A randomised controlled trial of early insulin therapy in very low birth weight infants, "NIRTURE" (neonatal insulin replacement therapy in Europe).
BACKGROUND
Studies in adult intensive care have highlighted the importance of insulin and improved glucose control on survival, with 32% reduction in mortality, 22% reduction in intensive care stay and halving of the incidence of bacteraemia. Very low birth weight infants requiring intensive care also have relative insulin deficiency often leading to hyperglycaemia during the first week of life. The physiological influences on insulin secretion and sensitivity, and the potential importance of glucose control at this time are not well established. However there is increasing evidence that the early postnatal period is critical for pancreatic development. At this time a complex set of signals appears to influence pancreatic development and beta cell survival. This has implications both in terms of acute glucose control but also relative insulin deficiency is likely to play a role in poor postnatal growth, which has been associated with later motor and cognitive impairment, and fewer beta cells are linked to risk of type 2 diabetes later in life.


METHODS
A multi-centre, randomised controlled trial of early insulin replacement in very low birth weight babies (VLBW, birth weight < 1500 g). 500 infants will be recruited from 10 centres in the UK and Europe. Babies will be randomised to receive a continuous insulin infusion (0.05 units/kg/h) or to receive standard neonatal care from the first day of life and for the next 7 days. If blood glucose (BG) levels fall infants will receive 20% dextrose titrated to maintain normoglycaemia (4-8 mmol/l). If BG is consistently above 10 mmol/l babies will receive standard treatment with additional insulin infusion. The primary end point will be mortality on or before expected date of delivery, secondary end points will be markers of morbidity and include episodes of sepsis, severity of retinopathy, chronic lung disease and growth.
Beardsall
Kathryn
K
Department of Paediatrics, University of Cambridge, Addenbrooke's Hospital NHS Trust, Hills Road, Cambridge, CB2 2QQ, UK. kb274@cam.ac.uk
Vanhaesebrouck
Sophie
S
Ogilvy-Stuart
Amanda L
AL
Ahluwalia
Jag S
JS
Vanhole
Christine
C
Palmer
Christopher
C
Midgley
Paula
P
Thompson
Mike
M
Cornette
Luc
L
Weissenbruch
Mirjam
M
Thio
Marta
M
de Zegher
Francis
F
Dunger
David
D
D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000379:methods; D005500:Follow-Up Studies; D005947:Glucose / Q000627:therapeutic use; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy* / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007231:Infant, Newborn; D019102:Infant, Very Low Birth Weight; D007262:Infusions, Intravenous; D007328:Insulin / Q000172:deficiency / Q000627:therapeutic use*; D016896:Treatment Outcome
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D005947:Glucose
Pediatrics. 1988 Oct;82(4):527-32
3174313
BMJ. 1997 May 24;314(7093):1512-5
9169397
Acta Paediatr Jpn. 1997 Apr;39 Suppl 1:S21-5
9200875
Diabetologia. 1997 Oct;40(10):1231-4
9349607
J Pediatr. 1998 Jun;132(6):948-53
9627584
Biol Neonate. 1998;74(3):214-21
9691162
Diabetologia. 1998 Sep;41(9):1114-20
9754832
J Clin Endocrinol Metab. 1998 Oct;83(10):3550-7
9768663
Brain Res Dev Brain Res. 1999 Apr 12;114(1):135-41
10209251
Biol Neonate. 2006;89(1):56-9
16155387
Pediatrics. 2006 Nov;118(5):1811-8
17079549
J Perinatol. 2006 Dec;26(12):737-41
16929343
J Perinatol. 2006 Dec;26(12):730-6
16929344
Arch Ophthalmol. 1987 Jul;105(7):906-12
3606449
Nutrition. 2000 Mar;16(3):221-5
10705078
Horm Res. 2000;53 Suppl 1:42-9
10895042
Am J Physiol Renal Physiol. 2000 Dec;279(6):F1067-76
11097625
Crit Care Clin. 2001 Jan;17(1):107-24
11219223
J Pediatr Endocrinol Metab. 2001 Feb;14(2):151-8
11305792
Proc Natl Acad Sci U S A. 2001 May 8;98(10):5804-8
11331770
J Trauma. 2001 Sep;51(3):540-4
11535907
N Engl J Med. 2001 Nov 8;345(19):1359-67
11794168
Endocrinology. 2001 Dec;142(12):5089-96
11713201
Pediatr Res. 2001 Dec;50(6):732-6
11726732
Infect Control Hosp Epidemiol. 2001 Oct;22(10):607-12
11776345
J Clin Endocrinol Metab. 2002 Jul;87(7):3413-6
12107259
Arch Dis Child Fetal Neonatal Ed. 2003 Jan;88(1):F23-8
12496222
Endocr J. 2002 Oct;49(5):531-7
12507271
Eur J Ophthalmol. 2002 Nov-Dec;12(6):506-11
12510720
Crit Care Med. 2003 Feb;31(2):359-66
12576937
J Pediatr Surg. 2004 Jun;39(6):898-901; discussion 898-901
15185221
J Pediatr. 1979 Mar;94(3):454-9
423036
Acta Paediatr Scand. 1982 May;71(3):379-83
6814175
Arch Ophthalmol. 1984 Aug;102(8):1130-4
6547831
Pediatrics. 1986 Oct;78(4):625-30
3763272
J Pediatr. 1986 Nov;109(5):905-7
3534204
Aust Paediatr J. 1988 Dec;24(6):362-5
3149465
Am J Obstet Gynecol. 1989 May;160(5 Pt 1):1091-4
2658601
Biol Neonate. 1990;57(2):107-18
2178691
J Pediatr. 1991 Jun;118(6):921-7
1904090
JPEN J Parenter Enteral Nutr. 1991 Jul-Aug;15(4):417-20
1910105
Diabetologia. 1991 Jul;34(7):500-6
1916055
Diabetes. 1991 Dec;40 Suppl 2:115-20
1748239
Diabetologia. 1992 Jun;35(6):542-9
1612227
Arch Dis Child Fetal Neonatal Ed. 1996 Nov;75(3):F152-7
8976679
J Pediatr. 1989 Feb;114(2):273-80
2492598