The risk of Insulin Resistence and
Metabolic Syndrome among
overweight/obese children born of
mothers with Gestational Diabetes
Mosca A., Vania A
Dept. of Paediatrics and Paediatric Neuropsychiatry,
“Sapienza” University of Rome, Italy
Gestational Diabetes Mellitus
• The incidence of Gestational Diabetes is increasing in the
context of the pandemics in obesity and type 2 Diabetes
Mellitus (1)
• the Prevalence of GDM ranges from 2% to 6%, with much
higher figures (up to 22%) in specific populations  Asian (2)
(1) Anna V et al.: Sociodemographic correlates of the increasing trend in prevalence of
gestational diabetes mellitus in a large population of women between 1995 and 2005.
Diabetes Care 2008;31:2288-93.
(2) Galtier F.: Definition, epidemiology, risk factors. Diabetes Metab 2010;36:628-51.
Definition of GDM
GDM is defined as a carbohydrate intolerance, of variable
severity, which is first recognized during pregnancy
GDM encompasses 2 different entities:
1- glucose tolerance defect, that generally
occurs in the second half of pregnancy and
disappears (at least temporarily) after the
delivery
2- prepregnancy diabetes (mainly DMT2 or
NIDDM), only discovered during pregnancy,
or triggered by pregnancy, that persists after
delivery.
Effect of Hyperglycemia
on Fetal Growth
In 2008, the Hyperglycemia and Adverse Pregnancy
Outcome (HAPO) study (3):
 Relationship between high maternal plasma
glucose and increased frequency of adverse
perinatal outcomes
 Association between high maternal glycemia and
fetal hyperinsulinism with birth weight >90th
percentile
 Association of maternal glycemia values with
excessive fetal growth, particularly of the fetus’
adipose tissue
(3) (HAPO) Study - Diabetes 2009;58:453-9.
Placental Modifications
 In GDM maternal metabolic environment is characterized
by insulin resistance and inflammation:
- The Insulin resistance facilitates maternal hypertriglyceridemia
that enhances substrates availability to the fetus.
 Placental abnormalities are frequent in diabetic
pregnancy::
- Genes for lipids transportation are upregulated in the placenta,
as well as genes for inflammation
- The epigenetic adaptations to a detrimental in-utero environment
may affect the short- and long-term metabolic regulation of the
newborn
Maternal Diabetes during pregnancy is a risk factor for
MACROSOMIA
Neonatal Complications
 Neonatal Respiratory Distress The risk of birth
injury was the highest for infants with a birth weight of
4500-4999 g and >5000 g (OR 2.4 [95% CI 2.2-2.5] and
3.5 [3.0-4.2]) (4)
Correlation between increased cord Cpeptide levels, macrosomia, and hypoglycemia (5)
 Fetal and Neonatal Malformations The risk for
congenital malformations in preexisting diabetes is 1.9- to
10-fold higher than that in the total population. (6)
(4)Esakoff TF et al.: The association between birthweight 4000 g or greater and perinatal outcomes in patients with and
without gestational diabetes mellitus. Am J Obstet Gynecol 2009;200:672.e1-e4.
(5) Sosenko IR et al.: The infant of the diabetic mother: correlation of increased cord C-peptide levels with macrosomia
and hypoglycemia. N Engl J Med 1979;301: 859-62.
(6) Allen VM et al.: Teratogenicity associated with pre-existing and gestational diabetes. J Obstet Gynaecol Can
2007;29:927-34.
Our study…
An increased risk of developing MS after 10 years of life in
children born to mothers with DG and showing higher
values of WC and BMI at the time has been found (7).
Insulin Resistance
Metabolic Syndrome
mothers with GDM
(7) Nehring I et al.: Gestational diabetes predicts the risk of childhood overweight
and abdominal circumference independent of maternal obesity. Diabet Med 2013
2380 Overweight or Obese Children
2042 children born to mothers NoGDM
Male
Female
338 children born to mother GDM
44,03
14,2
55,97
85,8
GDM
NoGDM
Anthropometric and laboratory parameters
Our study…
METABOLIC SYNDROMECRITERIA
WC ≥ 95°th
PAS-PAD ≥ 95°th
Tg ≥ 95°th
HDL ≤ 5°c
Gli ≥ 100mg/dl
HOMA-IR ≥ 2.5
*
*
NoGDM
GDM
*Mann-Whitney -test p<0.05
Odd Ratio
Insulin Resistence vs. GDM
95% CI, 8.44 -16.57, p=0.0001
Metabolic Syndrome vs. GDM
95% CI, 1.29 -2.39, p=0.003
Conclusions (1)
In
our
population,
overweight/obese children born
to mothers with GDM tend to
have a greater prevalence of
“central” obesity than children
born to mothers non-GDM.
All of them have a very high
risk
of
developing
Insulin
Resistance,
and
a
greater
likelihood
to
develop
a
Metabolic Syndrome.
Conclusions (2)
 The




specific
mechanisms
of
the
long-term
effects of GDM on the child remain unclear.
But
the
link
between
epigenetic
placental
changes
and
foetal
ones,
leading
to
Childhood Diabetes and Obesity, is more and more clear.
There is an association between an altered intrauterine
environment and some epigenetic changes in the
newborn.
Intrauterine exposure to hyperglycaemia has a negative
impact on long-term outcomes, although it is difficult to
separate these from the effects of maternal obesity.
Preventing GDM can be a valid way to prevent a certain
number of cases of Childhood Obesity or – at least – to
limit their progression to more severe expressions of it,
such as super-obesity, insulin resistance, and NIDDM.