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Latest insight into dietary strategies for gestational diabetes mellitus (GDM)
Katherine Macé, PhD
Head of Metabolic health department
Institute of Nutritional Science - Nestlé Research Center
Food Matters, ExCeL, London
Nutritional Management of Diabetes and Obesity
23rd November 2017
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Definition, screening and most widely accepteddiagnostic criteria
Hyperglycemia that is first detected during pregnancy* (WHO, 2013)
*most likely after 24 weeks
Plasma glucose
Fasting Random 1 hr 75 g
OGTT
2 hr 75 g
OGTT
WHO-1999 ≥ 7 mmol/L
(126 mg/dL)
≥ 11.1 mmol/L
(200 mg/dL)
- ≥ 11.1 mmol/L
(200 mg/dL)
IADPSG
WHO-2013
≥ 5.1 mmol/L
(92 mg/dL)
- ≥ 10.0 mmol/L
(180 mg/dL)
≥ 8.5 mmol/L
(153 mg/dL)
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GDM prevalence estimates
1From International Diabetes Federation (IDF)2Brown and Wyckoff. Curr Diab Rep (2017)
• 1 in 7 births is affected by gestational diabetes1
• ~17% of pregnancies worldwide
• Up to 45% in some regions2
BUT
Lack of systematic data on global prevalence
Depend on the screening criteria
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Reported prevalence of GDM by country
Previous criteria
HAPO
IADPSG
Brown and Wyckoff. Curr Diab Rep (2017)
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GDM risk factors are numerous…
• Non Caucasian ethnicity
• Older age
• High parity
• Overweight and obesity
• Excessive gestational weight gain
• Polycystic ovarian syndrome (PCOS)
• History of diabetes among relatives
• GDM in previous pregnancy
• Pre-eclampsia and multifetal pregnancy
• Short stature
Hod et al., Int. J. Gynecol. Obstet. 2015
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…as well as the maternal and offsprings short- and long-term adverse outcomes
Hod et al., Int. J. Gynecol. Obstet. 2015
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Risks of subsequent metabolic outcomes in mother and offspring
Outcome OR or RR (95% CI) vs women without the conditions
GDM GDM + overweight/obese
Postpartum T2DM (mother) 7.4 (4.8-11.5) 8.7 (2.3-32.9)
T2DM later in life (offspring) 3.9 (1.1-14.5) 19.2 (6.1-60.8)
High birth weight1 2.2 (1.9-2.5) 3.6 (3.0-4.3)
High neonatal adiposity1 2.0 (1.7-2.3) 3.7 (3.1-4.4)
Childhood obesity2 3.6 (1.3-9.9) 5.6 (1.7-18.2)
T2DM: type 2 diabetes mellitus, OR: odds ratio; RR: relative risk1>90th percentile; 2girls with BMI>85th percentile at age 6-8 yrs
From Silva-Zolezzi et al., Nutr. Rev. 2017
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Diet and Exercise are the first line therapy for GDM
+ Drug treatments (i.e., Insulin, oral agents)
Diabetes Care (2017) 40:S144-S119
Primary goal of therapy is to achieve normal blood
glucose while promoting adequate GWG
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Dietary strategies for GDM management Cochrane review
• Energy restriction 3 RCT, n=413 women with calorie restricted diet (-35 kcal/kg ideal BW; 1200 kcal/day; 30% E restriction) ->
Possible benefits for glycemic control (FPG, 1h-OGTT) (2 trials). No clear infant benefit.
• Fat: high vs low mono-unsaturated fat (MUFA) diet 2 RCT, n=111 women (High MUFA: 20% E; 50 vs 20 g sunflower oil/daily) ->
No clear maternal and infant benefits and some less favorable observations for maternal
glycemic/insulinemic control (1 trial)
• Proteins: Soy protein enriched diet1 RCT, n=68 women (0.8 g/kg protein with 35% vs no soy protein) ->
Possible benefit for maternal glycemic control (FPG) and less infant born with jaundice.
Han et al., Cochrane Database Syst. Rev. 2017
19 trials assessing different types of dietary interventions on >10 outcomes
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Dietary strategies for GDM management – Cond’tCochrane review
• Carbohydrate:
• Low vs high carb diet: 2 RCT, n= 182 women (45 vs 60% carb; 40 vs 55% carb) ->
No clear maternal and infant benefits. Decreased gestational weight gain (1 trial)
• Low-moderate GI vs moderate high GI diet: 4 RCT, n=224 women ->
Possible benefits for maternal glycemic control (2h-OGTT) (1 trial). Less insulin use (1 trial). No
clear infant benefit
• DASH diet:3 RCT, n=136 women (DASH diet vs control diet with matching macronutrient contents)
Fewer macrosomic babies, lower birth weight and HC (2 trials). Possible benefits for maternal
insulin sensitivity (HOMA) (1 trial) and glycemic control (FPG) (2 trials). Reduced risk of c-section
Han et al., Cochrane Database Syst. Rev. 2017
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No consensus about an optimal diet
• Limited number of good quality studies
• Small sample size
• Short duration of the intervention
• Low compliance
• Different outcomes
• Different GDM diagnosis criteria
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Lack of sufficient evidence to make strong dietary recommendations for GDM management
• Some guidelines not different than normal pregnancy1
• Some focus on carbohydrates: min of 175 g/day with 35-50% of total E,
predominantly low GI and distributed over 3 meals and 2-4 snacks2
• Trend to move towards “healthy/balanced diet” (i.e, high in fruits/vegetable, fibers,
whole grains, low in saturated fat and added sugars)
1ADA, 2ACOG, Endocrine Society
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On going GDM management RCT
• Carbohydrate Counting and DASH Intervention and Pregnancy
Outcomes (NCT03244579)
• A Mobile Smartphone Application to Promote a Healthy Diet and
Physical Activity (NCT02588729)
• Chrono Nutrition (CN) Intervention Program (NCT0291667)
From clinicaltrials.gov
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Does GDM management ameliorate long term suboptimal
metabolic effects on the offspring?
• Treatment of mild GDM has shown beneficial effects in outcomes at birth (macrosomia,
birthweight, adiposity), but no BMI differences have been yet observed in childhood (4-5 and
10 years of age).1,2
• Daughters of treated GDMs had shown reduced: 1) frequency of impaired fasting glucose, 2)
fasting glucose, and 3) log HOMA-IR.2
1) Gillman MW et al., 2010, Diabetes Care; 2) Landon et al., 2015, Diabetes Care
Lack of an effect on childhood BMI may be due to:
1) Lack of statistical power
2) Low severity of GDM
3) insufficient reduction of glucose levels
4) effects only later than when analyzed.
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Time for a paradigm shift?:From management to prevention
Preconception
1st trimester
0-13 weeks3rd trimester
28-41 weeks
2nd trimester
14-27 weeks
Pregnancy
OGTT test
24-28 weeks
“Late” prevention“Early” prevention Management
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Dietary strategies for GDM prevention in healthy or at risk pregnancy
From Silva-Zolezzi et al., Nutr. Rev. 2017 and Samuel et al., IUNS 21st ICN, 2017
Dietary supplement interventions
BUT small sample size and high heterogeneity in study
populations, baseline nutrient status & intervention dosage
Most interventions starting mid or late pregnancy
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Two supplements have shown promising results to help reduce GDM risk
* Lactobacillus rhamnosus NCC4007 is also known as LPR, and Bifidobacterium lactis NCC2818 is also known as BL818; 1. Croze M, Soulage CO. Biochimie. 2013; 95: 1811-1827. 2. Clements RS Jr, Darnell B. Am J Clin Nutr. 1980; 33: 1954-
1967. 3. Sanders ME. Clin Infect Dis. 2008; 48 (Suppl 2): S58-S61. 4. D’Anna R et al. Obstet Gynecol. 2015; 126: 310-5. 5. D’Anna R et al. Diabetes Care. 2013; 36: 854-857. 6. Matarrelli B et al. J Matern Fetal Neonatal Med. 2013; 26: 967-72. 7.
D’Anna R et al. Gynecol Endocrinol . 2012; 28: 440-442. 8. Luoto R et al. Br J Nutr. 2010; 103:1792-1799. 9. Allen SJ et al. J Nutr 2010; 140: 483–488.
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Two supplements have shown promising results to help reduce GDM risk, Cond’t
* Lactobacillus rhamnosus NCC4007 is also known as LPR, and Bifidobacterium lactis NCC2818 is also known as BL818; 1. Croze M, Soulage CO. Biochimie. 2013; 95: 1811-1827. 2. Clements RS Jr, Darnell B. Am J Clin Nutr. 1980; 33: 1954-
1967. 3. Sanders ME. Clin Infect Dis. 2008; 48 (Suppl 2): S58-S61. 4. D’Anna R et al. Obstet Gynecol. 2015; 126: 310-5. 5. D’Anna R et al. Diabetes Care. 2013; 36: 854-857. 6. Matarrelli B et al. J Matern Fetal Neonatal Med. 2013; 26: 967-72. 7.
D’Anna R et al. Gynecol Endocrinol . 2012; 28: 440-442. 8. Luoto R et al. Br J Nutr. 2010; 103:1792-1799. 9. Allen SJ et al. J Nutr 2010; 140: 483–488.
High quality large randomized clinical trials are needed
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On going GDM risk prevention RCT
• Effect of Probiotics (Vivomixx®) on Weight, Microbiota and Glucose
Tolerance in Obese Pregnant Women and Their Newborn (POP)
(NCT02508844) – wk 14-20
• Nutritional Intervention Preconception and During Pregnancy to
Maintain Healthy Glucose Metabolism and Offspring Health
(NiPPeR) (NCT02509988) - Preconception
From clinicaltrials.gov
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20
Nutritional Intervention Preconception and during Pregnancy to maintain
healthy glucosE levels and offspRing health
Analysis of a diverse population, with 5 different ethnic groups in 3 geographical locations
Primary outcome: maternal glucose metabolism (FPG and OGTT) at 28 weeks’ gestation
Follow-up examining the impact of intervention on both maternal and infant metabolic health - from
pre-conception to baby’s first year of life.
Building cutting-edge knowledge togetherGodfrey KM and the NiPPeR Study Group (2017) Trials
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Summary
• Increasing prevalence of GDM, a growing public health concern
• Health impact on the next generation (vicious circle)
• Lack of sufficient evidence to make strong dietary recommendations for GDM
management AND prevention
• Intervention of too short duration (mid to late pregnancy) -> preconception
• Potential benefit of nutritional supplements (myo-inositol, probiotics)
• Need of well-designed, large RCTs
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World Diabetes Day 2017 to focus on women and diabetes