Research Proposal - ICMR STS 2019 1. Title: Thyroid Auto-Immune Response in Pregnant Women With Gestational Diabetes Mellitus 2. Objective

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Aravind Karthik R

Research proposal - ICMR STS 2019

1. Title:

Thyroid auto-immune response in pregnant women with Gestational diabetes mellitus

2. Objective:

a. The present study is aimed to assess the thyroid biochemical profile Serum T4, T3, TSH and
estimate the anti TPO in pregnant women with GDM and control group

b. Background

Diabetes is one of the most prevalent endocrine disorders during pregnancy. Gestational diabetes
(GDM) is defined as any degree of carbohydrate intolerance that is first diagnosed during
pregnancy [1]. GDM is most frequent in women aged ≥35 years during 24-28 weeks of
pregnancy. Hyperglycemia in pregnancy is associated with adverse maternal and prenatal
outcome. GDM associated with serious complications for both the mother (preeclampsia,
stillbirths, macrosomia, and need for cesarean section) and child (hypoglycemia, respiratory
distress), and adverse consequences on the fetus and the mother increase linearly with increasing
maternal blood glucose level. Also it increases the risk of future Type 2 diabetes in mother as
well as the baby.

GDM prevalence usually reflects the magnitude of type 2 diabetes in the underlying population.
Wide variations in the prevalence of gestational diabetes mellitus (GDM), 1-21%, have been
reported globally. India has the highest number of diabetics after China; however, no national
data is available on the disease burden of GDM. The prevalence of gestational diabetes reported
in Tamilnadu as 17.9% [2].

The GDM prevalence was 3% (1991-2000), 11% (2001-2010) and 12% (2011-2015), the burden
goes increasing. However variations in diagnostic criteria, geographic region and the study
period showed a significant influence on this estimate. According to a report presented in 21st
International Epidemiological Association (IEA) World Congress of Epidemiology (WCE2017)
a recent systematic review and meta-analysis showed the gestational diabetes mellitus prevalence
in the Indian women as high as 8.7%. The pooled estimate of the GDM prevalence among Indian
women was 8.7% (95% Confidence Interval: 7.1% to 10.5%).

When compared to caucasian women and also among ethnic group in south asian countries,
Indian women have the high frequency of GDM [3]. It is important to screen, diagnose and treat
hyperglycemia in pregnancy to prevent an adverse outcome.14% case load of GDM is expected
in India in all Antenatal care (ANC) cases. Out of this 10-12% will be corrected with good
Aravind Karthik R

medical nutritional therapy, remaining 3% need Insulin therapy back up from government side.
On an average 5 units of insulin is required for 180 days which should be supported by
government to manage the condition.

Recent studies have reported increased incidence of thyroid autoimmunity in type 2 diabetes [4-
5], thus implying that diabetes can trigger the onset of thyroid autoimmunity. About 10- 15% of
pregnant women have thyroid dysfunction during the first half of pregnancy, which may be due
to hypo or hyperthyroidism. However, the prevalence of thyroid dysfunction in pregnant women
with type I diabetes is about three times more than general population and subclinical
hypothyroidism is more prevalent [6]. Few studies have reported high incidence of
hypothyroxinemia and high Anti TPO (anti Thyroid peroxidase antibodies) titer in GDM [7].
Prevalence of high titer of Anti TPO Ab in healthy pregnant women and type 1 diabetes also has
significant difference [8]. Delayed diagnosis of hypothyroidism in pregnancy leads to congenital
malformations and respiratory distress in newborns of these mothers [9].

Furthermore pregnant womans diabetes status during pregnancy can influence the secretion of
T3 or conversion of T4 to active T3 in the fetus and premature newborns [10]. When anti-thyroid
antibodies are positive, there is risk of premature rupture of amniotic sac and preterm labor [11].
Some studies have showed that even without the overt thyroid dysfunction, autoimmune thyroid
disease increases abortion rates up to 3 to 5 times. The purpose of this study was to evaluate
thyroid function tests and thyroid autoantibody level in pregnant patients with diabetes (GDM)
and comparison with a nondiabetic control group.

In our opinion, GDM offers a good opportunity to study if diabetes and hyperglycemia might
predispose to thyroid autoimmunity.

3. Methodology

a. Study design:
A prospective case control study

b. Study objectives

1. To estimate the thyroid profile (Free T3, Free T4 and TSH) in pregnant women with GDM
and without GDM
2. To estimate the anti TPO in pregnant women with GDM and without GDM.

c. Number of subjects:

100 pregnant women outpatients attending Department of obstetrics and gynaecology, hospital
and research Institute, were considered for the study. Among the pregnant woman 50 subjects
Aravind Karthik R

with GDM (study group) and 50 subjects without history of GDM (control group) will be
included in the study.
Calculation of sample size:
n=z2pq/l2 (p – prevalence, q- non occurrence) ; n= Sample size: n= 100

d. Subject selection:

4ml blood sample is taken from pregnant woman with and without GDM during 24-28 weeks
duration. GDM subjects taken following DIPSI recommendations

e. Inclusion criteria: Pregnant woman aged 19 to 47 years.

f. Exclusion criteria:

Women with a positive history for thyroid diseases and who are taking any drug known to
interfere with thyroid function or the immune system were excluded from the study.

g. Estimation method:

Serum Free T3, Free T4, TSH (Thyroid stimulating hormone) and anti TPO will be estimated by
chemiluminescence method.

4. Statistical methods:

SPSS software version 21 is used to analyze the data. To find out Mean comparison student t
Test will be used

5. Sources of funding and financial requirements for the proposal: Applying to ICMR STS
2019

6. Ethical issues involved and measures to be taken to prevent such:

The study will be conducted after obtaining approval by the institutional Human ethics
committee. Informed consent will be obtained from the patients who participate in the study. The
collected data will be kept confidential.

7. Implications and benefits of the project

This study expected to show that women with increased risk of GDM may have increased level
of Anti Thyroid peroxidase and it is normal in patients without GDM.
Aravind Karthik R

References:
1. American Diabetes Association, “Diagnosis and classification of diabetes mellitus (Position
Statement),” Diabetes Care, vol. 34, supplement 1, pp. S62–S69, 2011. 
2. Seshiah V, Balaji V, Balaji MS, Sanjeevi CB, Green A. Gestational diabetes mellitus in India. Japi. 2004
Sep;52:707-11
3. Bhavadharini B, Mahalakshmi MM, Anjana RM, Maheswari K, Uma R, Deepa M, Unnikrishnan R,
Ranjani H, Pastakia SD, Kayal A, Ninov L. Prevalence of Gestational Diabetes Mellitus in urban and rural
Tamil Nadu using IADPSG and WHO 1999 criteria (WINGS 6). Clinical diabetes and endocrinology. 2016
Dec;2(1):8.
4. S. A. P. Chubb, W. A. Davist, Z. Inman, and T. M. E. Davis, “Prevalence and progression of subclinical
hypothyroidism in women with type 2 diabetes: the fremantle diabetes study,” Clinical Endocrinology, vol.
62, no. 4, pp. 480–486, 2005. 
5. A. Olivieri, H. Valensise, F. Magnani et al., “High frequency of antithyroid autoantibodies in pregnant
women at increased risk of gestational diabetes mellitus,” European Journal of Endocrinology, vol. 143, no.
6, pp. 741–747, 2000. 
6. Gallas PR, Stolk RP, Bakker K, Endert E, Wiersinga WM. Thyroid dysfunction during pregnancy and in
the first postpartum year in women with diabetes mellitus type 1. European Journal of Endocrinology. 2002
Oct 1;147(4):443-51.
7. Agarwal MM, Dhatt GS, Punnose J, Bishawi B, Zayed R. Thyroid function abnormalities and antithyroid
antibody prevalence in pregnant women at high risk for gestational diabetes mellitus. Gynecol Endocrinol.
2006; 22(5):261-266.
8. Velkoska Nakova V, Krstevska B, Dimitrovski C, Simeonova S, Hadzi-Lega M, Serafimoski V. Prevalence
of thyroid dysfunction and autoimmunity in pregnant women with gestational and diabetes type 1.
Contributions, Sec. Biol. Med. Sci., MASA, XXXI, 2010; 2;31(2):51-9.
9. Soler NG, Nicholson H. Diabetes and thyroid disease during pregnancy. Obstet Gynecol. 1997; 54(3):318-
321.
10. Wilker RE, Fleischman AR, Saenger P, Pan C, Surks MI. Thyroid hormone levels in diabetic mothers and
their neonates. Am J Perinatol. 1984; 1(3):259-262.
11. Cleary-Goldman J, Malone FD, Lambert-Messerlian G, Sullivan L, Canick J, Porter TF,et al. Maternal
thyroid hypo function and pregnancy outcome. Obstet Gynecol. 2008; 112(1):85-92.

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