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

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Dr Bhanu K Bhakhri

"The Journal of Clinical and Diagnostic Research (JCDR) has been in operation since almost a decade. It has contributed a huge number of peer reviewed articles, across a spectrum of medical disciplines, to the medical literature.
Its wide based indexing and open access publications attracts many authors as well as readers
For authors, the manuscripts can be uploaded online through an easily navigable portal, on other hand, reviewers appreciate the systematic handling of all manuscripts. The way JCDR has emerged as an effective medium for publishing wide array of observations in Indian context, I wish the editorial team success in their endeavour"



Dr Bhanu K Bhakhri
Faculty, Pediatric Medicine
Super Speciality Paediatric Hospital and Post Graduate Teaching Institute, Noida
On Sep 2018




Dr Mohan Z Mani

"Thank you very much for having published my article in record time.I would like to compliment you and your entire staff for your promptness, courtesy, and willingness to be customer friendly, which is quite unusual.I was given your reference by a colleague in pathology,and was able to directly phone your editorial office for clarifications.I would particularly like to thank the publication managers and the Assistant Editor who were following up my article. I would also like to thank you for adjusting the money I paid initially into payment for my modified article,and refunding the balance.
I wish all success to your journal and look forward to sending you any suitable similar article in future"



Dr Mohan Z Mani,
Professor & Head,
Department of Dematolgy,
Believers Church Medical College,
Thiruvalla, Kerala
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."



Dr Kalyani R
Professor and Head
Department of Pathology
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.
As an experienced dentist and an academician, I proudly recommend this journal to the dental fraternity as a good quality open access platform for rapid communication of their cutting-edge research progress and discovery.
I wish JCDR a great success and I hope that journal will soar higher with the passing time."



Dr Saumya Navit
Professor and Head
Department of Pediatric Dentistry
Saraswati Dental College
Lucknow
On Sep 2018




Dr. Arunava Biswas

"My sincere attachment with JCDR as an author as well as reviewer is a learning experience . Their systematic approach in publication of article in various categories is really praiseworthy.
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

Important Notice

Original article / research
Year : 2010 | Month : December | Volume : 4 | Issue : 6 | Page : 3429 - 3436

Impaired Antioxidant Defence Mechanism In Diabetic Retinopathy

T VIVIAN SAMUEL1, D S JAYAPRAKASH MURTHY2, K DATTATREYA3, P SURESH BABU4, S SMILEE JOHNCY5

1,3,4 MBBS, MD, Reader, 2 MBBS, MD, Professor and HOD, Department of Biochemistry, 5 MBBS, MD, Assistant Professor, Department of Physiology, J J M Medical College, Davangere, Karnataka

Correspondence Address :
Dr T Vivian Samuel MD
Reader, Department of Biochemistry,
JJM Medical College,
Davangere – 577004,
Karnataka.
Mob no: 9448028229
e-mail: tviviansamuel@yahoo.co.in

Abstract

Background
Oxidative stress resulting from enhanced free-radical formation and a defect in antioxidant defences, has been implicated in the pathogenesis of diabetes and its complications include neuropathy, retinopathy, nephropathy, etc.

Aims
The aim of the present study was to evaluate the levels of selected oxidation and the antioxidant status with relevance to diabetic retinopathy and to correlate the antioxidant status with glycaemic control.

Materials and Methods
Thirty patients of type-2 diabetes mellitus (DM) without retinopathy, 30 patients of diabetic retinopathy and 30 normal subjects were included in this study. The degree of lipid peroxidation in terms of serum malondialdehyde (MDA) by the thiobarbituric acid method along with antioxidant defences, erythrocyte superoxide dismutase (SOD), reduced glutathione (GSH) and serum vitamin C was estimated in healthy controls and non-insulin dependent diabetes mellitus (NIDDM) subjects with and without retinopathy. Fasting blood glucose was also estimated and correlated with the antioxidant status. The statistical analysis was done by using the Students unpaired ‘t’ test and the correlation was done by using Pearson's correlation coefficient.
Results
The levels of serum MDA were found to be increased significantly in the diabetic retinopathy cases as compared to those in the cases with diabetes without retinopathy and in the healthy controls. The levels of superoxide dismutase (SOD), reduced glutathione (GSH) and vitamin C were significantly reduced in all diabetic patients, i.e., those with and without retinopathy. However, the lowest levels were found in the diabetic patients with retinopathy. A negative correlation was found between FBS and antioxidant enzymes in the diabetic retinopathy cases.

Conclusion
The results suggest that antioxidant deficiency and excessive peroxidation damage appear in NIDDM, and the severity is more with the development of complications. Therapeutic measures to increase the antioxidants and to control lipid peroxidation are warranted for the effective control of its complications.

Keywords

Ascorbic acid, Malondialdehyde, Reduced glutathione, Superoxide dismutase

INTRODUCTION
Retinopathy is one of the most severe ocular complications of diabetes and is a leading cause of acquired blindness in young adults. A prominent and early feature of the retinopathy of diabetes mellitus is a diffuse increase in vascular permeability. As the disease develops, the development of frank macular oedema may result in vision loss. The cellular components of the retina are highly coordinated but are very susceptible to the hyperglycaemic environment. (1) Oxidative stress has been implicated in the pathogenesis of diabetic retinopathy. It has been hypothesized that hyperglycaemia may damage the vascular endothelium and the retina by inducing the synthesis of oxidant reactive species and thereby causing oxidative stress. (2) Oxidative stress is defined as an increase in the steady-state levels of reactive oxygen species. Free radicals are very reactive chemical species and can cause oxidative injury to living beings by attacking the macromolecules like lipids, carbohydrates, proteins and nucleic acids. Under normal physiological conditions, there is a critical balance in the generation of oxygen free radicals and the antioxidant defence systems which are used by organisms to deactivate and protect themselves against free radical toxicity. (2) Impairment in the oxidant/antioxidant equilibrium creates an oxidative stress which is known to be a component of molecular and cellular tissue damage mechanisms in a wide spectrum of human diseases. (3) There are several endogenous enzyme systems that protect the cell and tissue from oxidative stress, for example superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-Px). Although there is controversy about the antioxidant status in diabetes, several studies report decreased levels of SOD and GSH-Px in both clinical and experimental diabetes, indicating an impaired defence system for free radical scavenging. The sources of reactive oxygen species in diabetes may include the autoxidation of glucose. (4) As oxidative stress plays an important role in the chronic complications of diabetes, it is postulated to be associated with increased lipid peroxidation. Hyperglycaemia and dyslipidaemia in diabetes mellitus induce increased lipid peroxidation and peroxyl radical formation which are important mechanisms in the genesis of microangiopathy. In this study, malondialdehyde (MDA) levels as an index of erythrocyte susceptibility to oxidative stress and antioxidant status in type − 2 DM patients with and without retinopathy, was studied and it was compared with a control non-diabetic group.

Material and Methods

This study was carried out in the Department of Biochemistry, JJM Medical College, Davengere. Our study group included 30 patients of DM type-2, without any complications, with a mean age of 50.6±10.5 years, 30 patients of DM type-2 with retinopathy, with a mean age of 49.5±11.7 years and 30 age and sex matched healthy controls with a mean age of 50.8 ± 14.8 years. The diabetic patients were normotensive, without the secondary causes of hyperglycaemia and were under treatment with oral hypoglycaemic agents. The detailed present and past history of the patients was collected on a pre-tested performa which included name, age, sex, dietary habits, family history, smoking and drinking habits, socio-economic status, community and occupation, along with their consent for the study. An experienced ophthalmologist performed the direct opthalmoscopic examination on the patients. Retinopathy was defined as mild to moderate non - proliferative, severe non - proliferative and clinically significant macular oedema. The selected subjects were asked to fast overnight and with all aseptic precautions, blood samples were collected from them for the estimation of fasting blood glucose, serum malondialdehyde (MDA), serum ascorbic acid (Vit C), erythrocyte SOD and reduced glutathione. Fasting blood glucose was estimated by the O-Toluidine method. (5) Serum MDA was estimated by the Thiobarbituric acid (TBA) method in which one molecule of MDA reacts with two molecules of TBA and yields a pink crystalline pigment which is measured at 535 nm. (6) Serum ascorbic acid was estimated by the 2, 4 – dinitrophenyl hydrazine (DNPH) method in which ascorbic acid is oxidized by copper to form dehydroascorbic acid, which when treated with DNPH and sulphuric acid, forms an orange colour which is measured at 520 nm. (7) Reduced glutathione was estimated by the 5, 5 dithiobis – 2 – nitrobenzoic acid (DTNB) method. DTNB is readily reduced by sulphydryl compounds, forming a highly coloured yellow anion. Optical density was measured at 412 nm. (8) Superoxide dismutase was estimated in haemolysates by using Nitroblue Tetrazolium (NBT).(9) The illumination of riboflavin in the presence of oxygen and electron donors like methionine or EDTA generates superoxide anions. The reduction of nitroblue tetrazolium by O2– was read at 560 nm by using a spectrophotometer. (10)

Statistical analysis
All the values were expressed as their Mean  S.D. The data were analysed by using the students unpaired‘t’ test for comparison between the two groups and the correlation between glycaemic control and the antioxidants was done by using Pearson's correlation coefficient.

Results

The results obtained from the control, diabetics without complications and diabetics with the retinopathy groups, are shown statistically in (Table/Fig 1). The levels of Vit C, GSH and SOD of diabetics without retinopathy were significantly lower (P<0.001), while the FBS and serum MDA levels were significantly higher, when compared with those of the control group (P<0.001) (Table/Fig 1).
The levels of FBS and serum MDA of the group with retinopathy were significantly higher (P<0.001), whereas the levels of Vit C, GSH and SOD were significantly lower with respect to those of the group without retinopathy (P<0.001) (Table/Fig 1). The levels of Vit C, GSH and SOD were significantly lower in the cases of diabetes with retinopathy when compared to those of the control group (P<0.001) (Table/Fig 1).
(Table/Fig 1): Comparison of FBS, MDA, Vit C, GSH and SOD between controls, NIDDM without complications and NIDDM with retinopathyAll values expressed as mean  SD

*Unpaired ‘t’ test
P > 0.05, Not Significant (NS), P < 0.05, P < 0.01Significant (S),
P < 0.001, Highly Significant (HS)


The mean percentage changes of the oxidant and antioxidant parameters in patients with diabetic retinopathy as compared to the controls are shown in (Table/Fig 2). A statistically significant negative correlation was found between FBS and Vit C, r = -0.9629 shown in (Table/Fig 3), between FBS and GSH, r = -0.8422 in (Table/Fig 4), and between FBS and SOD, r = -0.9081 in (Table/Fig 5) in cases of diabetic retinopathy.

(Table/Fig 2): Percentage change of mean oxidant and antioxidant parameters in patients with diabetic retinopathy compared to controls

(Table/Fig 3): Correlation between FBS (mg/dl) and Vit C (mg/dl) in diabetic retinopathy

(Table/Fig 4): Correlation between FBS (mg/dl) and GSH (mg/dl) in diabetic retinopathy

(Table/Fig 5): Correlation between FBS 9mg/dl) and SOD (U/ml) in diabetic retinopathy

Discussion

Diabetic retinopathy is perhaps the most specific of all the diabetic complications. The prevalence of retinopathy is related to the duration of diabetes. Rema et al. studied the prevalence of retinopathy in 6782 NIDDM patients, in which the overall prevalence was found to be 34.2%, of which 30.8% was non- proliferative diabetic retinopathy and 3.4% was proliferative diabetic retinopathy. In the same study, the prevalence of non- proliferative diabetic retinopathy and proliferative diabetic retinopathy were 7.2% and 0.2% at the onset of diabetes, which increased to 73% and 11.9% after 20 years of duration of diabetes. (10)

There has been a great deal of interest in the role of oxidant stress in the causation of tissue damage in a number of diseases. It is also proved that hyperglycaemia may damage the vascular endothelium and the retina by inducing the synthesis of oxidant reactive species. Oxidant stress is usually countered by an abundant supply of antioxidants. If concomitant antioxidant deficiency occurs, oxidant stress may produce tissue damage. Normally, the body has an abundant supply of "antioxidants" which are naturally occurring substances that delay or inhibit oxidation and neutralize the oxygen free radicals. In the nature, therefore, when there is a balance of "oxidant stress" and the "antioxidant supply", there is perfect harmony and no tissue destruction occurs. However, if there is an imbalance, i.e., either an excess of free radicals and reactive oxygen species or a deficiency of antioxidant supply, then tissue damage can occur. (11)

In our study, we found increased lipid peroxidation in terms of MDA in diabetics as compared to the controls and this increase was more in diabetic retinopathy. Gallau and his colleagues demonstrated that lipid peroxides (MDA) were higher in diabetics with retinopathy as compared to those in diabetics without retinopathy. (12) Yıldız and his coworkers also identified higher plasma and erythrocyte MDA levels in the group with retinopathy, as compared with those in the group without retinopathy. There are a few biochemical mechanisms that explain the reason for this rise. The increase in the blood free fatty acid levels depending on degree of lipolysis, results in an increase in MDA production. Increased MDA levels of diabetic individuals may take origin from the peroxidative damage of the membrane lipids. (13) Jennings et al. (1991) have shown that increased free radical activity leads to an increased thrombotic tendency and a reduction in prostacyclin stimulating factors depending on the increasing thrombocyte reactivity in diabetics, especially with retinopathy, and they have also demonstrated that intracellular SOD activity is reduced in patients with retinopathy. (14) Since lipid peroxides play a major role in the formation of vascular tissue damage, it is suggested that an increase in MDA in diabetes can be effective in the pathogenesis of diabetic angiopathy. It has been indicated that an increase in free fatty acids along with a lack of insulin contribute to high plasma MDA levels. (15)

One of the intracellular protective mechanisms against free radicals that form peroxidation in the membrane lipids is the glutathione and the redox systems. Reduced GSH is a non-specific reduction agent and it plays an important role in the oxidation mechanisms. (16) In cell metabolism, it performs important functions in the prevention of the sulphydryl groups of various proteins and lipoproteins in the cell membrane. GSH participates in antioxidative defense systems as a free radical inactivator. GSH is maintained at a concentration of 0.2-10 mM in all mammalian cells. Depletion of GSH in the cell renders it susceptible to oxidative injury. (16) Under in vivo conditions, GSH acts as an antioxidant and its decrease is reported in diabetes. Rathore et al. (2000) have observed a significant decrease in the GSH content in diabetic erythrocytes. The decrease in GSH content represents increased utilization due to oxidative stress. The depletion of GSH levels may also lower the GST activity, as GSH is required as a substrate for GST activity. Depression in the GPx activity was also observed in erythrocytes during diabetes. GPx has been shown to be an important adaptive response to and condition of increased peroxidative stress. (17)

The weakness of the antioxidant defence system may be the biochemical background for the pathogenesis of the endothelial dysfunction which is associated with diabetes. Ascorbic acid functions as an important component of the cellular defence against oxygen toxicity and lipid peroxidation which is caused by the free radical mechanism. Reduced levels and the altered metabolic turnover of ascorbic acid have been reported in diabetic patients. (18) A decrease in the plasma concentration of ascorbic acid has been observed in diabetic patients. In our study, we found decreased levels of Vitamin C in diabetic patients as compared to the controls and this decrease was found to be more in diabetic retinopathy. The uptake of ascorbic acid into the cell is mediated by processes which are related to glucose transport and it has been shown that the high extracellular glucose concentration in diabetes may further impair the cellular uptake of ascorbic acid and accentuate the problems which are associated with its deficiency. Vitamin C is a hydrophilic antioxidant in plasma, because it disappears faster than other antioxidants when plasma is exposed to the reactive oxygen species. The observed significant decrease in the levels of plasma vitamin C could be caused by the increased utilization of vitamin C as an antioxidant defence against the reactive oxygen species or by a decrease in GSH, which is required for the recycling of vitamin C. Earlier research has shown that diabetics have low levels of vitamin C and that vitamin supplementation can help in preventing the development of glucose intolerance and diabetes (19).

Vitamin C is an important component of the cell defence systems working against oxidative stress. These levels are significantly decreased in diabetics and more so, in diabetic retinopathy. Our study also suggested similar findings. The uptake of ascorbic acid into the cell is mediated by processes which are related to glucose transport and it has been shown that the high extracellular glucose concentration in diabetics may further impair cellular uptake and accentuate the problems which are associated with its deficiency. (17) Also, therapeutic doses of vitamin C are associated with the reversal of early signs of retinopathy in diabetics, thus confirming its protective role in the damage of the blood vessels. Thus, the increase in lipid peroxides in blood, coupled with the weakness of the defense antioxidant system in diabetics without complications, probably serves as a background for the pathogenesis of endothelial dysfunction which is associated with diabetes. (19)

A decrease in the activities of the antioxidant enzyme systems in diabetes is linked to the progressive glycation of the enzymatic proteins. Numerous reports indicate variations in the levels of antioxidants in the diabetic patients. (2) In our study, it was found that the levels of SOD, an enzyme which is responsible for the scavenging of oxidant stress factors in the body, is significantly decreased in diabetics with and without retinopathy. The superoxide anion which is believed to be one of the initiators of free radical reactions plays an important role in the determination of the levels of the antioxidant enzyme, SOD. The products of membrane lipid peroxidation and other oxidants like H2O2 may react with SOD, resulting in oxidative modification, thereby causing loss of enzyme activity. Also, diabetic hyperglycaemia leads to the glycation and inactivation of SOD, thus attributing to its decrease. (20)

These results indicate that there occur severe lipid peroxidation, protein oxidation, and oxidative DNA damages in diabetes. The augmented oxidative stress in diabetes may be speculated to contribute to the pathogenesis of diabetes mellitus. Oxidative stress is an important risk factor in the development of diabetic retinopathy. The present study also showed that type 2 diabetic patients have retinopathy as a complication and also have a low antioxidant status as compared to those of healthy individuals.

In conclusion, free radical formation along with antioxidant deficiency in diabetes mellitus increases over time and may play an important role in the development of diabetic retinopathy, which is an important complication of the disease. The present study revealed the importance of determining the antioxidant status in diabetes, in addition to the markers of oxidative stress, to enable the formulation of specific therapies for an early intervention and better management of the disease and its complications.

Key Message

Raised oxidative stress, decreased antioxidant status and antioxidant deficiency appears to be associated with a risk for diabetic retinopathy.

Acknowledgement

Authors are grateful to the Principal. J J M Medical College,Davengere for his support and encouragement. Authors are deeply indebted to all volunteers who participated in this study.

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