Familial hypercholesterolaemia: Experience of a tertiary paediatric lipid clinic.

AIM: To review the experience of a dedicated paediatric multidisciplinary lipid clinic in the management of familial hypercholesterolaemia (FH) by studying the demographics, clinical presentations as well as statin therapy and outcomes. METHODS: Retrospective database review of all patients under 18 years old seen in the lipid clinic at an Australian tertiary paediatric hospital between April 1999 and August 2017. Outcome measures collected included patient demographics, family history, lipid profile, age at treatment commencement, treatment outcomes and complications. RESULTS: One hundred and eight patients (53 males) were seen in the lipid clinic. Eighty-five had low-density lipoprotein cholesterol (LDL-C) levels at or above the 75th percentile for sex prior to treatment. Of these, 75 had a first-degree relative with hypercholesterolaemia and/or early cardiac death. Four patients had clinical manifestations. Thirty-two patients (14 males) were started on statin therapy for likely FH. LDL-C levels reduced by 2.4 mmol/L (1.4 to 2.7) in boys and 1.9 mmol/L (0.8 to 2.8) in girls at 12 month follow-up. Five patients reported side effects requiring adjustment in therapy. Main reasons for not starting statin therapy in eligible patients were parental refusal and/or lost to follow up (77%). CONCLUSION: A dedicated multidisciplinary lipid clinic is helpful for streamlining and monitoring management of paediatric FH. Clinical manifestations of FH are rare in children and may represent more severe form of FH or other lipid disorder. Statin therapy is efficacious and well tolerated but current recommended targets of treatment are difficult to attain. Greater awareness and coordinated services are required to overcome poor family engagement.

Fast track to health - Intermittent energy restriction in adolescents with obesity. A randomised controlled trial study protocol.

BACKGROUND: Intermittent energy restriction (IER) has shown early success in adolescents with obesity, however efficacy trials are needed. This study aims to determine if IER results in lower body mass index (BMI) z-score after 52 weeks in metabolically unhealthy adolescents with obesity compared with continuous energy restriction (CER). METHODS/DESIGN: This is a prospective, randomised, multi-centre trial conducted in tertiary care settings, with three phases: jumpstart (weeks 0-4); intensive intervention (weeks 5-16); continued intervention and/or maintenance (weeks 17-52). During the jumpstart phase, all participants follow a very low energy diet (∼800kcal/3350kJ/day), then transition to their allocated intervention: IER or CER. IER involves three energy-restricted days/week, consuming one-third of daily energy requirements (∼600-700kcal/2500-2950kJ/day), and four days/week of a healthy meal plan. The CER, which is current standard care, has individually tailored energy prescription based on age and sex (13-14years, 1430-1670kcal/6000-7000kJ/day; 15-17years, 1670-1900kcal/7000-8000kJ/day). The study will recruit 186 (93 per arm) treatment-seeking adolescents aged 13-17years with obesity and at least one metabolic co-morbidity. The primary outcome is change in BMI z-score at 52 weeks. Secondary outcomes are changes at 4, 16 and 52 weeks in: body composition; diet quality, food choices and food patterns; cardio-metabolic risk factors; physical activity and sedentary behaviour; sleep and psycho-behavioural measures. DISCUSSION: This study challenges existing clinical paradigms that CER is the only method for weight management in metabolically unhealthy adolescents. If successful, IER may offer an alternate medical nutrition therapy approach for those seeking treatment in tertiary settings. CLINICAL TRIAL REGISTRATION NUMBER: ACTRN12617001630303.

Can early weight loss, eating behaviors and socioeconomic factors predict successful weight loss at 12- and 24-months in adolescents with obesity and insulin resistance participating in a randomised controlled trial?

BACKGROUND: Lifestyle interventions in adolescents with obesity can result in weight loss following active intervention but individual responses vary widely. This study aimed to identify predictors of weight loss at 12- and 24-months in adolescents with obesity and clinical features of insulin resistance. METHODS: Adolescents (n = 111, 66 girls, aged 10-17 years) were participants in a randomised controlled trial, the RESIST study, examining the effects of two diets differing in macronutrient content on insulin sensitivity. Eighty-five completed the 12-month program and 24-month follow-up data were available for 42 adolescents. Change in weight was determined by BMI expressed as a percentage of the 95th percentile (BMI95). The study physician collected socioeconomic data at baseline. Physical activity and screen time, and psychological dimensions of eating behavior were self-reported using the validated CLASS and EPI-C questionnaires, respectively. Stepwise multiple regressions were conducted to identify models that best predicted change in BMI95 at 12- and 24-months. RESULTS: Mean BMI95 was reduced at 12-months compared with baseline (mean difference [MD] ± SE: -6.9 ± 1.0, P < 0.001) but adolescents had significant re-gain from 12- to 24-months (MD ± SE: 3.7 ± 1.5, P = 0.017). Participants who achieved greater 12-month weight loss had: greater 3-month weight loss, a father with a higher education, lower baseline external eating and parental pressure to eat scores and two parents living at home. Participants who achieved greater 24-month weight loss had: greater 12-month weight loss and a lower baseline emotional eating score. CONCLUSIONS: Early weight loss is consistently identified as a strong predictor of long-term weight loss. This could be because early weight loss identifies those more motivated and engaged individuals. Patients who have baseline factors predictive of long-term weight loss failure may benefit from additional support during the intervention. Additionally, if a patient does not achieve early weight loss, further support or transition to an alternate intervention where they may have increased success may be considered. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registration Number (ACTRN) 12608000416392 https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=83071.

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.

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. TRIAL REGISTRATION: Australian New Zealand Clinical Trail Registry ACTRN12608000416392 . Registered 25 August 2008.

Effect of a prescriptive dietary intervention on psychological dimensions of eating behavior in obese adolescents.

BACKGROUND: Overweight adolescents are more likely to have dysfunctional eating behaviours compared to normal weight adolescents. Little is known about the effects of obesity treatment on the psychological dimensions of eating behavior in this population. OBJECTIVE: To examine the effects of a prescriptive dietary intervention on external eating (eating in response to food cues, regardless of hunger and satiety), emotional eating and dietary restraint and their relation to weight loss. Parental acceptability was also examined. METHOD: This is a secondary study of a 12-month randomized trial, the RESIST study, which examined the effects of two diets on insulin sensitivity. Participants were 109 obese 10- to 17-year-olds with clinical features of insulin resistance. The program commenced with a 3-month dietary intervention using a structured meal plan, with the addition of an exercise intervention in the next 3 months and followed by a 6 month maintenance period.This paper presents changes in eating behaviors measured by the Eating Pattern Inventory for Children and parent rated diet acceptability during the first 6 months of the trial. As there was no difference between the diets on outcome of interest, both diet groups were combined for analyses. RESULTS: After 6 months, the proportion of participants who reported consuming more in response to external eating cues decreased from 17% to 5% (P = 0.003), whereas non- emotional eating increased from 48% to 65% (p = 0.014). Dietary restraint and parental pressure to eat remained unchanged. A reduction in external eating (rho = 0.36, P < 0.001) and a reduction in dietary restraint (r = 0.26, P = 0.013) were associated with greater weight loss at 3 and 6 months, respectively. Overall this approach was well accepted by parents with 72% of parents considered that their child would be able to follow the meal plan for the longer term. CONCLUSIONS: In the short to medium term, a prescriptive dietary intervention approach is a well-accepted and suitable option for obese adolescents with clinical features of insulin resistance. It may reduce external and emotional eating, led to modest weight loss and did not cause any adverse effect on dietary restraint. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registration Number (ACTRN) 12608000416392 https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=83071.

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.

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.

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.