Hiperglisemik Gebeliklere Bağlı Fetal Değişiklikler - Deneysel Perspektif
Yıl 2026,
Cilt: 10 Sayı: 1
,
94
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106
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30.04.2026
Serkan Karaçetin
,
Meryem Akpolat Ferah
,
Mete Keçeci
Öz
Gebelikte hiperglisemi, fetal komplikasyonlarla ilişkili diyabetik bir durum meydana getirir. Veriler incelendiğinde gebelerde diabetes
mellitus oranı ile paralel artan fetal kayıplar ve olumsuz değişiklikler göze çarpmaktadır. Gebe kalma yaşının ilerlemesi ve her geçen gün
uygun olmayan yaşam koşullarının artması ile hiperglisemik gebelikler ve buna bağlı olumsuz fetal değişiklikler artmakta ve neticede
gelecek nesilleri etkileyecek global bir sağlık riski ortaya çıkmaktadır. Uluslararası Diyabet Federasyonu’nun sunduğu verilere göre,
yaklaşık 21 milyon gebelik hiperglisemiden etkilenmektedir. Özellikle son yıllarda yapılan çok sayıda güncel çalışma, diyabetin meydana
getirdiği hasarların dişi üreme sistemi ve fetal sağlık sorunları ile yakın ilişkide olduğunu göstermiş ve dolayısıyla hiperglisemik
gebeliklerin önemini gözler önüne sermiştir.
Bu derlemedeki amaç gebelik öncesinde ve gebelikte deneysel modellerle oluşturulmuş diyabetin, gebelik sürecinde fetüs üzerinde
yapmış olduğu değişiklikler hakkında genel ve karşılaştırmalı bir bakış açısı sağlamaktır.
Kaynakça
-
1. van den Arend IJM, Stolk RP, Krans HMJ, Grobbee DE, Schri
jvers AJP. Management of type 2 diabetes: A challenge for pa
tient and physician. Patient Educ Couns. 2000; 40(2): 187-194.
doi: 10.1016/S0738-3991(99)00067-1.
-
2. Yang T, Qi F, Guo F, Shao M, Song Y, Ren G, Linlin Z, Qin
G, Zhao Y. An update on chronic complications of diabetes
mellitus: From molecular mechanisms to therapeutic strate
gies with a focus on metabolic memory. Mol Med. 2024; 30(1):
71. doi: 10.1186/s10020-024-00824-9.
-
3. Karamanou M, Protogerou A, Tsoucalas G, Androutsos G,
Poulakou-Rebelakou E. Milestones in the history of diabetes
mellitus: The main contributors. World J Diabetes. 2016; 7(1):
1-7. doi: 10.4239/wjd.v7.i1.1.
-
4. International Diabetes Federation. IDF Diabetes Atlas. 10th
ed. Brussels: International Diabetes Federation; 2021.
-
5. Çetin Avcı S, Daşıkan Z. Prekonsepsiyonel, gebelik ve postpar
tum döngüde maternal obeziteyi önlemek. Turk J Diab Obes.
2021; 5(3): 358-367. doi: 10.25048/tudod.927026.
-
6. Cavnar Helvacı B, Candemir B, Cinel M, Hepşen S, Canlar
Ş, Dağdeviren M, Çakal E. Assessing knowledge and aware
ness of preconception care among women with type 1 diabe
tes mellitus: Implications for optimizing maternal and fetal
health outcomes. Turk J Diab Obes. 2025; 9(2): 204-211. doi:
10.25048/tudod.1701369.
-
7. Harreiter J, Roden M. Diabetes mellitus: Definition, classifica
tion, diagnosis, screening and prevention (update 2023). Wien
Klin Wochenschr. 2023; 135(Suppl 1): 7-17. doi: 10.1007/
s00508-022-02122-y.
-
8. Meroni G, Valerio A, Vezzoli M, Croci E, Carruba MO. The
relationship between air pollution and diabetes: A study on
the municipalities of the Metropolitan City of Milan. Di
abetes Res Clin Pract. 2021; 174: 108748. doi: 10.1016/j.dia
bres.2021.108748.
-
9. Kırlangıç MM, Arici Halici BN. Evaluation of first trimester
fasting blood glucose, HOMA-IR and HbA1c in prediction of
gestational diabetes mellitus in non-obese pregnant women:
A retrospective study. Turk J Diab Obes. 2022; 6(3): 267-273.
doi: 10.25048/tudod.1198697.
-
10. Satman I, Omer B, Tutuncu Y, Kalaca S, Gedik S, Dinccag N,
Karsidag K, Genc S, Telci A, Canbaz B, Turker F, Yilmaz T,
Cakir B, Tuomilehto J; TURDEP-II Study Group. Twelve-year
trends in the prevalence and risk factors of diabetes and pre
diabetes in Turkish adults. Eur J Epidemiol. 2013; 28(2): 169
180. doi: 10.1007/s10654-013-9771-5.
-
11. Marquette GP, Klein VR, Niebyl JR. Efficacy of screening
for gestational diabetes. Am J Perinatol. 1985; 2(1): 7-9. doi:
10.1055/s-2007-999901.
-
12. American Diabetes Association. Classification and diagno
sis of diabetes: Standards of medical care in diabetes—2023.
Diabetes Care. 2023; 46(Suppl 1): S19-S40. doi: 10.2337/
dc23-S002.
-
13. Ojo OA, Ibrahim HS, Rotimi DE, Ogunlakin AD, Ojo AB. Di
abetes mellitus: From molecular mechanism to pathophysiol
ogy and pharmacology. Med Nov Technol Devices. 2023; 19:
100247. doi: 10.1016/j.medntd.2023.100247.
-
14. Dimitriadis G, Mitrou P, Lambadiari V, Maratou E, Raptis
SA. Insulin effects in muscle and adipose tissue. Diabetes Res
Clin Pract. 2011; 93(Suppl 1): S52-S59. doi: 10.1016/S0168
8227(11)70014-6.
-
15. Wu T, Rayner CK, Jones KL, Xie C, Marathe C, Horowitz
M. Role of intestinal glucose absorption in glucose toler
ance. Curr Opin Pharmacol. 2020; 55: 116-124. doi: 10.1016/j.
coph.2020.10.017.
-
16. Gurung P, Zubair M, Jialal I. Plasma glucose. StatPearls.
2024. Available from: https://www.ncbi.nlm.nih.gov/books/
NBK541081/
-
17. Eşrefoğlu M. Özel histoloji. İstanbul: Nobel Tıp Kitabevi; 2008.
18. Türkiye Diyabet Vakfı. Diyabet hakkında bilgiler. Available
from: https://www.turkdiab.org/bilgiler.asp?lang=TR&id=67
-
19. World Health Organization. Classification of diabetes melli
tus. 2019. Available from: https://www.who.int/publications/i/
item/classification-of-diabetes-mellitus
-
20. Garg SS, Gupta J. Polyol pathway and redox balance in di
abetes. Pharmacol Res. 2022; 182: 106326. doi: 10.1016/j.
phrs.2022.106326.
-
21. Zhou M, Zhang Y, Shi L, Li L, Zhang D, Gong Z, Wu Q. Acti
vation and modulation of the AGEs-RAGE axis: Implications
for inflammatory pathologies and therapeutic interventions - A review. Pharmacol Res. 2024; 206: 107282. doi: 10.1016/j.
phrs.2024.107282.
-
22. Uceda AB, Mariño L, Casasnovas R, Adrover M. An overview
on glycation: Molecular mechanisms, impact on proteins,
pathogenesis, and inhibition. Biophys Rev. 2024; 16(2): 189
218. doi: 10.1007/s12551-024-01188-4.
-
23. Mao L, Yin R, Yang L, Zhao D. Role of advanced glycation end
products on vascular smooth muscle cells under diabetic ath
erosclerosis. Front Endocrinol (Lausanne). 2022; 13: 983723.
doi: 10.3389/fendo.2022.983723.
-
24. Xiao Q, Wang D, Li D, Huang J, Ma F, Zhang H, Sheng Y, Zhang
C, Ha X. Protein kinase C: A potential therapeutic target for
endothelial dysfunction in diabetes. J Diabetes Complications.
2023; 37(9): 108565. doi: 10.1016/j.jdiacomp.2023.108565.
-
25. Newton AC. Protein kinase C: Perfectly balanced. Crit
Rev Biochem Mol Biol. 2018; 53(2): 208-230. doi:
10.1080/10409238.2018.1442408.
-
26. Guo J, Du L. Regulation of osteogenic differentiation in vascu
lar smooth muscle cells under high-glucose condition. Front
Endocrinol (Lausanne). 2025; 16: 1589160. doi: 10.3389/fen
do.2025.1589160.
-
27. Koya D, King GL. Protein kinase C activation and the develop
ment of diabetic complications. Diabetes. 1998; 47(6): 859-866.
doi: 10.2337/diabetes.47.6.859.
-
28. Ishii H, Koya D, King GL. Protein kinase C activation and its
role in the development of vascular complications in diabetes
mellitus. J Mol Med (Berl). 1998; 76(1): 21-31. doi: 10.1007/
s001090050187.
-
29. Pan D, Xu L, Guo M. The role of protein kinase C in diabetic
microvascular complications. Front Endocrinol (Lausanne).
2022; 13: 973058. doi: 10.3389/fendo.2022.973058.
-
30. Inoguchi T, Sonta T, Tsubouchi H, Etoh T, Kakimoto M,
Sonoda N, Sato N, Sekiguchi N, Kobayashi K, Sumimoto H,
Utsumi H, Nawata H. Protein kinase C-dependent increase
in reactive oxygen species (ROS) production in vascular tis
sues of diabetes: Role of vascular NAD(P)H oxidase. J Am
Soc Nephrol. 2003; 14(8 Suppl 3): S227-S232. doi: 10.1097/01.
asn.0000077407.90309.65.
-
31. Manoharan RR, Zachová K, Buzáš M, Pospíšil P, Křupka M,
Prasad A. NADPH oxidase-dependent free radical generation
and protein adduct formation in neutrophils. RSC Adv. 2024;
14(34): 24765-24780. doi: 10.1039/d4ra02739f.
-
32. Cipriano A, Viviano M, Feoli A, Milite C, Sarno G, Castella
no S, Sbardella G. NADPH oxidases: From molecular mecha
nisms to current inhibitors. J Med Chem. 2023; 66(17): 11632
11655. doi: 10.1021/acs.jmedchem.3c00770.
-
33. Paneque A, Fortus H, Zheng J, Werlen G, Jacinto E. The
hexosamine biosynthesis pathway: Regulation and function.
Genes (Basel). 2023; 14(4): 933. doi: 10.3390/genes14040933.
-
34. Wang Y, Eshwaran R, Beck SC, Hammes HP, Wieland T, Feng
Y. Contribution of the hexosamine biosynthetic pathway in
the hyperglycemia-dependent and -independent breakdown
of the retinal neurovascular unit. Mol Metab. 2023; 73: 101736.
doi: 10.1016/j.molmet.2023.101736.
-
35. TeSlaa T, Ralser M, Fan J, Rabinowitz JD. The pentose phos
phate pathway in health and disease. Nat Metab. 2023; 5(8):
1275-1289. doi: 10.1038/s42255-023-00863-2.
-
36. Ball LE, Berkaw MN, Buse MG. Identification of the major site
of O-linked beta-N-acetylglucosamine modification in the C
terminus of insulin receptor substrate-1. Mol Cell Proteomics.
2006; 5(2): 313-323. doi: 10.1074/mcp.M500314-MCP200.
-
37. Lee C, Kim SM, Kim DY, Han IO. O-GlcNAc cycling in
neuroinflammation: From molecular mechanisms and ther
apeutic perspectives. Neurobiol Dis. 2025; 217: 107160. doi:
10.1016/j.nbd.2025.107160.
-
38. Cooksey RC, Hebert LF Jr, Zhu JH, Wofford P, Garvey WT,
McClain DA. Mechanism of hexosamine-induced insulin
resistance in transgenic mice overexpressing glutamine:fruc
tose-6-phosphate amidotransferase: Decreased glucose trans
porter GLUT4 translocation and reversal by treatment with
thiazolidinedione. Endocrinology. 1999; 140(3): 1151-1157.
doi: 10.1210/endo.140.3.6563.
-
39. White MR, Garcin ED. D-glyceraldehyde-3-phosphate dehy
drogenase structure and function. Subcell Biochem. 2017; 83:
413-453. doi: 10.1007/978-3-319-46503-6_15.
-
40. Papachristoforou E, Lambadiari V, Maratou E, Makrilakis
K. Association of glycemic indices (hyperglycemia, glucose
variability and hypoglycemia) with oxidative stress and dia
betic complications. J Diabetes Res. 2020; 2020: 7489795. doi:
10.1155/2020/7489795.
-
41. Brownlee M. The pathobiology of diabetic complications: A
unifying mechanism. Diabetes. 2005; 54(6): 1615-1625. doi:
10.2337/diabetes.54.6.1615.
-
42. Çetiner Ö, Rakıcıoğlu N. Hiperglisemi, oksidatif stres ve tip 2
diyabette oksidatif stres belirteçlerinin tanımlanması. Turk J
Diab Obes. 2020; 4(1): 60-68. doi: 10.25048/tudod.638744.
-
43. Paul A, Kumar M, Das P, Guha N, Rudrapal M, Zaman MK.
Drug repurposing – A search for novel therapy for the treat
ment of diabetic neuropathy. Biomed Pharmacother. 2022;
150: 113846. doi: 10.1016/j.biopha.2022.113846.
-
44. American College of Obstetricians and Gynecologists. Gesta
tional diabetes mellitus. Obstet Gynecol. 2018; 131(2): e49-e64.
doi: 10.1097/AOG.0000000000002501.
-
45. Mittal R, Prasad K, Lemos JRN, Arevalo G, Hirani K. Unveil
ing gestational diabetes: An overview of pathophysiology and
management. Int J Mol Sci. 2025; 26(5): 2320. doi: 10.3390/
ijms26052320.
-
46. Sel G, Seyhan Baydağ S, Barut A, Akdemir AY, Özmen Ü, Har
ma M, Harma M. Gebelerde ilk trimester plazma D vitamini
düzeyleri ile gestasyonel diyabet arasında ilişki var mı? Turk J
Diab Obes. 2020; 4(1): 36-40. doi: 10.25048/tudod.700771.
-
47. Calvo MJ, Parra H, Santeliz R, Bautista J, Luzardo E, Villasmil
N, Martínez MS, Chacín M, Cano C, Checa-Ros A, D’Marco L,
Bermúdez V, De Sanctis JB. The placental role in gestational
diabetes mellitus: A molecular perspective. TouchREV Endo
crinol. 2024; 20(1): 10-18. doi: 10.17925/EE.2024.20.1.5.
-
48. Field CP, Cleary EM, Thung SF, Venkatesh K, Buschur EO.
Pregestational diabetes mellitus. Endotext. 2025.
-
49. Türkiye Endokrinoloji ve Metabolizma Derneği. Diyabetes
mellitus ve komplikasyonlarının tanı, tedavi ve izlem kılavuzu.
Ankara: TEMD Yayınları; 2024.
-
50. T.C. Sağlık Bakanlığı. Türkiye Diyabet Programı 2023–2027.
Ankara: T.C. Sağlık Bakanlığı; 2023.
-
51. International Federation of Gynecology and Obstetrics. The
FIGO initiative on gestational diabetes mellitus: A pragmat
ic guide for diagnosis, management, and care. Int J Gynecol
Obstet. 2015; 131(Suppl 3): S173-S211. doi: 10.1016/S0020
7292(15)30033-3.
-
52. Dodd JM, Crowther CA, Antoniou G, Baghurst P, Robinson
JS. Screening for gestational diabetes: The effect of varying
blood glucose definitions in the prediction of adverse mater
nal and infant health outcomes. Aust N Z J Obstet Gynaecol.
2007; 47(4): 307-312. doi: 10.1111/j.1479-828X.2007.00743.x.
-
53. Wang H, Li N, Chivese T, Werfalli M, Sun H, Yuen L, Hoeg
feldt CA, Powe CE, Immanuel J, Karuranga S, Divakar H,
Levitt N, Li C, Simmons D, Yang X; IDF Diabetes Atlas Com
mittee Hyperglycaemia in Pregnancy Special Interest Group.
IDF diabetes atlas: Estimation of global and regional gesta
tional diabetes mellitus prevalence for 2021 by International
Association of Diabetes in Pregnancy Study Group’s criteria.
Diabetes Res Clin Pract. 2022; 183: 109050. doi: 10.1016/j.dia
bres.2021.109050.
-
54. Bueno A, Sinzato YK, Sudano MJ, Alvarenga FdaC, Calderon
IM, Rudge MV, Damasceno DC. Short and long-term reper
cussions of experimental diabetes in embryofetal development.
Diabetes Metab Res Rev. 2014; 30(7): 575-581. doi: 10.1002/
dmrr.2521.
-
55. Malaza N, Masete M, Adam S, Dias S, Nyawo T, Pheiffer C.
A systematic review to compare adverse pregnancy outcomes
in women with pregestational diabetes and gestational diabe
tes. Int J Environ Res Public Health. 2022; 19(17): 10846. doi:
10.3390/ijerph191710846.
-
56. Poitout V, Robertson RP. Glucolipotoxicity: Fuel excess and
beta-cell dysfunction. Endocr Rev. 2008; 29(3): 351-366. doi:
10.1210/er.2007-0023.
-
57. Çalışkan L, Çolak H, Karakoyun Laçin B. Gestasyonel diy
abetli gebelerde sağlıklı yaşam biçimi davranışları ve ilişkili
faktörler: Bir kamu hastanesi örneği. Turk J Diab Obes. 2025;
9(2): 179-191. doi: 10.25048/tudod.1625814.
-
58. van Gerwen J, Shun-Shion AS, Fazakerley DJ. Insulin signal
ling and GLUT4 trafficking in insulin resistance. Biochem Soc
Trans. 2023; 51(3): 1057-1069. doi: 10.1042/BST20221066.
-
59. Drobiova H, Alhamar G, Ahmad R, Al-Mulla F, Al Madhoun
A. GLUT4 trafficking and storage vesicles: Molecular archi
tecture, regulatory networks and their disruption in insulin
resistance. Int J Mol Sci. 2025; 26(15): 7568. doi: 10.3390/
ijms26157568.
-
60. Plows JF, Stanley JL, Baker PN, Reynolds CM, Vickers MH.
The pathophysiology of gestational diabetes mellitus. Int J Mol
Sci. 2018; 19(11): 3342. doi: 10.3390/ijms19113342.
-
61. Wu Y, Liu B, Sun Y, Du Y, Santillan MK, Santillan DA, Snet
selaar LG, Bao W. Association of maternal prepregnancy dia
betes and gestational diabetes mellitus with congenital anom
alies of the newborn. Diabetes Care. 2020; 43(12): 2983-2990.
doi: 10.2337/dc20-0261.
-
62. Abdelmonem Mahrous RF, Ali Hassanin SH, Elemam Elbashir
RE, Gasm Elseed H, Ahmed Elnour SE, Elsayid NN. Neonatal
hypoglycemia and long-term pediatric neurodevelopmental
outcomes: A systematic review. Cureus. 2025; 17(6): e86183.
doi: 10.7759/cureus.86183.
-
63. Ananth CV, Basso O. Impact of pregnancy-induced hyperten
sion on stillbirth and neonatal mortality. Epidemiology. 2010;
21(1): 118-123. doi: 10.1097/EDE.0b013e3181c297af.
-
64. Galtier F. Definition, epidemiology, risk factors. Diabetes Me
tab. 2010; 36(6 Pt 2): 628-651. doi: 10.1016/j.diabet.2010.11.014.
-
65. Petitt DJ, Bennett PH, Knowler WC, Baird HR, Aleck KA.
Gestational diabetes mellitus and impaired glucose tolerance
during pregnancy: Long-term effects on obesity and glucose
tolerance in the offspring. Diabetes. 1985; 34(Suppl 2): 119
122. doi: 10.2337/diab.34.2.s119.
-
66. Francis EC, Kechris K, Jansson T, Dabelea D, Perng W. Nov
el metabolic subtypes in pregnant women and risk of early
childhood obesity in offspring. JAMA Netw Open. 2023; 6(4):
e237030. doi: 10.1001/jamanetworkopen.2023.7030.
-
67. Erkul A, Erbaş O. Complications of gestational diabetes: An
overview. J Exp Basic Med Sci. 2024; 5: 170-179. doi: 10.5606/
jebms.2024.1087.
-
68. Han Y, Sun Q, Chen W, Gao Y, Ye J, Chen Y, Wang T, Gao
L, Liu Y, Yang Y. New advances of adiponectin in regulating
obesity and related metabolic syndromes. J Pharm Anal. 2024;
14(5): 100913. doi: 10.1016/j.jpha.2023.12.003.
-
69. Lappas M, Hiden U, Desoye G, Froehlich J, Hauguel-de Mou
zon S, Jawerbaum A. The role of oxidative stress in the patho
physiology of gestational diabetes mellitus. Antioxid Redox
Signal. 2011; 15(12): 3061-3100. doi: 10.1089/ars.2010.3765.
-
70. Al Bekai E, Beaini CE, Kalout K, Safieddine O, Semaan S, Sa
hyoun F, Ghadieh HE, Azar S, Kanaan A, Harb F. The hidden
impact of gestational diabetes: Unveiling offspring complica
tions and long-term effects. Life (Basel). 2025; 15(3): 440. doi:
10.3390/life15030440.
-
71. Kalandyk-Osinko K, Baran J, Baran R, Gierek K, Juza A,
Kraśnianin E, Januszek S, Blajer-Olszewska B, Kluz T, Dar
mochwał-Kolarz D. The influence of gestational diabetes
mellitus on maternal and neonatal outcomes: A retrospective
study in Rzeszów, Poland. Med Sci Monit. 2024; 30: e943644.
doi: 10.12659/MSM.943644.
-
72. Ornoy A, Becker M, Weinstein-Fudim L, Ergaz Z. Diabetes
during pregnancy: A maternal disease complicating the course
of pregnancy with long-term deleterious effects on the off
spring: A clinical review. Int J Mol Sci. 2021; 22(6): 2965. doi:
10.3390/ijms22062965.
-
73. Kc K, Shakya S, Zhang H. Gestational diabetes mellitus and
macrosomia: A literature review. Ann Nutr Metab. 2015;
66(Suppl 2): 14-20. doi: 10.1159/000371628.
-
74. Orgul G, Ayık T, Şahin D, Yücel A. İlk trimester tarama test
biyobelirteçlerinin gestasyonel diyabetes mellitus ile ilişki
si. Turk J Diab Obes. 2020; 4(1): 41-45. doi: 10.25048/tu
dod.611537.
-
75. Karcz K, Królak-Olejnik B. Impact of gestational diabetes mel
litus on fetal growth and nutritional status in newborns. Nutri
ents. 2024; 16(23): 4093. doi: 10.3390/nu16234093.
-
76. Shimada H, Powell TL, Jansson T. Regulation of placental
amino acid transport in health and disease. Acta Physiol (Oxf).
2024; 240(7): e14157. doi: 10.1111/apha.14157.
-
77. Callanan S, Philippe K, Delahunt A, O’Keeffe LM, O’Neill
KN, Yelverton CA, Phillips CM, Twomey PJ, McDonnell CM,
Cody D, McAuliffe FM. Macrosomia and childhood growth
trajectories from birth to 10 years of age: Findings from the
ROLO longitudinal birth cohort study. J Obes. 2025; 2025:
8884369. doi: 10.1155/jobe/8884369.
-
78. Çakmak Genç G, Karakaş Çelik S, Hazaloğlu M, Harma M,
Dursun A. Gestasyonel diyabet ile IL8/CXCL8 rs4073 gen po
limorfizmi arasındaki ilişkinin araştırılması. Turk J Diab Obes.
2023; 7(1): 66-71. doi: 10.25048/tudod.1198053.
-
79. Flores-Le Roux JA, Sagarra E, Benaiges D, Hernandez-Rivas
E, Chillaron JJ, Puig de Dou J, Mur A, Lopez-Vilchez MA,
Pedro-Botet J. A prospective evaluation of neonatal hypogly
caemia in infants of women with gestational diabetes mellitus.
Diabetes Res Clin Pract. 2012; 97(2): 217-222. doi: 10.1016/j.
diabres.2012.03.011.
-
80. Diggikar S, Trif P, Mudura D, Prasath A, Mazela J, Ognean
ML, Kramer BW, Galis R. Neonatal hypoglycemia and neuro
developmental outcomes: An updated systematic review and
meta-analysis. Life (Basel). 2024; 14(12): 1618. doi: 10.3390/
life14121618.
-
81. Catalano PM, Hauguel-De Mouzon S. Is it time to revisit
the Pedersen hypothesis in the face of the obesity epidemic?
Am J Obstet Gynecol. 2011; 204(6): 479-487. doi: 10.1016/j.
ajog.2010.11.039.
-
82. Yang F, Liu H, Ding C. Gestational diabetes mellitus and risk
of neonatal respiratory distress syndrome: A systematic review
and meta-analysis. Diabetol Metab Syndr. 2024; 16(1): 294.
doi: 10.1186/s13098-024-01539-x.
-
83. Kawakita T, Bowers K, Hazrati S, Zhang C, Grewal J, Chen Z,
Sun L, Grantz KL. Increased neonatal respiratory morbidity
associated with gestational and pregestational diabetes: A ret
rospective study. Am J Perinatol. 2017; 34(11): 1160-1168. doi:
10.1055/s-0037-1604414.
-
84. Mills JL. Malformations in infants of diabetic mothers. Birth
Defects Res A Clin Mol Teratol. 2010; 88(10): 769-778. doi:
10.1002/bdra.20757.
-
85. Al-Biltagi M, El Razaky O, El Amrousy D. Cardiac changes
in infants of diabetic mothers. World J Diabetes. 2021; 12(8):
1233-1247. doi: 10.4239/wjd.v12.i8.1233.
-
86. Obut M, Çayönü Kahraman N, Sucu S, Keleş A, Arat Ö, Yücel
Çelik Ö, Bucak M, Çakır A, Şahin D, Yücel A. Comparison of
feto-maternal outcomes between emergency and elective ce
sarean deliveries in patients with gestational diabetes. Turk J
Diab Obes. 2023; 7(1): 52-59. doi: 10.25048/tudod.1233486.
-
87. Boney CM, Verma A, Tucker R, Vohr BR. Metabolic syn
drome in childhood: Association with birth weight, maternal
obesity, and gestational diabetes mellitus. Pediatrics. 2005;
115(3): e290-e296. doi: 10.1542/peds.2004-1808.
-
88. Kaaja R, Rönnemaa T. Gestational diabetes: Pathogenesis and
consequences to mother and offspring. Rev Diabet Stud. 2008;
5(4): 194-202. doi: 10.1900/RDS.2008.5.194.
-
89. Xiang AH, Wang X, Martinez MP, Walthall JC, Curry ES,
Page K, Buchanan TA, Coleman KJ, Getahun D. Association
of maternal diabetes with autism in offspring. JAMA. 2015;
313(14): 1425-1434. doi: 10.1001/jama.2015.2707.
-
90. Lee J, Lee NK, Moon JH. Gestational diabetes mellitus:
Mechanisms underlying maternal and fetal complications.
Endocrinol Metab (Seoul). 2025; 40(1): 10-25. doi: 10.3803/
EnM.2024.2264.
-
91. Muller YL, Yueh YG, Yaworsky PJ, Salbaum JM, Kappen C.
Caudal dysgenesis in Islet-1 transgenic mice. FASEB J. 2003;
17(10): 1349-1351. doi: 10.1096/fj.02-0856fje.
-
92. Sirasanagandla SR, Ranganath Pai KS, Potu BK, Bhat KM.
Protective effect of Cissus quadrangularis Linn. on diabetes
induced delayed fetal skeletal ossification. J Ayurveda Integr
Med. 2014; 5(1): 25-32. doi: 10.4103/0975-9476.128852.
-
93. Krause A, Schwab KO, Trost J, Thill M, Kunze M, Seufert J,
Hentschel R. Gestational diabetes mellitus: The role of IGF-1
and leptin in cord blood. J Perinat Med. 2025; 53(7): 937-944.
doi: 10.1515/jpm-2024-0379.
-
94. Antoniou MC, Quansah DY, Gilbert L, Arhab A, Schenk S, La
croix A, Stuijfzand B, Horsch A, Puder JJ. Association between
maternal and fetal inflammatory biomarkers and offspring
weight and BMI during the first year of life in pregnancies
with GDM: MySweetheart study. Front Endocrinol (Laus
anne). 2024; 15: 1333755. doi: 10.3389/fendo.2024.1333755.
-
95. Karakaş Çelik S, Yamak AS. Gestasyonel diyabette genetik ve
epigenetik değişimler. Turk J Diab Obes. 2018; 2(1): 9-15.
-
96. Damm P, Houshmand-Oeregaard A, Kelstrup L, Lauenborg
J, Mathiesen ER, Clausen TD. Gestational diabetes mellitus
and long-term consequences for mother and offspring: A view
from Denmark. Diabetologia. 2016; 59(7): 1396-1399. doi:
10.1007/s00125-016-3985-5.
-
97. Shashikadze B, Flenkenthaler F, Stöckl JB, Valla L, Renner S,
Kemter E, Wolf E, Fröhlich T. Developmental effects of (pre-)
gestational diabetes on offspring: Systematic screening using
omics approaches. Genes (Basel). 2021; 12(12): 1991. doi:
10.3390/genes12121991.
-
98. Moazzen H, Lu X, Liu M, Feng Q. Pregestational diabetes
induces fetal coronary artery malformation via reactive oxy
gen species signaling. Diabetes. 2015; 64(4): 1431-1443. doi:
10.2337/db14-0190
-
99. Lehtoranta L, Koskinen A, Vuolteenaho O, Laine J, Kytö V,
Soukka H, Ekholm E, Räsänen J. Gestational hyperglycemia
reprograms cardiac gene expression in rat offspring. Pediatr
Res. 2017; 82(2): 356-361. doi: 10.1038/pr.2017.42.
-
100. Golic M, Stojanovska V, Bendix I, Wehner A, Herse F, Haase
N, Kräker K, Fischer C, Alenina N, Bader M, Schütte T,
Schuchardt M, van der Giet M, Henrich W, Muller DN, Fel
derhoff-Müser U, Scherjon S, Plösch T, Dechend R. Diabetes
mellitus in pregnancy leads to growth restriction and epigen
etic modification of the Srebf2 gene in rat fetuses. Hyperten
sion. 2018; 71(5): 911-920. doi: 10.1161/HYPERTENSIONA
HA.117.10782.
-
101. Agarwal P, Brar N, Morriseau TS, Kereliuk SM, Fonseca MA,
Cole LK, Jha A, Xiang B, Hunt KL, Seshadri N, Hatch GM,
Doucette CA, Dolinsky VW. Gestational diabetes adversely
affects pancreatic islet architecture and function in the male
rat offspring. Endocrinology. 2019; 160(8): 1907-1925. doi:
10.1210/en.2019-00232.
-
102. Salazar-García M, Reyes-Maldonado E, Revilla-Monsalve
MC, Villavicencio-Guzmán L, Reyes-López A, Sánchez-Gó
mez C. Importance of maternal diabetes on the chronolog
ical deregulation of intrauterine development: An experi
mental study in rat. J Diabetes Res. 2015; 2015: 354265. doi:
10.1155/2015/354265.
-
103. Damasceno DC, Volpato GT, Calderon IMP, Rudge MVC.
Oxidative stress and diabetes in pregnant rats. Anim Re
prod Sci. 2002; 72(3-4): 235-244. doi: 10.1016/S0378
4320(02)00094-5.
-
104. Gäreskog M, Cederberg J, Eriksson UJ, Wentzel P. Maternal
diabetes in vivo and high glucose concentration in vitro in
crease apoptosis in rat embryos. Reprod Toxicol. 2007; 23(1):
63-74. doi: 10.1016/j.reprotox.2006.08.009.
-
105. Capobianco E, Fornes D, Linenberg I, Powell TL, Jans
son T, Jawerbaum A. A novel rat model of gestational dia
betes induced by intrauterine programming is associated
with alterations in placental signaling and fetal overgrowth.
Mol Cell Endocrinol. 2016; 422: 221-232. doi: 10.1016/j.
mce.2015.12.020.
-
106. Kiss AC, Lima PH, Sinzato YK, Takaku M, Takeno MA,
Rudge MV, Damasceno DC. Animal models for clinical and
gestational diabetes: Maternal and fetal outcomes. Diabetol
Metab Syndr. 2009; 1(1): 21. doi: 10.1186/1758-5996-1-21.
Fetal Changes Associated with Hyperglycemic Pregnancies – An Experimental Perspective
Yıl 2026,
Cilt: 10 Sayı: 1
,
94
-
106
,
30.04.2026
Serkan Karaçetin
,
Meryem Akpolat Ferah
,
Mete Keçeci
Öz
Hyperglycemia during pregnancy induces a diabetic condition associated with fetal complications. Examination of the data reveals that
fetal losses and adverse fetal outcomes increase in parallel with the prevalence of diabetes mellitus among pregnant women. Advancing
maternal age and the progressive deterioration of living conditions contribute to a rise in hyperglycemic pregnancies and associated
adverse fetal changes, ultimately posing a global health risk that may affect future generations. According to data provided by the
International Diabetes Federation, approximately 21 million pregnancies are affected by hyperglycemia during gestation. In recent years,
numerous contemporary studies have demonstrated that the damage caused by diabetes is closely linked to female reproductive system
dysfunctions and fetal health issues, thereby highlighting the significance of hyperglycemic pregnancies.
The aim of this review is to provide a general and comparative perspective on the changes induced in the fetus by diabetes, experimentally
modeled before and during pregnancy, throughout the gestational period
Kaynakça
-
1. van den Arend IJM, Stolk RP, Krans HMJ, Grobbee DE, Schri
jvers AJP. Management of type 2 diabetes: A challenge for pa
tient and physician. Patient Educ Couns. 2000; 40(2): 187-194.
doi: 10.1016/S0738-3991(99)00067-1.
-
2. Yang T, Qi F, Guo F, Shao M, Song Y, Ren G, Linlin Z, Qin
G, Zhao Y. An update on chronic complications of diabetes
mellitus: From molecular mechanisms to therapeutic strate
gies with a focus on metabolic memory. Mol Med. 2024; 30(1):
71. doi: 10.1186/s10020-024-00824-9.
-
3. Karamanou M, Protogerou A, Tsoucalas G, Androutsos G,
Poulakou-Rebelakou E. Milestones in the history of diabetes
mellitus: The main contributors. World J Diabetes. 2016; 7(1):
1-7. doi: 10.4239/wjd.v7.i1.1.
-
4. International Diabetes Federation. IDF Diabetes Atlas. 10th
ed. Brussels: International Diabetes Federation; 2021.
-
5. Çetin Avcı S, Daşıkan Z. Prekonsepsiyonel, gebelik ve postpar
tum döngüde maternal obeziteyi önlemek. Turk J Diab Obes.
2021; 5(3): 358-367. doi: 10.25048/tudod.927026.
-
6. Cavnar Helvacı B, Candemir B, Cinel M, Hepşen S, Canlar
Ş, Dağdeviren M, Çakal E. Assessing knowledge and aware
ness of preconception care among women with type 1 diabe
tes mellitus: Implications for optimizing maternal and fetal
health outcomes. Turk J Diab Obes. 2025; 9(2): 204-211. doi:
10.25048/tudod.1701369.
-
7. Harreiter J, Roden M. Diabetes mellitus: Definition, classifica
tion, diagnosis, screening and prevention (update 2023). Wien
Klin Wochenschr. 2023; 135(Suppl 1): 7-17. doi: 10.1007/
s00508-022-02122-y.
-
8. Meroni G, Valerio A, Vezzoli M, Croci E, Carruba MO. The
relationship between air pollution and diabetes: A study on
the municipalities of the Metropolitan City of Milan. Di
abetes Res Clin Pract. 2021; 174: 108748. doi: 10.1016/j.dia
bres.2021.108748.
-
9. Kırlangıç MM, Arici Halici BN. Evaluation of first trimester
fasting blood glucose, HOMA-IR and HbA1c in prediction of
gestational diabetes mellitus in non-obese pregnant women:
A retrospective study. Turk J Diab Obes. 2022; 6(3): 267-273.
doi: 10.25048/tudod.1198697.
-
10. Satman I, Omer B, Tutuncu Y, Kalaca S, Gedik S, Dinccag N,
Karsidag K, Genc S, Telci A, Canbaz B, Turker F, Yilmaz T,
Cakir B, Tuomilehto J; TURDEP-II Study Group. Twelve-year
trends in the prevalence and risk factors of diabetes and pre
diabetes in Turkish adults. Eur J Epidemiol. 2013; 28(2): 169
180. doi: 10.1007/s10654-013-9771-5.
-
11. Marquette GP, Klein VR, Niebyl JR. Efficacy of screening
for gestational diabetes. Am J Perinatol. 1985; 2(1): 7-9. doi:
10.1055/s-2007-999901.
-
12. American Diabetes Association. Classification and diagno
sis of diabetes: Standards of medical care in diabetes—2023.
Diabetes Care. 2023; 46(Suppl 1): S19-S40. doi: 10.2337/
dc23-S002.
-
13. Ojo OA, Ibrahim HS, Rotimi DE, Ogunlakin AD, Ojo AB. Di
abetes mellitus: From molecular mechanism to pathophysiol
ogy and pharmacology. Med Nov Technol Devices. 2023; 19:
100247. doi: 10.1016/j.medntd.2023.100247.
-
14. Dimitriadis G, Mitrou P, Lambadiari V, Maratou E, Raptis
SA. Insulin effects in muscle and adipose tissue. Diabetes Res
Clin Pract. 2011; 93(Suppl 1): S52-S59. doi: 10.1016/S0168
8227(11)70014-6.
-
15. Wu T, Rayner CK, Jones KL, Xie C, Marathe C, Horowitz
M. Role of intestinal glucose absorption in glucose toler
ance. Curr Opin Pharmacol. 2020; 55: 116-124. doi: 10.1016/j.
coph.2020.10.017.
-
16. Gurung P, Zubair M, Jialal I. Plasma glucose. StatPearls.
2024. Available from: https://www.ncbi.nlm.nih.gov/books/
NBK541081/
-
17. Eşrefoğlu M. Özel histoloji. İstanbul: Nobel Tıp Kitabevi; 2008.
18. Türkiye Diyabet Vakfı. Diyabet hakkında bilgiler. Available
from: https://www.turkdiab.org/bilgiler.asp?lang=TR&id=67
-
19. World Health Organization. Classification of diabetes melli
tus. 2019. Available from: https://www.who.int/publications/i/
item/classification-of-diabetes-mellitus
-
20. Garg SS, Gupta J. Polyol pathway and redox balance in di
abetes. Pharmacol Res. 2022; 182: 106326. doi: 10.1016/j.
phrs.2022.106326.
-
21. Zhou M, Zhang Y, Shi L, Li L, Zhang D, Gong Z, Wu Q. Acti
vation and modulation of the AGEs-RAGE axis: Implications
for inflammatory pathologies and therapeutic interventions - A review. Pharmacol Res. 2024; 206: 107282. doi: 10.1016/j.
phrs.2024.107282.
-
22. Uceda AB, Mariño L, Casasnovas R, Adrover M. An overview
on glycation: Molecular mechanisms, impact on proteins,
pathogenesis, and inhibition. Biophys Rev. 2024; 16(2): 189
218. doi: 10.1007/s12551-024-01188-4.
-
23. Mao L, Yin R, Yang L, Zhao D. Role of advanced glycation end
products on vascular smooth muscle cells under diabetic ath
erosclerosis. Front Endocrinol (Lausanne). 2022; 13: 983723.
doi: 10.3389/fendo.2022.983723.
-
24. Xiao Q, Wang D, Li D, Huang J, Ma F, Zhang H, Sheng Y, Zhang
C, Ha X. Protein kinase C: A potential therapeutic target for
endothelial dysfunction in diabetes. J Diabetes Complications.
2023; 37(9): 108565. doi: 10.1016/j.jdiacomp.2023.108565.
-
25. Newton AC. Protein kinase C: Perfectly balanced. Crit
Rev Biochem Mol Biol. 2018; 53(2): 208-230. doi:
10.1080/10409238.2018.1442408.
-
26. Guo J, Du L. Regulation of osteogenic differentiation in vascu
lar smooth muscle cells under high-glucose condition. Front
Endocrinol (Lausanne). 2025; 16: 1589160. doi: 10.3389/fen
do.2025.1589160.
-
27. Koya D, King GL. Protein kinase C activation and the develop
ment of diabetic complications. Diabetes. 1998; 47(6): 859-866.
doi: 10.2337/diabetes.47.6.859.
-
28. Ishii H, Koya D, King GL. Protein kinase C activation and its
role in the development of vascular complications in diabetes
mellitus. J Mol Med (Berl). 1998; 76(1): 21-31. doi: 10.1007/
s001090050187.
-
29. Pan D, Xu L, Guo M. The role of protein kinase C in diabetic
microvascular complications. Front Endocrinol (Lausanne).
2022; 13: 973058. doi: 10.3389/fendo.2022.973058.
-
30. Inoguchi T, Sonta T, Tsubouchi H, Etoh T, Kakimoto M,
Sonoda N, Sato N, Sekiguchi N, Kobayashi K, Sumimoto H,
Utsumi H, Nawata H. Protein kinase C-dependent increase
in reactive oxygen species (ROS) production in vascular tis
sues of diabetes: Role of vascular NAD(P)H oxidase. J Am
Soc Nephrol. 2003; 14(8 Suppl 3): S227-S232. doi: 10.1097/01.
asn.0000077407.90309.65.
-
31. Manoharan RR, Zachová K, Buzáš M, Pospíšil P, Křupka M,
Prasad A. NADPH oxidase-dependent free radical generation
and protein adduct formation in neutrophils. RSC Adv. 2024;
14(34): 24765-24780. doi: 10.1039/d4ra02739f.
-
32. Cipriano A, Viviano M, Feoli A, Milite C, Sarno G, Castella
no S, Sbardella G. NADPH oxidases: From molecular mecha
nisms to current inhibitors. J Med Chem. 2023; 66(17): 11632
11655. doi: 10.1021/acs.jmedchem.3c00770.
-
33. Paneque A, Fortus H, Zheng J, Werlen G, Jacinto E. The
hexosamine biosynthesis pathway: Regulation and function.
Genes (Basel). 2023; 14(4): 933. doi: 10.3390/genes14040933.
-
34. Wang Y, Eshwaran R, Beck SC, Hammes HP, Wieland T, Feng
Y. Contribution of the hexosamine biosynthetic pathway in
the hyperglycemia-dependent and -independent breakdown
of the retinal neurovascular unit. Mol Metab. 2023; 73: 101736.
doi: 10.1016/j.molmet.2023.101736.
-
35. TeSlaa T, Ralser M, Fan J, Rabinowitz JD. The pentose phos
phate pathway in health and disease. Nat Metab. 2023; 5(8):
1275-1289. doi: 10.1038/s42255-023-00863-2.
-
36. Ball LE, Berkaw MN, Buse MG. Identification of the major site
of O-linked beta-N-acetylglucosamine modification in the C
terminus of insulin receptor substrate-1. Mol Cell Proteomics.
2006; 5(2): 313-323. doi: 10.1074/mcp.M500314-MCP200.
-
37. Lee C, Kim SM, Kim DY, Han IO. O-GlcNAc cycling in
neuroinflammation: From molecular mechanisms and ther
apeutic perspectives. Neurobiol Dis. 2025; 217: 107160. doi:
10.1016/j.nbd.2025.107160.
-
38. Cooksey RC, Hebert LF Jr, Zhu JH, Wofford P, Garvey WT,
McClain DA. Mechanism of hexosamine-induced insulin
resistance in transgenic mice overexpressing glutamine:fruc
tose-6-phosphate amidotransferase: Decreased glucose trans
porter GLUT4 translocation and reversal by treatment with
thiazolidinedione. Endocrinology. 1999; 140(3): 1151-1157.
doi: 10.1210/endo.140.3.6563.
-
39. White MR, Garcin ED. D-glyceraldehyde-3-phosphate dehy
drogenase structure and function. Subcell Biochem. 2017; 83:
413-453. doi: 10.1007/978-3-319-46503-6_15.
-
40. Papachristoforou E, Lambadiari V, Maratou E, Makrilakis
K. Association of glycemic indices (hyperglycemia, glucose
variability and hypoglycemia) with oxidative stress and dia
betic complications. J Diabetes Res. 2020; 2020: 7489795. doi:
10.1155/2020/7489795.
-
41. Brownlee M. The pathobiology of diabetic complications: A
unifying mechanism. Diabetes. 2005; 54(6): 1615-1625. doi:
10.2337/diabetes.54.6.1615.
-
42. Çetiner Ö, Rakıcıoğlu N. Hiperglisemi, oksidatif stres ve tip 2
diyabette oksidatif stres belirteçlerinin tanımlanması. Turk J
Diab Obes. 2020; 4(1): 60-68. doi: 10.25048/tudod.638744.
-
43. Paul A, Kumar M, Das P, Guha N, Rudrapal M, Zaman MK.
Drug repurposing – A search for novel therapy for the treat
ment of diabetic neuropathy. Biomed Pharmacother. 2022;
150: 113846. doi: 10.1016/j.biopha.2022.113846.
-
44. American College of Obstetricians and Gynecologists. Gesta
tional diabetes mellitus. Obstet Gynecol. 2018; 131(2): e49-e64.
doi: 10.1097/AOG.0000000000002501.
-
45. Mittal R, Prasad K, Lemos JRN, Arevalo G, Hirani K. Unveil
ing gestational diabetes: An overview of pathophysiology and
management. Int J Mol Sci. 2025; 26(5): 2320. doi: 10.3390/
ijms26052320.
-
46. Sel G, Seyhan Baydağ S, Barut A, Akdemir AY, Özmen Ü, Har
ma M, Harma M. Gebelerde ilk trimester plazma D vitamini
düzeyleri ile gestasyonel diyabet arasında ilişki var mı? Turk J
Diab Obes. 2020; 4(1): 36-40. doi: 10.25048/tudod.700771.
-
47. Calvo MJ, Parra H, Santeliz R, Bautista J, Luzardo E, Villasmil
N, Martínez MS, Chacín M, Cano C, Checa-Ros A, D’Marco L,
Bermúdez V, De Sanctis JB. The placental role in gestational
diabetes mellitus: A molecular perspective. TouchREV Endo
crinol. 2024; 20(1): 10-18. doi: 10.17925/EE.2024.20.1.5.
-
48. Field CP, Cleary EM, Thung SF, Venkatesh K, Buschur EO.
Pregestational diabetes mellitus. Endotext. 2025.
-
49. Türkiye Endokrinoloji ve Metabolizma Derneği. Diyabetes
mellitus ve komplikasyonlarının tanı, tedavi ve izlem kılavuzu.
Ankara: TEMD Yayınları; 2024.
-
50. T.C. Sağlık Bakanlığı. Türkiye Diyabet Programı 2023–2027.
Ankara: T.C. Sağlık Bakanlığı; 2023.
-
51. International Federation of Gynecology and Obstetrics. The
FIGO initiative on gestational diabetes mellitus: A pragmat
ic guide for diagnosis, management, and care. Int J Gynecol
Obstet. 2015; 131(Suppl 3): S173-S211. doi: 10.1016/S0020
7292(15)30033-3.
-
52. Dodd JM, Crowther CA, Antoniou G, Baghurst P, Robinson
JS. Screening for gestational diabetes: The effect of varying
blood glucose definitions in the prediction of adverse mater
nal and infant health outcomes. Aust N Z J Obstet Gynaecol.
2007; 47(4): 307-312. doi: 10.1111/j.1479-828X.2007.00743.x.
-
53. Wang H, Li N, Chivese T, Werfalli M, Sun H, Yuen L, Hoeg
feldt CA, Powe CE, Immanuel J, Karuranga S, Divakar H,
Levitt N, Li C, Simmons D, Yang X; IDF Diabetes Atlas Com
mittee Hyperglycaemia in Pregnancy Special Interest Group.
IDF diabetes atlas: Estimation of global and regional gesta
tional diabetes mellitus prevalence for 2021 by International
Association of Diabetes in Pregnancy Study Group’s criteria.
Diabetes Res Clin Pract. 2022; 183: 109050. doi: 10.1016/j.dia
bres.2021.109050.
-
54. Bueno A, Sinzato YK, Sudano MJ, Alvarenga FdaC, Calderon
IM, Rudge MV, Damasceno DC. Short and long-term reper
cussions of experimental diabetes in embryofetal development.
Diabetes Metab Res Rev. 2014; 30(7): 575-581. doi: 10.1002/
dmrr.2521.
-
55. Malaza N, Masete M, Adam S, Dias S, Nyawo T, Pheiffer C.
A systematic review to compare adverse pregnancy outcomes
in women with pregestational diabetes and gestational diabe
tes. Int J Environ Res Public Health. 2022; 19(17): 10846. doi:
10.3390/ijerph191710846.
-
56. Poitout V, Robertson RP. Glucolipotoxicity: Fuel excess and
beta-cell dysfunction. Endocr Rev. 2008; 29(3): 351-366. doi:
10.1210/er.2007-0023.
-
57. Çalışkan L, Çolak H, Karakoyun Laçin B. Gestasyonel diy
abetli gebelerde sağlıklı yaşam biçimi davranışları ve ilişkili
faktörler: Bir kamu hastanesi örneği. Turk J Diab Obes. 2025;
9(2): 179-191. doi: 10.25048/tudod.1625814.
-
58. van Gerwen J, Shun-Shion AS, Fazakerley DJ. Insulin signal
ling and GLUT4 trafficking in insulin resistance. Biochem Soc
Trans. 2023; 51(3): 1057-1069. doi: 10.1042/BST20221066.
-
59. Drobiova H, Alhamar G, Ahmad R, Al-Mulla F, Al Madhoun
A. GLUT4 trafficking and storage vesicles: Molecular archi
tecture, regulatory networks and their disruption in insulin
resistance. Int J Mol Sci. 2025; 26(15): 7568. doi: 10.3390/
ijms26157568.
-
60. Plows JF, Stanley JL, Baker PN, Reynolds CM, Vickers MH.
The pathophysiology of gestational diabetes mellitus. Int J Mol
Sci. 2018; 19(11): 3342. doi: 10.3390/ijms19113342.
-
61. Wu Y, Liu B, Sun Y, Du Y, Santillan MK, Santillan DA, Snet
selaar LG, Bao W. Association of maternal prepregnancy dia
betes and gestational diabetes mellitus with congenital anom
alies of the newborn. Diabetes Care. 2020; 43(12): 2983-2990.
doi: 10.2337/dc20-0261.
-
62. Abdelmonem Mahrous RF, Ali Hassanin SH, Elemam Elbashir
RE, Gasm Elseed H, Ahmed Elnour SE, Elsayid NN. Neonatal
hypoglycemia and long-term pediatric neurodevelopmental
outcomes: A systematic review. Cureus. 2025; 17(6): e86183.
doi: 10.7759/cureus.86183.
-
63. Ananth CV, Basso O. Impact of pregnancy-induced hyperten
sion on stillbirth and neonatal mortality. Epidemiology. 2010;
21(1): 118-123. doi: 10.1097/EDE.0b013e3181c297af.
-
64. Galtier F. Definition, epidemiology, risk factors. Diabetes Me
tab. 2010; 36(6 Pt 2): 628-651. doi: 10.1016/j.diabet.2010.11.014.
-
65. Petitt DJ, Bennett PH, Knowler WC, Baird HR, Aleck KA.
Gestational diabetes mellitus and impaired glucose tolerance
during pregnancy: Long-term effects on obesity and glucose
tolerance in the offspring. Diabetes. 1985; 34(Suppl 2): 119
122. doi: 10.2337/diab.34.2.s119.
-
66. Francis EC, Kechris K, Jansson T, Dabelea D, Perng W. Nov
el metabolic subtypes in pregnant women and risk of early
childhood obesity in offspring. JAMA Netw Open. 2023; 6(4):
e237030. doi: 10.1001/jamanetworkopen.2023.7030.
-
67. Erkul A, Erbaş O. Complications of gestational diabetes: An
overview. J Exp Basic Med Sci. 2024; 5: 170-179. doi: 10.5606/
jebms.2024.1087.
-
68. Han Y, Sun Q, Chen W, Gao Y, Ye J, Chen Y, Wang T, Gao
L, Liu Y, Yang Y. New advances of adiponectin in regulating
obesity and related metabolic syndromes. J Pharm Anal. 2024;
14(5): 100913. doi: 10.1016/j.jpha.2023.12.003.
-
69. Lappas M, Hiden U, Desoye G, Froehlich J, Hauguel-de Mou
zon S, Jawerbaum A. The role of oxidative stress in the patho
physiology of gestational diabetes mellitus. Antioxid Redox
Signal. 2011; 15(12): 3061-3100. doi: 10.1089/ars.2010.3765.
-
70. Al Bekai E, Beaini CE, Kalout K, Safieddine O, Semaan S, Sa
hyoun F, Ghadieh HE, Azar S, Kanaan A, Harb F. The hidden
impact of gestational diabetes: Unveiling offspring complica
tions and long-term effects. Life (Basel). 2025; 15(3): 440. doi:
10.3390/life15030440.
-
71. Kalandyk-Osinko K, Baran J, Baran R, Gierek K, Juza A,
Kraśnianin E, Januszek S, Blajer-Olszewska B, Kluz T, Dar
mochwał-Kolarz D. The influence of gestational diabetes
mellitus on maternal and neonatal outcomes: A retrospective
study in Rzeszów, Poland. Med Sci Monit. 2024; 30: e943644.
doi: 10.12659/MSM.943644.
-
72. Ornoy A, Becker M, Weinstein-Fudim L, Ergaz Z. Diabetes
during pregnancy: A maternal disease complicating the course
of pregnancy with long-term deleterious effects on the off
spring: A clinical review. Int J Mol Sci. 2021; 22(6): 2965. doi:
10.3390/ijms22062965.
-
73. Kc K, Shakya S, Zhang H. Gestational diabetes mellitus and
macrosomia: A literature review. Ann Nutr Metab. 2015;
66(Suppl 2): 14-20. doi: 10.1159/000371628.
-
74. Orgul G, Ayık T, Şahin D, Yücel A. İlk trimester tarama test
biyobelirteçlerinin gestasyonel diyabetes mellitus ile ilişki
si. Turk J Diab Obes. 2020; 4(1): 41-45. doi: 10.25048/tu
dod.611537.
-
75. Karcz K, Królak-Olejnik B. Impact of gestational diabetes mel
litus on fetal growth and nutritional status in newborns. Nutri
ents. 2024; 16(23): 4093. doi: 10.3390/nu16234093.
-
76. Shimada H, Powell TL, Jansson T. Regulation of placental
amino acid transport in health and disease. Acta Physiol (Oxf).
2024; 240(7): e14157. doi: 10.1111/apha.14157.
-
77. Callanan S, Philippe K, Delahunt A, O’Keeffe LM, O’Neill
KN, Yelverton CA, Phillips CM, Twomey PJ, McDonnell CM,
Cody D, McAuliffe FM. Macrosomia and childhood growth
trajectories from birth to 10 years of age: Findings from the
ROLO longitudinal birth cohort study. J Obes. 2025; 2025:
8884369. doi: 10.1155/jobe/8884369.
-
78. Çakmak Genç G, Karakaş Çelik S, Hazaloğlu M, Harma M,
Dursun A. Gestasyonel diyabet ile IL8/CXCL8 rs4073 gen po
limorfizmi arasındaki ilişkinin araştırılması. Turk J Diab Obes.
2023; 7(1): 66-71. doi: 10.25048/tudod.1198053.
-
79. Flores-Le Roux JA, Sagarra E, Benaiges D, Hernandez-Rivas
E, Chillaron JJ, Puig de Dou J, Mur A, Lopez-Vilchez MA,
Pedro-Botet J. A prospective evaluation of neonatal hypogly
caemia in infants of women with gestational diabetes mellitus.
Diabetes Res Clin Pract. 2012; 97(2): 217-222. doi: 10.1016/j.
diabres.2012.03.011.
-
80. Diggikar S, Trif P, Mudura D, Prasath A, Mazela J, Ognean
ML, Kramer BW, Galis R. Neonatal hypoglycemia and neuro
developmental outcomes: An updated systematic review and
meta-analysis. Life (Basel). 2024; 14(12): 1618. doi: 10.3390/
life14121618.
-
81. Catalano PM, Hauguel-De Mouzon S. Is it time to revisit
the Pedersen hypothesis in the face of the obesity epidemic?
Am J Obstet Gynecol. 2011; 204(6): 479-487. doi: 10.1016/j.
ajog.2010.11.039.
-
82. Yang F, Liu H, Ding C. Gestational diabetes mellitus and risk
of neonatal respiratory distress syndrome: A systematic review
and meta-analysis. Diabetol Metab Syndr. 2024; 16(1): 294.
doi: 10.1186/s13098-024-01539-x.
-
83. Kawakita T, Bowers K, Hazrati S, Zhang C, Grewal J, Chen Z,
Sun L, Grantz KL. Increased neonatal respiratory morbidity
associated with gestational and pregestational diabetes: A ret
rospective study. Am J Perinatol. 2017; 34(11): 1160-1168. doi:
10.1055/s-0037-1604414.
-
84. Mills JL. Malformations in infants of diabetic mothers. Birth
Defects Res A Clin Mol Teratol. 2010; 88(10): 769-778. doi:
10.1002/bdra.20757.
-
85. Al-Biltagi M, El Razaky O, El Amrousy D. Cardiac changes
in infants of diabetic mothers. World J Diabetes. 2021; 12(8):
1233-1247. doi: 10.4239/wjd.v12.i8.1233.
-
86. Obut M, Çayönü Kahraman N, Sucu S, Keleş A, Arat Ö, Yücel
Çelik Ö, Bucak M, Çakır A, Şahin D, Yücel A. Comparison of
feto-maternal outcomes between emergency and elective ce
sarean deliveries in patients with gestational diabetes. Turk J
Diab Obes. 2023; 7(1): 52-59. doi: 10.25048/tudod.1233486.
-
87. Boney CM, Verma A, Tucker R, Vohr BR. Metabolic syn
drome in childhood: Association with birth weight, maternal
obesity, and gestational diabetes mellitus. Pediatrics. 2005;
115(3): e290-e296. doi: 10.1542/peds.2004-1808.
-
88. Kaaja R, Rönnemaa T. Gestational diabetes: Pathogenesis and
consequences to mother and offspring. Rev Diabet Stud. 2008;
5(4): 194-202. doi: 10.1900/RDS.2008.5.194.
-
89. Xiang AH, Wang X, Martinez MP, Walthall JC, Curry ES,
Page K, Buchanan TA, Coleman KJ, Getahun D. Association
of maternal diabetes with autism in offspring. JAMA. 2015;
313(14): 1425-1434. doi: 10.1001/jama.2015.2707.
-
90. Lee J, Lee NK, Moon JH. Gestational diabetes mellitus:
Mechanisms underlying maternal and fetal complications.
Endocrinol Metab (Seoul). 2025; 40(1): 10-25. doi: 10.3803/
EnM.2024.2264.
-
91. Muller YL, Yueh YG, Yaworsky PJ, Salbaum JM, Kappen C.
Caudal dysgenesis in Islet-1 transgenic mice. FASEB J. 2003;
17(10): 1349-1351. doi: 10.1096/fj.02-0856fje.
-
92. Sirasanagandla SR, Ranganath Pai KS, Potu BK, Bhat KM.
Protective effect of Cissus quadrangularis Linn. on diabetes
induced delayed fetal skeletal ossification. J Ayurveda Integr
Med. 2014; 5(1): 25-32. doi: 10.4103/0975-9476.128852.
-
93. Krause A, Schwab KO, Trost J, Thill M, Kunze M, Seufert J,
Hentschel R. Gestational diabetes mellitus: The role of IGF-1
and leptin in cord blood. J Perinat Med. 2025; 53(7): 937-944.
doi: 10.1515/jpm-2024-0379.
-
94. Antoniou MC, Quansah DY, Gilbert L, Arhab A, Schenk S, La
croix A, Stuijfzand B, Horsch A, Puder JJ. Association between
maternal and fetal inflammatory biomarkers and offspring
weight and BMI during the first year of life in pregnancies
with GDM: MySweetheart study. Front Endocrinol (Laus
anne). 2024; 15: 1333755. doi: 10.3389/fendo.2024.1333755.
-
95. Karakaş Çelik S, Yamak AS. Gestasyonel diyabette genetik ve
epigenetik değişimler. Turk J Diab Obes. 2018; 2(1): 9-15.
-
96. Damm P, Houshmand-Oeregaard A, Kelstrup L, Lauenborg
J, Mathiesen ER, Clausen TD. Gestational diabetes mellitus
and long-term consequences for mother and offspring: A view
from Denmark. Diabetologia. 2016; 59(7): 1396-1399. doi:
10.1007/s00125-016-3985-5.
-
97. Shashikadze B, Flenkenthaler F, Stöckl JB, Valla L, Renner S,
Kemter E, Wolf E, Fröhlich T. Developmental effects of (pre-)
gestational diabetes on offspring: Systematic screening using
omics approaches. Genes (Basel). 2021; 12(12): 1991. doi:
10.3390/genes12121991.
-
98. Moazzen H, Lu X, Liu M, Feng Q. Pregestational diabetes
induces fetal coronary artery malformation via reactive oxy
gen species signaling. Diabetes. 2015; 64(4): 1431-1443. doi:
10.2337/db14-0190
-
99. Lehtoranta L, Koskinen A, Vuolteenaho O, Laine J, Kytö V,
Soukka H, Ekholm E, Räsänen J. Gestational hyperglycemia
reprograms cardiac gene expression in rat offspring. Pediatr
Res. 2017; 82(2): 356-361. doi: 10.1038/pr.2017.42.
-
100. Golic M, Stojanovska V, Bendix I, Wehner A, Herse F, Haase
N, Kräker K, Fischer C, Alenina N, Bader M, Schütte T,
Schuchardt M, van der Giet M, Henrich W, Muller DN, Fel
derhoff-Müser U, Scherjon S, Plösch T, Dechend R. Diabetes
mellitus in pregnancy leads to growth restriction and epigen
etic modification of the Srebf2 gene in rat fetuses. Hyperten
sion. 2018; 71(5): 911-920. doi: 10.1161/HYPERTENSIONA
HA.117.10782.
-
101. Agarwal P, Brar N, Morriseau TS, Kereliuk SM, Fonseca MA,
Cole LK, Jha A, Xiang B, Hunt KL, Seshadri N, Hatch GM,
Doucette CA, Dolinsky VW. Gestational diabetes adversely
affects pancreatic islet architecture and function in the male
rat offspring. Endocrinology. 2019; 160(8): 1907-1925. doi:
10.1210/en.2019-00232.
-
102. Salazar-García M, Reyes-Maldonado E, Revilla-Monsalve
MC, Villavicencio-Guzmán L, Reyes-López A, Sánchez-Gó
mez C. Importance of maternal diabetes on the chronolog
ical deregulation of intrauterine development: An experi
mental study in rat. J Diabetes Res. 2015; 2015: 354265. doi:
10.1155/2015/354265.
-
103. Damasceno DC, Volpato GT, Calderon IMP, Rudge MVC.
Oxidative stress and diabetes in pregnant rats. Anim Re
prod Sci. 2002; 72(3-4): 235-244. doi: 10.1016/S0378
4320(02)00094-5.
-
104. Gäreskog M, Cederberg J, Eriksson UJ, Wentzel P. Maternal
diabetes in vivo and high glucose concentration in vitro in
crease apoptosis in rat embryos. Reprod Toxicol. 2007; 23(1):
63-74. doi: 10.1016/j.reprotox.2006.08.009.
-
105. Capobianco E, Fornes D, Linenberg I, Powell TL, Jans
son T, Jawerbaum A. A novel rat model of gestational dia
betes induced by intrauterine programming is associated
with alterations in placental signaling and fetal overgrowth.
Mol Cell Endocrinol. 2016; 422: 221-232. doi: 10.1016/j.
mce.2015.12.020.
-
106. Kiss AC, Lima PH, Sinzato YK, Takaku M, Takeno MA,
Rudge MV, Damasceno DC. Animal models for clinical and
gestational diabetes: Maternal and fetal outcomes. Diabetol
Metab Syndr. 2009; 1(1): 21. doi: 10.1186/1758-5996-1-21.