A randomized cross-over trial to identify the optimal use of insulin glargine in prepubertal children using a three-times daily insulin regimen.
OBJECTIVE
The long-acting insulin analogue glargine reduces nocturnal hypoglycaemia and stabilizes morning blood glucose levels in patients with Type 1 diabetes (T1DM) on multiple injection therapy. However, young children may not tolerate such intensive insulin regimens. We investigated the effects of glargine in various three-injections-daily insulin combinations on 24-h glucose control in prepubertal children.


METHODS
Seventeen T1DM prepubertal children (10 boys), median age 10.2 years (range 6.0-12.4), glycated haemoglobin (HbA(1c)) 8.8% (6.8-11.5) were recruited to a randomized, open-label, cross-over study. After a 2-week run-in period (with NPH pre-bed), every child underwent three different 3-week treatment blocks in random order. All treatment blocks included glargine pre-bed, but used different morning insulins: block 1, soluble only; block 2, soluble + NPH; block 3, aspart + NPH. Continuous glucose monitoring was performed for 3 days at the end of the run-in and each treatment block.


RESULTS
Compared with the run-in period on NPH, the three glargine treatment blocks were associated with lower (P < 0.0001) and less variable (P < 0.05) pre-breakfast glucose levels, and with an 8-15% reduction in total daily insulin dose (P < 0.0001). Risk of nocturnal hypoglycaemia detected by continuous glucose monitoring varied significantly between the three glargine treatment blocks, and was lowest when children were given aspart + NPH in the morning (block 3).


CONCLUSIONS
Insulin glargine pre-bed can be used in three-injections-daily regimens in prepubertal children to lower and stabilize pre-breakfast glucose levels. However, to avoid the risk of nocturnal hypoglycaemia, the pre-bed glargine dose should be lowered by giving a further long-acting insulin, such as NPH, in the morning.
Department of Paediatrics, University of Cambridge, Cambridge, UK.
E E
EE
Fröhlich-Reiterer
K K
KK
Ong
F
F
Regan
G
G
Salzano
C L
CL
Acerini
D B
DB
Dunger
D001786:Blood Glucose / Q000032:analysis; D002648:Child; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D007328:Insulin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting; D008297:Male; D011446:Prospective Studies
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D049528:Insulin, Long-Acting; D000069036:Insulin Glargine