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Title: Mechanisms of insulin resistance in obese pregnant women : potential therapeutic interventions
Author: Maitland, Rahat Ashraf
ISNI:       0000 0004 5990 9323
Awarding Body: King's College London
Current Institution: King's College London (University of London)
Date of Award: 2016
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Maternal obesity is associated with adverse pregnancy outcomes, especially the development of gestational diabetes mellitus (GDM), with associated risks for mother and infant. Improved understanding of glucose intolerance in obese women and better prediction and prevention of GDM is key to improving the health of mother and her child. This thesis reports two related projects. The first explored mechanisms of insulin resistance and prediction of GDM in obese pregnant women participating in the pilot study for the UK Pregnancies Better Eating and Activity Trial (UPBEAT), a lifestyle intervention RCT. The second investigated the potential of a dietary intervention to improve glycaemic profiles in this high-risk group. Following an 8 week dietary and physical activity intervention, a panel of biomarkers associated with obesity and insulin resistance were measured in 117 women in the pilot trial. At 27+0-28+6 weeks’ no difference was observed between the intervention and control arms but at 34+0-35+6 weeks’, significant reductions in plasma visfatin, cholesterol and LDL cholesterol were observed. Analysis by GDM status, confirmed greater concentrations of fructosamine, AST and insulin and lower plasma leptin and adiponectin in women who developed GDM. An algorithm based on clinical factors alone (age, parity, ethnicity and blood pressure at 15+0-18+6 weeks’ gestation) showed predictive potential which increased significantly with the addition of plasma adiponectin measured at 15+0-18+6 weeks. In obese pregnant women without GDM (n=16,) the effect of a slow-digesting low glycaemic index (SD-LGI) supplement drink was evaluated at 24+0-28+6 weeks’ gestation. Linear regression analysis with mixed modelling (LMM) showed a significant reduction in glycaemia over the 24 hour period following consumption of the test compared to the control supplement and habitual diet. Fasting and nocturnal glucose concentrations were also significantly improved. In summary biomarkers associated with insulin resistance were identified as potential targets for lifestyle interventions aimed at reducing GDM in obese women. A prediction model for GDM identified those at greatest risk and pending validation in the UPBEAT RCT may have the potential for translation into clinical care. Extending the role of interventions further, multiple improvements in parameters of glycaemic control were demonstrated using a SD-LGI nutritional supplement.
Supervisor: Poston, Lucilla ; academic, affiliated Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available