ArticlePDF Available

Abstract

1. In order to assess the efficacy of the use of the diurnal plasma glucose profile rather than that of the glucose tolerance test (GTT) to predict hyperglycemia during pregnancy, we compared the results of the two tests. A total of 192 pregnant women seen at the Prenatal Clinic of the Faculty of Medicine of Botucatu were submitted to the glucose tolerance test (GTT) and determination of diurnal plasma glucose profile. 2. On the basis of two blood tests (GTT and diurnal plasma glucose profile), the subjects were divided into four groups: Group I-A, normal GTT and profile (79 patients, 41.2%); Group I-B, normal GTT and altered profile (63 patients, 32.8%); Group II-A, altered GTT and normal profile (18 patients, 9.4%); Group II-B, altered GTT and profile (32 patients, 16.7%). 3. Large babies were delivered by 25.6% of Group I-A, 53.8% of Group I-B, 28.6% of Group II-A and 51.9% of Group II-B patients. Group I-A patients are normoglycemic, Group I-B patients have intolerance to carbohydrates, protein and lipids, Group II-A patients have intolerance to high carbohydrate amounts, especially in the form of glucose, and Group II-B patients are diabetic. 4. We propose that Group I-A patients should receive no treatment, Group II-A patients should be advised to avoid excess carbohydrate intake and Groups I-B and II-B patients should be placed on a low-calorie diet and treated with insulin if necessary to obtain normal blood glucose levels. 5. Routine determination of blood glucose levels under fasting conditions represents a screening method for diabetes and values of greater than or equal to 90 mg/dl identify a population at risk that should be submitted to GTT and determination of plasma glucose profile.
Backx
et
al,
OGTT
poorly
predicts
hyperglycemia
253
Original
articles
J.
Perinat.
Med.
17
(1989)
253
Oral
glucose tolerance test
is a
poor
predictor
of
hyperglycemia
during
pregnancy
Carolina
Julia
Maria
Backx,
Frederik
Karel
Lotgering,
Hendrikus
Cornells,
and
Silvester
WaUenburg
Department
of
Obstetrics
and
Gynaecology, Erasmus University, Medical
School, Rotterdam,
The
Netherlands
1
Introduction
Gestational
diabetes
mellitus (GDM)
is the
most
common metabolic disorder
in
pregnancy.
The
condition
is
considered
to be
associated with
increased perinatal morbidity
and
mortality [6],
which
may be
reduced
by
adequate diagnosis
and
management.
The
diagnosis
of GDM is
gen-
erally
established
by
means
of an
oral glucose
tolerance test (OGTT), that
is
regarded
as ab-
normal
on the
basis
of
predefined criteria.
The
aim
of
treatment
in
gestational diabetic patients
is
to
obtain
normoglycemia,
which usually
re-
quires dietary measures with
or
without insuline
therapy.
In an
effort
to
study
the
efficacy
of the
glucose
tolerance test
to
detect those patients
with
GDM who
require therapeutic measures
to
maintain normoglycemia,
we
compared
the re-
sults
of a
glucose tolerance test with those
of a
glucose profile consisting
of
three
postprandial
glucose
values,
and
with pregnancy outcome.
2
Subjects
and
methods
During
a
two-year period,
from
September 1985
to
August 1987,
we
prospectively studied
250
Caucasian pregnant women considered
to be at
risk
for
GDM. Each woman
had one or
more
of
the
following
risk
factors:
a
past history
of
GDM,
a
previous
macrosomic
or
hypoglycemic
infant,
a
positive
family
history,
age 35
years
or
more, obesity, recurrent
glycosuria,
or
acceler-
ated
fetal
growth
in the
present pregnancy.
Pa-
tients with known type
1 or
type
2
diabetes
mellitus,
and
women with multiple pregnancy
were
excluded.
Curriculum
vitae
CAROLINA JULIA
MARIA
BACKX,
M.D.,
was
born
in
Breda,
The
Nether-
lands,
in
1958.
She
gra-
duated
at the
Erasmus
University
Medical
School, Rotterdam,
in
1983,
and she
participa-
ted
in
experimental
onco-
gynaecologic
studies
at U
John
Hopkins University
I
Baltimore, USA,
in
1979.
She
currently
finishes up her
specialty training
in Ob-
stetrics
and
Gynaecology
at the
University Hospital,
Dijkzigt,
in
Rotterdam,
and
is a
member
of the
Consi-
lium
Gynaecologicum
et
Obstetricum.
Her
main
interest
is
in
high risk obstetrics.
In all
subjects
a
50-g
OGTT
was
performed
following
three days
of
glucose
loading
with
at
least
50 g
glucose/day
and
capillary blood
was
sampled
at 0,
0.5,
and 1
hour.
On the
same
day
one of the
staff
nurses taught
the
women
how
to
take their
own
capillary blood samples
at
home. Samples were collected
in
prelabeled
fluoride
oxalate tubes,
on the
following
day one
hour
after
breakfast, lunch
and
dinner. Glucose
levels
were measured
the
next
day in
whole blood
using
the
hexokinase
method
(Boehringer
Mann-
heim). Only
one
50-g OGTT
and one
home glu-
cose profile (HGP) were obtained
from
each
subject
to be
used
for
comparison.
The
gesta-
tional
age at the
time
of
testing ranged
from
16
to 36
weeks, with
a
median
of 29
weeks.
1989
by
Walter
de
Gruyter
& Co.
Berlin
· New
York
254
Backx
et
al,
OGTT
poorly predicts
hyperglycemia
The
OGTT
was
considered
to be
abnormal
if
one or
more
of the
glucose values exceeded
the
upper limits
as
used
in our
institution,
of
5.3,
9.1
and 8.7
mmol/L
at 0, 0.5 and 1.0
hour,
respectively, prior
to
28th weeks' gestation,
and
of
5.5,
8.4 and 9.2
mmol/L thereafter
[4].
The
home glucose
profile
(HOP)
was
considered
ab-
normal
if one or
more
of the
glucose values
exceeded
the
value
of 7.0
mmol/L
[4].
A
diagnosis
of
GDM was
rejected when both OGTT
and
glucose
profile
were normal,
and no
treatment
was
instituted. When both
the
OGTT
and the
glucose
profile
were abnormal,
a
diagnosis
of
GDM was
made. These patients were treated
with
dietary measures alone
or, if
necessary
to
maintain glucose values
at of
below
7.0
mmol/L,
in
combination with insulin. When
one of
both
tests
was
abnormal,
the
diagnosis
of GDM as
well
as the
necessity
for
therapeutic measures
was
considered
to be
questionable,
and a
third
test
was
performed.
This third test
was
used
as a
gold standard,
and
consisted
of a
clinically monitored glucose
profile
(CGP). Subjects were
on a
standard hospital diet
(approximately
40%
fat,
45%
glucose,
15%
pro-
tein,
30
kcal/kg.day)
during
the
test,
and
capil-
lary
whole blood samples were taken
one
hour
after
each
of the
three main meals.
GDM was
considered
to be
absent
and no
specific
treatment
was
given
if
glucose values
did not
exceed
the
level
of 7.0
mmol/L.
Patients
in
whom
one or
more glucose concentrations exceeded
the
value
of
7.0
mmol/L were considered
to
have gesta-
tional
diabetes,
and
therapeutic measures were
instituted.
Differences
in
relative frequencies between
groups were tested with
the
X2-test,
and a p
value
of
<
0.05
was
regarded
as
significant.
Women
at risk for
gestations!
diabetes
250
OGTT
normal
HGP
normal
197
OGTT normal
HGP
abnormal
14
therapy
CGP
CGP
normal
abnormal
diet
±
insulin
OGTT
abnormal
HGP
normal
22
CGP
normal
therapy
OGTT
abnormal
HGP
abnormal
17
CGP
abnormal
diet
±
insulin
diet
±
insulin
Figure
1.
Diagnosis
and
management
of
GDM.
OGTT
oral
glucose tolerancetest
HGP
home-monitored glu-
cose profile.
CGP
clinically monitored glucose profile.
3
Results
The
glucose test results
are
shown
in figure
1.
Both OGTT
and HGP
were normal
in 197
women
and
abnormal
in 17
women, while
in 36
women
only
one of the two
tests
was
found
to
be
abnormal. These
36
women were tested again,
using
the CDP as a
gold standard.
Of
these
36
women,
only
19
had an
abnormal
CGP and
were
treated with diet with
or
without additional
in-
sulin
therapy.
Fetal outcome
as
related
to the
OGTT
and HGP
test results
is
presented
in
table
I. An
abnormal
OGTT
was
associated with
the
birth
of a
large-
for-gestational
age
infant (weight
>
90th centile)
in
6 of 39, or
15%
of
cases,
a
normal
OGTT
with
21 of 214
large infants
(no
significant dif-
ference).
An
abnormal
HGP
preceded
the
birth
of
a
large infant
in 7 of 31, or 23% of
cases,
Table
I.
Fetal
outcome related
to
glucose test results
OGTT
+
OGTT
or
OGTT
+
Total
HGP
HGP
HGP
normal
abnormal
abnormal
n
197
36
17
250
>
90th instrumental
percentile infant delivery
n
18
5
4
27
(%)
(9.1)
(13.8)
(23.5)
(10.8)
n
35
7
3
45
(%)
(17.8)
(19.4)
(17.6)
(18.0)
5'-Apgar
score
n
4
0
0
4
<7
(2.0)
(0.0)
(0.0)
(1.6)
perinatal
deaths
n
3
0
1
4
(%)
(1.5)
(0.0)
(5.3)
(1.6)
J.
Perinat.
Med.
17
(1989)
Backx
et
al,
OGTT poorly predicts
hyperglycemia
255
while
a
normal
HGP was
associated with
20 of
219,
or 9%,
large-for-gestational
age
infants,
again
no
significant
difference.
The
frequency
of
occurrence
of
instrumental deliveries
was
similar
between groups.
Four
perinatal deaths occurred
(1.6%).
In
three
of
these cases both OGTT
and
HGP had
been normal
and
fetal
or
neonatal
death appeared
to be
unrelated
to
glucose
me-
tabolism
(one second trimester birth
due to
cerv-
ical
insufficiency,
one
stillbirth
of a
severely
growth
retarded
fetus,
one
asphyxiated
infant
born
after
placental abruption).
In the
fourth
case
both OGTT
and HGP had
been abnormal.
Despite treatment with diet
and
insulin,
the in-
fant
had a
birth
weight
of
4380
g at 39
weeks
(>
P
90).
The
infant
was in
good clinical con-
dition
and had
normal glucose levels during
the
first
48
hours
after
delivery,
but
died suddenly
on
the
third
day
after
birth. Postmortem exam-
ination
failed
to
demonstrate
the
cause
of
death.
4
Discussion
Patients
with
GDM
tend
to
deliver large
babies,
which
may
increase
the risk of
perinatal morbid-
ity
[3] and
mortality
[6].
The
most
important
risks
are: prolonged labor
and
delivery, hyper-
bilirubinemia,
traumatic
injury
and
neonatal
hy-
poglycemia
[3].
In
order
to
reduce these
risks,
considerable
effort
is put
into
the
detection
and
treatment
of
GDM. However,
no
agreement
ex-
ists about
the
criteria
on
which
the
diagnosis
should
be
based,
about
the
question
how
accu-
rate
the
diagnosis
can
predict increased
risks, or
on
the
effectiveness
of
treatment
to
reduce those
risks
[2,
7].
The
diagnosis
of GDM is
usually based
on a
abnormal OGTT. However, important
differ-
ences
exist with regard
to
patient selection,
op-
timum
timing, dose
and
duration
of
glucose
loading,
site
and
frequency
of
sampling, method
of
glucose assay,
and
normal ranges
[1].
An ab-
normal
OGTT
does
not
necessarily mean
that
glucose values under less
unphysiologic
circum-
stances, that
is on a
normal
diet,
are
abnormal.
In
addition, healthy pregnant women
at no in-
creased
risk of GDM
have
a
2.3%
risk of an
abnormal test
if 2
standard
deviations above
the
mean
in
uncomplicated pregnancy
is
used
as a
cut-off
level.
In the
present study
the
OGTT
was
abnormal
in 39 of 250
women,
or
16%,
at risk
for
GDM. However,
11 of
these
39
women
(or
28%)
with
a
abnormal OGTT subsequently
had
two
normal glucose
day
profiles (HGP
and
CGP). Consequently,
the
OGTT overestimated
the
occurrence
of
hyperglycemia
by
28%.
Other investigators screen
for GDM by
sampling
at one or
several
occasions
during
the
day,
either
at
random,
or
before
and
after
one of the
main
meals,
or
after
a
glucose load
[5].
Again, 2.3%
of
healthy pregnant women will have abnormal
test results
by
statistical definition
in
many stud-
ies.
In the
present study,
11
of 219
women,
or
5%,
with
a
normal HGP,
had
both
an
abnormal
OGTT
and an
abnormal CGP. This suggests
that
the HGP in
this study underestimated
the oc-
currence
of
hyperglycemia
by
5%.
Even
if one
assumes
that
the
OGTT
overesti-
mates
by
28%,
and the HGP
underestimates
by
5%
the
chance
of
hyperglycemia, this still leaves
unanswered
the
question
as to
what extent mild
to
moderate hyperglycemia increases
the risks in
the
perinatal
period,
or how
effective
treatment
of
such hyperglycemia
is to
prevent these
risks.
Our
study cannot provide
the
answer
to
this
question, because
all
women
in
whom hypergly-
cemia
was
identified,
were
treated.
The
percent-
ages
of
large-for-gestational
age
infants, instru-
mental
deliveries,
low
Apgar scores,
and
peri-
natal
deaths,
were slightly,
but not
significantly,
higher than those
in the
normoglycemic,
un-
treated
group. Although this could indicate
that
treatment
was
indeed
effective,
alternative expla-
nations
are
that
the
numbers were
too
small
to
allow valid
statistical
comparison,
or
that
out-
come
would have been just
as
good without
therapy. Twenty-one large-for-gestational
age in-
fants
were born
from
214
normoglycemic
un-
treated
mothers. This suggests
that
one
cannot
effectively
identify
the 10%
largest infants
in the
population
by
screening
for
GDM.
The
percentages
of
instrumental deliveries,
low
Apgar scores
and
perinatal deaths
in the
nor-
moglycemic
women
are
comparable
to
those
in
the
population
of
pregnant women
in our
high-
risk
obstetric unit; they were apparently
not re-
lated
to
birth weight. This suggests
that
in
women
considered
to be at
increased
risk for
GDM
also other
risk
factors than poor
glycemic
control alone
may
contribute
to a
fetal
outcome
that
is
less favorable than that
in the
general
population
[6].
Although several authors have argued that treat-
ment
of GDM
should result
in
improved out-
J.
Perinat.
Med.
17
(1989)
256
Backx
et
al,
OGTT poorly predicts
hyperglycemia
come,
the
effect
of
treatment
can
only
be
dem-
onstrated
in a
large
randomized
study
in
which
the
hyperglycemic
controls
remain
untreated.
Considering
the
inconvenience,
anxiety
and
costs
of
glucose
tolerance
testing
for the
patient,
a
randomized
controlled
study
of the
efficacy
of
screening
and
treatment
programs
for GDM
may
be
warranted
and
ethically
justified.
Abstract
In an
effort
to
assess
the
efficacy
of the
oral
glucose
tolerance test
to
detect patients with gestational dia-
betes
mellitus
who
require therapeutic measures
to
maintain
normoglycemia,
we
compared
the
results
of
an
oral
glucose tolerance test with those
of a
home
glucose profile consisting
of
three
postprandial
glucose
values
in 250
pregnant women.
The
OGTT overestimated
the
occurrence
of
hypergly-
cemia
by
28%, while
the
home glucose
profile
under-
estimated
the
occurrence
of
hyperglycemia
by 5%.
Pregnancy
outcome
was not
significantly
different
be-
tween
spontaneously
normoglycemic
women
and
those
who
required therapy.
One
cannot
effectively
identify
the ten
percent largest
infants
in the
population
by
screening
for
gestational diabetes.
Keywords:
Diabetes
and
pregnancy, diabetes screening, gestational diabetes, glucose tolerances test.
der
beiden
Tests
pathologisch aus, wurde
die
Diagnose
GDM in
Zweifel
gezogen.
In
diesen
Fällen
wurde
ein
dritter Test durchgeführt, wobei
ein
klinisch über-
wachtes
Glukoseprofil (CGP) erhoben
und als
Gold-
Standard benutzt wurde.
Abb.
l
zeigt
die
Ergebnisse. Beide Tests waren
bei 197
Frauen normal
und bei
17
Frauen pathologisch, wäh-
rend
bei 36
Frauen lediglich einer
der
beiden Tests
pathologisch
ausfiel.
Diese
36
Frauen wurden noch-
mals
mit
einem
CGP als
Gold-Standard überprüft,
der
bei
19
Frauen pathologisch
ausfiel.
Hier wurde eine
Diät und, wenn erforderlich, eine Insulintherapie
an-
gesetzt.
Der
OGTT
war bei 39 von 250
Frauen
mit
Risikofaktoren
pathologisch,
das
entspricht
16%.
Je-
doch hatten
11
dieser
39
Frauen
(^
28%) anschließend
zwei
normale Blutzuckertagesprofile
(HCP
und
CGP).
Das
heißt,
daß der
OGTT
in 28% das
Auftreten
von
Hyperglykämien
überschätzte.
Es
gab
keinen signifikanten Unterschied bezogen
auf
das
Schwangerschaftsoutcome
zwischen spontan nor-
moglykämischen
Frauen
und
denen,
wo
eine Therapie
erforderlich
war.
Ein
Screening
auf
Gestationsdiabetes
ist in der Tat
keine
effektive
Methode,
um die 10%
hypertropher
Kinder
in der
Population
zu
identifizie-
ren.
Oraler
Glukose-Toleranztest
als
Parameter
mit
geringer
Aussagekraft
r
eine
Hyperglykämie
in der
Schwan-
gerschaft
Um die
Effizienz
eines oralen Glukose-Toleranztestes
zur
Aufeckung eines Gestationsdiabetes,
der
therapeu-
tische Maßnahmen
zur
Einhaltung
normoglykämi-
scher Werte erfordert,
zu
überprüfen, verglichen
wir
die
Ergebnisse
des
oralen Glukose-Toleranztestes
mit
denen
von
Blutzuckerprofilen
in
häuslicher Umge-
bung.
Prospektiv wurden
250
Schwangere
mit
Risikofakto-
renr
einen Gestationsdiabetes (GDM) untersucht.
Bei
allen Patientinnen wurde nach
3
Tagen glukose-
reicher
Ernährung
ein
oraler
Glukose-Toleranztest
(50g)
mit
Blutentnahmen
bei 0, 0.5 und l
Stunde
durchgeführt.
Um ein
häusliches Glukoseprofil
zu er-
halten, wurde
am
folgenden
Tag
jeweils eine Stunde
nach Frühstück, Mittag-
und
Abendessen Blut abge-
nommen.
Von
einem pathologischen OGTT gingen
wir
aus, wenn
die
Werte
vor der 28.
Schwangerschafts-
woche
höher
als
5.3,
9.1 und 8.7
mmol/1
bei 0, 0.5 und
l
Stunde lagen, später wurden
die
Grenzwerte
bei
5.5,
8.4
und 9.2
mmol/1 angesetzt.
Das
häusliche Glukose-
Profil
(HGP) galt
als
pathologisch, wenn mindestens
einer
der
Werte
7.0
mmol/1 überstieg. Fiel
nur
einer
Schlüsselwörter:
Diabetes-Screening, Diabetes
und
Schwangerschaft, Gestationsdiabetes, Glukose-Toleranztest.
Resume
Le
test
de
tolerance
au
glucose
par
vote
orale
est
un
mauvais
predicateur
de
l'hyperglycemie
au
cours
de
la
Nous avons compare
les
resultats
d'un test
de
tolerance
au
glucose
par
voie orale avec ceux d'un cycle
glyce-
mique
a
domicile
afin
d'evaluer
Pefficacite
du
test
de
tolerance
au
glucose
par
voie orale
a
depister
les pa-
tientes
presentant
un
diabete
sucre
gestationnel
qui
necessitent
des
mesures
therapeutiques
pour maintenir
une
normoglycemie.
Nous avons
etudie
250
femmes
enceintes
a risque de
diabete gestationnel.
Une H. G. P. O. (50 g) a
etc
realise
J.
Perinat.
Med.
17
(1989)
Backx
et
al,
OGTT poorly predicts
hyperglycemia
257
chez
tous
les
sujets
apres
3
jours
de
charge
en
glucose
et
des
prelevements
sanguins
ont
etc
realises
ä 0;
0,5
et
1
heure. Pour
le
cycle glycemique
des
prelevements
sanguins
ont
etc
effectues
le
lendemain
une
heure apres
le
petit dejeuner,
le
dejeuner
et le
diner.
Les H. G. P. O.
ont ete
considerees
comme
anormales
si
1'une
ou
plus
des
valeurs
de la
glycemie
depassaient 5,3;
9,1 et 8,7
mmol/L
respectivement
ä 0; 0,5 et l
heure avant
la
28e
semaine
et
5,5;
8,4 et 9,2
mmol/L apres.
Le
cycle
glycemique
etait considere comme anormal
si
Tune
ou
plusieures
glycemies
depassaient
7
mmol/L.
Lorsqu'un
seul
test etait anormal,
le
diagnostic
de
diabete gesta-
tionnel etait considere comme
sujet
ä
caution. Dans
ces
cas,
un
troisieme
test etait realise
ä
savoir
un
cycle
glycemique
surveille
cliniquement
et
servait
de
stan-
dard
de
reference.
Les
resultats
des
tests sont
representes
dans
la
figure
1,
chez
197
femmes
les
deux,
H.G.P.O.
et
cycle gly-
cemique, sont
normaux
et
anormaux
chez
17
femmes,
alors
que
chez
36
femmes,
un
seul
des
deux tests
est
trouve
comme anormal.
Ces 36
femmes
ont ete
etudiees
de
nouveau,
en
prenant
le
cycle glycemique surveille
cliniquement
comme standard
de
reference.
Parmi
ces
36
femmes,
seules
19
avaient
un
cycle anormal
et ont
ete
traitees
par le
regime avec
ou
sans
insulinotherapie
additionnelle.
L'H.
G. P. O.
etait anormale chez
39 des 250
femmes,
soit
16%,
ä risque de
diabete gestationnel.
Toutefois,
11
parmi
ces 39
femmes
(soit 28%) avec
H.G
P.O.
anormale
presentaient
ensuite deux cycles
glycemiques
normaux.
De
teile
sorte
que,
PH.G.P.O.
surrestime
l'occurence
de
Fhyperglycemie
de
28%.
Uevolution
de la
grossesse
n'est
pas
signiflcativement
differente
entre
les
femmes
spontanement
normogly-
cemiques
et
celles
ayant
necessite
une
therapeutique.
En
pratique,
on ne
peut
identifier
les 10%
d'enfants
macrosomes dans
la
population
a
Faide
de
depistage
du
diabete gestationnel.
Mots-cles:
Depistage
du
diabete,
diabetes
et
grossesse,
diabetes
gestationnels,
test
de
tolerance
au
glucose.
References
[1]
CARPENTER
MW:
Testing
for
gestational diabetes.
In:
REECE
EA, DR
COUSTAN:
Diabetes
mellitus
in
pregnancy.
Chruchill
Livingstone,
New
York, 1988
[2]
COUSTAN
DR:
Management
of
gestational diabetes.
In:
REECE
EA, DR
COUSTAN:
Diabetes mellitus
in
pregnancy. Churchill Livingstone,
New
York, 1988
[3]
GABBE
SG, JH
MESTMAN,
RK
FREEMAN,
GV AN-
DERSON,
RI
LOWENSOHN:
Management
and
out-
come
of
Class
A
diabetes mellitus.
Am J
Obstet
Gynecol
127
(1977)
465
[4]
KUIJKEN
JPJA: Diabetes mellitus
in de
zwanger-
schap.
Doctoral
thesis, Rotterdam, 1983
[5]
LIND
T:
Antenatal screening using random blood
glucose values.
Diabetes
34
(suppl
2)
(1985)
17
[6]
O'SULLIVAN
JB, D
CHARLES,
CM
MAHAN,
RV
DANDROW:
Gestational diabetes
and
perinatal
mortality rate.
Am J
Obstet Gynecol
116
(1973)
901
[7]
WIDNESS
JA, RM
COWETT,
DR
COUSTAN,
MW
CARPENTER,
W OH:
Neonatal morbidities
in
infants
of
mothers with glucose intolerance
in
pregnancy.
Diabetes
34
(suppl
2)
(1985)
61
Received
November
2,
1988. Accepted
May 5,
1989.
F.
K.
Lotgering,
M.
D.,
Ph. D.
Department
of
Obstetrics
and
Gynaecology
Erasmus University Medical School
EE
2283
P.O.
Box
1738
3000
DR
Rotterdam
The
Netherlands
J.
Perinat.
Med.
17
(1989)
... Regardless of normal OGTT, the abnormal GP test indicated hyperglycemia in some pregnant women; when hyperglycemia was untreated, the perinatal mortality rate was 4.16%, which is similar to the rate observed in the GDM group and ten times greater than that observed in the nondiabetic control group. These cases are subjected to strict glucose control, similar to diabetes in pregnant women, and are classified as mild gestational hyperglycemia (MGH) [9,10]. ...
... Pairs of mothers and newborns assisted at our center between 1 January 2008 and 31 December 2014 were included. The inclusion criteria were as follows: underwent the diagnostic protocol for hyperglycemia in pregnancy [9,10]; had birth assistance at our referral center. The exclusion criteria were as follows: cases of multiple pregnancies; long-term use of corticosteroids; and a history of diabetes mellitus (overt DM, T1DM or T2DM). ...
... The GP test was performed over a oneday hospital stay with the women on a 2840 kcal diet fractionated in five meals. Plasma glucose measurements were taken every 2 h between 8 a.m. and 6 p.m. [9,10]. ...
Article
Full-text available
Background: While sufficient evidence supporting universal screening is not available, it is justifiable to look for specific risk factors for gestational diabetes mellitus (GDM) or hyperglycemia in pregnancy (HIP). The objective of this study is to identify independent risk factors for HIP and its adverse perinatal outcomes in a Brazilian public referral center. Methods: We included 569 singleton pregnant women who were split into three groups by glucose status: GDM (n = 207), mild gestational hyperglycemia (MGH; n = 133), and control (n = 229). Women who used corticosteroids or had a history of DM were excluded. HIP comprised both GDM and MGH, diagnosed by a 100 g- or 75 g-oral glucose tolerance test (OGTT) and a glucose profile at 24-28 weeks. Maternal characteristics were tested for their ability to predict HIP and its outcomes. Bivariate analysis (RR; 95% CI) was used to identify potential associations. Logistic regression (RRadj; 95% CI) was used to confirm the independent risk factors for HIP and its perinatal outcomes (p < 0.05). Results: Age ≥ 25 years [1.83, 1.12-2.99], prepregnancy BMI ≥ 25 kg/m2 [2.88, 1.89-4.39], family history of DM [2.12, 1.42-3.17] and multiparity [2.07, 1.27-3.37] were independent risk factors for HIP. Family history of DM [169, 1.16-2.16] and hypertension [2.00, 1.36-2.98] were independent risk factors for C-section. HbA1c ≥ 6.0% at birth was an independent risk factor for LGA [1.99, 1.05-3.80], macrosomia [2.43, 1.27-4.63], and birthweight Z-score > 2.0 [4.17, 1.57-11.10]. Conclusions: MGH presents adverse pregnancy outcomes similar to those observed in the GDM group but distinct from those observed in the control (no diabetes) group. In our cohort, age ≥ 25 years, prepregnancy BMI ≥ 25 kg/m2, family history of DM, and multiparity were independent risk factors for HIP, supporting the use of selective screening for this condition. These results should be validated in populations with similar characteristics in Brazil or other low- and middle-income countries.
... Large for gestational age babies were delivered by 25.6% of Group I-A, 53.8% of Group IeB, 28.6% of Group II-A and 51.9% of Group II-B patients. Our first publication in 1990 [12,13] was simultaneous with that of Backx et al. [14] in the Netherlands, which confirmed similar rates for LGA, newborns with a birthweight greater than the 90th percentile in both MGH and GDM mothers. The prevalence of MGH some years after was 13.8% and GDM was 6%, or almost 20% of all positively screened pregnant women presented hyperglycemia in pregnancy in our centre [15]. ...
... In Rudge et al. [13] and the HAPO [17] study, the mean fasting and postprandial glucose concentrations were very similar (Table 1). These data highlight the real need to reduce cutoff points to diagnose hyperglycemia in pregnancy. ...
... The main reason for this controversy is that the cutoff for OGTT was established to detect long-term maternal risk for type 2 diabetes mellitus (T2DM), not perinatal outcomes [20,21]. The GP has a higher sensibility and positive predictive value for the detection of LGA and macrosomic newborns than OGTT [13,14], which reflects the hyperglycemic intrauterine environment responsible for the deleterious effects on the fetus and newborn [22]. ...
Article
Full-text available
Mild gestational hyperglycemia (MGH), as assessed using the normal oral glucose tolerance test (OGTT) and detection of an altered glycemic profile, is associated with adverse perinatal outcome. This study described the results of 40 years of research conducted at the Perinatal Diabetes Research Centre at São Paulo State University (UNESP), Brazil, on the maternal MGH environment and placental markers. This study also described the unidirectional relationship between MGH and excessive fetal growth, also supplying moderator analysis. In addition to hyperglycemia, MGH is associated with an increased incidence of hypertension, metabolic syndrome, persistent insulin resistance after pregnancy, and high risk of developing type 2 diabetes mellitus (T2DM) after pregnancy. Structural changes and functional abnormalities resulting from MGH were observed in placenta. The fully adjusted model concluded that the predictor variable (MGH), which creates a complex environment for the fetus, has a direct effect on excessive birth weight and produces a z-score for ratios of birth weight to gestational age of ≥2. Maternal age, pre-pregnancy BMI, number of previous pregnancies, numbers of prenatal visits, and 1 h OGTT are moderator variables that impact MGH and excessive fetal growth. These results show that maternal MGH has some characteristics associated with similar long-term T2DM development and similar adverse perinatal results to those of gestational diabetes mellitus (GDM) mothers, making it an intermediate maternal and placental marker between normoglycemic and GDM mothers.
... These complications are not restricted to pregnancies associated with pre-gestational (type 1 dia- betes mellitus, DM1, or DM2) or gestational diabetes (GDM). It also occurs in pregnant women diagnosed with mild gestational hypergly- cemia (MGH), a condition in which the pregnant woman has a normal glucose tolerance test, but altered glycemic profile [5,6]. Increased rates of perinatal mortality (tenfold compared with non-diabetic preg- nant women) and augmented incidence of infants born large-for-ge- stational-age or with macrosomia (rates similar to those seen in diabetic pregnant women [2,7]) and, incidence of type 2 diabetes (DM2) after pregnancy equivalent to GDM have been reported in pregnant women with MGH [8]. ...
... Pregnant women with DM2 (n = 15) were referred to the Diabetes and Pregnancy Service of Botucatu Medical School with a confirmed diagnosis. The diagnosis of GDMor MGHwas established between 24 and 28th gestational weeks, by the 75-g glucose tolerance test (75 g-GTT) according to ADA's criteria [26] and/or the glucose profile (GP -fasting glucose ?90 mg/dL or postprandial glucose ?130 mg/dL) test according to Rudge [6]. From the data, the women were classified into the following study groups: non-diabetic (ND; normal 75-g GTT and GP; n = 15), MGH (n = 15; normal 75-g GTT and abnormal GP) GDM (abnormal 75-g GTT first reported during the pregnancy; n = 15). ...
... At this time, MGH and GDM pregnant women were initially treated with diet and exercise; insulinwasadministered only if necessary. All DM2 pregnant women were treated with diet, exercise and insulin at the first attendance in our service, and were readjusted weekly [6,7,12]. ...
... GDM Diagnosis. The diagnostic protocol for GDM at the PDRC consists of a 75 g oral glucose tolerance test (OGTT) [33,34] and a glycemic profile (GP) between 24 and 28 weeks of pregnancy [35,36]. The GP consisted of an assessment of maternal plasma glucose every two hours from 8 a.m. to 6 p.m., with a total daily consumption of a 2840 kcal diet, divided into five meals: breakfast, lunch, dinner, and two daytime snacks. ...
... The GP consisted of an assessment of maternal plasma glucose every two hours from 8 a.m. to 6 p.m., with a total daily consumption of a 2840 kcal diet, divided into five meals: breakfast, lunch, dinner, and two daytime snacks. Fasting glucose levels of !92 mg/dL and postprandial levels of !130 mg/dL were set as GDM [36]. All participants underwent a combination of OGTT and PG tests. ...
Article
Aims To evaluate the effects of gestational diabetes mellitus (GDM) on the structural characteristics of the rectus abdominis muscle (RAM) and its indirect effects on pregnancy-specific urinary incontinence (PSUI). Methods A total of 92 pregnant women were divided into four groups, according to their clinical conditions: non-GDM continent, non-GDM associated PSUI, GDM continent and GDM associated PSUI. The muscle morphometry (histochemistry and immunohistochemistry) for the fiber types and collagen fiber distribution, the ultrastructural analysis (transmission electron microscopy), the protein expression of fiber types and calcium signaling (Western blotting), and the content of types I and III collagen fiber (ELISA) in RAM collected at delivery were assessed. Results The GDM groups presented a significantly increased number of slow fibers and slow-twitch oxidative fiber expression; decreased fiber area, number of fast fibers, and area of collagen; an increase in central nuclei; ultrastructural alterations with focal lesion areas such as myeloid structures, sarcomere disorganization, and mitochondrial alteration. The PSUI groups presented a considerable decrease in types I and III collagen contents and the localization of collagen fiber. Conclusions Our data reveal that GDM causes morphological, biochemical and physiological changes in the RAM, and this might predispose women to PSUI.
... In milder forms of GDM, which do not fully meet diagnostic criteria, hyperglycemia and adverse effects to the mother and offspring are also present 10 . In the Perinatal Diabetes Research Centre (PDRC), Botucatu Medical School-UNESP (Sao Paulo State University), Brazil, women with a glycemic profile indicative of hyperglycemia and a normal response to glucose tolerance testing have been identified as having Mild Gestational Hyperglycemia (MGH) and offered the same treatment given to those with GDM for over two decades 11,12 . Today, women with MGH account for 17.3% of our cases 13 . ...
Article
Full-text available
The aim was to assess the role of Metabolic Syndrome (MetS) diagnostic markers, recommended by three different guidelines, in the prediction of hyperglycemia in pregnancy. This cross-sectional cohort study included 506 non-diabetic women, with a singleton pregnancy, who underwent a diagnostic test for hyperglycemia at 24–28 weeks. Clinical, anthropometric, and laboratory data were obtained. The relationship between MetS markers and the risk of hyperglycemia was evaluated by backward stepwise logistic regression analysis (OR, 95% CI). The limit of statistical significance was 95% (p < 0.05). Triglycerides (TG) ≥ 150 mg/dL, blood pressure (BP) ≥ 130/85 mmHg, fasting glucose (FG) ≥ 100 mg/dL, and waist circumference (WC) > 88 cm were identified as independent risk factors for hyperglycemia in pregnancy. These results might help the selective screening of hyperglycemia in pregnancy.
... When criteria for GDM are not fully met, less severe degrees of GDM also produce adverse effects on the mother and newborn [3][4][5]. Nevertheless, women with mild gestational hyperglycemia (MGH)-those with hyperglycemia in the glycemic profile, despite a normal response to oral glucose tolerance test (OGTT)-have been identified in specialized obstetrical centers [6,7]. This subgroup of women is at higher risk of maternal and perinatal adverse outcomes, suggesting that their glycemic levels should also be controlled during pregnancy. ...
Article
Full-text available
Background: Hyperglycemia in pregnancy (HIP) has been recently differentiated between diabetes in pregnancy (DIP) and gestational diabetes mellitus (GDM). The proposed protocol is relevant, and clinical concern is due to the higher risk of adverse pregnancy outcomes (APO) and long-term effects on both the mother and the fetus. Fasting plasma glucose level (FPG) and oral glucose tolerance test (OGTT) are current diagnostic tools. However, controversy persists concerning diagnostic criteria, cut-off points, and even selective or universal screening. The objective of this systematic review is to assess the performance of metabolomic markers in the prediction of HIP. Methods: This is a protocol for a systematic review with potential meta-analysis. The primary outcome is GDM, defined as glucose intolerance identified in the second and third trimesters of pregnancy (any FPG ≥ 92 mg/dL and < 126 mg/dL OR when 75-g OGTT shows one altered value among these: FPG ≥ 92 mg/dL or 1-h post glucose load ≥ 180 mg/dL or 2-h post glucose load ≥ 153 mg/dL); the secondary outcome is HIP, defined as hyperglycemia detected in the first trimester of pregnancy (any FPG ≥ 126 mg/dL). A detailed systematic literature search will be carried out in electronic databases and conference abstracts, using the keywords "gestational diabetes mellitus," "metabolomics," "pregnancy," and "screening" (and their variations). We will include original peer-reviewed articles published from Jan 1, 1999, to Dec 31, 2018. Original studies including diabetes diagnosed before pregnancy (T2DM and T1DM), multiple pregnancies, and congenital malformations will be excluded. All results regarding samples, participant characteristics, metabolomic techniques, and diagnostic accuracy measures will be retrieved and analyzed. Since this is a systematic review, no ethical approval is necessary. Discussion: This systematic review may have the potential to provide significant evidence-based findings on the prediction performance of metabolomics. There are short and long-term repercussions for the mother and the newborn. Therefore, both may benefit from an accurate prediction technique for HIP. Systematic review registration: This protocol was registered in the PROSPERO platform under number CRD42018100175 .
... The present study set the cutoff value for the development of type 2 diabetes mellitus at 95 mg/dL, which is lower than the acceptable cutoffs for the neonatal shortterm outcome [3]. This accords with the findings that even mild forms of hyperglycemia induced measurable DNA damage [35] and unfavorable maternal and neonatal outcomes [38][39][40]. Indeed, it was suggested that glucose values in pregnant women without GDM are much lower than estimated previously and that target glucose values should be lowered in order to decrease GDMrelated complications. ...
Article
Full-text available
Background: To examine whether glycemic control of gestational diabetes mellitus (GDM) could modify the risk for future maternal metabolic and cardiovascular morbidities. Methods: A retrospective cohort study of women with a first diagnosis of GDM who delivered between 1991 and 2011. Women were divided into groups of good and poor glycemic control, defined as a mean daily glucose of up to 95 mg/dL (N = 230) and more than 95 mg/dL (N = 216), respectively. In addition, a control group of women without GDM (N = 352) was also analyzed. The primary outcomes were the development of type 2 diabetes mellitus (T2DM), obesity, hypertension, or dyslipidemia. Results: Mean follow-up time was 15.8 ± 5.1 years. Assessment was performed at a maternal age of 45 ± 7 years. The rates of the study outcomes in the control, GDM with good glycemic control and GDM with poor glycemic control were as follows: T2DM [19 (5.4%), 87 (38%), 127 (57%)]; hypertension [44 (13%), 42 (18%), 44 (20%)]; obesity [111 (32%), 112 (48%), 129 (58%)]; and dyslipidemia [49 (14%), 67 (29%), 106 (48%)]. Glycemic control was an independent risk factor for T2DM in multivariate Cox regression analysis (hazard ratio (HR) for poor glycemic control vs. controls 10.7 95% CI [6.0-19.0], good glycemic control vs. control HR 6.0 [3.3-10.8], and poor glycemic control vs. good glycemic control HR 1.8 [1.3-2.4]). Glycemic control was also an independent risk factor for dyslipidemia (poor glycemic control vs. controls HR 3.7 [2.3-5.8], good glycemic control vs. controls HR 2.0 [1.2-3.2], and poor glycemic control vs. good glycemic control HR 1.8 1.8 [1.3-2.6]). The fasting glucose level during oral glucose tolerance test (OGTT) was also an independent risk factor for these complications. The interaction term between glycemic control and the fasting value of the OGTT was not statistically significant, suggesting that the effect of glycemic control on the rate of future T2DM and dyslipidemia was not modified by the baseline severity of GDM. Conclusion: GDM and especially poor glycemic control are associated with T2DM and dyslipidemia. Strict glycemic control for reducing that risk should be evaluated in prospective trials.
Article
Objective To determine the occurrence and severity of pregnancy-specific urinary incontinence (PSUI) in women with gestational hyperglycaemia, and its impact on quality of life (QoL) over the first year post partum. Study design Three hundred and eighty-eight pregnant women with PSUI were distributed into two groups (normoglycaemic and hyperglycaemic) and analysed at five timepoints during pregnancy and the first year post partum. Gestational hyperglycaemia was defined according to the criteria of the American Diabetes Association and the glucose profile test. Relationships with outcome were analysed using Chi-squared test for categorical variables and Student’s t-test for quantitative variables. Results The overall prevalence rate of PSUI was 54.1%, with prevalence rates of 43.3% and 56.7% in normoglycaemic and hyperglycaemic Brazilian pregnant women, respectively. Women with gestational hyperglycaemia had a higher amount of urine loss (p < 0.0027), frequency of UI (p < 0.0014), impact of UI on QoL (p < 0.0001), severity of UI (p = 0.0003) and total scores on the International Consultation on Incontinence Questionnaire-Urinary Incontinence-Short Form (ICIQ-SF) and Incontinence Severity Index (ISI) (p<0.0001) at the two timepoints during pregnancy; and a higher amount of urine loss (p = 0.0079), frequency of UI (p = 0.0382), impact of UI on QoL (p < 0.0001), severity of UI (p = 0.0053) and questionnaire scores (p < 0.0001 for ICIQ-SF and p = 0.003 for ISI) over the first year post partum. Conclusions PSUI in women with gestational hyperglycaemia worsens the occurrence and severity of UI, and the impact of UI on QoL over the first year post partum. These results emphasize the interaction between PSUI, gestational hyperglycaemia and long-term maternal outcome.
Article
We investigated whether mitochondrial-related genes and proteins are modulated by hyperglycemia promoted by gestational diabetes (GDM), thereby increasing neonate obesity predisposition. 19 healthy pregnant women, 16 pregnant women with GDM and their respective neonates were enrolled. Additionally, 19 obese and 19 eutrophic adults were recruited as a reference population. Umbilical cord, peripheral blood and placental (villous and decidua) tissues were collected to evaluate SOD2, PPAR-α and PPARGC-1β and their respective protein expressions. Data from the reference population confirmed that the three genes and proteins were overexpressed in blood cells of obese compared to eutrophic subjects. Only SOD2 was found upregulated in placental villous (fetal side) tissue of GDM women. Therefore, our findings showed an interaction between the hyperglycemic environment and SOD2 modulation, but also indicated that none of the three genes is useful as potential biomarkers for obesity development.
Article
Patients who have a normal fasting serum glucose (FSG) and an abnormal glucose tolerance test, and who require little dietary regulation, have been designated as Class A diabetics by White. During the period 1970 through 1972, 261 Class A women were delivered at Los Angeles County (LAC) Women's Hospital. These patients were managed by a uniform protocol which included dietary supervision and continued surveillance for the onset of overt diabetes. Elective intervention prior to 40 weeks' gestation was to be avoided. Twenty-five per cent of the Class A patients--those who had had a previous stillbirth or who developed pre-clampsia--were considered at greater risk for perinatal death and were managed as if they had overt diabetes. The perinatal death rate for the entire Class A group was 19/1,000 as compared to 32/1,000 in the general population. Five perinatal deaths occurred, three associated with congenital malformations. There were no unexplained stillbirths or deaths due to trauma or iatrogenic prematurity. Our data thus indicate that as long as the FSG remains normal, an unexplained intrauterine death is a rare event. Twenty-five per cent of the infants did experience some morbidity.
Article
The treatment of gestational diabetes is based on maintaining near-normal maternal glucose levels. To accomplish this goal, dietary counseling is used. circulating glucose is measured regularly, and exogenous insulin is sometimes necessary. Early delivery is not routine. Cesarean section is reserved for obstetric indications, but the presence of fetal macrosomia may be responsible for increasing the overall cesarean section rate in individuals with this disorder. The most important component of the treatment of gestational diabetes is probably the identification of the individual with this condition.
Article
Of 1839 pregnant women screened prospectively, 52 were identified to have glucose intolerance. Ten additional pregnant women identified as having glucose intolerance before the universal screening were also included in the study cohort. These 62 patients were followed in a perinatal high-risk clinic with weekly plasma glucose determinations. The patients were treated with diet and, in addition, 21 of 62 were treated with insulin therapeutically. By observational cohort design, the infants and a comparable number of matched controls were evaluated for evidence of neonatal morbidities and classified into percentile for birth weight. Compared with the control group, the operative mode of delivery, the mean birth weight, the birth-weight percentile, the male/female ratio, the frequency of low Apgar score (less than or equal to 6 at 1 min), and the number of infants with congenital anomalies were significantly higher in the infants born to the glucose-intolerant mothers. Although the mean maternal blood sugar was maintained within a reasonably euglycemic range, the usual neonatal morbidities were not eliminated entirely. Further understanding and management of glucose intolerance in pregnancy is necessary to further diminish or eliminate neonatal morbidities.
Article
For many years it has been established practice to test the urine of pregnant women for the presence of glucose in the belief that this is an efficient way to detect diabetes mellitus. It is now becoming recognized that one of the normal maternal physiologic adaptations during pregnancy is an increase in the renal excretion of glucose; on examination, up to 50% of healthy pregnant women will have detectable glycosuria at some stage. As the definition of diabetes mellitus is based on random blood glucose values or the concentrations achieved at defined times after an oral glucose load, it would seem logical that any antenatal screening procedure should be similarly based. A total of 2403 consecutive antenatal patients had a random venous whole blood glucose concentration determined between 28 and 32 wk gestation. Calculated 99% cutoff values were 110 mg/dl (6.1 mmol/L) within 2 h of a meal or 101 mg/dl (5.6 mmol/L) more than 2 h postprandial. Four patients were found to have previously unsuspected but unequivocal diabetes mellitus and four more had impaired glucose tolerance on the basis of the 1980 WHO criteria. Screening all antenatal patients by this method is efficient, does not inconvenience patients, and is relatively cost efficient in terms of staff and laboratory resources.
Article
Significantly higher perinatal mortality rates were found in a prospective study of 187 gestational diabetic patients and 259 randomly selected negative control patients. Since the gestational diabetic patients were older and obese, further analyses were made to determine the role of these variables. Age was found to have a disproportionately adverse effect, enhanced slightly by obesity, on the pregnancies of gestational diabetic patients when compared with those of negative control patients. Two classes of gestational diabetic patients are outlined on the basis of age. The first includes those below 25 years of age who show no increased fetal wastage in pregnancy but may be more susceptible to this problem in unfavorable obstetric circumstances. The second class includes gestational diabetic patients 25 years of age or older who have high risk pregnancies even in centers administering good prenatal care.
Article
Gestational diabetes mellitus is defined as carbohydrate intolerance of variable severity first diagnosed during pregnancy. Although universal screening for gestational diabetes mellitus is practiced by more than 75% of obstetricians in the United States, agreement is lacking worldwide regarding the appropriateness of this approach. This article discusses the assumption that some type of screening program is desirable and considers how best to conduct screening and diagnostic testing for gestational diabetes mellitus.
Diabetes mellitus in de zwangerschap
  • Kuijken Jpja
KUIJKEN JPJA: Diabetes mellitus in de zwangerschap. Doctoral thesis, Rotterdam, 1983