RANDOMIZED PLACEBO-CONTROLLED TRIAL OF HUMAN RECOMBINANT INSULIN-LIKE-GROWTH-FACTOR-I PLUS INTENSIVE INSULIN THERAPY IN ADOLESCENTS WITH INSULIN-DEPENDENT DIABETES-MELLITUS

Background Good glycaemic control in insulin-dependent diabetes mellit us (IDDM) to prevent complications may be difficult to achieve during adolescence, because abnormalities in production of growth hormone or insulinlike growth-factor-I (IGF-I) can lead to lower insulin sensitiv ity. Recombinant human IGF-I (rhIGF-I) given as an adjunct to insulin therapy in IDDM, might improve glycaemic control in adolescents; we in vestigated the effects of the addition of IGF-I in a randomised, doubl e-blind, placebo-controlled trial. Methods 53 patients with IDDM (26 m ale, 27 female) with a median age of 16.1 years (range 10.8-20.6) and diabetes of more than 2 years' duration were randomly assigned subcuta neous rhIGF-1 (20 or 40 mu g/kg daily [n=18, n=18, respectively]) or p lacebo (n=17), both in addition to multiple-injection insulin therapy for 24 weeks. The primary endpoint, glycated haemoglobin (HbA(1c)) and routine biochemistry were measured every 4 weeks. Retinal photographs and glomerular-filtration rates were assessed at base line and at the end of the study. Data were analysed by intention to treat. Findings With a dose of 40 mu g/kg rhIGF-1 daily, we found significant reductio ns in HbA(1c) compared with placebo (p=0.03), without changes in body- mass index, rate of hypoglycaemia, insulin dose, or circulating concen trations of IGF-binding proteins 1 and 3. The greatest median change i n HbA(1c) of -0.6% (range -2.8 to -1.5%) was seen with rhIGF-I 40 mu g /kg at week 12, but was not sustained at week 24. The greatest reducti ons in HbA(1c) at week 24 were seen among patients with the greatest c hanges in IGF-I concentrations (r=0.442, p=0.002]. Retinal photographs , renal function (glomerular filtration rate and urinary albumin excre tion), and routine biochemistry showed no adverse events. Interpretati on Our data confirm that rhIGF-I as an adjunct to insulin therapy can improve HbA(1c) values in adolescents with IDDM without overt toxic ef fects, but they raise questions about whether these effects can be sus tained in cases of poor compliance or reduced bioefficacy.