Insulin sensitivity in preterm appropriate-for-gestational-age and small-for-gestational-age infants

• Register: ISRCTN
• Last refreshed on: 7 September 2021
• Main ID: ISRCTN45943101
• Date of registration: 26/02/2007
• Prospective Registration: Yes
• Primary sponsor: Diabetes Fonds Nederland (The Netherlands)
• Public title: Insulin sensitivity in preterm appropriate-for-gestational-age and small-for-gestational-age infants
• Scientific title: Insulin sensitivity in preterm appropriate-for-gestational-age and small-for-gestational-age infants
• Date of first enrolment: 01/04/2007
• Target sample size: 16
• Recruitment status: Completed
• URL: https://www.isrctn.com/ISRCTN45943101
• Study type: Observational
• Study design: Observational study (Other)
• Phase: Not Specified

Countries of recruitment

Netherlands

Contacts

• Name: H P Sauerwein

Key inclusion & exclusion criteria

Inclusion criteria:
1. Premature infants 28 to 32 weeks gestational age
2. Presence of a (central) venous and arterial catheter for clinical reasons
3. For preterm SGA infants: growth retardation caused by placental insufficiency, assessed by maternal history (pregnancy induced hypertension, preeclampsia), and confirmed by Doppler flow measurements of the umbilical arteries (Pulsatility Index [PI] more than +2 Standard Deviation [SD] for gestational age, measured on two occasions)

Exclusion criteria:
1. For preterm SGA infants: growth retardation based on other causes (e.g. congenital infections, congenital malformations)
2. Major congenital malformations
3. Severe perinatal asphyxia defined as five minute Apgar score less than seven
4. Severe disturbances of glucose metabolism (glucose intake less than 4 or more than 8 mg.kg-1.min-1, or need for insulin therapy to maintain the glucose concentration between 2.6 and 8 mmol/l)
5. Severe respiratory distress. Mild ventilatory support is allowed:
a. nasal Continuous Positive Airway Pressure (nCPAP) with maximum Fraction of Inspired Oxygen (FiO2) of 0.40, maximum Positive End Expiratory Pressure (PEEP) 6 cm Water (H2O)
b. Synchronised Intermittent Mandatory Ventilation (SIMV) with maximum inspiratory peak pressure of 18 cm H2O and maximum FiO2 of 0.40
c. High Frequency Oscillatory Ventilation (HFOV) with maximum continuous distending pressure of 12 cm H2O and maximum FiO2 of 0.30
6. Need of vasopressor support for hypotension
7. Treatment with systemic corticosteroids
8. Clinical or laboratory evidence of sepsis: lethargy or irritability, hypo- or hyperthermia, temperature instability, tachypnea, apnea, bradycardia, hypotension, gastric retention, abdominal distension, pallor, elevated C- Reactive Protein (CRP)-level, leukocytosis or leukocytopenia and increased number of band neutrophils
9. Low haemoglobin level at the study days with need for a blood transfusion
10. Positive family history for type two diabetes in first degree relatives
11. No informed consent from parents or legal guardians


Age minimum:
Age maximum:
Gender: Not Specified

Health Condition(s) or Problem(s) studied

Small for gestational age, prematurity, insulin sensitivity
Pregnancy and Childbirth
Prematurity

Intervention(s)

Methods used:
1. Glucose concentration: this will be measured with the glucose oxidase method using a Beckman Glucose Analyzer 2 (Beckman, Fullerton, CA)
2. Insulin: this will be determined with a chemiluminescent immunometric assay (Immulite 2000, Diagnostic Products Corporation, Los Angeles, USA)
3. Free Fatty Acid (FFA) concentration: this will be determined with an enzymatic colorimetric method (NEFA-C test kit, Wako Chemicals GmbH, Neuss, Germany)
4. Cortisol: this will be determined with a chemiluminiscent immunoassay (Immulite 2000, Diagnostic Products Corporation, Los Angeles, USA)
5. Adiponectin: this will be determined by a radioimmunoassay (Linco, St. Charles, USA)
6. Stable isotope measurements: Newborns are infused with [U-13C] glucose and [2-13C] glycerol. Isotope dilution and label incorporation will be determined by gas chromatography mass spectrometry (GCMS) and mass isotopomer distribution analysis (MIDA) in glucose, isolated from plasma

Calculations:
1. Rate of appearance (Ra) of glucose during steady state is calculated by the isotope dilution technique from the [U-13C] enrichment of glucose, using calculations for steady state kinetics, adapted for the use of stable isotopes: Ra = (Ei/Ep) × I, where Ei and Ep are the enrichments of infusate and plasma respectively, and I is the infusion rate of [U-13C] glucose
2. Rate of disappearance (Rd): rate of exogenous glucose infusion plus the rate of endogenous glucose production
3. Endogenous glucose production: Rate of appearance minus rate of exogenous glucose infusion
4. Absolute gluconeogenesis: fractional glucon

Primary Outcome(s)

Rate of appearance and disappearance of glucose during insulin infusion

Secondary Outcome(s)

1. Rate of gluconeogenesis and glycogenolysis
2. Plasma Free Fatty Acid (FFA) concentrations
3. Plasma concentrations of insulin, cortisol and adiponectin

Secondary ID(s)

NL874 (NTR888)

Nil known

Source(s) of Monetary Support

Academic Medical Centre (AMC) (The Netherlands)

Ethics review

Status:
Approval date:
Contact:

Approval received from the Central Committee on Research inv. Human Subjects on the 30th January 2006 (ref: P05.1488C).

Results

• Results available: Yes
• Date Completed: 01/04/2008