Mothers who develop gestational diabetes have a higher risk of developing type 2 diabetes in later life, and their children are known to develop greater adiposity and have an increased risk of young-onset obesity and type 2 diabetes. Gestational diabetes is an example of an exposure that programmes the fetus through an oversupply of nutrients (glucose, lipids and amino acids).

The Mysore Parthenon Study (link to Mysore Parthenon Cohort) was set up to study the long-term effects of gestational diabetes mellitus (GDM) on children. It has shown that babies born to GDM mothers were larger at birth and had more subcutaneous fat than children of non-GDM mothers. The difference in adiposity continued throughout childhood (Figure (a)), and at 9 and 13 years the children of GDM mothers had higher glucose and insulin concentrations (Figure (b)) and higher insulin resistance.

We have also measured children’s ‘stress responses’: cortisol levels (reflecting HPA axis activation) and cardiovascular responses (reflecting sympathetic nervous system activation) during a Trier Social Stress Test (TSST). In the TSST, participants are asked to perform a public speaking task and mental arithmetic task in front of a panel of unfamiliar ‘judges’; it takes about 20 minutes. It is a method used in research to create a feeling of stress. The study showed that children of GDM mothers had normal cortisol responses during the TSST, but had greater cardiovascular responses (higher pulse rate, blood pressure, stroke volume and cardiac output) than children of non-GDM mothers (Figure (c).

How are we taking this work forward?

  • The Mysore Parthenon Cohort members are now aged ~20 years. In 2019-2020 we are repeating the TSST measurements to examine whether the above changes in relation to fetal GDM exposure still hold true as the participants reach adulthood
  • In 2019-2021 we are studying the effects of GDM on children in other birth cohorts in Pune and Mumbai
  • We are partnering with an intervention study taking place in Vellore, India and The Gambia, which aims to test whether increasing maternal physical activity and/or a probiotic (a daily portion of live yoghurt intake) starting before 18 weeks’ gestation will reduce the incidence of GDM compared with standard care. The PRIMORDIAL study (Pregnancy Interventions in Mothers Relating to Diabetes in Asian Indian and Low-income countries, 2019-2022) is led by Prof Fredrik Karpe (Director, Oxford Centre for Diabetes, Endocrinology and Metabolism) in collaboration with Dr Senthil Vasan Kandaswamy, Dr Jiji Matthews, Department of Obstetrics, Christian Medical College, Vellore and Prof Andrew Prentice, MRC The Gambia at the London School of Hygiene and Tropical Medicine. If the interventions are successful in reducing the incidence of GDM, we plan to follow up the children, to look at the longer-term impact on their health.

Selected recent publications on gestational diabetes:

  • Krishnaveni GV, Veena SR, Hill JC, Kehoe S, Karat SC, Fall CHD. Intra-uterine exposure to maternal diabetes is associated with higher adiposity and insulin resistance and clustering of cardiovascular risk markers in Indian children. Diabetes Care 2010; 33: 402-4. PMID: 19918007
  • Veena SR, Krishnaveni GV, Srinivasan K, Kurpad AV, Muthayya S, Hill JC, Kiran KN, Fall CHD. Childhood Cognitive Ability: Relationship to Gestational Diabetes Mellitus in India. Diabetologia 2010 53:2134-2138. PMID: 20614102
  • Krishnaveni GV, Veena SR, Hill JC, Karat SC Fall CHD. Cohort Profile: Mysore Parthenon Birth Cohort. Int J Epidemiol 2015; 44: 28-36. PMID: 24609067
  • Krishnaveni GV, Veena SR, Jones A, Srinivasan K, Osmond C, Karat SC, Kurpad AV, Fall CHD. Exposure to maternal gestational diabetes is associated with higher cardiovascular responses to stress in adolescent Indians. J Clin Endocrinol Metab 2015; 100:986-93. PMID: 25478935