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Article ; Online: Energy expenditure deficits drive obesity in a mouse model of Alström syndrome.

Stephenson, Erin J / Kinney, Clint E / Stayton, Amanda S / Han, Joan C

2023 Volume 31, Issue 11, Page(s) 2786–2798

Abstract: Objective: Alström syndrome (AS) is a rare multisystem disorder of which early onset childhood obesity is a cardinal feature. Like humans with AS, animal models with Alms1 loss-of-function mutations develop obesity, supporting the notion that ALMS1 is ... ...

Abstract	Objective: Alström syndrome (AS) is a rare multisystem disorder of which early onset childhood obesity is a cardinal feature. Like humans with AS, animal models with Alms1 loss-of-function mutations develop obesity, supporting the notion that ALMS1 is required for the regulatory control of energy balance across species. This study aimed to determine which component(s) of energy balance are reliant on ALMS1. Methods: Comprehensive energy balance phenotyping was performed on Alms1 Results: It was found that adiposity gains occurred early and rapidly in Alms1 Conclusions: Either loss of ALMS1 causes a developmental delay in the mechanisms controlling early life EE or activation of compensatory mechanisms occurs after obesity is established in AS. Future studies will determine how ALMS1 modulates EE and how sex moderates this process.
MeSH term(s)	Female ; Male ; Child ; Humans ; Mice ; Animals ; Aged ; Alstrom Syndrome/genetics ; Cell Cycle Proteins/genetics ; Pediatric Obesity ; Disease Models, Animal ; Adipose Tissue
Chemical Substances	Cell Cycle Proteins
Language	English
Publishing date	2023-09-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2230457-5
ISSN	1930-739X ; 1071-7323 ; 1930-7381
ISSN (online)	1930-739X
ISSN	1071-7323 ; 1930-7381
DOI	10.1002/oby.23877
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Article: Review of Insulin Resistance in Dilated Cardiomyopathy and Implications for the Pediatric Patient Short Title: Insulin Resistance DCM and Pediatrics.

Mak, Daniel / Ryan, Kaitlin A / Han, Joan C

Frontiers in pediatrics

2021 Volume 9, Page(s) 756593

Abstract: Energy metabolism in the heart is affected during states of dysfunction. Understanding how the heart utilizes substrates in cardiomyopathy may be key to the development of alternative treatment modalities. Myocardial insulin resistance has been proposed ... ...

Abstract	Energy metabolism in the heart is affected during states of dysfunction. Understanding how the heart utilizes substrates in cardiomyopathy may be key to the development of alternative treatment modalities. Myocardial insulin resistance has been proposed as a possible barrier to effective glucose metabolism in the heart. Extensive literature on the topic in adult individuals exists; however, review in the pediatric population is sparse. The pathophysiology of disease in children and adolescents is unique. The aim of this paper is to review the current knowledge on insulin resistance in dilated cardiomyopathy while also filling the gap when considering care in the pediatric population.
Language	English
Publishing date	2021-10-28
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2711999-3
ISSN	2296-2360
ISSN	2296-2360
DOI	10.3389/fped.2021.756593
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Article ; Online: Management of Monogenic and Syndromic Obesity.

Han, Joan C / Rasmussen, Marcus C / Forte, Alison R / Schrage, Stephanie B / Zafar, Sarah K / Haqq, Andrea M

Gastroenterology clinics of North America

2023 Volume 52, Issue 4, Page(s) 733–750

Abstract: Similar to the general population, lifestyle interventions focused on nutrition and physical activity form the foundation for treating obesity caused by rare genetic disorders. Additional therapies, including metreleptin and setmelanotide, that target ... ...

Abstract	Similar to the general population, lifestyle interventions focused on nutrition and physical activity form the foundation for treating obesity caused by rare genetic disorders. Additional therapies, including metreleptin and setmelanotide, that target defects within the leptin signaling pathway can effectively synergize with lifestyle efforts to treat monogenic disorders of leptin, leptin receptor, proopiomelanocortin (POMC), and proprotein convertase subtilisin/kexin type 1 (PCSK1) and syndromic conditions, such as the ciliopathies Bardet-Biedl and Alström syndromes, whose pathophysiological mechanisms also converge on the leptin pathway. Investigational treatments for Prader-Willi syndrome target specific defects caused by reduced expression of paternally derived genes within the chromosome 15q region.
MeSH term(s)	Humans ; Leptin/genetics ; Obesity/genetics ; Obesity/therapy ; Obesity/metabolism ; Prader-Willi Syndrome/genetics ; Prader-Willi Syndrome/therapy
Chemical Substances	Leptin
Language	English
Publishing date	2023-09-27
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	92114-2
ISSN	1558-1942 ; 0889-8553
ISSN (online)	1558-1942
ISSN	0889-8553
DOI	10.1016/j.gtc.2023.08.005
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Article ; Online: Prediction of resting energy expenditure for adolescents with severe obesity: A multi-centre analysis.

Rydin, Amy A / Severn, Cameron / Pyle, Laura / Morelli, Nazeen / Shoemaker, Ashley H / Chung, Stephanie T / Yanovski, Jack A / Han, Joan C / Higgins, Janine A / Nadeau, Kristen J / Fox, Claudia / Kelly, Aaron S / Cree, Melanie G

Pediatric obesity

2024 , Page(s) e13123

Abstract: Background and objectives: Resting energy expenditure (REE) assessments can help inform clinical treatment decisions in adolescents with elevated body mass index (BMI), but current equations are suboptimal for severe obesity. We developed a predictive ... ...

Abstract	Background and objectives: Resting energy expenditure (REE) assessments can help inform clinical treatment decisions in adolescents with elevated body mass index (BMI), but current equations are suboptimal for severe obesity. We developed a predictive REE equation for youth with severe obesity and obesity-related comorbidities and compared results to previously published predictive equations. Methods: Data from indirect calorimetry, clinical measures, and body composition per Dual x-ray absorptiometry (DXA) were collected from five sites. Data were randomly divided into development (N = 438) and validation (N = 118) cohorts. A predictive equation was developed using Elastic Net regression, using sex, race, ethnicity, weight, height, BMI percent of the 95th%ile (BMIp95), waist circumference, hip circumference, waist/hip ratio, age, Tanner stage, fat and fat-free mass. This equation was verified in the validation cohort and compared with 11 prior equations. Results: Data from the total cohort (n = 556, age 15 ± 1.7 years, 77% female, BMIp95 3.3 ± 0.94) were utilized. The best fit equation was REE = -2048 + 18.17 × (Height in cm) - 2.57 × (Weight in kg) + 7.88 × (BMIp95) + 189 × (1 = male, 0 = female), R Conclusion: This new equation provides an updated REE prediction that accounts for severe obesity and metabolic complications frequently observed in contemporary youth.
Language	English
Publishing date	2024-04-24
Publishing country	England
Document type	Journal Article
ZDB-ID	2655527-X
ISSN	2047-6310 ; 2047-6302
ISSN (online)	2047-6310
ISSN	2047-6302
DOI	10.1111/ijpo.13123
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Article ; Online: Delayed Onset of Sleep in Adolescents With PAX6 Haploinsufficiency.

Hanish, Alyson E / Han, Joan C

Biological research for nursing

2018 Volume 20, Issue 2, Page(s) 237–243

Abstract: Objective: PAX6 haploinsufficiency ( +/-) can occur due to mutations involving only PAX6 in patients with isolated aniridia or as contiguous gene deletions in patients with Wilms tumor, aniridia, genitourinary anomalies, and range of developmental and ... ...

Abstract	Objective: PAX6 haploinsufficiency ( +/-) can occur due to mutations involving only PAX6 in patients with isolated aniridia or as contiguous gene deletions in patients with Wilms tumor, aniridia, genitourinary anomalies, and range of developmental and intellectual disabilities syndrome. Given the role of PAX6 in pineal development and circadian regulation, adolescents with PAX6+/- may experience sleep-wake disturbances. The purpose of this observational study was to explore sleep-related phenotypes in adolescents with PAX6+/-. Methods: This study compared sleep phenotypes of nine subjects with PAX6+/- (aged 10-19 years) with previously published data on healthy adolescents ( n = 25, aged 10-18 years). Subjects completed the Cleveland Adolescent Sleepiness Questionnaire (CASQ), Patient Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance (v. 1.0; 8a), and PROMIS Sleep-Related Impairment (v. 1.0; 8b) Questionnaires and wore actigraphs for seven nights to record sleep patterns. Results: Total CASQ, PROMIS sleep-related impairment, and PROMIS sleep disturbance scores were not statistically different between the groups ( ps > .15). Actigraph data for lights off to sleep-onset time were found to be significantly higher in subjects with PAX6+/- versus the healthy comparison group (adjusted mean [95% confidence interval]: 20.1 min [8.1, 49.8] vs. 6.2 min [3.7, 10.4], respectively, p = .04). Conclusion: Both adolescents with PAX6+/- and the healthy comparison group on average slept less than 8 hr/night, and overall sleep deprivation in adolescents may have masked differences between groups. This study used rare genetic disorders with biological vulnerability to sleep problems as a genotype-phenotype model. Knowledge of sleep-related phenotypes will assist in designing studies to manage sleep-related symptoms in adolescents.
MeSH term(s)	Adolescent ; Child ; Female ; Haploinsufficiency/genetics ; Haploinsufficiency/physiology ; Humans ; Male ; Mutation ; PAX6 Transcription Factor/genetics ; Phenotype ; Sleep/genetics ; Sleep/physiology ; Sleep Wake Disorders/genetics ; Sleep Wake Disorders/physiopathology ; Surveys and Questionnaires
Chemical Substances	PAX6 Transcription Factor ; PAX6 protein, human
Language	English
Publishing date	2018-01-17
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
ZDB-ID	2145107-2
ISSN	1552-4175 ; 1099-8004
ISSN (online)	1552-4175
ISSN	1099-8004
DOI	10.1177/1099800417753670
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Article ; Online: The efficacy and safety of setmelanotide in individuals with Bardet-Biedl syndrome or Alström syndrome: Phase 3 trial design.

Haws, Robert M / Gordon, Gregory / Han, Joan C / Yanovski, Jack A / Yuan, Guojun / Stewart, Murray W

Contemporary clinical trials communications

2021 Volume 22, Page(s) 100780

Abstract: Background: A phase 2 trial has suggested that treatment with the melanocortin-4 receptor (MC4R) agonist setmelanotide is associated with a decrease in hunger and weight-related outcomes in participants with Bardet-Biedl syndrome (BBS) and Alström ... ...

Abstract	Background: A phase 2 trial has suggested that treatment with the melanocortin-4 receptor (MC4R) agonist setmelanotide is associated with a decrease in hunger and weight-related outcomes in participants with Bardet-Biedl syndrome (BBS) and Alström syndrome. Here, we present the study design of an ongoing, randomized, double-blind, placebo-controlled, phase 3 trial to assess the long-term efficacy and safety of setmelanotide for the treatment of obesity and hyperphagia in individuals with BBS or Alström syndrome (ClinicalTrials.gov identifier: NCT03746522). Methods: It was initially planned that ~30 participants aged ≥6 years with a clinical diagnosis of BBS or Alström syndrome would be enrolled. Participants with obesity as defined by a body mass index ≥30 kg/m Conclusions: This pivotal trial is designed to evaluate the efficacy and safety of setmelanotide for the treatment of obesity and hyperphagia in individuals with BBS and Alström syndrome. Submission category: Study Design, Statistical Design, Study Protocols.
Language	English
Publishing date	2021-05-03
Publishing country	Netherlands
Document type	Journal Article
ISSN	2451-8654
ISSN (online)	2451-8654
DOI	10.1016/j.conctc.2021.100780
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Article ; Online: Prenatal metabolomic profiles mediate the effect of maternal obesity on early childhood growth trajectories and obesity risk: the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) Study.

Hu, Zunsong / Han, Luhang / Liu, Jiawang / Fowke, Jay H / Han, Joan C / Kakhniashvili, David / LeWinn, Kaja Z / Bush, Nicole R / Mason, W Alex / Zhao, Qi

The American journal of clinical nutrition

2023 Volume 116, Issue 5, Page(s) 1343–1353

Abstract: Background: Maternal prepregnancy obesity is an important risk factor for offspring obesity, which may partially operate through prenatal programming mechanisms.: Objectives: The study aimed to systematically identify prenatal metabolomic profiles ... ...

Abstract	Background: Maternal prepregnancy obesity is an important risk factor for offspring obesity, which may partially operate through prenatal programming mechanisms. Objectives: The study aimed to systematically identify prenatal metabolomic profiles mediating the intergenerational transmission of obesity. Methods: We included 450 African-American mother-child pairs from the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) Study pregnancy cohort. LC-MS was used to conduct metabolomic profiling on maternal plasma samples of the second trimester. The childhood growth outcomes of interest included BMI trajectories from birth to age 4 y (rising-high-, moderate-, and low-BMI trajectories) as well as overweight/obesity (OWO) risk at age 4 y. Mediation analysis was conducted to identify metabolite mediators linking maternal OWO and childhood growth outcomes. The potential causal effects of maternal OWO on metabolite mediators were examined using the Mendelian randomization (MR) method. Results: Among the 880 metabolites detected in the maternal plasma during pregnancy, 14 and 11 metabolites significantly mediated the effects of maternal prepregnancy OWO on childhood BMI trajectories and the OWO risk at age 4 y, respectively, and 5 mediated both outcomes. The MR analysis suggested 6 of the 20 prenatal metabolite mediators might be causally influenced by maternal prepregnancy OWO, most of which are from the pathways related to the metabolism of amino acids (hydroxyasparagine, glutamate, and homocitrulline), sterols (campesterol), and nucleotides (N2,N2-dimethylguanosine). Conclusions: Our study provides further evidence that prenatal metabolomic profiles might mediate the effect of maternal OWO on early childhood growth trajectories and OWO risk in offspring. The metabolic pathways, including identified metabolite mediators, might provide novel intervention targets for preventing the intrauterine development of obesity in the offspring of mothers with obesity.
MeSH term(s)	Child, Preschool ; Humans ; Female ; Pregnancy ; Pediatric Obesity/etiology ; Obesity, Maternal/complications ; Body Mass Index ; Prenatal Exposure Delayed Effects ; Prospective Studies ; Overweight/complications ; Vitamins
Chemical Substances	Vitamins
Language	English
Publishing date	2023-02-10
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	280048-2
ISSN	1938-3207 ; 0002-9165
ISSN (online)	1938-3207
ISSN	0002-9165
DOI	10.1093/ajcn/nqac244
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Article ; Online: Waitlist management in a pediatric weight management clinic: implementing an orientation session.

Smith, Webb A / Gray, Emily / Jones, Tamekia L / Han, Joan C / Burton, E Thomaseo

BMC pediatrics

2021 Volume 21, Issue 1, Page(s) 416

Abstract: Background: This study evaluates implementation of an orientation session to address a waitlist of more than 2000 referrals to a pediatric weight management clinic in the Mid-South United States.: Methods: An hour-long group-based orientation to the ... ...

Abstract	Background: This study evaluates implementation of an orientation session to address a waitlist of more than 2000 referrals to a pediatric weight management clinic in the Mid-South United States. Methods: An hour-long group-based orientation to the pediatric weight management clinic was implemented to provide information about the structure and expectations of the clinic as well as education on healthy lifestyle recommendations. Families were contacted from the waitlist by telephone and invited to attend an orientation session prior to scheduling a clinic appointment. Results: Of 2251 patients contacted from the waitlist, 768 scheduled an orientation session, of which 264 (34 %) attended. Of the 264 orientation participants, 246 (93 %) scheduled a clinic appointment. Of those, 193 (79 %) completed a clinic visit. Waitlist times decreased from 297.8 ± 219.4 days prior to implementation of orientation sessions to 104.1 ± 219.4 days after. Conclusions: Orientation has been an effective and efficient way to triage patient referrals while maximizing attendance in limited clinic slots for patients and families demonstrating interest and motivation. Elements of this approach are likely generalizable to other pediatric clinical settings that must strategically manage a large volume of patient referrals.
MeSH term(s)	Ambulatory Care ; Ambulatory Care Facilities ; Appointments and Schedules ; Child ; Humans ; Motivation ; Referral and Consultation ; United States
Language	English
Publishing date	2021-09-22
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2041342-7
ISSN	1471-2431 ; 1471-2431
ISSN (online)	1471-2431
ISSN	1471-2431
DOI	10.1186/s12887-021-02868-w
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Article ; Online: The contribution of platelets to peripheral BDNF elevation in children with autism spectrum disorder.

Farmer, Cristan A / Thurm, Audrey E / Honnekeri, Bianca / Kim, Paul / Swedo, Susan E / Han, Joan C

Scientific reports

2021 Volume 11, Issue 1, Page(s) 18158

Abstract: Brain-derived neurotrophic factor (BDNF), a key peptide in neurocognitive development, has been reported to be elevated in the serum of children with autism spectrum disorder (ASD). In a few studies, however, no differences or the converse have been ... ...

Abstract	Brain-derived neurotrophic factor (BDNF), a key peptide in neurocognitive development, has been reported to be elevated in the serum of children with autism spectrum disorder (ASD). In a few studies, however, no differences or the converse have been documented. As a secondary analysis of a natural history study, we examined differences in ELISA serum BDNF between a group of children aged 1 to 9 years (69% white) with ASD (n = 94) and those with typical development (n = 52) or non-ASD developmental delay (n = 21), while accounting for the potential confounding effects of platelet quantity. Platelet counts were measured within 4 h of blood draw using an automated cell counter. Taqman single nucleotide polymorphism (SNP) assays were used to genotype 11 SNPs within the BDNF locus. Unadjusted mean BDNF concentration was higher in children with ASD than in children with typical development (standardized mean difference = 0.23; 95% CI 0.07, 0.38), but not children with non-ASD developmental delay. The magnitude of this difference was reduced after adjusting for platelet count (standardized mean difference = 0.18; 95% CI 0.02, 0.33). Although some BDNF SNPs were related to BDNF concentration, the distributions of these genotypes did not differ across diagnostic groups. This study replicates previous work suggesting that average serum BDNF concentration is higher in ASD compared to typical development, and extends that work by highlighting the potentially confounding role of platelet counts. The etiology of platelet count differences warrants further elucidation. Nonetheless, our results suggest that elevation in BDNF may be partially explained by higher platelet counts in children with ASD, an association that should be considered in future analysis and interpretation.Registration: NCT00298246.
MeSH term(s)	Autism Spectrum Disorder/blood ; Blood Platelets/metabolism ; Brain-Derived Neurotrophic Factor/blood ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Models, Biological
Chemical Substances	Brain-Derived Neurotrophic Factor ; BDNF protein, human (7171WSG8A2)
Language	English
Publishing date	2021-09-13
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-97367-4
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Article: Acceptability of Time-Limited Eating in Pediatric Weight Management.

Tucker, Jared M / Siegel, Robert / Murray, Pamela J / Han, Joan C / Boyer, Katherine / Reed, Nichole / Allenby, Taylor / Novick, Marsha

Frontiers in endocrinology

2022 Volume 13, Page(s) 811489

Abstract: Background: Adherence to dietary interventions is a significant barrier in the treatment of childhood obesity. Time-limited eating (TLE) is a simple dietary approach that limits food intake to a given number of consecutive hours per day, but parental ... ...

Abstract	Background: Adherence to dietary interventions is a significant barrier in the treatment of childhood obesity. Time-limited eating (TLE) is a simple dietary approach that limits food intake to a given number of consecutive hours per day, but parental and youth acceptability of TLE in youth with obesity is unknown. This study explored the feasibility of utilizing TLE among parents and youth attending pediatric weight management (PWM). Methods: Members of COMPASS (Childhood Obesity Multi-Program Analysis and Study System) developed a survey to assess the acceptability of TLE in families attending PWM, which included patient characteristics, current diet and sleep schedules, and interests in trying TLE. The survey was administered electronically Results: Patients (n=213) were 13.0 ± 2.5 years old, 58% female, 52% White, 22% Black, 17% Hispanic/Latino, and 47% reported a diagnosed psychological disorder. On average, parents reported their child's daily eating spanned 12.5 ± 1.9 hours (7:35am - 8:05pm) and included 5.6 ± 1.6 eating bouts (meals + snacks). Most parents reported being likely to try TLE ≤12 hours/d (TLE12: 66%), which was similar to the likelihood of following a nutrient-balanced diet (59%). Likelihood was lower for TLE ≤10 hours/d (TLE10: 39%) or ≤8 hours/d (TLE8: 26%) (p<0.001 for both). Interest in TLE was not consistently related to patient age, sex, or ethnicity, but was lower in patients with a psychiatric diagnosis vs. no diagnosis (TLE8: 19% vs. 32%; p=0.034). Patients of parents who reported being likely to try TLE, compared to those unlikely to try TLE, had shorter eating windows (p<0.001) and ate fewer snacks (p=0.006). Conclusions: Two-thirds of parents with children attending PWM programs report interest in TLE ≤12 hours/d regardless of demographic characteristics, but interest wanes when limiting eating to ≤10 or ≤8 hours per day. Time-limited eating appears to be a feasible option in PWM settings provided treatment options are individualized based on the interests and barriers of patients and their families.
MeSH term(s)	Adolescent ; Child ; Diet ; Ethnicity ; Feeding Behavior/psychology ; Female ; Humans ; Male ; Pediatric Obesity/therapy ; Time Factors
Language	English
Publishing date	2022-04-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2022.811489
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