Endocrine Abstracts

Introduction: Distinguishing between gestational diabetes and MODY (Maturity Onset Diabetes of the Young) during pregnancy is relevant for therapeutic approaches and potential maternal-fetal complications. However, performing genetic study for MODY in pregnant women is uncommon.

Aim: To describe 2 cases in which the hypothesis of MODY was considered during pregnancy. Case 1: Woman, 35 years old, G1P0A1, BMI 25 kg/m². At 5 weeks of gestation, she developed polyuria and polydipsia, prompting blood glucose measurement: glucose 293 mg/dl, A1C 9.3%. She started metformin 1.5 g/day. At the first Diabetes appointment, she demonstrated inadequate glycemic control. C-peptide was 3.9 ng/ml (reference range 1.1-4.4) and anti-GAD, and anti-IA2 antibodies were negative. Insulin therapy was initiated with progressive titration, and adequate glycemic control was achieved at 13 weeks. At the end of pregnancy, she was on metformin 2 g/day, detemir 28 U/day, and lispro 5U at dinner. Fetal macrosomia was identified without other ultrasound abnormalities. She underwent cesarean section at 38 weeks, with no complications; live birth with a weight of 4365 g, without malformations. She has maintained euglycemia without therapy in the 3 months postpartum. Due to a significant family history of Diabetes mellitus (DM), a genetic study for MODY was performed, revealing a result of uncertain significance - c.31A>G p.(Thr11Ala) in heterozygosity in the PDX1 gene (unreported variant). Case 2: Woman, 37 years old, G3P0, BMI 27 kg/m², diagnosed with DM in 2019, with no complications. Several maternal relatives with history of DM. She was referred to the Diabetes clinic for preconception assessment: HbA1C 5.6% on glargine 16U/day. Analytically: C-peptide 1.26ng/ml (reference range 1.1-4.4), anti-GAD and anti-IA2 antibodies were negative. At 12 weeks of gestation, she started prandial insulin, with no significant dosage increase since then. Currently, she is in the third trimester, with good glycemic control under glargine 24U and aspart 5U/day; fetal ultrasounds and echocardiogram without abnormalities. Genetic study for MODY revealed an inconclusive result - c.-152C>A in heterozygosity in the promoter region of the INS gene (reported variant).

Conclusion: In the described cases, the pre-existing DM/early diagnosis during pregnancy, the need for IT, significant family history of DM, and the exclusion of pancreatic autoimmunity, raised MODY suspicion. Pregnancy is associated with insulin resistance and may reveal pre-existing dysfunction in individuals with mutations associated with MODY. Genetic studies may provide a better understanding and classification of hyperglycemia during pregnancy.