Kumar, Seema

SummaryBackgroundAlthough obesity affects approximately one in five youths, only a fraction is treated in pediatric weight management clinics. Characteristics distinguishing youth with obesity who seek weight management treatment from those who do not are largely unknown. Yet identification of specific health characteristics which differentiate treatment‐seeking from non‐treatment seeking youth with obesity may shed light on underlying motivations for pursuing treatment.ObjectivesCompare the cardiometabolic profiles of an obesity treatment‐seeking sample of youth to a population‐based sample of youth with obesity, while controlling for body mass index (BMI).MethodsThis cross‐sectional study included participants, ages 12–17 years, with obesity from the Pediatric Obesity and Weight Evaluation Registry (POWER) and National Health and Nutrition Examination Survey, representing the treatment‐seeking and population samples, respectively. Mean differences were calculated for systolic and diastolic blood pressure percentiles, total cholesterol, low‐density and high‐density lipoprotein‐cholesterol, triglycerides, fasting glucose, glycated hemoglobin and alanine aminotransferase, while adjusting for age, sex, race/ethnicity, insurance status, and multiple of the 95th BMI percentile.ResultsThe POWER and National Health and Nutrition Examination Survey cohorts included 1,823 and 617 participants, respectively. The POWER cohort had higher systolic blood pressure percentile (mean difference 17.4, 95% confidence interval [14.6, 20.1], p < 0.001), diastolic blood pressure percentile (21.8 [19, 24.5], p < 0.001), triglycerides (42.3 [28, 56.5], p < 0.001) and alanine aminotransferase (7.5 [5.1, 9.8], p < 0.001) and lower fasting glucose (−6.9 [−8.2, −5.6], p < 0.001) and high‐density lipoprotein‐cholesterol (−2.3 [−3.8, −0.9], p < 0.002). There were no differences in total cholesterol or low‐density lipoprotein‐cholesterol or clinical differences in glycated hemoglobin.ConclusionFor a given BMI, obesity treatment‐seeking youth are more adversely affected by cardiometabolic risk factors than the general population of youth with obesity. This suggests that treatment‐seeking youth may represent a distinct group that is at particularly high risk for the development of future cardiometabolic disease.

SummaryPurposeSpexin, a novel peptide, has potential implications in obesity, satiety and energy homeostasis. The current study examined the relationship of spexin with various biomarkers of cardiovascular disease and endothelial function in adolescents with obesity.MethodsNineteen adolescents with obesity (age, 15.8 ± 1.7 years) were studied. Spexin, leptin and various cardiovascular disease biomarkers were measured. Endothelial function was assessed by high‐resolution Doppler ultrasonography of the right brachial artery.ResultsSpexin concentration (median [interquartile range] 0.38 ng/mL [0.29–0.59 ng/mL]) was inversely correlated (r = −0.50, P = 0.03) with leptin. When participants were clustered into two groups (‘high spexin and low leptin’ vs. ‘low spexin and high leptin’), the odds of having ‘low spexin and high leptin’ in participants with higher hs‐CRP (≥ 3 mg/L) were 12.25 times (95 per cent CI −1 to139, P = 0.026) higher than those of participants with lower hs‐CRP (<3 mg/L). Spexin levels, however, were not associated with measures of endothelial function.ConclusionsThe inverse association between spexin and leptin and the presence of higher concentrations of hs‐CRP in adolescents with obesity in the setting of ‘low spexin and high leptin’ suggest a potential role for spexin in the regulation of satiety and certain cardiovascular risk factors in children with obesity.

Severe obesity is associated with abnormal lipids and increased risk for cardiovascular disease. Obesity is a risk factor for vitamin D deficiency. We examined relationship between 25-hydroxy vitamin D (25(OH)D) concentrations and lipids in children with severe obesity. Medical records of 376 children were reviewed. Linear regression models and logistic regression were used to examine the relationship between 25(OH)D and lipids after adjustment for age, gender, season of blood draw, body mass index (BMI) z-score, and BMI % of 95th percentile. Two-hundred sixty-three out of 376 children (70%) had 25(OH)D concentrations < 30 ng/mL. Concentrations of 25(OH)D were positively correlated with those of high-density lipoprotein cholesterol (HDL-C) (r2 = 0.08, r = 0.22, β = 0.16, 95% CI = 0.05–0.27, p = 0.004). HDL-C was lower in children with 25(OH)D < 30 ng/mL (n = 263) compared to those with 25(OH)D ≥ 30 ng/mL (n = 113) (41.3 ± 10.2 vs. 46.4 ± 12 mg/dL, p < 0.0001). Children with 25(OH)D concentrations < 30 ng/mL had greater adjusted odds of low HDL-C (<40 mg/dL) compared with those with 25(OH)D ≥ 30 ng/mL (47.9% vs. 29.2%, OR 2.15 (1.33–3.51), p = 0.0019). Total cholesterol and non-HDL-C were not correlated with 25(OH)D concentrations. Vitamin D deficiency is highly prevalent in children with severe obesity. Prospective clinical trials are warranted to determine if vitamin D supplementation can improve HDL-C and potentially decrease risk for cardiovascular disease in children with obesity.

Obesity in children is associated with several co-morbidities including dyslipidemia. Obstructive sleep apnea (OSA) is commonly seen in obese children. In adults, diagnosis of OSA independent of obesity is associated with cardiometabolic risk factors including dyslipidemia. There is limited data on the impact of treatment of OSA on lipids in children. The objective of the study was to examine the impact of treatment of OSA on lipids in 24 obese children. Methods: Seventeen children were treated with continuous positive airway pressure (CPAP) and five underwent adenotonsillectomy. Mean apnea hypopnea index prior to treatment was 13.0 + 12.1 and mean body mass index (BMI) was 38.0 + 10.6 kg/m2. Results: Treatment of OSA was associated with improvement in total cholesterol (mean change = −11 mg/dL, p < 0.001), and low-density lipoprotein cholesterol (mean change = –8.8 mg/dL, p = 0.021). Conclusion: Obese children should be routinely screened for OSA, as treatment of OSA favorably influences lipids and therefore decreases their cardiovascular risk.

The prevalence of childhood obesity has increased over the past 3 decades. This study was designed to understand how childhood body mass index (BMI) influences later risk of obesity. We calculated BMIs for children residing in Olmsted County, Minnesota, between January 1, 2005 and December 31, 2012 using medical records data. We defined homogenous BMI trajectory clusters using a nonparametric hill-climbing algorithm. Overall, 16,538 (47%) children had >3 weight assessments at least 1 year apart and were included in the analyses. Within the 8-year follow-up period, children who were younger than 2 years and overweight had a 3- fold increase of obesity (adjusted hazard ratio [HR] = 3.24; 95% confidence interval [CI] = 2.69-3.89) and those aged 5 years and overweight had a 10-fold increased risk of obesity (adjusted HR = 9.97, 95% CI = 8.55-11.62). Three distinct BMI trajectories could be distinguished prior to 5 years of age. The risk of developing obesity in those who are overweight increased dramatically with increasing age. Interventions to prevent obesity need to occur prior to school age to prevent children from entering unhealthy BMI trajectories.

ObjectiveTo assess the safety and efficacy of short‐term meal replacement therapy followed by topiramate for body mass index (BMI) reduction in adolescents with severe obesity.MethodsAdolescents (ages 12–18 years) with severe obesity (BMI ≥1.2 times the 95th percentile or BMI ≥35 kg/m2) were recruited for this double‐blind, randomized, placebo‐controlled trial. Participants completed 4 weeks of meal replacement therapy followed by randomization (1:1) to either 24 weeks of topiramate 75 mg/day or placebo. Mean changes were compared between groups.ResultsThirty adolescents (mean age 15.2 ± 1.7 years, mean BMI 40.3 ± 4.6 kg/m2) completed the meal replacement phase and were randomized; 21 completed the study. The difference in mean percent change in BMI between the topiramate and placebo groups was not significant (−1.9%; 95% CI: −5.2% to +1.5%; P = 0.291). Significant improvements in visceral fat and very‐low‐density lipoprotein cholesterol were observed in the topiramate compared with the placebo group. There were no concerning changes in neurocognitive function or bone health.ConclusionsIn this pilot study, 4 weeks of meal replacement therapy followed by 24 weeks of low‐dose topiramate compared with meal replacement therapy alone did not result in significant BMI reduction for adolescents with severe obesity.

The term disappearing HDL syndrome refers to development of severe high density lipoprotein cholesterol (HDL-C) deficiency in noncritically ill patients with previously normal HDL-C and triglyceride levels. Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of the immune system due to an inability to regulate lymphocyte homeostasis resulting in lymphadenopathy and hepatosplenomegaly. We describe a 17-year-old boy who was evaluated in the lipid clinic for history of undetectable or low HDL-C and low density lipoprotein cholesterol (LDL-C) levels. Past medical history was significant for ALPS IA diagnosed at 10 years of age when he presented with bilateral cervical adenopathy. He was known to have a missense mutation in one allele of the FAS protein extracellular domain consistent with ALPS type 1A. HDL-C and LDL-C levels had been undetectable on multiple occasions, though lipids had not been measured prior to the diagnosis of ALPS. He had been receiving sirolimus for immunosuppression. The HDL-C and LDL-C levels correlated with disease activity and improved to normal levels during times when the activity of ALPS was controlled. This case highlights the importance of considering ALPS as a cause of low HDL-C and LDL-C levels in a child with evidence of lymphoproliferation.

AbstractBackgroundChildhood obesity is underdiagnosed in primary care practices. Our study aimed to compare rates of documentation of diagnosis of obesity and counselling for nutrition and physical activity at an academic primary care practice prior to and following implementation of a body mass index (BMI)‐based electronic point of care clinical reminder tool.MethodsWe performed a retrospective record review of children aged 2–18 years undergoing well child visits during any of three calendar years (2009, 2011 and 2013). The electronic clinical reminder tool was implemented in September 2010. Records of children with BMI > 95th percentile were electronically searched for terms of documentation of diagnosis of obesity and nutrition and physical activity counselling. Multivariable logistic regression models were used to adjust for potential patient and provider confounders.ResultsAmong those with BMI ≥ 95th percentile, there was a statistically significant increase in documentation of diagnosis of obesity (45.5% in 2009 vs. 52.4% in 2011; P < 0.001; adjusted odds ratio 1.36; 95% CI 1.13–1.65) and in counselling for physical activity and nutrition (66.8% in 2009 vs. 75.2% in 2011; P < 0.001; adjusted odds ratio 1.33; 95% CI 1.06–1.66) following implementation of the tool. Compared with 2011, there was no statistically significant increase in documentation of obesity (50.4%) or nutrition and physical activity counselling (77.9%) in 2013.ConclusionsThe implementation of a point of care clinical reminder tool was associated with improvement in documentation of diagnosis of obesity and counselling for nutrition and physical activity. Further studies are needed to determine the impact of these automated tools on weight outcomes in children.

SummaryBackgroundObesity in children is associated with vitamin D deficiency and endothelial dysfunction. It is not known if treatment with vitamin D improves endothelial function in obese adolescents.ObjectiveThis study aimed to determine whether treatment with vitamin D3 improves endothelial function in obese adolescents.MethodsNineteen obese adolescents, 13–18 years of age, with 25‐hydroxy vitamin D (25[OH]D) levels <75 nmol L−1 were treated with 100 000 IU vitamin D3 orally once a month for 3 months in an open‐label, single‐centre prospective trial. Endothelial function was assessed by flow‐mediated dilatation (FMD) of the brachial artery at study entry and 1 month after the third dose of vitamin D3. Biochemical parameters, including calcium, fasting lipids, glucose, insulin and high‐sensitivity C‐reactive protein, were also obtained.ResultsMean 25(OH)D levels increased from 55.9 ± 12.2 to 86.9 ± 16.7 nmol L−1 (P < 0.01). There was no correlation between 25(OH)D levels and brachial artery FMD. The brachial artery FMD (%) did not change significantly following vitamin D3 treatment (9.5 ± 3.53 vs. 10.3 ± 3.83, P = 0.83). Serum parathyroid hormone declined from 3.8 ± 1.5 to 3.1 ± 1 pmol L−1 (P = 0.01). The remainder of biochemical measurements did not show a significant change.ConclusionsTreatment with vitamin D3, 100 000 IU once a month for 3 months was effective in increasing 25(OH)D levels in obese adolescents but did not impact endothelial function.