Management of early gestational glucose intolerance to improve pregnancy outcomes

Rajesh Jain, Sadhana Tiwari, Renu Gupta, Neena Gupta, Divya Dwivedi, Shweta Verma, Palak Taneja, V Seshiah, Pikee Saxena

Abstract


Diabetes during pregnancy detection does not mean prevention. A 2-hour postprandial blood glucose (PPBG) ≥110 mg/d at 8-10 weeks is crucial for predicting Gestational Diabetes Mellitus (GDM). Intervention should start at week 8 to prevent GDM as fetal beta cells start insulin secretion by 11th weeks. To Evaluate the efficacy of metformin in high-risk GDM pregnant women having postprandial blood glucose levels ≥110 mg/dL at 8-10 Weeks of gestation; Assess if Medical Nutrition Therapy (MNT) with or without metformin can prevent GDM in women with PPBG ≥110mg/dl at 8-10 weeks and Evaluate complications and outcomes in pregnant women and neonatal morbidities in Early Gestational Glucose Intolerance (EGGI) in intervention groups. A Prospective cohort study included pregnant women at 8 to 10 weeks of gestation, divided into two groups based on their blood sugar levels of ≥110 mg/dl. Those with higher levels ≥110 mg/dl received two different interventions: metformin MNT and MNT only. Follow-up outcomes were done until delivery. The mean PPBG levels were significantly lower in the metformin MNT group compared to the MNT group at 16 weeks (110.74 vs. 118.23), 24 weeks (109.54 vs. 117.78), and 32 weeks (112.8 vs. 118.8), with P-values ≤0.001. Additionally, the primary adverse neonatal composite outcomes were significantly higher in the MNT group (55 cases, 52.3%) compared to the metformin-MNT group (35 cases, 37.6%) with P ≤ 0.038. The MNT group also reported 20 spontaneous abortions (16%) and 12 stillbirths (9.6%), while the metformin group reported none. Neonatal morbidity was significantly lower in the metformin-MNT group (48 cases, 51.6%) compared to the MNT group (80 cases, 76.2%), with P < 0.001. These findings highlight the superior effectiveness of the MNT-metformin intervention. In conclusion, it is essential to keep maternal 2-hour PPBG levels below 110 mg/dl by the 10th week of pregnancy to prevent fetal hyperinsulinemia. Fetal beta cells typically begin secreting insulin around 11th week. Maintaining good glycemic control during pregnancy is crucial for preventing gestational diabetes and ensuring the health of the fetus.

Keywords


Diabetes/Metabolism;Public Health, Health Policy

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References


International Diabetes Federation. IDF Diabetes Atlas, 10th edn. Brussels, Belgium: 2021. Available at: https://www.diabetesatlas.org.

Mezuk B, Allen JO; Rethinking the goals of diabetes prevention programs. Diabetes Care 1, 44:2457–2459, 2021.

Mokdad AH, Bowman BA, Ford ES, Vinicor F, Marks JS, Koplan JP. The continuing epidemics of obesity and diabetes in the United States. JAMA 286:1195-200, 2001.

Centers for Disease Control and Prevention. National Diabetes Statistics Report 2021; website. https://www.cdc. gov/diabetes/data/statistics-report/index.html.

Piper K, Brickwood S, Turnpenny LW, et al. Beta cell differentiation during early human pancreas development. J Endocrinol 181:11-23, 2004.

K, Devaskar SU: Fetal origins of adult disease. Curr Probl Pediatr Adolesc Health Care 41:158-176, 2011.

Goyal D, Limesand SW, Goyal R, et al.: Epigenetic responses and developmental origins of health and disease. J Endocrinol 242:T105-119, 2019..

Hernandez TL, Friedman JE, Van Pelt RE, Barbour LA. Patterns of glycemia in normal pregnancy: should the current therapeutic targets be challenged? Diabetes Care 34:1660-1668, 2011.

American Diabetes Association. Classi-fication and Diagnosis of Diabetes: Standards of Medical Care in Diabetes—2020. Diabetes Care 43, S14–S31, 2020.

Hinkle SN, Tsai MY, Rawal S, Albert PS, Zhang C. HbA1c measured in the first trimester of pregnancy and the association with gestational diabetes. Sci Rep 8:12249, 2018.

Saxena P, Yadav A, Singh M, et al. Correlation between the first trimester two-hour postprandial blood glucose greater than 110 mg/dL for the prediction of gestational diabetes mellitus. Cureus 16:e66652, 2024.

Seshiah V, Bronson SC, Balaji V, Jain R, Anjalakshi C. Prediction and prevention of gestational diabetes mellitus and its sequelae by administering metformin in the early weeks of pregnancy. Cureus 15: 31532, 2022.

Seshiah, V., Balaji, V., Chawla, R. et al. Diagnosis and management of gestational diabetes mellitus guidelines by DIPSI (Revised). Int J Diabetes Dev Ctries 43:485–501, 2023.

Desoye G, Nolan CJ. The fetal glucose steal: an underappreciated phenomenon in diabetic pregnancy. Diabetologia 59:1089-1094, 2016.

Das S, Behera MK, Misra S, Baliarsihna AK. Beta-cell function and insulin resistance in pregnancy and their relation to fetal development. Metabolic Syndrome Related Disorder 8:25-32, 2010.

Krishnaveni GV, Veena SR, Hill JC, Kehoe S, Karat SC, Fall CH. Intrauterine exposure to maternal diabetes is associated with higher adiposity and insulin resistance and clustering of cardiovascular risk markers in Indian children. Diabetes Care 33:402-404, 2010.

Brand KMG, Saarelainen L, Sonajalg J, Boutmy E, Foch C, Vääräsmäki M, Morin-Papunen L, Schlachter J, CLUE Study Group, Hakkarainen KM, Korhonen P. Metformin in pregnancy and risk of adverse long-term outcomes: a register-based cohort study. BMJ Open Diabetes Res Care 10:e002363, 2022.

Linh Nguyen, Shiao-Yng Chan, Adrian Kee Keong Teo. Metformin from mother to unborn child - Are there unwarranted effects? EBioMedicine 35:394-404, 2018.

Sciacca L. Bianchi C, Burlina S, Formoso G, Manicardi E, Sculli MA, Resi V. Position paper of the Italian Association of Medical Diabetologists (AMD), Italian Society of Diabetology (SID), and the Italian Study Group of Diabetes in pregnancy: Metformin uses in pregnancy. Acta Diabetol 60:1421–1437, 2023.

National Institute for Health and Care Excellence Diabetes in pregnancy: Management from preconception to the postnatal period. [Accessed on March 10, 2023]. Available at: https://www.nice.org.uk/guidance/ng3/ resources/diabetes-in-pregnancy-management-of-diabetes-and-its-complications-from-preconception-to-the-postnatal-period-5103844 6021.

Barbour LA, Scifres C, Valent AM, Friedman JE, Buchanan TA, Coustan D, et al. A cautionary response to SMFM statement: pharmacological treatment of gestational diabetes. Am J Obstet Gynecol 219:367.e1-367.e7, 2018.

Dornhorst A, Rossi M. Risk and prevention of type 2 diabetes in women with gestational diabetes. Diabetes Care 21 Suppl 2: B43-B49, 1998.

Bronson SC, Seshiah V. Transgenerational Transmission of Non-communicable Diseases: How to Break the Vicious Cycle?. Cureus 13:18754, 2021.

Report of the fifth meeting of the WHO Technical Advisory Group on Diabetes: hybrid meeting, 7–8 June 2023. Geneva: World Health Organization P.1-27, 2023.

Jain, Rajesh, Veeraswamy S, Chandeshekar A et al. Early detection and treatment of impaired glucose and hyperinsulinemia in early pregnancy to prevent diabetes and cardiovascular disease in adults. J Hypertension 41(Supp): pe288, 2023.

Tiwari, S. Agarwal, R. Jain, P. Saxena, V. Seshiah, A. Chandraseka. An interventional study for prevention of gestational diabetes mellitus and its sequelae by administering metformin. Diabetes Res Clin Practice. 2024: 209S1111459, 2024.

Tirado-Aguilar OA, Martinez-Cruz N, Arce-Sanchez L, Borboa-Olivares H, Reyes-Muñoz et al. Earlier detection of gestational diabetes impacts on medication requirements, neonatal and maternal outcomes. Diabetes Obes Metab 1–9, 2024.

Simmons D, Immanuel J, Hague WM, Teede H, et al. TOBOGM Research Group. Treatment of Gestational Diabetes Mellitus Diagnosed Early in Pregnancy. N Engl J Med 388:2132-2144, 2023.

V Seshiah, Pikee Saxena, Anjalakshi C, NBhavatharani, Geetha Lakshmi , B Madhuri , Rajesh Jain. Treatment of early gestational glucose intolerance. Diabetes Asia Journal 1:19-22, 2024.

Veeraswamy S, Divakar H, Gupte S, Datta M, Kapur A, Vijayam B. Need for testing glucose tolerance in the early weeks of pregnancy. Indian J Endocrinol Metab 20:43-46, 2016.


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