Untreated Obesity Research Articles

Abstract 14470: Novel Autophagy Mechanisms of NP-6A4 Protection in Heart Disease Induced by Untreated Obesity

Introduction & Hypothesis: Untreated obesity induces insulin resistance and heart disease affecting 42% of the US population. Autophagy, a conserved homeostatic process for cellular quality control, plays a critical role in maintaining health. Heart tissues of obese humans and rodent models show impaired autophagy. Drugs that can regulate autophagy are thus of high clinical significance. We reported recently that NP-6A4, a new peptide agonist of the cardiovascular protective angiotensin receptor AT2R, mitigated obesity-induced cardiac dysfunction and damage in rats with untreated obesity and pre-diabetes. We hypothesized that activation of autophagy by NP-6A4 is involved in NP-6A4-AT2R-induced cardioprotection in untreated obesity. Methods & Results: 7-week old female ZDF rats fed high fat diet (D12468, Research Diet) for 6 weeks were randomized to receive either NP-6A4 (10mg/kg/day), NP6A4+AT2R antagonist PD123319 (PD, 5mg/kg/day) delivered subcutaneously (N=6/group), or vehicle (N=5) for 4 weeks. Echocardiography showed that NP-6A4 reduced abnormal E/A ratio from 2.1 to 1.45 (P<0.006), and isovolumic contraction (P<0.004) and relaxation times (P<0.02), and increased myocardial radial strain (P<0.019) and radial strain rate (P<0.033). PD reversed these effects. Immunohistochemistry (IHC) and Western blot analysis revealed a significant 5.9-fold increase (p<0.0006) in LC3 puncta (Fig. A-B) and 2.2-fold increase (p<0.0008) in lipidated autophagy marker LC3-II (Fig. C) compared to vehicle controls. The autophagy activation by NP-6A4 was not seen with the co-administration of PD (Fig. A-C). Cardiac proteome analysis showed that Sec16a, an important partner of autophagy initiators ULK1/2 is increased in ZDF rat heart by NP-6A4 (2.75 fold; P<0.020), but PD suppressed this effect. Conclusions: We identified NP-6A4’s dual targeting of AT2R and novel autophagy regulation to mitigate cardiac dysfunction induced by untreated obesity in female rats

Abstract 14318: Sex Differences in Treatment Responses to NP-6A4, a Cardiomyopathy Drug With the FDA Designation, in Heart Disease Induced by Untreated Obesity

Introduction: Obesity affects 42% of the US population and exacerbates heart disease. Currently there are no effective treatments for obesity-induced cardiac pathology. We reported that NP-6A4, a peptide agonist of the Angiotensin receptor AT2R mitigates cardiac dysfunction and damage in male rats with untreated obesity. Since cardiac pathology of male and female rats with untreated obesity differ, we hypothesized that there can be differences in their cardiac response to NP-6A4. Methods and Results: Echocardiographic analysis was performed in 15-week old male and female healthy Wistar (N=8) or Zucker lean (N=7) rats treated with saline, and obese and pre-diabetic Zucker rats treated with saline or NP-6A4 (1.8-10mg/kg/day in saline) for four weeks (N=8/group for females, N=7/group for males; subcutaneous delivery). Compared to healthy males, obese males showed significant (P<0.05) reduction in heart rate and increase in anterior wall thickness and left ventricular (LV) filling pressure (E/E’) suggesting concentric hypertrophy. Compared to healthy females, obese females showed significant (P<0.05) reduction in relative wall thickness, heart rate, and ejection fraction (although preserved) and increase in LV internal diameter at both diastole and systole indicating eccentric hypertrophy. NP-6A4 treatment suppressed the pathologic changes in both obese males and females (P<0.05). In another cohort of obese female rats NP-6A4 treatment from 13-to 17-weeks significantly (P<0.05) reduced abnormal E/A ratio and isovolumic contraction and relaxation time, and improved myocardial radial strain. Treatment with AT2R antagonist PD123319 (N=8: 5mg/kg/day delivered subcutaneously) abolished NP-6A4 effects. Cardiac proteome analysis of 18 tissue samples from this cohort using data independent acquisition (DIA) resulted in a total proteome of 4520 proteins and 296 differentially expressed proteins that were significant (P<0.01). Ingenuity pathway analysis predicted that inhibition of NP-6A4-mediated signaling by PD123319 may increase infection of cells (P=<0.001). Conclusion: NP-6A4 attenuated cardiac pathology induced by untreated obesity by altering different cardiac parameters in male and female rats.

Ameliorating Effect of Pineapple Juice on the Obesity-Induced Testicular Impairment in Male Wistar Rat.

<b>Background and Objective:</b> Obesity exerts negative influences on male reproductive capacity via changing the molecular and physical structure of male germ cells. This study was conducted to evaluate the mitigating effects of raw juice of pineapple on obesity-associated testicular impairment in male Wistar rats. <b>Materials and Methods:</b> Rats included the control group (G<sub>I</sub>, n = 6) who received a Normal Diet (ND) and the obese group (G<sub>II</sub>, n = 18) who received a High-Fat Diet (HFD). Obese rats (G<sub>II</sub>) were subdivided into 3 groups (6 rats each): G<sub>II</sub> represents the untreated obesity group that continued to receive HFD with plain Drinking Water (DW), G<sub>III</sub> received ND along with raw juice (15% v/v) in DW and G<sub>IV</sub> continued to receive HFD with raw juice (15% v/v) in DW. Rats were sacrificed at the end of the trial and testis was processed for histopathology and immunohistochemistry. <b>Results:</b> Testis from obese rats revealed a significant increment in spermatogenic cell degeneration, pro-inflammatory Nuclear factor of kappa B (NF-κB) and pro-apoptotic Caspase-3 immunoreactivities. Yet, Proliferating Cell Nuclear Antigen (PCNA) displayed poor immunoreactivity in obese rats' testis relative to controls. Administration of raw juice of pineapple to obese rats significantly reduced degeneration of spermatogenic cells, NF-κB and Caspase-3 immunoreactivities. Additionally, treatment with the juice significantly increased immunoreactivity to PCNA in obese rats. These ameliorating effects were more obvious in rats who received juice along with ND (G<sub>III</sub>) than in those who received it along with HFD (G<sub>IV</sub>). <b>Conclusion:</b> Treatment of obese rats with pineapple juice restored testicular homeostasis, indicating its potential validity to overcome obesity-induced male fertility disorders.

Maternal Obesity: A Focus on Maternal Interventions to Improve Health of Offspring.

Maternal obesity has many implications for offspring health that persist throughout their lifespan that include obesity and cardiovascular complications. Several different factors contribute to obesity and they encompass interplay between genetics and environment. In the prenatal period, untreated obesity establishes a foundation for a myriad of symptoms and negative delivery experiences, including gestational hypertensive disorders, gestational diabetes, macrosomia, and labor complications. However, data across human and animal studies show promise that nutritional interventions and physical activity may rescue much of the adverse effects of obesity on offspring metabolic health. Further, these maternal interventions improve the health of the offspring by reducing weight gain, cardiovascular disorders, and improving glucose tolerance. Mechanisms from animal studies have also been proposed to elucidate the signaling pathways that regulate inflammation, lipid metabolism, and oxidative capacity of the tissue, ultimately providing potential specific courses of treatment. This review aims to pinpoint the risks of maternal obesity and provide plausible intervention strategies. We delve into recent research involving both animal and human studies with maternal interventions. With the increasing concerning of obesity rates witnessed in the United States, it is imperative to acknowledge the long-term effects posed on future generations and specifically modify maternal nutrition and care to mitigate these adverse outcomes.

Suppression of Inflammatory Cardiac Cytokine Network in Rats with Untreated Obesity and Pre-Diabetes by AT2 Receptor Agonist NP-6A4.

Obesity affects over 42% of the United States population and exacerbates heart disease, the leading cause of death in men and women. Obesity also increases pro-inflammatory cytokines that cause chronic tissue damage to vital organs. The standard-of-care does not sufficiently attenuate these inflammatory sequelae. Angiotensin II receptor AT2R is an anti-inflammatory and cardiovascular protective molecule; however, AT2R agonists are not used in the clinic to treat heart disease. NP-6A4 is a new AT2R peptide agonist with an FDA orphan drug designation for pediatric cardiomyopathy. NP-6A4 increases AT2R expression (mRNA and protein) and nitric oxide generation in human cardiovascular cells. AT2R-antagonist PD123319 and AT2RSiRNA suppress NP-6A4-effects indicating that NP-6A4 acts through AT2R. To determine whether NP-6A4 would mitigate cardiac damage from chronic inflammation induced by untreated obesity, we investigated the effects of 2-weeks NP-6A4 treatment (1.8 mg/kg delivered subcutaneously) on cardiac pathology of male Zucker obese (ZO) rats that display obesity, pre-diabetes and cardiac dysfunction. NP-6A4 attenuated cardiac diastolic and systolic dysfunction, cardiac fibrosis and cardiomyocyte hypertrophy, but increased myocardial capillary density. NP-6A4 treatment suppressed tubulointerstitial injury marker urinary β-NAG, and liver injury marker alkaline phosphatase in serum. These protective effects of NP-6A4 occurred in the presence of obesity, hyperinsulinemia, hyperglycemia, and hyperlipidemia, and without modulating blood pressure. NP-6A4 increased expression of AT2R (consistent with human cells) and cardioprotective erythropoietin (EPO) and Notch1 in ZO rat heart, but suppressed nineteen inflammatory cytokines. Cardiac miRNA profiling and in silico analysis showed that NP-6A4 activated a unique miRNA network that may regulate expression of AT2R, EPO, Notch1 and inflammatory cytokines, and mitigate cardiac pathology. Seventeen pro-inflammatory and pro-fibrotic cytokines that increase during lethal cytokine storms caused by infections such as COVID-19 were among the cytokines suppressed by NP-6A4 treatment in ZO rat heart. Thus, NP-6A4 activates a novel anti-inflammatory network comprised of 21 proteins in the heart that was not reported previously. Since NP-6A4’s unique mode of action suppresses pro-inflammatory cytokine network and attenuates myocardial damage, it can be an ideal adjuvant drug with other anti-glycemic, anti-hypertensive, standard-of-care drugs to protect the heart tissues from pro-inflammatory and pro-fibrotic cytokine attack induced by obesity.

Zielona herbata a otyłość – wpływ katechin na metabolizm energetyczny

Streszczenie Otyłość jest chorobą metaboliczną, która obecnie zyskała rangę epidemii, stanowiąc jeden z najważniejszych problemów zdrowotnych, społecznych i ekonomicznych na świecie. Nieleczonej otyłości towarzyszy pogorszenie jakości życia oraz występowanie chorób towarzyszących, takich jak cukrzyca czy schorzenia układu sercowo-naczyniowego. W związku z tym poszukuje się nowych metod mających zastosowanie zarówno w profilaktyce otyłości, jak i w obniżaniu nadmiernej masy ciała. Zawarte w zielonej herbacie związki katechinowe, szczególnie galusan epigallokatechiny (EGCG), są jednymi z najintensywniej badanych substancji biologicznie czynnych. Przypisuje się im właściwości przeciwutleniające, przeciwzapalne, przeciwnowotworowe, a także wspomagające regulację masy ciała oraz zawartości tkanki tłuszczowej w organizmie. Liczne badania z udziałem ludzi wykazują, że regularne picie zielonej herbaty jest związane z mniejszą masą ciała, niższym BMI oraz z mniejszym obwodem pasa. Wyniki doświadczeń in vitro oraz na zwierzętach potwierdzają korzystny wpływ katechin na metabolizm energetyczny. Związki te obniżają wchłanianie lipidów i węglowodanów w przewodzie pokarmowym. Wpływają również na metabolizm tych związków, obniżając intensywność lipogenezy i adipogenezy, jednocześnie pobudzając lipolizę i utlenianie kwasów tłuszczowych, a także zwiększając wydatek energetyczny. Udowodniono, że katechiny mają wpływ na wychwyt glukozy przez komórki docelowe pobierające ten cukier poprzez insulinozależny transporter – GLUT4. W artykule omówiono literaturę przedmiotu oraz usystematyzowano zagadnienia związane z rolą katechin obecnych w zielonej herbacie w profilaktyce i wspomaganiu leczenia otyłości.

Prevalence of obesity and hypertension among teenage girls in an emerging metropolitan city of Central Rajasthan

Background: The problem of overweight, obesity, and hypertension is not only limited to adults but also extended to children and adolescents. The increasing prevalence of obesity and hypertension in girls reaching reproductive capacity is particularly disturbing, because untreated obesity contributes to its perpetuation in their offspring through maternal fetal transmission. Aims and Objectives: The aims of the study were as follows: (1) To evaluate the prevalence of overweight, pre-hypertension, and hypertension among teenage girls of Jaipur city and (2) to compare these observations in affluent and non-affluent category girls. Materials and Methods: Design: A school-based, cross-sectional, observational study was carried out from January to June 2011 involving 500 teenage girl students of age 13–17 years. One government and one public school were selected randomly in Jaipur. From each selected school, 250 teenage girls of 13–17 years of age group were examined and asked to fill out a pro forma. Category A: Teenage girls of private school belonging to affluent class; Category B: Teenage girls from government school and belonged to non-affluent class. Each girl height and weight was recorded to calculate body mass index. Blood pressure of each girl was recorded. The collected data were analyzed using SPSS version 11.5 and Chi-square test. Results: The prevalence of overweight among category A girls was 17.6% and in category B was 5.2% of girls (P = 0.0001). About 5.2% of girls were pre-hypertensive and 3.6% were hypertensive in category A while 5.6% were pre-hypertensive and 2.0% were hypertensive in category B (P = 0.416 and 1.00 for hypertension and pre-hypertension, respectively). Conclusion: The prevalence of overweight and hypertension was higher among affluent teenage girls. The prevalence of pre-hypertension was comparable between two categories. The underlying factors for pre-hypertension were different in two categories.

4311 Inflammatory biomarkers of cognitive dysfunction in pediatric obesity: associations between Executive Function, C-Reactive Protein, Interleukin 6, and Tumor Necrosis Factor alpha

OBJECTIVES/GOALS: Executive function (EF) deficits lead to poorer adherence and weight loss in obesity treatment. Conversely, untreated obesity leads to both EF impairments and risk of chronic disease. EF deficits in children with obesity have begun to be associated with biomarkers of chronic disease risk such as glucose and cortisol. Elevated pro-inflammatory biomarkers, such as C-Reactive Protein (CRP), Interleukin 6 (IL-6), and Tumor Necrosis Factor a (TNFa), indicate risk for obesity-associated chronic disease and may represent another candidate biomarker of EF deficits in pediatric obesity. These inflammatory markers tend to be elevated in obesity but have yet to be examined in association with EF in pediatric obesity. This represents an opportunity to identify potential biomarkers of EF which may serve as novel treatment targets that could improve outcomes and chronic disease prevention. Thus, the present study aims to explore associations between EF and blood serum CRP, IL-6, and TNFa. METHODS/STUDY POPULATION: Treatment-seeking children aged 8-12 years with BMI>95th percentile were recruited from a pediatric weight management clinic and attended baseline assessments for a family-based behavioral intervention program for pediatric obesity. Demographics and medical history were assessed via parent questionnaire. Height and weight were measured by research staff and converted to zBMI. Child performance-based EF was assessed via the NIH Toolbox Cognitive Battery iPad application. Blood draws, assays, and Dual-energy X-ray Absorptiometry (DXA; measuring adiposity) were conducted by trained research personnel. Pearson’s correlations were conducted to explore associations between EF (NIH Toolbox Cognitive Battery, fully corrected T-scores) and CRP, IL-6, and TNFa. RESULTS/ANTICIPATED RESULTS: Children (n = 12) were primarily female (76.5%) and African American (64.7%). Correlation coefficients between inflammatory markers and EF were highly variable (r = −0.39 to 0.52). CRP showed small, negative associations with Cognitive Flexibility (r = −0.39) and Inhibitory Control (r = −0.34). IL-6 also demonstrated a small, negative association with Inhibitory Control (r = −0.37). TNFa was positively and moderately associated with working memory (r = 0.53). Remaining associations were weak (−0.3<r<0.3). DISCUSSION/SIGNIFICANCE OF IMPACT: Signals of higher inflammation, measured via CRP and IL-6, in association with EF deficits were identified in a small sample of children with obesity, as hypothesized. However, signals in the opposite direction were identified as well, measured via TNFa. CRP and IL-6 may represent candidate biomarkers of executive dysfunction in obesity that warrant further domain and biomarker-specific research, with potential long-term implications for improving pediatric obesity treatment.

0570 Apnea-Hypopnea Index is Positively Correlated with Mood Disturbance

Abstract Introduction The prevalence of mood disorders such as depression is higher in individuals with obstructive sleep apnea (OSA). Previous studies have found no significant correlation between the apnea-hypopnea index (AHI) and measures of mood and have only included participants who met diagnostic criteria for OSA. The current analysis sought to determine whether mood correlated with AHI in individuals with any AHI values including those that did not meet diagnostic criteria for OSA. Methods 31 volunteers were studied (BMI=29.2±1.0 kg/m2, mean±SE), free from medication and without psychiatric illness or chronic medical conditions with the exception of untreated OSA, uncomplicated hypertension (BP<160/100), or obesity. Following 1-3 weeks of an 8h habitual at home sleep schedule, participants completed the POMS-Brief questionnaire (POMS-B) to assess mood after undergoing overnight polysomnography to determine AHI. Total mood disturbance (TMD) scores were calculated by adding the scores on the POMS-B for each mood state subscale and subtracting the score for vigor-activity. Results The average AHI was 15.3±3.1 (range of 1.1-74.1) events per hour. The average POMS-B TMD score was 21±1.5 (range of 4-46). There was a significant correlation between the POMS-B TMD score and AHI (p=0.037, r2=0.14). This result was also seen in only those individuals with AHI scores >5 (p=0.002, r2=0.4). Conclusion In this sample, individuals with higher AHI values displayed higher TMD scores. These results differ from previous data that showed no significant correlation between AHI and TMD. This is the first analysis to demonstrate a correlation between TMD and AHI while including individuals who didn’t meet diagnostic criteria for OSA. However, the relationship between AHI and TMD was also significant in those with AHI>5. More data on these measures with larger sample sizes and a more equal representation of AHI values should be gathered to provide additional evidence for this relationship. Support: Support NIH R01-HL125893; CTSA UL1TR000128, R21HL140377

Long-term clinical effectiveness of continuous positive airway pressure therapy versus non-invasive ventilation therapy in patients with obesity hypoventilation syndrome: a multicentre, open-label, randomised controlled trial

Obesity hypoventilation syndrome is commonly treated with continuous positive airway pressure or non-invasive ventilation during sleep. Non-invasive ventilation is more complex and costly than continuous positive airway pressure but might be advantageous because it provides ventilatory support. To date there have been no long-term trials comparing these treatment modalities. We therefore aimed to determine the long-term comparative effectiveness of both treatment modalities. We did a multicentre, open-label, randomised controlled trial at 16 clinical sites in Spain. We included patients aged 15-80 years with untreated obesity hypoventilation syndrome and an apnoea-hypopnoea index of 30 or more events per h. We randomly assigned patients, using simple randomisation through an electronic database, to receive treatment with either non-invasive ventilation or continuous positive airway pressure. Both investigators and patients were aware of the treatment allocation. The research team was not involved in deciding hospital treatment, duration of treatment in the hospital, and adjustment of medications, as well as adjudicating cardiovascular events or cause of mortality. Treating clinicians from the routine care team were not aware of the treatment allocation. The primary outcome was the number of hospitalisation days per year. The analysis was done according to the intention-to-treat principle. This study is registered with ClinicalTrials.gov, number NCT01405976. From May 4, 2009, to March 25, 2013, 100 patients were randomly assigned to the non-invasive ventilation group and 115 to the continuous positive airway pressure group, of which 97 patients in the non-invasive ventilation group and 107 in the continuous positive airway pressure group were included in the analysis. The median follow-up was 5·44 years (IQR 4·45-6·37) for all patients, 5·37 years (4·36-6·32) in the continuous positive airway pressure group, and 5·55 years (4·53-6·50) in the non-invasive ventilation group. The mean hospitalisation days per patient-year were 1·63 (SD 3·74) in the continuous positive airway pressure group and 1·44 (3·07) in the non-invasive ventilation group (adjusted rate ratio 0·78, 95% CI 0·34-1·77; p=0·561). Adverse events were similar between both groups. In stable patients with obesity hypoventilation syndrome and severe obstructive sleep apnoea, non-invasive ventilation and continuous positive airway pressure have similar long-term effectiveness. Given that continuous positive airway pressure has lower complexity and cost, continuous positive airway pressure might be the preferred first-line positive airway pressure treatment modality until more studies become available. Instituto de Salud Carlos III, Spanish Respiratory Foundation, and Air Liquide Spain.

Differences in Metabolic Factors Between Antipsychotic-Induced Weight Gain and Non-pharmacological Obesity in Youths

Youth exposed to antipsychotics may experience several metabolic consequences that often limit the effectiveness of this class of drugs. The aim of this study was to compare several metabolic markers between subjects who experienced antipsychotic-induced weight gain and untreated obese patients. Nineteen non-diabetic youth (mean age 159months, mean body mass index z-score 1.81) experiencing antipsychotic-induced weight gain and an age-, sex-, and body mass index-matched group of non-diabetic obese patients with no record of treatment (n=19, mean age 147months, mean body mass index z-score 2) were compared for a wide range of metabolic factors using a Bioplex Multiplex system. C-peptide, glucose-dependent insulinotropic polypeptide, and adipsin were significantly higher in the antipsychotic-induced weight gain group, whereas visfatin was significantly higher in the untreated obese patients. When age, sex, pubertal status, and body mass index were controlled, C-peptide, glucose-dependent insulinotropic polypeptide, and visfatin remained significant, whereas adipsin fell slightly below the threshold of statistical significance. No other statistically significant difference emerged. Antipsychotic-induced weight gain and untreated obesity showed some similarities, confirming that levels of some hormones, such as leptin and ghrelin, are related to body mass index rather than to antipsychotic exposure. Some differences were also noted; for example, the antipsychotic-induced weight gain group displayed higher C-peptide, glucose-dependent insulinotropic polypeptide, and adipsin, which may reflect β-cell stress and may suggest susceptibility to insulin resistance and lower visfatin, possibly indicating a lower inflammatory status.

Depression and Anxiety: Lack of Associations with an Inadequate Diet in a Sample of Pregnant Women with a History of Bariatric Surgery-a Multicenter Prospective Controlled Cohort Study.

Anxiety and depression levels are higher in obese compared to those in normal weight pregnant women. The aims of this study are to examine anxiety and depression in pregnancy following bariatric surgery and to compare with obese pregnant controls considering the dietary intake of polyunsaturated fatty acids (PUFA), folate, and vitamin B12. Anxiety (State-Trait Anxiety Inventory) and depression (Edinburgh Postnatal Depression Scale) were examined in the first (T1) and third (T3) pregnancy trimester in 54 women with bariatric surgery and 25 obese. T1 and T3 dietary intake of PUFA, folate, and vitamin B12 intake was assessed using a 3-day food record. Mixed models with a compound symmetry covariance structure and regression models were applied. About half of the women with surgery had high state and trait anxiety scores (≥ 40), which did not significantly change during pregnancy. Every 10-kg postoperative weight loss was associated with an increase in T1 state and trait anxiety with respectively 2.7 and 2.3 points. A smoking woman had a 8.6-point higher state anxiety score than a non-smoking woman in T1. In T3, every additional hour of sleep was associated with a decrease in trait anxiety score with 1.59 points. Anxiety and depression scores were not associated with and could not be explained by inadequate PUFAs, folate, and vitamin B12 intakes. Anxiety scores were higher following surgery than those in untreated obesity at both time points. Pregnancy following bariatric surgery induces high levels of anxiety that are not associated with an inadequate maternal diet.

Hypertension in Low-Income Adolescents.

Disadvantaged adolescents are at higher risk for undiagnosed and untreated obesity and hypertension. Using nurse-measured weight, height, and blood pressure (BP) as well as self-reported age and activity/lifestyle behaviors, we assessed the prevalence of obesity and hypertension in 573 adolescent patients aged 13.0 to 17.9 years (females: n = 267, 46.6%; males: n = 306, 53.4%) from a clinic serving low-income, ethnically diverse pediatric patients. Body mass index distribution was as follows: 11, underweight (1.9%); 330, healthy weight (57.6%); 105, overweight (18.3%); and 127, obese (22.2%). The age-adjusted height percentile was normally distributed, but distribution by BP category was 326 normotensive (56.9%), 147 prehypertensive (25.7%), 60 with stage 1 hypertension (10.5%), and 40 with stage 2 hypertension (7.0%). Activity and lifestyle behaviors did not adequately explain obesity and hypertension rates. Efforts to prevent/reduce childhood overweight, obesity, and hypertension in underserved populations need to include dietary education, weight control interventions, and physical activity programs specifically tailored to overweight/obese youth and parents.

Moral challenges

‘Eat less and move more’ strategies alone will not solve the UK obesity epidemic…we need to consider ways of reducing the downstream costs of untreated obesity

Public Health Implications of Obstructive Sleep Apnea Burden

To assess the implications of obstructive sleep apnea (OSA) burden among Indian children. MonteCarlo simulations were performed in order to estimate the number of OSA related obesity cases among Indian children (1-14 y of age) and the number of cases of stroke, coronary heart disease (CHD) and type 2 diabetes, considered as main adverse outcomes of OSA related childhood obesity, according to untreated and treated [adenotonsillectomy (AT) alone and AT associated to continuous positive airway pressure (CPAP)] pediatric OSA. Data used to perform MonteCarlo simulations were derived from a review about current literature exploring OSA related obesity. The analysis on the number of adverse outcomes according to treated and untreated obesity related to OSA showed that treatments reduce the number of obesity cases, resulting in a great reduction of the amount of stroke, CHD and type 2 diabetes cases. However, the cost for treating adverse outcome was higher in patients treated for obesity related to OSA compared to those not receiving any treatment. The reduction in the number of adverse outcomes due to treatment of obesity related OSA implicates the urgent need for public health policies in providing screening for OSA among children population: an early detection and a consequently prompt reaction to pediatric OSA could improve the burden of OSA related obesity.

Validation of respiratory inductive plethysmography (LifeShirt) in obesity hypoventilation syndrome

Validation of respiratory inductive plethysmography (LifeShirt system) (RIPLS) for tidal volume (VT), minute ventilation (V˙E), and respiratory frequency (fB) was performed among people with untreated obesity hypoventilation syndrome (OHS) and controls. Measures were obtained simultaneously from RIPLS and a spirometer during two tests, and compared using Bland Altman analysis. Among 13 OHS participants (162 paired measures), RIPLS-spirometer agreement was unacceptable for VT: mean difference (MD) 3mL (1%); limits of agreement (LOA) −216 to 220mL (±36%); V˙E MD 0.1Lmin−1 (2%); LOA −4.1 to 4.3Lmin−1 (±36%); and fB: MD 0.2brmin−1 (2%); LOA −4.6 to 5.0brmin−1 (±27%). Among 13 controls (197 paired measures), RIPLS-spirometer agreement was acceptable for fB: MD −0.1brmin−1 (−1%); LOA −1.2 to 1.1brmin−1 (±12%), but unacceptable for VT: MD 5mL (1%); LOA −160 to 169mL (±20%) and V˙E: MD 0.1Lmin−1 (1%); LOA −1.4 to 1.5Lmin−1 (±20%). RIPLS produces valid measures of fB among controls but not OHS patients, and is not valid for quantifying respiratory volumes among either group.

LOS Function and Obesity: The Impact of Untreated Obesity, Weight Loss, and Chronic Gastric Balloon Distension

Background/Aims: In obesity, many gastro-oesophageal reflux promoting factors are present. Weight reduction is advised to symptomatic overweight subjects. The aim of the present study was to investigate the influences of untreated obesity, weight loss, and chronic gastric balloon distension on the lower oesophageal sphincter (LOS) function. Methods: Patients entering a randomized, double-blind, sham-controlled study of balloon treatment, consisting of 4 months of either sham balloon or balloon treatment followed by 4 months of balloon treatment. Manometry and 24-hour pH measurements were performed at the start of the study and after 13 and 26 weeks. Results: Before treatment, LOS dysfunction was present in 7 of 32 patients (21.9%). Increased upright and supine reflux was present in 8 patients (25%). Sham treatment resulted in a weight loss of 9.7% with improved LOS function (a significant 0.6-cm increase in LOS length and a non-significant 2.6 mm Hg higher LOS pressure) and in a significantly decreased upright reflux (acid reflux time decreasing from 8.0 to 5.5% and number of meal-related and postprandial reflux episodes decreasing from 49 to 32). These improved values deteriorated after 4 months of balloon placement, with significantly increasing total, upright, and supine reflux to 7.5, 7.6, and 6.7% of the time, respectively, with oesophageal lesions after an overall 17.8% weight loss. Four months of balloon treatment induced a similar weight loss (9.9%) with significantly increased supine reflux from 1.6 to 6.7% of the time. After a second 4-month balloon period and an overall 13.8% weight loss, LOS and reflux values returned towards baseline values. A comparison of both groups demonstrated the adverse effects of balloon positioning after a period of substantial sham-induced weight loss. Conclusions: Impaired LOS function and increased gastro-oesophageal reflux were observed in one quarter of the untreated obese subjects. Weight loss ameliorated manometry and pH values, but subsequent balloon positioning tended to counteract these beneficial changes. In patients on balloon treatment from the start, adverse effects seemed to wear off with prolonged treatment.

Liver and gallbladder disease before and after very-low-calorie diets

Hepatobiliary characteristics of untreated obese patients and those of patients reducing weight through very-low-calorie diets (VLCDs) are reviewed. In untreated obesity, hepatobiliary abnormalities are prevalent. Fatty change is common and may be related to insulin resistance. Moreover, portal inflammation and fibrosis are prevalent findings, also in the absence of alcohol abuse. The liver plays a key role in the hyperinsulinism and hyperlipidemia, and hepatic drug metabolism is influenced by enhanced glucuronidation and sulphatation. Predisposition to gallstone formation can be ascribed to increased biliary cholesterol secretion in concert with changed nucleating factors and altered gallbladder motility. Weight loss by VLCD reduces fatty change but may induce slight portal inflammation and fibrosis. Insulin resistance and pharmacokinetic abnormalities regress. During VLCD the risk of gallstone formation is markedly increased. The deleterious effects described of a rapid weight loss should draw some attention to the liver and biliary tract during VLCD treatment.

Serum Selenium and Zinc Concentrations in Morbid Obesity: Comparison of Controls and Patients with Jejunoileal Bypass

The concentrations of serum selenium and zinc (both in micromoles per litre) were determined in 18 patients 5-12 years after jejunoileal bypass and in 13 controls with untreated morbid obesity. Selenium concentrations were significantly lower in the operated patients than among controls, whereas there was no significant difference with regard to zinc. Ninety-five per cent confidence limits for the median difference between pre- and post-operative concentrations were 0.03-0.41 with regard to selenium and -0.3 to 2.7 with regard to zinc. Even though little is known about the clinical consequences of chronic selenium deficiency, substitution might prove beneficial.