Towards Precision Medicine for Diabetes in Pregnancy

Study Overview
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Brief Summary
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Rationale: Gestational diabetes is currently treated by the one-size-fits-all-approach. Treatment efficacy is poorly defined and inconsiderate of patients clinical presentation Objective: To characterize the efficacy of pharmacological treatment of gestational diabetes mellitus between patients with distinct metabolic phenotypes Study design: Prospective observational study, in metformin-treatment efficacy is compared between patients with GDM caused by insulin resistance and patients with GDM caused by low insulin secretion. Study population: A prospective cohort of 103 women with diagnosed gestational diabetes mellitus treated by metformin. Main study parameters/endpoints: Primary outcomes is the glucose-disposition-index in late pregnancy (35-37 weeks gestation) and requirement for supplemental insulin-treatment. Secondary outcomes include insulin sensitivity (Matsuda-index), insulin secretion (Stumvoll-index), HbA1c, gestational weight gain, body composition, physical activity, eating behavior, plasma biomarkers, glucose control, and maternal and infant pregnancy outcomes.

Official Title
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Towards Precision Medicine for Diabetes in Pregnancy

Conditions
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Gestational Diabetes, Gestational Diabetes Mellitus

Intervention / Treatment
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* Drug: Metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: having a confirmed single, viable pregnancy past 20 weeks gestation. assigned to pharmacological (ie metformin) treatment for GDM. Exclusion Criteria: pre-existing diabetes, hypertension (SBP >160 mmHg & DBP >110 mmHg) using medication related to study outcomes prior to GDM diagnosis (insulin, metformin, glyburide, systemic steroids, mood stabilizers, ADHD medication) smoking or using recreational drugs that may affect pregnancy outcomes

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Low insulin sensitivity<br>Women will be classified as having low insulin sensitivity, if their Matsuda-index is in the lowest quartile of a reference cohort | Drug: Metformin<br>* All patients are diagnosed with gestational diabetes and treated with metformin (per routine clinical practice<br>|
| Low insulin secretion<br>Women will be classified as having low insulin secretion if their Stumvoll-index is in the lowest quartile of a reference cohort | Drug: Metformin<br>* All patients are diagnosed with gestational diabetes and treated with metformin (per routine clinical practice<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| glucose-disposition-index | glucose-disposition-index is calculated as product of Stumvoll- and Matsuda-index, assessed during a 75g-oral glucose tolerance test, | 35-37 weeks gestation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin treatment | requirement for additional insulin treatment | 35-37 weeks gestation | 
| HbA1c | HbA1c concentration | 24-28 and 35-37 weeks gestation | 
| Body weight | Fasting body weight, kg | 24-28 and 35-37 weeks gestation | 
| Body fat mass | Fasting body fat mass, in kg | 24-28 and 35-37 weeks gestation | 
| Physical Activity | Average steps per day, measured over 7-day period using accelerometry | 24-28 and 35-37 weeks gestation | 
| Dietary intake | Average energy intake, measured over 7 days using online dietary records | 24-28 and 35-37 weeks gestation | 
| Glucose control | Time in range (3-10 mol/l), measured over 7 days using continuous glucose monitors | 24-28 and 35-37 weeks gestation | 
| Delivery complications | occurence and type of complications during delivery | Birth | 
| Neonatal body weight | Neonatal body weight | at birth, and at 6 weeks of age | 
| Neonatal body length | Neonatal body length | at birth, and at 6 weeks of age | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metformin, insulin sensitivity, insulin secretion, continuous glucose monitoring, physical activity