Features of the functional state of the enteropancreatic hormonal system in pregnant women with gestational diabetes mellitus

Features of the functional state of the enteropancreatic hormonal system in pregnant women with gestational diabetes mellitus

© Fatima O. Ushanova1*, Tatiana Y. Demidova1, Tatiana N. Korotkova2

1Pirogov Russian National Research Medical University, Moscow, Russia

2Federal Research Centre of Nutrition, Biotechnology and Food Safety, Moscow, Russia

BACKGROUND: The prevalence of gestational diabetes mellitus (GDM) is growing rapidly, along with which the typical portrait of a pregnant woman with this disease is changing. Frequent detection of GDM in the early stages of pregnancy causes a high interest in the study of new mechanisms of its development.

AIM: Evaluation of the state of the incretin response based on the analysis of the secretion of GLP-1, glucagon, insulin and c-peptide in pregnant women with different periods of GDM development.

MATERIALS AND METHODS: A single-center prospective comparative uncontrolled study that included pregnant women with GSD, divided into 2 groups depending on the duration of the disease: group 1 — pregnant women who were diagnosed at <24 weeks of gestation (n=65), group 2 — at ≥24 weeks of gestation (n=26). All patients underwent a set of diagnostic measures, including a stress test with the determination of GLP-1, glucagon, insulin, c-peptide before and after a mixed breakfast, and an assessment of insulin resistance. Glucose monitoring was performed for pregnant women with GSD using the FreeStyle Libre Flash system (Abbott Diabetes Care Ltd., UK).

RESULTS: The total number of subjects was 91. The average age was 32.05±5.6 (95% CI 30.9; 33.2) years. Pregnant women of both groups were comparable in age, body weight and glycemic level at the time of diagnosis. The basal blood insulin level in the general group was 7.2 [4.9; 12.1] µme/ml, C-peptide — 1.5 [1.17; 2.24] ng/m, glucagon — 70.1 [56.2; 100] pg/ml, GLP-1 — 1.16 [0.94; 1.22] ng/ml. In 31% For women, the HOMA-IR index was ≥2.7. The basal level of glucagon was significantly higher in the group of early development of GSD: 70.9 [57.7; 109.2] pg/ml versus 61.7 [46.6; 87] pg/ml, p=0.04. In both groups of pregnant women, the decrease in glucagon secretion was not statistically significant, most had a paradoxical increase in glucagon secretion. When assessing the dynamics of GPP-1, a significant increase in the indicator was detected only in the 1st group: Δ GPP-1 0.15 [-0.07; 0.96], p <0.01. In the second, the dynamics of the indicator was not statistically significant (p=0.211). Negative correlation of the increase in GLP-1 with MAGE (r=-0.34, p<0.05), glycemic lability index LI (r=-0.4, p<0.05) and J-index (r=0.44, p<0.05) was revealed.

CONCLUSION: The preservation of the physiological secretion of insulin and c-peptide in the form of a satisfactory increase in indicators after a food load was established. A violation of postprandial suppression of glucagon secretion was revealed. The increase in GPP-1 in response to food loading was disrupted in the case of the development of GSD during pregnancy ≥ 24 weeks.

1. Dedov II, Shestakova MV, Mayorov AYu, et al. Standards of specialized diabetes care (10-th edition). Diabetes Mellitus. 2021;24(S1):1-235 (In Russ.). doi: https://doi.org/10.14341/DM12802

2. International Diabetes Federation. IDF Diabetes Atlas, 10th edn. Brussels, Belgium: 2021 [cited 15.11.2023]. Available from: https://www.diabetesatlas.org

3. Fritsche L, Heni M, Eckstein SS, et al. Incretin hypersecretion in gestational diabetes mellitus. J Clin Endocrinol Metab. 2022;107(6):e2425-e2430. doi: https://doi.org/10.1210/clinem/dgac095

4. Hillier TA, Pedula KL, Ogasawara KK, et al. A pragmatic, randomized clinical trial of gestational diabetes screening. N Engl J Med. 2021;384(10):895-904. doi: https://doi.org/10.1056/NEJMoa2026028

5. Diabetes in pregnancy: management from preconception to the postnatal period. London: National Institute for Health and Care Excellence (NICE); 2020.

6. Gascho CLL, Leandro DMK, Ribeiro e Silva T, Silva JC. Predictors of cesarean delivery in pregnant women with gestational diabetes mellitus. Rev Bras Ginecol e Obs. 2017;39(02):060-065. doi: https://doi.org/10.1055/s-0037-1598644

7. You H, Hu J, Liu Y, et al. Risk of type 2 diabetes mellitus after gestational diabetes mellitus: A systematic review &amp; meta-analysis. Indian J Med Res. 2021;154(1):62. doi: https://doi.org/10.4103/ijmr.IJMR_852_18

8. Daly B, Toulis KA, Thomas N, et al. Increased risk of ischemic heart disease, hypertension, and type 2 diabetes in women with previous gestational diabetes mellitus, a target group in general practice for preventive interventions: A populationbased cohort study. PLOS Med. 2018;15(1):e1002488. doi: https://doi.org/10.1371/journal.pmed.1002488

9. Carr DB, Utzschneider KM, Hull RL, et al. Gestational diabetes mellitus increases the risk of cardiovascular disease in women with a family history of type 2 diabetes. Diabetes Care. 2006;29(9):2078-2083. doi: https://doi.org/10.2337/dc05-2482

10. Tobias DK, Stuart JJ, Li S, et al. Association of history of gestational diabetes with long-term cardiovascular disease risk in a large prospective cohort of US women. JAMA Intern Med. 2017;177(12):1735. doi: https://doi.org/10.1001/jamainternmed.2017.2790

11. Lowe WL Jr, Scholtens DM, Kuang A, et. al. HAPO followup study cooperative research group. Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study (HAPO FUS): Maternal gestational diabetes mellitus and childhood glucose metabolism. Diabetes Care. 2019;42(3):372-380. doi: https://doi.org/10.2337/dc18-1646

12. Rayanagoudar G, Hashi AA, Zamora J, et. al. Quantification of the type 2 diabetes risk in women with gestational diabetes: a systematic review and meta-analysis of 95,750 women. Diabetologia. 2016;59(7):1403-1411. doi: https://doi.org/10.1007/s00125-016-3927-2

13. Burlina S, Dalfrà MG, Chilelli NC, Lapolla A. Gestational diabetes mellitus and future cardiovascular risk: An update. Int J Endocrinol. 2016;2016(12):1-6. doi: https://doi.org/10.1155/2016/2070926

14. Retnakaran R. Hyperglycemia in pregnancy and its implications for a woman’s future risk of cardiovascular disease. Diabetes Res Clin Pract. 2018;145(12):193-199. doi: https://doi.org/10.1016/j.diabres.2018.04.008

15. Scholtens DM, Kuang A, Lowe LP, et al. Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study (HAPO FUS): Maternal glycemia and childhood glucose metabolism. Diabetes Care. 2019;42(3):381-392. doi: https://doi.org/10.2337/dc18-2021

16. Catalano PM. Trying to understand gestational diabetes. Diabet Med. 2014;31(3):273-281. doi: https://doi.org/10.1111/dme.12381

17. 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. doi: https://doi.org/10.2337/dc07-s202

18. Rieck S, White P, Schug J, et al. The transcriptional response of the islet to pregnancy in mice. Mol Endocrinol. 2009;23(10):1702-1712. doi: https://doi.org/10.1210/me.2009-0144

19. Deacon CF, Ahrén B. Physiology of incretins in health and disease. Rev Diabet Stud. 2011;8(3):293-306. doi: https://doi.org/10.1900/RDS.2011.8.293

20. Geloneze B, Repetto EM, Geloneze SR, et. al. The threshold value for insulin resistance (HOMA-IR) in an admixtured population IR in the Brazilian metabolic syndrome study. Diabetes Res Clin Pract. 2006;72(2):219-220. doi: https://doi.org/10.1016/j.diabres.2005.10.017

21. Herrmann C, Göke R, Richter G, et. al. Glucagon-like peptide-1 and glucose-dependent insulin-releasing polypeptide plasma levels in response to nutrients. Digestion. 1995;56(2):117-126. doi: https://doi.org/10.1159/000201231

22. Tura A, Muscelli E, Gastaldelli A, et. al. Altered pattern of the incretin effect as assessed by modelling in individuals with glucose tolerance ranging from normal to diabetic. Diabetologia. 2014;57(6):1199-1203. doi: https://doi.org/10.1007/s00125-014-3219-7

23. Saprina TV, Timokhina ES, Goncharevich OK, et al. The associations of incretin hormone concentration with gestational diabetes mellitus. Diabetes mellitus. 2016;19(2):150-157. (In Russ.). doi: https://doi.org/10.14341/DM2004134-37

24. Gardner DG, Shoback D. Greenspan’s basic & clinical endocrinology. 10th ed. New York: McGraw-Hill Education; 2018.

25. Pagana KD, Pagana TJ, Pagana TN. Mosby’s diagnostic & laboratory test reference. 14th ed. St. Louis, Mo: Elsevier; 2019.

26. Forbes S, Godsland IF, Taylor-Robinson SD, et al. A history of previous gestational diabetes mellitus is associated with adverse changes in insulin secretion and VLDL metabolism independently of increased intrahepatocellular lipid. Diabetologia. 2013;56(9):2021-2033. doi: https://doi.org/10.1007/s00125-013-2956-3

27. Mosavat M, Omar SZ, Jamalpour S, Tan PC. Serum GlucoseDependent Insulinotropic Polypeptide (GIP) and Glucagon-Like Peptide-1 (GLP-1) in association with the risk of gestational diabetes: A prospective case-control study. J Diabetes Res. 2020;2020(10):1-7. doi: https://doi.org/10.1155/2020/9072492

28. Fritsche L, Heni M, Eckstein SS, et al. Incretin hypersecretion in gestational diabetes mellitus. J Clin Endocrinol Metab. 2022;107(6):e2425-e2430. doi: https://doi.org/10.1210/clinem/dgac095

29. Nadkarni P, Chepurny OG, Holz GG. Regulation of glucose homeostasis by GLP-1. Prog Mol Biol Transl Sci. 2014:(121):23-65. doi: https://doi.org/10.1016/B978-0-12-800101-1.00002-8

30. Bonde L, Vilsbøll T, Nielsen T, et al. Reduced postprandial GLP‐1 responses in women with gestational diabetes mellitus. Diabetes, Obes Metab. 2013;15(8):713-720. doi: https://doi.org/10.1111/dom.12082