Effects of Moderate Carbohydrate Consumption on Metabolic and Obstetric Outcomes in Pregnant Women With Insulin-treated Diabetes- A Randomized Controlled Trial

NCT ID: NCT06355154

Last Updated: 2025-10-02

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-05-28
• Study Completion Date: 2028-02-01

Brief Summary

Diabetes during pregnancy increases maternal and fetal complications, necessitating optimal glycemic control. The standard care diet (SCD, ≥175g/day carbohydrate) lacks robust evidence, particularly for pregnancies requiring intensive insulin treatment (IIT). This RCT investigates whether a moderate carbohydrate diet (MCD, ≤120g/day) versus SCD improves glycemic control and alters metabolomic profiles in pregnant individuals on IIT.

Aims: To compare the efficacy and safety of a SCD versus MCD on glycemic control, metabolomic signatures, and pregnancy outcomes in pregnant individuals on IIT.

Detailed Description

Effects of moderate carbohydrate consumption on metabolic and obstetric outcomes in pregnant women with insulin-treated diabetes- A randomized controlled trial

1. Scientific Background:

1.1 Diabetes Mellitus in Pregnancy: Diabetes during pregnancy (pre-gestational type 1 or 2, or gestational diabetes) is associated with complications for both the mother (polyhydramnios, miscarriage, hypertension, preeclampsia, need for instrumental delivery) and the fetus/neonate (birth defects, macrosomia, shoulder dystocia, respiratory distress, hyperbilirubinemia, hypoglycemia). (1),(2) ,(3),(4). The incidence of all forms of diabetes during reproductive age is increasing(5).

1.2 Dietary carbohydrate consumption during pregnancy: Current guidelines recommend a minimum carbohydrate consumption of 175g/day for all pregnant women, regardless of diabetes status. This is based on a theoretical calculations rather than clinical evidence (6). Some concerns with carbohydrate restriction during pregnancy include disrupting the maternal-fetal glucose gradient, increased fetal ketone exposure, micronutrient deficiency, and increased maternal triglycerides/free fatty acids(7).

However, recent studies found no correlation between moderate carbohydrate restriction (<175g/day but >120g/day) and increased ketosis(8),(9),(10). Reducing carbohydrates may help reduce postprandial hyperglycemia in patients on intensive insulin therapy(11),(12).These findings call into question the hypothetical assumption that a minimum of 175 gr of CHO is required during pregnancy.

2. Research Objective:

The primary objectives of the trial are to determine:

• To assess the effectiveness and safety of moderate carbohydrate consumption restriction (MCD) in enhancing glycemic control.
• To investigate the impact of MCD on the metabolomic profile of pregnant individuals with diabetes requiring intensive insulin treatment (MDI/CII).

3. Expected Significance:

The importance of this study lies in:

1. Challenging the commonly accepted but theoretical recommendation of 175g/day minimum carbohydrate intake during pregnancy.

2. Evaluating if moderate carbohydrate restriction can improve glycemic control and pregnancy outcomes in women with diabetes requiring intensive insulin therapy, without major adverse effects.

4.Detailed Description of the Proposed Research: 4.1 Study Design: This is an open label, randomized controlled trial comprising 120 pregnant individuals (18-45 years) with any form of diabetes requiring intensive insulin therapy. Pregnant individuals on IIT will be randomized to standard carbohydrate diet (>175g/day) or moderate carbohydrate diet (120g/day) group.

Key Measurements/Data Collection:

• Continuous glucose monitoring (CGM) to assess time in range (TIR) and other glycemic parameters.
• Anthropometrics (weight, height, BMI).
• Dietary intake data (FFQs, 24-hr recalls, 3-day food diaries).
• Blood tests (HbA1c, glucose, c-peptide, lipids, etc).
• Fetal growth monitoring via ultrasound.
• Cord blood c-peptide at delivery.
• Neonatal and maternal post-delivery outcomes (mode of delivery, weight, complications, etc).
• Maternal metabolomics (fasting blood sample). 4.3 Study Visits:
• Screening/baseline visit to assess eligibility.
• Dietary counseling and medical team visits every 2 weeks until 32 weeks, then weekly or as be decided by the medical team according to patients needs.
• Fetal ultrasounds start at 28 weeks, twice monthly or more.
• Final visit at 35-38 weeks for metabolomics sample. 4.4 Safety Monitoring:
• No intended calorie restriction.
• CGM to adjust insulin and avoid hypoglycemia.
• Home ketone monitoring.
• Ultrasound fetal growth monitoring. 4.5 Metabolomics Analysis:
• LC-MS analysis to detect >400 metabolites.
• Assess effects on micronutrients, carbs, lipids, ketones, amino acids.
• Identify metabolic pathways affected and correlate with pregnancy outcomes. 4.6 Research Calculation: 120 participants total (60 per group). 80% power to detect 7% difference in time in range (TIR) between group. Assumptions based on literature, including CONCEPTT study standard deviation 4.7 Ethical Approval: Study will follow Declaration of Helsinki. Institutional ethics approval obtained 5. Research Environment: The study will be conducted at 3-4 major medical centers in Israel with expertise in high-risk pregnancies. Qualified clinical staff including doctors, nurses, dietitians and researchers will be involved in participant recruitment, intervention delivery, data collection and analysis. Necessary equipment like CGMs, metabolomics instruments, etc. are available at these sites.

Conditions

Diabetes in Pregnancy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

The Standard of Care diet

(a diet that includes at least 175 grams of carbohydrates per day or more/ \>40% CHO, SCD)

Group Type: NO_INTERVENTION

No interventions assigned to this group

The moderate carbohydrate diet

(a diet with 120 grams of carbohydrates and customized according to pregnancy requirements/ \<40% CHO, MCD)

Group Type: EXPERIMENTAL

Nutritional intervention

Intervention Type: OTHER

The intervention will contain a diet with a reduced amount of carbohydrates compared to the standard treatment today but without caloric restriction.

Interventions

Nutritional intervention

The intervention will contain a diet with a reduced amount of carbohydrates compared to the standard treatment today but without caloric restriction.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• • Pregnant women with singleton pregnancies.

• Over 18 years old.
• Diagnosis of GDM- 3-h 100-g OGTT according to the American College of Obstetricians and Gynecologists supported by the American Diabetes Association, Or Diagnosis of type 1 or 2 diabetes before pregnancy, Or Diagnosis of early GDM by either OGTT in the first trimester or elevated blood glucose measurements in the fasting (above 95mg/dl) or the postprandial (above 140 mg/dl) state.
• Are already on or intended to start intensive insulin treatment (at leased 2 injections of insulin per day) or wear an insulin pump.
• Are willing to wear a continuous glucose monitoring system.
• BMI of 18.5-42 kg/m2 at the time of diagnosis.

Exclusion Criteria

• Individual with risk factors for:

• Placental insufficiency.
• Hypertension.
• Renal disease.
• Thrombophilia
• Rheumatologic disease.
• A history of preeclampsia, or fetal growth restriction (IUGR).
• Individuals with a history of preterm labor, or concomitant therapy with β-blockers or glucocorticoids.
• Individuals who smoke and/or consume any amount of alcohol during pregnancy.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Hadassah Medical Organization

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Hadassah Hospital

Jerusalem, , Israel

Site Status: RECRUITING

Countries

Israel

Central Contacts

Genya Aharon Hananel, DR MD PHD

Role: CONTACT

Genyah@hadassah.org.il

0525576455

naama shirazi, mrs

Role: CONTACT

naamon20@gmail.com

0524664668

Facility Contacts

Genya hananel aharOn, MD PHD

Role: primary

Genyah@hadassah.org.il

+972- 52-557-6455

Naama Shirazi, RD MSC

Role: backup

naamon20@gmail.com

+972-52-466-4668

References

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Reference Type: BACKGROUND

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Shalit1 R, Dayan2 N, Yoeli-Ullman2 R, , T. Cukierman-Yaffe1 3; The relationship between low carbohydrate diet and pregnancy outcomes in women with pre_gestational diabetes: a historical prospective study. EASD [Internet]. Barcelona; 2019. Available from: https://www.easd.org/media-centre/home.html#!resources/the-relationship-between-low-carbohydrate-diet-and-pregnancy-outcomes-in-women-with-pre-gestational-diabetes-a-historical-prospective-study

Reference Type: BACKGROUND

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Other Identifiers

069823- HMO-CTIL

Identifier Type: -

Identifier Source: org_study_id