Trajectory of body mass index and height changes from childhood to adolescence: a nationwide birth cohort in Japan

To investigate the dynamics of body mass index (BMI) and height changes in childhood leading to obesity in adolescents. BMI Z-scores were calculated using the LMS (lambda–mu–sigma) method based on yearly height and weight information (age 1.5–15 years) from a nationwide Japanese birth cohort that started in 2001 (n = 26,711). We delineated the trajectories of BMI and height changes leading to obesity at age 15 years using mixed effect models. Children who became obese at the age of 15 years kept relatively high BMI z-scores through childhood for both genders, and had an increasing trend over time as opposed to the normal weight group, with an increasing slope during puberty. Early adiposity rebound was associated with overweight or obesity at the age of 15 years. Age at peak height velocity (APHV) occurred earlier in the obese/overweight group at age 15 years than in the normal weight group, and occurred later in the underweight group. Obese adolescents experienced early adiposity rebound timing and maintained a serial BMI z-score increase throughout childhood, with a greater slope at puberty. An earlier peak in height gain during puberty may have contributed to the observed patterns of BMI change.

Decreased DNA Repair Ability: A Mechanism for Low Early Embryonic Development Potential of Oocytes From Overweight Patients After Fertilization in IVF Cycles

BackgroundWhether female BMI impacts the DNA repair ability in the oocytes after fertilization has not been investigated. The aim of this study is to assess the early embryo quality and reproductive outcomes of oocytes from overweight women when fertilized with sperm with varying degrees of DNA fragmentation.MethodsA total number of 1,612 patients undergoing fresh autologous in vitro fertilization (IVF) cycles was included. These patients were divided into two groups according to maternal body mass index (BMI): normal weight group (18.5–24.9 kg/m2; n=1187; 73.64%) and overweight group (≥25 kg/m2; n=425; 26.36%). Each group was then subdivided into two groups by sperm DNA fragmentation index (DFI): low fragmentation group (<20% DFI, LF) and high fragmentation group (≥20% DFI, HF). Laboratory and clinical outcomes were compared between subgroups.ResultsFor the normal-weight group, there was no statistical significance in embryo quality and reproductive outcomes between the LF and HF groups. But in the overweight group, significantly lower fertilization rate (LF: 64%; HF: 59%; p=0.011), blastocyst development rate (LF: 57%; HF: 44%; p=0.001), as well as high-quality blastocyst rate (LF: 32%; HF: 22%; p=0.034) were found in the HF group, despite the similar pregnancy rates (LF: 56%; HF: 60%; p=0.630).ConclusionsDecreased DNA repair activity in oocytes may be a possible mechanism for the low early development potential of embryos from overweight patients in in vitro fertilization cycles.

Effect of BCR-ABL1 Transcript Type and Body Weight on Outcome in Chronic Myeloid Leukemia

Introduction The hallmark of CML is BCR-ABL1 (breakpoint cluster region gene-Abelson murine leukemia viral oncogene homolog 1) on Philadelphia chromosome, which is the result of a reciprocal translocation between the long arms of chromosomes 9 and 22 (t[9;22][q34;q11]) [1]. Chromosome 22 breakpoints influence the BCR portions preserved in the BCL-ABL1 fusion mRNA and protein and are mainly localized to one of three BCRs, namely major-BCR (M-BCR), minor BCR (m-BCR) and micro-BCR (µ-BCR). In comparison, breaks in chromosome 9 arise most frequently by alternative splicing of the two first ABL1 exons, and can also be generated in a large genetic region, upstream of exon Ib at the 5' end, or downstream of exon Ia at the 3' end. In the majority of CML cases, the breakpoint lies within the M-BCR and gives rise to e13a2 or e14a2 fusion mRNAs (previously denoted as b2a2 and b3a2) and a p210BCR-ABL fusion protein [2]. [3] Methodology We conducted a retrospective analysis of the files of 79 patients being treated in our center for CML with known BCR-ABL1 breakpoints; there were few more patients with known transcript type but excluded because either travelled immediately on diagnosis or had a failure due to confirmed compliance issues. Patients' management and response assessment was done based on ELN 2013 guidelines. The analysis is done based on two main groups, obese versus normal BMI, and then based on BCR-ABL1 transcripts: e13a2 versus e14a2. Ethical approval was obtained from Medical Research Center for Hamad Medical Corporation (MRC-01-18-337). Results Patients included 62 males (78.5%) and 17 females (21.5%) with the mean age at diagnosis 38.8±11.8 years (median, 38; range 21 to 69 years). The characteristics (demographics, anthropometric, hematological and clinico-pathological) of the patients and their association with transcript types and obesity are summarized in Table 1. Patient outcomes, cytogenetic and molecular responses The median follow-up was 30 months (range 6 to 196 months) and 38 months (range 3 to 192 months) in normal weight and obesity groups, respectively. The median follow-up was 28 months (range 3 to 196 months) and 39 months (range 10 to 192 months) in e14a2 and e13a2 patients, respectively. A total of 22 patients distributed among different groups ended up leaving the country (censored) after a variable duration of follow-up (6 - 196 months), 18 of them CML-CP, and 4 CML-AP. 3 patients died in our cohort, all of them had e14a2 transcript, one of them was in the normal weight/BMI group, two were in the obesity group. In e14a2 group, more patients were on imatinib at the time of analysis (15 (39.5%) vs 7 (17.1%) in e13a2 group, p = 0.026). The percentage of patients of had to switch TKI was similar in both groups (47.4% vs 53.7%, p = 0.576). However, less patients in e14a2 group had to switch TKI because of failure/progression (10 (55.6%) vs 17 (77.3%), p = 0.145); however, this didn't translate into a significant difference of achieving MMR at 1 year, where in e14a2 group, 10 patients achieved MMR at 1 year (31.3%), same as in e13a2 group (10 patients = 29.3%) p 0.331 (all shown in table 1). When comparing long-term outcomes, there was also no significant difference between groups based on transcript type with regards to MMR (44.7% vs 46.3% in e14a2 vs e13a2 respectively) or DMR (26.3% vs 22% respectively) as shown in figure. In the obesity group, there were 2 patients using ponatinib due to T315I mutation, compared to none in normal weight group. However, there were no significant differences in TKI used, switch of TKI, or reason for switch. Same applies for achieving MMR at 1 year, as 11 patients in the obesity group achieved MMR (28.2%) compared to 9 patients in normal weight group (33.3%), p = 0.778 (as shown in table 1). Regarding the long-term outcomes, more patients in the obesity group achieved MMR (53.2%) compared to normal weight group (34.3%), and this response was faster, but not statistically significant. This difference was less clear with regards to DMR (25.5% in the obesity group compared to 21.9% in normal weight group) as shown in figure. Conclusion In the patient-cohort studied there were no significant differences in molecular response based on transcript type or body weight/BMI. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Long-Term Cardiac Assessment in a Sample of Adolescent-Onset Anorexia Nervosa

Background: High mortality rates have been reported in patients with anorexia nervosa, mainly due to cardiovascular alterations. The purpose of the present study was to assess cardiac structural and functional abnormalities some 20 years after initial treatment in a sample of adolescent-onset anorexia nervosa (A-AN) and to compare them with matched healthy controls (HC). Methods: A sample of 29 women diagnosed and treated for AN during adolescence (A-AN) were assessed more than 20 years later. A complete cardiac evaluation was carried out including an electrocardiogram (ECG) and a standard 2D echocardiography. Thirty matched HC were also assessed. Results: In the A-AN group, four subjects had a body mass index lower than 18.5 and met full DSM 5 criteria for AN at follow-up (Low-Weight group). They were compared with the rest of the sample (n=25) who had normalized their weight (Normal-Weight group), though some still showed some eating disorder symptoms. Both groups were compared with the HC group. Subjects in the Low-Weight group presented statistically significant decreases in the left ventricular end-diastolic and left atrium dimensions and left ventricular mass in comparison with the Normal-Weight group and the HC. No other differences in cardiac parameters were found between groups. Conclusions Echocardiographic and ECG parameters of adults who had presented A-AN twenty years earlier and currently maintained normal weight were similar to those of HC who had never been treated or diagnosed with AN. Adult subjects with A-AN who still had low weight in the long term present certain cardiac abnormalities similar to those seen in short-lasting disease. More studies are needed to confirm these results in a larger sample.

An EEG study on the effect of being overweight on anticipatory and consummatory reward in response to pleasant taste stimuli

Two-thirds of adults in the United Kingdom currently suffer from overweight or obesity, making it one of the biggest contributors to health problems. Within the framework of the incentive sensitisation theory, it has been hypothesised that overweight people experience heightened reward anticipation when encountering cues that signal food, such as pictures and smells of food, but that they experience less reward from consuming food compared to normal-weight people. There is, however, little evidence for this prediction. Few studies test both anticipation and consumption in the same study, and even fewer with electroencephalography (EEG). This study sought to address this gap in the literature by measuring scalp activity when overweight and normal-weight people encountered cues signalling the imminent arrival of pleasant and neutral taste stimuli, and when they received these stimuli. The behavioural data showed that there was a smaller difference in valence ratings between the pleasant and neutral taste in the overweight than normal-weight group, in accordance with our hypothesis. However, contrary to our hypothesis, the groups did not differ in their electrophysiological response to taste stimuli. Instead, there was a reduction in N1 amplitude to both taste and picture cues in overweight relative to normal-weight participants. This suggests that reduced attention to cues may be a crucial factor in risk of overweight.

Tolerance to glucose and lipid high metabolic reactions after burns in an obese rat model

The goal of this study was to determine what effect obese body weight and a burn injury can have on the metabolism of glucose and lipids in rats. We used a 3*3 factorial model design to provide basic glucose and lipid metabolic data characterizing the interaction between different weight and burn injury groups. Two hundred Sprague Dawley (SD) rats were categorized into three weight groups (normal, overweight, obese) and then further divided into control, second degree, and third degree burn groups. Our model compared interactions between weight and burn injury factors according to the above groups. Blood glucose and lipid metabolism indicators were monitored on the 1st, 3rd, 7th and 14th days after burn injury occurred, and burned skin and blood samples were collected for testing. Compared with the normal weight group, the overweight group’s fast blood glucose (FBG), fast insulin (FINS) and homeostasis model assessment of insulin resistance (HOMA-IR) were higher (P<0.05), and FBG in the obese group was higher than the normal weight group (P<0.05).Burn injuries combined with obese body weight had an interactive effect on FBG, FINS and HOMA-IR after burn injury (P<0.05). Burn injury combined with obese body weight had an interaction on low density lipoprotein cholesterol (LDL-C) on the 3rd day after burn injury (P<0.05). Burn injury combined with obese weight had no interaction on triglyceride (TRG), total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C) (P>0.05).Rats in the overweight and obese weight groups were observed to develop an adaptation and tolerance to a higher metabolic rate after burn injuries occurred.

Effect of Body Mass Index on the Prognosis of Liver Cirrhosis

Objective: At present, the association of body mass index (BMI) with the prognosis of liver cirrhosis is controversial. Our retrospective study aimed to evaluate the impact of BMI on the outcome of liver cirrhosis.Methods: In the first part, long-term death was evaluated in 436 patients with cirrhosis and without malignancy from our prospectively established single-center database. In the second part, in-hospital death was evaluated in 379 patients with cirrhosis and with acute gastrointestinal bleeding (AGIB) from our retrospective multicenter study. BMI was calculated and categorized as underweight (BMI <18.5 kg/m2), normal weight (18.5 ≤ BMI < 23.0 kg/m2), and overweight/obese (BMI ≥ 23.0 kg/m2).Results: In the first part, Kaplan–Meier curve analyses demonstrated a significantly higher cumulative survival rate in the overweight/obese group than the normal weight group (p = 0.047). Cox regression analyses demonstrated that overweight/obesity was significantly associated with decreased long-term mortality compared with the normal weight group [hazard ratio (HR) = 0.635; 95% CI: 0.405–0.998; p = 0.049] but not an independent predictor after adjusting for age, gender, and Child–Pugh score (HR = 0.758; 95%CI: 0.479–1.199; p = 0.236). In the second part, Kaplan–Meier curve analyses demonstrated no significant difference in the cumulative survival rate between the overweight/obese and the normal weight groups (p = 0.094). Cox regression analyses also demonstrated that overweight/obesity was not significantly associated with in-hospital mortality compared with normal weight group (HR = 0.349; 95%CI: 0.096-1.269; p = 0.110). In both of the two parts, the Kaplan–Meier curve analyses demonstrated no significant difference in the cumulative survival rate between underweight and normal weight groups.Conclusion: Overweight/obesity is modestly associated with long-term survival in patients with cirrhosis but not an independent prognostic predictor. There is little effect of overweight/obesity on the short-term survival of patients with cirrhosis and with AGIB.

Evaluation of the Relationship Between Body Mass Index (BMI) and DNA Fragmentation Index Changes in Primary Infertile Patients Following Microscopic Sub Inguinal Varicocelectomy

Objectives: To investigate changes in DNA fragmentation index in primary infertile patients with varicocele, which is followed by microscopic subingual varicocelectomy in different groups based on body mass index (BMI). Methods: This study was performed in 100 patients with primary infertility with varicocele. Patients were divided into three groups (normal (N), overweight (OW), and obese (OB)) based on BMI index. DNA fragmentation index (DFI) parameters were evaluated before and 6 months after varicocelectomy. For DFI analysis, the SCD (sperm chromatin dispersion test) method was used. Data were analyzed using t-test, Chi-square, and ANOVA. Results: In this study, the mean age of participants was 33.6 and their mean BMI was 28.6, that 51 patients underwent bilateral varicocelectomy and 49 patients underwent left varicocelectomy surgery. In this study, a comparison of DFI before and 6 months after surgery showed a decrease in DFI in all three groups. The difference was 23 in the normal weight group, 11.2 in the overweight group and 9.58 in the obese group, which is statistically significant (PV < 0.05). Also, in comparison with the rate of DFI reduction between groups, the normal weight group showed a greater decrease than the overweight and obese group. This difference was statistically significant (PV < 0.05), while comparing the rate of DFI reduction between the two groups of overweight and obese, was observed no significant difference (PV = 0.635). Conclusions: Although DFI level decreased significantly 6 months after surgery in all groups with different body mass index. However, the rate of reduction was not the same in different groups and was higher in normal-weight patients than in overweight and obese individuals. But there was no significant difference in the rate of reduction between the overweight and obese groups.

Influence of Cerebral Vasodilation on Blood Reelin Levels in Growth Restricted Fetuses

Fetal growth restriction (FGR) is one of the most important obstetric pathologies. It is frequently caused by placental insufficiency. Previous studies have shown a relationship between FGR and impaired new-born neurodevelopment, although the molecular mechanisms involved in this association have not yet been completely clarified. Reelin is an extracellular matrix glycoprotein involved in development of neocortex, hippocampus, cerebellum and spinal cord. Reelin has been demonstrated to play a key role in regulating perinatal neurodevelopment and to contribute to the emergence and development of various psychiatric pathologies, and its levels are highly influenced by pathological conditions of hypoxia. The purpose of this article is to study whether reelin levels in new-borns vary as a function of severity of fetal growth restriction by gestational age and sex. We sub-grouped fetuses in: normal weight group (Group 1, n = 17), FGR group with normal umbilical artery Doppler and cerebral redistribution at middle cerebral artery Doppler (Group 2, n = 9), and FGR with abnormal umbilical artery Doppler (Group 3, n = 8). Our results show a significant association of elevated Reelin levels in FGR fetuses with cerebral blood redistribution compared to the normal weight group and the FGR with abnormal umbilical artery group. Future research should focus on further expanding the knowledge of the relationship of reelin and its regulated products with neurodevelopment impairment in new-borns with FGR and should include larger and more homogeneous samples and the combined use of different in vivo techniques in neonates with impaired growth during their different adaptive phases.

POS0212 COMPARISON OF PATIENT CHARACTERISTICS AND TREATMENT PATTERNS ACROSS BODY MASS INDEX CATEGORIES IN PATIENTS WITH PSORIATIC ARTHRITIS AND RHEUMATOID ARTHRITIS

Background:Higher prevalence of obesity has been observed in psoriatic arthritis (PsA) and rheumatoid arthritis (RA) versus the general population, and abnormal body mass index has been associated with worse rheumatic markers.Objectives:To describe PsA and RA patients in Switzerland, stratified by body mass index (BMI) category.Methods:We performed a descriptive cohort study in PsA and RA patients registered in the Swiss Clinical Quality Management in Rheumatic Diseases (SCQM) database. Two distinct cohorts were generated based on patient diagnosis (PsA or RA) and analysed separately but using similar approaches. In both cohorts, we included patients treated for the first time with biologics or targeted synthetic disease-modifying anti-rheumatic drugs (tsDMARDs), and considered the treatment start as index date. Patients without baseline BMI were excluded. Patients were stratified by BMI category at the start of biologic/tsDMARD treatment, defined as underweight (BMI<18.5), normal weight (BMI 18.5-24.9), overweight (BMI 25.0-29.9), and obese (BMI≥30). In the PsA cohort, underweight and normal weight groups were merged due to low numbers. The proportion of patients categorized as overweight or underweight were compared to national statistics from the Swiss Federal Statistical Office. Information on patient demographics (e.g., age, sex, BMI, life-habits), disease-specific characteristics (e.g., disease activity scores, health questionnaires, biomarkers), co-medications and comorbidities were summarized at the start of the first biologic/tsDMARD treatment. Patient characteristics across BMI categories were compared, using the normal weight category as reference group. Additionally, we summarized the frequency and reasons for recorded treatment stop/switch at ≤6 months, 6 to 12 months, and >12months from treatment start, and illustrated the prescription patterns for first and second biologic/tsDMARD treatment, stratifying by BMI.Results:We identified 819 PsA [39.7% normal weight, 36.5% overweight, 23.8% obese] and 3217 RA patients [4.4% underweight, 46.8% normal weight, 31.8% overweight, 17.0% obese]. Figure 1 illustrates the prevalence of overweight and obesity in each cohort stratified by sex, compared to the national average. When comparing obese patients to those with normal weight, both PsA and RA obese patients had significantly higher C-reactive protein, worse disease activity score, lower quality of life (QoL) measures, and more frequent cardiovascular disease and diabetes. Among PsA patients, the overweight and obese had worse physician-assessed skin manifestation and patient-reported pain compared to the normal weight group. While in RA, the obese patients had higher erythrocyte sedimentation rate, smaller prevalence of seropositive patients, lower frequency of fractures/surgeries, and higher tender joint counts, but similar swollen joint counts, when compared to the normal weight group.Adalimumab and etanercept, were the most commonly prescribed drugs as first biologic/tsDMARD treatment in both PsA and RA cohorts and among every BMI category. Overall, 55% PsA and 56% RA patients had recorded treatment stop/switch. Among RA patients, significantly fewer obese patients reported treatment stop/switch at >12 months from treatment start, compared to the normal weight group. Adalimumab and etanercept were also the most commonly prescribed second biologic/tsDMARD treatment, but for the obese group among PsA patients (adalimumab, golimumab) and the obese group in the RA cohort (adalimumab, rituximab).Conclusion:In this national wide study, we observed that the prevalence of obesity in RA and PsA was higher than that of the general Swiss population. Obese PsA/RA patients starting first biologic/tsDMARD treatment presented worse disease activity and poorer QoL than normal weight patients. Results suggest to take BMI into consideration when treating PsA and RA patients.Acknowledgements:We would like to thank all patients and rheumatologists contributing to the SCQM registry, as well as the entire SCQM staff. A list of rheumatology offices and hospitals which contribute to the SCQM registry can be found at http://www.scqm.ch/institutions. The SCQM is financially supported by pharmaceutical industries and donors. A list of financial supporters can be found at http://www.scqm.ch/sponsors.Disclosure of Interests:Enriqueta Vallejo-Yagüe: None declared, Theresa Burkard: None declared, Burkhard Moeller Speakers bureau: AbbVie, Bristol Myers, Eli Lilly, Janssen, Pfizer, Roche, Novartis, Merck, Axel Finckh Speakers bureau: Pfizer, Eli-Lilly, Paid instructor for: Pfizer, Eli-Lilly, Consultant of: AbbVie, AB2Bio, BMS, Gilead, Pfizer, Viatris, Grant/research support from: Pfizer, BMS, Novartis, Andrea Michelle Burden: None declared