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Dr. Nashita Patel
On behalf of the UPBEAT Consortium
Clinical Research Fellow to Professor Lucilla Poston
*
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Long term risk
• T2DM
• Maternal and childhood obesity
• Abnormal offspring glucose
homeostasis
Neonatal
• SGA/LGA
• >NICU admission
• Birth injuries
Obstetric
• Infection
• > CS
• PPH
• VTE
Maternal
• 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
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*
*
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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.’
*
Background
Adipose tissue
Leptin
IL-2, IL-12,
IFN-γ
Adiponectin
TNF-α,
IL-6
GDM
Glucose,
Lipids, insulin
Macrosomia
IL-4, IL-5,
IL-10, IL-13
Fetal
hypothalamus
Fetal Metabolic memory
IL-2, IL-12,
IFN-γ
Fetal
hypothalamic
neuro-peptides
Offspring obesity
Offspring insulin
resistance
*
20
PNS
15
P=0.04
10
5
0
Upper arm Subscapular Biceps skin
circ
skin fold
fold
Total fat
2 year old Children of
Diabetic Women
Treated with Metformin
Metformin Have Higher Skin Folds
Thickness than
Insulin
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 >90th Customised Centile )
*Secondary Outcomes:
* Childhood adiposity at 6mths and 3 years
Recruitment BMI >30kg/m2
Randomisation 15+0-17+6 weeks’ gestation
All women
Baseline Physical Activity (PA), Diet
Intervention arm
1:1 Health Trainer Interview
Handbook
Exercise DVD
8 weekly sessions
(SMART goals)
28 weeks’ gestation OGTT, PA, Diet
36 weeks’ gestation PA, Diet
Pregnancy outcome
18
Childhood follow up
PILOT
(183 Obese Pregnant Women)
Influence of Intervention on Diet (Poston et al, BMC Pregnancy Childbirth 2013)
Control
Total Energy Intake
(MJ/d)
Dietary Glycemic Load
(g/d)
Total fat (%E)
Saturated FA (%E)
Intervention
Baseline
7.53 (2.2)
7.26 (2.29)
28 weeks
7.71 (2.30)
6.75(2.57)
Baseline
133 (48)
129 (41)
28 weeks
146 (55)
111 (39)
Baseline
36.0(8.2)
34.9(9.3)
28weeks
35.9(7.7)
32.5 (7.4)
Baseline
12.7 (3.9)
28weeks
12.9 (3.9)
Difference
(95% CI)
-0.94
(-1.72 to -0.18)
p
0.016
−33
(−47 to −20)
<0.001
−3.2
(−5.6 to −0.8)
0.010
−1.6
(−2.8 to −0.3)
0.015
12.0 (4.3)
11.1 (3.8)
PILOT
Influence of Intervention on Dietary Patterns
Control
Intervention
p
Western Diet
Score
0.42
(-0.49 to 1.47)
-0.40
(-1.13 to 0.58)
0.001
Meat and Rice
Diet Score
0.10
(-0.74 to 0.59)
-0.10
(-0.78 to 0.29)
0.497
Healthyunhealthy
choices diet
score
0.50 (-0.62 to
1.42)
-0.47
(-1.51 to 0.37)
<0.001
PILOT
Influence of Intervention on Plasma Cholesterol
Control
Control
Intervention
7
Intervention
4
3.5
LDL (mmol/L)
Cholesterol (mmol/L)
6.5
6
3
5.5
2.5
5
15-17+6
27-28+6
34-36+6
Gestational age
15-17+6
27-28+6
34-36+6
Gestational age
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 15-18 weeks’ gestation in obese women; a
preliminary study
Significant clinical
variables: age, parity,
ethnicity, BP, triceps &
sum of skinfolds
Clinical risk factors alone
AUC=0.7955
basic model + Adiponectin
AUC= 0.8571
Basic model + Adiponectin + AST
(aspartate aminotransferase)
AUC=0.8660
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
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