department of Biochemistry, Vydehi Institute of Medical Sciences and RC, Bengaluru, Karnataka, India.

Correspondence Address :
Dr. Mangala Narayan Sirsikar,
Associate Professor, Department of Biochemistry, Vydehi Institute of Medical Sciences and Research Centre, Nallurhalli, Whitefield, Bengaluru-560066, Karnataka, India.
E-mail: biochem_mangala2931@vimsmail.com

Abstract

Introduction: Diabetes mellitus is characterised by hyperglycaemia. Chronic elevation of hyperglycaemia lead to generation of free radicals and Advanced Glycation End products (AGEs) which results in damage of many organs such as heart, kidney, eyes, nerves and blood vessels. Diabetic Retinopathy (DR) is the leading cause of blindness among diabetic patients. Vitamin B12 is a vital micronutrient that is essential for the proper functioning of the central nervous, cardiovascular and haemopoetic systems. It is also found that its deficiency is more prevalent in Type 2 Diabetes Mellitus (T2DM) and evident clinically.

Aim: To compare the serum vitamin B12 levels and Glycated Haemoglobin (HbA1c) levels in patients with and without diabetic retinopathy.

Materials and Methods: This was hospital based observational case-control study conducted in Biochemistry Department in collaboration with Ophthalmology Department at the Oxford Medical College, Hospital and Research Centre, Yadavanahalli, Bengaluru, Karnataka, India, from January 2018 to June 2018 with total of 90 subjects. Among 90 patients, 30 patients were with diabetes mellitus with Retinopathy (DR), 30 were with diabetes mellitus without retinopathy (NDR) and 30 were also recruited as control (healthy individuals). The mean and standard deviation were used to describe continuous data. Analysis of Variance (ANOVA) was used to statistically compare the mean difference between more than two sets of quantitative data.

Results: The mean plasma blood glucose levels were higher in T2D patients with DR, Fasting Blood Glucose (FBG) (270.4±94.2 mg/dL) and Postprandial Blood Glucose (PPBG) (425.6±131.8 mg/dL) compared to control subjects FBG (95.4±10.7 mg/dL). Among the T2D patients the plasma HbA1c concentration of DR group was found to be higher (11.0±2.3%) compared to the NDR group (p-value <0.001). While, the blood levels of vitamin B12 were comparable between the groups, serum vitamin B12 levels were significantly lower (p-value <0.001) in T2DM group with DR (200.7±201.9 pg/mL) compared to the control group (1004.8±304 pg/mL).

Conclusion: The patients with diabetic retinopathy showed that low serum vitamin B12 is associated with elevated Glycated haemoglobin (HbA1c) levels, as a result of poor glycaemic control, endothelial dysfunction and oxidative stress leading to development and progression of DR.

Keywords

Endothelial dysfunction, Fasting blood glucose, Glycated haemoglobin, Microvascular complication, Postprandial blood glucose

Diabetes Mellitus is a chronic disorder caused due to insulin deficiency or resistance, resulting in hyperglycaemia. There is an estimated 451 million people with diabetes worldwide, as of 2017; these figures are expected to increase to 693 million by 2045 (1),(2). The patients suffering from long term uncontrolled diabetes mellitus are prone to develop life threatening complications like microvascular complications (stroke, peripheral artery disease, ischaemic heart disease) and macrovascular complications (retinopathy, neuropathy and nephropathy) (3).

Diabetic Retinopathy (DR) is considered as one of the most common microvascular complications of diabetes and listed first cause of blindness across the world (4). Both the duration of diabetes and its metabolic control have been predicted as the risk factors for the development of DR (5). DR occurs in 70% individuals having diabetes for more than 15 years. Diabetic retinopathy is characterised by the appearance of altered vascular lesions of increasing severity. Early or Non Proliferative DR (NPDR) is marked by retinal vascular microaneurysms, blot haemorrhages, cotton-wool spots, loss of retinal pericytes, increased vascular retinal permeability, alterations in regional blood flow and abnormal retinal microvasculature, all of which lead to retinal ischaemia macular oedema and vision damage (6). Proliferative DR (PDR), the more severe state, leads to formation of abnormal, fragile new blood vessels that are susceptible to haemorrhage leading to neovascularization, vitreous haemorrhage, retinal detachment and early blindness (7),(8).

Although genetic susceptibility appears to be the primary predisposing factor for DR, the role of environmental factors like nutrition and dietary factors are not to be forgotten. Concentrations of folic acid and other B12 vitamins are associated with increased risk of vascular damage through homocysteine. It is a by-product of transmethylation reactions and detoxified by methionine synthetase, which is dependent on vitamin B12 and folate as co-enzymes for its proper function (9),(10),(11),(12). It is proved that the development of DR is due to poor glycaemic control, hypercoagulability, ischaemic and anoxia of the retina leading to oxidative stress, increases Nicotinamide Adenine Dinucleotide Phosphate (NADPH) oxidase activity promotes uncoupling of endothelial nitric oxide synthase (13),(14), and functional inhibition of Glutathione peroxidase and superoxide dismutase, the most common intracellular antioxidant enzymes (15). Increased endothelial cell production of adhesion molecules occurs as a result of these inflammatory processes, contributing to leucocyte accumulation and attachment to retinal capillaries (leucostasis) (16). Leucostasis, which is thought to be a precursor to DR, can lead to a breach of the blood-retinal barrier, as well as persistent leucocyte-mediated cell damage and death.

Very few studies have been done regarding the association between vitamin B12 and DR. Hence, the aim of the present study was to compare the serum vitamin B12 levels and Glycated haemoglobin (HbA1c) levels in patients with and without diabetic retinopathy.

Material and Methods

This was hospital based case-control study conducted in Biochemistry Department in collaboration with Ophthalmology Department at the Oxford Medical College, Hospital and Research Centre, Yadavanahalli, Bengaluru, Karnataka, India, from January 2018 to June 2018. Ethical Clearance was taken from the Institutional Ethical Committee with reference no (IEC/TOMCH&RC/055/17-18 dated 15/02/2018).

Sample size calculation: Sample size was determined assuming 95% Confidence Interval (CI) and 80% power, using SD of respective vitamins.

A total of 90 subjects were included in the study and divided into three groups; each group had 30 subjects. The subjects were grouped as- Type 2 Diabetes Mellitus (T2DM) patients with retinopathy (n=30), Type 2 Diabetes Mellitus patients without retinopathy (n=30) and healthy individuals (n=30).

Inclusion criteria:

1. All patients of type 2 diabetes mellitus having DR irrespective of their control level and duration of disease;
2. Patients who did not know the duration and did not follow the treatment;
3. Patients who were willing to participate in the study.

Exclusion criteria:

1. Patients with a history of vascular disease (myocardial infarct or angina, stroke, peripheral arterial disease, and deep-venous thrombosis), renal, hepatic, chronic gastroenterologic, thyroid or blood disease, dementia, and neoplasm;
2. Patients receiving vitamin supplementation.
3. Patients on drugs such as theophylline, statins, fibrates, levodopa, protons pump inhibitors, anticonvulsives, and contraceptives;
4. Chronic smoker and alchoholics;
5. Patient with indefinite duration non compliant with treatment were excluded.

Detailed medical history, physical examination and ophthalmic examination was carried out for all the study subjects. Self-declared diabetic condition was encouraged. The diagnosis of diabetes mellitus was made, based on current World Health Organisation (WHO) diagnostic criteria for diabetes (14). All subjects underwent a thorough ophthalmic examination, which included visual acuity measurement using Snellen’s chart, slit lamp evaluation of the anterior segment and fundus examination using indirect ophthalmoscopy, slit lamp microscopy, fluoroscein angiography and optical coherence tomography when indicated. Retinopathy was graded as the presence of any of such characteristic lesions such as microaneurysms, haemorrhage, cotton wool spots, intraretinal microvascular abnormalities, hard exudates, venous beading, new vessels (15).

Diagnostic Criteria for DR Non Proliferative Diabetic Retinopathy (NPDR) (16),(17)

Atleast one micro aneurysm indicates a mild condition. Moderate condition was characterised by haemorrhages, micro aneurysms, and hard exudates. Severe condition included haemorrhages, micro aneurysms, and hard exudates present in all four quadrants with definite venous beading in two or more quadrants or Intra Retinal Microvascular Abnormality (IRMA) in one or more quadrants.

Blood samples were collected from the three groups for determination of Fasting Blood Glucose (FPG), Postprandial Blood Glucose (PPBG), HbA1c and vitamin B12 levels. FBG and PPBG were analysed by fully auto-analyser by Glucose Oxidase (GOD) and Peroxidase (POD) method. HbA1c was assessed by fully automated Immunoturbidometric method. Vitamin B12 concentrations >300 pg/dL were considered as normal. Mild vitamin B12 deficiency was defined as serum concentration of <200 pg/dL and borderline deficiency as 200-300 pg/dL (18),(19).

Statistical Analysis
The data was put into a Microsoft Excel data sheet and analysed with Statistical Package for the Social Sciences (SPSS) version 22.0 software. Frequencies and proportions were used to represent categorical data. For qualitative data, the Chi-square test was employed as a measure of significance. The mean and standard deviation were used to describe continuous data. The Analysis of Variance (ANOVA) was a statistical test used to determine the statistical difference between more than two sets of quantitative data. Data Graphical Representation like MS Excel and MS Word were used to generate several types of graphs, including the bar diagrams. After assuming that all the variables were equal, a p-value (probability that the result is true) of 0.05 was considered statistically significant.

Results

(Table/Fig 1) shows the age distribution of the study population. Mean age of subjects in DM with DR group was 60.8±9.7 years, DM without DR group was 52.1±9.5 years and controls was 38.9±10.7 years.

In DM with DR group, 53.3% were males and 46.7% were females. In DM without DR group, 56.7% were males and 43.3% were females. In control group, 76.7% were females and 23.3% were males. There was significant difference in sex distribution between three groups (Table/Fig 2). (Table/Fig 3) shows that there was no significant difference in smoking, alcohol consumption between the three groups. There was significant difference in diet pattern between three groups. There was significant difference in duration of DM between the groups and mean duration of DM was 7.4±4.1 years in DM with DR (Table/Fig 4).

Most of the diabetics were on Oral Hypoglycaemic Agents (OHA) as compared to insulin. A 66.7% of DM with DR group and and 70% of DM without DR group were on OHA. A 33.3% of diabetics with DR were on Insulin. There was no significant difference in treatment between DM groups (Table/Fig 5).

Higher mean HbA1c was noted in DM with DR group (11.0±2.3%). DM without DR had a mean HbA1c level as 9.8±2.0%. There was significant difference in mean HbA1c between three the groups (Table/Fig 6).

The mean Fasting Blood Glucose (FBG) was 270.4±94.2 mg/dL and mean Postprandial Blood Glucose (PPBG) was 425.6±131.8 mg/dL in DM with DR group. In DM without DR group, mean FBG was 240.2±72.1 mg/dL and mean PPBG was 313.3±79.8 mg/dL. In control group, mean FBG was 95.4±10.7 mg/dL and mean PPBG was 116.1±12.2 mg/dL. There was significant difference in mean FBG and PPBG between three groups. In DM with DR group, mean vitamin B12 was 200.7±201.9. There was a significant difference in mean vitamin B12 between three groups (Table/Fig 6), (Table/Fig 7).

Out of 30 patients with Diabetic Retinopathy (DR), six patients belonged to mild NPDR. Among the mild NDPR patients, five patients had vitamin serum B12 levels below 200 pg/mL and one had serum vitamin B12 levels above 200 pg/mL. Five patients belonged to moderate NPDR. Out of five patients, three patients had serum vitamin B12 levels below 200 pg/mL and two patients had serum vitamin B12 levels higher than 200 pg/mL. Eight patients belonged to severe NPDR. Out of eight patients, seven patients had serum vitamin B12 levels below 200 pg/mL while one had serum vitamin B12 levels over 200 pg/mL. 11 patients belonged to PDR. Eight patients with PDR had a serum vitamin B12 level less than 200 pg/mL, while three had a serum vitamin B12 level greater than 200 pg/ mL (Table/Fig 8).

Discussion

This study aimed to compare the serum vitamin B12 levels and Glycated haemoglobin (HbA1c) levels in patients with and without diabetic retinopathy. Approximately, 5% of the global prevalence of blindness is considered to be due to DR, with estimates of 15%-17% in developed countries (1). In the present study, mean age of subjects in DM with DR group was 60.8±9.7 years, DM without DR group was 52.1±9.5 years and controls were 38.9±10.7 years. Satyanarayana A et al., conducted a study that was almost identical to that of the present study population (55.3±5.4 years and 54.8±6.1 years in Poliferative DR and no DR group respectively) (19). In a study conducted by Brazionis L et al., (median age of 66.5 years in DR and 65 years in No DR) and Fotiou P et al., (median age of 68 years in DR and 61 years in No DR group), the research populations were considerably older than our study population (20),(21).

In the study conducted by Satyanarayana A et al., (10.3±2.9% vs. 9±2.5%; p-value <0.01), they found that the mean/median HbA1c levels were significantly higher in patients with DR compared to patients without DR (19). The result was comparable to our study. However, it is assumed that perfect glycemic control is impossible for most diabetic patients and glucose control has a tendency to worsen over time. The decreased serum vitamin B12 concentration is related with elevated fasting and postpandrial blood glucose level, which was a major observation in our research. This shows the known detrimental effect of hyperglycemia on the development and progression of DR.

In DM with DR group, mean vitamin B12 was 200.7±201.9 pg/mL. There was a significant difference in mean vitamin B12 between three groups. Out of 30 patients with DR, six patients belonged to mild NPDR, five patients belonged to moderate NPDR and eight patients belonged to severe NPDR. The result was very much consistent with study published by Patel Z et .al., (22). In our study we also found that 42.7% elderly patient of age above 60 years, their serum vitamin B12 was low and 56.7% of them were males.

In a study conducted by Qureshi S et al., they considered vitamin B12 deficiency to be less than 150 pg/mL in serum and showed that 33% of diabetic patients had vitamin B12 deficiency (18). Although there is no published guideline on routine screening for vitamin B12, it is still important that T2DM patients should be assessed for deficiency.

Vitamin B12 is an enzyme co-factor which assists the cytoplasmic regeneration of methionine from homocysteine and facilitates the conversion of methylmalonic MMA-coenzyme A (CoA) to succinyl-CoA in the mitochondria. These processes help in DNA regulation, Hcy (homocysteine) metabolism, myelin synthesis, nerve growth, and neuron maintenance; all of which impact vision and DR. Active forms of methylcobalamin easily transfers a methyl group to lower Hcy, converting it to methionine. Therefore reduced B12 level in serum indirectly increases Hcy metabolism which leads to decreased cerebral blood flow, lower retinal blood flow, reduced calibre of the central retinal artery, vascular endothelial growth factor (VEGF) expression and DR (9),(10).

In the present study, serum vitamin B12 levels were lower in men compared to women and men had higher risk for vitamin B12 deficiency. Shahwan M et al., have reported that serum vitamin B12 levels were lower in women than men, which is contradictory to our findings (23).

People who eat vegetarian diet are more likely to have vitamin B12 deficiency than non vegetarians (24). In addition, vegetarian are more likely to suffer vitamin B12 deficiency. According to our findings.

Most of the Diabetics were on Oral Hypoglycaemic Agents (OHA) as compared to insulin. A 66.7% of DM with DR group and 70% of DM without DR group were in OHA. A 33.3% of Diabetics with DR were on Insulin. There was no significant difference in treatment between DM groups (Table/Fig 5). The mean duation of diabetes in DM with DR group was 7.4 years, whereas the mean duation of diabetes in DM without DR was 5 years. Similarly, Fotiou P et al., and Brazionis L et al., found that the duration of diabetes in the retinopathy group was considerably greater as compared to the no retinopathy category (20),(21).

The mechanism by which metformin affects the uptake of vitamin B12 is unknown. The most likely explanation is that the drug acts by interfering with the calcium-dependent membrane action of the vitamin B12 intrinsic factor, albeit without direct evidence as showed in study by Bauman WA et al., (24).

Limitation(s)

The study was conducted on patients with type 2 diabetes. There was a major difference between two groups that used oral hypoglycemic medications such as metformin and also on a vegetarian diet, both of which were known to affect vitamin B12 levels. This may have impaired the finding between groups and may have contributed in false positive results. Authors also did not assess the serum levels of homocysteine and folate in the study subjects as vitamin B12 metabolism is finally linked with homocysteine. Therefore, the relationship whether serum vitamin B12 levels were influenced by the homocysteine and folate levels were not studied. Also, the cases and control were not age matched.

Conclusion

The vitamin B12 levels were significantly low in the T2DM patients with DR. The low serum vitamin B12 levels and elevated Glycated haemoglobin (HbA1c) levels may be due to the result of poor glycaemic control, endothelial dysfunction and oxidative stress. Monitoring serum vitamin B12 concentration, as well as HbA1c status in T2DM patients may help in assessing microvascular risk in DM. Treatment with vitamin B12 and vitamin B6 may be useful in reducing the risk of microvascular complications in T2DM.

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DOI and Others

10.7860/JCDR/2021/48346.15376

Date of Submission: Dec 31, 2020
Date of Peer Review: Mar 06, 2021
Date of Acceptance: May 27, 2021
Date of Publishing: Sep 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

PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Jan 01, 2021
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• iThenticate Software: Aug 18, 2021 (25%)

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