Supplementary Table 1. Evidence supporting a role for intra-uterine
hyperglycaemia or gestational diabetes in the pathogenesis of diabetes and
obesity in subsequent generations
Study type
Findings
Ref.
Maternal history of diabetes is more common
than paternal diabetes among subjects with
type 2 diabetes
Offspring of mothers with type 1 diabetes or
type 2 diabetes (overt hyperglycaemia) have
increased risk of diabetes or obesity
Offspring of mothers with gestational diabetes
(mild hyperglycaemia) have greater risk of
diabetes or metabolic syndrome traits
Siblings born after mother has been diagnosed
with diabetes have greater risk of diabetes
compared to offspring born before diabetes
diagnosed
Offspring of mothers who had diabetes during
pregnancy are diagnosed to have diabetes at a
younger age
Risk of diabetes in offspring of mothers with
Type 1 DM is related to level of glucose control
Offspring exposed to mild hyperglycaemia have
increased adiposity
Poorly controlled maternal diabetes is
associated with macrosomia
Mild maternal hyperglycaemia is associated
with increased macrosomia
Mild maternal hyperglycaemia is associated
with increased fetal adiposity
Continuous association between maternal
glycaemia and adverse pregnancy outcome
including macrosomia
Exposure to maternal GDM is associated with
increased overall and abdominal adiposity in
offspring
Gestational diabetes is associated with other
cardiometabolic risk factors including
dyslipidaemia which may also contribute to
adverse outcome in the offspring
1 2,3
Treatment of GDM is associated with better
obstetric outcome
Treatment of GDM lowers rate of macrosomia
in the offspring
20
A. Human studies
1) Epidemiological
observations
2) Clinical Trials
4 5,6
7,8 9
6
10
3
11
12,13 14
15
16
17
13
18
19
14
21
3) Mechanistic
studies
Maternal hyperglycaemia is associated with
epigenetic changes in metabolism genes in the
placenta
Mice exposed to maternal hyperglyacemia have
abnormal methylation of IGF2/H19, with
reduced expression of IGF2 and H19 in the
pancreatic islet
22 23
In-utero hyperglyceamia in rats lead to
macrosomia in offspring
Rats exposed to intra-uterine hyperglycaemia
have impaired insulin secretion
Diabetic pregnancy leads to impaired glucose
metabolism in offspring
Offspring of diabetic mothers have reduced
insulin sensitivity
In utero exposure to maternal diabetes induces
a salt-sensitive hypertension in the offspring
In utero exposure to maternal diabetes lead to
impaired renal function and hypertension in the
offspring
25
24
B. Animal studies
25
25
25
26
2
7