Detailed Review on Gestational Diabetes Mellitus with Emphasis on Pathophysiology, Epidemiology, Related Risk Factors, and its Subsequent Conversion to Type 2 Diabetes Mellitus

Abstract

Any degree of glucose intolerance during the pregnancy of a women is termed as Gestational Diabetes Mellitus (GDM). It may further develop into Type 2 Diabetes Mellitus (T2DM) later in life. GDM affects both mother and infant in multiple ways and there are various factors that predispose the development of GDM.The primary objective of this review is to describe the various aspects related to GDM and the subsequent risk of developing T2DM later in life.We reviewed freely accessible, full-text articles, available in PubMed, Google Scholar, and MEDLINE in the English language, till August 2022 pertaining to GDM.The pathophysiology of underlying glucose intolerance has been discussed, including the various factors like β-Cell dysfunction, chronic insulin resistance, adiponectin, insulin resistance. GDM affects pregnancies world-wide, but it is higher in the South-east Asia, northern America and Caribbean, south and central America regions. Along with ethnicity, various modifiable and non-modifiable risk factors also play a major role in development of disease. Although no standard diagnostic criteria is accepted world-wide for screening of GDM, but the one-step and two-step approach has made quite a difference. The risk of developing T2DM after GDM is well documented, and it increases with age. GDM leads to an onset of diabetes in the family at a young age, it leads to poor consequences on the health of both the mother and infant. Standard diagnostic criteria, proper education and counselling of the mother is required to tackle the condition.

Key words

gestational diabetes mellitus - diabetes mellitus type 2  - Impaired glucose tolerance  - metabolic syndrome

Publication History

Received: 05 January 2023

Accepted after revision: 24 March 2023

Accepted Manuscript online:
24 March 2023

Article published online:
02 May 2023

• References

• 1 HAPO Study Cooperative Research Group. The hyperglycemia and adverse pregnancy outcome (HAPO) study. Int J Gynecol Obstet 2002; 78: 69-77
• 2 Kouhkan A, Najafi L, Malek M. et al. Gestational diabetes mellitus: Major risk factors and pregnancy-related outcomes: A cohort study. Int J Reprod Biomed 2021; 19: 827
• 3 Noctor E, Dunne FP. Type 2 diabetes after gestational diabetes: the influence of changing diagnostic criteria. World J Diabetes 2015; 6: 234
• 4 Grieger JA, Hutchesson MJ, Cooray SD. et al. A review of maternal overweight and obesity and its impact on cardiometabolic outcomes during pregnancy and postpartum. Therap Adv Reprod Health 2021; 15: 2633494120986544
• 5 Herath H, Herath R, Wickremasinghe R. Gestational diabetes mellitus and risk of type 2 diabetes 10 years after the index pregnancy in Sri Lankan women–A community based retrospective cohort study. PloS one 2017; 12: e0179647
• 6 Plows JF, Stanley JL, Baker PN. et al. The pathophysiology of gestational diabetes mellitus. Int J Mol Sci 2018; 19: 3342
• 7 Toren E, Burnette KS, Banerjee RR. et al. Partners in crime: beta-cells and autoimmune responses complicit in type 1 diabetes pathogenesis. Front Immunol 2021; 12: 756548
• 8 Plows JF, Stanley JL, Baker PN. et al. The pathophysiology of gestational diabetes mellitus. Int J Mol Sci 2018; 19: 3342
• 9 Ashcroft FM, Rohm M, Clark A. et al. Is type 2 diabetes a glycogen storage disease of pancreatic β cells?. Cell Metab 2017; 26: 17-23
• 10 Barbour LA, McCurdy CE, Hernandez TL. et al. Cellular mechanisms for insulin resistance in normal pregnancy and gestational diabetes. Diabetes Care 2007; 30: S112-S119
• 11 Friedman JE, Kirwan JP, Jing M. et al. Increased skeletal muscle tumor necrosis factor-α and impaired insulin signaling persist in obese women with gestational diabetes mellitus 1 year postpartum. Diabetes 2008; 57: 606
• 12 https://www.mdpi.com/1422-0067/19/11/3342/htm
• 13 Chen J, Tan B, Karteris E. et al. Secretion of adiponectin by human placenta: differential modulation of adiponectin and its receptors by cytokines. Diabetologia 2006; 49: 1292-1302
• 14 Kishida K, Funahashi T, Shimomura I. Molecular mechanisms of diabetes and atherosclerosis: role of adiponectin. Endocr Metab Immune Disord Drug Targets (Formerly Curr Drug Targets Immune, Endocri Metab Disord) 2012; 12: 118-131
• 15 Bouchard L, Hivert MF, Guay SP. et al. Placental adiponectin gene DNA methylation levels are associated with mothers’ blood glucose concentration. Diabetes 2012; 61: 1272-1280
• 16 Augustin R. The protein family of glucose transport facilitators: It's not only about glucose after all. IUBMB Life 2010; 62: 315-333
• 17 Jones HN, Jansson T, Powell TL. IL-6 stimulates system A amino acid transporter activity in trophoblast cells through STAT3 and increased expression of SNAT2. Am J Physiol Cell Physiol 2009; 297: C1228-C1235
• 18 Radaelli T, Lepercq J, Varastehpour A. et al. Differential regulation of genes for fetoplacental lipid pathways in pregnancy with gestational and type 1 diabetes mellitus. Am J Obstet Gynecol 2009; 201: 209-e1
• 19 Reichetzeder C, Dwi Putra SE, Pfab T. et al. Increased global placental DNA methylation levels are associated with gestational diabetes. Clin Epigenet 2016; 8: 1-0
• 20 https://apps.who.int/iris/bitstream/handle/10665/85975/WHO_NMH_MND_13.2_eng.pdf
• 21 Genevay M, Pontes H, Meda P. Beta cell adaptation in pregnancy: a major difference between humans and rodents?. Diabetologia 2010; 53: 2089-2092
• 22 Li G, Wei T, Ni W. et al. Incidence and risk factors of gestational diabetes mellitus: a prospective cohort study in Qingdao, China. Front Endocrinol 2020; 636
• 23 Kwak SH, Jang HC, Park KS. Finding genetic risk factors of gestational diabetes. Genom Inform 2012; 10: 239
• 24 Mills GW, Avery PJ, McCarthy MI. et al. Heritability estimates for beta cell function and features of the insulin resistance syndrome in UK families with an increased susceptibility to type 2 diabetes. Diabetologia 2004; 47: 732-738
• 25 Spellacy WN, Miller S, Winegar A. et al. Macrosomia – maternal characteristics and infant complications. Obstet Gynecol 1985; 66: 158-161
• 26 Morales-Suárez-Varela M, Peraita-Costa I, Perales-Marín A. et al. Risk of gestational diabetes due to maternal and partner smoking. Int J Environ Res Pub Health 2022; 19: 925
• 27 Marshall JC, Dunaif A. Should all women with PCOS be treated for insulin resistance?. Fertil Steril 2012; 97: 18-22
• 28 Jenum AK, Mørkrid K, Sletner L. et al. Impact of ethnicity on gestational diabetes identified with the WHO and the modified International Association of Diabetes and Pregnancy Study Groups criteria: a population-based cohort study. Eur J Endocrinol 2012; 166: 317-324
• 29 Savitz DA, Janevic TM, Engel SM. et al. Ethnicity and gestational diabetes in New York City, 1995–2003. BJOG: Int J Obstet Gynaecol 2008; 115: 969-978
• 30 Zito G, Della Corte L, Giampaolino P. et al. Gestational diabetes mellitus: Prevention, diagnosis and treatment. A fresh look to a busy corner. J Neonatal Perinatal Med 2020; 13: 529-541
• 31 Tsakiridis I, Giouleka S, Mamopoulos A. et al. Diagnosis & management of gestational diabetes mellitus. Obstet Gynecol Surv 2021; 76: 367-381
• 32 Caissutti C, Khalifeh A, Saccone G. et al. Are women positive for the One Step but negative for the Two Step screening tests for gestational diabetes at higher risk for adverse outcomes?. Acta Obstet Gynecol Scand 2018; 97: 122-134
• 33 Rich SS, Concannon P. Role of Type 1 Diabetes-associated SNPs on autoantibody positivity in the type 1 diabetes genetics consortium: overview. Diabetes Care 2015; 38: S1-S3
• 34 O’Sullivan JB, Mahan CM, Charles D. et al. Screening criteria for high-risk gestational diabetic patients. Am J Obstet Gynecol 1973; 116: 895-900
• 35 National Diabetes Data Group. Classification and Diagnosis of Diabetes Mellitus and Other Categories of Glucose Intolerance. Diabetes 1979; 28: 1039-1057
• 36 Carpenter MW, Coustan DR. Criteria for screening tests for gestational diabetes. Am J Obstet Gynecol 1982; 144: 768-773
• 37 Rani PR, Begum J. Screening and diagnosis of gestational diabetes mellitus, where do we stand. J Clin Diagnost Res. 2016; 10: QE01
• 38 International Association of Diabetes and Pregnancy Study Groups Consensus Panel. International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care 2010; 33: 676-682
• 39 Shirazian N, Mahboubi M, Roya E. et al. Comparison of different diagnostic criteria for gestational diabetes mellitus based on the 75-g oral glucose tolerance test: a cohort study. Endocr Pract 2008; 14: 312-317
• 40 Bellamy L, Casas JP, Hingorani AD. et al. Type 2 diabetes mellitus after gestational diabetes: a systematic review and meta-analysis. Lancet 2009; 373: 1773-1779
• 41 Ornoy A, Becker M, Weinstein-Fudim L. et al. Diabetes during pregnancy: a maternal disease complicating the course of pregnancy with long-term deleterious effects on the offspring. A clinical review. Int J Mol Sci 2021; 22: 2965
• 42 Yessoufou A, Moutairou K. Maternal diabetes in pregnancy: early and long-term outcomes on the offspring and the concept of “metabolic memory”. Exp Diabetes Res 2011; 218598
• 43 Farahvar S, Walfisch A, Sheiner E. Gestational diabetes risk factors and long-term consequences for both mother and offspring: a literature review. Exp Rev Endocrinol Metab 2019; 14: 63-74
• 44 Mierzyński R, Poniedziałek-Czajkowska E, Sotowski M. et al. Nutrition as prevention factor of gestational diabetes mellitus: a narrative review. Nutrients 2021; 13: 3787
• 45 Luoto R, Laitinen K, Nermes M. et al. Impact of maternal probiotic-supplemented dietary counselling on pregnancy outcome and prenatal and postnatal growth: a double-blind, placebo-controlled study. Br J Nutr 2010; 103: 1792-1799
• 46 Karamanos B, Thanopoulou A, Anastasiou E. et al. A relation of the Mediterranean diet with the incidence of gestational diabetes. Eur J Clin Nutr 2014; 68: 8-13
• 47 Badon SE, Enquobahrie DA, Wartko PD. et al. Healthy lifestyle during early pregnancy and risk of gestational diabetes mellitus. Am J Epidemiol 2017; 186: 326-333
• 48 Asemi Z, Tabassi Z, Samimi M. et al. Favourable effects of the dietary approaches to stop hypertension diet on glucose tolerance and lipid profiles in gestational diabetes: a randomised clinical trial. Br J Nutr 2013; 109: 2024-2030
• 49 Padayachee C, Coombes JS. Exercise guidelines for gestational diabetes mellitus. World J Diabetes 2015; 6: 1033