Improved insulin sensitivity and body composition, irrespective of macronutrient intake, after a 12 month intervention in adolescents with pre-diabetes; RESIST a randomised control trial

© 2014 Garnett et al..Background: A higher protein to carbohydrate ratio in the diet may potentiate weight loss, improve body composition and cardiometabolic risk, including glucose homeostasis in adults. The aim of this randomised control trial was to determine the efficacy of two structured lifestyle interventions, differing in dietary macronutrient content, on insulin sensitivity and body composition in adolescents. We hypothesised that a moderate-carbohydrate (40-45% of energy), increased-protein (25-30%) diet would be more effective than a high-carbohydrate diet (55-60%), moderate-protein (15%) diet in improving outcomes in obese, insulin resistant adolescents. Methods: Obese 10-17 year olds with either pre-diabetes and/or clinical features of insulin resistance were recruited at two hospitals in Sydney, Australia. At baseline adolescents were prescribed metformin and randomised to one of two energy restricted diets. The intervention included regular contact with the dietician and a supervised physical activity program. Outcomes included insulin sensitivity index measured by an oral glucose tolerance test and body composition measured by dual-energy x-ray absorptiometry at 12 months. Results: Of the 111 adolescents recruited, 85 (77%) completed the intervention. BMI expressed as a percentage of the 95th percentile decreased by 6.8% [95% CI: -8.8 to -4.9], ISI increased by 0.2 [95% CI: 0.06 to 0.39] and percent body fat decreased by 2.4% [95% CI: -3.4 to -1.3]. There were no significant differences in outcomes between diet groups at any time. Conclusion: When treated with metformin and an exercise program, a structured, reduced energy diet, which is either high-carbohydrate or moderate-carbohydrate with increased-protein, can achieve clinically significant improvements in obese adolescents at risk of type 2 diabetes.Link_to_subscribed_fulltex

Individual common variants exert weak effects on the risk for autism spectrum disorders.

While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating the association of individual single nucleotide polymorphisms (SNPs), we also sought evidence that common variants, en masse, might affect the risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest P-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. In contrast, allele scores derived from the transmission of common alleles to Stage 1 cases significantly predict case status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele score results, it is reasonable to conclude that common variants affect the risk for ASD but their individual effects are modest

Browse and Search Patterns in a Digital Image Database

A prototype image retrieval system with browse and search capabilities was developed to investigate patterns of searching a collection of digital visual images, as well as factors, such as image size, resolution, and download speed, which affect browsing. The subject populations were art history specialists and non-specialists. Through focus group interviews, a controlled test, post-test interviews and an online survey, data was gathered to compare preferences and actual patterns of use in browsing and searching. While specialists preferred direct search to browsing, and generalists used browsing as their preferred mode, both user groups found each mode to play a role depending on information need, and found value in a system combining both browse and direct search. There were no significant differences in performance among the search modes of browse, search, and combined browse/search models when the quasi-controlled study tested the different modes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45984/1/10791_2004_Article_252664.pd

Researching Effective Strategies to Improve Insulin Sensitivity in Children and Teenagers - RESIST. A randomised control trial investigating the effects of two different diets on insulin sensitivity in young people with insulin resistance and/or pre-diabetes.

Abstract Background Concomitant with the rise in childhood obesity there has been a significant increase in the number of adolescents with clinical features of insulin resistance and prediabetes. Clinical insulin resistance and prediabetes are likely to progress to type 2 diabetes and early atherosclerosis if not targeted for early intervention. There are no efficacy trials of lifestyle intervention in this group to inform clinical practice. The primary aim of this randomised control trial (RCT) is to determine the efficacy and effectiveness of two different structured lifestyle interventions differing in diet composition on insulin sensitivity, in adolescents with clinical insulin resistance and/or prediabetes treated with metformin. Methods/design This study protocol describes the design of an ongoing RCT. We are recruiting 108 (54 each treatment arm) 10 to 17 year olds with clinical features of insulin resistance and/or prediabetes, through physician referral, into a multi-centred RCT. All participants are prescribed metformin and participate in a diet and exercise program. The lifestyle program is the same for all participants except for diet composition. The diets are a high carbohydrate, low fat diet and a moderate carbohydrate, increased protein diet. The program commences with an intensive 3 month dietary intervention, implemented by trained dietitians, followed by a 3 month intensive gym and home based exercise program, supervised by certified physical trainers. To measure the longer term effectiveness, after the intensive intervention trial participants are managed by either their usual physician or study physician and followed up by the study dietitians for an additional 6 months. The primary outcome measure, change in insulin sensitivity, is measured at 3, 6 and 12 months. Discussion Clinical insulin resistance and prediabetes in the paediatric population are rapidly emerging clinical problems with serious health outcomes. With appropriate management these conditions are potentially reversible or at least their progression can be delayed. This research study is the first trial designed to provide much needed data on the effective dietary management for this cohort. This study will inform clinical practice guidelines for adolescents with clinical insulin resistance and may assist in preventing metabolic complications, type 2 diabetes and early cardiovascular disease. Trial registration Australian and New Zealand Clinical Trials Registration Number ACTRN12608000416392</p

Optimal macronutrient content of the diet for adolescents with prediabetes: RESIST a randomised control trial

CONTEXT: Prediabetes and clinical insulin resistance in adolescents are rapidly emerging clinical problems with serious health outcomes. OBJECTIVE: The objective of this study was to determine the efficacy of 2 structured lifestyle interventions, both differing in diet macronutrient composition, on insulin sensitivity. DESIGN: This study was a randomized controlled trial, known as Researching Effective Strategies to Improve Insulin Sensitivity in Children and Teenagers, in 2 hospitals in Sydney, Australia. PARTICIPANTS: Participants included overweight or obese 10- to 17-year-olds with either prediabetes and/or clinical features of insulin resistance. INTERVENTION: At baseline adolescents were prescribed metformin and randomized to a structured diet, which was either high carbohydrate or moderate carbohydrate with increased protein. The program commenced with a 3-month dietary intervention, with the addition of an exercise intervention in the next 3 months. OUTCOMES: The outcomes included an insulin sensitivity, anthropometry, and cardiometabolic profile at 6 months. RESULTS: One hundred eleven subjects (66 girls) were recruited and 98 subjects (58 girls) completed the 6-month intervention. After 3 months the mean insulin sensitivity index increased by 0.3 [95% confidence interval (CI) 0.2–0.4]. After 6 months the mean insulin (picomoles per liter) to glucose ratio (millimoles per liter) decreased by 7.2 [95%CI −12.0 to −2.3], body mass index, expressed as a percentage of the 95th centile, decreased by 9% (95% CI −3 to −15), but there was no significant change in the lipids. There were no significant differences in outcomes between the diet groups at any time point. CONCLUSIONS: These results are in contrast with our hypothesis that adolescents randomized to the increased protein diet would have better outcomes. Further strategies are required to better address prediabetes and clinical features of insulin resistance in adolescents. AFFILIATIONS Institute of Endocrinology and Diabetes (S.P.G., M.G., J.H., S.S., G.R.A., C.T.C.), The Children's Hospital Institute of Sports Medicine (C.R.B.), and Nutrition and Dietetics, Weight Management Services (S.B., K.C.), and The Centre for Research into Adolescent's Health (M.R.K.), The Children's Hospital at Westmead, The Children's Hospital at Westmead Clinical School (S.P.G., M.G., M.H., L.A.B., G.R.A., C.T.C.), University of Sydney, Westmead, New South Wales 2145, Australia; Commonwealth Scientific and Industrial Research Organisation Food and Nutritional Sciences (M.N.), Adelaide Business Centre, South Australia 5000, Australia; Department of Paediatrics (H.J.W.), Campbelltown Hospital, Campbelltown, New South Wales 2560, Australia; Department of Diabetes and Endocrinology (H.J.W.), Sydney Children's Hospital Network, Randwick, New South Wales 2031, Australia; and Academic Department of Adolescent Medicine (K.S.), Sydney Medical School, University of Sydney, New South Wales 2066, AustraliaSarah P. Garnett, Megan Gow, Mandy Ho, Louise A. Baur, Manny Noakes, Helen J. Woodhead, Carolyn R. Broderick, Susie Burrell, Kerryn Chisholm, Jocelyn Halim, Sukanya De, Katherine Steinbeck, Shubha Srinivasan, Geoffrey R. Ambler, Michael R. Kohn, and Chris T. Cowel