Sunteți pe pagina 1din 7

Volume: 2: Issue-1: Jan-Mar -2011 ISSN 0976-4550

Review Ari!le
T. Sharmilakrishna, J.N.Nai!, an D.R.Ra"#s$ari
D#%ar&m#n& '( Bi')h#mis&r*, Nara*ana M#i)al +'ll#,#, N#ll'r#.
ABSTRA+T: The prevalence of diabetes is rapidly rising all over the globe at an alarming rate.
Gestational diabetes mellitus (GDM) is defined as carbohydrate intolerance occurring for the first
time during pregnancy. The prevalence of GDM varies in direct proportion to the prevalence of
Type 2 diabetes for a given ethnic group or population. It is crucial to detect women with GDM
as the condition is associated with diverse range of adverse maternal and neonatal outcomes. In
addition having a history of GDM puts the mother at ris! for the development of Type 2 diabetes
mellitus or recurrent GDM. "arious screening guidelines have been introduced depending upon
the suitability of test to the population characteristics cost and screening accuracy. #till there are
lots of controversies to which test to be used when should the screening be done and who
should be screened.
$owever recogni%ing GDM is becomimg a ma&or health challenge for clinicians and treating it
results in lowering of both maternal and fetal complications. 'lso clinicians must followup
women with GDM postpartum so that the prevalence of Type 2 diabetes may start declining.
-E.WORDS: Gestational diabetes mellitus (ral glucose tolerance test (ral glucose challenge
Gestational diabetes mellitus (GDM) is defined as carbohydrate intolerance of varying degrees of
severity with onset or first recognition during pregnancy ()ala&i " 2**+).
The prevalence of GDM is increasing worldwide especially in developing countries.
In India the prevalence of GDM is high and varies according to geographical areas and diagnostic
methods employed ( ,argar '$ 2**- Diva!ar $ 2**.). 'ccording to a random
national survey conducted in 2**- the prevalence was /0.112 ( #eshiah " 2**-). In
2**. a hospital based survey showed a combined prevalence of GDM and IGT to be 2/.02
( #wami #3 2**.).
RIS- STRATI0I+ATION ( 'runa 4igam*/*)
5resently according to fifth international wor!shop conference on GDM 2**1 GDM ris!
stratification is done at first antenatal visit. The pregnant females are divided into low middle
and high ris! and managed accordingly.
6ow ris! 7 4o blood glucose testing is done if 7
'ge 8 21 years
9aucasian :member of other ethnic group
)MI 8 2+
4o history of GDM or glucose intolerance
4o family history of diabetes in first degree relative
4o history of GDM associated adverse pregnancy outcome
Inernaional Journal o" A##lie$ %iolo&' an$ ()arma!eui!al *e!)nolo&' (a&e:226
Availa+le online a www,i-a+#,!om
S)armila e al ISSN 0976-4550
'verage ris! 7 )lood glucose testing is done at 2- 7 2. wee!s with one step or two step
techni;ue in pregnant females of Indian $ispanic 'fro<'merican 'sian ethnic groups.
$igh ris! 7 )lood glucose testing is done at the earliest and if found normal then repeated at 2-
7 2. wee!s or at any time when there are features of hyperglycemia in pregnant females having
=amily history of type 2 diabetes mellitus
5revious history of GDM impaired glucose intolerance glycosuria
+OM/LI+ATIONS O0 GDM (Tracy 6.#et&i 2**1)>
There are both fetal and maternal complications associated with GDM.
0#&al )'m%li)a&i'ns:
These include macrosomia neonatal hypoglycemia perinatal mortality congenital
malformation hyperbilirubinemia polycythemia hypocalcaemia and respiratory distress
syndrome. 4eonatal hypoglycemia can occur within a few hours of delivery. This results from
maternal hyperglycemia causing fetal hyperinsulinemia. 6ong term complications to the offspring
include an increased ris! of glucose intolerance and obesity.
Ma&#rnal )'m%li)a&i'ns:
These include hypertension preeclampsia and an increased ris! of cesarean delivery.
More important is women with GDM have an increased ris! of developing diabetes after
pregnancy when compared to the general population with a conversion rate of upto ?2 per year.
' number of screening procedures and diagnostic criteria ('merican Diabetes 'ssociation
('D') @orld $ealth (rganisation (@$() 4ational Diabetes Data group(4DDG) and
'ustralian criteria ) are being followed in the same as well as in different countries.
'D' ('MA3I9'4 DI')ATA# '##(9I'TI(4) recommends #A6A9TI"A #93AA4I4G in
pregnant women having ( 'runa 4igam 2*/*)
/. 'ge B 21 yrs
2. (verweight before pregnancy
?. Athnic group with high prevalence of GDM such as native 'mericans 'sians
$ispanics and 'frican<'merican women
-. $istory of abnormal glucose tolerance
1. $istory of poor obstetric outcome
ADA 1+ar%#n&#r an +'!s&'n2 /r')#!r# ( #eshiah " 2**C)>
It is a T@( step procedure.
#tep / > ' 1* grams glucose challenge test (G9T) is used for screening without regard to
the time of last meal or time of the day.
#tep2> If / hour G9T value is B /-* mg:dl /** g (3'6 G6D9(#A T(6A3'49A
TA#T((GTT) is recommended and plasma glucose is estimated at * / 2 and ? hr .
GDM is diagnosed if any of two or more values meet or eEceed as shown in Table /.
Inernaional Journal o" A##lie$ %iolo&' an$ ()arma!eui!al *e!)nolo&' (a&e:227
Availa+le online a www,i-a+#,!om
S)armila e al ISSN 0976-4550
Table /> 5lasma glucose is estimated at * / 2 and ? hr
/**<g (GTT
+1<g (GTT
+1<g (GTT
=asting (mg:dl) C1 C1 /20
/<hour(mg:dl) /.* /.* <<<
2<hour(mg:dl) /11 /11 /-*
?<hour (mg:dl) /-* <<< <<<
=or the 'D' criteria two or more of the values from either the /** or +1<g (GTT must be met
or eEceeded to ma!e the diagnosis of GDM. =or the @$( criteria one of the two values from
the +1<g (GTT must be met or eEceeded to ma!e the diagnosis of GDM.
@hen two step approach is employed a glucose threshold value B/-* mg:dl (+..mmol:l)
identifies approEimately .*2 of women with GDM and the yield is further increased to C*2 by
using a cut<off value of B /?* mg:dl but it has high false positive rate (+.2 mmol:l) ( Tracy
6.#et&i 2**1).
W3O /r')#!r#
@$( recommends D4I"A3#'6 #93AAI4G =(3 GDM which is used in many countries.
Diagnosis is based on a 2hr +1 g (GTT. GDM is diagnosed if either =asting plasma glucose is
B/20 mg:dl or 2 hr plasma glucose B /-* mg:dl (shown in Table /) ( Tracy 6. #et&i et. al. 2**1).
DRAWBA+-S O0 VARIOUS /RO+EDURES (#eshiah " 2**C) >
'D' 5rocedure
/. The glycemic cutoff was originally validated against the future ris! of these women
developing diabetes and 4(T on fetal outcome.
2. =urther many women in community health centres are reluctant to undergo 'D'
procedure for following reasons
a) number of blood samples drawn are many
i) for screening and ii) for subse;uent ? hr (GTT to confirm the diagnosis (-
blood samples).
b) they have to visit the antenatal clinic on two occasions 7 once for
screening and again for diagnosis.
W3O /r')#!r#
This criteria was also not based on the maternal and fetal outcome but probably the criteria was
recommended for its A'#F adaptability in clinical practice.
In I4DI'4 #9A4'3I( screening is essential in all pregnant women as I4DI'4# have // fold
increased ris! of developing glucose intolerance during pregnancy as compared to 9aucasian
women. The pic! up rate by @$( criteria is ? times more than that of 'D' criteria ( 'runa
4igam 2*/*) . #o universal screening is suitable for the Indian setting as recommended
by @$( that serves as one step screening and diagnostic procedure which is simple to
perform besides being economical ( " #eshiah 2**.).
Inernaional Journal o" A##lie$ %iolo&' an$ ()arma!eui!al *e!)nolo&' (a&e:22.
Availa+le online a www,i-a+#,!om
S)armila e al ISSN 0976-4550
Insulin is detectable in the fetal pancreas as early as C wee!s after conception. 'n increase in
pancreatic beta cell mass and insulin secretion in the fetus occurs by the /0
wee! of gestation in
response to maternal hyperglycemia ( $ 3eiher 4ahum GG**2 ). The
priming of the fetal beta cells may account for the persistence of fetal hyperinsulinemia
throughout pregnancy and the ris! of accelerated fetal growth ( 9arpenter M@ 2**/)
even when the mother en&oys good metabolic control in later pregnancy ( 3 #chwart% /CC-
). This necessitates performing the test procedures to diagnose GDM in the first trimester itself.
=urther early detection and care results in a better fetal outcome (" #eshiah 2**.). )y
following the usual recommendation for screening between 2- and 2. wee!s of gestation the
chance of detecting unrecogni%ed type 2 diabetes before pregnancy (pre<GDM) is li!ely to be
missed ( )en<$aroush**- Gose 6.)artha***). If the 2<h 5G is B 2** mg:dl in the
early wee!s of pregnancy she may be pre<GDM and '/c of B 0 is confirmatory ( )ala&i
"**+ ). H4ormal '/c levels during pregnancy is 1.? < 0.I ' pregnant woman found to
have normal glucose tolerance J4GTK in the first trimester should be tested for GDM again
around 2-
< 2.
wee! and finally around ?2
7 ?-
wee! ( #eshiah "**+ " #eshiah 2**.) .
/. 5atient Aducation
2. Medical 4utrition Therapy (M4T)
?. Insulin
-. (ral drugs
/a&i#n& E!)a&i'n:
It is essential educating women with GDM about the condition and its management. The
compliance with treatment plan depends on the patientLs understanding of
a. The implication of GDM for her baby and her self.
b. Dietary recommendations .
c. #elf monitoring of blood glucose.
d. #elf administration of insulin and ad&ustment of these insulin doses.
e. Identification and treatment of hypoglycemia (5atient M family members)
( #eshiah " 2**C).
M#i)al N!&ri&i'n Th#ra%* 1MNT2
The goals of M4T are to provide ade;uate nutrition for the mother and fetus provides sufficient
calories for appropriate maternal weight gain maintain normoglycemia and avoid !etosis ('D'
Diabetes 9are 2**?).
Insulin is the pharmacological therapy that has most consistently been shown to reduce fetal
morbidities when added to M4T. @hen maternal glucose levels are used insulin therapy is
recommended when M4T fails to maintain self<monitored glucose at the following levels
( 'D' Diabetes 9are 2**?)>
Inernaional Journal o" A##lie$ %iolo&' an$ ()arma!eui!al *e!)nolo&' (a&e:229
Availa+le online a www,i-a+#,!om
S)armila e al ISSN 0976-4550
=asting plasma glucose N /*1 mg:dl (1.. mmol:l)
/<h postprandial plasma glucose N/11 mg:dl (..0 mmol:l)
2<h postprandial plasma glucose N/?* mg:dl (+.2mmol:l)
In normal pregnancy the mean plasma glucose (M5G)O#D value for fasting is .C mg:dl
and 2 hour is /22 mg:dl. Thus maintenance of mean plasma glucose (M5G) level P/*1mg:dl to
//* mg:dl is desirable for a good fetal outcome . This is possible if =5G and 2 hr postprandial
pea!s are P C*mg:dl and P/2*mg:dl ( #eshiah " 2**C).
It is ideal to use human insulins as they are least immunogenicthough insulin doesnot cross the
placenta insulin antibodies due to animal source insulin can cross the placenta
and stress the fetal beta cell increase insulin production and induce macrosomia.
3apid acting insulin analogues(4ovorapid :$umalog ) have been found to be safe and effective
in achieving the targeted postprandial glucose value during pregnancy (" #eshiah 2**0).
6ispro appears to be safe in pregnancy if started after /- wee!s of gestation and it is the first
analogue to get category ) approval by D#=D' ( Tracy 6.#et&i 2**1) and 'spart has also
been found to be safe and effective in management of GDM (" #eshiah 2**0).
3eports have shown good fetal outcome in GDM women who were on glyburide ( microni%ed
form of glibenclamide). ' randomi%ed unblinded clinical trial compared the use of insulin and
glyburide in women with GDM who were not able to meet glycemic control goals on M4T.
Treatment with either agent resulted in similar perinatal outcomes. 'll patients were beyond the
first trimester of pregnancy at the initiation of therapy ( 6anger ( 2***). $owever further
studies regarding use of glyburide are needed in a larger patient population to establish its safety (
' randomi%ed controlled study found that in women with GDM metformin (alone or with
insulin) was not associated with increased perinatal complications as compared with insulin
( Ganet '.3owan 2**.). Metfromin has been found to be useful in women with polycystic
ovarian disease (59(D ) who failed to conceive ( Misra #**- Daniela G. Ga!ubowic% 2**2). 9ontinuing this drug after conception is still a controversy but there are few studies
favouring continuation of metformin throughout pregnancy in these women (Daniela G .
$owever more studies are re;uired before routinely recommending oral anti<diabetic agents
during pregnancy.
Most obstetricians still advocate delivery at ?. wee!s as perinatal mortality and morbidity appear
to increase after this time. Induction at ?. wee!s gestation may be slow due to unfavourable
conditions of the cerviE but this also has to be balanced against the poorly defined and
predictable ris! of late intrauterine death if pregnancy is allowed to continue more than ?.
wee!s .=etal health may deteriorate suddenly hence obstetric management should not be rigid
and each case needs individual care and attention . ' neonatologist support at the time of delivery
is advisable (" #eshiah 2**0).
Inernaional Journal o" A##lie$ %iolo&' an$ ()arma!eui!al *e!)nolo&' (a&e:2/0
Availa+le online a www,i-a+#,!om
S)armila e al ISSN 0976-4550
Gestational diabetic women re;uire follow up. Glucose tolerance test with +1 g oral glucose is
performed after 0 wee!s of delivery and if necessary repeat after 0 months and every year to
determine whether the glucose tolerance has returned to normal or progressed. ' considerable
proportion of gestational diabetic women may continue to have glucose intolerance (" #eshiah 2**0).
GDM recurs approEimately in 1*2 of subse;uent pregnancies. The future ris! of developing
diabetes for a gestational diabetic is two fold if she becomes overweight ( " #eshiah
@omen with GDM have to receive counselling with regard to their increased ris! of developing
permanent diabetes. Indian women with GDM have a high ris! of developing diabetes (especially
type 2 diabetes mellitus) and metabolic syndrome at a comparatively younger age. They should
be made aware of the symptoms of hyperglycemia and advice should be given about the
importance of healthy eating habits and eEercise patterns for maintaining ideal body weight.
9ontraceptive advice and counselling about planning future pregnancies should be given
( #eshiah " 2**C).
GDM is a common medical problem that results from an increased severity of insulin resistance
as well as an impairment of the compensatory increase in insulin secretion. 5regnancy in
essence serves as a metabolic stress test and uncovers underlying insulin resistance and beta<cell
dysfunction. GDM is associated with a variety of maternal and fetal complications most notably
@$( recommends universal screening of all pregnant women for GDM.
Ma&ority of guidelines suggest screening between 2-<2. wee!s but few studies
suggest screening to diagnose GDM in the first trimester itself as early detection and care
results in a better fetal outcome. In Indian setting one step procedure recommended by
@$((+1g (GTT) is feasible in terms of better detection rate saves time limits cost due to
repeated visits to health centre and reduces repeated invasive sampling.
GDM women have a high ris! of developing diabetes in the future . They are ideal group to be
targeted for lifesylte modifications and pharmacologic intervention inorder to delay or postpone
the onset of overt diabetes. (ffspring of women with GDM should be followed carefully for the
development of obesity and : or abnormalities of glucose tolerance .
The maternal and fetal outcome depends upon the care by the committed team of diabetologists
obstetricians and neonatologists . ' short term intensive care gives a long term pay off in the
primary prevention of obesity impaired gluose tolerance(IGT) and diabetes in the offspring as
the preventive medicine starts before birth .
'merican Diabetes 'ssociation(2**?) Gestational Diabetes Mellitus. Diabetes 9are 20 (suppl.)> /*? 7 /*1.
'runa 4igam 5oo&a Dwivedi 5i!ee #aEena (2*/*) #creening for Gestational Diabetes Mellitus> 'n update. Indian
Gournal of Medical #pecialities /(/)>/?</..
)ala&i " Madhuri )# #eshiah " 'shalatha # #heela 3 #uresh #(2**+) '/9 in Gestational Diabetes Mellitus in
'sian Indian women . Diabetes 9are ?*(+)> /.01<+.
)en<$aroush ' Fogev F $(D M (2**-) Apidemiology of gestational diabetes mellitus and its association with
Type2 diabetes. Diabet Med . 2/(2)> /*?</?.
Inernaional Journal o" A##lie$ %iolo&' an$ ()arma!eui!al *e!)nolo&' (a&e:2/1
Availa+le online a www,i-a+#,!om
S)armila e al ISSN 0976-4550
9arpenter M@ 9anic! G' $ogan G@ #hellum 9 #omers M #tar G' (2**/)'mniotic fluid insulin at /-<2* wee!sL
gestation > association with later maternal glucose intolerance and birth macrosomia . Diabetes care 2-(+)> /21C 7 0?.
Daniela G. Ga!ubowic% Maria G . luor no #alomon Ga!ubowic% Qatherina ' . 3oberts and Gohn A . 4estler (2**2)
Affects of Metformin on Aarly 5regnancy loss in the 5olycystic ovary syndrome. The Gournal of 9linical
Andocrinology M Metabolism .+(2)> 212- 7 12C.
Diva!ar $ Tyagi # $osmani 5 Manyonda IT( 2**.) Diagnostic criteria influence prevalence rates for gestational
diabetes> implications in an Indian pregnant population .
5erinatology /*(0)> /11<0/.
$ 3eiher Q =uhrmann # 4oac! Q 5 @oltans!i A Gut%i $ $ahn von Dorsche $ G $ahn(/C.?) 'ge 7dependent
insulin secretion of the endocrine pancreas in vitro from fetuses of diabetic and nondiabetic patients . Diabetes 9are
0(1)> --0<1/ .
Ganet ' 3owan @illiam M $ague @an%hen Gao Malcolm 3 .)attin M 5eter Moore (2**.) Metformin versus
Insulin for the Treatment of Gestational Diabetes. 4 Angl G Med ?1.> 2**? 7 /1.
Gose 6.)artha 5ilar Martine% <Del<=renso 3afael 9omino<Delgado (2***) Gestational diabetes mellitus diagnosed
during early pregnancy. 'm G (bstet Gynecol /.2(2)> ?-0 7 1*.
6anger ( 9onway D6 )er!us MD Rena!is AM Gon%ales ( (2***) ' comparison of glyluride and insulin in women
with gestational diabetes mellitus. 4 Angl G Med. ?-?(/0)> //?- 7 ..
Misra # 5arida 4 Das # 5ari&a )# 5adhi M )aig M' (2**-) Affect of metformin in asian Indian women with
polycystic ovarian syndrome. Metab #yndr 3elat Disord .2(?)> /C2<+.
4ahum GG @ilson #) #tanislaw $ (2**2) Aarly 7 pregnancy glucose screening for gestational diabetes mellitus . G
3eprod Med . -+(.)> 010 7 02.
3 #chwart% 5 ' Gruppuso Q 5et%old D )rambilla " $iilesmaa Q ' Teramo (/CC-) $yperinsulinemia and
macrosomia in the fetus of the diabetic mother . Diabetees 9are /+(+)> 0-*<..
#eshiah " )ala&i " )ala&i M # 5aneerselvam ' 'rthi T Thami%harsi M Datta M
(2**+) Gestational diabetes mellitus manifests in all trimesters of pregnancy. Diabetes 3es 9lin 5ract . ++(?)> -.2 7 -.
#eshiah " )ala&i " )ala&i M# #an&eevi 9) Green ' (2**-) Gestational diabetes mellitus in India. G 'ssoc
5hysicians India 12> +*+<//.
#eshiah " #ahay )Q Das ' Q #iddarth #hah #amar )aner&ee 3ao 5" 'mmini ' )ala&i " #unil Gupta $ema
Diva!ar #u&atha Misra Dday Thanawala (2**C) Gestational Diabetes Mellitus 7 Indian Guidelines . G Indian Med
'ssoc ./*+(//)> +CC 7 .*2 .*-<0.
#wami #3 Mehetre 3 #hivane " )andgar T3 Menon 5# #hah 4# (2**.) 5revalence of 9arbohydrate intolerance
of varying degrees in pregnant females in western India (Maharastra) 7 a hospital based study. G Idnian Med 'ssoc .
/*0(//)> +/2<- +?1.
Tracy 6. #et&i 'nn G. )rown Mar! 4. =einglos (2**1) Gestational Diabetes Mellitus. 9linical Diabetes ?*(/)> /+<2-.
" #eshiah 'Q Das )ala&i " #hashan! 3 Goshi M4 5ari!h #unil Gupta (2**0) Gestational Diabetes Mellitus 7
Guidelines. G'5I 1-> 022<02..
" #eshiah 'leEander 9ynthiab " )ala&i Madhuri #. )ala&i # 'shalata 3a&an #heela M.Thami%harasi T 'rthi
(2**.) Detection and care of women with gestational diabetes mellitus from early wee!s of pregnancy results in birth
weight of new born babies appropriate for gestational age . Diabetes 3es 9lin 5ract . .*(2)> /CC<2*2.
" #eshaih " )ala&i Madhuri # )ala&i ' 5aneerselvam T 'rthi M Thami%harasi Man&ula Datta (2**.) 5revalence
of Gestational Diabetes Mellitus in #outh India (Tamil 4adu) < ' community )ased #tudy. G'5I 10 >?2C 7 ??.
,argar '$ #hei!h MI )ashir MI Masoodi #3 6away )' @ani 'I )hat M$ Dar = ' (2**-) 5revalence of
gestational diabetes mellitus in Qashmiri women form the Indian subcontinent . Diabetes 3es 9lin 5ract. 0s0(2)> /?C 7
Inernaional Journal o" A##lie$ %iolo&' an$ ()arma!eui!al *e!)nolo&' (a&e:2/2
Availa+le online a www,i-a+#,!om