Pediatric Diabetes 2008: 9(Part I): 326–334 doi: 10.1111/j.1399-5448.2008.00383.x All rights reserved # 2008 The Authors Journal compilation # 2008 Blackwell Munksgaard Pediatric Diabetes Original Article The addition of rosiglitazone to insulin in adolescents with type 1 diabetes and poor glycaemic control: a randomized- controlled trial Stone ML, Walker JL, Chisholm D, Craig ME, Donaghue KC, Crock P, Anderson D, Verge CF. The addition of rosiglitazone to insulin in adolescents with type 1 diabetes and poor glycaemic control: a random- ized controlled trial. Pediatric Diabetes 2008: 9(Part I): 326–334. 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 (Tanner breast stage 2 or testicular volume .4 mL), insulin dose 1.1 units/kg/day, and haemo- globin 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 ¼ 0.02), increased serum adiponectin (84.8% increase vs. 26.0% decrease, p , 0.01), increased cholesterol (10.5 mmol/L vs. no change, p ¼ 0.02), but no significant change in HbA1c (20.3 vs. 20.1, p ¼ 0.57) or BMI- SDS (0.08 vs. 0.04, p ¼ 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. Conclusion: The addition of rosiglitazone to insulin did not improve HbA1c in this group of normal weight adolescents with T1DM. Monique L Stone a,b , Jan L Walker a,b , Donald Chisholm c , Maria E Craig d , Kim C Donaghue d , Patricia Crock e , Donald Anderson e and Charles F Verge a,b a Department of Endocrinology, Sydney Children’s Hospital, Randwick, New South Wales, Australia; b The School of Women’s and Children’s Health, University of New South Wales, New South Wales, Australia; c The Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia; d Institute of Diabetes and Endocrinology, Children’s Hospital at Westmead, Westmead, Australia; and e Department of Endocrinology, John Hunter Children’s Hospital, New Lambton, New South Wales, Australia Key words: Type 1 Diabetes – insulin resistance – poor glycaemic control Corresponding author: Dr Monique L Stone Department of Paediatric Endocrinology and Diabetes Royal North Shore Hospital Level 5, Douglas Building NSW 2065 Australia. Tel: 61 2 9926 6904; fax: 61 2 9926 6738; e-mail: stonem@med.usyd.edu.au Submitted 16 August 2007. Accepted for publication 8 January 2008 In type 1 diabetes mellitus (T1DM), achieving optimal glycaemic control during adolescence is difficult because of physical, social and psychological factors (1). Physical factors include increased insulin require- ment with growth, increased carbohydrate consump- tion and insulin resistance. Insulin resistance is a feature 326