Background: Early-onset severe obesity and hyperphagia may indicate an underlying genetic cause. Individuals with a pathogenic or likely pathogenic variant in the leptin melanocortin-4 receptor ...(MC4R) pathway (eg, in SH2B1) may benefit from targeted treatment. The specific MC4R agonist setmelanotide may safely reduce body weight and hunger in individuals with SH2B1 haploinsufficiency. Methods: This Phase 2 study (NCT03013543) assessed setmelanotide in individuals with obesity (body mass index BMI >95th percentile for those aged 6-15 years or BMI >30 kg/m2 for those aged >16 years) due to heterozygous SH2B1 variants or chromosomal deletion of the 16p11.2 locus involving SH2B1. Participants were enrolled from August 2019 and the study is ongoing. Following dose titration, participants received 3 months of open- label treatment. Body weight, BMI, and hunger outcomes were assessed at month 3. Results: Thirty-five participants (22 with SH2B1 variants and 13 with 16p11.2 deletion) enrolled; 15 (43%) achieved >0.15 reduction in BMI Z score (if aged <18 years) or >5% reduction in body weight (if aged >18 years) and were classified as responders. Mean (SD) change in BMI Z score in participants aged <18 years was -0.2 (0.1; n = 7) for responders versus 0.0 (0.1; n = 6) for nonresponders. Mean (SD) percent weight change in participants aged >18 years was -7.2% (2.1%; n = 8) for responders versus -0.8% (2.3%; n = 14) for nonresponders. Mean (SD) percent change in most hunger score for participants aged >12 years was -28% (67%; n = 14) for responders versus -26% (36%; n = 18) for nonresponders. Adverse events (AEs) included skin hyperpigmentation (71%), nausea (49%), and headache (37%). One serious AE of melanocytic nevus occurred and was not considered melanoma or treatment related. Conclusions: A 3-month trial of setmelanotide may identify individuals with obesity due to functional genetic disturbance of SH2B1 who respond to setmelanotide. The next step is to evaluate long-term benefits.
Background: Tyrosine kinase inhibitors (TKIs) have improved survival in patients with chronic myeloid leukemia (CML). Despite the major prognostic benefits of TKIs, there are a range of endometabolic ...out- comes that may be impacted by their off-target effects, including obesity (Body Mass Index (BMI) > 30 kg/m2). This systematic review assessed the association between TKIs and obesity in CML patients. Methods: Literature searches were conducted in multiple databases up to October 2020. Eligible studies included male and female CML patients > 18 years of age receiving TKIs. We used GRADE to assess the quality of evidence. Results: Eight studies reported BMI data in adults with CML on TKI therapy, including Imatinib, Dasatinib, Nilotinib and Ponatinib used over 0.1-165.6 months. Five studies reported pre-trial BMI only, and were not analyzed further. Two before-and-after studies investigating the effects of Nilotinib reported a non-significant trend on lowering BMI. These studies reported only median and range values, which precluded ascertain- ment of how many patients developed obesity with treatment. One before-and-after study reported individual BMI data in adults with type 2 diabetes and CML (n = 4), receiving Imatinib treatment. Baseline BMI was 38.4 ± 3.59 kg/m2, and follow-up BMI was 36.43 ± 5.79. All participants maintained their BMI at similar levels after treatment. The quality of the evidence using GRADE was very low. Conclusions: Limited evidence suggests that TKIs do not appear to impact BMI in adults with CML on TKI therapy. However, the high heterogeneity, small sample size, and low quality of evidence suggests a need for longitudinal studies on obesity in CML patients to determine the trajectory of BMI changes with TKI therapy.
Background: Normal weight obesity (NWO) is having a normal body mass index (BMI) with excess body fat percent (BF%), and they have a higher risk for cardiovascular disease risks compared to normal ...weight lean (NWL; normal BMI with normal BF%). We aimed to determine the differences in moderate-to-vigorous physical activity (MVPA), perceived health, and perceived body size among NWL, NWO, and obesity (OB) groups. Methods: We studied 2056 adults (>19 years) in the National Health and Nutrition Examination Survey (NHANES) 2003-2006 cycles. Normal BMI was defined as 18.5-24.9 kg/m2. Excess BF% was defined as BF% of >23.1% and >33.3% for men and women, respectively. Participants were grouped as 1) NWL, 2) NWO, and 3) OB: BMI> 25kg/ m2 with excess BF%. BF% and MVPA were measured using dual-energy absorptiometry, and accelerometers (ActiGraph), respectively. MVPA and sedentary time were defined as the presence of >2020 and <100 counts per minute, respectively for 1 minute or more. Group differences were examined using multiple regression and chi-square tests. Results: When adjusted for age, sex, race, education, income, smoking, alcohol consumption, and NHANES cycles, MVPA was significantly lower in both NWO and OB compared to NWL by 8.80 (95% CI = -15.12, -2.47) and 10.57 (95%CI = -14.96, -6.18), respectively. There was no significant difference in sedentary time between the groups (p >.05). Perceived health status and perceived weight had a significant relationship with groups (chi-square p < .001). ~71%, 62%, and 52% of NWL, NWO, and OB, respectively perceived their health as excellent or very good. ~78%, 63%, and 22% of NWL, NWO, and OB, respectively perceived they have the right weight. Conclusions: Both NWO and OB groups engaged in less MVPA compared to NWL. The majority of individuals with NWO did not perceive that they have increased BF% and the associated health risks and this may be a barrier to engage in PA. However, this hypothesis needs to be confirmed by future studies.
Abstract
Introduction
The Psychomotor Vigilance Test (PVT) is a behavioral attention measure widely used to describe sleep loss deficits. Although there are reported differences in PVT performance ...for various demographic groups, no study has examined the relationship between measures on the 10-minute PVT (PVT10) and the 3-minute PVT (PVT3) within sex, age, and body mass index (BMI) groups throughout a highly controlled sleep deprivation study.
Methods
Forty-one healthy adults (mean±SD ages, 33.9±8.9y) participated in a 13-night experiment 2 baseline nights (10h-12h time in bed, TIB) followed by 5 sleep restriction (SR1-5) nights (4h TIB), 4 recovery nights (R1-R4; 12h TIB), and 36h total sleep deprivation (TSD). A neurobehavioral test battery, including the PVT10 and PVT3 was completed every 2h during wakefulness. Repeated measures correlation (rmcorr) compared PVT10 and PVT3 lapses (reaction time RT >355ms PVT3 and >500ms PVT10) and response speed (1/RT) by examining correlations by day (e.g., baseline day 2) and time point (e.g., 1000h-2000h) within sex groups (18 females), within age groups defined by a median split (median=32, range=21-49y), and within BMI groups defined by a median split (median=25, range=17-31).
Results
PVT10 and PVT3 1/RT was significantly correlated at all study days and time points excluding at baseline for the younger group and at R2 for the higher BMI group. PVT10 and PVT3 lapses showed overall lower correlations across the study relative to 1/RT. Lapses were not significantly correlated at baseline for any group, for males across recovery (R1-R4), for the high BMI group at R2-R4, for the older group at R2-R3, or for the younger group at SR5 or R3.
Conclusion
Differentiating participants based on age, sex, or BMI revealed important variation in the relationship between PVT10 and PVT3 measures across the study. Surprisingly, lapses were not significantly correlated at baseline for any demographic group or across recovery for males or the high BMI or older group. Thus, PVT10 and PVT3 lapses may be less comparable in certain populations when well-rested. These findings add to a growing literature suggesting demographic factors may be important factors to consider when evaluating the effects of sleep loss.
Support (if any)
ONR Award N00014-11-1-0361;NIH UL1TR000003;NASA NNX14AN49G and 80NSSC20K0243; NIHR01DK117488
Abstract
Introduction
Few studies have examined circadian phase after job loss, an event that upends daily routine. It is common that a daily routine begins with the consumption of breakfast, and ...breakfast behavior may contribute to health status in adults. Therefore, we sought to examine whether a later midpoint of sleep was associated with breakfast skipping among adults whose schedules were no longer dictated by employment.
Methods
Data were obtained from the Assessing Daily Activity Patterns Through Occupational Transitions (ADAPT) study. The sample of 155 participants had involuntarily lost their jobs in the last 90 days. Both cross-sectional and 18-month longitudinal analyses assessed the relationship between sleep midpoint after job loss and current and later breakfast skipping. Assessment periods were 14 days. Sleep was measured via actigraphy, and breakfast skipping was measured via daily diary (1 = had breakfast; 0 = did not have breakfast). The midpoint of sleep was calculated as the circular center based on actigraphy sleep onset and offset times.
Results
The midpoint of sleep at baseline was negatively associated with breakfast consumption at baseline (B = -.09, SE = .02, p = .000). Also, a later midpoint was associated with breakfast skipping over the next 18 months (estimate = -.08; SE = .02; p = .000). Prospective findings remained significant when adjusting for gender, ethnicity, age, perceived stress, body mass index (BMI), education, and reemployment over time. Education (estimate = 14.26, SE = 6.23, p < .05) and BMI (estimate = -.51, SE = .25, p < .05) were the only significant covariates. No other sleep indices predicted breakfast behavior cross-sectionally or prospectively.
Conclusion
Consistent with research in adolescents, unemployed adults with a later circadian phase are more likely to skip breakfast more often. Breakfast skipping was also associated with higher BMI. Taken together, these findings provide support for the future testing of sleep/wake scheduling interventions to modify breakfast skipping and potentially mitigate weight gain after job loss.
Support (if any)
#1R01HL117995-01A1
Abstract
Introduction
Polysomnography (PSG) is the gold standard for the diagnosis of obstructive sleep apnea (OSA). Given cost, insurance restrictions and in some cases limited access to sleep ...center testing, the use of home based sleep apnea testing is becoming increasingly more common. A proportion of patients with technically adequate HSAT who are negative end up having significant disease on PSG. The characteristics of patients who are found to have moderate to severe sleep apnea on polysomnogram (PSG) after a negative home sleep apnea test (HSAT) are not known. We aim to phenotype these patients.
Methods
We conducted a retrospective chart review from March 2018 to February 2020. A total of 953 adult patients (18 years old and older) underwent HSAT, 248 tests resulted negative (apnea-hypopnea index <5/h). Out of the negative HSAT, 17 patients had moderate to severe obstructive sleep apnea on PSG. Those were included for analysis. Data on patient characteristics such as age, body mass index (BMI), gender, STOP-BANG, ESS and comorbidities was gathered. Respiratory disturbance index, recording time, flow time, oximetry time on HSAT was recorded. PSG recording time, baseline AHI, supine AHI and non-supine AHI were also noted. Technically inadequate HSAT were excluded from analysis.
Results
The percentage of patients with negative HSAT who were found to have moderate to severe sleep apnea on PSG and were included for analysis was 6.85% (n17). Mean age was 41 years. Mean BMI was 33 kg/m2. Common comorbidities were hypertension (29%), asthma (17.6 %), depression (17.6%), anxiety (11.7%) and reflux (5.9%). Average ESS was 11.7 and STOP-BANG was 3.8. The mean recording time was 477 minutes, flow time 391 minutes and oximetry time was 426 minutes on HSAT. Average PSG recording time was 433 minutes. Average AHI was 24 with supine being 33.2/h and non-supine 17.9/h.
Conclusion
A proportion of patients with negative HSAT have moderate to severe OSA on follow-up polysomnogram. These patients were young, with lower-class obesity, more positional OSA, and no associated complex comorbidities. Re-evaluation of current diagnostic algorithms and further research is needed to phenotype this at-risk group, as first-line PSG may be more cost-effective and efficient.
Support (if any):
PDF
