Randomised 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 mellitus (IDDM) to prevent complications may be difficult to achieve during adolescence, because abnormalities in production of growth hormone or insulin-like growth-factor-l (IGF-I) can lead to lower insulin sensitivity. Recombinant human IGF-I (rhlGF-l) given as an adjunct to insulin therapy in IDDM, might improve glycaemic control in adolescents; we investigated the effects of the addition of IGF-I in a randomised, doubleblind, placebo-controlled trial. Methods 53 patients with IDDM (26 male, 27 female) with a median age of 16·1 years (range 10·38-20·6) and diabetes of more than 2 yearsʹ duration were randomly assigned subcutaneous rhlGF-l (20 or 40 μg/kg daily [n=18, n=18, respectively]) or placebo (n=17), both in addition to multiple-injection insulin therapy for 24 weeks. The primary endpoint, glycated haemoglobin (HbA1c) 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 μg/kg rhlGF-l daily, we found significant reductions in HbA1c compared with placebo (p=O.O3), without changes in body-mass index, rate of hypoglycaemia, insulin dose, or circulating concentrations of IGF-binding proteins 1 and 3. The greatest median change in HbA1c of −O.6% (range −2·8 to −1·5%) was seen with rhlGF-l 40 μg/kg at week 12, but was not sustained at week 24. The greatest reductions in HbA1c at week 24 were seen among patients with the greatest changes in IGF-I concentrations (r=0·442, p=0·002). Retinal photographs, renal function (glomerular filtration rate and urinary albumin excretion), and routine biochemistry showed no adverse events. Interpretation Our data confirm that rhlGF-l as an adjunct to insulin therapy can improve HbA1c values in adolescents with IDDM without overt toxic effects, but they raise questions about whether these effects can be sustained in cases of poor compliance or reduced bioefficacy. Article Outline Introduction Patients and methods Assays Statistics Results Discussion Acknowledgements References 10 You are not entitled to access the full text of this document Randomised placebo-controlled trial of rhesus-human reassortant rotavirus vaccine for prevention of severe rotavirus gastroenteritis Original Research Article Pages 1205-1209 Jaana Joensuu, Eeva Koskenniemi, Xiao-Li Pang, Timo Vesikari Close Close preview | Purchase PDF (78 K) | Related articles | Related reference work articles AbstractAbstract | Figures/TablesFigures/Tables | ReferencesReferences Summary Background Rotavirus is the most common cause of acute childhood gastroenteritis. Vaccination with live oral heterologous rotavirus vaccines may prevent rotavirus gastroenteritis. We assessed the efficacy of rhesus-human reassortant rotavirus tetravalent vaccine (RRV-TV) against severe rotavirus gastroenteritis in Finnish children in a randomised placebo-controlled double-blind trial. Methods Placebo or RRV-TV (titre 4·105 plaque-forming units) was given to infants at ages 2, 3, and 5 months. The children were followed up for one or two rotavirus epidemic seasons. The main outcome measure was protection against severe rotavirus gastroenteritis (score greater-or-equal, slanted11 on a 20-point severity scale). 2398 children were enrolled and received at least one dose of RRV-TV (n=1191) or placebo (n=1207). The primary efficacy analysis was based on children who received three doses of RRV-TV (n=1128) or placebo (n=1145). Findings 256 episodes of rotavirus gastroenteritis occurred at any time during the study; 65 were among 1191 RRV-TV recipients, and 191 among 1207 placebo recipients (vaccine efficacy 66% [95% Cl 55–74]; intention-to-treat analysis). 226 episodes were included in the primary efficacy analysis of fully vaccinated children (54 among 1128 RRV-TV recipients, 172 among 1145 placebo recipients; vaccine efficacy 68% [57–76]). 100 episodes were severe, eight in RRV-TV recipients and 92 in placebo recipients (vaccine efficacy 91% [82–96]). Interpretation RRV-TV vaccine was highly effective against severe rotavirus gastroenteritis in young children. Incorporation of this vaccine into routine immunisation schedules of infants could reduce severe rotavirus gastroenteritis by 90% and severe gastroenteritis of all causes in young children by 60%.