Kristy Wittmeier

Metabolic Consequences of Hepatic Steatosis in Overweight and Obese Adolescents

OBJECTIVE To test the hypothesis that hepatic steatosis is associated with risk factors for type 2 diabetes in overweight and obese youth, mediated by cardiorespiratory fitness. RESEARCH DESIGN AND METHODS This was a cross-sectional study comparing insulin sensitivity between 30 overweight and obese adolescents with hepatic steatosis, 68 overweight and obese adolescents without hepatic steatosis, and 11 healthy weight adolescents without hepatic steatosis. Cardiorespiratory fitness was determined by a graded maximal exercise test on a cycle ergometer. Secondary outcomes included presence of metabolic syndrome and glucose response to a 75-g oral glucose challenge. RESULTS The presence of hepatic steatosis was associated with 55% lower insulin sensitivity (P = 0.02) and a twofold greater prevalence of metabolic syndrome (P = 0.001). Differences in insulin sensitivity (3.5 vs. 4.5 mU ⋅ kg−1 ⋅ min−1, P = 0.03), prevalence of metabolic syndrome (48 vs. 20%, P = 0.03), and glucose area under the curve (816 vs. 710, P = 0.04) remained between groups after matching for age, sex, and visceral fat. The association between hepatic steatosis and insulin sensitivity (β = −0.24, t = −2.29, P < 0.025), metabolic syndrome (β = −0.54, t = −5.8, P < 0.001), and glucose area under the curve (β = 0.33, t = 3.3, P < 0.001) was independent of visceral and whole-body adiposity. Cardiorespiratory fitness was not associated with hepatic steatosis, insulin sensitivity, or presence of metabolic syndrome. CONCLUSIONS Hepatic steatosis is associated with type 2 diabetes risk factors independent of cardiorespiratory fitness, whole-body adiposity, and visceral fat mass.

Dietary determinants of hepatic steatosis and visceral adiposity in overweight and obese youth at risk of type 2 diabetes

BACKGROUNDnDietary determinants of hepatic steatosis, an important precursor for nonalcoholic fatty liver disease, are undefined.nnnOBJECTIVEnWe explored the roles of sugar and fat intake as determinants of hepatic steatosis and visceral obesity in overweight adolescents at risk of type 2 diabetes.nnnDESIGNnThis was a cross-sectional study of dietary patterns and adipose tissue distribution in 74 overweight adolescents (aged: 15.4 ± 1.8 y; body mass index z score: 2.2 ± 0.4). Main outcome measures were hepatic steatosis (≥5.5% fat:water) measured by magnetic resonance spectroscopy and visceral obesity (visceral-to-subcutaneous adipose tissue ratio ≥0.25) measured by magnetic resonance imaging. Main exposure variables were dietary intake and habits assessed by the Harvard Youth Adolescent Food Frequency Questionnaire.nnnRESULTSnHepatic steatosis and visceral obesity were evident in 43% and 44% of the sample, respectively. Fried food consumption was more common in adolescents with hepatic steatosis than in adolescents without hepatic steatosis (41% compared with 18%; P = 0.04). Total fat intake (β = 0.51, P = 0.03) and the consumption of >35% of daily energy intake from fat (OR: 11.8; 95% CI: 1.6, 86.6; P = 0.02) were both positively associated with hepatic steatosis. Available carbohydrate (β = 0.54, P = 0.02) and the frequent consumption of soda were positively associated with visceral obesity (OR: 6.4; 95% CI: 1.2, 34.0; P = 0.03). Daily fiber intake was associated with reduced odds of visceral obesity (OR: 0.82; 95% CI: 0.68, 0.98; P = 0.02) but not hepatic steatosis.nnnCONCLUSIONnHepatic steatosis is associated with a greater intake of fat and fried foods, whereas visceral obesity is associated with increased consumption of sugar and reduced consumption of fiber in overweight and obese adolescents at risk of type 2 diabetes.

StaR Child Health: Developing Evidence-Based Guidance for the Design, Conduct, and Reporting of Pediatric Trials

* Abbreviations:n DMC — : data monitoring committeen SDG — : standard development groupn StaR Child Health — : Standards for Research in Child Healthn WHO — : World Health Organizationnn“Lack of research, poor research, and poorly reported research are violations of children’s human rights,” declared Dr Richard Horton in his plenary address to the audience of the first summit of Standards for Research in (StaR) Child Health.nnStaR Child Health was founded in 2009 to address the paucity and shortcomings of pediatric clinical trials. This initiative involves international experts who are dedicated to developing practical, evidence-based standards to enhance the reliability and relevance of pediatric clinical research. Through a systematic “knowledge to action” plan, StaR Child Health will make efforts to improve and expand the evidence-base for child health across the world. This article introduces the StaR Child Health agenda, the 11 initial priority topics that have been identified, and methods used to address these issues.nnApproximately 180 participants, including representatives from the World Health Organization (WHO), the US Food and Drug Administration, and the European Medicines Agency, gathered in Amsterdam for the first StaR Child Health summit in October 2009 (Table 1). The summit was held on the eve of the 20th anniversary of the adoption of the United Nations Convention on the Rights of the Child, which recognizes the right of all children “to the enjoyment of the highest attainable standard of health.”1 One impediment to achieving this universal right is the paucity and well documented shortcomings of pediatric research and more specifically clinical trials.2 It is recognized that the quantity, quality, and relevance of data involving children are substantially lower than for adults,3–5 despite data demonstrating that inadequate testing of interventions in children can result in ineffective or harmful treatments being offered or beneficial treatments being withheld.6nnView this table:nnTABLE 1 nChronology of Key Events for StaR Child HealthnnnnThe mission of StaR Child Health is to improve the design, conduct, and reporting of … nnAddress correspondence to Martin Offringa, MD, PhD, Senior Scientist and Program Head Child Health Evaluative Sciences, Research Institute, The Hospital for Sick Children, 555 University Ave, Toronto, Ontario, Canada M5G 1X8. E-mail: martin.offringa{at}sickkids.ca

Cardiorespiratory fitness and adiposity in metabolically healthy overweight and obese youth.

OBJECTIVE: Controversy exists surrounding the contribution of fitness and adiposity as determinants of the Metabolically Healthy Overweight (MHO) phenotype in youth. This study investigated the independent contribution of cardiorespiratory fitness and adiposity to the MHO phenotype among overweight and obese youth. METHODS: This cross-sectional study included 108 overweight and obese youth classified as MHO (no cardiometabolic risk factors) or non-MHO (≥1 cardiometabolic risk factor), based on age- and gender-specific cut-points for fasting glucose, triglycerides, high-density lipoprotein cholesterol, systolic and diastolic blood pressure, and hepatic steatosis. RESULTS: Twenty-five percent of overweight and obese youth were classified as MHO. This phenotype was associated with lower BMI z-score (BMI z-score: 1.8 ± 0.3 vs 2.1 ± 0.4, P = .02) and waist circumference (99.7 ± 13.2 vs 106.1 ± 13.7 cm, P = .04) compared with non-MHO youth. When matched for fitness level and stratified by BMI z-score (1.6 ± 0.3 vs 2.4 ± 0.2), the prevalence of MHO was fourfold higher in the low BMI z-score group (27% vs 7%; P = .03). Multiple logistic regression analyses revealed that the best predictor of MHO was the absence of hepatic steatosis even after adjusting for waist circumference (odds ratio 0.57, 95% confidence interval 0.40–0.80) or BMI z-score (odds ratio 0.59, 95% confidence interval 0.43–0.80). CONCLUSIONS: The MHO phenotype was present in 25% of overweight and obese youth and is strongly associated with lower levels of adiposity, and the absence of hepatic steatosis, but not with cardiorespiratory fitness.

Hepatic Steatosis and Low Cardiorespiratory Fitness in Youth With Type 2 Diabetes

The purpose of this study was to examine the association between cardiorespiratory fitness, ectopic triglyceride accumulation, and insulin sensitivity among youth with and without type 2 diabetes. Subjects included 137 youth ages 13–18 years including 27 with type 2 diabetes, 97 overweight normoglycemic controls, and 13 healthy weight normoglycemic controls. The primary outcome measure was cardiorespiratory fitness defined as peak oxygen uptake indexed to fat free mass. Secondary outcomes included liver and muscle triglyceride content determined by 1H‐magnetic resonance spectroscopy and insulin sensitivity determined by frequently sampled intravenous glucose tolerance test. Despite similar measures of adiposity, peak oxygen uptake was 11% lower (38.9 ± 7.9 vs. 43.9 ± 6.1 ml/kgFFM/min, P = 0.002) and hepatic triglyceride content was nearly threefold higher (14.4 vs. 5.7%, P = 0.001) in youth with type 2 diabetes relative to overweight controls. In all 137 youth, cardiorespiratory fitness was negatively associated with hepatic triglyceride content (r = −0.22, P = 0.02) and positively associated with insulin sensitivity (r = 0.29, P = 0.002) independent of total body and visceral fat mass. Hepatic triglyceride content was also negatively associated with insulin sensitivity (r = −0.35, P < 0.001), independent of adiposity, sex, age, and peak oxygen uptake. This study demonstrated that low cardiorespiratory fitness and elevated hepatic triglyceride content are features of type 2 diabetes in youth. Furthermore, cardiorespiratory fitness and hepatic triglyceride are associated with insulin sensitivity in youth. Taken together, these data suggest that cardiorespiratory fitness and hepatic steatosis are potential clinical biomarkers for type 2 diabetes among youth.

Mobile Medical Data Synchronization on Cloud-Powered Middleware Platform

Our research focuses on supporting patients (persons with mild hemophilia) to self-manage injuries in cases of minor incidents. This involves bi-directional exchanges of the Electronic Health Record (EHR) between patients and the care facility. However, mobile devices rely on wireless communication channels (e.g., Wi-Fi, 3.5/4G, etc.) to transmit data and these channels can experience sporadic disconnections due to bandwidth fluctuations and user mobility. As a result, the collected medical data may not be transmitted back to the Health Information system (HIS) in soft-real time. Further, when new updates are submitted by the patients who are disconnected (remote and offline), synchronization can fail; leading to decision-making based on outdated or incomplete information. In this work, we focus on how to ensure efficient synchronization of the EHR in unreliable mobile environments. This work took advantage of the ubiquitous nature of mobile cloud computing and proposes a middleware, which facilitates efficient process of medical data synchronization, and with minimal latency. The work details state-of-the-art architecture of the cloud-based middleware that is built and tested for real-world use following four methodologies namely: reflective, tuple space, context-awareness, and event-based.

Fitness is a determinant of the metabolic response to endurance training in adolescents at risk of type 2 diabetes mellitus

The purpose of this prospective cohort study was to determine whether changes in cardiorespiratory fitness are associated with the metabolic response to endurance training in adolescents at risk of type 2 diabetes mellitus (T2DM).

Moving towards a more inclusive patient and public involvement in health research paradigm: the incorporation of a trauma-informed intersectional analysis

BackgroundThe concept of patient engagement in health research has received growing international recognition over recent years. Yet despite some critical advancements, we argue that the concept remains problematic as it negates the very real complexities and context of people’s lives. Though patient engagement conceptually begins to disrupt the identity of “researcher,” and complicate our assumptions and understandings around expertise and knowledge, it continues to essentialize the identity of “patient” as a homogenous group, denying the reality that individuals’ economic, political, cultural, subjective and experiential lives intersect in intricate and multifarious ways.DiscussionPatient engagement approaches that do not consider the simultaneous interactions between different social categories (e.g. race, ethnicity, Indigeneity, gender, class, sexuality, geography, age, ability, immigration status, religion) that make up social identity, as well as the impact of systems and processes of oppression and domination (e.g. racism, colonialism, classism, sexism, ableism, homophobia) exclude the involvement of individuals who often carry the greatest burden of illness — the very voices traditionally less heard in health research. We contend that in order to be a more inclusive and meaningful approach that does not simply reiterate existing health inequities, it is important to reconceptualize patient engagement through a health equity and social justice lens by incorporating a trauma-informed intersectional analysis.SummaryThis article provides key concepts to the incorporation of a trauma-informed intersectional analysis and important questions to consider when developing a patient engagement strategy in health research training, practice and evaluation. In redefining the identity of both “patient” and “researcher,” spaces and opportunities to resist and renegotiate power within the intersubjective relations can be recognized and addressed, in turn helping to build trust, transparency and resiliency — integral to the advancement of the science of patient engagement in health research.

A clinically relevant method to screen for hepatic steatosis in overweight adolescents: a cross sectional study

BackgroundTo develop a screening algorithm to detect hepatic steatosis in overweight and obese adolescents.MethodsWe performed a cross sectional study of 129 overweight adolescents 13–18xa0yrs. The primary outcome, hepatic steatosis was defined as an intracellular triglyceride contentu2009>u20095.5xa0mg/g and quantified using 1H-magenetic resonance spectroscopy. Primary predictor variables included, alanine and aspartate transaminases (ALT/AST) and features of the metabolic syndrome.ResultsHepatic steatosis was present in 33xa0% of overweight and obese adolescents. Adolescents with hepatic steatosis were more likely to be boys (adjusted OR: 4.8; 95xa0% CI: 2.5–10.5), display a higher waist circumference (111u2009±u200912 vs 100u2009±u200913xa0cm, pu2009<u20090.001) and have metabolic syndrome (adjusted OR: 5.1; 95xa0% CI: 1.6–16.4). Serum ALT predicted hepatic steatosis in boys (AUC: 0.82; 95xa0% CI: 0.70–0.95; pu2009<u20090.001) but not girls (AUCu2009=u20090.63; 95xa0% CI: 0.46–0.75, pu2009=u20090.16). An ALT >20 U/L, combined with the presence of metabolic syndrome, male gender and an elevated waist circumference provided the best model (AUC 0.85) with high sensitivity (72xa0%) and specificity (82xa0%) and positive and negative predictive values of 61xa0% and 89xa0% respectively.ConclusionsSerum transaminases provide modest predictive value for hepatic steatosis in youth. The ALT threshold for predicting hepatic steatosis is significantly lower than current clinical thresholds for predicting non-alcoholic fatty liver disease. The addition of ALT, presence of the metabolic syndrome and male gender significant improve the ability to predict hepatic steatosis.

Physical activity intensity and type 2 diabetes risk in overweight youth: a randomized trial

Background:The chronic effects of high-intensity endurance training on metabolic health outcomes in overweight adolescents remains poorly understood.Objective:To test the hypothesis that high-intensity endurance training (ET) is superior to moderate-intensity ET for improving risk factors for type 2 diabetes in overweight adolescents.Design and methods:In this randomized trial, 106 overweight and obese adolescents (15.2 years; 76% female; 62% Caucasian) were randomly assigned to high-intensity ET (70–85% of heart rate reserve, n=38), moderate-intensity ET (40–55% heart rate reserve; n=32) or control for 6 months (n=36). The primary and secondary outcome measures were insulin sensitivity assessed using a frequently sampled intravenous glucose tolerance test and hepatic triglyceride content with magnetic resonance spectroscopy. Exploratory outcomes were cardiorespiratory fitness, physical activity and MRI and dual x-ray absorptiometry-derived measures of adiposity.Results:The study had 96% retention and attendance was 61±21% and 55±24% in the high- and moderate-intensity ET arms. Intention-to-treat analyses revealed that, at follow-up, insulin sensitivity was not different between high-intensity (−1.0u2009mUu2009kg−1u2009min−1; 95% confidence interval (CI): −1.6, +1.4u2009mUu2009kg−1u2009min−1) and moderate-intensity (+0.26u2009mUu2009kg−1u2009min−1; 95% CI: −1.3, +1.8u2009mUu2009kg−1u2009min−1) ET arms compared with controls (interaction, P=0.97). Similarly, hepatic triglyceride at follow-up was not different in high-intensity (−1.7% fat/water (F/W); 95% CI: −7.0, +3.6% F/W) and moderate-intensity (−0.40% FW; 95% CI: −6.0, +5.3% F/W) ET compared with controls. Both high intensity (+4.4u2009ml per kg-FFM (fat-free mass) per minute; 95% CI: 1.7, 7.1u2009mlu2009kg-FFM−1u2009min−1) and moderate intensity (+4.4u2009mlu2009kg-FFM−1u2009min−1; 95% CI: 1.6, 7.3u2009mlu2009kg-FFM−1u2009min−1) increased cardiorespiratory fitness, relative to controls (interaction P<0.001).Conclusions:ET improves cardiorespiratory fitness among obese adolescents; however, owing to lack of compliance, the influence of exercise intensity on insulin sensitivity and hepatic triglycerides remains unclear.