Concurrent Weight Research Articles

Anemia in patients with cartilage hair hypoplasia: a narrative review and recommendations.

Cartilage hair hypoplasia (CHH) can lead to the development of anemia as a possible complication of this rare genetic disease. Despite various publications on anemia in CHH patients, a comprehensive review on this topic has not been conducted. This article reviews publications on anemia in CHH patients published from 1981 to 2022. Most authors have reported macrocytic anemia and blood transfusion as a common treatment approach in this patient group. Recommended guidelines for managing anemia in CHH patients include iron chelation therapy for those requiring multiple blood transfusions, regular assessment of anemia symptoms, red blood cell parameters, and immune system function. Future studies should evaluate the erythroid system in a larger cohort of CHH patients, considering key factors such as concurrent illnesses, age, height, and weight.

A low-glucose eating pattern is associated with improvements in glycemic variability among women at risk for postmenopausal breast cancer: an exploratory analysis.

High glycemic variability (GV) is a biomarker of cancer risk, even in the absence of diabetes. The emerging concept of chrononutrition suggests that modifying meal timing can favorably impact metabolic risk factors linked to diet-related chronic disease, including breast cancer. Here, we examined the potential of eating when glucose levels are near personalized fasting thresholds (low-glucose eating, LGE), a novel form of timed-eating, to reduce GV in women without diabetes, who are at risk for postmenopausal breast cancer. In this exploratory analysis of our 16-week weight loss randomized controlled trial, we included 17 non-Hispanic, white, postmenopausal women (average age = 60.7 ± 5.8 years, BMI = 34.5 ± 6.1 kg/m2, HbA1c = 5.7 ± 0.3%). Participants were those who, as part of the parent study, provided 3-7 days of blinded, continuous glucose monitoring data and image-assisted, timestamped food records at weeks 0 and 16. Pearson's correlation and multivariate regression were used to assess associations between LGE and GV, controlling for concurrent weight changes. Increases in LGE were associated with multiple unfavorable measures of GV including reductions in CGM glucose mean, CONGA, LI, J-Index, HBGI, ADDR, and time spent in a severe GV pattern (r = -0.81 to -0.49; ps < 0.044) and with increases in favorable measures of GV including M-value and LBGI (r = 0.59, 0.62; ps < 0.013). These associations remained significant after adjusting for weight changes. Low-glucose eating is associated with improvements in glycemic variability, independent of concurrent weight reductions, suggesting it may be beneficial for GV-related disease prevention. Further research in a larger, more diverse sample with poor metabolic health is warranted.Clinical trial registration: ClinicalTrials.gov, NCT03546972.

Abstract P476: Changes in Olive Oil Consumption and Weight Changes in US Men and Women

Background: Olive oil intake is inversely associated with the risk of chronic diseases and mortality. However, it is unclear whether there is an association between olive oil intake and weight changes; because it is an energy-dense food concerns have been raised that high intake may contribute to weight gain. Therefore, we aimed to determine the associations between long-term changes in olive oil consumption and changes in weight. Methods: We examined data from 116,243 women and men from the Nurses’ Health Study (NHS, 1990-2010), NHSII (1991-2015), and Health Professional Follow-up Study (HPFS, 1990-2014), who were free from chronic diseases at baseline. We applied multivariable linear regression models with robust variance estimators to assess the association of changes in olive oil intake within each 4-year interval with concurrent weight changes. Results across the three cohorts were pooled using inverse-variance weights. Results: At baseline, mean ± SD age was 54.8 ± 6.6 years in the NHS, 45.3 ± 8.0 years in the NHS2, and 53.9 ± 7.2 years in the HPFS. Mean body mass index was 25 kg/m2 at baseline across the three cohorts. The mean weight gain over each 4-year follow-up cycle was highest in the NHS2 (1.8; 95%CI -6.8 to 11.3 kg), followed by the NHS (1.0; 95%CI -6.8 to 9.1 kg), and lastly the HPFS (0.6; 95%CI -5.4 to 6.8 kg). Pooling across the cohorts after adjustment for sociodemographic, lifestyle, and set of dietary factors (fruits, vegetables, red and processed meat, sugar sweetened beverages, coffee, refined grains), each ½ Tablespoon (7 grams) serving per day increment in olive oil was associated with a slightly lower 4-year weight gain of -0.06 kg (95%CI -0.08 to -0.04 kg; p&lt;0.0001). This inverse association was observed in the three cohorts, with a greater magnitude of association in the NHS2 (-0.08; 95%CI -0.10 to -0.05 kg; p&lt;0.0001), followed by the HPFS (-0.07; 95%CI -0.12 to -0.02 kg; p=0.003) and lastly the NHS (-0.05; 95%CI -0.07 to -0.01 kg; p=0.02). Results were attenuated after adjustment for the Alternative Healthy Eating index (pooled -0.03; 95%CI -0.05 to -0.02; p=0.0003). Conclusions: Long-term habitual increase in olive oil consumption was not associated with increased weight gain in middle-aged and older adults.

Circulating MicroRNA-19 and cardiovascular risk reduction in response to weight-loss diets

MicroRNA-19 (miR-19) plays a critical role in cardiac development and cardiovascular disease (CVD). We examined whether change in circulating miR-19 was associated with change in CVD risk during weight loss. This study included 509 participants with overweight or obesity from the 24-month weight-loss diet intervention study (the POUNDS Lost trial) and with available data on circulating miR-19a-3p and miR-19b-3p at baseline and 6 months. The primary outcome for this analysis was the change in atherosclerotic CVD (ASCVD) risk at 6 and 24 months, which estimates the 10-year probability of hard ASCVD events. Secondary outcomes were the changes in ASCVD risk score components. Circulating miR-19a-3p and miR-19b-3p levels significantly decreased during the initial 6-month dietary intervention period (P=0.008, 0.0004, respectively). We found that a greater decrease in miR-19a-3p or miR-19b-3p was related to a greater reduction in ASCVD risk (β[SE]=0.33 [0.13], P=0.01 for miR-19a-3p; β[SE]=0.3 [0.12], P=0.017 for miR-19b-3p) over 6 months, independent of concurrent weight loss. Moreover, we found significant interactions between change in miR-19 and sleep disturbance on change in ASCVD risk over 24 months of intervention (P interaction=0.01 and 0.008 for miR-19a-3p and miR-19b-3p, respectively). Participants with a greater decrease in miR-19 without sleep disturbance had a greater reduction of ASCVD risk than those with slight/moderate/great amounts of sleep disturbance. In addition, change in physical activity significantly modified the associations between change in miR-19 and change in ASCVD risk over 24 months (P interaction=0.006 and 0.004 for miR-19a-3p and miR-19b-3p, respectively). A greater decrease in miR-19 was significantly associated with a greater reduction in ASCVD risk among participants with an increase in physical activity, while non-significant inverse associations were observed among those without an increase in physical activity. In conclusion, decreased circulating miR-19 levels during dietary weight-loss interventions were related to a significant reduction in ASCVD risk, and these associations were more evident in people with no sleep disturbance or increase in physical activity. ClinicalTrials.gov NCT00072995.

Concurrent vestibular activation and postural training recalibrate somatosensory, vestibular and gaze stabilization processes.

Postural instability is a common symptom of vestibular dysfunction that impacts a person's day-to-day activities. Vestibular rehabilitation is effective in decreasing dizziness, visual symptoms and improving postural control through several mechanisms including sensory reweighting of the vestibular, visual and somatosensory systems. As part of the sensory reweighting mechanisms, vestibular activation exercises with headshaking influence vestibular-ocular reflex (VOR). However, combining challenging vestibular and postural tasks to facilitate more effective rehabilitation outcomes is under-utilized. Understanding how and why this may work is unknown. The aim of the study was to assess sensory reweighting of postural control processing and VOR after concurrent vestibular activation and weight shift training (WST) in healthy young adults. Forty-two participants (18-35years) were randomly assigned into four groups: No training/control (CTL), a novel visual feedback WST coupled with a concurrent, rhythmic active horizontal or vertical headshake activity (HHS and VHS), or the same WST with no headshake (NHS). Training was performed for five days. All groups performed baseline- and post-assessments using the video head impulse test, sensory organization test, force platform rotations and electro-oculography. Significantly decreased horizontal eye movement variability in the HHS group compared to the other groups suggests improved gaze stabilization (p = .024). Significantly decreased horizontal VOR gain (p = .040) and somatosensory downweighting (p = .050) were found in the combined headshake groups (HHS and VHS) compared to the other two groups (NHS and CTL). The training also showed a significantly faster automatic postural response (p = .003) with improved flexibility (p = .010) in the headshake groups. The concurrent training influences oculomotor function and suggests improved gaze stabilization through vestibular recalibration due to adaptation and possibly habituation. The novel protocol could be modified into progressive functional activities that would incorporate gaze stabilization exercises. The findings may have implications for future development of vestibular rehabilitation protocols.

Changes in Coffee Intake, Added Sugar and Long-Term Weight Gain - Results from Three Large Prospective US Cohort Studies

BackgroundConsumption of both caffeinated and decaffeinated coffee has been reported to attenuate long-term weight gain. Whether the association between coffee consumption and weight gain depends on the addition of sugar, cream, or coffee whitener remains unclear. ObjectiveWe aimed to study the associations between changes in coffee consumption, caffeine intake, and weight changes by considering the addition of sugar, cream, or a nondairy coffee whitener. MethodsWe used 3 large prospective cohorts – the Nurses’ Health Study (1986 – 2010), Nurses’ Health Study II (1991 – 2015) and Health Professional Follow-up Study (1991 – 2014). We applied multivariable linear regression models with robust variance estimators to assess the association of changes in coffee habits within each 4-y interval with concurrent weight changes. Results across the 3 cohorts were pooled using inverse-variance weights. ResultsAfter multivariable adjustment, each 1 cup per day increment in unsweetened caffeinated coffee was associated with a reduction in 4-y weight gain of -0.12 kg (95 % CI: -0.18, -0.05 kg) and of -0.12 kg (95 % CI: -0.16, -0.08 kg) for unsweetened decaffeinated coffee. The habits of adding cream or nondairy coffee whitener were not significantly linked to weight changes. Adding a teaspoon of sugar was associated with a 4-y weight gain of +0.09 kg (0.07, 0.12 kg). Stratified analyses suggested stronger magnitude of the observed associations with younger age and higher baseline BMI. Neither caffeine nor coffee modified the association of adding sugar to any food or beverage with weight changes. ConclusionsAn increase in intake of unsweetened caffeinated and decaffeinated coffee was inversely associated with weight gain. The addition of sugar to coffee counteracted coffee’s benefit for possible weight management. To the contrary, adding cream or coffee whitener was not associated with greater weight gain.

A study of Caseous lymphadenitis in goats from a smallholder farm in Ukraine

Caseous lymphadenitis (CLA) is a chronic infectious disease of a wide range of animal species around the world, which leads to abscesses in lymph nodes and internal organs. The aim of these studies was to characterize the Corynebacterium pseudotuberculosis isolate obtained from infected goat from a smallholder farm in Ukraine. Clinical observation revealed two goats with concurrent external abscesses, fever, anorexia, and weight loss. Blood samples from the suspect animals were tested by ELISA. According to the obtained results, four (18.2%) from 22 sera samples were positive and one sample was questionable. C. pseudotuberculosis was isolated from the lymph nodes, liver, and lungs whereas the spleen, kidney, uterus, and udder did not show any growth. Finally, the obtained isolate was characterized both by biochemical tests and using multiplex PCR based on the detection of 16s rRNA, rpoB, and pld genes of C. pseudotuberculosis. Disease control should include elimination of infected and suspected animals from the herd, carrying out a comprehensive disinfection, and providing constant monitoring of the entire herd. Due to the absence of available data concerning the prevalence of CLA in Ukraine, further surveillance is required and an effective disease control strategy and eradication measures need to be developed

Effects of Isotonic Core Exercise with Weight Loss on Low Back Pain, Core Strength and Balance in Obese Middle-Aged Women

PURPOSE: This study aimed to investigate the effects of concurrent core exercises and weight loss on lower back pain, core muscle strength, and balance in middle-aged obese women.METHODS: Eighteen middle-aged obese women were randomly assigned to the core exercise with weight loss (CE+WL, n=6), core exercise (CE, n=6), and control (CON, n=6) groups. Moreover, CE was conducted for 60 minutes, three times a week for 8 weeks, with a weight loss goal of approximately 0.5-1 kg per week. All participants underwent measurements of body composition (weight, body mass index, percentage body fat, muscle mass, waist-to-hip ratio (WHR), low back pain (visual analogue scale [VAS]), core muscle strength (hip flexor), and balance (sensory organization, reaction time, and motor control)) before the experiment, at 4 and 8 weeks.RESULTS: A significant decrease in WHR was observed at 4 and 8 weeks of exercise compared to that before exercise in both the CE+WL and CE groups (&lt;i&gt;p&lt;/i&gt;&lt;.05). Additionally, VAS scores significantly decreased at 4 and 8 weeks compared to those before exercise in the CE+WL group and a decrease was observed at 8 weeks in the CE group (&lt;i&gt;p&lt;/i&gt;&lt;.05). Hip flexor strength significantly increased at 8 weeks of exercise compared to that before exercise in the CE+WL group (&lt;i&gt;p&lt;/i&gt;&lt;.05). Furthermore, hip flexor strength also significantly increased at 4 and 8 weeks in the CE group (&lt;i&gt;p&lt;/i&gt;&lt;.05). Sensory organization significantly increased at C2 after 8 weeks of exercise compared with that before exercise in the CE+WL group (&lt;i&gt;p&lt;/i&gt;&lt;.05).CONCLUSION: The results of this study suggested that combining CE with WL concurrently leads to improvements in WHR, back pain, hip flexor strength, and sensory organization in middle-aged obese women.

Deep Neural Network-Based Approximate Optimal Tracking for Unknown Nonlinear Systems

The infinite horizon optimal tracking problem is solved for a deterministic, control-affine, unknown nonlinear dynamical system. A deep neural network (DNN) is updated in real-time to approximate the unknown nonlinear system dynamics. The developed framework uses a multi-timescale concurrent learning-based weight update policy, with which the output-layer DNN weights are updated in real-time, but the internal DNN features are updated discretely and at a slower timescale (i.e., with batch-like updates). The design of the output-layer weight update policy is motivated by a Lyapunov-based analysis, and the inner features are updated according to existing DNN optimization algorithms. Simulation results demonstrate the efficacy of the developed technique and compare its performance to existing techniques.

Overlapping and distinct relationships between hedonic hunger, uncontrolled eating, food craving, and the obesogenic home food environment during and after a 12-month behavioral weight loss program

Hedonic hunger, reward-driven eating outside of biological need, is a newer construct in eating behavior research. During behavioral weight loss (BWL), greater improvements in hedonic hunger are associated with higher weight loss, but it remains unclear if hedonic hunger predicts weight loss independent of more well-established, similar constructs (uncontrolled eating and food craving). Research also is needed to understand how hedonic hunger interacts with contextual factors (e.g., obesogenic food environment) during weight loss. Adults (N = 283) in a 12-month randomized controlled trial of BWL were weighed at 0, 12, and 24 months, and completed questionnaires assessing hedonic hunger, food craving, uncontrolled eating, and the home food environment. All variables improved at 12 and 24 months. Decreases in hedonic hunger at 12 months were associated with higher concurrent weight loss, but not when accounting for improvements in craving and uncontrolled eating. At 24 months, reduction in craving was a stronger predictor of weight loss than hedonic hunger, but improvement in hedonic hunger was a stronger predictor of weight loss than change in uncontrolled eating. Changes to the obesogenic home food environment failed to predict weight loss, regardless of levels of hedonic hunger. This study adds novel information on the individual and contextual factors associated with short- and long-term weight control, which can help refine conceptual models and treatment strategies.

Total energy expenditure as assessed by doubly labeled water and all-cause mortality in a cohort of postmenopausal women

BackgroundThe association of TEE with all-cause mortality is uncertain, as is the dependence of this association on age. ObjectivesTo examine the association between TEE and all-cause mortality, and its age interaction, in a Women’s Health Initiative (WHI) cohort of postmenopausal United States women (1992–present). MethodsA cohort of 1131 WHI participants having DLW TEE assessment of ∼10.0 y (median) following WHI enrollment with ∼13.7 y (median) of subsequent follow-up, was used to study the EE associations with all-cause mortality. To enhance the comparability of TEE and total EI, key analyses excluded participants having >5% weight change between WHI enrollment and DLW assessment. The influence of participant age on mortality associations was examined, as was the ability of concurrent and earlier weight and height measurements to explain the results. ResultsThere were 308 deaths following the TEE assessment through 2021. TEE was unrelated to overall mortality (P = 0.83) in this cohort of generally healthy, older (mean 71 y at TEE assessment) United States women. However, this potential association varied with age (P = 0.003). Higher TEE was associated with a higher mortality rate at the age of 60 y and a lower mortality rate at the age of 80 y. Within the weight-stable subset (532 participants, 129 deaths), TEE was weakly positively related to overall mortality (P = 0.08). This association also varied with age (P = 0.03), with mortality HRs (95% CIs) for a 20% increment in TEE of 2.33 (1.24, 4.36) at the age of 60 y, 1.49 (1.10, 2.02) at 70 y of age, and 0.96 (0.66, 1.38) at 80 y of age. This pattern remained, although was somewhat attenuated, following control for baseline weight and weight changes between WHI enrollment and TEE assessment. ConclusionsHigher EE is associated with higher all-cause mortality among younger postmenopausal women, only partially explained by weight and weight change.This study is registered with clinicaltrials.gov identifier: NCT00000611.

Abstract P619: DNA Methylation at SREBF1 and Long-Term Changes in Body Composition: The POUNDS Lost Trial

Introduction: A previous epigenome-wide association study has causally linked DNA methylation (DNAm) at the SREBF1 gene (cg11024682) with obesity and lipids. However, little is known about whether DNAm at SREBF1 is associated with long-term changes in body adiposity and composition. Hypothesis: We hypothesized that participants with different DNAm at SRBF1 might respond differently to dietary weight-loss interventions on changes in body adiposity and composition. Methods: The current study included 314 individuals with overweight or obese, who participated in POUNDS Lost: a 2-year randomized dietary weight-loss trial. The blood DNAm level was profiled by methylC-capture sequencing at baseline. Regional DNAm at SREBF1 was calculated as the average methylation level over CpGs within ±250 bp of cg11024682. Body composition, including total fat mass (FM), percentage of FM (FM%), total fat-free mass (FFM), percentage of FFM (FFM%), and percentage of trunk fat (TF%) were measured by dual-energy X-ray absorptiometry (DEXA) at baseline, 6 months, and 2 years. Results: Lower regional DNAm at SREBF1 was significantly associated with changes in body composition across 2 years ( Table ). At 6 months, per SD lower regional DNAm at SREBF1 was significantly associated with greater reductions in FM (β [SE] -0.23 [0.07], p=0.002), FM% (-0.30 [0.09], p&lt;0.001), and TF% (-0.44 [0.13], p&lt;0.001), and greater increases in FFM (0.18 [0.08], p=0.028) and FFM% (0.30 [0.09], p&lt;0.001), regardless of dietary intervention groups and independent of concurrent weight loss. Such association remained at 2 years: FM (β [SE] -0.21 [0.10], p=0.045), FM% (-0.32 [0.11], p=0.004), TF% (-0.36 [0.16], p=0.026), FFM (0.22 [0.12], p=0.07) and FFM% (0.32 [0.11], p=0.004). Conclusions: Overweight and obese individuals with a lower regional DNAm at SREBF1 achieved greater improvement in body composition across the 2-year intervention, independent of concurrent weight loss, suggesting DNAm at SREBF1 is predictive of individuals’ response to treatment.

Abstract 11963: Blood Level of Coffee-Eelated DNA Methylation and Long-Term Changes in Blood Pressure in Response to Weight-Loss Diet Interventions: The Pounds Lost Trial

Introduction: Coffee intake has been associated with a lower risk of hypertension. Recent epigenome-wide association studies linked DNA methylation (DNAm) at PHGDH (cg14476101) with coffee consumption and blood pressure, which may explain the mechanism underlying coffee intake and blood pressure. However, little is known about whether the coffee-related DNAm is associated with long-term changes in blood pressure in response to dietary weight-loss interventions. Hypothesis: We hypothesized that participants with varying coffee-related DNAm levels may respond differently to dietary weight-loss interventions on long-term changes in blood pressure. Methods: The current study included 669 participants with overweight/obesity, who were randomly assigned to 1 of 4 diets varying in macronutrient components. Blood DNAm levels were profiled by a high-resolution methylC-capture sequencing at baseline. The regional DNAm at PHGDH was defined as the average methylation level over CpGs within ±250 bp of cg14476101. Two-year changes in blood pressure were calculated. Linear regression models were used to examine the associations between DNAm at PHDGH and 2-year changes in blood pressure in response to dietary weight-loss interventions, adjusting for age, race, sex, body mass index, anti-hypertensive medications, and concurrent weight loss. Results: Regional DNAm at PHDGH was not associated with 2-year changes in blood pressure in the total population. We found significant interactions between regional DNAm at PHDGH and dietary protein intake on 2-year changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP) (p-interaction=0.018 and 0.005, respectively). Among participants assigned to an average-protein diet (15% of energy intake), higher baseline regional DNAm at PHDGH was associated with greater reductions in SBP (beta [SE]: -9.7 [3.4], p=0.005) and DBP (beta [SE]: -6.5 [2.4], p=0.007); while no association was observed among those assigned to a high-protein diet (25% of energy intake; p=0.40 for SBP, p=0.15 for BP). Conclusion: Our data indicate that participants with a higher regional DNAm level at PHDGH benefited more in long-term improvement in blood pressure when consuming an average-protein weight-loss diet.

S1345 Weight Loss Outcomes With and Without Diabetes in Patients With NAFLD in a Specialty Fatty Liver Disease Program

Introduction: Nonalcoholic fatty liver disease (NAFLD) is strongly linked to insulin resistance. As a result, type 2 diabetes mellitus (T2DM) is commonly comorbid in NAFLD and can increase morbidity and reduce weight loss treatment efficacy. We studied weight loss in adult NAFLD patients without and with T2DM (NAFLD-DM) receiving care in the Yale Fatty Liver Disease Program (YFLDP), which focuses on the integration of medical weight management treatments and hepatology care. Methods: We analyzed retrospective data for adult patients with diagnostic codes for NAFLD and T2DM with complete data on body weight and at least one clinic visit between 5/23/2018 and 5/02/2022. Patients were categorized as NAFLD or NAFLD-DM. Total body weight loss (WL) was quantified using 0%, 5%, and 10% thresholds. Between NAFLD and NAFLD-DM groups, we compared total body weight loss (WL) and across WL threshold groups, we also compared initial weights, follow-up time, medical interventions received, and results of non-invasive liver fibrosis tests. Results: There were 933 patients with NAFLD, of whom 463 (49.6%) had NAFLD-DM. After a median follow-up of 7.7 months, 632 (67.7%) of all patients achieved any weight loss. Significantly more patients with NAFLD-DM lost weight compared to NAFLD alone (73.9 vs 61.7%, p< 0.0001). Weight loss between NAFLD and NAFLD-DM groups varied, respectively: 0-5% WL: 34.7% vs. 34.8% (p=0.98); 5-10% WL: 13.2% vs. 19.2% (p=0.01), >10% WL: 13.8% vs. 19.9% (p=0.01). Compared to those not losing weight, NAFLD and NAFLD-DM patients with >10% WL had significantly greater proportion of participation in a complete meal replacement program (Optifast®) or treatment with GLP-1 agonist semaglutide. For NAFLD and NAFLD-DM groups, there was no significant difference between initial Fibroscan stiffness or FIB-4 index and subsequent WL percentages (Table). Conclusion: The majority of NAFLD and NAFLD-DM patients receiving care in a specialty clinic incorporating medical weight management with liver care successfully achieved weight loss in a relatively short period. Patients with NAFLD-DM did not have significantly worse outcomes with weight loss, and NAFLD-T2DM patients lost more weight than NAFLD patients. These findings suggest that an integrative care liver clinic with concurrent weight management care can help patients improve metabolic diseases associated with NAFLD, particularly T2DM, and in turn improve liver-related outcomes.Figure 1.: Comparison of Clinic Interventions between No Weight Loss (WL) versus >10% WL patients with NAFLD (top panel, a) and NAFLD-DM (bottom panel, b). *Statistically significant p-values using chi-square analysis, which can be found in Table Table 1. - Characteristics of and Clinical Interventions for NAFLD and NAFLD-DM Patients in the Yale Fatty Liver Disease Program (YFLDP). There was a significantly lower proportion of patients with NAFLD compared to NAFLD-DM who were able to achieve > 10% Weight Loss (13.8 vs. 19.9, p=0.014), and significantly more NAFLD patients compared to NAFLD-DM who did not achieve any weight loss (38.3 vs. 26.1, p<0.001) NAFLD (n=470 patients) NAFLD-DM (n=463 patients) Patient Categories n (%) No WL180 (38.3) >10% WL65 (13.8) p No WL121 (26.1) >10% WL92 (19.9) p Clinic Interventions n (%) Nutrition Consultation 80 (44.4) 31 (47.7) 0.652 58 (47.9) 40 (43.5) 0.518 OPTIFAST® Program 4 (2.2) 5 (7.7) 0.045 2 (1.7) 8 (8.7) 0.016 Naltrexone/Buproprion 6 (3.3) 5 (7.7) 0.146 16 (13.2) 6 (6.5) 0.111 Semaglutide 15 (8.3) 17 (26.2) < 0.001 30 (24.8) 37 (40.2) 0.016 Liraglutide 11 (6.1) 7 (10.8) 0.217 21 (17.4) 7 (7.6) 0.037 Phentermine 9 (5.0) 10 (15.4) 0.007 15 (12.4) 17 (18.5) 0.219 Bariatric Surgery Referral 13 (7.2) 5 (7.7) 0.901 21 (17.4) 31 (33.7) 0.006 Health Outcomes mean (SD) Follow-Up Time, days 256 (276.5) 422 (296.8) < 0.001 271 (280.2) 403 (297.3) 0.001 Initial FibroScan® Stiffness, kPa 8.63 (6.72) 13.18 (14.01) 0.663 13.18 (14.01) 12.48 (12.49) 0.701 Initial FIB-4 Score 1.32 (1.13) 1.70 (1.98) 0.068 1.70 (1.98) 1.83 (2.11) 0.648 Initial Weight, kg 93.82 (25.45) 102.20 (24.90) 0.015 102.20 (24.90) 109.61 (25.07) 0.056 *Denotes statistical significance p<0.05. WL = Weight Loss.

Time-Restricted Eating in Metabolic Syndrome-Focus on Blood Pressure Outcomes.

Purpose of the ReviewTime-restricted eating (TRE) is a promising dietary intervention for weight loss and improvement of cardiometabolic risk factors. We aim to provide a critical review of blood pressure outcomes reported in clinical TRE studies in adults with metabolic syndrome, in the context of the proposed mechanisms that underlie the relationship between timing of eating and blood pressure.Recent FindingsClinical TRE studies report mixed results pertaining to blood pressure outcomes, likely due to significant heterogeneity in study design and TRE protocols. Mechanistically, TRE’s metabolic benefits have been speculated to be mediated by alignment of meal timing with circadian regulation of metabolic processes and/or enhancement of catabolism as a result of prolonging the fasting period. TRE protocols that start and end earlier appear to have more pronounced blood pressure lowering effects. Blood pressure also tends to be lower with narrower eating windows. Concurrent weight loss is not consistently linked to blood pressure reduction, while lower insulin levels may be an important factor for blood pressure reduction. Notably, no published studies have reported 24-h blood pressure profiles or data on blood pressure variability.SummaryBlood pressure has only been examined in limited TRE studies, measured at a single time point. Given the clinical relevance of blood pressure’s diurnal variability and the mechanistic evidence underlying timing of eating and blood pressure effects, more studies are needed to investigate TRE’s effects on the diurnal variability of blood pressure.

553-P: Changes in Circulating Bile Acids and the Improvements in Glucose and Insulin Metabolism in Response to Weight-Loss Diets: The POUNDS Lost Trial

Bile acids (BAs) are synthesized from cholesterol in the liver and are essential for nutrient absorption. The host-derived primary BAs are transformed into secondary BAs in the intestine. Various BA subtypes may play pivotal roles as endocrine molecules to affect glucose and insulin metabolism. We tested whether changes in distinct BA subtypes were associated with improved glucose and insulin metabolism among adults with overweight and obesity who participated in a weight-loss diet intervention trial. Circulating primary and secondary unconjugated BAs and their taurine-/glycine-conjugates were measured at baseline and 6 months after the intervention; 6-month changes in BAs were calculated (n=515) . When we analyzed associations of BA changes with changes in fasting glucose, insulin, and insulin resistance at 6 months, more decreases in several primary BAs (CDCA, taurocholate [TCA], and taurochenodeoxycholate [TCDCA]) and secondary TDCA were associated with larger reductions of glucose (PFDR &amp;lt;0.for all) , although the associations were dependent on concurrent weight changes. The decreases in primary BAs (including CA, CDCA, TCA, TCDCA) and secondary BAs (including DCA, GDCA, TDCA, GUDCA) were significantly related to improved hyperinsulinemia and insulin resistance, independent of weight changes. Also, we found significant interactions between dietary fat intake and changes in lithocholate and glycolithocholate for changes in insulin metabolism. Further, the initial changes in several primary and secondary BAs showed significant associations for 2-year improvements in glucose/insulin metabolism. In conclusion, decreases in distinct primary and secondary BAs during weight-loss dietary interventions were associated with improved glucose and insulin metabolism. Changes in various BA subtypes were related to the improved insulin metabolism independent of weight loss status during the interventions. Disclosure Y.Heianza: None. X.Wang: None. H.Ma: None. J.Rood: None. C.B.Clish: None. G.Bray: None. F.Sacks: None. L.Qi: None. Funding National Institutes of Health (DK091718, DK100383, DK115679)

The Glucocorticoid Receptor-Dependent Stress Response in Human Erythropoiesis Is BCL11A-Dependent

Extrapolations from data in mouse models and from human erythroid cells expanded ex vivo with the glucocorticoid receptor (GR) agonist Dexamethasone (Dex), suggest that GR plays an important role in the regulation of stress erythropoiesis 1. However, the mechanistic details of stress erythropoiesis are still poorly understood.By exploring the effects of Dex on erythroid expansion of CD34+ cells from a large number of healthy adult donors (n=25), we documented that Dex expands a population of immature erythroid cells which express high levels of BCL11A. In addition, in these cells BCL11A is mostly in the nuclei, compared to cells grown without Dex. These results suggest that GR regulates the transcriptional activity of BCL11A.To validate the role of BCL11A in the Dex response, we made observations in cells from patients with BCL11A deficiencies 2. We found that BCL11A-deficient CD34+ cells generate lower numbers of maturing erythroid cells compared to controls with Dex addition, suggesting that they respond poorly to Dex (Fig 1). Of note, RNAseq analyses indicate that erythroid cells expanded from the patients express levels of BCL11A lower than that of their parent cells while the levels of expression of other genes known to mediate the response to Dex of erythroid cells (ZFP36L2, CDKNIC and PPARA 3-5) expressed by these cells is normal.Further we extended our observations to Cushing's patients with highier cortisol levels, before(V1) and after their treatment(V2) using concurrent age and weight matched healthy controls (MC). There is no significant difference in frequency of CD34+ cells among V1, V2 and MC (range 0.3-2% in all cases). CD34 pos cells from all groups express similar levels of cKIT, IL-3Rβ, CXCR4 and CALR. However, a greater proportion of CD34+ cells from V1 express CD36 and CD110 (the thrombospondin and thrombopoietin receptor) and CD133 (the hematopoietic stem cell marker prominin) than those from V2 and MC (60-80% vs 10-20%), suggesting that the circulating progenitor cells from active Cushing's patients are a unique population likely generated in response to their high cortisol levels given that the phenotype of CD34+ cells from the blood of V2 patients is similar to that found in MC. The phenotype of CD34+ cells from Cushing's patients in vivo is similar to that of CD34+ cells generated in vitro after 2-4 days of culture with Dex 3,6,7. V1 progenitor cells generate similarly large number of immature erythroid cells in culture with and without Dex. By contrast with normal cells, these active cells also express lower levels of the cytoplasm-restricted form of GRα (GRS203) and greater levels of GILZ and BCL11A than normal or V2 cells.In conclusion, the data presented here indicate that GR activation switches the erythroid differentiation program from the steady-state to the stress mode and that activation of BCL11A is part of the response of erythroid cells to Dex.References1) Varricchio et al Am J Blood Res. 2014;4:53; 2) Funnell et al Blood 2015; 126:89; 3) Ashley et al JCI 2020;130:2097; 4) Zhang L et al Nature 2013;499:92; 5) Lee et al Nature 2015;522:474; 6) Heideveld et al Haematologica 2015; 100:1396; 7) Xiang et al Blood 2015;125:1803. [Display omitted] DisclosuresMigliaccio: Dompe farmaceutici Spa R&D: Other: received funding for reserach .

Body mass index mediates the effect of the DASH diet on hypertension: Common metabolites underlying the association.

The Dietary Approaches to Stop Hypertension (DASH) diet is beneficial in reducing blood pressure; however, this may be a consequence of concurrent weight reduction. In the present study, we investigated whether body mass index (BMI) mediates the association between the DASH diet and hypertension and investigate common metabolic pathways. We included 2424 females from the cross-sectional TwinsUK cohort, with blood pressure, BMI and dietary intake measured within 1.01 (SD = 0.68) years and serum metabolomics profiling (591 metabolites). We constructed a mediation model to test the mediation effects of BMI on the total effect of the DASH diet on hypertension. To identify a metabolite panel associated with the DASH diet and BMI, we built random forest models for each trait, and selected the common metabolic contributors using five-fold cross-validation error. We found that BMI fully mediates the association between the DASH diet and hypertension, explaining 39.1% of the variance in hypertension. We then identified a panel of six common metabolites predicting both the DASH diet and BMI with opposing effects. Interestingly, at the univariate level, the metabolites were also associated with hypertension in the same direction as BMI. The strongest feature, 1-nonadecanoyl-GPC (19:0), was positively associated with the DASH diet (β [SE] = 0.65 [0.12]) and negatively with BMI (β [SE] = -1.34 [0.12]) and hypertension (odds ratio = 0.71, 95% confidence interval=0.6-0.84). We highlight the role of BMI in the mechanisms by which the DASH diet influences hypertension and also highlight common metabolic pathways. Further studies should investigate the underlying molecular mechanisms to increase our understanding of the beneficial ways of treating hypertension.

Changes in the Global Diet Quality Score, Weight, and Waist Circumference in Mexican Women

BackgroundEvidence on concurrent changes in overall diet quality and weight and waist circumference in women of reproductive age from low- and middle-income countries is limited. ObjectiveWe examined the associations of changes in the Global Diet Quality Score (GDQS) and each GDQS food group with concurrent weight and waist circumference change in Mexican women. MethodsWe followed prospectively 8967 nonpregnant nonlactating women aged 25–49 y in the Mexican Teachers’ Cohort between 2006 and 2008. We assessed diet using an FFQ of the previous year and anthropometric measures were self-reported. Regression models were used to examine 2-y changes in the GDQS and each food group (servings/d) with weight and waist circumference changes within the same period, adjusting for demographic and lifestyle factors. ResultsCompared with those with little change in the GDQS (−2 to 2 points), women with the largest increase in the GDQS (>5 points) had less weight (β: −0.81 kg/2 y; 95% CI: −1.11, −0.51 kg/2 y) and waist circumference gain (β: −1.05 cm/2 y; 95% CI: −1.62, −0.48 cm/2 y); likewise, women with the largest decrease in the GDQS (<−5 points) had more weight (β: 0.36 kg/2 y; 95% CI: 0.06, 0.66 kg/2 y) and waist circumference gain (β: 0.71 cm/2 y; 95% CI: 0.09, 1.32 cm/2 y). Increased intake of dark green leafy vegetables, cruciferous vegetables, deep orange vegetables, citrus fruits, and fish and shellfish was associated with less weight gain. In addition, deep orange vegetables, low fat and high fat dairy, whole grains, and fish were associated with less waist circumference gain within the 2-y period. ConclusionsImprovements in diet quality over a 2-y period reflected by an increase in the GDQS and changes in consumption of specific components of the GDQS were associated with less weight and waist circumference gain in Mexican women.

Higher Global Diet Quality Score Is Associated with Less 4-Year Weight Gain in US Women

BackgroundWe have developed a simple and globally applicable tool, the Global Diet Quality Score (GDQS), to measure diet quality. ObjectiveTo test the utility of the GDQS, we examined the associations of the GDQS with weight change and risk of obesity in US women. MethodsHealth, lifestyle, and diet information were collected from women (n = 68,336) in the Nurses’ Health Study II (aged 27–44 y in 1991) through repeated questionnaires (1991–2015). The GDQS has 25 food groups (maximum = 49 points) and scoring higher points reflects a healthier diet. The association between GDQS change in 4-y intervals and concurrent weight change was computed with linear models adjusted for confounders. ResultsMean ± SD weight gain across 4-y periods was 1.68 ± 6.26 kg. A >5-point improvement in GDQS was associated with −1.13 kg (95% CI: −1.19, −0.77 kg) weight gain compared with a score change of <±2 points. For each 5-point increase, weight gain was 0.83 kg less for age <50 y compared with 0.71 kg less for age ≥50 y (P-interaction < 0.05). A >5-point score decrease was associated with 1.13 kg (95% CI: 1.04, 1.22 kg) more weight gain in women aged <50 y and 0.81 kg more (95% CI: 0.63, 0.98 kg) in women aged ≥50 y. Compared with little change in score, obesity RR was 0.77 (95% CI: 0.74, 0.81) for a >5-point increase and 1.32 (95% CI: 1.26, 1.37) for a >5-point decrease. Risk of obesity did not differ by age. Compared with other diet quality scores, the Alternate Healthy Eating Index-2010 had somewhat stronger associations than the GDQS (P < 0.05) but the GDQS had stronger associations than the Minimum Dietary Diversity for Women score (P < 0.05). ConclusionsImprovement of diet quality as measured by the GDQS was associated with less weight gain and risk of obesity in US women. The association was stronger for women aged <50 y. Associations similar in direction and magnitude were observed between the GDQS and obesity across age groups.