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

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On Sep 2018




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Lucknow
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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.
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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

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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.


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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.
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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 : June | Volume : 16 | Issue : 6 | Page : QC06 - QC09 Full Version

Assessment of Serum Ferritin, CRP and Insulin Levels in First Trimester of Pregnancy as a Predictive Biomarker of Gestational Diabetes Mellitus: A Longitudinal Study


Published: June 1, 2022 | DOI: https://doi.org/10.7860/JCDR/2022/55162.16464
Mayukh Chakraborty, Amit Kumar Sil, Sanghamitra Chakraborty

1. Medical officer, Department of Gynaecology and Obstetrics, Chatna M/S Speciality Hospital, Bankura, West Bengal, India. 2. Professor, Department of Gynaecology and Obstetrics, Medical College and Hospital, Kolkata, West Bengal, India. 3. Assistant Professor, Department of Biochemistry, Bankura Sammilani Medical College, Bankura, West Bengal, India.

Correspondence Address :
Dr. Mayukh Chakraborty,
IA-298/7, Sector-3, Salt Lake, Kolkata, West Bengal, India.
E-mail: drmayukh10@gmail.com

Abstract

Introduction: Gestational Diabetes mellitus (GDM) increases the risk of foetal morbidity and mortality heralding the future risk of development of type 2 diabetes in mother. GDM develops mainly due to insulin resistance along with interplay of risk factors like advancing maternal age, family history of diabetes, obesity, ethnicity, history of macrosomia.

Aim: To detect whether estimation of serum ferritin, C-reactive protein and insulin in 1st trimester can predict the subsequent occurrence of GDM and whether susceptible mothers can be managed cautiously to prevent foeto-maternal complications.

Materials and Methods: This hospital-based longitudinal study was done in Department of Gynaecology and obstetrics in collaboration with the Department of Biochemistry, Medical College and Hospital, Kolkata, West Bengal, India, from January 2018 to June 2019. The study included 80 antenatal mothers attending the Antenatal Outpatient Department in first trimester. The blood samples were collected from them during first trimester and serum ferritin, C-reactive Protein (CRP) and insulin were estimated using different methods as specified later. The anthropometric measurements of the mother {Body Mass Index (BMI), skin fold thickness and waist hip ratio} were measured. These enrolled study participants have undergone Oral Glucose Tolerance Test (OGTT) with 75 gm of anhydrous glucose at 24-28 weeks of gestation. The performance parameters like sensitivity, specificity, positive predictive value, negative predictive value and likelihood ratio of ferritin and CRP was calculated.

Results: The mean age of participants who developed diabetes (n=12) 25.75±2.92 and who did not developed diabetes (n=68) 23.91±3.74 years. There was 15% prevelance of GDM in study population. The median concentration of serum ferritin and CRP was significantly higher in patients who developed GDM (n=12) among the study population (n=80). The sensitivity of serum ferritin {83.33% (95% confidence interval=51.59-97.91%)} was higher in comparison to C-reactive protein {31.82% (95% CI=13.86-54.87%)}.

Conclusion: There was a remarkable decline of insulin sensitivity with the advancement of pregnancy. This implies that latent insulin resistance may start from first trimester and screening in high risk ethnicity group like India should be a routine protocol.

Keywords

C-reactive protein, Insulin resistance, Macrosomia, Type 2 diabetes mellitus

Gestational Diabetes Mellitus (GDM) is described by American College of Obstetrics and Gynaecology (2013) as “any degree of glucose intolerance that either has onset during pregnancy or first detected during pregnancy” (1). In India, the toll of GDM has increased to 5 million with a random prevalence of 11.69% in West Bengal (2). The aetiopathogenesis of gestational diabetes is still innocuous, though insulin resistance is main contributing factor due to pregnancy hormones like human placental lactogen (somatomamotropin), progesterone, cortisol (3). However, literature reviews also suggest that gestational diabetes mellitus may simulate type 2 diabetes mellitus identified by the metabolic defects from β cell dysfunction (4). There is about 20% risk of subsequent development of type 2 diabetes in mothers (5). The occurrence of GDM has been attributed to interplay of multiple risk factors like advancing maternal age (>35 years), family history of type 2 diabetes in first degree relatives, obesity, macrosomia in previous pregnancy.

Gestational diabetes mellitus is associated with array of deadly maternal and foetal complications (6). Thus, monitoring the longitudinal changes that takes place in carbohydrate metabolism during pregnancy plays is of immense importance. However, the screening and diagnostic guidelines varies in Indian clinical setting (7). In low-resource, highly populated and high-risk setting of India the oral glucose tolerance test with 75 gm of anhydrous glucose at 24-28 weeks provides a cost effective and logistical screening test (8). Despite advances in diagnostic tools, gestational diabetes is detected in late second and third trimester till date. This keeps a lacunae that some markers in first trimester may help in identifying or detecting the risk of the disease and arresting the complications.

Recent research has suggested the role of inflammatory markers like C-Reactive Protein (CRP), ferritin related to insulin resistance, an already established aetiology of GDM. But, there are very few studies like that of Feroz A et al., in this regard in Indian scenario especially in this part of the sub-continent (9). In this Instance, the rationale or justification behind this work is early assessment of the inflammatory markers like ferritin, CRP and insulin levels in first trimester may help to assess the risk of development of GDM. The study was designed to determine whether there is a relationship between serum ferritin, CRP and insulin in early pregnancy and risk of development of GDM and to differentiate GDM and non GDM.

Material and Methods

This hospital-based longitudinal study was done in Department of Gynaecology and Obstetrics in collaboration with the Department of Biochemistry at Medical College and Hospital, Kolkata, West Bengal, India, from January 2018 to June 2019. Ethical Clearance from the Institutional Ethics Committee (MC/Kol/Non-Spons/IEC/678/11-2017 dated 18/11/2017) was obtained. Informed consent was obtained from the subjects. Random sampling was used.

Sample size calculation: The sample size was calculated based on a formula used for cohort study:

N= (Z/e)2, where,
Z=1.96 (two tailed) at 95% Confidence Interval (CI),
e=Allowable error around the expected/reported incidence of event of interest (here, it is prevalence of GDM=20%).

Considering 20%= 0.2 error the sample size was 96 (approximately). The sample size was rounded about to 100 considering the non responder rate, however, during final data calculation the sample size approximated to 80 (due to non responders/dropouts).

Inclusion criteria: Antenatal mothers attending the antenatal Outpatient Department during first trimester with singleton pregnancy without any past history of GDM or previous history of DM were enrolled in the study.

Exclusion criteria: Antenatal mothers with previous history of GDM or any type of Diabetes Mellitus, iron deficiency anaemia, haemoglobinopathy or haematological disorder, Polycystic Ovary Syndrome (PCOS) or cardiovascular diseases, multiple pregnancies, infection, fever were excluded from the study.

Procedure

The participants were interviewed in person, during their routine antenatal visit to ensure their comfort and to have their fullest co-operation. Required venous blood sample were collected with a standard aseptic procedure after obtaining informed consent, processed and the desired parameters were estimated to derive the results.

Anthropometric measurements like Body Mass Index (BMI), waist hip ratio and skin fold thickness were done in each of the antenatal mothers during first trimester. Blood parameters like plasma glucose, CRP, insulin, ferritin, haemoglobin and haematocrit were estimated. The estimation of plasma glucose and CRP was done by hexokinase and immunoturbidimetry (10). The estimation of serum ferritin and insulin were done using electrochemiluminiscence in Roche Cobas e411 (11). All patients enrolled in the study have undergone oral glucose tolerance test between 24-28 weeks. The American Diabetes Association criteria were used as cut-off values (7). The cut-off for fasting plasma glucose, 1 hour post prandial sample and 2 hour post prandial sample was <92 mg/dL, <180 mg/dL and <153 mg/dL respectively. The deviation of any one of the values was used as criteria for GDM.

Statistical Analysis

Results of the study were compiled; tabulated and analysed using appropriate statistical methods using Microsoft excel 2010 and IBM Statistical Package for Social Sciences (SPSS) version 21.0. The biological data of the individual were checked for Gaussian distribution using Kolmogorov Smirnov test and was considered in Gaussian (normal) distribution if p-value >0.05. Continuous data was expressed as Mean±SD. Man-whitney test was used for comparison median for non parametric distributed data. The binary logistic regression was done and odd’s ratio was calculated to assess the risk with the predictive biomarkers. The performance parameters like sensitivity, specificity, positive predictive value, negative predictive value and likelihood ratio of ferritin and CRP was calculated.

Results

It was observed that 12 pregnant patients among the 80 enrolled participants had developed GDM in the third trimester. The median and Inter-quartile Range (IQR) haemoglobin, haematocrit concentration of the participants were 11.35±1.37 gm/dL and 34.95±3.68% respectively. The age range of the study population was 18-31 years. The mean age of participants who developed diabetes (n=12) 25.75±2.92 and who did not developed diabetes (n=68) 23.91±3.74 years (Table/Fig 1). The baseline anthropometric measurements like BMI, waist-hip ratio and skin fold thickness of the study participants (n=80) was 22.81±1.80 kg/m2, 0.78±0.05 and 24.18±3.68 mm respectively. The mean BMI, waist-hip ratio and skin fold thickness of the study participants who developed diabetes (n=12) was 22.63±1.95 kg/m2, 0.79±0.06 and 25.08±5.07 mm respectively.

The highest quartile or 75th percentile of the distribution of ferritin was considered for cut-off. The highest quartile of ferritin was > 31.35 ng/mL. Among the study participants, 20 antenatal mothers had ferritin above 31.35 ng/mL whereas 60 antenatal mothers had ferritin below 31.35 ng/mL. The Fisher’s-exact was employed to analyse the data and it was found that the p-value <0.00001, thus a significantly higher number of study participants developed GDM who had ferritin concentration >31.35 ng/mL (the third quartile or 75th percentile of the study population) in comparison to the lower quartile (Table/Fig 2).

Moreover, the subjects who developed GDM (n=12) had significantly higher concentration of ferritin (121.64 ng/mL) in comparison to the patient who did not develop GDM (n=68, 19.05 ng/mL) (Table/Fig 3).

The Mann-Whitney U-test was used to compare the median concentration (z=-5.060, p-value <0.05). Similarly, the 75th percentile for C-reactive protein was found to be 3.6 mg/L. It was found that seven out of 22 pregnant subjects who had C-reactive protein above this cut-off, developed GDM. This was significantly higher than the patients who did not develop diabetes as shown in (Table/Fig 4).

The median concentration of CRP was higher in the subjects who developed GDM was significantly higher than subjects who did not develop GDM [Tab/Fig-3].

The unpaired Student’s t-test detailed that there was no significant statistical difference (p-value=0.36) among the subjects who developed GDM (n=12, mean insulin concentration= 13.14±3.91 μU/mL) in comparison to subjects who did not develop GDM (n=68, mean insulin concentration= 13.12±4.78. μU/mL) in first trimester. The homeostasis Model of Insulin Resistance (HOMA-IR) was estimated using Oxford’s software considering Insulin resistance as the pathophysiology of GDM. However, there was no significant statistical difference (p-value=0.49) between the subjects who developed GDM (n=12) than who did not develop GDM (n=68).

Antenatal mothers having higher concentration of CRP {OR=1.56 (95% CI=0.73-3.34)} and waist-hip ratio {OR=2.84(95% CI=(0.74-10.98)} in first trimester are at more risk of development of GDM (Table/Fig 5). The pearson correlation co-efficient suggested that there was a weak yet significant correlation between CRP and ferritin (r-value=0.274, p-value=0.014).

The sensitivity of serum ferritin was 83.33% (95%CI= 51.59-97.91%) was higher in comparison to C-reactive protein 31.82% (95%CI= 13.86-54.87%) (Table/Fig 6).

Discussion

The prevalence of diabetes in the present study population was 15% (12 out of 80). This was in concordance with the findings of Sain S et al., whose studies illustrated the prevalence of GDM in rural district of West Bengal was 11.69% (6). The findings of the current study corroborate with the findings of Seshiah V et al., whose study demonstrated prevalence of 18.9% among urban population (2). Among the 12 patients who developed GDM in the current study, 50% were more than 25 years and 50% less than 25 years. This data is contrary to the report of Savvidou M et al., which reported that women, who developed gestational diabetes, were older and mandates the recommendation of screening of GDM irrespective of the demographic parameters and risk stratification of antenatal mothers as per International Association of Diabetes and Pregnancy Study Group (IADPSG) protocol (8). It is evident from (Table/Fig 2), that raised serum ferritin concentration is associated with GDM. This study findings are in accordance with the findings of historic Camden study (n=1456), a prospective study on Iran (n=1384) and case-control study conducted Vali-e-sar Hospital of Tehran (12),(13),(14). In the Camden study, cases had a significant higher concentration of ferritin (62.8 ng/mL) as compared to the control (38.3 ng/mL). However, the values of ferritin were segmented in quintiles. The comparison of the highest segment of distribution of ferritin values with the present study is shown in (Table/Fig 7). However, for the Camden study the values of ferritin were segmented in quintiles. The fact about iron reserve and related oxidative stress causing insulin resistance was uncertain. However, the aforementioned Iran study clearly detailed that iron within normal limits may decrease insulin production (oxidative damage of β cells) and increase insulin resistance (causes co-localisation of insulin dependent GLUT4 and IGF II receptor in adipocyte). It also causes glycation of the transferrin receptors and the glycated transferrin receptors cannot bind iron. This causes a spurious elevation of ferritin, as elevated free iron need to be stored as ferritin (15),(16). Thus, catalytic iron may affect glucose metabolism even in normal concentration. Thus, ferritin in absence of anaemia can be used as a surrogate marker of risk assessment of GDM. The raised CRP concentration among subjects who developed GDM are in concordance with the findings of nested case control study the famous Massachusetts General Hospital Obstetric Maternal Study (MOMS) where they elucidated that first trimester CRP levels were significantly raised in GDM compared with control subjects (3.1mg/L vs 2.1 mg/L, p-value<0.01) (17). The CRP increases in the physiological course of gestation (18). Literature survey has reported that physical activity and insulin sensitivity increasing drugs like thiazolidinedione and metformin may be lead to lowering of CRP and in turn reduction of Insulin resistance (19),(20). A weak yet significant correlation of CRP with ferritin (r-value=0.274, p-value=0.014) suggested that inflammation, insulin resistance and GDM might share an interrelated molecular mechanism of causation. However, the current study had HOMA-IR to predict GDM an odds ratio 2.65. Yet there was no significant difference between the Insulin concentrations. This is in agreement with the fact that exaggerated insulin sensitivity in first trimester and like the findings of Ozgu-Erdinc AS et al. The present study similarly could not show first trimester insulin sensitivity indices test to have any diagnostic value for subsequent GDM (21),(22). In (Table/Fig 6), the CRP test shows a low sensitivity (31.82%) and high specificity (91.36%). However, the test has a negative predictive value of 77.94%, thus CRP has weaker potential than ferritin to predict the risk of GDM alone.

Limitation(s)

The sample size of the study population was small. Further studies with large number of population is warranted. Moreover, there are strong genetic, racial and ethnic differences among the study participants, so whether the genetic association of this study population was also a confounding factor in statistical analysis cannot be ruled out. The dietary pattern of the study participants were not included in the study. Foetal outcome in cases that developed GDM has not been studied in this prospective study. Lastly, the serum insulin estimation was done in first trimester only and not re-estimated in third trimester, where the insulin resistance develops mostly. Further studies are needed for biochemical characterization of inflammation biomarkers in order to work out whether any therapeutic intervention can affect the prognostic impact of them.

Conclusion

In the present study, authors were able to detect higher first trimester CRP, ferritin and HOMA-IR levels among women diagnosed with GDM at 24-28 weeks of gestation. Thus, estimation of CRP, Ferritin and insulin in the first trimester is easy and can categorize patients who have a substantial risk of developing GDM. Though there was a no significant difference in the insulin concentration estimated during first trimester but HOMA-IR was higher in the GDM group well established by the odds ratio of 2.65. It is easier to stop something happening in the first place than to repair the damage after it has happened. Thus, early intervention for these patients may lead to a good perinatal outcome.

Acknowledgement

The authors are immensely grateful and acknowledge the inspiration to authors/editors/publishers of all those articles/journals/books from where literatures for the discussion have been collected and cited. All those who have significantly contributed in this study are included as author.

References

1.
Brussels, Belgium: International Diabetes Federation; 2013. International Diabetes Federation. IDF Diabetes Atlas. 6th ed.
2.
Seshiah V, Balaji V, Balaji MS, Sanjeevi CB, Green A. Gestational diabetes mellitus in India. J Assoc Physicians India. 2004;52:707-11.
3.
Clark CM, Qiu C, Amerman B, Porter B, Fineberg N, Aldasouqi S, Golichowski A. Gestational diabetes: should it be added to the syndrome of insulin resistance? Diabetes Care. 1997;20:867-71. [crossref] [PubMed]
4.
Babu GR, Tejaswi B, Kalavathi M, Vatsala GM, Murthy GV, Kinra S, Neelon SE. Assessment of screening practices for gestational hyperglycaemia in public health facilities: a descriptive study in bangalore, India. J Public Health Res. 2015;9;4(1):448. [crossref] [PubMed]
5.
American Diabetes Association. Standards of medical care in diabetes - 2015. Diabetes Care. 2015;38:S1-S93. [crossref] [PubMed]
6.
Sain S, Mukhopadhyay P, Saha TK, Ghosh R. Gestational diabetes: How risky are the mothers of rural Bengal, India. Global Journal Of Medicine And Public Health. 2012;1(06);01-09.
7.
American Diabetes Association: Gestational diabetes mellitus. Diabetes Care 2018 January 42(Supp1):S165-S172. [crossref] [PubMed]
8.
Savvidou M, Nelson S M, Makgoba M, Messow C M, Sattar N, Nicolaides K. First-Trimester Prediction of Gestational Diabetes Mellitus: Examining the Potential of Combining Maternal Characteristics and Laboratory Measures. Diabetes. 2010; 59:3017-22. [crossref] [PubMed]
9.
Feroz A, Surabhi G, Nasreen N, Shagufta M. Role of Maternal Serum Ferritin in Gestational Diabetes Mellitus. Int J Cur Res Rev. 2021;13 (01):161-164. [crossref]
10.
Price CP, Trull AK, Berry D, Gorman EG. Development and validation of a particleenhanced turbidimetric immunoassay for C-reactive protein. J Immunol Methods. 1987;99:205-211. [crossref]
11.
Lotz J, Hafner G, Prellwitz W. Reference Study for Ferritin Assays. Kurzmitteilung Clin Lab. 1997;43(11):993-994.
12.
Chen X, Scholl TO, Stein TP. Association of elevated serum ferritin levels and the risk of gestational diabetes mellitus in pregnant women: The Camden study. Diabetes Care. 2006;29(5):1077-82. [crossref] [PubMed]
13.
Amiri F, Basirat Z, Omidvar S, MajidSharbatdaran M, HajianTilaki K, Mahdi Pouramir M. Comparison of the serum iron, ferritin levels and total iron-binding capacity between pregnant women with and without gestational diabetes. J Nat Sci Biol Med. 2013;4:302-05. [crossref] [PubMed]
14.
Sharifi F, Ziaee A, Feizi A, Mousavinasab N, Anjomshoaa A, Mokhtari P. Serum ferritin concentration in gestational diabetes mellitus and risk of subsequent development of early postpartum diabetes mellitus. Diabetes Metab Syndr Obes. 2010;3:413-19. [crossref] [PubMed]
15.
Jiang R, Manson JE, Meigs JB, Ma J, RifaiN , Hu FB. Body iron stores in relation to risk of type 2 diabetes in apparently healthy women. JAMA. 2004;291:711-17. [crossref] [PubMed]
16.
De Frozo RA. The triumvirate: β-cells, muscle, liver: A collusion responsible for NIDDM. Diabetes. 1988;37:667-87. [crossref] [PubMed]
17.
Wolf M, Sandler L, Hsu K, Vossen-Smirnakis K, Ecker JL, Thadhani R. First-trimester C-reactive protein and subsequent gestational diabetes.Diabetes Care. 2003;26(3):819-24. [crossref] [PubMed]
18.
Romem Y, Artal R: C-reactive protein in pregnancy and in the postpartum period. Am J Obstet Gynecol. 1985;151:380-83. [crossref]
19.
Lopez Caudana AE, Lopez Ridaura R, Gonzalez Villalpando C, Lazcano Ponce EC, Casanuevay Lopez EM, Hernandez Avila M, Tellez-Rojo Solis MM Prediction of alterations in glucose metabolism by glucose and insulin measurements in early pregnancy. Arch Med Res 2011. 42 (1):70-76. [crossref] [PubMed]
20.
Saisho Y, Miyakoshi K, Tanaka M, Shimada A, Ikenoue S, Kadohira I, Yoshimura Y, Itoh H Beta cell dysfunction and its clinical significance in gestational diabetes. Endocr J 2010:57 (11):973-980. [crossref] [PubMed]
21.
Grewal E, Kansara S, Kachhawa G, Ammini AC, Kriplani A, Aggarwal N, Gupta N, Khadgawat R Prediction of gestational diabetes mellitus at 24 to 28 weeks of gestation by using first-trimesterinsulin sensitivity indices in Asian Indian subjects. Metabolism 2012.61 (5):715-720. [crossref] [PubMed]
22.
Ozgu-Erdinc AS, Yilmaz S, Yeral MI, Seckin KD, Erkaya S, Danisman AN. Prediction of gestational diabetes mellitus in the first trimester: comparison of C-reactive protein, fasting plasma glucose, insulin and insulin sensitivity indices. J Matern Fetal Neonatal Med. 2015:28(16):1957-62. [crossref] [PubMed]

DOI and Others

DOI: 10.7860/JCDR/2022/55162.16464

Date of Submission: Jan 23, 2022
Date of Peer Review: Feb 16, 2022
Date of Acceptance: Mar 25, 2022
Date of Publishing: Jun 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. No

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