Gestational Diabetes Clinical Trial
— InDiaGDMOfficial title:
The Role of Epigenetics in the Vicious Cycle of Diabetes and Pregnancy (VICYDIP)
Verified date | March 2019 |
Source | Kem Hospital, Pune, India |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Observational |
India is one of the diabetes capitals in the world. Indians are susceptible to develop diabetes at a younger age and at a lower BMI compared to Europeans. Current prevention strategies focus on reducing risk in those with the established disease or risk factors. The Developmental Origins of Health and Disease (DOHaD) hypothesis suggests that chronic non-communicable diseases (NCDs) are programmed by disturbances in maternal and fetal undernutrition. This offers an alternative primordial prevention strategy to reduce NCDs in future generations by improving health and nutrition of young women. Previous work in the Diabetes Unit, KEM Hospital, Pune has described the role of maternal micronutrients affecting 1-Carbon metabolism in the fetal programming of diabesity. In this application, the investigators offer to study other pathways of fetal programming i.e. maternal hyperglycemia and gestational diabetes mellitus (GDM) using an 'OMICs' approach. It is believed that epigenetic changes may be the main driver of programming. The investigators hypothesize that offspring of diabetic mothers will have different epigenetic signatures in cord blood and placenta compared to offspring of non-diabetic mothers. The investigators propose to study the effect of gestational hyperglycemia on newborn epigenetic signatures using the most appropriate technologies available and associate them with the underlying genotype. This will be performed on cord blood of 150 offspring of women with GDM and compared with a similar number of offspring of non-diabetic mothers recruited at Pune. The differentially methylated regions (DMRs) identified will then be validated by pyrosequencing in ~300 stored GDM cord blood samples in Pune. The investigators from Pune will also validate these markers in 200 newly recruited offspring of GDM and 200 controls from a different cohort in Punjab which has a different diet and lifestyle. The DMRs will also be validated in placental samples from both Pune and Punjab. The investigators will further test the stability of these markers and their associations with phenotype in a follow-up study of offspring of GDM mothers in upto 500 individuals. The investigators will compare the findings with the DNBC-GDM cohort in Denmark, allowing for differences in age, genetic make up, nutritional status and lifestyle. This study will help understand contribution of maternal diabetes to the current epidemic of diabesity and its molecular basis.
Status | Completed |
Enrollment | 1178 |
Est. completion date | November 30, 2018 |
Est. primary completion date | November 30, 2018 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | N/A and older |
Eligibility |
Inclusion Criteria: Arm 1 and 2: 1. GDM or NGT on 75g OGTT (IADPSG Criteria). 2. Willing to participate and sign consent 3. Planned delivery at study site 4. Age > 18 years 5. Singleton pregnancy. Arm 3: 1. Offspring of diabetic mothers and non diabetic mothers ( >2 years of age). Exclusion Criteria: Arm 1 and 2: 1. Severe medical/ surgical illness detrimental to pregnancy or delivery (Severe liver, renal, cardiovascular, pulmonary, hematologic, endocrine disorder or long term steroid use for any reason) 2. K/C/O Diabetes (Type 1 or Type 2 or any other type) 3. Severe anemia (Hemoglobin< 9 gm% in first trimester and < 8 gm% in second or third trimester) 4. IVF pregnancy. Arm 3: None. |
Country | Name | City | State |
---|---|---|---|
India | KEM Hospital | Pune | Maharashtra |
Lead Sponsor | Collaborator |
---|---|
Kem Hospital, Pune, India | Centre for Cellular and Molecular Biology, Hyderabad, India |
India,
Dabelea D, Pettitt DJ. Intrauterine diabetic environment confers risks for type 2 diabetes mellitus and obesity in the offspring, in addition to genetic susceptibility. J Pediatr Endocrinol Metab. 2001 Sep-Oct;14(8):1085-91. Review. — View Citation
Gluckman PD, Hanson MA, Cooper C, Thornburg KL. Effect of in utero and early-life conditions on adult health and disease. N Engl J Med. 2008 Jul 3;359(1):61-73. doi: 10.1056/NEJMra0708473. Review. — View Citation
Kale SD, Kulkarni SR, Lubree HG, Meenakumari K, Deshpande VU, Rege SS, Deshpande J, Coyaji KJ, Yajnik CS. Characteristics of gestational diabetic mothers and their babies in an Indian diabetes clinic. J Assoc Physicians India. 2005 Oct;53:857-63. — View Citation
Kale SD, Yajnik CS, Kulkarni SR, Meenakumari K, Joglekar AA, Khorsand N, Ladkat RS, Ramdas LV, Lubree HG. High risk of diabetes and metabolic syndrome in Indian women with gestational diabetes mellitus. Diabet Med. 2004 Nov;21(11):1257-8. — View Citation
Ma RC, Tutino GE, Lillycrop KA, Hanson MA, Tam WH. Maternal diabetes, gestational diabetes and the role of epigenetics in their long term effects on offspring. Prog Biophys Mol Biol. 2015 Jul;118(1-2):55-68. doi: 10.1016/j.pbiomolbio.2015.02.010. Epub 2015 Mar 16. Review. — View Citation
Petitt DJ, Bennett PH, Knowler WC, Baird HR, Aleck KA. Gestational diabetes mellitus and impaired glucose tolerance during pregnancy. Long-term effects on obesity and glucose tolerance in the offspring. Diabetes. 1985 Jun;34 Suppl 2:119-22. — View Citation
Wu L, Cui L, Tam WH, Ma RC, Wang CC. Genetic variants associated with gestational diabetes mellitus: a meta-analysis and subgroup analysis. Sci Rep. 2016 Jul 29;6:30539. doi: 10.1038/srep30539. Review. — View Citation
Yajnik CS. Fetal programming of diabetes: still so much to learn! Diabetes Care. 2010 May;33(5):1146-8. doi: 10.2337/dc10-0407. — View Citation
Yajnik CS. Transmission of obesity-adiposity and related disorders from the mother to the baby. Ann Nutr Metab. 2014;64 Suppl 1:8-17. doi: 10.1159/000362608. Epub 2014 Jul 23. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Epigenetic signatures in the cord blood of the offspring of GDM mothers. | The Illumina Infinium Human Methylation 450K array will be used for DNA methylation study. It generates a quantitative measurement of DNA methylation for >480,000 CpG sites spanning all annotated genes and other functional motifs. Markers influencing risk of diabetes and obesity will be of special interest. Approximately 150 GDM and 150 normal glucose tolerant pregnancies will contribute the samples. | Upto 3 years from the start of the study | |
Secondary | Association of the genotype with differentially methylated DNA regions. | The Human OmniExpress Exome BeadChip will be used for generating genome wide data. It provides a backbone of >700,000 genome-wide markers (SNPs >5% minor allele frequencies) and 240,000 coding SNPs of all frequencies. This will allow to identify the variants that act as meQTLS. | Upto 3.5 years from the start of the study | |
Secondary | Validation of the epigenetic signatures generated in Primary Outcome 1. | Quantitative profile of DNA methylation at specific CpG sites will be done using Bisulfite Pyrosequencing [Sequenom EpiTYPER], in cord blood samples obtained in Pune and in Ludhiana. | Upto 3.5 years from the start of the study | |
Secondary | Stability of epigenetic signatures discovered in the cord blood in offspring GDM mothers from childhood through adolescence. | The cord blood differential epigenetic signatures will be investigated in the blood sample of the offspring of GDM mothers during childhood and adolescence. These children were born to GDM patients attending the diabetes clinic at KEM hospital, Pune over last 2 decades. | Upto 4 years from the start of the study | |
Secondary | Association between epigenetic signatures and offspring phenotype at birth , and in childhood and adolescence. | Following phenotype measures will be tested : Weight (Kg) Height (cm) BMI (Kg/m^2) Waist circumference (cm) Hip circumference (cm) Skinfolds (mm) DXA [ body composition measures: fat, lean and bone] Plasma Glucose concentration (mg/dl) in the cord blood and during an OGTT in childhood and adolescence. Plasma Insulin (mU/L) in the cord blood and during an OGTT in childhood and adolescence Glucose and insulin indices (HOMA measures) in 8, 9. Blood lipids (Cholesterol, HDL, LDL and Triglycerides) in the cord blood and during an OGTT in childhood and adolescence. |
Upto 4 years from the start of the study | |
Secondary | Qualitative and quantitative comparison of epigenetic signatures in the offspring of GDM mothers [Indian and Danish cohort]. | Epigenetic signatures from Indian and Denmark cohorts will be compared, taking into account differences in genetic background, nutrition and lifestyle. Comparison will focus on the direction and strength of associations, and the metabolic pathways implicated in the above analysis. |
Upto 4.5 years from the start of the study |
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