Kara L. Marlatt

The influence of gender on carotid artery compliance and distensibility in children and adults

Given the role of arterial wall elasticity in the development of cardiovascular disease, carotid artery compliance and distensibility have been used commonly over the last decade as predictors of cardiovascular risk, although their gender differences remain unknown. The purpose of our study was to evaluate the impact of gender on carotid arterial elasticity in a large sample of children and adults.

Changes in inflammation, oxidative stress and adipokines following bariatric surgery among adolescents with severe obesity

Background/Objectives:Inflammation, oxidative stress and dysregulation of adipokines are thought to be pathophysiological mechanisms linking obesity to the development of insulin resistance and atherosclerosis. In adults, bariatric surgery reduces inflammation and oxidative stress, and beneficially changes the levels of several adipokines, but little is known about the postsurgical changes among adolescents.Subjects/Methods:In two separate longitudinal cohorts we evaluated change from baseline of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), monocyte chemo-attractant protein-1 (MCP-1), oxidized low-density lipoprotein cholesterol (oxLDL), adiponectin, leptin and resistin up to 12 months following elective laparoscopic Roux-en-Y gastric bypass (RYGB) or vertical sleeve gastrectomy (VSG) surgery in adolescents with severe obesity.Results:In cohort 1, which consisted of 39 adolescents (mean age 16.5±1.6 years; 29 females) undergoing either RYGB or VSG, IL-6 (baseline: 2.3±3.4 pg ml−1 vs 12 months: 0.8±0.6 pg ml−1, P<0.01), leptin (baseline: 178±224 ng ml−1 vs 12 months: 41.4±31.9 ng ml−1, P<0.001) and oxLDL (baseline: 41.6±11.6 U l−1 vs 12 months: 35.5±11.1 U l−1, P=0.001) significantly decreased and adiponectin significantly increased (baseline: 5.4±2.4 μg ml−1 vs 12 months: 13.5±8.9 μg ml−1, P<0.001). In cohort 2, which consisted of 13 adolescents (mean age 16.5±1.6 years; 10 females) undergoing RYGB, results were similar: IL-6 (baseline: 1.7±0.9 pg ml−1 vs 12 months: 0.4±0.9 pg ml−1, P<0.05) and leptin (baseline: 92.9±31.3 ng ml−1 vs 12 months: 37.3±33.4 ng ml−1, P<0.001) significantly decreased and adiponectin significantly increased (baseline: 6.1±2.9 μg ml−1 vs 12 months: 15.4±8.0 μg ml−1, P<0.001). When the cohorts were combined to evaluate changes at 12 months, oxLDL also significantly decreased (baseline: 39.8±16.7 U l−1 vs 12 months: 32.7±11.9 U l−1, P=0.03).Conclusions:Bariatric surgery produced robust improvements in markers of inflammation, oxidative stress and several adipokines among adolescents with severe obesity, suggesting potential reductions in risk for type 2 diabetes and cardiovascular disease.

Topiramate for Weight Reduction in Adolescents With Severe Obesity

Background. Medications for use as an adjunct to lifestyle modification therapy (LSM) for severe adolescent obesity are limited. Topiramate results in weight reduction in adults with obesity, but has not been studied in adolescents. Objective. To examine the effect of topiramate plus LSM on body mass index (BMI) reduction in adolescents with severe obesity. Methods. Data for this retrospective chart review were collected from patients attending a pediatric weight management program who were treated with LSM plus topiramate for 3 months minimum. Mean BMI percent change from baseline was evaluated using t-tests. Results. Twenty-eight patients (mean age 15.2 ± 2.5 years, mean baseline BMI 46.2 ± 10.3 kg/m2) were identified for inclusion. The 6-month percent change in BMI was −4.9, 95% confidence interval (−7.1, −2.8), P < .001. Conclusions. Topiramate with concurrent LSM was associated with clinically meaningful BMI reduction in adolescents with severe obesity. Randomized controlled clinical trials examining efficacy and safety of topiramate for severe obesity in adolescents are needed.

Breakfast and fast food consumption are associated with selected biomarkers in adolescents.

Objective: Skipping breakfast and consuming fast food are related to the risk of obesity and are common adolescent behaviors. The relationship between these behaviors and biomarkers related to diabetes and CVD is understudied in this population. Methods: Data are from a study of the etiologic factors related to obesity risk in adolescents. Breakfast and fast food consumption were assessed using a self-report survey. Anthropometrics, fasting lipids, glucose, insulin, and homeostatic model assessment for insulin resistance (HOMA-IR) were assessed. Multivariate analyses were used to examine the relationship between dietary behaviors and selected biomarkers, controlling for calories consumed, body mass index (BMI), and demographic covariates. Results: 367 adolescents (11 to 18-years; mean 14.7 ± 1.8 years) were assessed at the University of Minnesota-Twin Cities from 2006–2008. Breakfast consumption was significantly associated with lower BMI, body fat, insulin, HOMA-IR, and metabolic syndrome (MetS) cluster score, while fast food consumption was associated with higher BMI, body fat, low-density lipoprotein cholesterol, triglycerides, glucose, insulin, HOMA-IR, and MetS cluster score. Some gender differences were observed. Conclusion: Breakfast and fast food consumption appear to be related to important metabolic syndrome biomarkers for chronic disease in a sample of healthy adolescents. The importance of this finding needs to be validated by examining the stability of this pattern over time and to assess the pattern in other populations.

Younger age is associated with lower reactive hyperemic index but not lower flow-mediated dilation among children and adolescents.

BACKGROUND The use of digital reactive hyperemia as a measure of endothelial function among children and adolescents is becoming increasingly common. However, unexpected observations of low reactive hyperemic index values in younger children in our laboratory led us to conduct a study evaluating the influence of age, sex, height, weight, blood pressure, body mass index (BMI), and finger volume on RHI values. METHODS Endothelial function, measured by digital reactive hyperemia (reactive hyperemic index: RHI) was assessed in 113 children and adolescents (mean age 12.4 ± 3.8 years; 64 males), with 102 also assessed for brachial artery flow-mediated dilation (FMD) using ultrasound imaging. Associations with age, sex, height, weight, systolic and diastolic blood pressure (SBP, DBP), BMI, and finger volume were evaluated. RESULTS Using GLM regression, age (β = 0.03, P = 0.014) and SBP (β = 0.015, P = 0.004) were significantly associated with RHI. No measures were associated with FMD. In the subset of individuals with measured finger volume, age (β = 0.025, P = 0.037) was the only measure significantly associated with log RHI. Similarly, no measures were associated with FMD. CONCLUSION Younger age is associated with lower RHI but not lower FMD among children and adolescents. These findings call into question the validity and usefulness of digital reactive hyperemia as a method to quantify endothelial function among younger children.

Impact of Pubertal Development on Endothelial Function and Arterial Elasticity

OBJECTIVES Little is known about the relation of pubertal development on endothelial function and arterial elasticity in children and adolescents; therefore, we compared brachial artery flow-mediated dilation and carotid artery elasticity across Tanner (pubertal) stages in children and adolescents. STUDY DESIGN Blood pressure, fasting lipids, glucose and insulin, body fat, insulin sensitivity adjusted for lean body mass, brachial flow-mediated dilation (percent dilation and area under the curve), endothelium-independent dilation (peak dilation and area under the curve), and carotid artery elasticity were evaluated across pubertal stages (Tanner I vs Tanner II-IV vs Tanner V) in 344 children and adolescents (184 males, 160 females; ages 6 to 21 years). RESULTS One hundred twenty-four subjects (mean age 8.23 ± 0.15 years; 52 females) were Tanner stage I; 105 subjects (mean age 13.19 ± 0.17 years; 47 females) were Tanner stages II-IV; and 115 subjects (mean age 17.19 ± 0.16 years; 61 females) were Tanner stage V. There were no significant differences for any of the measures of vascular structure and function across pubertal stages. CONCLUSION Results of the current study indicate that smooth-muscle and endothelial function, as well as carotid artery elasticity, do not differ throughout pubertal development and that accounting for pubertal stage when reporting vascular data in children and adolescents may be unnecessary.

Evaluation of gender differences in endothelium- independent dilation using peripheral arterial tonometry

Background:  A change in peripheral arterial tonometry (PAT) in response to reactive hyperaemia is often used to provide a non‐invasive measure of endothelium‐dependent dilation (EDD). Reactive hyperaemia does not allow one to quantify endothelium‐independent dilation (EID), which is part of overall vascular function. Although most research examining vascular function and cardiovascular disease has focused on EDD, there is evidence that cardiovascular risk factors may impair EID.

Endothelium-independent dilation in children and adolescents.

Peak brachial artery dilation post‐nitroglycerin (NTG) administration occurs between 3 and 5 min in adults. The purpose of this study was to identify the time to peak dilation response to sublingual NTG (0·3 mg) in youth. Endothelium‐independent dilation (EID) was measured in 198 healthy (113 males, 85 females) youth (6–18 years) via ultrasound imaging of the brachial artery following NTG administration. Time to peak EID was 268 s following NTG administration, with no significant (P = 0·6) difference between males and females. There was a significant (P<0·001) difference between EID post‐NTG at the 3 versus 4 min, 4 versus 5‐min, and 3 versus 5 min time points. Peak EID (males: 24·8 ± 0·5 versus females: 25·3 ± 0·6%, P = 0·6) was not significantly different after accounting for baseline diameter. Peak response to NTG administration occurs between 4 and 5 min. The results demonstrate the importance of measuring EID up to 5‐min post‐NTG administration in youth.

Age and sex relationship with flow-mediated dilation in healthy children and adolescents

Flow-mediated dilation (FMD) is a noninvasive technique used to measure conduit artery vascular function. Limited information is available on normative FMD values in healthy children and adolescents. The objective of this study was to assess relationships between age and sex with FMD across childhood and adolescence. Nine hundred and seventy-eight asymptomatic children (12 ± 3 yr, range 6-18 yr, 530 male) underwent ultrasonic brachial artery assessment before and after 5 min of forearm ischemia. Sex differences in FMD and baseline artery diameter were assessed using mixed linear models. Baseline artery diameter was smaller in females than males [2.96 mm (95% CI: 2.92-3.00) vs. 3.24 mm (3.19-3.28), P < 0.001] and increased with age across the cohort (P < 0.001). Diameter increased between ages 6 and 17 yr in males [from 2.81 mm (2.63, 3.00) to 3.91 mm (3.68, 4.14)] but plateaued at age 12 yr in females. Males had a lower FMD [7.62% (7.33-7.91) vs. 8.31% (7.95-8.66), P = 0.024], specifically at ages 17 and 18 yr. There was a significant effect of age on FMD (P = 0.023), with a reduction in FMD apparent postpuberty in males. In conclusion, the brachial artery increases structurally with age in both sexes; however, there are sex differences in the timing and rate of growth, in line with typical sex-specific adolescent growth patterns. Males have a lower FMD than females, and FMD appears to decline with age; however, these findings are driven by reductions in FMD as males near maturity. The use of age- and sex-specific FMD data may therefore not be pertinent in childhood and adolescence.

Brown Adipose Tissue: an Update on Recent Findings

Purpose of ReviewNew treatment approaches to weight loss and weight loss maintenance in humans are critical. Given its potential role in stimulating energy expenditure, brown adipose tissue (BAT) activation has become a trending topic as an anti-obesity treatment.Recent FindingsMost studies on BAT stimulation have been conducted in rodents and used cold stimulation. To date, few human trials exist that tested the effect of cold exposure on BAT. Those studies show that BAT contributes a small amount to overall energy metabolism which is unlikely to cause weight loss. Nonetheless, improvements in glucose metabolism have been demonstrated in humans. While new pharmacological approaches demonstrate some contribution of BAT to overall energy expenditure, the potential cardiovascular risk (increased heart rate and blood pressure to sustain the extra energy expenditure) may preclude their use.SummaryThere is no convincing evidence yet to indicate that BAT may be a viable pharmaceutical target for body weight loss or even weight loss maintenance. More research is needed to confirm the relevance of BAT and beige tissue to whole-body energy metabolism in humans.