RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA
BANGALORE
ANNEXURE II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1. / Name of the Candidate and address(in BLOCK letters) / DR PRIYANK UDAGANI
SHIVASHAKTI NILAYA,
NEHARU NAGAR
BYADGI –581106.
HAVERI ( DT).
2. / Name of the Institution / BANGALORE MEDICAL COLLEGE
& RESEARCH INSTITUTE,
FORT,
BANGALORE-560 002.
3. / Course of study and subject / M.D. BIOCHEMISTRY
4. / Date of admission to the course / 30/05/2011
5. / Title of topic / “STUDY OF SEX HORMONE BINDING
GLOBULIN AND HIGH SENSITIVE
C-REACTIVE PROTEIN IN
PREECLAMPSIA’’
6.
7.
8. / BRIEF RESUME OF THE INTENDED WORK:
6.1 Need for the study:
Preeclampsia is a multisystem disorder of unknown etiology characterized by development of hypertension of 140/90 mmHg or more with proteinuria after 20weeks of gestation in previously normotensive and non proteinuric patients1. It is a common complication of pregnancy, causing maternal and fetal morbidity and mortality. Endothelial dysfunction and inflammation are considered to have a crucial role in the pathophysiological mechanism of preeclampsia2. Insulin resistance appears to be a potential mechanism linking preeclampsia and future cardiovascular diseases3.
Sex hormone binding globulin (SHBG) is a glycoprotein, produced by liver4,5. Production of SHBG is inhibited by insulin, therefore low level of SHBG are associated with elevated insulin levels. Other studies have shown low SHBG levels as a marker of insulin resistance both in preeclampsia and cardiovascular diseases5. Features of insulin resistance syndrome associated with preeclampsia are hypertension, hyperinsulinemia, glucose intolerance, reduced SHBG and abnormal lipid profile6.
An increased level of high sensitive C- reactive (hsCRP) is a sensitive marker of endothelial dysfunction which is associated with preeclampsia. Although normal pregnancy is associated with increased pro-inflammatory markers, it has been suggested that the cause of serum hsCRP elevation in preeclamptic women may be the result of reduced plasma volume in these patients2.
6.2Review of literature:
Study by Hossein Ayatollali et al, observed that serum hsCRP levels is higher in mild and severe preeclampsia than normal pregnancy2 . Study by Milan Stefanovic et al, SHBG showed no significant difference between preeclamptic and normotensive women, although in multivariate analysis SHBG emerged as significant factor in insulin resistance7.
1 Study by Anil Bargale et al, shows that serum hsCRP levels higher in preeclamptic women (3.733±1.096) as compared to normotensive pregnant woman (1.216±0.552)8. Study by Myles Wolf et al, identifies the evidence of increased insulin resistance in first trimester among woman who subsequently develop preeclampsia, long before preeclampsia becomes clinically evident 9.
Study by Risto Kaaja et al, shows that insulin resistance and the inflammatory marker studied were not associated in established preeclampsia. In multiple regression analysis only SHBG (p=0.01) and TG (p=0.0036) were associated with insulin sensitivity10.
Study by Berkowitz KM et al, showed that preeclampsia is at least partially mediated by insulin resistance and that individuals with preeclampsia may have clinically silent but persistent alternation in insulin resistance11.
6.3 Objectives of the study :
To conduct a case control study on patients with preeclampsia and determine the correlation of following parameters with controls.
a. Serum Sex Hormone Binding Globulin (SHBG).
b. Serum High Sensitive C-Reactive Protein (hsCRP).
MATERIALS AND METHODS:
7.1 Source of data :
The study will comprise of preeclamptic primigravida patients of gestational age above 20 weeks in Department of Obstetrics and Gynecology, Vani Vilas Hospital and Bowring & Lady Curzon Hospital attached to Bangalore Medical College and Research Institute. Study is from November 2011 to May 2013.
A. Inclusion criteria
a. Preeclamptic primigravida of gestational age above 20 weeks.
b. The diagnosis of preeclampsia was made according to the criteria by American College of Obstetrics and Gynecology 8
1. Blood pressure higher than 140/90 mmHg.
2. Edema.
3. Proteinuria >300mg/24 hours or 1+ dipstic method after 20th weeks of gestation.
B. Exclusion criteria
a. Patients with history of Gestational Diabetes Mellitus.
b. Patients with history of Essential Hypertension, Diabetes Mellitus and other Cardio-Vascular Diseases.
c. Patients with history of Hypothyroidism.
d. Patients with history of taking Corticosteroid Therapy.
e. Patients with history of any Inflammatory Diseases.
C. Controls
Normal pregnant women of same gestational age group without any complications
7.2 Method of collection of data:
7.2a Method of sample collection:
After obtaining informed consent from the cases and controls for the proposed study, about 5 ml of venous blood will be obtained by venepuncture under aseptic conditions, centrifuged and the separated serum will be used for estimation of the parameters required for the study.
7.2b Sample size:
After consulting statistician, sample size is estimated to be 60, with 30 cases and 30 normal pregnant women, selected randomly.
7.2c Type of study:
Case control study
7.2d Statistical analysis:
Chi square test
Fischer Exact test.
Any other appropriate test method will be used at the time of analysis if necessary.
7.3 Does the study require any investigations, interventions to be conducted on patients or other humans or animals? If so please describe briefly.
YES
The study requires the following investigations to be conducted on patients and controls.
Parameters to be studied
1. Sex hormone binding globulin (SHBG).
2. High sensitive C- reactive protein (hsCRP).
3. Urine for Proteins.
4. Estimation of Blood sugar (FBS, PPBS).
5. Lipid profile.
6. Liver function test.
7. Estimation of Urea.
8. Estimation of Creatinine.
9. Estimation of Uric acid.
10. Complete Haemogram.
11. Antenatal ultrasonography.
7.4 Has ethical clearance been obtained from your institution in case of 7.3?
YES.
LIST OF REFERENCES
1. D C Dutta Textbook of Obtetrics Including Perinatalology and Contraception; Hypertensive Disorders In Pregnancy.2011;7:219 .
2. Hossein Ayatollahi, Maliheh Hasanzade, Madi Farzadnia, Mahdi Khabbaz Khoob, Atefeh Rahmanian. Serum Level Of High Sensitive C-reactive Protein In Normal And Preeclamptic Pregnancies. Iranian Journal Of Pathology. 2007;2(3):100-04.
3. Myles Wolf, Carl A. Hubel, Chun Lam, Marybeth Sampson, Jeferry L. Ecker et al. Preeclampsia And Future Cardiovascular Disease: Potential Role Of Altered Angiogenesis And Insulin Resistance. Journal Of Clinical Endocrinology & Metabolism. 2004;89(12):6239-43.
4. Laurence M. Demers, Ronald J. Whittey; Functions Of Adrenal Cortex; Tietz Book Of Clinical Chemistry; Carl A. Burtis, Edward R. Ashwood. W. B. Saudders company. 1999;3;1539.
5. David M. Carty, Christian Delles, Anna F. Dominiczak. Novel Biomarkers For Predicting Preeclampsia. Trends In Cardiovascular Medicine 2008;18(5-24):186-94.
6. Ellen W. Seely, Caren G. Solomon. Insulin Resistance And Its Potential Role In Pregnancy Induced Hypertention. Journal Of Endocrinology And Metabolism. 2003;88(6):2393-98.
7. Milan Stefanovic, Predrag Vukomanovic, Mileva Milosavljevic, Ranko Kutlesic, Jasmina Popovic et al. Insulin Resistance And C-Reactive Protein In Preeclampsia. Bosnian Journal Of Basic Medical Sciences. 2009;9(3):235-38.
8. Anil Bargale, Jayashree V. Ganu, Dhiraj J. Trivedi, Nitin Nagale, Rakesh Mudaraddi et al. Serum HS-CRP And Uric Acid As Indicator Of Severity In Preeclampsia. International Journal Of Pharma And Biosciences. 2011;2(3):340- 45.
9. Myles Wolf, Laura Sandler, Kristine Munoz, Karen Hsu, Jeffery l. Ecker et al. First Trimester Insulin Resistance And Subsequent Preeclampsia: A Prospective Study. Archive.2002;87(4):1563-72.
10. Risto Kaaja, Hannele Laivuori, Pekka Pulkki, Matti J. Tikkanen , Vilho Hiilesmaa et al. Is There Any Link Between Insulin Resistance And Inflammation In Established Preeclampsia? Journal Of Metabolism. 2004;53(11):1433-5.
11. Berkowitz KM. Insulin Resistance And Preeclampsia. Clinical Perinatology. 1998;25(4 ):873-85.
9. / Signature of the candidate:
10. / Remarks of the guide : / In view of preeclampsia being a life threatening condition, which is associated with insulin resistance and endothelial dysfunction, checking for SHBG as a marker of insulin resistance and hsCRP as a marker of endothelial dysfunction in our population is of great significance as these patients are at risk of developing cardiovascular diseases in later life.
11. / Name and Designation of Guide: ( in block letters)
11.1 Guide: / Dr. VIBHA. C M.D
Associate Professor,
Department of Biochemistry,
Bangalore Medical College and Research Institute, Bangalore.
11.2 Signature :
11.3 Co-Guide: / Dr. K. V. MALINI. M.D DGO, MICOG, PGDMLE
Professor Of Obstetrics And Gynecology,
Department of Obstetrics and Gynecology,
Bangalore Medical College and Research Institute, Bangalore.
11.4 Signature:
11.5 Head of the Department: / Dr. H. L. VISHWANATH M.D.
Professor and Head,
Department of Biochemistry,
Bangalore Medical College and Research Institute, Bangalore.
11.6 Signature:
12. / 12.1 Remarks of the chairman
and Principal:
12.2 Signature: