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

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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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Sri Devaraj Urs Medical College
Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
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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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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 : 2022 | Month : November | Volume : 16 | Issue : 11 | Page : BC10 - BC15 Full Version

Serum Adiponectin as a Diagnostic Marker of Nephropathy among Patients with Type 2 Diabetes Mellitus: A Cross-sectional Study


Published: November 1, 2022 | DOI: https://doi.org/10.7860/JCDR/2022/57489.17158
Ganesh Veluri, M Murugan, Siva Prasad Palem, Vijay Kumar Gangannagari

1. PhD Scholar, Department of Biochemistry, Arupadai Veedu Medical College and Hospital, Puducherry, Vinayaka Mission’s Research Foundation (Deemed to be University), Salem, India. 2. Professor, Department of Biochemistry, Arupadai Veedu Medical College and Hospital, Puducherry, Vinayaka Mission’s Research Foundation (Deemed to be University), Salem, India. 3. Associate Professor, Department of Biochemistry, JJM Medical College, Davanagere, Karnataka, India. 4. Tutor, Department of Microbiology, Akash Institute of Medical Sciences and Research Centre, Bengaluru Rural, Karnataka, India.

Correspondence Address :
Dr. M Murugan,
Professor, Department of Biochemistry, Arupadai Veedu Medical College and Hospital, Puducherry, India.
E-mail: avmcbiochemistryedu@gmail.com

Abstract

Introduction: Diabetic Nephropathy (DN) is the leading cause of End-Stage Renal Disease (ESRD) among Type 2 Diabetes Mellitus (T2DM) patients and it is diagnosed by laboratory investigation like albuminuria. Albuminuria is a conventional and not a sensitive, specific marker for diagnosis of nephropathy. Additionally some of the patients shows advanced renal pathological changes without albuminuria and some of the patients with microalbuminuria revert back to normoalbuminuria. However, there is need for early detection, sensitive and specific marker for nephropathy. Serum adiponectin is an adipocytokine synthesised from adipose tissue, liver, kidney, heart, salivary glands. This has physiological properties like antidiabetic, antioxidative and anti-inflammatory properties beneficial for particularly in patient with T2DM. Adiponectin activates Adenosine Mono Phosphate (AMP) Kinase and Nicotinamide Adenine Dinucleotide Phosphate (NADPH) pathways results in improved insulin sensitivity and prevent albumin excretion in urine. Increased adiponectin levels are beneficial to patients with T2DM and its complications.

Aim: To determine serum adiponectin levels for the prediction of early onset of nephropathy in patients with T2DM.

Materials and Methods: This cross-sectional study was conducted from March 2018 to May 2019 at the Department of Biochemistry and Endocrine at the Basaveshwara Medical University Hospital and Research Centre in Karnataka, India, with a total of 120 subjects. Out of the 120 subjects, 80 were T2DM subjects and 40 were age, gender and Body Mass Index (BMI) matched controls (group 1). Eighty T2DM subjects were further categorised into two groups based on urinary Albumin-to-Creatinine Ratio (ACR) levels, such as 40 T2DM with normoalbuminuria [(Group 2), Urine ACR: <30 mg/g], and 40 T2DM with microalbuminuria, [(Group 3) urinary ACR: 30-299 mg/g]. Comparisons were made between groups based on socio-demographic and clinical parameters. Pearson’s correlation was used to test the relationship between estimated Glomerular Filtration Rates (eGFR), Glycated Haemoglobin (HbA1c), urine ACR, and serum adiponectin. The Receiver Operating Characteristic (ROC) curve was used to test the sensitivity and specificity of a marker for nephropathy. The Statistical Package for the Social Sciences (SPSS) version 20.0 and Medcalc Software were used to analyse data.

Results: The mean values of serum adiponectin were significantly higher in patients with T2DM 11.92±3.86 mg/dL when compared to controls 3.84±1.98 mg/dL. The serum adiponectin had a significantly very high positive correlation with HbA1c, urinary ACR r=0.726, 0.642, p-value=0.0001 and also a significantly very high negative correlation with estimated glomerular filtration rate, r=-0.399, p-value=0.0001 was observed. In ROC analysis serum adiponectin was found to be proportionately elevated in T2DM with normoalbuminuria and it was statistically significant, with a sensitivity of 92.5% and specificity of 87.50, p-value=0.0001. The urinary ACR also has shown significance with low sensitivity of 62.5% and specificity of 80%, p-value=0.0250.

Conclusion: The serum adiponectin might be a sensitive and specific marker to predict the early onset of nephropathy in T2DM patients and therefore can be used as a diagnostic marker for DN. These concentrations were positively correlated with urinary ACR and negatively correlated with eGFR.

Keywords

Albumin creatinine ratio, Diabetic nephropathy, Estimated glomerular filtration rate, Glycated haemoglobin

The T2DM is a chronic metabolic disease characterised by hyperglycaemia due to both deficiency of insulin from the pancreatic beta cells and inactivation of insulin (1). The prevalence of T2DM was 415 million people worldwide by 2015 and is expected to raise upto 650 million people by 2030. In India, 65 million people were affected in 2013 and are expected to raise to 103 million by 2030 (2),(3). The DN is considered a major healthcare issue and is listed first cause of kidney damage across the world, which is the common clinical manifestation, characterised by persistent albuminuria, reduced eGFR, and increased cardiovascular morbidity and mortality due to damage to the kidney caused by chronic hyperglycaemia and hypertension (4).

Chronic hyperglycaemia in the blood and the skeletal muscles leads to the production of Advanced Glycation End Products (AGEs) by the glycosylation of amino acids, these compounds will trigger the generation of hormones, free radicals, and infiltration of inflammatory cytokines resulting in vascular damage of podocytes, glomerulus, and tubules of the kidney (5). Along with that excess mobilisation of lipids and proteins leads to increased generation of reactive oxygen species and decreased antioxidants accelerate renal impairment in patients with T2DM (6),(7). Albuminuria was considered a gold standard declining marker kidney function in patients with T2DM. Albuminuria is the mainspring for early detection of renal impairment, some of the patients showed kidney dysfunction without excretion of protein. Despite being a conventional marker, even though albuminuria is detected, it could be too late to prevent developing nephropathy. It is also elevated in other pathological conditions such as hypertension, urinary tract infections, cardiovascular diseases, and other types of kidney disorders (8). Hence there is a need for other markers which may be sensitive, specific, and early predictable markers for the diagnosis of nephropathy in patients with T2DM.

Adiponectin is considered a protein that has 244 amino acids produced majorly from white adipose tissue, as well as the kidney, liver, bones, skeletal muscles, salivary glands, and other organs (9),(10). Its three receptors, ADIPO R1, ADIPO R2, and T-cadherin, are highly active in organs like liver, kidney, and skeletal muscles, and their physiological properties like antidiabetic, antioxidative, and anti-inflammatory which are beneficial to patients with T2DM (11),(12),(13). It acts as an antidiabetic through its ADIPO R1 receptor, by activation of AMP kinase is a transmembrane protein in the tissues that results in insulin sensitivity, glucose uptake, and fatty acid activation (14). The ADIPO R2 triggers the hypothalamus and enhances food intake, whereas the AMP kinases activated by high molecular weight protein results in glucose uptake in the tissues and lipolysis (15). Albuminuria is prevented by adiponectin’s renoprotective activities, which are mediated through AMP kinase and NADPH activation (16). In T2DM patients, fluctuating levels of serum adiponectin cause various metabolic disorders, especially nephropathy. For this reason, the measurement of serum adiponectin is more sensitive and specific than albuminuria for the assessment of nephropathy. Thus, the present study aimed to evaluate serum adiponectin as an early diagnostic marker of nephropathy and to determine the correlation between eGFR, urinary ACR, and serum adiponectin in T2DM patients.

Material and Methods

This cross-sectional study was conducted from March 2018 to May 2019 at the Department of Biochemistry and Endocrinology at the Basaveshwara Medical College Hospital and Research Centre in Karnataka, India, with a total of 120 subjects. After obtaining the approval by Basaveshwara Medical College Hospital and Research Centre, Institutional Ethics Committee (IEC) with reference number (BMC&H/IEC/2018-2019/07) the study was conducted.

Sample size calculation: The sample size was determined based on the mean and standard deviation of adiponectin levels, with 80% power and a 95% of confidence interval. Out of the 120 subjects, 80 were T2DM subjects and 40 were healthy controls (group 1). Eighty T2DM subjects were further categorised into two groups based on urinary ACR levels, such as 40 T2DM with normoalbuminuria [(group 2), Urine ACR: <30 mg/g], and 40 T2DM with microalbuminuria, [(group 3) urinary ACR: 30-299 mg/g].

Inclusion criteria: All of the subjects were between 30-70 years old. This study includes patients who were diagnosed with T2DM according to the American Diabetes Association (ADA) criteria and the Kidney Disease Improving Global Outcomes (KDIGO) criteria (17),(18).

Exclusion criteria: Patients with smoking, alcoholism, type 1 diabetes mellitus, arterial hypertension, liver disease, thyroid disease, cardiovascular disease, cerebrovascular disease, and peripheral vascular lesions, as well as persons with T2DM treated with thiazolidine, and anti-inflammatory drugs, were excluded from the study.

Study Procedure

Blood samples were collected after an overnight fast and 3 mL of postprandial venous blood samples were collected under strict aseptic precautions. A 3 mL of blood was transferred to a sodium fluoride vacutainer for estimation of Fasting Blood Glucose (FBS), Post Prandial Blood Glucose (PPBS), and 3 mL to Ethylene Diamine Tetraacetic Acid (EDTA) vacuole for HbA1c estimation. The remaining 4 mL was transferred for serum urea, creatinine, and adiponectin. Ordinary red capped vacuum blood collection tubes for measurement. In addition to blood samples, on-site urine samples were collected for urine ACR analysis. The FBS, PPBS and HbA1c were estimated using the Glucose Oxidase and Peroxidase (GOD POD) method on the Erba 200, Transasia automated analyser, and serum urea and creatinine were estimated using the glutamate dehydrogenase method on the Erba 200, Transasia automated analyser was analysed using modified Jaffe’s kinetic method (19). HbA1c is fully automated and measured by latex immunoturbidimetry (20). The eGFR were calculated using the Epidemiological Collaboration for Chronic Kidney Disease (CKD-EPI) formula, and for measurement of urine, ACR was calculated by urinary protein/urinary creatinine×1000 formula (urinary protein measured by immunoturbidometric method and urinary creatinine by Modified Jaffe’s rate kinetic method) [21,22]. Serum adiponectin was analysed using an enzyme linked immunosorbent assay (Euro immune Analyser I-2p ELISA Kit obtained from Genxbio health sciences Pvt. Ltd. Noida, India).

Statistical Analysis

The SPSS version 20.0 and Medcalc Software were used to analyse the data. Descriptive statistical measures were employed to summarise the data. Normal distribution by the Kolmogorov-Smirnov test and the data were presented as the mean±standard deviation, data comparison was performed by a one way Analysis of Variance (ANOVA) followed by a Tukey posthoc test to analyse the statistical significance difference between the groups. A Pearson correlation analysis was performed between serum adiponectin and HbA1c, urinary ACR and eGFR. The ROC curves were constructed to investigate the diagnostic accuracy of identifying markers of diabetic nephropathy in T2DM patients with normoalbuminuria compared to controls. The statistical significance was defined as p<0.05.

Results

In this current study, 120 people were included, of whom 40 subjects T2DM with normoalbuminuria (group 2) and 40 subjects T2DM with microalbuminuria (group 3), respectively. The controls were involved in group 1. The comparison of mean±SD of the anthropometric, biochemical, urinary ACR and serum adiponectin data were analysed among T2DM patients and controls. The FBS, PPBS, creatinine, serum urea, HbA1c, urinary ACR, and serum adiponectin had a statistically significant difference between cases and controls with p-value=0.0001. Patients with T2DM showed no statistically significant difference of height, weight and eGFR when compared to controls p-value=0.433, 0.295 and 0.096. The other two parameters of age and BMI were statistically significant, with p-value=0.003 and p-value=0.01, respectively (Table/Fig 1).

The comparison of the anthropometric, routine biochemical parameters, urinary ACR, and serum adiponectin biomarkers in the different study groups were analysed using ANOVA. There was a significantly very high levels of FBS, PPBS, urinary ACR and serum adiponectin, respectively p-value=0.0001 and there were no significant difference of serum urea, creatinine and HbA1c were observed in group 2 when compared to group 1. In group 3 subjects showed a highly significant increased levels of PPBS, urea, creatinine, HbA1c, urinary ACR and serum adiponectin p=0.0001** and reduced levels of e GFR were observed when compared with group 1 and group 2, p-value=0.0001 (Table/Fig 2), (Table/Fig 3).

The Pearson’s correlation between HbA1c, eGFR, and urinary ACR with serum adiponectin among study group is shown in (Table/Fig 4).

The distribution of urinary ACR levels in all three groups of study subjects is graphically represented. There were significantly elevated levels in group 3 subjects when compared to group 1 and group 3 (Table/Fig 5). In the graphical representation of eGFR levels in different groups of study subjects, statistically decreased levels were observed in T2DM patients with microalbuminuria when compared with T2DM with normoalbuminuria and healthy controls (Table/Fig 6).

The serum adiponectin was significantly elevated in T2DM with normoalbuminuria and microalbuminuria when compared to healthy individuals; the data distribution was represented graphically (Table/Fig 7).

There was no significant area under the curve with sensitivity ranging from 62.50-22.50 and specificity ranging from 100-80.00 for HbA1c and urinary ACR with p-value <0.0420 and p=0.0250, respectively. The eGFR and serum adiponectin showed a statistically significant area under the curve with sensitivity ranging from 85.00-92.50 and specificity from 45.00-87.50 and p-value <0.001 and p-value <0.0001, respectively (Table/Fig 8), (Table/Fig 9).

Discussion

The T2DM patients were more likely to develop kidney diseases characterised by the occurrence of persistent albuminuria, reduced kidney function, hypertension, and an increased risk of cardiovascular morbidity and mortality (23). Various factors have contributed to an increase in its pathophysiology and available treatment modalities. This develops as a result of complex interactions between metabolism, haemodynamic, inflammation, oxidant-antioxidant, and other pathways that ultimately affect glomerular cells as well as tubulointerstitial tissue via signalling pathways that involve nuclear factor kappa B (NF-κB) and protein kinase C activation (24). The key pathological events in Glomerular Basement Membrane (GBM) result from proteinuria in diabetic nephropathy; persistent development of albuminuria is a critical event since intervention at this stage prevents further progression of nephropathy because of the reduction of albuminuria using therapeutic interventions was shown to preserve renal function.

Albuminuria is a currently used clinical investigation for the diagnosis of nephropathy in patients with T2DM. According to these studies, this is a conventional marker and it’s not a golden standard, specific and sensitive marker for early prediction of nephropathy because it is elevated in other diseased conditions like obesity, hypertension, and other types of kidney diseases, along with that some of the T2DM patients with microalbuminuria revert back to normoalbuminuria (25),(26). Because of the limitations of urine ACR, there is a need for other markers to early predict nephropathy in T2DM patients. It shows that hyperglycaemia, AGEs, mean arterial blood pressure, HbA1c, aldosterone, and atrial natriuretic peptide cause protein excretion in urine, and the authors also observed that some T2DM patients with microalbuminuria revert to a normoalbuminuric stage (27),(28),(29).

In the present study, it was also found that there were statistically highly significant elevated levels of FBS, PPBS, urea, creatinine, HbA1c, urinary ACR, serum adiponectin, and reduced levels of eGFR also observed in T2DM patients (not significant) with microalbuminuria when compared to T2DM with normoalbuminuria and healthy controls. Similarly, another recent study reported that elevated levels of serum adiponectin might be useful for predicting the early onset of nephropathy (30). A cross-sectional study done with the 60 T2DM patients found elevated FBS, PPBS, HbA1c and serum adiponectin levels, the adiponectin was positively correlated with urinary ACR and HbA1c, and they reported that adiponectin measurement might be useful for early detection of nephropathy in patients with T2DM (31). Furthermore another recent research studies discovered that adiponectin, rather than urinary albuminuria, is used for the early prediction and progression of nephropathy in patients with T2DM (32),(33). Adiponectin is an adipocytokine produced by the white adipose tissue. The beneficial effects of this improved insulin sensitivity by its antidiabetic property, protect the tissue from damage by reactive oxygen species by inhibiting NADPH oxidase activity by its antioxidative property, and decrease the adverse effects of inflammatory cytokines by its anti-inflammatory properties (34),(35). There is a conflict with serum adiponectin; either it is a sensitive, specific, and accurate marker to predict early renal impairments in patients with T2DM.

In the present study also, the ELISA method was used for the quantification of serum adiponectin in patients with T2DM compared to healthy controls. It is particularly important that authors found a statistically significant difference in the concentration of serum adiponectin in T2DM patients with normoalbuminuria compared with healthy individuals. These results indicate that before the appearance of microalbuminuria, in addition to that, the present study found statistically significant elevated levels of serum adiponectin in T2DM patients with microalbuminuria, and the glomerular filtration rate was found to be lower in comparison to normal eGFR. Similarly another cross-sectional study also found similar results, where significantly elevated levels of serum adiponectin positively correlated with microalbumin and negatively correlated with eGFR and also they suggested adiponectin measurement can be useful for early onset of nephropathy in T2DM (36). Previous studies have also found elevated levels of adiponectin in T2DM patients with Chronic Kidney Disease (CKD) and ESRD (37),(38). Other studies found that serum adiponectin was negatively correlated with urinary albumin and that adiponectin deficiency was directly associated with renal dysfunction; it could be one of the triggering factors that increases protein kinase activation, protects podocytes from damage, and prevents albuminuria all at the same time (39). Furthermore, in this study, serum adiponectin strongly correlated with HbA1c and urinary ACR and negatively correlated with eGFR, indicating that serum adiponectin is a marker of renal impairment. Similarly, previous studies reported that the serum adiponectin levels were inversely proportional to the eGFR levels and also reported that ADIPO R1 enhances the AMPK pathways and inhibits the free radicals, which simultaneously protects the development of albuminuria (28),(40).

The eGFR and serum adiponectin showed a statistically significant area under the curve with sensitivity ranging from 85.00-92.50 and specificity from 45.00-87.50 and p<0.001 and p<0.0001, respectively. According to the current study findings, serum adiponectin is the best marker for early prediction of Diabetic Nephropathy than urinary ACR in patients with T2DM because, before excretion of albuminuria, these serum adiponectin levels were significantly elevated in T2DM patients with normoalbuminuria.

Limitation(s)

Limitations of the present study were small sample size as well as authors didn’t follow-up the T2DM cases with different stages of nephropathy. Secondly, statistically significant difference was found for age and BMI among both the groups (T2DM and controls). Moreover, it was a single centre study. Further longitudinal and follow-up studies are required to prove that adiponectin can be used for early prediction and progression of nephropathy in T2DM patients.

Conclusion

According to the study findings, serum adiponectin levels are proportionately elevated in T2DM patients with normoalbuminuria to microalbuminuria and also positively correlated with urinary ACR and negatively correlated with eGFR. The ROC curve analysis revealed that serum adiponectin had higher diagnostic accuracy, sensitivity, and specificity in T2DM patients with normoalbuminuria than urinary ACR. Hence, serum adiponectin might be a sensitive and specific marker to predict the early onset of nephropathy in T2DM patients and therefore can be used as a diagnostic marker for DN.

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DOI and Others

DOI: 10.7860/JCDR/2022/57489.17158

Date of Submission: May 01, 2022
Date of Peer Review: Jul 19, 2022
Date of Acceptance: Sep 20, 2022
Date of Publishing: Nov 01, 2022

AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. NA

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