The addition of rosiglitazone to insulin in adolescents with type 1 diabetes and poor glycaemic control: a randomized-controlled trial.
OBJECTIVE
To evaluate the effect of rosiglitazone, an insulin sensitizer, on glycaemic control and insulin resistance in adolescents with type 1 diabetes mellitus (T1DM) RESEARCH DESIGN AND METHODS: Randomized, double-blind, placebo-controlled crossover trial of rosiglitazone (4 mg twice daily) vs. placebo (24 wk each, with a 4 wk washout period). Entry criteria were diabetes duration >1 yr, age 10-18 yr, puberty (>or=Tanner breast stage 2 or testicular volume >4 mL), insulin dose >or=1.1 units/kg/day, and haemoglobin A1c (HbA1c) >8%. Responses to rosiglitazone were compared with placebo using paired t-tests.


RESULTS
Of 36 adolescents recruited (17 males), 28 completed the trial. At baseline, age was 13.6 +/- 1.8 yr, HbA1c 8.9 +/- 0.96%, body mass index standard deviation scores (BMI-SDS) 0.94 +/- 0.74 and insulin dose 1.5 +/- 0.3 units/kg/day. Compared with placebo, rosiglitazone resulted in decreased insulin dose (5.8% decrease vs. 9.4% increase, p = 0.02), increased serum adiponectin (84.8% increase vs. 26.0% decrease, p < 0.01), increased cholesterol (+0.5 mmol/L vs. no change, p = 0.02), but no significant change in HbA1c (-0.3 vs. -0.1, p = 0.57) or BMI-SDS (0.08 vs. 0.04, p = 0.31). Insulin sensitivity was highly variable in the seven subjects who consented to euglycaemic hyperinsulinaemic clamps. There were no major adverse effects attributable to rosiglitazone.


CONCLUSIONS
The addition of rosiglitazone to insulin did not improve HbA1c in this group of normal weight adolescents with T1DM.
Stone
Monique L
ML
Department of Endocrinology, Sydney Children's Hospital, Randwick, New South Wales, Australia. stonem@med.usyd.edu.au
Walker
Jan L
JL
Chisholm
Donald
D
Craig
Maria E
ME
Donaghue
Kim C
KC
Crock
Patricia
P
Anderson
Donald
D
Verge
Charles F
CF
D052242:Adiponectin / Q000097:blood; D000293:Adolescent; D001786:Blood Glucose / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000008:administration & dosage*; D007333:Insulin Resistance; D008297:Male; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage*; D016896:Treatment Outcome
D052242:Adiponectin; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D000077154:Rosiglitazone; D045162:Thiazolidinediones