Defining Heterogeneity Among Women With Gestational Diabetes Mellitus

Overview

Journal Diabetes

Specialty Endocrinology

Date 2020 Aug 27

PMID 32843565

Citations 26

Authors

Camille E Powe

Marie-France Hivert

Miriam S Udler

Affiliations

Soon will be listed here.

Abstract

Attention to precision medicine in type 2 diabetes (T2D) has provided two favored approaches to subclassifying affected individuals and parsing heterogeneity apparent in this condition: phenotype-based and genotype-based. Gestational diabetes mellitus (GDM) shares phenotypic characteristics with T2D. However, unlike T2D, GDM emerges in the setting of profound pregnancy-related physiologic changes in glucose metabolism. T2D and GDM also share common genetic architecture, but there are likely to be unique genetic influences on pregnancy glycemic regulation that contribute to GDM. In this Perspective, we describe efforts to decipher heterogeneity in T2D and detail how we and others are applying approaches developed for T2D to the study of heterogeneity in GDM. Emerging results reveal the potential of phenotype- and genotype-based subclassification of GDM to deliver the promise of precision medicine to the obstetric population.

Citing Articles

How should we define subtypes of gestational diabetes mellitus?.

Gobl C, Tura A Diabetologia. 2025; .

PMID: 39954058 DOI: 10.1007/s00125-025-06374-x.

Subtypes of Gestational Diabetes Mellitus Are Differentially Associated With Newborn and Childhood Metabolic Outcomes.

Osmulski M, Yu Y, Kuang A, Josefson J, Hivert M, Scholtens D Diabetes Care. 2025; 48(3):390-399.

PMID: 39787502 PMC: 11870284. DOI: 10.2337/dc24-1735.

Gestational Diabetes, the Human Milk Metabolome, and Infant Growth and Adiposity.

Nagel E, Pena A, Dreyfuss J, Lock E, Johnson K, Lu C JAMA Netw Open. 2024; 7(12):e2450467.

PMID: 39666338 PMC: 11638796. DOI: 10.1001/jamanetworkopen.2024.50467.

Gestational Diabetes: An Update 60 Years After O'Sullivan and Mahan.

McIntyre H, Kampmann U, Clausen T, Laurie J, Ma R J Clin Endocrinol Metab. 2024; 110(1):e19-e31.

PMID: 39389786 PMC: 11651698. DOI: 10.1210/clinem/dgae709.

Analysis of early-pregnancy metabolome in early- and late-onset gestational diabetes reveals distinct associations with maternal overweight.

Masalin S, Klavus A, Rono K, Koistinen H, Koistinen V, Karkkainen O Diabetologia. 2024; 67(11):2539-2554.

PMID: 39083240 PMC: 11519293. DOI: 10.1007/s00125-024-06237-x.

References

. 2. Classification and Diagnosis of Diabetes: . Diabetes Care. 2019; 43(Suppl 1):S14-S31. DOI: 10.2337/dc20-S002. View

Udler M, McCarthy M, Florez J, Mahajan A . Genetic Risk Scores for Diabetes Diagnosis and Precision Medicine. Endocr Rev. 2019; 40(6):1500-1520. PMC: 6760294. DOI: 10.1210/er.2019-00088. View

Bonomo M, Cetin I, Pisoni M, Faden D, Mion E, Taricco E . Flexible treatment of gestational diabetes modulated on ultrasound evaluation of intrauterine growth: a controlled randomized clinical trial. Diabetes Metab. 2004; 30(3):237-44. DOI: 10.1016/s1262-3636(07)70114-3. View

Law G, Alnaji A, Alrefaii L, Endersby D, Cartland S, Gilbey S . Suboptimal Nocturnal Glucose Control Is Associated With Large for Gestational Age in Treated Gestational Diabetes Mellitus. Diabetes Care. 2019; 42(5):810-815. DOI: 10.2337/dc18-2212. View

Khera A, Chaffin M, Aragam K, Haas M, Roselli C, Choi S . Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations. Nat Genet. 2018; 50(9):1219-1224. PMC: 6128408. DOI: 10.1038/s41588-018-0183-z. View

Balsells M, Garcia-Patterson A, Gich I, Corcoy R . Ultrasound-guided compared to conventional treatment in gestational diabetes leads to improved birthweight but more insulin treatment: systematic review and meta-analysis. Acta Obstet Gynecol Scand. 2013; 93(2):144-51. DOI: 10.1111/aogs.12291. View

Udler M, Powe C, Austin-Tse C . Case 6-2020: A 34-Year-Old Woman with Hyperglycemia. N Engl J Med. 2020; 382(8):745-753. PMC: 8063267. DOI: 10.1056/NEJMcpc1913475. View

Scott R, Lagou V, Welch R, Wheeler E, Montasser M, Luan J . Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways. Nat Genet. 2012; 44(9):991-1005. PMC: 3433394. DOI: 10.1038/ng.2385. View

Crowther C, Hiller J, Moss J, McPhee A, Jeffries W, Robinson J . Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. N Engl J Med. 2005; 352(24):2477-86. DOI: 10.1056/NEJMoa042973. View

10.

Landon M, Spong C, Thom E, Carpenter M, Ramin S, Casey B . A multicenter, randomized trial of treatment for mild gestational diabetes. N Engl J Med. 2009; 361(14):1339-48. PMC: 2804874. DOI: 10.1056/NEJMoa0902430. View

11.

Garcia-Patterson A, Gich I, Amini S, Catalano P, de Leiva A, Corcoy R . Insulin requirements throughout pregnancy in women with type 1 diabetes mellitus: three changes of direction. Diabetologia. 2009; 53(3):446-51. DOI: 10.1007/s00125-009-1633-z. View

12.

Metzger B, Lowe L, Dyer A, Trimble E, Chaovarindr U, Coustan D . Hyperglycemia and adverse pregnancy outcomes. N Engl J Med. 2008; 358(19):1991-2002. DOI: 10.1056/NEJMoa0707943. View

13.

Hivert M, Cardenas A, Allard C, Doyon M, Powe C, Catalano P . Interplay of Placental DNA Methylation and Maternal Insulin Sensitivity in Pregnancy. Diabetes. 2019; 69(3):484-492. PMC: 7213861. DOI: 10.2337/db19-0798. View

14.

Moen G, LeBlanc M, Sommer C, Prasad R, Lekva T, Normann K . Genetic determinants of glucose levels in pregnancy: genetic risk scores analysis and GWAS in the Norwegian STORK cohort. Eur J Endocrinol. 2018; 179(6):363-372. DOI: 10.1530/EJE-18-0478. View

15.

Lassance L, Haghiac M, Leahy P, Basu S, Minium J, Zhou J . Identification of early transcriptome signatures in placenta exposed to insulin and obesity. Am J Obstet Gynecol. 2015; 212(5):647.e1-11. PMC: 4700505. DOI: 10.1016/j.ajog.2015.02.026. View

16.

Cheney C, Shragg P, Hollingsworth D . Demonstration of heterogeneity in gestational diabetes by a 400-kcal breakfast meal tolerance test. Obstet Gynecol. 1985; 65(1):17-23. View

17.

Rauh-Hain J, Rana S, Tamez H, Wang A, Cohen B, Cohen A . Risk for developing gestational diabetes in women with twin pregnancies. J Matern Fetal Neonatal Med. 2009; 22(4):293-9. DOI: 10.1080/14767050802663194. View

18.

Schwartz N, Nachum Z, Green M . The prevalence of gestational diabetes mellitus recurrence--effect of ethnicity and parity: a metaanalysis. Am J Obstet Gynecol. 2015; 213(3):310-7. DOI: 10.1016/j.ajog.2015.03.011. View

19.

Desoye G, Nolan C . The fetal glucose steal: an underappreciated phenomenon in diabetic pregnancy. Diabetologia. 2016; 59(6):1089-94. PMC: 4861753. DOI: 10.1007/s00125-016-3931-6. View

20.

Powe C, Allard C, Battista M, Doyon M, Bouchard L, Ecker J . Heterogeneous Contribution of Insulin Sensitivity and Secretion Defects to Gestational Diabetes Mellitus. Diabetes Care. 2016; 39(6):1052-5. PMC: 4878218. DOI: 10.2337/dc15-2672. View