Insulin Resistance in Gestational Diabetes Mellitus (IRIS)

This prospective cohort study investigates glycaemic variability, assessed by continuous glucose monitoring (CGM), in pregnant women with gestational diabetes mellitus (GDM) and its association with fetal growth and related maternal and neonatal outcomes. Participants will undergo 14 days of CGM during pregnancy to characterise individual glycaemic patterns. Clinical and paraclinical data, including fasting plasma glucose, HbA1c, lipid profile, organ markers of pregnancy-related medical conditions, maternal weight gain, and blood pressure will be collected at two study visits. Oral glucose tolerance test (OGTT) 2-hour values will be obtained at diagnosis. All participants will receive standard GDM care and routine obstetric follow-up for assessment of fetal growth and wellbeing. Birth weight, birth weight z-scores, and relevant neonatal outcomes will be recorded after delivery.

Statistical analyses will be performed using Stata statistical software (StataCorp LLC, College Station, TX, USA). Continuous and categorical variables will be summarised using appropriate descriptive statistics. Associations between maternal glycaemic variability and neonatal as well as other maternal metabolic outcomes will be explored using suitable statistical methods, with adjustment for relevant covariates. Exploratory analyses may include additional glycaemic variability metrics and lipid parameters to further characterise maternal metabolic patterns.

Study Overview

• Status: Recruiting
• Conditions: Gestational Diabetes Mellitus (GDM)

Detailed Description

The aim of this prospective cohort study is to investigate glycaemic variability, assessed by continuous glucose monitoring (CGM), in pregnant women with gestational diabetes mellitus (GDM), and its association with fetal growth and related maternal and neonatal outcomes.

Participants will undergo CGM for 14 consecutive days during pregnancy to characterise individual patterns of glycaemic variability. Relevant clinical and paraclinical parameters, including fasting plasma glucose, HbA1c, lipid profile (total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides), organ markers of pregnancy-related medical conditions (including liver and renal function parameters), maternal weight gain, and blood pressure will be recorded at both the commencement and after completion of the monitoring period. Oral glucose tolerance test (OGTT) 2-hour values will be retrieved from the diagnostic visit.

All participants will receive standard clinical care for GDM, including dietary counselling and routine obstetric follow-up for assessment of fetal growth and wellbeing. Following delivery, clinically relevant maternal and neonatal data, including birth weight, birth weight z-scores, and information on pregnancy or neonatal complications, will be obtained from electronic medical records.

Statistical analysis plan

Continuous variables will be assessed for distributional characteristics and summarised using appropriate descriptive statistics. Categorical variables will be presented as frequencies and percentages.

Associations between maternal glycaemic variability indices and study outcomes - including neonatal birth weight z-scores and other secondary maternal and neonatal parameters (e.g., 2-hour OGTT values, HbA1c, fasting glucose, and neonatal hypoglycaemia) will be explored using appropriate statistical methods according to data type and distribution. Multivariable models may be applied to adjust for relevant maternal and pregnancy-related covariates, including maternal age, pre-pregnancy BMI, gestational age at delivery, parity, HbA1c, and other relevant covariates where applicable.

Comparisons of glycaemic and metabolic parameters between relevant subgroups will be conducted using suitable statistical techniques selected based on data characteristics and study objectives. Categorical outcomes will be analysed using appropriate methods for comparison of proportions.

Additional glycaemic variability metrics (SD, MAGE, CONGA, and J-index) will be considered as pre-specified exploratory outcomes and may be analysed, contingent on data completeness and scientific relevance, to further characterise maternal glycaemic patterns. Exploratory analyses of associations between maternal glycaemic variability and lipid parameters (total, HDL, and LDL cholesterol, and triglycerides) may likewise be conducted on a non-primary, hypothesis-generating basis. Lipid measures may also be included as covariates in multivariable models evaluating neonatal outcomes.

All analyses will be two-tailed, and statistical significance will generally be inferred at p < 0.05. Statistical analyses will be performed using Stata statistical software (StataCorp LLC, College Station, TX, USA; current version at time of analysis).

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Ninna L Larsen, MD; Phone Number: 0045 26533336; Email: nll@clin.au.dk

Study Locations

• Denmark
  • Aarhus, Denmark, 8200
    • Recruiting
    • Aarhus University Hospital
    • Contact: Ninna L Larsen, MD; Phone Number: 0045 26533336; Email: nll@clin.au.dk
  • Herning, Denmark, 7400
    • Recruiting
    • Gødstrup Hospital
    • Contact: Ninna L Larsen, MD; Phone Number: 0045 26533336; Email: nll@clin.au.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Stated in eligibility criteria. According to in- and exculsion criteria the study population will be singleton pregnant women > 18 years of age, with gestational diabetes mellitus (GDM) between gestational age (GA) 28+0 and 34+6, without poorly controlled chronic diseases who are non-smokers and not treated with systemic corticosteroids.

Description

Inclusion Criteria:

• All singleton pregnant women with gestational diabetes mellitus (GDM) between gestational age (GA) 28+0 and 34+6 attending the obstetric outpatient clinic at Aarhus University Hospital, Aarhus, Denmark or Gødstrup Hospital, Herning, Denmark will be offered participation.

Exclusion Criteria:

• Pre-gestational diabetes
• Age < 18 years
• Multiple pregnancies
• Chronic disease that is not well-controlled and is expected to influence study outcomes (including inflammatory diseases such as rheumatologic, gastroenterological, etc.)
• Treatment with systemic corticosteroids
• Smoking
• Women who are unable to understand the oral and written patient information

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Pregnant women diagnosed with gestational diabetes mellitus; Continuous glucose monitoring for 14 days during pregnancy in women diagnosed with gestational diabetes mellitus. Delivery data are recorded, thus participants are followed up to 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Birth weight z-scores	Calculated using reference standards adjusted for gestational age and sex. Unit of measure: z-score (SD units).	Recorded immediately after delivery.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maternal glycaemic variability, Coefficient of Variation (CV)	Coefficient of variation (%) of interstitial glucose derived from 14 consecutive days of continuous glucose monitoring (CGM).	Measurements will be commenced between gestational week 28+0 and 34+6.
Maternal Time in Range (TIR)	Percentage of time with blood glucose levels within the pregnancy target range (3.9 - 7.0 mmol/l) during the 14-day CGM period.	Measurements will be commenced between gestational week 28+0 and 34+6.
Maternal Time Above Range (TAR)	Percentage of time with blood glucose levels above the pregnancy target range (3.9 - 7.0 mmol/l) during the 14-day CGM period.	Measurements will be commenced between gestational week 28+0 and 34+6.
Maternal Time Below Range (TBR)	Percentage of time with blood glucose levels below the pregnancy target range (3.9 - 7.0 mmol/l) during the 14-day CGM period.	Measurements will be commenced between gestational week 28+0 and 34+6.
2-hour oral glucose tolerance test (OGTT)	2-hour venous plasma glucose following a 75-g oral glucose tolerance test performed during routine GDM screening. Unit of measure: mmol/L.	Measured at diagnosis of gestational diabetes mellitus.
HbA1c	Maternal HbA1c levels (mmol/mol, IFCC).	Maternal HbA1c levels measured at first study visit (gestational week 28+0 to 34+6) and at the second study visit (gestational week 30+0 to birth).
Fasting blood glucose	Fasting venous plasma glucose (mmol/L).	Measured at first study visit (gestational week 28+0 to 34+6) and after completion of the measurement period, at the second study visit (gestational week 30+0 to birth).
Neonatal hypoglycaemia	Neonatal blood glucose <2.5 mmol/l.	From birth to 24 hours of life.
Birth weight	Absolute neonatal birth weight measured after delivery (grams).	Immediately after delivery.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maternal glycaemic variability, Standard Deviation (SD)	Standard deviation of interstitial glucose from continuous glucose monitoring (CGM) over 14 consecutive days. Unit of measure: mmol/L. Measurement tool: FreeStyle Libre Pro IQ.	Measurements will be commenced between gestational week 28+0 and 34+6.
Maternal glycaemic variability, Mean Amplitude of Glycaemic Excursions (MAGE)	MAGE calculated from CGM profiles over 14 consecutive days using a standard algorithm. Unit of measure: mmol/L.	Measurements will be commenced between gestational week 28+0 and 34+6.
Maternal glycaemic variability, J-index	J-index computed from mean glucose and SD over the 14-day CGM period, using the prespecified formula (J-index = 0.001 × (mean + SD)²). Unit of measure: mmol/L.	Measurements will be commenced between gestational week 28+0 and 34+6.
Maternal glycaemic variability, CONGA	Continuous Overall Net Glycaemic Action (CONGA) calculated over the prespecified lag (e.g., CONGA-1 or CONGA-2) from 14-day CGM data. Unit of measure: mmol/L.	Measurements will be commenced between gestational week 28+0 and 34+6.
Maternal lipid profile (total, HDL, and LDL cholesterol)	Maternal total cholesterol, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol measured in maternal venous blood using standardized enzymatic colorimetric assays at an accredited clinical laboratory. Unit of measure: mmol/L.	Measured at first study visit (gestational week 28+0 to 34+6) and after completion of the measurement period (gestational week 30+0 to birth).
Maternal triglycerides	Serum triglyceride concentration measured in maternal venous blood using a standardized enzymatic colorimetric assay at an accredited clinical laboratory. Unit of measure: mmol/L.	Measured at first study visit (gestational week 28+0 to 34+6) and after completion of the measurement period (gestational week 30+0 to birth).

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: Aarhus University Hospital
• Investigators: Principal Investigator: Ninna L Larsen, MD, University of Aarhus

Study record dates

Study Major Dates

• Study Start (Actual): September 22, 2022
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: September 22, 2025
• First Submitted That Met QC Criteria: November 13, 2025
• First Posted (Actual): November 17, 2025

Study Record Updates

• Last Update Posted (Actual): November 17, 2025
• Last Update Submitted That Met QC Criteria: November 13, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Pregnancy; CGM; GDM; Continuous glucose monitoring; Gestational diabetes mellitus; Diabetes in pregnancy
• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Female Urogenital Diseases and Pregnancy Complications; Metabolic Diseases; Pregnancy Complications; Glucose Metabolism Disorders; Diabetes Mellitus; Nutritional and Metabolic Diseases; Diabetes, Gestational
• Other Study ID Numbers: 1-10-72-350-21

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No