Gestational Diabetes
Conditions
Brief summary
The main objective of the study is to investigate the metabolic effects of whey protein (whey protein isolate, WPI, (Lacprodan® ISO.Water. from Arla Foods Ingredients) compared with placebo when consumed by women with gestational diabetes mellitus (GDM) from diagnosis (around gestational week 28) to delivery. Any changes in substrate metabolism and energy expenditure using indirect calorimetry will also be investigated. Differences in hunger and satiety parameters as well as blood pressure and gestational weight gain will also be assessed. Furthermore, analysis on the glucose response when the women consume the intervention (whey or placebo) at home in their own environment 30 minutes before breakfast at time of diagnosis (earliest week 28) and week 36 (four days following each time point) will be made. The women will be monitored with continuous glucose monitors, activity monitors and all meals will be provided for two days following the study days in the laboratory. At delivery cord blood will be sampled for analysis on metabolic parameters and investigations on epigenetics/DNA methylations. Complications to the delivery, neonatal outcomes, anthropometrics of the child will also be assessed. Breast milk composition will also be analyzed.
Interventions
DIETARY_SUPPLEMENTWhey
20 g protein of whey protein isolate WPI (Lacprodan® ISO.Water. from Arla Foods Ingredients)
DIETARY_SUPPLEMENTPlacebo
The placebo contains \<1 kcal and 0 g protein
Sponsors
University of Aarhus
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* GDM (OGTT level of blood glucose ≥ 9 mmol/L) * Normal blood pressure * Age \> 18 years
Exclusion criteria
* Special dietary regimes \> 1 month at time of inclusion e.g. ketogenic diet * Daily intake of protein supplements * Milk allergy or phenylketonuria * Medication with effect on glucose metabolism e.g. steroids * Do not speak or understand Danish * Twin pregnancy * PCOS * PI finds the patient unfit (like mental illness, too nervous or other) * Severe chronic illness * Severe nausea/vomiting * Non-breakfast eaters * Celiac disease The initiation of insulin treatment during the trial will not lead to exclusion from the trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maternal glycemic variability (GV) | 24 hours | The Coefficient of Variation, power: n = 50 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Blood pressure | at diagnosis, week 32 and week 36 | Systolic and diastolic blood pressure |
| Non-targeted metabolomics will be performed on a sample of breast milk using Nuclear Magnetic Resonance | Day 1 postpartum | Analysis generating metabolites from pathways on amino acids, peptides, carbohydrates and lipids measured in folds increase/decrease when comparing placebo with whey |
| 24 hours interstitial fluid glucose measures | 24 hours | Continuous glucose monitoring |
| mean glucose | 24 hours | Continuous glucose monitoring |
| maximum glucose | 24 hours | Continuous glucose monitoring |
| Interstitial fluid glucose concentrations | 3 hours following breakfast | Continuous glucose monitoring |
| Total energy expenditure | 24 hours | Measured with a combined accelerometer and heart rate monitor, reported in kcal |
| Activity energy expenditure | 24 hours | Measured with a combined accelerometer and heart rate monitor, reported in kcal |
| Activity count | 24 hours | Measured with a combined accelerometer and heart rate monitor, reported in counts |
| Heart rate | 24 hours | Measured with a combined accelerometer and heart rate monitor, reported in beats per minute |
| Resting energy expenditure (REE) (Resting Metabolic Rate) | Performed for 20 minutes | Indirect calorimetry |
| Respiratory quotient (RQ) | Performed for 20 minutes | Indirect calorimetry |
| Oxidation rates of lipid, carbohydrate and protein | Performed for 20 minutes | Indirect calorimetry |
| Diet diary | 24 hours | Total energy intake, composition of macronutrients |
| Self-reported appetite | 3,5 hours following intake of whey/placebo at diagnosis, week 32 and week 36 | Questionnaire: A numerical rating scale ranging from not at all = 0 to extremely = 10 will be used to assess Hunger, Fullness, Satiety, Desire, Prospective consumption (Quantity). |
| Body Mass Index | at diagnosis, week 32 and week 36 | weight and height will be combined to report BMI in kg/m\^2 |
| Gestational weight change | at diagnosis, week 32 and week 36 | — |
| Medications | from diagnosis to delivery | number of participants prescribed insulin, dose of insulin, time to insulin. Methyldopa, nifidipin or labetalol (medication to lower blood pressure) |
| Pregnancy data | from diagnosis to delivery | Number of participants with hypertension, preeclampsia, maternal weight gain |
| Concentration differences in lactate (cord blood, offspring) | at delivery | — |
| Concentration differences in Insulin like growth factor I (IGF-1) (mother) | at diagnosis, week 32 and week 36 | — |
| Concentration differences in IGF-binding protein 3 (IGFBP-3) (mother) | at diagnosis, week 32 and week 36 | — |
| Concentration differences in IGF-binding protein 1 (IGFBP-1) (mother) | at diagnosis, week 32 and week 36 | — |
| Concentration differences in FGF-21 (mother) | at diagnosis, week 32 and week 36 | — |
| Concentration differences in Leptin (mother) | at diagnosis, week 32 and week 36 | — |
| Concentration differences in Adiponectin (mother) | at diagnosis, week 32 and week 36 | — |
| Concentration differences in CRP (mother) | at diagnosis, week 32 and week 36 | — |
| Concentration differences in Prolactin (mother) | at diagnosis, week 32 and week 36 | — |
| Concentration differences in Cortisol (mother) | at diagnosis, week 32 and week 36 | — |
| Concentration differences in Insulin (mother) | at diagnosis, week 32 and week 36 | — |
| Concentration differences in Free Fatty Acids (mother) | at diagnosis, week 32 and week 36 | — |
| Concentration differences in lactate (mother) | at diagnosis, week 32 and week 36 | — |
| Concentration differences in grehlin (mother) | at diagnosis, week 32 and week 36 | — |
| Concentration differences in inflammatory markers (IL-6, IL-10, IL-1α, IFN-γ, TNF-α)(mother) | at diagnosis, week 32 and week 36 | — |
| Concentration differences in glucose independent peptide (GIP) (mother) | at diagnosis, week 32 and week 36 | — |
| Concentration differences in glucagon like peptide 1 (GLP-1) (mother) | at diagnosis, week 32 and week 36 | — |
| Concentration differences in glucagon (mother) | at diagnosis, week 32 and week 36 | — |
| Concentration differences in c-peptide (mother) | at diagnosis, week 32 and week 36 | — |
| Concentration differences in amino acids (AA) (mother) | at diagnosis, week 32 and week 36 | — |
| Concentration differences in progesterone (mother) | at diagnosis, week 32 and week 36 | — |
| Concentration differences in steroid hormone binding protein (SHBP) (mother) | at diagnosis, week 32 and week 36 | — |
| Concentration differences in carboxy-terminal collagen crosslinks (CTx) (mother) | at diagnosis, week 32 and week 36 | — |
| Concentration differences in osteocalcin (OCN) (mother) | at diagnosis, week 32 and week 36 | — |
| Concentration differences in Pro-collagen I, N-term. pro-peptide (PINP) (mother) | at diagnosis, week 32 and week 36 | — |
| Concentration differences in Human chorionic gonadotropin (HCG) (mother) | at diagnosis, week 32 and week 36 | — |
| Concentration differences in CD163 (mother) | at diagnosis, week 32 and week 36 | — |
| Concentration differences in estradiol (mother) | at diagnosis, week 32 and week 36 | — |
| Concentration differences in hb1ac (mother) | at diagnosis, week 32 and week 36 | — |
| Concentration differences in lipids (cholesterol, triglyceride) (mother) | at diagnosis, week 32 and week 36 | — |
| Concentration differences in Insulin (cord blood, offspring) | at delivery | — |
| Concentration differences in c-peptide (cord blood, offspring) | at delivery | — |
| Concentration differences in glucagon (cord blood, offspring) | at delivery | — |
| Concentration differences in glucose (cord blood, offspring) | at delivery | — |
| Differences in pH (cord blood, offspring) | at delivery | Measurement of acidity of the blood. Standard measurement performed on a sample of cord blood when a baby is delivered to evaluate possible oxygen deficiency during delivery. |
| non-targeted metabolomics analysis (cord blood, offspring) | at delivery | Analysis generating metabolites from pathways on amino acids, peptides, carbohydrates, lipids and energy measured in folds rise/fall in when comparing placebo with whey |
| DNA methylations measured with 850K-Illumina Infinium assay. | at delivery | Differentially methylated sites or regions associated with the intervention will be assessed. |
| RNA-Seq transcriptome profiling | at delivery | Up and down-regulated genes associated with the intervention will be assessed |
| Body fat (offspring) | at delivery | Sum of skinfolds measured with a caliper |
| Birth weight (offspring) | at delivery | — |
| Head circumference (offspring) | at delivery | — |
| Delivery data | at delivery | Number of patients with cesarean section, shoulder dystocia, induction of labour |
| Length (offspring) | at delivery | — |
| Number of infants with icterus | through hospital admission immediately after delivery | — |
| Apgar-score | at delivery | Apgar score, range from 0-10, with the higher score the better outcome. |
| number of patients needing early feeding | through hospital admission immediately after delivery | — |
| Number of days admitted immediately after delivery | through hospital admission immediately after delivery | — |
| Number of infants with hypoglycemia | at delivery | — |
| Weight of placenta | at delivery | — |
| abdominal circumference (offspring) | at delivery | — |
Countries
Denmark
Outcome results
None listed