BMI Measures Research Articles

OR26-06 Fecal Microbiota Transplantation Trial for the Improvement of Metabolism (FMT-TRIM): A Randomized Double-Blind Placebo-Controlled Pilot Trial

Background: There is intense interest about the therapeutic potential of altering gut microbiota to improve metabolism, based primarily on intriguing animal studies. One prior trial of fecal microbiota transplantation (FMT) in obese men found that improved metabolic response after FMT was predicted by low baseline microbiome diversity. In the current trial, we investigated the safety and efficacy of weekly oral FMT capsules to improve glycemic outcomes in obese adults, and also explored determinants of successful microbiome engraftment and metabolic improvement after FMT. Methods: FMT-TRIM was a double-blind randomized placebo-controlled pilot trial of weekly oral FMT vs placebo capsules for 6 weeks in 24 obese adults with mild-moderate insulin resistance. Each participant in the FMT arm received capsules derived from one of 4 metabolically healthy lean donors (BMI 18.5-23 kg/m2). The primary outcome was change in insulin sensitivity assessed by hyperinsulinemic euglycemic clamp at 0 and 6 weeks. Secondary outcomes included body weight, metabolic labs, and body composition assessed by DXA over 12 weeks. 16SV4 rRNA sequencing was performed to assess microbiome composition and engraftment. Post-hoc exploratory analyses investigated metabolic outcomes after stratification by baseline microbiome diversity. Results: FMT and placebo groups were well balanced in terms of age (mean±SD 40±9 yrs), BMI (40±6 kg/m2), sex (72% female), and baseline metabolic measures. During the study, there were no statistically significant differences in insulin sensitivity between the FMT and placebo groups (+5 ± 12% FMT vs -3 ± 32% placebo, mean percent difference 9%, 95% CI -5% to 28%; p=0.16). There was a minor improvement in HbA1c at 12 weeks after FMT as compared to placebo (mean difference -0.1, 95% CI -0.3-0.01), but no significant differences in other metabolic labs, body weight, or body composition. Microbial engraftment varied by donor but was present in most FMT recipients, with persistence of engrafting strains throughout the 12-week study. Subgroup analyses of subjects with low microbiome diversity at baseline (FMT n=4, placebo n=7) showed a relative benefit of FMT over placebo at 12 weeks for HbA1c (mean difference -0.2, 95% CI -0.4 to -0.01), total cholesterol (-22 mg/dL, 95% CI -40 to -4 mg/dL), and fasting glucose (-10 mg/dL, 95% CI -19 to -1 mg/dL). There were no significant differences in adverse events between FMT and placebo groups. Conclusion: Weekly administration of FMT capsules results in gut microbiota engraftment for at least 12 weeks but does not meaningfully alter human metabolism in an unselected population of obese adults. Future studies are needed to elucidate the role of baseline recipient microbial diversity and other factors on the impact of FMT.

The Effect Of Stretching Exercises Applıed Following 6 Week Aerobıc Exercise On Women In Various Age Groups

Objective: This study was carried out to determine the differences between exercises of women in different age groups. Material and Methods: Aerobic exercise was administered to 20 exercise and control groups each at ages ranging between 17-24 and 30-45. Before and after the study, Sit and Reach Test, Shuttle test, BMI measure were carried out. Results: In terms of BMI, there was a significant difference between pretest and posttest and there was no difference in BMI between middle-age exercise and young age exercise and young age control group. When all age groups were evaluated in terms of shuttle movement, no difference was found between exercise groups, and there was a significant difference between exercise and control groups. It was observed that there was a significant difference between pretest and posttest in terms of the length of the long jump and double leg sit length test and there was a significant increase in the elasticity values ​​of the exercise groups in the scale score. C onclusion: This study showed that the flexibility of jointo movement of the individuals can be improved with the appropriate stretching exercises after warming, and that these exercises can be applied in every age group.

During two years, what is the difference between an exclusive two-day educational program on OA and a program that adds multimodal attention for 6 moths in the treatment of OA?

Purpose: Osteoarthritis (OA) is the leading skeletal cause of years lived in disability. Education/self-management, diet if overweight and exercise are considered core treatment in several guidelines including OARSI’s 2014 and 2019. The aim of this study was to evaluate the effectiveness in reducing body fat and secondarily reducing knee pain, improving function and increasing exercise hours of a six months (20 interventions) educational/multiprofessional care program to a two-day educational program. Methods: Prospective randomized clinical trial with 116 patients with grades II and III K&L knee OA (KOA) and multiple OA were randomized to one of two groups: control (usual care with medical appointments at inclusion, six, 12 and 24 months) and two periods of 5 hours of lectures, two month apart, about OA with a multiprofessional group) and a group with an extended intervention program (same as the control group and seven sessions of collective physical therapy, seven sessions of group physical fitness, two group sessions of discussion about diet with the nutritionist and two about engaging the program with the psychotherapist) along the first six months of the program. Six months after inclusion, patients of the extended interventation group (EIG) were oriented to continue diet and to exercise at local gyms or at home. All patients were evaluated at inclusion, six, 12 and 24 months. VAS, WOMAC, Lequesne, and measures of BMI, percentage of lean and body fat, Body weight, fat weight, lean weight, Hip-waist ratio (HWR), timed up and go (TUG), 30 second chair stand test (30CST), Timed up and down stairs (TUDS), 6-minute walk test (6MWT) and adherence to physical activity (IPAQ) were taken at baseline, six, twelve and 24 months. Results: Tables 1, 2 and 3 summarize the results. Groups were similar at baseline (p>0.05) except for WOMAC stiffness, that in all moments was, in average, 0.68 less in the study group (p=0.019) despite both groups improving progressively throughout the study period (p<0.05). Control group had a higher number of dropouts at one year (15 in total (25%), 13 in the first six months, without dropouts in the second year), whereas seven (12%) abandoned the EIG (six in the first six months and one before one year). At six months evaluation, all parameters were better in the study group (p<0.05) with the exception of HWR, TUG and lean weight. HWR and TUG did not vary during the study. Only the EIG improved pain (VAS) from baseline to all moments (p<0,002), but both groups improved pain by WOMAC pain with similar results at 2 years. Lequesne, TUDS, 6MWT, IPAQ results improved in all moments for both groups without a significant difference between groups. WOMAC function and total and the 30CST improved faster in the EIG with more than 15 points difference in WOMAC at 6 months (At two years, groups presented similar results with loss of the EIG results and continued gain of the CG). Only the EIG reduced body weight (p<0.001), BMI (p=0.002), fat weight (p<0.05) in all moments. Both groups reduced and had similar percentage of body fat at two years follow-up (with gain in body fat percentage of the EIG in the second year and continued loss of the CG during the study period). Conclusions: In patients with multiple OA (and knee OA), both methods improve pain and function. The extended intervention program improves more rapidly pain, adherence to the program and physical activity level, and function when compared to a two-day class only group. Loss of body weight, fat weight and BMI was only achieved by the extended program with partial loss of results probably due to ceasing group interventions after 6 months.View Large Image Figure ViewerDownload Hi-res image Download (PPT)View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Newborn feeding recommendations and practices increase the risk of development of overweight and obesity

BackgroundThe prevalence of obesity among infants less than 2 years of age has increased by more than 60% over the last three decades. Obese infants and toddlers are at an increased risk for staying overweight into adolescence and adulthood. Metabolic programming has been demonstrated in animal models whereby early life feeding habits result in life-long changes in hormone balance and metabolism. Our study explores if newborn over-nutrition on the first day of life (DOL1) is associated with risk for future overweight and obesity in childhood.MethodsRetrospective chart data was collected for full term formula-fed infants born between January 2008 and December 2012 who continued care at the same institution. Data included the volume of formula (ml) consumed on DOL1 as well, as subsequent yearly BMI measures from well child checkups (WCC). Overfeeding was categorized as any feed greater than or equal to 30 ml on any of the first seven feeds while controlling for birth weight.ResultsThe final data set included 1106 infants (547 male; 559 female). 1023 of the 1106 newborns (93%) were overfed at least once during DOL1, while 789 of 1106 (71%) were overfed 3 or more times during their first 7 feeds. After adjusting for birth weight, infants who were overfed 5 of the first 7 feeds were 5 times as likely to be overweight or obese at their 4th year well child check-up (p < 0.05) compared to children not overfed. Infants who were overfed on all 7 of their first 7 feeds were 7 times more likely to be overweight or obese at their 4th year WCC (p = 0.017).ConclusionsInfants overfed on DOL1 were significantly more likely to be overweight or obese at their 4th year WCC, compared to infants not overfed on their first day of life. Newborn families may benefit from counseling regarding age-appropriate volumes of formula during this critical time period. Future studies will aim to look at effect of implementation of smaller feeding bottle size on reducing overfeeding practices and future risk of overweight and obesity.

Participating in Kinesiology Activities in Primaryeducation Students’ Free Time

The objective of the research was to investigate to what extent students of first and second grades of primary school participate in physical activities in their free time. We are living in the age of sedentary lifestyle, which is becoming a problem of public health. 189 respondents took part in this research of which 93 girls and 96 boys aged 7 to 9. To assess the level of students’ activity in their free time, a poll was used consisting of eight questions from the questionnaire “Fels physical activity questionnaire for children” (FPAQ). Based on queries from the questionnaire, indices were calculated from the area of sports (IS), free time (ISV; household chores (IKP) and total physical activity result (UTA). To assess body composition, anthropometric measures of height, mass, BMI and percentage of fat in the body were used. To assess those, we used the device for measuring physical composition– Omron BF500 Body Composition Monitor. Results indicate that 59.26% do not meet daily recommendations for participating in physical activities. As regards the difference in students’ age, it is notable that second grade students are somewhat more physically active. Observing average results, it is clear that students were most physically active in their free time. The lowest values were recorded in the area of sports at school, (1.15), yet lower values were also obtained from sports club activities (2.06). It is evident that students of that age are minimally active during their PE classes and this is a segment where the number of physically active students can be increased. Increasing physical activity at school shall encourage students to participate in physical activity outside educational institutions.

Abstract P527: Body Mass Index (bmi, Kg/m 2 ) vs. Body Fat % (bf%): Battle of Obesity Classification Metrics to Inform Underlying Cardiometabolic Risk

Introduction: The WHO defines overweight and obesity as abnormal or excessive fat accumulation that may impair health. However, for population and clinical classification of overweight and obesity BMI is most commonly used as a proxy for adiposity. Despite the strength of the association between higher BMI and cardiometabolic disease risk across populations, and minimal direct comparison of BMI v. BF%, BMI draws significant criticism as a metric to classify obesity and screen for cardiometabolic risk. Hypothesis: BF% defined obesity classification categories have higher underlying cardiometabolic risk compared to equivalent BMI categories. Methods: We analyzed data from CARDIA study participants from the year 20 exam with concurrent measures of BMI, and BF% measured by Dual-energy X-ray absorptiometry (DXA), plus clinical measures. Sex specific BF% obesity classification categories were defined by evidence-based diagnostic and classification performance measures vs. standard BMI cut points. Underlying cardiometabolic risk was defined by a continuous metabolic syndrome risk score (MetS), consisting of the averaged standardized deviates of the 5 ATP III components. Higher MetS z-scores indicate higher overall risk. MetS z-scores between categories (e.g. obesity defined by BMI v. BF%) were compared by z-tests. Results: The figure reports the distribution of obesity classification categories by the different metrics and underlying cardiometabolic risk. The MetS risk score was significantly higher in BMI defined overweight and obesity compared to BF% defined categories; and BF% defined obesity categories classify a greater prevalence of the population as obese compared to BMI. Results for MetS risk did not differ by race/sex or when including prevalent cardiometabolic disease. Conclusions: Physiologically defined BF% obesity categories classify a greater prevalence of obesity in CARDIA at year 20, whereas there was higher underlying cardiometabolic risk in BMI defined obesity classification categories.

Increased Brain Volume from Higher Cereal and Lower Coffee Intake: Shared Genetic Determinants and Impacts on Cognition and Metabolism

Background: It is unclear how different diets may affect human brain development and if genetic and environmental factors play a part.Methods: We used cross-sectional observational data from UK Biobank. Only white British individuals free of Alzheimer's or dementia diseases were included in the study. We conducted linear regression analysis and mediation models to examine the association between diets, gerey matter volume, genetic variants, lifestyle, and metabolic measures. We tested the association between the GMV-association patterns of the cereal/coffee intake, the GMV-association patterns of cognitive functions and the gene-expression patterns.Findings: Overall, 336517 participants were included in our analysis. We discovered anti-correlated brain-wide grey matter volume (GMV)-association patterns between coffee and cereal intake, coincidence with their anti-correlated genetic constructs. These genetic factors may further affect people’s lifestyle habits and body/blood fat levels through the mediation of cereal/coffee intake, and the brain-wide expression pattern of gene CPLX3, a dedicated marker of subplate neurons that regulate cortical development and plasticity, may underlie the shared GMV-association patterns among the coffee/cereal intake and cognitive functions.Interpretation: Our findings thus revealed that high-cereal and low-coffee diets shared similar brain and genetic constructs, leading to long-term beneficial associations regarding cognitive, BMI and other metabolic measures. This study has important implications for public health, especially during the pandemic, given the poorer outcomes of COVID-19 patients with greater BMIs.Funding Statement: This work received support from the following sources: the National Key Research and Development Program of China (2018YFC1312900 and 2019YFA0709502), the National Natural Science Foundation of China (91630314 and 81801773), the 111 Project (B18015), The Key Project of Shanghai Science &Technology Innovation Plan(16JC1420402), the Shanghai Municipal Science and Technology Major Project (2018SHZDZX01) and Zhangjiang Lab. Declaration of Interests: The authors declare no competing interests.Ethics Approval Statement: All participants provided written informed consent to UK Biobank. The UK Biobank study received ethical approval from the NHS National Research Ethics Service North West (reference number: 16/NW/0274). Data access permission was granted under UKB application 19542 (PI Jianfeng Feng).

Interventions including diet and physical activity shown to be effective in preventing obesity in children: a Cochrane review

Review of Brown T, Moore TH, Hooper L, et al . Interventions for preventing obesity in children. Cochrane Database Syst Rev 2019 Jul 23;(7). Study question : Are interventions that...

In utero teratogen exposure and cardiometabolic risk in 5-year-old children: a prospective pediatric study

Background Aorta and carotid intima-media thickness (IMT) is a measure of subclinical atherosclerosis and useful to assess cardiometabolic risk in the young. The in utero milieu may involve cardiometabolic programing and the development of cardiometabolic risk factors in children. Maternal smoking, alcohol consumption, and micronutrient deficiencies during pregnancy influence the development of the cardiovascular system through a process of DNA methylation. Aim To explore an association between maternal smoking and alcohol consumption during pregnancy and intima media thickness in 5-year-old children for a low-income setting. Methods Data were collected from 500 mother–child pairs at antenatal clinic visit, at birth, and at age 5 years. Anthropometric measurements were collected at birth and again at age 5 years. As well as clinical and ultrasound measurements at age 5 years. Clinical measurements, at age 5 years, included blood pressure, mean arterial pressure, and heart rate. Ultrasound measurements of the aorta and carotid arteries IMT were performed at age 5 years. Main outcome of interest was effect of dual teratogen exposure on the ultrasound measures IMT as indication of cardiometabolic risk. Results cIMT was significantly higher in children exposed to both alcohol and nicotine during pregnancy compared to those not exposed (p = .008). In separate linear models, dual in utero exposure (beta = 0.12; p = .01) and male sex (beta = 0.14; p = .01) were associated with higher right cIMT values (F(6,445) = 5.20; R 2 = 0.07, p < .01); male sex (beta = 0.13; p = .01) and low birth weight (beta = 0.07; p = .01) with higher left cIMT value (F(4,491) = 4.49; R 2 = 0.04; p = .01); and males sex (beta = 0.11; p = .02) with higher aorta IMT (F(6,459) = 5.63; R 2 = 0.07; p < .01). Significant positive correlations between maternal measures of adiposity, maternal MUAC (r = 0.10; p = .03), and maternal BMI (r = 0.12; p < .01) and right cIMT measurements adjusted for the BMI of the child at age 5 years as covariate. Blood pressure measurements at age 5 years were not significantly associated with IMT but, instead, correlated significantly and positively with the BMI of the child at age 5 years (p < .01). Conclusion Children exposed to both maternal smoking and alcohol consumption during pregnancy presented with cardiometabolic risk factors 5 years after birth. In addition, maternal adiposity, male sex, and low birth weight were associated with higher IMT at age 5 years.

Hyperglycemia During Pregnancy and Long-Term Offspring Outcomes.

This review will focus on the long-term outcomes in offspring exposed to in utero hyperglycemia and gestational diabetes (GDM), including obesity, adiposity, glucose metabolism, hypertension, hyperlipidemia, nonalcoholic fatty liver disease, and puberty. There is evidence, mostly from observational studies, that offspring of GDM mothers have increased risk of obesity, increased adiposity, disorders of glucose metabolism (insulin resistance and type 2 diabetes), and hypertension. In contrast, evidence from the two intervention studies of treatment of mild GDM and childhood measures of BMI, adiposity, and glucose tolerance do not demonstrate that GDM treatment significantly reduces adverse childhood metabolic outcomes. Thus, more evidence is needed to understand the impact of maternal GDM on offspring's adiposity, glucose metabolism, lipid metabolism, risk of fatty liver disease, and pubertal onset. Offspring of GDM mothers may have increased risk for metabolic and cardiovascular complications. Targeting this group for intervention studies to prevent obesity and disorders of glucose metabolism is one potential strategy to prevent adverse metabolic health outcomes.

CHANGES OVER TIME IN DAYTIME SLEEPINESS AMONG OLDER ADULTS RECEIVING LONG-TERM SERVICES AND SUPPORTS

The purpose of this study was to examine the predictors of excessive daytime sleepiness (EDS) over the first two years of long-term services and supports (LTSS) for 470 older adults in assisted living communities (ALCs), nursing homes (NHs), or their homes. Mixed effects linear regression modeling using a backward elimination process was used to build a final multivariable model. In the final model, being female (p<0.001) and fewer functional deficits (p<0.001) at baseline were associated with decreases in EDS, while higher baseline measures of BMI (p=0.004) and number of symptoms (p<0.001) were associated with higher EDS. Compared to older adults living in the community and receiving LTSS, those in NHs and ALCs had higher EDS (p<0.001). Greater feelings of belonging and depressive symptoms at baseline were associated with slower rates of increase in EDS over time (both p<0.001). Modifiable predictors of EDS and clinical implications will be discussed.

Impact of Acipimox Therapy on Free Fatty Acid Efflux and Endothelial Function in the Metabolic Syndrome: A Randomized Trial.

Insulin resistance is associated with increased lipolysis and elevated concentrations of free fatty acids (FFA), which in turn contribute to impaired vascular function. It was hypothesized that lowering FFA with acipimox, a nicotinic acid derivative that impairs FFA efflux, would improve endothelial function, measured by flow-mediated dilation (FMD), in individuals with metabolic syndrome. A total of 18 participants with metabolic syndrome and 17 healthy controls were enrolled and treated with acipimox 250 mg orally every 6 hours or placebo for 7 days in a randomized, double-blind, crossover trial. Acipimox reduced FFA concentrations among individuals with metabolic syndrome to near normal levels (P=0.01), but there was no change among healthy controls (P=0.17). Acipimox did not improve endothelial-dependent FMD in either group (metabolic syndrome: P = 0.42; healthy controls: P = 0.16), although endothelial-independent nitroglycerin-mediated dilation among those with metabolic syndrome tended to increase (20.3%, P = 0.06). There were no changes in blood lipids or markers of inflammation following therapy. There was minimal correlation between change in FMD and baseline measures of BMI ( ρ = -0.09) or waist circumference ( ρ = -0.15). In groups with normal or elevated baseline FFA, short-term reductions do not improve endothelial function assessed by FMD.

Maltreatment experience in childhood and average excess body mass from adolescence to young adulthood

BackgroundPrior studies have suggested maltreatment is a strong predictor of later weight outcomes, such that maltreatment experiences in childhood increase the likelihood of being overweight or obese in adulthood. Estimates of this relationship may be biased due to: 1) inadequate selection of covariates; 2) improper operationalization of child maltreatment; and 3) restricting analyses to cross-sectional outcomes. ObjectivesEvaluate how latent classes of child maltreatment experiences are associated with a longitudinal BMI measure from adolescence to adulthood. ParticipantsData from the National Longitudinal Study of Adolescent to Adult Health. MethodsWe evaluated how previously developed latent classes of child maltreatment experiences were associated with average excess BMI from adolescence to adulthood using multivariate linear regression. ResultsIn the unadjusted model, individuals in the poly-maltreatment class (b = 0.46, s.e. = 0.20) and individuals who experienced adolescent-onset maltreatment (b = 0.36, s.e. = 0.11) had higher average excess BMI compared to individuals in the no maltreatment class. After adjusting for confounders, the relationship between poly-maltreatment and average excess BMI abated, whereas the relationship between adolescent-onset maltreatment and average excess BMI sustained (b = 0.28, s.e. = 0.11). ConclusionsContrary to previous findings, our analyses suggest the association between maltreatment experiences and longitudinal weight outcomes dissipates after controlling for relevant confounders. We did find a relationship, however, between adolescent-onset maltreatment and average excess BMI from adolescence to adulthood. This suggests the importance of maltreatment timing in the relationship between maltreatment and weight.

Abstract 4209: Codon 72 polymorphisms of p53 are associated with obesity, diabetes, and race in breast cancer

Abstract Background: As a tumor suppressor and a factor in glucose metabolism, p53 is an alluring point of focus in the study of obesity and cancer. Population-based studies show that single nucleotide polymorphisms (SNPs) at codon 72 of p53 are individually linked with development of breast cancer, high BMI, and type II diabetes. In this study cohort of African American (AA) and Caucasian (CA) women with breast cancer, we assessed the relationships between arginine (Arg) and proline (Pro) phenotypic variants and obesity and type II diabetes, accounting for confounding molecular and demographic influences. We also evaluated the prognostic relevance of these factors. Methods: DNA samples isolated from breast tumor tissues collected from 190 (AA=90 and CA= 100) women were genotyped to detect SNPs at codon 72 of the p53 gene and were sequenced by using exon-specific primers (4 through 9). These exons were selected because more than 90% of mutations are located in these exons of p53. For all women, information on BMI and type II diabetes status was collected from electronic health records. Obese was defined as BMI ≥ 30. The closest measure of BMI within 5 years of the date of the diagnostic sample was used, and the time difference between BMI and sample date was included as a confounding variable in adjusted analyses. Only pre-tumor sample diagnoses of type II diabetes were considered. Clinical and demographic variables were evaluated for their association to p53 SNPs, using χ2 tests for categorical analysis and F-tests for continuous variables. Linear regression models were used to examine interactions with BMI. Cox proportional hazard regression models were used for all time-to-event analyses. Separate models were built for each BMI-defined category of weight (underweight, normal, overweight, or obese). Results: Both SNP72 and BMI were strongly associated with race. For AAs, 68% were obese, and 49% were Pro/Pro phenotype. CAs were less obese (24%), and most were Arg/Arg (60%). Most cases of type II diabetes (78%) were AAs, but 23 total patients with diabetes was insufficient for BMI-stratified analysis. As determined in a linear regression model, there was an interaction between race, SNP72 and BMI. AAs with Arg/Arg had significantly higher BMI values than other SNP/race groups (P=0.003). In a Cox model of obese-only patients, adjusted for race, p53 somatic mutation, time of BMI measure, tumor stage, and molecular subtype, Arg/Arg women had 3.81 times higher hazard of death from cancer than Pro/Pro women (95% CI: 1.08,13.48). Type II diabetes apparently did not influence survival, but this observation may be due to insufficient sample size. Conclusions: The association between SNP 72 and BMI varied according to race. African American women who exhibited Arg/Arg had an average BMI of 35. For obese patients, Arg/Arg had a negative influence upon survival, which was independent of established risk factors, including race. Citation Format: Michael Behring, Bunyamin Ozaydin, Upender Manne. Codon 72 polymorphisms of p53 are associated with obesity, diabetes, and race in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4209.

Copeptin relates to a fatty liver and measures of obesity in a South African population with mixed ethnicities

PurposeElevated copeptin, a vasopressin marker, is linked to metabolic disease, and obese rats with low-vasopressin concentration had a decreased risk of liver steatosis. We here investigated the association between copeptin and nonalcoholic fatty liver disease (NAFLD) and possible differences in copeptin concentration between ethnicities.MethodsIn this cross-sectional study of 361 South Africans (n = 172 African black, 189 = Caucasian) with a mean age of 45 years and 45% men, plasma copeptin was measured and associated with NAFLD according to a validated fatty liver index accounting for measures of BMI, waist, triglycerides, and gamma-glutamyltransferase.ResultsThere was no significant difference in copeptin concentrations between ethnicities after age and gender adjustment (p = 0.24). Increasing copeptin tertile levels were significantly associated with obesity, overweight, and abdominal obesity, respectively, after multivariate adjustment for age, gender, ethnicity, and high HOMA-IR (p = 0.02 for all). Individuals in the second and third copeptin tertile had an increased odds (95% CI) of NAFLD of 1.77 (1.04–3.02) and 2.97 (1.74–5.06), respectively, compared to the bottom tertile (p < 0.001). The association between increasing copeptin tertile and NAFLD remained significant after adjustment for age, gender, ethnicity, high HOMA-IR, self-reported current alcohol intake, and statin treatment (p = 0.01).ConclusionsElevated plasma copeptin is independently associated with NAFLD in a population with mixed ethnicities, pointing at the pharmacologically modifiable vasopressin system as a new mechanism behind NAFLD.

1356-P: Comparison of Serum Adipokines and Anthropometric Measures in Children with Type 1 Diabetes (T1D) and Obesity

Obesity or overweight occur in 40% of U.S. youth with T1D. While BMI is used to define obesity, it may not accurately reflect excess adiposity, which correlates better with metabolic dysfunction. However, it is difficult to measure adiposity without a research setting. In contrast, adipokines, which are produced by the adipose tissue, can be measured in serum. We aimed to analyze, in youth with T1D and obesity, the relationships of serum adipokines with measures of adiposity and cardiovascular risk factors. We studied participants in the T1D Exchange Metformin Study with a serum sample obtained before randomization (n=61, mean age=8.0 years [SD=3.0], 27.9% male, 82.0% non-Hispanic white, mean BMI percentile=99.0 ([SD=1.0], mean BMI Z-score=2.7 [SD=0.78], mean % of the 95th BMI percentile (%95th BMI pctle)=134.6 [SD=20.0]). We measured serum levels of adipokines and inflammatory markers. We studied the correlations between DEXA scan-derived measures of adiposity (e.g., % body fat) with adipokines (e.g., leptin, adiponectin) or anthropometric measures (e.g., % 95th BMI pctle [recommended measure for extreme obesity], BMI-Z score). DEXA % body fat was significantly correlated with % 95th BMI pctle (r=0.494, p&amp;lt;0.0001) or leptin (r=0.467, p=0.0002), without statistical difference between these two correlations (p = 0.857). The correlation between % body fat and BMI Z-score was weaker (r=0.29, p=0.0270). Higher adiponectin was correlated with cardiovascular protective factors, such as lower systolic blood pressure (p=0.039) and higher HDL cholesterol (p=0.001), while neither % 95th BMI pctle nor BMI Z-score were. Children with high adiponectin (&amp;gt;26.5 mg/L, distribution mean) were less likely to have high CRP &amp;gt;6 mg/L (1.6%) vs. children with low adiponectin (23.0%, p&amp;lt;0.05). Serum adipokines levels could be used as more convenient markers of adiposity than BMI measures, and potentially become therapeutic targets to improve clinical outcomes in children with T1D and obesity. Disclosure M.J. Redondo: None. X. Gu: None. S. Sisley: Advisory Panel; Self; Rhythm Pharmaceuticals, Inc. M. Tosur: None. A.F. Siller: None. M. Bondy: None. S. Devaraj: None.

122-OR: Impact of Withdrawal of Interventions in the Restoring Insulin Secretion (RISE) Pediatric Medication Study

The RISE Pediatric Medication Study showed, in 91 obese 10-19 yo youth with impaired glucose tolerance (IGT, 60%) or recent-onset type 2 diabetes (T2D, 40%), that 12 mo of intervention with metformin alone (M) or glargine for 3 mo followed by metformin for 9 mo (G+M) resulted in no change in BMI or HbA1c and a decline in β-cell function measured by hyperglycemic clamp. These outcomes worsened 3 mo after withdrawal of the interventions. We expand our findings to mo 21 (M21) post randomization (9 mo after withdrawal of M or G+M) using oral glucose tolerance test (OGTT) measures of β-cell responsiveness (C-peptide index, CPI; insulinogenic index, IGI; incremental C-peptide/glucose area under the curve), BMI and HbA1c. Paired t-tests were used to compare treatment groups on changes from baseline (BL, n=91) to mo 12 (M12, n=86) and M21 (n=82), and from treatment withdrawal at M12 to M21. At M12 vs. BL, no measures differed in either group (Table). At M21 vs. BL, HbA1c increased in both groups, and BMI increased and CPI and IGI declined in the G+M group. At M21 vs. M12, BMI, HbA1c, fasting and 2-h glucose increased in both groups, and CPI declined in the G+M group. Our findings contrast with studies in adults showing durable benefits of metformin and insulin on HbA1c and β-cell responsiveness. Further investigation is needed to find effective treatments that prevent progression of dysglycemia in youth with IGT or recent-onset T2D. Disclosure T.S. Hannon: Advisory Panel; Self; Eli Lilly and Company. S. Edelstein: None. S.A. Arslanian: None. S. Caprio: None. P. Zeitler: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Janssen Research &amp; Development, Merck &amp; Co., Inc., Novo Nordisk Inc. T.A. Buchanan: Research Support; Self; Allergan, Apollo EndoSurgery. D.A. Ehrmann: None. K.J. Mather: Advisory Panel; Self; Roche Diabetes Care. Research Support; Self; Abbott, Merck &amp; Co., Inc., Novo Nordisk A/S, Sanofi. E. Leschek: None. M. Tripputi: None. S.E. Kahn: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc., Novo Nordisk A/S. Consultant; Self; Neurimmune. Other Relationship; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck &amp; Co., Inc., Novo Nordisk A/S. K.J. Nadeau: None. R. Consortium: None. Funding American Diabetes Association (1-14-RISE-01 to S.E.K.); National Institute of Diabetes and Digestive and Kidney Diseases

1907-P: GLP-1RA and iSGLT2 Combination Treatment Effects over Fatty Liver Index

Aim: To analyze changes in Fatty Liver Index (FLI) in obese and T2DM patients under treatment with GLP-1RA - SGLT2i combination. Methods: Observational, prospective, multicenter study. Patients were stratified according to predetermined treatment schedule groups (successively vs. simultaneously). Results: We included 142 patients (59.1% men, mean age 60.8±8.9 years). 76.7% had hypertension and 81.7% dyslipidemia. The BMI was 36.9 ±.7.1 kg/m2, FLI was 97±11, A1C was 8.0% ±1.5%, Triglyceride (Tg) was 158±102 mg/dl, Waist circumference (WC) 120.3 cm and gamma-glutamyl-transferase (GGT) was 43±45 UI/L. At 26 weeks follow-up we found a significant reduction in FLI (-5 points; p&amp;lt;0.0000), A1C (-1.1%; p&amp;lt;0.0001), BMI (-2.1 kg/m2; p&amp;lt;0.00003), GGT (-11 UI/L; p&amp;lt;0.0003), WC (-6.7 cm; p&amp;lt;0.000) and Tg (-28.5; p&amp;lt;0.01). Table 1 expands results in predetermined groups. Discussion: Nonalcoholic fatty liver disease (NAFLD) is characterized by the accumulation of fat in the absence of other causes of steatosis. FLI is an accurate algorithm which can be used as a surrogate marker of steatosis; it combines measures of Tg, GGT, WC and BMI. GLP-1RA have direct effects on hepatocytes improving liver histology and reducing GGT levels. However, data on SGLT2i over the liver fat are scarce. Our study demonstrated that the combination of GLP-1RAs-SGLT2i reduces liver fat in patients with T2DM being positively correlated with improvement in A1C, BMI, WC and GGT. Disclosure J. Carretero Gómez: None. J. Arevalo Lorido: None. R. Gómez-Huelgas: None. J. Seguí-Ripoll: None. M. Suarez Tembra: None. J. Casas: None. J. Carrasco: None.

Testing Bidirectional Associations Between Childhood Aggression and BMI: Results from Three Cohorts.

ObjectiveThis study examined the prospective, potentially bidirectional association of aggressive behavior with BMI and body composition across childhood in three population‐based cohorts.MethodsRepeated measures of aggression and BMI were available from the Generation R Study between ages 6 and 10 years (N = 3,974), the Netherlands Twin Register (NTR) between ages 7 and 10 years (N = 10,328), and the Swedish Twin Study of Child and Adolescent Development (TCHAD) between ages 9 and 14 years (N = 1,462). In all samples, aggression was assessed with the Child Behavior Checklist. Fat mass and fat‐free mass were available in the Generation R Study. Associations were examined with cross‐lagged modeling.ResultsAggressive behavior at baseline was associated with higher BMI at follow‐up in the Generation R Study (β = 0.02, 95% CI: 0.00 to 0.04), in NTR (β = 0.04, 95% CI: 0.02 to 0.06), and in TCHAD (β = 0.03, 95% CI: −0.02 to 0.07). Aggressive behavior was prospectively associated with higher fat mass (β = 0.03, 95% CI: 0.01 to 0.05) but not fat‐free mass. There was no evidence that BMI or body composition preceded aggressive behavior.ConclusionsMore aggressive behavior was prospectively associated with higher BMI and fat mass. This suggests that aggression contributes to the obesity problem, and future research should study whether these behavioral pathways to childhood obesity are modifiable.

Parental Education and Genetics of BMI from Infancy to Old Age: A Pooled Analysis of 29 Twin Cohorts.

Objective:To analyze how parental education modifies the genetic and environmental variances of body mass index (BMI) from infancy to old age in three geographic-cultural regions.Methods:A pooled sample of 29 cohorts including 143 499 twin individuals with information on parental education and BMI from 1 to 79 years (299 201 BMI measures) was analyzed by genetic twin modeling.Results:Until 4 years of age, parental education was not consistently associated with BMI. Thereafter, higher parental education was associated with lower BMI in males and females. Total and additive genetic variances of BMI were smaller in the offspring of highly educated parents than in those whose parents had low education. Especially in North American and Australian children, environmental factors shared by co-twins also contributed to the higher BMI variation in the low educational category. In Europe and East Asia, the associations of parental education with mean BMI and BMI variance were weaker than in North America and Australia.Conclusions:Lower parental education is associated with higher mean and larger genetic variance of BMI after early childhood, especially in the obesogenic macro-environment. The interplay between genetic predisposition, childhood social environment and macro-social context is important for socio-economic differences in BMI.