Me abolic synd ome in Finnish women
7 yea s a e a ges a ional diabe es
p e en ion ial
Ja a Puhkala,
1
Jani Rai anen,
1,2
Päi i Kolu,
1
Pipsa Tuominen,
1
Pauliina Husu,
1
Rii a Luo o
1,2
To ci e: Puhkala J,
Rai anen J, Kolu P, e al.
Me abolic synd ome in
Finnish women 7 yea s a e
a ges a ional diabe es
p e en ion ial. BMJ Open
2017;7:e014565.
doi:10.1136/bmjopen-2016-
014565
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To iew hese iles please
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bmjopen-2016-014565).
Recei ed 3 Oc obe 2016
Re ised 2 Janua y 2017
Accep ed 13 Janua y 2017
1
UKK Ins i u e o Heal h
P omo ion Resea ch,
Tampe e, Finland
2
School o Heal h Sciences,
Uni e si y o Tampe e,
Tampe e, Finland
Co espondence o
Ja a Puhkala;
ja[email p o ec ed]
ABSTRACT
Backg ound: Risk o de eloping me abolic synd ome
(MeS) a e deli e y is high among women wi h
ges a ional diabe es melli us (GDM), bu li le is known
abou de elopmen o MeS among women wi h isk
ac o s o GDM du ing p egnancy. In he p esen
s udy, we s udied he p e alence o MeS 7 yea s
pos pa um among women wi h GDM isk ac o s
du ing p egnancy, women wi h ea ly GDM diagnosis
and women wi hou GDM isk ac o s. We also
analysed he ea ly p egnancy isk ac o s associa ed
wi h MeS.
Me hods: A Finnish clus e andomised con olled
GDM p e en ion ial was conduc ed in 2007–2009.
The p e alence o MeS acco ding o In e na ional
Diabe es Fede a ion c i e ia was de e mined in he
ollow-up s udy 7 yea s a e o iginal ial. Eligible
pa icipan s (n=289) in 4 s udy g oups (in e en ion
(n=83) and usual ca e (n=87) wi h GDM isk ac o s;
ea ly GDM (n=51), and heal hy con ol wi hou GDM
isk ac o s (n=68)) we e e alua ed o MeS. Bina y
logis ic eg ession models we e used o analyse isk
ac o s associa ed wi h MeS.
Resul s: 7 yea s pos pa um, he MeS p e alence was
14% (95% CI 8% o 25%) in he in e en ion g oup;
15% (CI 8% o 25%) in he usual ca e g oup; 50%
(CI 35% o 65%) in he ea ly GDM g oup and 7% (CI
2% o 18%) in he heal hy con ol g oup. OR o MeS
in women wi h GDM isk ac o s did no di e om he
heal hy con ol g oup. Body mass index (BMI)-adjus ed
OR o MeS was 9.18 (CI 1.82 o 46.20) in he ea ly
GDM g oup compa ed wi h he heal hy con ol g oup.
Inc eased p ep egnancy BMI was associa ed wi h MeS
(OR, 1.17, CI 1.08 o 1.28, adjus ed o g oup).
Conclusions: Inc eased p ep egnancy BMI and ea ly
GDM diagnosis we e he s onges isk ac o s o
de eloping MeS 7 yea s pos pa um. O e weigh and
obese women and especially hose wi h ea ly GDM
should be moni o ed and counselled o
ca diome abolic isk ac o s a e deli e y.
INTRODUCTION
Me abolic synd ome (MeS) is a clus e ing o
a he oscle o ic isk ac o s, including abdom-
inal obesi y, ele a ed plasma iglyce ides,
dec eased high densi y lipop o ein (HDL)
choles e ol, ele a ed blood p essu e and
ele a ed as ing glucose.
12
Insulin esis ance
and low-g ade inflamma ion a e cen al
d i e s in he pa hogenesis o MeS.
34
In add-
i ion o gene ic ea u es, obesogenic li es yle
defined by unheal hy die and physical
inac i i y inc ease he isk o MeS.
5–9
The
p e alence o MeS is inc easing wo ldwide,
along wi h he obesi y epidemic and popula-
ion ageing.
10 11
Es ima es o MeS p e alence
a y be ween 15% and 34% in adul popula-
ions,
12–15
and a ound 8–19% in ep oduc -
i e-aged women in indus ial coun ies.
16–18
I is ele an o iden i y pa ien s wi h MeS, as
hey a e a wice he isk o de eloping ca -
dio ascula disease o e he nex 5–10 yea s,
and a fi e old li e ime isk o de eloping
ype 2 diabe es compa ed wi h indi iduals
wi hou he synd ome.
1
Ges a ional diabe es melli us (GDM) is a
diso de in glucose and insulin me abolism
fi s diagnosed du ing p egnancy.
19
The
mos impo an isk ac o s o GDM a e p e-
p egnancy o e weigh , high ma e nal age
and a amily his o y o ype 2 diabe es.
20
Women wi h a his o y o GDM a e a
S eng hs and limi a ions o his s udy
▪Ou s udy was a long- e m ollow-up o a la ge
ges a ional diabe es melli us (GDM) p e en ion
ial.
▪The s udy was one o he i s ollow-up s udies
on he p e alence o me abolic synd ome (MeS)
a e deli e y among women wi h isk ac o s o
GDM.
▪The esul s include da a o he MeS p e alence
among di e en isk g oups.
▪Thi y-se en pe cen o he in i ed women
en e ed he measu emen s o MeS, and he ou
subg oups we e ela i ely small.
▪The esul s may ha e been mode a ely a ec ed
by a heal hy selec ion bias.
Puhkala J, e al.BMJ Open 2017;7:e014565. doi:10.1136/bmjopen-2016-014565 1
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inc eased isk o de eloping ca diome abolic diso de s,
such as ype 2 diabe es and MeS a e deli e y.
21 22
MeS
and GDM sha e mu ual isk ac o s, sugges ing ha
women wi h isk ac o s o GDM may be a inc eased
isk o u u e MeS, e en in he absence o GDM.
23 24
O e weigh and excessi e ges a ional weigh gain ha e
been linked o de elopmen o GDM and la e ca dio-
me abolic diso de s.
23 25–27
Long- e m ollow-up s udies
on de elopmen o MeS among women a inc eased
GDM isk a e lacking.
Ou clus e andomised con olled ial (RCT) in
Finnish p egnan women a inc eased GDM isk showed
ha li es yle counselling was e ec i e in con olling he
p opo ion o la ge- o -ges a ional-age new-bo ns and
imp o ing he women’s die , and p e en ing excessi e
ges a ional weigh gain and dec ease in physical ac i -
i y.
28–31
One yea a e deli e y, he p e alence o MeS
among women wi h GDM isk ac o s was 16–18%
depending on he c i e ia; wi h no di e ences be ween
he in e en ion and usual ca e g oup.
24
Ou aim is o s udy MeS and i s componen s 7 yea s
pos pa um among Finnish women who in ea ly p eg-
nancy we e a inc eased isk o de eloping GDM (in e -
en ion o usual ca e), among women wi h ea ly
p egnancy GDM diagnosis and among women wi hou
GDM isk ac o s du ing p egnancy (heal hy con ol).
We also s udied isk ac o s associa ed wi h he de elop-
men o MeS 7 yea s pos pa um.
METHODS
Pa icipan s and s udy design
The s udy is a 7-yea ollow-up o a clus e RCT on GDM
p e en ion (ISRCTN33885819). De ailed desc ip ions
o he design and me hods o he o iginal s udy ha e
been published p e iously.
32
The s udy was conduc ed in
14 p ima y heal hca e ma e ni y clinics in Wes e n
Finland in 2007–2009, a 1-yea pos pa um ollow-up in
2009–2011 and he 7-yea ollow-up in 2014–2016.
The p ima y aim o he ial was o p e en GDM and
excessi e ges a ional weigh gain among p egnan
women wi h an inc eased isk o GDM. Ma e ni y
clinics we e andomised in o se en in e en ion and
se en con ol clinics. P egnan women we e ec ui ed by
nu ses a hei fi s isi (8–12 weeks’ges a ion) in
ma e ni y clinics. Women we e eligible i hey had a
leas one o he ollowing GDM isk ac o s: age≥40
yea s, p ep egnancy body mass index (BMI) ≥25 kg/m²,
GDM o any sign o glucose in ole ance in any p e ious
p egnancy, a mac osomic baby (≥4500 g) in any p e i-
ous p egnancy o diabe es in fi s -deg ee o second-
deg ee ela i es. The main exclusion c i e ia we e
age<18 yea s, a GDM diagnosis a 8–12 weeks’ges a ion,
win p egnancy, physical es ic ions ha p ecluded
exe cise o a clinical his o y o ch onic disease. A diag-
nosis o GDM was based on a 2-hou 75 g o al glucose
ole ance es (OGTT) acco ding o a leas one o
he ollowing c i e ia: as ing plasma glucose o
≥5.3 mmol/L, >10.0 mmol/L a 1 hou o >8.6 mmol/
La 2hou s.
33
The o iginal in e en ion included indi idual counsel-
ling on weigh gain, die and physical ac i i y by public
heal h nu ses du ing fi e ou ine isi s o ma e ni y
clinics. The women in he con ol clinics ecei ed usual
ma e nal ca e, which also included some li es yle ad ice.
O 888 p egnan women who pa icipa ed in he base-
line assessmen s a 8–12 weeks’ges a ion, 442 (50%)
we e eligible o he o iginal s udy (in e en ion and
usual ca e g oup) (figu e 1). Fu he , 374 we e
excluded, o whom 174 due o a GDM diagnosis a 8–12
weeks’ges a ion (ea ly GDM g oup). The heal hy
con ol g oup consis ed o 176 women who did no
mee he inclusion c i e ia.
Se en hund ed and eigh y-eigh women we e in i ed o
pa icipa e in he ollow-up s udy 7 yea s (mean 7.2, ange
5.6–8.3) a e deli e y, and 289 women pa icipa ed.
The s udy was conduc ed in acco dance wi h he
Decla a ion o Helsinki (2000), and i was app o ed by
Pi kanmaa Uni e si y Hospi al Dis ic E hics (Re .
numbe R14039). The pa icipan s comple ed a w i en
in o med consen be o e pa icipa ion.
Labo a o y measu emen s
In o ma ion on ma e nal measu emen s by he nu ses
was ob ained om he s anda d ma e ni y ca ds. Heigh
was measu ed a he fi s ma e ni y ca e isi (8–
12 weeks’ges a ion), and weigh was measu ed a each
ma e ni y ca e isi , and a 1 and 7 yea s pos pa um.
Wais ci cum e ence was measu ed a 1 and 7 yea s pos -
pa um, and he a e age o h ee measu emen s was
used in he analysis. Blood p essu e was measu ed in
duplica e a each ma e ni y ca e isi and a 1 and
7 yea s pos pa um.
Blood samples o glucose, choles e ol, HDL choles-
e ol and iglyce ide analysis a e a 12-hou as , and a
2-hou OGTT we e collec ed a baseline and a 1 and
7 yea s pos pa um. All blood analyses we e pe o med
a he UKK Ins i u e. Du ing he OGTT, he pa icipan s
d ank 75 g glucose in 330 mL wa e (Glucodyn,
Ul imed, Finland), and he samples we e aken a e 60
and 120 min. Plasma glucose concen a ions we e mea-
su ed esh wi hin 24 hou s a e he OGTT. Plasma
samples o lipid analysis we e s o ed ozen a −80°C
un il analysed. Ci ic acid/fluo ide and EDTA ubes
we e used o glucose and lipid analysis o enous blood.
Glucose, o al choles e ol, HDL choles e ol and iglyce -
ide concen a ions we e de e mined in enzyma ic assays
using a Roche Cobas Mi a Plus analyse . All es ing was
pe o med in duplica e.
MeS was diagnosed acco ding o In e na ional
Diabe es Fede a ion (IDF) c i e ia.
1
The diagnosis was
se i any h ee o he fi e c i e ia we e p esen :
inc eased wais ci cum e ence (>80 cm); ele a ed igly-
ce ides (≥1.7 mmol/L), o specific medica ion; educed
HDL choles e ol (<1.3 mmol/L), o specific medica ion,
ele a ed as ing glucose (≥5.6 mmol/L), o specific
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medica ion, and ele a ed blood p essu e (≥130 o
85 mm Hg), o specific medica ion.
S a is ical analyses
The backg ound cha ac e is ics and desc ip i e in o ma-
ion on componen s and he p e alence o MeS a e
epo ed as means and SDs o equencies and p opo -
ions. The Wilson sco e me hod wi hou con inui y
co ec ion was used o calcula e 95% CIs o p e alence.
Aχ
2
es was used o in es iga e whe he dis ibu ions o
ca ego ical a iables di e ed om one ano he .
Con inuous a iables we e no mally dis ibu ed. We used
one-way analysis o a iance o compa e means ac oss
g oups. Di e ences in con inuous a iables be ween he
heal hy con ol o he ea ly GDM g oup compa ed wi h
he o he h ee g oups me ged oge he we e es ed by
independen samples - es . Bina y logis ic eg ession
models we e used o ob ain ORs and hei 95% CIs o
s udy associa ions be ween MeS and i s explana o y a i-
ables. Explana o y a iables we e g oup ( he in e en-
ion, he usual ca e, he ea ly GDM and he heal hy
con ol as a e e ence g oup), age (con inuous), BMI
(con inuous) and he fi e GDM isk ac o s which we e
used in en ance c i e ia o he o iginal s udy: BMI
≥25 kg/m², age≥40 yea s, GDM o any sign o glucose
in ole ance in any p e ious p egnancy, a mac osomic
baby (≥4500 g) in any p e ious p egnancy, and diabe es
in fi s -deg ee o second-deg ee ela i es. Based on he
ule o 10 e en s pe a iable, mul i a iable logis ic
eg ession models we e adjus ed only o BMI and GDM
o any sign o glucose in ole ance in any p e ious p eg-
nancy. The esul s we e conside ed o be s a is ically sig-
nifican i p<0.05. All analyses we e pe o med wi h SPSS
so wa e (V.20.0).
RESULTS
Backg ound cha ac e is ics
Table 1 shows he cha ac e is ics o he 289 women who
pa icipa ed in he ollow-up s udy 7 yea s pos pa um.
The mean age o he pa icipan s was 37.8 yea s ( ange
25–52 yea s) and he mean numbe o deli e ies was 2.5
( ange 1–9). Twen y-nine (10%) women smoked e-
quen ly o occasionally. The mos common inclusion c i-
e ia o he s udy we e p ep egnancy o e weigh o
obesi y, and diabe es in fi s -deg ee o second-deg ee
ela i es. Women wi h ea ly GDM ulfil he inclusion c i-
e ia o being o e weigh (p<0.001) and ha ing a his o y
o GDM (p=0.002) mo e o en han o he s. Heal hy con-
ols did no mee inclusion c i e ia (GDM isk ac o s)
a baseline. The p e alence o o e weigh and obesi y
7 yea s pos pa um (53%, 69%, 80%) had s ayed a ound
he same le el, o sligh ly inc eased, compa ed wi h
ea ly p egnancy (48%, 68%, 78%) among women in he
in e en ion, usual ca e and ea ly GDM g oup, espec -
i ely. Fou women (2 in he ea ly GDM and 2 in he
heal hy con ol g oup) had medica ion o ype 2 dia-
be es. Six een (5%) women had medica ion o dyslipi-
daemias and eigh (3%) o hype ension, wi h no
Figu e 1 Flow diag am o he s udy. The wo in e en ion g oups (in e en ion and usual ca e), ea ly ges a ional diabe es
melli us and heal hy con ol g oups we e in i ed o ollow-up measu emen s 7 yea s a e in e en ion.
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di e ence be ween g oups. Eigh y-one (28%) women
epo ed ho monal con acep ion.
Women wi h ea ly GDM had highe mean weigh
(p<0.001) and BMI (p<0.001) compa ed wi h women in
he o he h ee g oups. Significan associa ion be ween
g oup and o e weigh (p<0.001) and obesi y (p<0.001)
was ound, so ha women wi h ea ly GDM we e mo e
o en o e weigh and obese han women in he o he
g oups. Heal hy con ols, on he o he hand, had lowe
mean weigh (p<0.001) and lowe BMI (p<0.001). They
we e less o en o e weigh o obese compa ed wi h
women in he o he h ee g oups, bo h o he associa-
ions being significan (p<0.001). The e we e no o he
be ween-g oup di e ences in he backg ound cha ac e -
is ics. Compa ed wi h baseline (a 8–12 weeks’p eg-
nancy), he women had gained weigh on a e age 3.1 kg
(SD 7.0, ange −33.2 o 25.1 kg). The g oups did no
di e s a is ically significan ly om each o he . The
heal hy con ol g oup seemed o ha e had gained less
weigh han he o he h ee g oups (1.8 s 3.5, p=0.13).
Twel e (9%) women o he in e en ion g oup and
se en (5%) women o he usual ca e g oup and none o
he heal hy con ol g oup had been diagnosed o GDM
a 26–28 weeks’p egnancy.
MeS and i s componen s 7 yea s pos pa um
The p e alence o MeS among all women was 19%
(95% CI 15% o 25%) ( able 2). Among women wi h
GDM isk ac o s, he p e alence was 14% (95% CI 9%
o 21%), wi h no di e ence be ween he in e en ion
(14%, 95% CI 8% o 25%) and he usual ca e g oup
(15%, 95% CI 8% o 25%). The p e alence was highes
among he ea ly GDM g oup (50%, 95% CI 35% o
65%) and lowes among he heal hy con ol g oup (7%,
95% CI 2% o 18%). Two (11%) o he 19 women wi h
he GDM diagnosis a 26–28 weeks’ges a ion had MeS
a 7 yea s pos pa um.
Se en y- wo pe cen o he women exceeded he wais
ci cum e ence limi o 80 cm (inc eased wais ci cum e -
ence) and almos hal exceeded he limi o 88 cm
(abdominal obesi y). HDL was educed (≤1.3 mmol/L)
among hal o he women. All women wi h he MeS
diagnosis exceeded he wais ci cum e ence o 80 cm.
Women in he ea ly GDM g oup had a la ge mean
wais ci cum e ence (p<0.001), highe as ing glucose
(p<0.001), highe sys olic blood p essu e (p=0.047) and
highe TG (p<0.0001). They mo e o en exceeded he
limi s o inc eased wais ci cum e ence and abdominal
obesi y (p<0.001 and p=0.002), impai ed as ing glucose
(p<0.001) and inc eased TG (p<0.001) compa ed wi h
he h ee o he g oups. Heal hy con ols had a smalle
mean wais ci cum e ence (p<0.001), lowe sys olic
(p=0.01) and dias olic (p=0.03) blood p essu e and
highe HDL (p=0.02), and hey less o en exceed he
limi s o inc eased wais ci cum e ence (p<0.001) and
dec eased HDL (p=0.03) compa ed wi h he o he
Table 1 Backg ound cha ac e is ics o women a 7 yea s pos pa um
In e en ion
(n=83)
Usual ca e
(n=87)
Ea ly GDM
(n=51)
Heal hy con ol
(n=68)
All
(n=289)
Age (yea s) 37.7±4.5 38.0±4.9 38.6±4.3 37.0±5.2 37.8±4.8
Weigh (kg) 75.6±17.3 76.9±13.1 84.5±16.3 62.9±7.6 74.6±15.7
BMI (kg/m
2
) 27.2±5.5 28.1±5.1 30.1±5.6 22.7±2.5 26.9±5.4
BMI 25–29.9 kg/m
2
17 (20) 39 (45) 41 (35) 12 (18) 86 (29)
BMI ≥30 kg/m
2
27 (33) 21 (24) 23 (45) 0 (0) 71 (25)
Smoking
No 73 (91) 77 (91) 45 (94) 57 (84) 252 (90)
Occasionally o daily 7 (9) 8 (9) 3 (6) 11 (16) 29 (10)
Educa ion
Basic o seconda y educa ion 25 (31) 25 (28) 19 (37) 20 (31) 89 (31)
Poly echnic educa ion 28 (34) 40 (46) 20 (39) 29 (45) 117 (41)
Uni e si y deg ee 29 (35) 23 (26) 13 (25) 16 (25) 81 (28)
Pa i y 2.4±1.0 2.6±1.2 2.6±1.6 2.5±1.0 2.5±1.2
1 8 (10) 12 (14) 6 (13) 6 (9) 32 (12)
2–3 66 (84) 60 (71) 35 (74) 50 (75) 211 (76)
≥4 5 (6) 12 (14) 6 (13) 11 (16) 34 (12)
GDM isk c i e ia (a 8–12 weeks’
p egnancy)
BMI ≥25 kg/m
2
40 (48) 59 (68) 39 (78) NA 138 (48)
Mac osomic child in any p e ious
p egnancy
3 (4) 3 (3) 5 (10) NA 11 (4)
GDM in any p e ious p egnancy 13 (16) 7 (8) 13 (39) NA 33 (12)
Diabe es in i s -deg ee o
second-deg ee ela i es
53 (64) 43 (49) 25 (50) NA 121 (42)
Age ≥40 yea s 3 (4) 5 (6) 0 (0) NA 8 (3)
Means and SDs o equencies (and p opo ions) o pa icipan s (n=289). BMI, body mass index; GDM, ges a ional diabe es melli us.
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g oups. The e we e no di e ences in he componen s
MeS be ween he in e en ion and usual ca e g oups.
Fi y-fi e (27%) women did no mee he c i e ia o
any MeS componen : 14 (23%) women in he in e en-
ion g oup, 14 (22%) in he usual ca e g oup, 7 (18%)
in he ea ly GDM g oup and 20 (46%) in he heal hy
con ol g oup. Mos women (n=115, 56%) me one o
wo MeS componen s.
Risk ac o s o MeS
Uni a iable bina y logis ic eg ession models
In uni a iable logis ic eg ession models, he OR o
de eloping MeS 7 yea s pos pa um among women wi h
inc eased GDM isk du ing p egnancy (in e en ion and
usual ca e) did no di e s a is ically significan ly om
he heal hy con ol g oup ( able 3). OR o MeS among
women wi h ea ly GDM was 21.0 (95% CI 4.47 o 98.7)
compa ed wi h he heal hy con ols, and 6.0 (95% CI
2.7 o 13.2) compa ed wi h he in e en ion and he
usual ca e g oups (no p esen ed). P ep egnancy BMI
(OR 1.20, 95% CI 1.11 o 1.29, p<0.001), p ep egnancy
o e weigh o obesi y (OR 8.06, 95% CI 3.21 o 20.2,
p<0.001) and GDM o any sign o glucose in ole ance in
any p e ious p egnancy (OR 3.21, 95% CI 1.34 o 7.69,
p<0.01) we e associa ed wi h inc eased occu ence o
MeS. The o he GDM isk ac o s (mac osomic baby in
any p e ious p egnancy, diabe es in ela i es o age)
we e no associa ed wi h he MeS occu ence 7 yea s
pos pa um.
Mul i a iable bina y logis ic eg ession models
In a mul i a iable eg ession model 1, adjus ed o p e-
p egnancy BMI, he OR o de eloping MeS 7 yea s
pos pa um among women wi h inc eased GDM isk
du ing p egnancy (in e en ion and usual ca e) did no
di e significan ly om he heal hy con ol g oup
( able 3). Women wi h ea ly p egnancy GDM had
inc eased odds o MeS compa ed wi h he heal hy
con ol g oup (OR 9.18, 95% CI 1.82 o 46.20, p=0.007).
Also inc eased p ep egnancy BMI was associa ed wi h
inc eased odds o MeS (OR 1.20, 95% CI 1.11 o 1.29,
p<0.001). In a mul i a iable eg ession model 2,
adjus ed o BMI and GDM o any sign o glucose
in ole ance in any p e ious p egnancy, ea ly GDM when
compa ed wi h he heal hy con ol g oup (OR 97.75,
95% CI 1.50 o 40.0, p=0.014), and inc eased p ep eg-
nancy BMI (OR 1.19, 95% CI 1.09 o 1.31, p<0.001)
we e associa ed wi h he MeS occu ence. GDM o any
sign o glucose in ole ance in any p e ious p egnancy
was no associa ed wi h he MeS occu ence 7 yea s
pos pa um.
D opou analyses
Da a o 7-yea ollow-up o MeS we e a ailable o 37%
o he women who we e in i ed o pa icipa e a e 7
yea s (n=788). O he women in i ed o ollow-up s udy,
17% we e no willing o pa icipa e, 26% we e ou o
each and 20% only comple ed a ollow-up ques ion-
nai e. D opou analyses showed ha he women pa ici-
pa ing he 7-yea ollow-up s udy we e olde a he
baseline (30.2 s 29.2, p<0.01), we e less o en equen
o occasional smoke s be o e p egnancy (17% s 30%,
p<0.001) and we e highe educa ed (uni e si y deg ee
28% s 19%, p<0.009) compa ed wi h he non-
pa icipan s. The e we e no di e ences be ween he
g oups in o he backg ound cha ac e is ic (BMI, pa i y
Table 2 Componen s o me abolic synd ome (MeS) and he p e alence o MeS acco ding o In e na ional Diabe es
Fede a ion c i e ia
In e en ion
(n=64–74)
Usual ca e
(n=66–78)
Ea ly GDM
(n=40–45)
Heal hy
con ol
(n=44–51)
All
(n=217–248)
Missing
alues (N)*
Wais ci cum e ence (cm)* 89.9±13.0 90.9±12.8 97.9±14.6 79.5±6.5 89.5±13.5 0, 3, 0, 0
Wais ≥80 cm 52 (70) 59 (79) 42 (93) 24 (47) 177 (72)
Wais ≥88 cm 41 (55) 42 (56) 32 (71) 6 (12) 121 (49)
Fas ing glucose (mmol/L) 5.2±0.5 5.2±0.4 5.6±0.5 5.2±0.4 5.3±0.5 5, 12, 3, 6
Fas ing glucose ≥5.6 mmol/L o
medica ion
10 (15) 7 (11) 21 (49) 4 (9) 42 (19)
Sys olic p essu e (mm Hg) 119±13 118±12 122±11 114±14 118±12 2, 3, 1, 4
Dias olic p essu e (mm Hg) 77±10 78±10 79±7 75±10 77±10 2, 3, 1, 4
Blood p essu e ≥130 o
≥85 mm Hg o medica ion
10 (14) 13 (17) 8 (18) 6 (13) 37 (16)
HDL choles e ol (mmol/L) 1.30±0.27 1.28±0.38 1.28±0.36 1.41±0.30 1.32±0.34 10, 0, 2, 1
HDL choles e ol ≤1.3 mmol/L
o medica ion
33 (52) 41 (53) 25 (58) 18 (36) 117 (50)
T iglyce ides (mmol/L) 0.91±0.34 1.05±0.67 1.36±0.88 0.95±0.38 1.05±0.61 10, 0, 2, 1
T iglyce ides ≥1.7 mmol/L 1 (2) 9 (12) 12 (28) 5 (10) 27 (12)
Me abolic synd ome 9 (14) 10 (15) 20 (50) 3 (7) 42 (19) 10, 7, 5, 7
Means and SDs o equencies (and p opo ions) o pa icipan s. GDM, ges a ional diabe es melli us.
*Numbe o missing alues in he in e en ion, usual ca e, ea ly GDM, heal hy con ol g oups, espec i ely.
Puhkala J, e al.BMJ Open 2017;7:e014565. doi:10.1136/bmjopen-2016-014565 5
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o GDM isk c i e ia), labo a o y measu emen s o
g oup dis ibu ion.
DISCUSSION
Se en yea s pos pa um, MeS was diagnosed among 14%
(95% CI 9% o 21%) o he women wi h isk ac o s o
GDM du ing p egnancy. The MeS p e alence was
highes among women wi h a diagnosis o ea ly GDM
(50%, 95% CI 35% o 65%), and lowes among he
heal hy con ol g oup (7%, 95% CI 2% o 18%).
Diagnosis o ea ly GDM and inc eased p ep egnancy
BMI we e he s onges isk ac o s o de eloping MeS.
P ep egnancy and p esen o e weigh o obesi y we e
common among women wi h GDM isk ac o s, and
especially among hose wi h ea ly GDM.
In a p ospec i e Finnish popula ion s udy among
women aged 36 and 39, he MeS p e alence was 18%
and 23% acco ding o he IDF defini ion.
18
Compa ed
wi h hese le els, he MeS p e alence in ou s udy was
somewha lowe among women wi h an inc eased isk
o GDM. The e o e, inc eased GDM isk seemed no o
be associa ed wi h a highe MeS p e alence 7 yea s pos -
pa um. Compa ed wi h he women aged 35–45 and 25–
60 yea s in a Finnish popula ion s udy in 2012, howe e ,
he women wi h inc eased GDM isk we e mo e o en
obese (28% s 16%),
34
and abdominally obese (wais ci -
cum e ence >88 cm) (56% s 30%).
35
These di e ences
a e ele an , as especially abdominal obesi y is he mos
impo an independen ac o in he de elopmen o
MeS.
10
The finding may indica e u u e isk in ou pa i-
cipan s. O e weigh was also he mos common inclusion
c i e ia (GDM isk c i e ia) in ou s udy, which appa -
en ly had an influence on he high p e alence o o e -
weigh and obesi y pos pa um.
Howe e , he in e en ion (14%, 95% CI 8% o 25%)
and usual ca e (15%, 95% CI 8% o 25%) g oup did
no di e om each o he in he p e alence o MeS o
i s componen s a e 7 yea s, e en hough counselling
had posi i e e ec s on women’s weigh gain and li es yle
du ing p egnancy.
28–31
Howe e , 7 yea s a e a long ime,
and se e al ac o s ha e a ec ed women’s li es yle.
Mo he s wi h small child en may ha e had lack o ime
and may ha e go i ed o ollow he ecommended li e-
s yle habi s which we e discussed du ing he in e en-
ion. Fu he , pa icipa ion in a GDM p e en ion s udy
may ha e imp o ed heal h consciousness and li es yle
habi s in he in e en ion and he usual ca e g oup.
Addi ionally, also usual ca e includes some li es yle coun-
selling in Finland. D opou a e was a he high, bu
since i was non-di e en ial o g oup, he possibili y o
bias in he di e ences be ween g oups emains low.
Ou subg oups di e ed in he p e alence o MeS.
Women in he ea ly GDM and women in he heal hy
con ol g oups ep esen ed he ex emes (50% s 7%).
Ea lie s udies ha e ound ha his o y o GDM is
s ongly associa ed wi h a highe isk o u u e MeS and
o he ca diome abolic diso de s.
36 37
In a Finnish
Table 3 Logis ic eg ession models wi h ORs and 95% CIs and p alues (n=217) o occu ence o me abolic synd ome (acco ding o In e na ional Diabe es Fede a ion
c i e ia) by i s explana o y a iables (g oup, age, body mass index and i e ges a ional diabe es melli us isk ac o s)
Uni a iable logis ic
eg ession models
Mul i a iable logis ic
eg ession model 1
Mul i a iable logis ic
eg ession model 2
OR (95% CI) p Value OR (95% CI) p Value OR (95% CI) p Value
G oup ( e e ence=heal hy con ol)
In e en ion 3.44 (0. 71 o 16.8) 0.13 1.64 (0.31 o 8.79) 0.56 1.29 (0.23 o 7.18) 0.77
Usual ca e 3.15 (0.65 o 15.3) 0.16 1.39 (0.26 o 7.41) 0.70 1.17 (0.21 o 6.41) 0.85
Ea ly GDM 21.0 (4.47 o 98.7) <0.001 9.18 (1.82 o 46.20) 0.007 7.75 (1.50 o 40.0) 0.014
Age (ea ly p egnancy, con inuous) 1.07 (1.00 o 1.15) 0.052
BMI (p ep egnancy, con inuous) 1.20 (1.11 o 1.29) <0.001 1.17 (1.08 o 1.28) <0.001 1.19 (1.09 o 1.31) <0.001
GDM isk ac o s du ing ea ly p egnancy
BMI ≥25 kg/m
2
(p ep egnancy) 8.06 (3.21 o 20.2) <0.001
A mac osomic baby (≥4500 g) in any p e ious p egnancy 0.74 (0.09 o 6.34) 0.78
GDM o any sign o glucose in ole ance in any p e ious p egnancy 3.21 (1.34 o 7.69) <0.01 2.07 (0.74 o 5.78) 0.17
Type 1 o 2 diabe es in i s -deg ee o second-deg ee ela i es 1.04 (0.52 o 2.09) 0.91
Age ≥40 yea s 0.74 (0.09 o 6.34) 0.78
GDM, ges a ional diabe es; BMI, body mass index.
Uni a iable logis ic eg ession models: sepa a e models o each explana o y a iables wi hou adjus men s.
Mul i a iable logis ic eg ession model 1: adjus ed o one explana o y a iable (BMI).
Mul i a iable logis ic eg ession model 2: adjus ed o wo explana o y a iables (BMI, and GDM o any sign o glucose in ole ance in any p e ious p egnancy).
6Puhkala J, e al.BMJ Open 2017;7:e014565. doi:10.1136/bmjopen-2016-014565
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coho among 240 women, he isk o de eloping MeS
2–6 yea s a e p egnancy complica ed by GDM was
2.4- old highe compa ed wi h no mal p egnancy.
21
In ou ea lie epo o he same o iginal ial, he
MeS p e alence among women wi h ea ly GDM was
al eady ele a ed (31%) a 1-yea pos pa um compa ed
wi h he in e en ion g oup (11%).
24
Se en yea s
pos pa um, he MeS p e alence among women wi h
ea ly GDM had inc eased o 50%. Fu he , women
wi h ea ly GDM had inc eased odds o MeS compa ed
wi h o he h ee g oups (in e en ion, usual ca e and
heal hy con ols). The associa ion emained a e
adjus men o BMI. Also his o y o GDM was associa ed
wi h he MeS occu ence. These findings a es he
la e ca diome abolic isk associa ed wi h GDM.
Ne e heless, GDM diagnosis a 26–28 weeks’ges a ion
among he 19 women in he in e en ion and usual
ca e g oup seemed no o be associa ed wi h highe
MeS p e alence in ou da a. The e o e, ou s udy sug-
ges s ha GDM was associa ed wi h an inc eased MeS
p e alence 7 yea s pos pa um i i was diagnosed in
ea ly p egnancy (8–12 weeks). Women wi h ea ly GDM
a e a special high isk g oup o la e ca diome abolic
diso de s. A la ge me a-analysis ound ha women wi h
ea ly p egnancy GDM we e a a wo old isk o u u e
ype 2 diabe es compa ed wi h women wi h la e
GDM.
26
Se e al ca diome abolic isk ac o s we e clus e ed in
he women in he ea ly GDM g oup. In ea ly p egnancy,
hey had been mo e o en o e weigh o obese, and
7 yea s pos pa um, hey s ill we e mo e o en o e weigh
o obese, and had componen s o MeS mo e equen ly
han he o he women. Fu he , compa ed wi h Finnish
emale popula ion, he women wi h ea ly GDM in ou
s udy we e h ee imes mo e o en obese (45% s
16%),
34
and o e wo imes mo e o en abdominally
obese (wais ci cum e ence >88cm) (71% s 30%).
35
P esen obesi y pa ly explains he inc eased MeS p e a-
lence. Clus e ing o li es yle- ela ed isk ac o s is
common.
38–40
P egnancy- ela ed weigh e en ion ends
o be highes among hose women who ha e been o e -
weigh o obese be o e p egnancy.
41 42
Fu he , many
women e ain weigh a e p egnancy, and he mean
weigh gain associa ed wi h pa i y is a ound 0.5–3.2 kg,
wi h a high pe sonal a ia ion.
39 43 44
In a Finnish popu-
la ion s udy, pa i y- ela ed weigh e en ion was asso-
cia ed wi h isce al obesi y.
45
High p e alence o obesi y p omo ing insulin esis -
ance was p obably he common denomina o o he
inc eased p e alence o ea ly p egnancy GDM and MeS
a e 7 yea s.
46 47
This finding clea ly unde lines ha i
is pa icula ly impo an o in es in li es yle counselling
among o e weigh and obese p egnan women en e ing
ma e ni y ca e. P e en ion o excessi e weigh gain
du ing p egnancy and p omo ing pos pa um weigh
educ ion by indi idually ailo ed li es yle modifica ions
ha e been e ec i e agains weigh e en ion, and in p e-
en ing u he ca diome abolic diso de s, such as MeS
in pa ous women.
48–52
A weigh educ ion o 5–10% is
associa ed wi h significan dec eases in ca diome abolic
isk ac o s.
53 54
The possibili ies o eaching p egnan
women in many coun ies a e good due o ma e ni y
ca e sys ems, bu he e is o en lack o long- e m
ollow-up as he heal hca e p o ide s change.
55
Ac ions
o inc ease coope a ion be ween di e en p o ide s a e
needed.
Heal hy con ols we e heal hie han he o he h ee
g oups wi h GDM isk ac o s, as assessed by com-
ponen s and he p e alence o MeS a 7 yea s pos -
pa um. Also compa ed wi h he Finnish popula ion,
hey ep esen ed an unexcep ionally heal hy g oup, in
wha comes o he p e alence o obesi y (0% s 16%),
abdominal obesi y (12% s 30%) as well as MeS (7% s
17–23%).
34 35
The esul s sugges ha keeping no mal
weigh and p e en ion o excessi e p egnancy- ela ed
weigh e en ion a e impo an in no only p e en ing
GDM, bu also in p e en ing la e MeS.
S eng hs and limi a ions
Ou s udy has se e al s eng hs. I was a long- e m
ollow-up, om ea ly p egnancy un il 7 yea s pos -
pa um. I was also one o he fi s ollow-up s udies o
ges a ional ials, in which he p e alence o MeS has
been de e mined among women wi h isk ac o s o
GDM. To he bes o ou knowledge, he only p e ious
ollow-up epo was ou s on he MeS p e alence among
women wi h GDM isk ac o s a 1-yea pos pa um.
24
In
gene al, he e is a limi ed amoun o s udies o he MeS
p e alence among ep oduc i e-aged emale popula-
ions, e en hough obesi y is apidly inc easing wo ld-
wide, especially among young adul s.
11 56
Ou s udy
esul s include da a o he MeS p e alence among di e -
en isk g oups—women wi h an inc eased GDM isk,
women diagnosed wi h ea ly GDM and heal hy p egnan
women. Also associa ions be ween isk ac o s assessed in
ea ly p egnancy and MeS 7 yea s pos pa um ha e no
been iden ified ea lie . Ou o iginal ial
32
was one o
he la ges RCTs abou p e en ing he de elopmen o
GDM in women wi h GDM isk ac o s.
A e 7 yea s, he ec ui men o he women o he o i-
ginal s udy was di ficul , and e en ually, 37% o he
in i ed women en e ed he measu emen s o analyses
o MeS. Thi y-se en pe cen we e ei he no willing o
pa icipa e o only comple ed he ollow-up ques ion-
nai e. D opou analyses showed ha he esul s may ha e
been a ec ed by a heal hy selec ion bias, as he women
who pa icipa ed in he ollow-up s udy we e less o en
smoke s and we e highe educa ed. On he o he hand,
he bias a ec ed all ou subg oups en e ing he
ollow-up s udy, as hey did no di e om each o he
ega ding o he pa icipa ion a e. The subg oups we e
ela i ely small, which weakened he powe o compa e
he subg oups. The s udy was implemen ed among
Finnish women, and hus, he esul s can only be gene -
alised o Caucasian popula ions.
Puhkala J, e al.BMJ Open 2017;7:e014565. doi:10.1136/bmjopen-2016-014565 7
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CONCLUSIONS
Se en yea s pos pa um, MeS was diagnosed among 14%
o he women wi h isk ac o s o GDM du ing p eg-
nancy, which is less han a e age. The MeS p e alence
was he highes among women wi h a diagnosis o ea ly
GDM (50%), and he lowes among he heal hy con ol
g oup (7%). Ea ly GDM diagnosis and inc eased p e-
p egnancy BMI we e he s onges isk ac o s o de el-
oping MeS. P ep egnancy and p esen o e weigh o
obesi y we e common among women wi h GDM isk
ac o s, and especially among hose wi h ea ly GDM.
O e weigh and obese women and especially hose wi h
ea ly GDM should be moni o ed and counselled o ca -
diome abolic isk ac o s a e deli e y. P e en ion o
p egnancy- ela ed weigh e en ion, including excessi e
ges a ional and pos pa um weigh gain, is impo an o
he p e en ion o MeS. O e weigh and obesi y among
ep oduc i e-aged women is inc easing, which ep esen s
e en a g ea e challenge in moni o ing and managing
isk ac o s o ch onic diseases. La ge popula ion
s udies on he MeS p e alence and e alua ion o p e en-
ion s a egies a e needed among ep oduc i e-aged
women, especially among hose wi h GDM isk ac o s.
Acknowledgemen s The au ho s hank hospi al chemis , Anne Rauhio, om
Fimlab Labo a o ies who was esponsible o he labo a o y es ing. Päi i
Vii anen, Ta u Helenius, Ulla Hakala, Ulla Honkanen and Si ke Rasinpe ä
ec ui ed he s udy pa icipan s, pa icipa ed in he da a collec ion and
managed he s udy da a.
Con ibu o s RL, JP, PK, PT and PH ini ia ed he s udy design; JR and JP
pe o med s a is ical analyses; JP w o e he pape . All au ho s con ibu ed o
e inemen o he s udy p o ocol and app o ed he inal manusc ip . JP and
RL ha e he p ima y esponsibili y o he inal con en .
Funding This wo k was suppo ed by Academy Finland (g an numbe
277079), Compe i i e Resea ch Funding o he Tampe e Uni e si y Hospi al
(9R030, 9S034, 9N041, 9M053) and he Juho Vainio Founda ion.
Compe ing in e es s None decla ed.
E hics app o al Pi kanmaa Uni e si y Hospi al Dis ic E hics.
P o enance and pee e iew No commissioned; ex e nally pee e iewed.
Da a sha ing s a emen All da a p esen ed in his s udy a e a ailable o
u he collabo a ion a e eques o RL ([email p o ec ed]).
Open Access This is an Open Access a icle dis ibu ed in acco dance wi h
he C ea i e Commons A ibu ion Non Comme cial (CC BY-NC 4.0) license,
which pe mi s o he s o dis ibu e, emix, adap , build upon his wo k non-
comme cially, and license hei de i a i e wo ks on di e en e ms, p o ided
he o iginal wo k is p ope ly ci ed and he use is non-comme cial. See: h p://
c ea i ecommons.o g/licenses/by-nc/4.0/
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