Insulin Resistance in Gestational Diabetes Mellitus

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).

• Maternal glycaemic variability, Coefficient of Variation (CV) [Срок оценки: Measurements will be commenced between gestational week 28+0 and 34+6.]
• Maternal Time in Range (TIR) [Срок оценки: Measurements will be commenced between gestational week 28+0 and 34+6.]
• Maternal Time Above Range (TAR) [Срок оценки: Measurements will be commenced between gestational week 28+0 and 34+6.]
• Maternal Time Below Range (TBR) [Срок оценки: Measurements will be commenced between gestational week 28+0 and 34+6.]
• 2-hour oral glucose tolerance test (OGTT) [Срок оценки: Measured at diagnosis of gestational diabetes mellitus.]
• HbA1c [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: From birth to 24 hours of life.]
• Birth weight [Срок оценки: Immediately after delivery.]