title: Early insulin therapy in very-low-birth-weight infants.
abstract: BACKGROUND
  Studies involving adults and children being treated in intensive care units indicate that insulin therapy and glucose control may influence survival. Hyperglycemia in very-low-birth-weight infants is also associated with morbidity and mortality. This international randomized, controlled trial aimed to determine whether early insulin replacement reduced hyperglycemia and affected outcomes in such neonates.
  
  
  METHODS
  In this multicenter trial, we assigned 195 infants to continuous infusion of insulin at a dose of 0.05 U per kilogram of body weight per hour with 20% dextrose support and 194 to standard neonatal care on days 1 to 7. The efficacy of glucose control was assessed by continuous glucose monitoring. The primary outcome was mortality at the expected date of delivery. The study was discontinued early because of concerns about futility with regard to the primary outcome and potential harm.
  
  
  RESULTS
  As compared with infants in the control group, infants in the early-insulin group had lower mean (+/-SD) glucose levels (6.2+/-1.4 vs. 6.7+/-2.2 mmol per liter [112+/-25 vs. 121+/-40 mg per deciliter], P=0.007). Fewer infants in the early-insulin group had hyperglycemia for more than 10% of the first week of life (21% vs. 33%, P=0.008). The early-insulin group had significantly more carbohydrate infused (51+/-13 vs. 43+/-10 kcal per kilogram per day, P<0.001) and less weight loss in the first week (standard-deviation score for change in weight, -0.55+/-0.52 vs. -0.70+/-0.47; P=0.006). More infants in the early-insulin group had episodes of hypoglycemia (defined as a blood glucose level of <2.6 mmol per liter [47 mg per deciliter] for >1 hour) (29% in the early-insulin group vs. 17% in the control group, P=0.005), and the increase in hypoglycemia was significant in infants with birth weights of more than 1 kg. There were no differences in the intention-to-treat analyses for the primary outcome (mortality at the expected date of delivery) and the secondary outcome (morbidity). In the intention-to-treat analysis, mortality at 28 days was higher in the early-insulin group than in the control group (P=0.04).
  
  
  CONCLUSIONS
  Early insulin therapy offers little clinical benefit in very-low-birth-weight infants. It reduces hyperglycemia but may increase hypoglycemia (Current Controlled Trials number, ISRCTN78428828.)
authors.affiliation: University of Cambridge, Cambridge, United Kingdom.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Beardsall
authors.forename: Sophie
authors.initials: S
authors.lastname: Vanhaesebrouck
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Ogilvy-Stuart
authors.forename: Christine
authors.initials: C
authors.lastname: Vanhole
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Palmer
authors.forename: Mirjam
authors.initials: M
authors.lastname: van Weissenbruch
authors.forename: Paula
authors.initials: P
authors.lastname: Midgley
authors.forename: Michael
authors.initials: M
authors.lastname: Thompson
authors.forename: Marta
authors.initials: M
authors.lastname: Thio
authors.forename: Luc
authors.initials: L
authors.lastname: Cornette
authors.forename: Iviano
authors.initials: I
authors.lastname: Ossuetta
authors.forename: Isabel
authors.initials: I
authors.lastname: Iglesias
authors.forename: Claire
authors.initials: C
authors.lastname: Theyskens
authors.forename: Miranda
authors.initials: M
authors.lastname: de Jong
authors.forename: Jag S
authors.initials: JS
authors.lastname: Ahluwalia
authors.forename: Francis
authors.initials: F
authors.lastname: de Zegher
authors.forename: David B
authors.initials: DB
authors.lastname: Dunger
mesh_terms: D001786:Blood Glucose / Q000032:analysis; D016903:Drug Monitoring / Q000295:instrumentation / Q000379:methods; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy*; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007226:Infant Mortality; D007231:Infant, Newborn; D019102:Infant, Very Low Birth Weight / Q000097:blood*; D007262:Infusions, Intravenous; D007328:Insulin / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin