Impact on Birth Weight of Two Therapeutic Strategies (Insulin Therapy From the Beginning of Pregnancy vs. Insulin Therapy Initiated According to Fetal Growth Evaluated by Ultrasonography Measurements) in Pregnant Women With Monogenic Diabetes

NCT02556840 | Completed

• 2 other identifiers: P1409192015-A00261-48
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

Maturity-onset diabetes of youth (MODY) are the most frequent monogenic diabetes with autosomic dominant inheritance (2% of diabetes). The MODY2 diabetes is related to a defect in the glucokinase (GCK) enzyme, the first limiting step of insulin secretion. An abnormal GCK leads to a delayed insulin secretion. Patients with GCK mutations have only mild raised fasting plasma glucose. Treatment is usually unnecessary since hyperglycemia is stable and MODY2 patients have no microvascular complications of diabetes. In contrast, pregnancy in MODY2 women is a challenging situation. A non-mutated fetus will produce excess insulin in response to raised maternal blood glucose leading to an accelerated growth and a higher risk of macrosomia. The mother of non-mutated fetus should therefore be treated to normalize her blood glucose levels. On contrary, a mutated fetus will produce a delayed insulin secretion (as his MODY2 mother) in response to maternal hyperglycemia. Consequently insulin therapy during pregnancy would reduce fetal insulin secretion and result in a low birth weight. Moreover, insulin therapy exposes pregnant women to more labor induction, prematurity and cesarean deliveries. In these MODY2 women whose glucose set point is physiologically higher, glycemic goals are difficult to achieve while often requiring extensive insulin therapy. An optimal situation would consist in initiating insulin therapy only for women with non-mutated offsprings. Unfortunately no antenatal diagnosis of the GCK mutation on fetal cells is available yet. In literature, birth weight differences between mutated and non-mutated neonates may reach up to 700g. In clinical practice, two strategies are used but without standardized protocol on glycemic targets, delay and doses of insulin : 1) insulin at diagnosis of pregnancy 2) treatment based on fetal abdominal circumference and fetal weight measurements by ultrasonography (US) and initiated if fetal biometry is greater than the 75th percentile. The purpose of the study is to evaluate for the first time these two management strategies through a prospective and standardized study. Hypothesis: US assessment would be sufficient to identify fetuses at risk of macrosomia and to initiate insulin treatment in mothers.

Conditions

Maturity-Onset Diabetes of the Young

Keywords

Monogenic diabetes; maturity-onset diabetes of the young; MODY; Pregnancy; Gestational diabetes; Glucokinase; Insulin therapy during pregnancy; Evaluation of fetal growth by ultrasonography measurements

Outcome Measures

Primary Outcomes (1)

• Birth weight for gestational age

  this end point will sustain two derived criteria: birth weight for gestational age as a quantitative criterion and birth weight considered as small (below the 10th percentile), normal, or large (above the 90th percentile).

  at birth

Secondary Outcomes (26)

• Number of neonatal hypoglycaemia

  at birth

• Number of hyperinsulinemia

  at birth

• Neonatal leptin level

  at birth

• Number of fetal and neonatal complications

  at birth

• Composite obstetrical outcome

  at birth

Study Arms (2)

Insulin therapy from the beginning of pregnancy

ACTIVE COMPARATOR

Insulin therapy (Glargine/Lantus®, Détémir/Levemir® , Insulatard® , Umuline NPH® , Lispro/Humalog® , Asparte/Novorapid® or Actrapid ®) administered from the beginning of pregnancy according to maternal blood glucose (if fasting blood glucose \> 0.95g/l or post-prandial blood glucose \> 1.20g/l) as recommended by the national guidelines for gestational diabetes mellitus. Insulin administered to patients either by subcutaneous injections or by pump.

Other: insulin therapy

Insulin therapy initiated according to fetal growth

EXPERIMENTAL

Insulin therapy (Glargine/Lantus®, Détémir/Levemir® , Insulatard® , Umuline NPH® , Lispro/Humalog® , Asparte/Novorapid® or Actrapid ®) initiated according to fetal growth evaluated by ultrasonography measurements. MODY2 women will not be treated with insulin until delivery, except when the fetal abdominal circumference exceeds ≥ the 75 percentile on one US or maternal fasting capillary blood glucose is ≥ 1,20 g/L or maternal post-prandial capillary blood glucose is ≥ 2,00 g/L. Insulin administered to patients either by subcutaneous injections or by pump.

Other: insulin therapy

Interventions

insulin therapy OTHER

Insulin therapy from the beginning of pregnancy; Insulin therapy initiated according to fetal growth

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women diagnosed with a GCK mutation before pregnancy
• Aged ≥ 18 years old
• Pre-gestational BMI \< 30kg/m²
• Term of pregnancy \< 14 WG , if delay overdue, to be validated by investigators
• Written informed consent

You may not qualify if:

• Twin pregnancy
• Not able to understand and sign written informed consent
• Not affiliated to the French Social Security

Sponsors & Collaborators

• URC-CIC Paris Descartes Necker Cochin: collaborator
• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

La Pitié Salpêtrière Hospital

Paris, 75651, France

Location

Related Publications (1)

• Ciangura C, Seco A, Saint-Martin C, Ancel PY, Bouvet D, Jacqueminet S, Hartemann A, Lepercq J, Nizard J, Timsit J, Bellanne-Chantelot C; Monogenic Diabetes Study Group of the Societe Francophone du Diabete. Pregnancy and neonatal outcomes in women with GCK-MODY: an observational study based on standardised insulin modalities. Diabetologia. 2025 May;68(5):981-992. doi: 10.1007/s00125-025-06363-0. Epub 2025 Feb 19.

  PMID: 39971752 RESULT

MeSH Terms

Conditions

Mason-Type Diabetes; Diabetes Mellitus, Type 2; Diabetes, Gestational; Maturity-Onset Diabetes of the Young, Type 2

Interventions

Convulsive Therapy

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Psychiatric Somatic Therapies; Behavioral Disciplines and Activities

Study Officials

• Christine Bellanné-Chantelot, PharmaD, PhD

  Assistance Publique - Hôpitaux de Paris

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2015
• First Posted: September 22, 2015
• Study Start: April 25, 2016
• Primary Completion: August 1, 2020
• Study Completion: December 9, 2020
• Last Updated: March 27, 2026

Record last verified: 2026-03

Locations

FR (1)