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




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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."



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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.
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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.
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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 : October | Volume : 4 | Issue : 5 | Page : 3181 - 3186

The Effect Of Hyperglycaemia On Some Biochemical Parameters In Diabetes Mellitus

GITANJALI G,* SUDEEP G**, NEERJA***, MILI G****, DEEPAK A*****, PRIYANKA S******

*MD, Deptt. Of Biochemistry, G G S Medical College, Faridkot, Punjab; **MBBS, Deptt Of Anesthesia, PGIMS Rohtak, Haryana; ***MBBS; ****MD, Deptt. Of Biochemistry, H. S. Judge University College of Dental Sciences, Chandigarh; *****MD, Deptt Of Microbiology, G.G.S.Medical College, Faridkot, Punjab; ******MD, Deptt. Of Biochemistry, GMC Sector 32, Chandigarh.

Correspondence Address :
Gitanjali Goyal,
Backside Civil Vet. Hospital,
Sikhan Wala Road, Prem Nagar,
P.O. Kotkapura -151204.
Distt. Faridkot, Punjab.
Mob: 09914031449
Email: gitanjaligoyal@yahoo.co.in

Abstract

Diabetes Mellitus (DM) is the most common endocrinological disorder which is characterized by metabolic abnormalities and long term complications. The purpose of this study was to investigate the role of hyperglycaemia on various parameters like 1) Malondialdehyde (MDA), a parameter to study increased oxidative stress, as hyperglycaemia leads to increased lipid peroxidation 2) Adenosine Deaminase (ADA) activity which is suggested to be an important enzyme for modulating the bioactivity of insulin and 3) Free Fatty acids (FFA) to study dyslipidaemias which are associated with diabetes. Design and Methods: MDA, ADA and FFA levels in serum were measured spectrophotometrically in 50 patients of type 2 Diabetes Mellitus (DM) and also in 25 healthy controls. The patients were divided into three groups according to the levels of Glycosylated haemoglobin (HbA1c); Group I (with HbA1c 6-10%), Group II (with HbA1c 10-13%) and Group III (with HbA1c >13%). The results were also compared with the control group which had HbA1c of 4-6%. Results: All the three parameters, ADA, MDA and FFA levels were found to be significantly higher in the case subjects as compared to the controls (p<0.001). In addition to this correlation, the study revealed that MDA levels are positively associated with FBS and PPBS and also, that ADA is positively correlated with MDA (r = +0.57, p <0.001). Conclusion: These findings suggest that hyperglycaemia is associated with increased levels of ADA and that it is one of the factors which lead to the increased production of oxidative stress and also the derangements of lipid metabolism which are associated with DM. Also, ADA has got a role in increasing lipid peroxidation by reactive oxygen species (ROS) generation, as reflected by increasing MDA levels.

Keywords

Diabetes Mellitus, Glycosylated Haemoglobin, Adenosine Deaminase, Malondialdehyde, Free Fatty Acids

Introduction
Diabetes is a major worldwide health problem, leading to markedly increased mortality and serious morbidity. It is a state which is characterized by chronic hyperglycaemia resulting from a diversity of aetiologies and environmental and genetic factors acting together. Hyperglycaemia itself leads to increased oxidative stress and dyslipidaemias. The long term control of DM is judged by levels of HbA1c, which was first isolated by Allen et al. (1).

Lipid peroxidation is a chain reaction which provides a continuous supply of free radicals. MDA is a secondary product of lipid peroxidation and it is derived from lipid peroxides of polyunsaturated fatty acids with two or more double bonds. It is used to measure the degree of lipid peroxidation. Chronic hyperglycaemia has an adverse effect on ß cell function, which eventually leads to worse hyperglycaemia. This vicious cycle has led to the adage that ‘hyperglycaemia begets hyperglycaemia’. This phenomenon has been designated as ‘glucose toxicity’. Although the mechanism of glucose toxicity is unknown, recent in vitro (2),(3) studies show that ROS (oxidative stress) promotes the formation of cytotoxic lipid peroxides.

ADA (Adenosine aminohydrolase, EC 3.5.3.3) is an enzyme of purine metabolism. It acts on adenosine and several other adenosine nucleoside analogues. It was concluded that increased adenosine activity mimics the activity of insulin on glucose and lipid metabolism in adipose tissue (4). Also, it was found to be a marker of T cell activation and a producer of ROS (5). Free fatty acids are the unesterified, transport form of fatty acids in the plasma. These are the most active metabolic plasma lipids. Insulin regulates the formation of free fatty acids. In diabetes mellitus, insulin deficiency leads to the increased breakdown of triglycerides. So, in diabetes, there is an increased release of free fatty acids.

The present study was done to evaluate the role of hyperglycaemia in increasing the levels of ADA, lipid peroxidation, and FFA in DM and to know the role of ADA in DM as an independent marker, as well as a stimulator of lipid peroixdation.

Material and Methods

The study was conducted on 50 known patients of type 2 DM reporting to the Govt. Medical College and Hospital, Patiala. The patients were divided into Group I (with HbA1c 6-10%), Group II (with HbA1c 10-13%) and Group III (with HbA1c >13%). The criteria for the diagnosis of DM were the same as the one which was given by the National Diabetes Data Group:

Symptoms of diabetes plus random blood glucose conc. ≥ 11.1 mmol/l (200mg/dl)

Fasting plasma glucose > 7.0 mmol/l (126 mg/dl)

25 subjects of similar age, sex and socioeconomic status served as controls. The controls were free from any major ailment which could affect the parameters under study (No clinical history or investigative results showing involvement of any organ). The exclusion criteria for the patients were Tuberculosis (TB), Infectious Mononucleolus, Breast cancer and Behcet’s disease. Informed consent was obtained for venipuncture. A detailed history was taken to know duration of the disease, treatment history and any complication of the disease.

Blood was drawn in the fasting state for Fasting Blood Sugar (FBS) and two hours after meals for Post Prandial Blood Sugar (PPBS) estimation. The samples were collected in fluoridated vials. For HbA1c, the sample was collected in a heparinised vial, as whole blood was required for its estimation. The samples were collected in plain vials for the estimation of ADA, MDA and FFA. Sera were separated from the samples within half an hour and these were stored at the appropriate temperature till analysis was done. FBS and PPBS were measured by Asatoor and King’s method (6).

HbA1c was estimated by the chromatographic spectrophotometer ion exchange method of Bisse and Abraham (7). After preparing the haemolysate, where the labile fraction was eliminated, the haemoglobins were retained by a cationic exchange resin. HbA1c was specially eluted after washing away the HbA1a+b fraction and it was quantified by direct photometric reading at 415nm. ADA was estimated by the method of Giusti G. (8). Ammonia which is liberated by the reaction of ADA on adenosine forms an intensely blue indophenol complex with sodium hypochlorite and phenol in an alkaline solution. The intensity of the colour formed was measured spectrophotometrically at 620nm.

MDA was measured by measuring the complex which was formed between MDA and Thiobarbituric Acid (TBA) with Sodiumdodecyl Sulphate (SDS) (9). The free fatty acids from the aqueous phase in serum were transferred into chloroform, in which a copper complex of free fatty acids was formed. FFA was measured spectrophotometrically from the copper complex by using sodium diethyl dithiocarbamate(10).

Results

This study was an exercise to evaluate the role of hyperglycaemia on the levels of MDA(for the extent of lipid peroxidation), ADA and FFA in DM. MDA was taken as a marker of lipid peroxidation and the control of diabetes was assessed by measuring HbA1c. The study and the control groups were compared according to age, sex distribution and routine investigations, which showed non significant results, except for blood sugar levels.

(Table/Fig 1): showing age, sex distribution and blood sugar in control & study groups.

The mean fasting and postprandial sugar levels were found to be significantly higher in the study group as compared to the control group (p< 0.001), thus showing poor control of blood glucose in diabetic patients as compared to the control group.

The levels of these parameters were also compared with different ranges of HbA1c to study the effect of hyperglycaemia on these parameters.

(Table/Fig 2): showing different parameters in control and study group


In all the groups, the levels of MDA were found to be significantly higher (p<0.001) as compared to the control group. When the levels were compared between the groups, they were found to be non significant between groups I vs. II, but were significant between groups II vs. III and groups I vs. II (p<0.05).The levels of ADA were found to be significantly higher in all the study groups as compared to the control group (p<0.001).When the levels were compared between the groups, they were found to be significant between groups I and II, between groups II and III and between groups 1vs. III (p<0.001) When the levels of FFA were compared between the groups, they were found to be non significant between the three study groups (p >0.05), but were significant between the control group and all the three study groups. (p <0.001).

The correlation studies showed a strong positive correlation between MDA and FBS levels and also between MDA and PPBS levels.

(Table/Fig 3): showing correlation between MDA, FBS and PPBS


(Table/Fig 4): and (Table/Fig 5): showing correlation between MDA, FBS and PPBS

(Table/Fig 6) showing correlation between ADA and MDA

The data revealed that with the increase in ADA levels there was increase in oxidative stress.

Discussion

The number of people affected with type 2 diabetes has reached epidemic proportions worldwide. It is estimated that by the year 2020, there will be approximately 250 million people who will be affected worldwide. Diabetes is associated with a variety of metabolic abnormalities, principal among which is hyperglycaemia, which is linked to oxidative stress. In addition to advanced glycosylation end (AGE) product formation, the most direct effect is the auto oxidation of glucose which is subjected to enediol rearrangements that result in the formation of an enediol radical ion. This species is capable of reducing molecular oxygen to form superoxide anion, which may contribute to the oxidation of lipids or to the activation of platelets. The Advanced Glycosylation End products induce cellular lipid peroxidation by interacting with their specific surface receptors (11). Also, there is overproduction of nitric acid by inducible nitric oxide synthase in diabetes, which further damages the beta cells (12).

The chronic hyperglycaemia status favours auto-oxidation and the glycation reaction, thereby leading to advanced glycosylation end products. Via their recognition by the cell receptors, these advanced glycosylation end products also participate in the development of oxidative stress and inflammatory status. The involvement of oxidative stress and AGE in diabetic complications is the basis of the development of adjuvant therapies with antioxidants (13),(14). Amelioration of oxidative stress might slow down apoptosis at the same time when it repairs the existing beta cells, which could lead to the improvement of insulin secretion independently from conventional therapy (15).

Hyperglycaemia is also associated with increased levels of ADA. It was seen that adenosine in the extracellular space modulates stimulated glucose transport in striated muscle. In heart and adipocytes, adenosine potentiates insulin stimulated glucose transport. It was found that in muscles, removing adenosine with adenosine deaminase markedly reduced the responsiveness of glucose transport to stimulation by (i) insulin alone, (ii) contraction alone and (iii) by both. It was concluded that ADA treatment markedly reduced cell surface Glucose Uptake Transporter (GLUT) - 4 labelling. The results showed that adenosine potentiated insulin and contraction stimulated glucose transport in skeletal muscles by enhancing the increase in GLUT - 4 at the cell surface and raised the possibility that decreased adenosine production or action could play a causative role in insulin resistance (16). In the present study, the values of ADA were significantly higher in the case subjects as compared to the controls. Markedly increased ADA levels showed their role in DM, maybe by causing insulin resistance and ADA was also found to increase lipid peroxidation, as shown by our correlation study which showed a positive correlation between ADA and MDA (r=+0.57, p<0.001) levels. This indicated increased oxidative stress with increased levels of ADA. The proposed mechanisms for increased oxidative stress can be 1) role of ADA as a marker of T cell activation and 2) its relation to the production of ROS with the production of NO, O2, H2O2 and OH, as studied by Erkilic (5). Plasma ADA amplifies the release of toxic oxygen radicals from neutrophils through a down regulation of the inhibitory adenosine-c-AMP system (17). MDA, ADA and xanthine oxidase levels were found to be higher in maternal and foetal plasma in preeclampsia than in normal pregnancy and also, similar findings were there in patients of acute myeloid leukaemia (18),(19).

Recent studies showed that elevated plasma levels of FFA might increase insulin resistance in the muscles and the liver. It was proposed that the earliest effect of high plasma FFA levels were 1) the inhibition of carbohydrate oxidation 2) the inhibition of glucose transport/phosphorylation and 3) the inhibition of glycogen synthesis. These studies support the hypothesis that elevated FFA levels induce insulin resistance principally at the level of glucose transport (20). The acute elevation of plasma free fatty acids is necessary for insulin secretion. Sustained elevation however leads to the apoptosis of pancreatic beta cells and it is a major risk factor for cardiovascular disease and sudden death in patients with insulin resistance (21).

It can be concluded from the present study, that hyperglycaemia aggravates oxidative stress, as well as increased levels of adenosine deaminase in diabetes, which plays an important role in DM, which may be because of local insulin resistance in the target organs and also because of the increased production of free radicals and oxidative stress. Along with this, there are also increased levels of FFA, which also cause insulin resistance. The limitation of this study is that the exact role of adenosine deaminase in the pathogenesis of diabetes mellitus is not clear. Further studies at the molecular level are required to know the role of ADA levels in modifying the effect of insulin and oxidative stress in DM.

References

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Allen DW, Schroeder WA and Balog. Observation on the chromatographic heterogenicity of normal adult and foetal Hb : A study of the effect of crystallization and chromatography as the heterogenicity and isoleucine content. Am J Chem Soc 1958 ; 80 : 1628-1634.
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Matsuoka T, Kajimoto Y, Watada H et al. Glycation dependent, reactive oxygen species mediated suppression of the insulin gene promoter activity in HIT cells. J Clin Invest.1997; 99:144-150.
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Bottino R, Balamurugan AN, Bertera S, Pietropaolo M, Trucco M, Piganelli JD. Preservation of human islet cell functional mass by anti-oxidative action of a novel SOD mimic compound. Diabetes 2002;51 : 2561-2567.
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McLane MP, Black PR, Law WR et al. Diabetes 1990; 39 : 123-129.
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Erkilic K, Evereklioglu C, Cekmen M et al. Adenosine deaminase enzyme activity is increased and negatively correlates with catalase, SOD and GSH in patients Behcet’s disease : original contributions/clinical and laboratory investigations. Mediaters Inflamm 2003 ;12 (2) : 107-116.
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Asatoor AM and King EG : Biochem,1954 ; 56 : XIiv.
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Bisse E and Abraham EC. New less temperature sensitive micro chromatographic method for the separation and quantization of glycosylated haemoglobin using a noncyanide buffer system. J Chromatog 1985;344 : 81-91.
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Giusti G. Colorimetry method for adenosine deaminase estimation. In: HU Bergmeyer, Methods of Enzymatic Analysis. Academic Press, New York, 2nd Edition ; 1947 ; 1092-1099.
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