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Observational Study
. 2025 May;68(5):981-992.
doi: 10.1007/s00125-025-06363-0. Epub 2025 Feb 19.

Pregnancy and neonatal outcomes in women with GCK-MODY: an observational study based on standardised insulin modalities

Cécile Ciangura  1   2 , Aurélien Seco  3 , Cécile Saint-Martin  4   5 , Pierre-Yves Ancel  3   6 , Delphine Bouvet  4   5 , Sophie Jacqueminet  7   4 , Agnès Hartemann  7   4 , Jacques Lepercq  8 , Jacky Nizard  9 , José Timsit  4   10 , Christine Bellanné-Chantelot  4   5 ; Monogenic Diabetes Study Group of the Société Francophone du Diabète
Collaborators, Affiliations
Observational Study

Pregnancy and neonatal outcomes in women with GCK-MODY: an observational study based on standardised insulin modalities

Cécile Ciangura et al. Diabetologia. 2025 May.

Abstract

Aims/hypothesis: The management of GCK-MODY during pregnancy remains challenging. We evaluated the impact on pregnancy and neonatal outcomes of two standardised insulin strategies.

Methods: In this prospective observational study, participants chose (in agreement with their physician) to be treated with insulin either when maternal capillary blood glucose (CBG) ≥ thresholds for gestational diabetes (5.3 mmol/l before or 6.7 mmol/l 2 h after meals) (MG group) or when fetal abdominal circumference ≥75th percentile (FG group). In the FG group, insulin was also initiated if CBG ≥ safety levels (6.7 mmol/l before meals or 11.1 mmol/l 2 h after meals). Data on glycaemic management, modalities and timing of insulin therapy and maternal and neonatal outcomes were recorded.

Results: In the MG group (n=25), insulin was initiated more frequently (100% vs 75%, p=0.01) and earlier (p=0.001), with lower CBG and more frequent hypoglycaemic episodes compared with the FG group (n=21). However, there were no differences in pregnancy and neonatal outcomes. In the total cohort, the rate of large for gestational age (LGA) neonates, preterm deliveries and Caesarean sections was 22.2%, 2.2% and 40%, respectively. The rate of LGA was 0% among the neonates with the GCK variant vs 36% in those without (p=0.005). There were no associations between LGA and pregnancy characteristics, insulin therapy strategy or glycaemic management.

Conclusions/interpretation: In our study, the rate of LGA primarily depended on the fetal GCK genotype rather than the treatment strategy or glycaemic management. Our results suggest that a standardised strategy based on ultrasound monitoring of fetal growth and glycaemic safety thresholds, leading to delayed insulin initiation, offers a good fetal prognosis and minimises the risk of maternal hypoglycaemia.

Trial registration: ClinTrials.gov NCT02556840.

Keywords: GCK-MODY; Fetal abdominal circumference; Glucokinase; Insulin therapy; Large for gestational age; Macrosomia; Neonatal outcomes; Pregnancy; Ultrasound.

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Conflict of interest statement

Acknowledgements: The authors would like to thank all participants of the study, all the clinicians involved in the follow-up of the participants, the members of the Monogenic Diabetes Study Group of the Société Francophone du Diabète and the Unité de Recherche Clinique (URC) of Cochin Hospital in Paris, France, for expert help and support in conducting this study. The collaborators/members of the Monogenic Diabetes Study Group of the Société Francophone du Diabète are as follows: Salha Fendri (University Hospital of Amiens-Picardie, Department of Endocrinology, Metabolic Disease and Nutrition, Amiens, France); Ingrid Allix, Sandrine Laboureau (Angers University Hospital, Department of Endocrinology, Diabetology and Nutrition, Angers, France); Annie Clergeot, Sylvie Grandperret-Vauthier (University Hospital of Besançon, Department of Diabetology-Endocrinology, Besançon, France); Emmanuel Sonnet (University Hospital of Brest, Hospital La Cavale Blanche, Department of Diabetology and Endocrinology, Brest, France); Yves Reznik, Anne Rod (University Hospital Caen-Normandie, Department of Diabetology and Endocrinology, Caen, France); Anne Mayer (Hospital Métropole Savoie, Department of Endocrinology-Diabetology, Chambéry, France); Marie Batisse-Lignier, Magalie Miolane (University Hospital of Clermont-Ferrand, Department of Endocrinology and Metabolic Diseases, Clermont-Ferrand, France); Alfred Penfornis, Rabah Bensebaa (Hospital Sud Francilien, Department of Diabetology and Endocrinology, Corbeil-Essonnes; Université Paris-Saclay, France); Hélène Affres, Isabelle Le Roux (AP-HP, Bicêtre Hospital, Department of Reproductive Endocrinology, Le Kremlin Bicêtre, France); Anne Vambergue (Claude Huriez Hospital, Department of Diabetology, Endocrinology, Metabolism and Nutrition, Lille, France); Noémie Dubois, Marie-Françoise Jannot-Lamotte, Catherine Mattei, René Valéro (Aix Marseille Univ, APHM, Inserm, INRAE, C2VN, University Hospital La Conception, Department of Nutrition, Metabolic Diseases and Endocrinology, Marseille, France); Stéphanie Malvaux, Térésa Créa (Regional Hospital of Metz-Thionville, Department of Diabetology and Endocrinology, Metz-Thionville, France); Sylvie Hieronimus (University Hospital of Nice, Department of Endocrinology, Diabetology, Reproduction, Nice, France); Marc Diedisheim, David Joseph Levy, Jocelyne M Bemba (AP-HP, Cochin-Port-Royal Hospital, Department of Diabetology, Paris, France); Anne Dierick-Gallet (AP-HP, Pitié-Salpêtrière Hospital, Department of Diabetology Paris, France); Nathalie Bourcigaux (AP-HP, Saint-Antoine, Department of Endocrinology, Diabetology and Endocrinology of Reproduction, Paris France); Régis Cohen (Hospital of Saint Denis, Department of Diabetology-Endocrinology, Saint Denis, France); Sylvie Sanchis (University Hospital of Strasbourg, Department of Endocrinology, Diabetology and Nutrition, Strasbourg, France); Magali Coustols-Valat, Frédérique Rimareix (Rangueil et Paule de Viguier Hospital, Department of Diabetology, Toulouse, France). Data availability: The data are available on request from the corresponding author. Funding: Our study was supported by grant 14-0247 from the Programme Hospitalier de Recherche Clinique (PHRC, France). Authors’ relationships and activities: The authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work. Contribution statement: CC, JT, CB-C, JL, JN, SJ, AH, CS-M, DB, P-YA and AS were involved in the conception, design, conduct of the study and the analysis and interpretation of the results. CC, JT and CB-C wrote the first draft of the manuscript, and all authors edited, reviewed and approved the final version of the manuscript. CC is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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