Katherine Steinbeck

Clinical research in adolescents : challenges and opportunities using obesity as a model

Adolescent medicine is relatively young, compared to paediatric or adult medicine. Descriptive and observational studies have dominated the adolescent literature, including those studies published in the International Journal of Obesity. In addition, many studies have combined child and adolescent age groups, making it difficult to determine adolescent-specific outcomes. It is important that high quality intervention studies in adolescents occur. Adolescence is a time of extraordinary plasticity. Habits, attitudes and physical morbidity that develop during adolescence set up trajectories that have a profound influence on health and wellbeing for the long term. Overweight and obesity are an excellent example of the need for high quality intervention studies and yet in the last two decades there have been very few randomized, controlled trials of overweight and obesity management in adolescents. There are a number of complexities in adolescent research that create additional challenges to those that accompany any clinical research. These include recruitment and retention, issues around consent and confidentiality and the central role that parents play in supporting the research protocol. Pubertal stage is a potential confounder and needs to be accurately measured. This is certainly true for studies in overweight and obesity where excess adiposity influences pubertal and other hormones. The opportunities to undertake quality research in adolescents are likely to be enhanced by the use of novel approaches which acknowledge the unique features of adolescents and their world.

Optimal Macronutrient Content of the Diet for Adolescents With Prediabetes; RESIST a Randomised Control Trial

CONTEXTnPrediabetes and clinical insulin resistance in adolescents are rapidly emerging clinical problems with serious health outcomes.nnnOBJECTIVEnThe objective of this study was to determine the efficacy of 2 structured lifestyle interventions, both differing in diet macronutrient composition, on insulin sensitivity.nnnDESIGNnThis 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.nnnPARTICIPANTSnParticipants included overweight or obese 10- to 17-year-olds with either prediabetes and/or clinical features of insulin resistance.nnnINTERVENTIONnAt 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.nnnOUTCOMESnThe outcomes included an insulin sensitivity, anthropometry, and cardiometabolic profile at 6 months.nnnRESULTSnOne 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.nnnCONCLUSIONSnThese 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.

Postprandial Vascular Reactivity in Obese and Normal Weight Young Adults

As humans spend a significant amount of time in the postprandial state, we examined whether vascular reactivity (a key indicator of cardiovascular health) was different after a high‐fat meal in 11 obese (median BMI 46.4, age 32.1 ± 6.3 years, 7 men) and 11 normal weight (median BMI 22.6) age‐ and sex‐matched controls. At baseline and 1 and 3 h postmeal, blood pressure (BP), heart rate (HR), reactive hyperemia peripheral artery tonometry (RH‐PAT) index, radial augmentation index adjusted for HR (AIx75), brachial pulse wave velocity (PWVb), glucose, insulin, total and high‐density lipoprotein (HDL) cholesterol, and triglycerides were measured. Brachial flow‐mediated dilatation (FMD) and, by venous plethysmography, resting and hyperemic forearm blood flows (FBFs) were measured at baseline and 3 h. At baseline, obese subjects had higher systolic BP, HR, resting FBF, insulin and equivalent FMD, RH‐PAT, hyperemic FBF, AIx75, PWVb, glucose, total cholesterol, triglycerides, and lower HDL cholesterol. In obese and lean subjects, FMD at baseline and 3 h was not significantly different (6.2 ± 1.7 to 5.8 ± 4.3% for obese and 4.7 ± 4.1 to 4.3 ± 3.9% for normal weight, P = 0.975 for group × time). The meal did not produce significant changes in RH‐PAT, hyperemic FBF, and PWVb in either group (P > 0.1 for the effect of time and for group × time interactions). In conclusion, the vascular responses to a high‐fat meal are similar in obese and normal weight young adults. An exaggerated alteration in postprandial vascular reactivity is thus unlikely to contribute importantly to the increased cardiovascular risk of obesity.

Severe Obesity Is Associated With Impaired Arterial Smooth Muscle Function in Young Adults

The degree of arterial dilatation induced by exogenous nitrates (nitrate‐mediated dilatation, NMD) has been similar in obese and normal‐weight adults after single high‐dose glyceryl trinitrate (GTN). We examined whether NMD is impaired in obesity by performing a GTN dose‐response study, as this is a potentially more sensitive measure of arterial smooth muscle function. In this cross‐sectional study, subjects were 19 obese (age 31.0 ± 1.2 years, 10 male, BMI 44.1 ± 2.1) and 19 age‐ and sex‐matched normal‐weight (BMI 22.4 ± 0.4) young adults. Blood pressure (BP), triglycerides, high‐density lipoprotein (HDL), and low‐density lipoprotein (LDL)‐cholesterol, glucose, insulin, high‐sensitivity C‐reactive protein (hs‐CRP), carotid intima‐media thickness (CIMT), and flow‐mediated dilatation (FMD) were measured. After incremental doses of GTN, brachial artery maximal percent dilatation (maximal NMD) and the area under the dose‐response curve (NMD AUC) were calculated. Maximal NMD (13.4 ± 0.9% vs. 18.3 ± 1.1%, P = 0.002) and NMD AUC (54,316 ± 362 vs. 55,613 ± 375, P = 0.018) were lower in obese subjects. The obese had significantly higher hs‐CRP, insulin, and CIMT and lower HDL‐cholesterol. Significant bivariate associations existed between maximal NMD or NMD AUC and BMI‐group (r = −0.492, P = 0.001 or r = −0.383, P = 0.009), hs‐CRP (r = −0.419, P = 0.004 or r = −0.351, P = 0.015), and HDL‐cholesterol (r = 0.374, P = 0.01 or r = 0.270, P = 0.05). On multivariate analysis, higher BMI‐group remained as the only significant determinant of maximal NMD (r2 = 0.242, β = −0.492, P = 0.002) and NMD AUC (r2 = 0.147, β = −0.383, P = 0.023). In conclusion, arterial smooth muscle function is significantly impaired in the obese. This may be important in their increased cardiovascular risk.

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

BackgroundA 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.MethodsObese 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.ResultsOf 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.ConclusionWhen 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 registrationAustralian 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

BackgroundOverweight 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.ObjectiveTo 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.MethodThis 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 3xa0months and followed by a 6xa0month 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 6xa0months of the trial. As there was no difference between the diets on outcome of interest, both diet groups were combined for analyses.ResultsAfter 6xa0months, the proportion of participants who reported consuming more in response to external eating cues decreased from 17% to 5% (Pu2009=u20090.003), whereas non- emotional eating increased from 48% to 65% (pu2009=u20090.014). Dietary restraint and parental pressure to eat remained unchanged. A reduction in external eating (rhou2009=u20090.36, Pu2009<u20090.001) and a reduction in dietary restraint (ru2009=u20090.26, Pu2009=u20090.013) were associated with greater weight loss at 3 and 6xa0months, 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.ConclusionsIn 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 registrationAustralian New Zealand Clinical Trial Registration Number (ACTRN) 12608000416392 https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=83071

Increased tissue factor activity in monocytes from obese young adults

1. The relationship between inflammation, obesity‐related proteins and tissue factor (TF), the major initiator of the extrinsic clotting cascade, is not well understood. We examined if basal and stimulated peripheral blood mononuclear cell (PBMC) TF‐procoagulant activity (PCA) was higher in obese subjects and examined the effects of leptin, resistin and serum amyloid A (SAA).

The adverse health consequences of the use of multiple performance-enhancing substances--a deadly cocktail.

CONTEXTnThe harmful consequences of abuse of performance-enhancing substances (PESs), stimulants, and masking agents among athletes, recreational weight lifters, and physical trainers are common. However, the adverse health outcomes with severe unexpected and dramatic consequences are unrecognized or under-reported at the expense of short-term glory or body-image effects, especially in elite sports.nnnOBJECTIVEnWe report the case of a recreational weight lifter/physical trainer to help summarize the adverse health consequences and outcomes of polypharmacy among athletes and growing subsets in our population engaged in physical/fitness training. We show that in addition to the risk inherent to stacking of PESs, the users are predisposed to harmful consequences, including risk of exposure to toxic contaminants.nnnDESIGN AND SETTINGnA previously healthy man with chronic use of multiple PESs, stimulants, and masking agents presented to a tertiary-care hospital with jaundice and mild hepatitis with rapid progression into liver and multisystem organ failure. This is followed by a brief overview of the specific toxicity (arsenic) and PESs that contributed to the poor outcome in this case.nnnCONCLUSIONnSurreptitiously or self-administered cocktails of potential PESs including anabolic agents, emerging classes of GH-releasing peptides, androgen precursors, stimulants, and masking agents could lead to adverse consequences including early mortality, multisystem pathology, unmask/accelerate malignancy, and expose or predispose users to extreme danger from contaminants. This cautionary case reinforces the need to increase awareness and highlights the challenges that testing agencies, regulators, and clinicians face in the fast-developing licit/illicit trade of these products.