Dr. Nashita Patel On behalf of the UPBEAT Consortium Clinical Research Fellow to Professor Lucilla Poston

Long term risk Neonatal Obstetric Maternal T2DM Maternal and childhood obesity Abnormal offspring glucose homeostasis SGA/LGA >NICU admission Birth injuries Infection > CS PPH VTE PET PIH GDM

 Strong association between maternal BMI and healthcare costs  Mean costs 23% higher among overweight women  Mean costs 37% higher among obese women UK: normal weight £3546; overweight £4244; obese £4717

Re the IOM GUIDELINES * ‘ The recommendations were not validated by intervention studies. Without evidence from large-scale trials, it is not clear whether or not adhering to the recommended ranges lowers the risk of adverse outcomes for mothers and their babies.’

Adipose tissueAdiponectinGDMFetal Metabolic memory Macrosomia Offspring obesityOffspring insulin resistance TNF-α, IL-6 Leptin IL-2, IL-12, IFN-γ IL-4, IL-5, IL-10, IL-13 Fetal hypothalamic neuro-peptides Fetal hypothalamus IL-2, IL-12, IFN-γ Glucose, Lipids, insulin Background

2 year old Children of Diabetic Women Treated with Metformin Have Higher Skin Folds Thickness than Children of Mothers Treated with Insulin

LIMIT trial; Dodd et al (BMJ 2014) The first lifestyle RCT powered for clinical outcomes 2152 Overweight and obese women Primary outcome: LGA Results: No significant difference in primary outcome Significant reduction (20%) in BW>4kg No reduction in GWG

IG POP study Pilot trial of a slow digesting low GI supplement on blood glucose during an obese pregnancy Inform the design of a nutritional intervention RCT of dietary advice with LGI supplement in an obese pregnancy

1.Significant reduction in post prandial glycaemia at breakfast & dinner 2.Significant reduction in overall daytime glucose vs. control and habitual diet 3.Significant reduction in nocturnal glucose vs. habitual diet

* Complex intervention in 1546 obese women * Diet; Low Glycemic load, reduce saturated fat and free sugars * Exercise; Mild to moderate exercise * Primary Outcome: * Maternal: OGTT 28 weeks. (IADPSG criteria) * Neonatal; Delivery of Large for Gestational Age infant * (LGA >90 th Customised Centile ) * Secondary Outcomes: * Childhood adiposity at 6mths and 3 years

18 Recruitment BMI >30kg/m 2 Randomisation weeks’ gestation All women Intervention arm Baseline Physical Activity (PA), Diet 28 weeks’ gestation OGTT, PA, Diet 36 weeks’ gestation PA, Diet 1:1 Health Trainer Interview Handbook Exercise DVD 8 weekly sessions (SMART goals) 1:1 Health Trainer Interview Handbook Exercise DVD 8 weekly sessions (SMART goals) Pregnancy outcome Childhood follow up

PILOT ControlInterventionDifference (95% CI) p Total Energy Intake (MJ/d) Baseline7.53 (2.2)7.26 (2.29) 28 weeks7.71 (2.30)6.75(2.57)-0.94 (-1.72 to -0.18) Dietary Glycemic Load (g/d) Baseline133 (48)129 (41) < weeks146 (55)111 (39)−33 (−47 to −20) Total fat (%E)Baseline36.0(8.2)34.9(9.3) weeks35.9(7.7)32.5 (7.4)−3.2 (−5.6 to −0.8) Saturated FA (%E)Baseline12.7 (3.9)12.0 (4.3) weeks12.9 (3.9)11.1 (3.8)−1.6 (−2.8 to −0.3) (183 Obese Pregnant Women) Influence of Intervention on Diet (Poston et al, BMC Pregnancy Childbirth 2013)

PILOT ControlInterventionp Western Diet Score 0.42 (-0.49 to 1.47) (-1.13 to 0.58) Meat and Rice Diet Score 0.10 (-0.74 to 0.59) (-0.78 to 0.29) Healthy- unhealthy choices diet score 0.50 (-0.62 to 1.42) (-1.51 to 0.37) <0.001 Influence of Intervention on Dietary Patterns

PILOT Influence of Intervention on Plasma Cholesterol

PILOT Assessment of physical activity 1. Using accelerometer 2. RPAQ self report questionnaire NO change Minor increase as reported by questionnaire

PILOT Only intervene in obese women at risk of GDM?

PILOT Prediction of GDM at weeks’ gestation in obese women; a preliminary study Significant clinical variables: age, parity, ethnicity, BP, triceps & sum of skinfolds Clinical risk factors alone AUC= basic model + Adiponectin AUC= Basic model + Adiponectin + AST (aspartate aminotransferase) AUC= Maitland et al, Diabetic Medicine 2014; 8:963

PILOT Microalbuminuria as a predictor of GDM in obese pregnant women? UPBEAT pilot trial. Clinical risk factors alone Clinical risk factors alone + ACR

Summer 2014: Recruitment target reached (n=1556) End November 2014: All maternal and neonatal outcome data available January 2015: UPBEAT MAIN TRIAL RESULTS