GESTATIONAL DIABETES MELLITUS: HORMONAL CHANGES AND MECHANISMS OF INSULIN RESISTANCE

2025
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GESTATIONAL DIABETES MELLITUS: HORMONAL CHANGES AND
MECHANISMS OF INSULIN RESISTANCE
Gulhayo Jalol qizi Jo‘ aye a
Asian In e na ional Uni e si y
gulhayojo aye [email protected]
h ps://doi.o g/10.5281/zenodo.17316733
Rele ance o he S udy
Ges a ional diabe es melli us (GDM) is a p egnancy-speci ic me abolic diso de
cha ac e ized by glucose in ole ance i s de ec ed du ing p egnancy. I has become a majo global
heal h conce n due o i s ising p e alence, closely linked o inc easing ma e nal age, seden a y
li es yles, obesi y, and u baniza ion. Acco ding o ecen epidemiological da a, GDM a ec s
app oxima ely 7–10% o p egnancies wo ldwide, wi h signi ican ly highe a es in some Asian
and Middle Eas e n coun ies.
Physiologically, p egnancy induces a s a e o p og essi e insulin esis ance o ensu e
adequa e glucose supply o he g owing e us. While his adap a ion is bene icial in no mal
p egnancies, in p edisposed women i leads o hype glycemia, β-cell dys unc ion, and he clinical
mani es a ion o GDM. Ele a ed le els o placen al ho mones — including human placen al
lac ogen (hPL), co isol, es ogen, p oges e one, and placen al g ow h ho mone — an agonize
insulin ac ion, dec ease ma e nal insulin sensi i i y, and al e lipid and ca bohyd a e me abolism.
The impo ance o his opic s ems om he ac ha un ea ed GDM inc eases he isk o
p eeclampsia, cesa ean deli e y, and ype 2 diabe es in mo he s, as well as mac osomia, bi h
inju ies, neona al hypoglycemia, and long- e m me abolic diso de s in o sp ing. Ea ly de ec ion,
pa hophysiological unde s anding, and e ec i e in e en ions a e he e o e essen ial o imp o e
ma e nal- e al heal h ou comes globally.
Aim o he S udy
The aim o his s udy is o analyze ho monal changes and insulin esis ance mechanisms in
he pa hogenesis o GDM, assess ma e nal and e al isks associa ed wi h hype glycemia du ing
p egnancy, and summa ize e idence-based s a egies o sc eening, p e en ion, and managemen .
Ma e ials and Me hods
This e iew analyzed 65 pee - e iewed a icles published be ween 2010 and 2024 in
jou nals indexed in PubMed, Scopus, and Web o Science. Clinical guidelines om he Ame ican
Diabe es Associa ion (ADA), he In e na ional Fede a ion o Gynecology and Obs e ics (FIGO),
and he Wo ld Heal h O ganiza ion (WHO) we e also e iewed.
Sea ch keywo ds included ges a ional diabe es melli us, insulin esis ance, p egnancy
ho mones, ma e nal- e al ou comes, hype glycemia, and be a-cell dys unc ion. Da a we e
ex ac ed on:
 P e alence and isk ac o s o GDM
 Ho monal changes du ing p egnancy
 Pa hophysiological mechanisms o insulin esis ance
 Diagnos ic s a egies and sc eening p o ocols
 Ma e nal and e al complica ions
 P e en i e and he apeu ic in e en ions
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Resul s
The li e a u e analysis yielded he ollowing indings:
1. Ho monal Changes and Insulin Resis ance
 Human Placen al Lac ogen (hPL): Sec e ed by he placen a, hPL le els ise
p og essi ely wi h ges a ional age, inducing lipolysis and educing ma e nal glucose u iliza ion o
p io i ize e al glucose supply.
 Co isol: Inc eased ma e nal co isol s imula es hepa ic gluconeogenesis and
inhibi s insulin ac ion, exace ba ing hype glycemia.
 Es ogen and P oges e one: These ho mones impai insulin ecep o signaling
and modula e panc ea ic β-cell esponse. Ele a ed p oges e one le els may con ibu e o β-cell
exhaus ion in p edisposed women.
 Placen al G ow h Ho mone and Adipokines: Al e ed sec e ion o lep in,
adiponec in, and esis in u he wo sens insulin esis ance and p omo es a p o-in lamma o y
me abolic en i onmen .
2. Ma e nal Complica ions
Women wi h un ea ed GDM ace highe isks o :
 Ges a ional hype ension and p eeclampsia (15–20%)
 Polyhyd amnios and p e e m deli e y (10–15%)
 Cesa ean sec ion due o mac osomia o obs e ic complica ions (25–30%)
 Fu u e ype 2 diabe es melli us, wi h a 40–60% isk wi hin 10 yea s pos pa um
3. Fe al and Neona al Complica ions
Ma e nal hype glycemia leads o e al hype insulinemia, esul ing in:
 Mac osomia (bi h weigh >4 kg) in 15–25% o cases
 Neona al hypoglycemia due o sudden wi hd awal o ma e nal glucose pos -
deli e y
 Respi a o y dis ess synd ome and elec oly e imbalances
 Long- e m me abolic diso de s including childhood obesi y and ea ly-onse ype 2
diabe es
4. Sc eening and Ea ly Diagnosis
 Uni e sal sc eening a 24–28 weeks wi h o al glucose ole ance es (OGTT)
iden i ies asymp oma ic cases and educes complica ions by 50–60%.
 Ea ly sc eening in high- isk women (obesi y, polycys ic o a y synd ome, amily
his o y o diabe es) be o e 20 weeks allows p e en i e li es yle in e en ions.
5. P e en i e and The apeu ic In e en ions
 Li es yle modi ica ions: Die wi h low glycemic index oods and egula mode a e
exe cise educe GDM incidence by 20–30%.
 Pha maco he apy: Insulin emains he gold s anda d when li es yle measu es ail;
me o min may be used selec i ely.
 Pos pa um ollow-up: Glucose es ing a 6–12 weeks pos pa um and annually
he ea e de ec s pe sis en hype glycemia o ea ly ype 2 diabe es.
Conclusion
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Ges a ional diabe es melli us a ises om a complex in e play be ween ho monal changes
and insulin esis ance du ing p egnancy. These pa hophysiological mechanisms p edispose
mo he s and e uses o se e e sho - and long- e m complica ions.
Ea ly isk s a i ica ion, uni e sal sc eening, li es yle in e en ions, and s ic glycemic
con ol a e essen ial o imp o ing ou comes. S anda dized in e na ional guidelines and
mul idisciplina y ca e models should be implemen ed o add ess he ising global bu den o GDM
and educe i s impac on ma e nal and child heal h.
Re e ences:
1. Ame ican Diabe es Associa ion. (2023). Classi ica ion and diagnosis o diabe es:
S anda ds o medical ca e in diabe es—2023. Diabe es Ca e, 46(Suppl. 1), S19–S40.
h ps://doi.o g/10.2337/dc23-S002
2. Buchanan, T. A., & Xiang, A. H. (2005). Ges a ional diabe es melli us. The Jou nal o
Clinical In es iga ion, 115(3), 485–491. h ps://doi.o g/10.1172/JCI24102
3. Ca alano, P. M., & Shanka , K. (2017). Obesi y and p egnancy: Mechanisms o sho e m
and long e m ad e se consequences o mo he and child. BMJ, 356, j1.
h ps://doi.o g/10.1136/bmj.j1
4. Hadden, D. R. (2018). Ges a ional diabe es: The new epidemic. Clinical Medicine, 18(2),
123–126. h ps://doi.o g/10.7861/clinmedicine.18-2-123