Adjustment For Weight Change Research Articles

Glycated haemoglobin is a major predictor of disease severity in patients with NAFLD

ObjectivesCurrently, non-invasive scoring systems to stage the severity of non-alcoholic fatty liver disease (NAFLD) do not consider markers of glucose control (glycated haemoglobin, HbA1c); this study aimed to define the relationship between HbA1c and NAFLD severity in patients with and without type 2 diabetes. Research design and methodsData were obtained from 857 patients with liver biopsy staged NAFLD. Generalized-linear models and binomial regression analysis were used to define the relationships between histological NAFLD severity, age, HbA1c, and BMI. Paired biopsies from interventional studies (n = 421) were used to assess the impact of change in weight, HbA1c and active vs. placebo treatment on improvements in steatosis, non-alcoholic steatohepatitis (NASH), and fibrosis. ResultsIn the discovery cohort (n = 687), risk of severe steatosis, NASH and advanced fibrosis correlated positively with HbA1c, after adjustment for obesity and age. These data were endorsed in a separate validation cohort (n = 170). Predictive modelling using HbA1c and age was non-inferior to the established non-invasive biomarker, Fib-4, and allowed the generation of HbA1c, age, and BMI adjusted risk charts to predict NAFLD severity. Following intervention, reduction in HbA1c was associated with improvements in steatosis and NASH after adjustment for weight change and treatment, whilst fibrosis change was only associated with weight change and treatment. ConclusionsHbA1c is highly informative in predicting NAFLD severity and contributes more than BMI. Assessments of HbA1c must be a fundamental part of the holistic assessment of patients with NAFLD and, alongside age, can be used to identify patients with highest risk of advanced disease.

Effect of weight change on the association between overall and source of carbohydrate intake and risk of metabolic syndrome: Tehran lipid and glucose study

BackgroundIn this prospective cohort study, we aimed to evaluate the association between dietary carbohydrates, whole grains, refined grains, and simple sugar with the risk of metabolic syndrome (MetS) and assess the effect of weight change on these associations.MethodsThis study was conducted within the framework of the Tehran Lipid and Glucose Study (TLGS). We included 1915 healthy participants with complete demographic, anthropometric and dietary measurements, among whom 591 developed MetS during 8.9 years of follow-up. Intake of dietary carbohydrates, whole grains, refined grains, and simple sugar was assessed with a validated semi-quantitative food frequency questionnaire. Multivariable adjusted Cox regression was used to estimate hazard ratios (HRs) for MetS events across tertiles of dietary variables. Using joint classification, the effect of weight change on the association between dietary variables and risk of MetS was assessed by Cox regression.ResultsCarbohydrate intake was not associated with the risk of MetS in multivariable-adjusted models. Whole grains intake was inversely associated with the risk of MetS (HR: 0.78, CI: 0.63–0.98), while this association disappeared after adjustment for weight change. The risk of MetS increased by 11% (1.11, 1.09–1.14) for each 3% energy increment from simple sugar, and by 5% (1.05, 1.03–1.08) for each 1 serving/day increment in refined grains. Consumption of refined grains increased the risk of MetS; an effect modification of this association was found by weight change. Among subjects with weight loss, intake of refined grains < median intake decreased the risk of MetS (0.59, 0.41–0.87). However, consumption of refined grains ≥ median intake increased the risk of MetS in individuals with weight gain (1.47, 1.08–2.01). Simple sugar was positively associated with an increased risk of MetS, after adjustment for weight change (3.00, 2.37–3.82). In joint classification, intake of simple sugar greater than median intake increased the risk of MetS, independent of weight change.ConclusionOur findings suggest an effect modification by weight change on the association between carbohydrates, and refined grains intake and the risk of MetS. Weight loss along with lower consumption of carbohydrates, and refined grains reduced the risk of MetS. However, simple sugar intake, regardless of weight change, was associated with an increased risk of MetS.

Abstract P4-03-14: Proinflammatory Dietary Patterns and Risk of Total and Subtypes of Breast Cancer Among US Women

Abstract Background: Dietary patterns promoting chronic inflammation, including the empirical dietary inflammatory pattern (EDIP), have been shown to strongly influence risk of weight gain, type 2 diabetes, cardiovascular disease, and colorectal cancer. However, it is unclear if this dietary pattern is associated with other tumors in which the mechanisms are not totally understood such as breast cancer. Methods: We prospectively followed 76,295 women from the Nurses’ Health Study (NHS, 1984-2016) and 91,078 women from the Nurses’ Health Study II (NHSII, 1991-2017). Diet was assessed by food frequency questionnaires (FFQs) every 4 years. The inflammatory potential of diet was evaluated using the previously established EDIP based on plasma C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha receptor 2 (TNF-αR2). Higher scores indicate higher inflammatory potential of the diet. Results: During 4,153,676 person-years of follow-up, we documented 10,632 invasive breast cancer cases (6,807 NHS; 3,825 NHSII). In the pooled multivariable-adjusted analyses, women in the highest, compared with the lowest, EDIP quintile were at higher breast cancer risk (HRQ5vsQ1=1.12; 95% CI 1.05, 1.20; P-trend&amp;lt; 0.001). This association was attenuated after adjusting for weight change since age 18 y, although it remained significant (HRQ5vsQ1=1.07; 95% CI 1.00, 1.14; P-trend=0.01). In subtype analyses, we found evidence that the inflammatory potential of diet influenced breast cancer risk differentially by ER status (P-heterogeneity=0.038) and by molecular phenotype (P-heterogeneity=0.007), with the association between EDIP and breast cancer limited to ER-negative tumors (HRQ5vsQ1=1.31; 95% CI: 1.11, 1.55; P-trend=0.002; for ER-positive tumors, HR Q5vsQ1=1.03; 95% CI, 0.96, 1.12;P-trend=0.10) and basal-like tumors (HRQ5vsQ1=1.78; 95% CI: 1.19, 2.65; P-trend=0.004). Further adjustment for weight change since age 18 y did not materially alter the association for these subtypes. Conclusions: Dietary patterns with high potential to contribute to chronic systemic inflammation, based on higher EDIP scores, were associated with a modestly increased risk of breast cancer, which was more pronounced for ER-negative and basal-like breast tumors. Citation Format: Andrea Romanos-Nanclares, Walter C Willett, Bernard A Rosner, Daniel G Stover, Sarah Asad, Sagar Sardesai, Michelle D Holmes, Wendy Y Chen, Rulla M. Tamimi, Fred K Tabung, A Heather Eliassen. Proinflammatory Dietary Patterns and Risk of Total and Subtypes of Breast Cancer Among US Women [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-03-14.

Effect of Chemotherapy on the Gut Microbiome of Breast Cancer Patients During the First Year of Treatment.

There is accumulating information of the effects of chemotherapy and weight changes on the gut microbiome of breast cancer patients. In this 1-year follow-up study, we investigated gut microbiome of 33 breast cancer patients who donated fecal samples at baseline and after completion of treatment. We compared alpha diversity and mean taxa abundance at baseline and absolute taxa abundance changes (final-baseline) by treatment (16 neoadjuvant [neoADJ], 13 adjuvant [ADJ], 4 no chemotherapy [noC]) and specific chemotherapy agent using Wilcoxon rank sum and negative binomial mixed model (NBMM) analysis. All four gut alpha diversity measures changed in association with chemotherapy treatment; they increased in the neoADJ (+16.4% OTU p = 0.03; +51.6% Chao1 p = 0.03; +7.0% Shannon index p = 0.02; +11.0% PD whole tree p = 0.09) but not in the ADJ and noC group (ADJ+noC). The difference in Chao1 index change between groups was statistically significant (pneoADJ vs. ADJ+noC=0.04). Wilcoxon p values of 0.03-0.003 were observed for five taxa. In NBMM analysis, changes in taxa abundance differed (Bonferroni-adjusted p ≤ 0.0007) for two Bacteroidetes taxa (g_Alistipes, f_S24-7) and two Firmicutes taxa (g_Catenibacterium, g_Eubacterium). NBMM analysis results remained unchanged with adjustment for weight changes. Alpha diversity changes were also found by receipt of chemotherapy agents. Consistent increases in alpha diversity were observed among those treated with TCHP (OTU p = 0.009; Chao1 p = 0.02; Shannon p = 0.02; PD whole tree p = 0.05) but not AC, Taxol or Herceptin. Those treated with TCHP or Herceptin showed increases in Verrucomicrobia (g_Akkermansia) but decreases of Bacteroidetes(g_Alistipes); the differences in changes in taxa abundance were statistically significant. Results from this pilot longitudinal study support an effect of chemotherapy, particularly neoADJ on the gut microbiome of breast cancer patients even after adjustment for weight changes. Further investigations are needed to confirm these findings in larger studies and with longer follow-up and to assess the impact of these microbiome changes on patient outcome.

Effect of dietary approaches to stop hypertension (DASH) diet, high in animal or plant protein on cardiometabolic risk factors in obese metabolic syndrome patients: A randomized clinical trial

AimsThis study aimed to investigate the effect of replacing plant proteins with animal proteins in the dietary approaches to stop hypertension (DASH) diet on cardiometabolic risk factors in obese metabolic syndrome participants. MethodsIn this double-blind randomized controlled clinical trial, 90 obese patients with metabolic syndrome, aged 30–70 years were randomly allocated into the DASH diet based on plant or animal proteins for 8 weeks. Fasting blood samples were collected to assess the biochemical markers. Also, blood pressure, weight, and waist circumference (WC) were measured at the beginning and end of the trial. ResultsThe participants in both groups experienced significant reductions in the fasting plasma glucose (FPG), systolic blood pressure (SBP) and diastolic blood pressure (DBP), triglyceride (TG) concentrations, weight and WC. However the reduction in FPG and SBP was higher in the plant-based DASH group, compared to the animal-based DASH group, after adjustment for weight change. No significant changes were found within or between groups with regard to total cholesterol, LDL-C, HDL-C. ConclusionsSubstituting plant proteins with animal proteins in the DASH diet improves FPG and SBP in obese individuals with metabolic syndrome, independent of weight change. IRCT registration number: IRCT20090203001640N16.

Abacavir Dosing in Neonates from Birth to 3 Months of Life

Background: No evidence-based dosing guidance is available for abacavir (ABC) liquid formulation use from birth. Newly available ABC pharmacokinetic (PK) data from neonates and immature infants were used to determine the optimal ABC dosing strategy (mg/kg) for infants 0-3 months and propose dosing per World Health Organization (WHO) weight-bands for neonates. Methods: Abacavir PK and safety data were pooled from three studies: (1) PACTG 321 (2) the Tygerberg Cohort and (3) IMPAACT P1106. Studies 1 and 2 were performed in neonates exposed to HIV receiving a single dose of ABC. Study 3 included predominantly low birth weight (LBW; <2500g) infants on antiretroviral therapy enrolled <3 months of life. We developed a population PK model and performed simulations to achieve ABC exposures (AUC 0-12 ) within the range 3·2-25·2 mcg.hr/mL reported in children. Findings: Forty-five infants contributed 308 ABC concentrations; 21 neonates were <15 days of life. At first PK assessment, median post-natal age was 1·0, 9·5 and 73 days, and median weight was 3·1, 3·3 and 3·8 kg for each study, respectively. ABC clearance was ~5-fold lower than adults at birth but rapid increased in early life. Therapeutic targets were achieved with exact ABC doses of 2·0 mg/kg BID from 0-4 weeks and 4·0 mg/kg BID from 4-12 weeks. A fixed weight-band dosing strategy of 8 mg (2-3 kg), 10 mg (3-4 kg) and 12 mg (4-5 kg) ABC BID achieved target exposures throughout the first 4 weeks of life without dose adjustment for weight changes were necessary. No Grade 3 or more adverse event was ABC related. Interpretation: We propose the first evidence-based ABC dosing strategy from birth using both exact and weight-band dosing for the liquid formulation. Integration of these new ABC dosing recommendations into National and International guidelines will provide an additional antiretroviral option from birth that is easily implementable. Trial Registration: Clinical trial.gov Identifier: NCT02383849 (P1106), NC0864 (PACTG 321) Funding: For PACTG321 and IMPAACT P1106, overall support for the International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT) was provided by the National Institute of Allergy and Infectious Diseases (NIAID) with co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Institute of Mental Health (NIMH), all components of the National Institutes of Health (NIH), under Award Numbers UM1AI068632 (IMPAACT LOC), UM1AI068616 (IMPAACT SDMC) and UM1AI106716 (IMPAACT LC), and by NICHD contract number HHSN275201800001I. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The Tygerberg Cohort study was supported by the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) - Growing the Leaders of Tomorrow Fellowship Programme. Declaration of Interest: AB, EVC, AV, MFC, RM, HR and MM received funding from the IMPAACT Network. MM received funding from Gilead Sciences, Merck & Co, and ViiV Healthcare. HR received funding from Abbvie. INCOMPLETE Ethical Approval: All studies were approved by the institutional review board responsible for study oversight. Written informed consent was obtained from all infants’ mothers/legal caregivers prior to entry.

Sexual Dimorphism in Body Weight Loss, Improvements in Cardiometabolic Risk Factors and Maintenance of Beneficial Effects 6 Months after a Low-Calorie Diet: Results from the Randomized Controlled DiOGenes Trial.

A low-calorie diet (LCD) is an effective strategy to lose weight and improve cardiometabolic risk factors, however, sexual dimorphism may be present. This study aims to investigate sexual dimorphism in cardiometabolic risk factors following weight loss and after weight maintenance. 782 overweight/obese participants (65% women) of the DiOGenes trial followed an 8-week LCD (~800 kcal/day), with a 6-months follow-up weight maintenance period on ad libitum diets varying in protein content and glycemic index. Men lost more body weight during the LCD period (−12.8 ± 3.9 vs. −10.1 ± 2.8 kg, respectively, p < 0.001), but regained more weight during the follow-up period than women (1.5 ± 5.4 vs. −0.5 ± 5.5 kg, respectively, p < 0.001). Even though beneficial LCD-induced changes in cardiometabolic risk factors were found for both sexes, improvements in HOMA-IR, muscle and hepatic insulin sensitivity, triacylglycerol, HDL−, LDL− and total cholesterol, diastolic blood pressure, cholesterol esters, sphingomyelins and adiponectin were more pronounced in men than women (std. ß range: 0.073–0.144, all q < 0.05), after adjustment for weight change. During follow-up, women demonstrated a lower rebound in HDL-cholesterol, triacylglycerol and diacylglycerol (std. ß range: 0.114–0.164, all q < 0.05), independent of changes in body weight. Overall, we demonstrated sexual dimorphism in LCD-induced changes in body weight and cardiometabolic risk profile, which may be attributed to differences in body fat distribution and metabolic status.

Fasting Glucose State Determines Metabolic Response to Supplementation with Insoluble Cereal Fibre: A Secondary Analysis of the Optimal Fibre Trial (OptiFiT).

Background: High intake of cereal fibre is associated with reduced risk for type 2 diabetes and long-term complications. Within the first long-term randomized controlled trial specifically targeting cereal fibre, the Optimal Fibre Trial (OptiFiT), intake of insoluble oat fibre was shown to significantly reduce glycaemia. Previous studies suggested that this effect might be limited to subjects with impaired fasting glucose (IFG). Aim: We stratified the OptiFiT cohort for normal and impaired fasting glucose (NFG, IFG) and conducted a secondary analysis comparing the effects of fibre supplementation between these subgroups. Methods: 180 Caucasian participants with impaired glucose tolerance (IGT) were randomized to twice-a-day fibre or placebo supplementation for 2 years (n = 89 and 91, respectively), while assuring double-blinded intervention. Fasting blood sampling, oral glucose tolerance test and full anthropometry were assessed annually. At baseline, out of 136 subjects completing the first year of intervention, 72 (54%) showed IFG and IGT, while 64 subjects had IGT only (labelled “NFG”). Based on these two groups, we performed a stratified per-protocol analysis of glycometabolic and secondary effects during the first year of intervention. Results: The NFG group did not show significant differences between fibre and placebo group concerning anthropometric, glycometabolic, or other biochemical parameters. Within the IFG stratum, 2-h glucose, HbA1c, and gamma-glutamyl transferase levels decreased more in the fibre group, with a significant supplement x IFG interaction effect for HbA1c. Compared to NFG subjects, IFG subjects had larger benefits from fibre supplementation with respect to fasting glucose levels. Results were robust against adjustment for weight change and sex. An ITT analysis did not reveal any differences from the per-protocol analysis. Conclusions: Although stratification resulted in relatively small subgroups, we were able to pinpoint our previous findings from the entire cohort to the IFG subgroup. Cereal fibre can beneficially affect glycemic metabolism, with most pronounced or even isolated effectiveness in subjects with impaired fasting glucose.

1571-P: Dietary Quality, Weight Loss, and Diabetes Incidence in the Diabetes Prevention Program (DPP)

We evaluated whether dietary quality is a predictor of reduced diabetes risk and/or weight loss, independent of caloric intake in the diverse DPP cohort, a randomized clinical trial of adults at risk for diabetes. This secondary analysis included the 2920 participants (90.3% of randomized) with complete baseline and 1-year data (967 intensive lifestyle (ILS), 979 metformin, 974 placebo). Dietary intake was assessed using a 117-item food frequency questionnaire. Dietary quality was quantified using the Alternative Healthy Eating Index 2010 (AHEI), which ranges from 0 to 110 with higher scores corresponding to healthier diets. Participants were 50.8 ±10.6 years, 67.5% female, 44.7% minority race/ethnicity and baseline AHEI was 44.2 ±10.4. ILS participants had greater improvement (p&amp;lt;0.001) in AHEI over 1-year (4.2 ±9.0) compared to metformin (1.2 ±8.5) and placebo (1.4 ±8.4). We examined the association between AHEI change and weight change from baseline to 1 year using linear regression. One-year AHEI change and incident diabetes, based on fasting and 2h OGTT glucose, was evaluated using Cox proportional hazards models over an average 3 years follow-up. All models were evaluated within treatment group and adjusted for demographics, smoking, alcohol use, family history of diabetes, caloric intake, physical activity, BMI and AHEI, and change in caloric intake and physical activity. Models testing incident diabetes were further adjusted for baseline fasting and 2h glucose. AHEI change was associated with weight loss in ILS [β per unit increase (SE) -0.12 kg (0.03, p&amp;lt;0.001)], metformin [-0.09 kg (0.02, p&amp;lt;0.001)] and placebo [-0.05 kg (0.02, p=0.01)]. However, AHEI change did not predict incident diabetes in any group: hazard ratio per unit increase (95% CI) 1.00 (0.98-1.03) for ILS, 1.00 (0.98-1.02) in metformin and 1.00 (0.98-1.02) in placebo, before or after adjustment for weight change. Our results suggest that diet quality helps achieve weight loss, an important factor in diabetes prevention. Disclosure B. Allaire: None. A.H. Tjaden: None. J.W. Apolzan: None. D. Dabelea: None. L.M. Delahanty: Advisory Panel; Self; Jana Care Inc., Omada Health, Inc., Weight Watchers International, Inc. S. Edelstein: None. M.A. Hoskin: None. L.M. Jaacks: None. K.A. Temple: None. E.M. Venditti: None. J. Wylie-Rosett: None. DPP Research Group: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases

Abstract P069: Serum Uric Acid Trajectories and Type 2 Diabetes and Hypertension in Middle Age

Objective: To identify SUA level trajectories throughout 12 years and to examine their associations with incident diabetes and hypertension among middle-aged men and women. Methods: A total of 7187 participants from the Mudanjiang Chronic Non-communicable Diseases Study, who were aged 30-60 years and without diabetes or hypertension at baseline, were included. The participants were followed for an average of 10.5 years by annual examinations. Latent mixture modeling was used to identify trajectories of SUA over time. Results: Consistently among women and men, five distinct trajectories of SUA were identified: low-stable, low-increasing, moderate-stable, moderate-increasing, and high-stable. In multivariate models, compared with low-stable group, for women, the adjusted hazards ratio of diabetes was 2.11 (95%CI 1.08-4.23) in the low-increasing group, 1.78 (0.81-3.92) in the moderate-stable group, 2.01 (1.02-3.97) in the moderate-increasing group, 3.00 (1.55-5.83) in the high-stable group, whereas no association was found among men. In addition, compared with low-stable group, all other trajectory groups had an increased risk of hypertension in both men and women, except for moderate-stable group in women. Participants in the moderate-increasing group exhibited the highest risk of hypertension (for women, 2.42 [1.72-3.39], for men, 2.57 [2.05-3.24]). Further adjustment for weight change during follow-up period completely ablated the trajectories-diabetes associations, except for the high-stable group in women, but the trajectories-hypertension associations remained significant in each group. Conclusions: We found that a persistent elevated or an increasing trend of SUA levels was significant associated with an increased risk of hypertension among middle-aged women and men; only persistently high UA level was associated with diabetes among women.

A Low-Fat Dietary Pattern and Diabetes: A Secondary Analysis From the Women’s Health Initiative Dietary Modification Trial

We performed a secondary analysis to evaluate the effect of the Women's Health Initiative dietary intervention on incident diabetes and diabetes treatment in postmenopausal women. A total of 48,835 women were randomized to a comparison group or an intervention group that underwent a behavioral/nutritional modification program to decrease fat and increase vegetable, fruit, and grain intake for an average of 8.1 years. Ninety-three percent of participants completed the intervention, and 71% participated in active follow-up through 30 September 2015 (median 17.3 years). We measured time to development of treated diabetes and progression from oral antihyperglycemic agents to insulin. Serum glucose and insulin were measured in a subsample of women (N = 2,324) at baseline and years 1, 3, and 6. During the trial, intervention group women had lower rates of initiation of insulin therapy (hazard ratio [HR] 0.74 [95% CI 0.59, 0.94]; P = 0.01). Moreover, women with baseline waist circumference ≥88 cm (P interaction = 0.01) and worse metabolic syndrome scores (P interaction = 0.02) had the greatest reduction in risk of initiating insulin therapy. The decreased risk from the intervention was present during the cumulative follow-up (HR 0.88 [95% CI 0.78, 0.99]; P = 0.04). In participants with measured biomarkers (5.8% subsample) who had baseline glucose <100 mg/dL, the intervention reduced the risk of developing glucose ≥100 mg/dL by 25% (odds ratio 0.75 [95% CI 0.61, 0.93]; P = 0.008). Adjustment for weight change did not alter the results. In this secondary analysis, a dietary intervention in postmenopausal women aimed at reducing fat and increasing intake of vegetables, fruits, and grains did not increase risk of diabetes and may have slowed progression.

Effects of a lifestyle intervention on REM sleep-related OSA severity in obese individuals with type 2 diabetes.

The aim of this study was to determine if an intensive lifestyle intervention (ILI) reduces the severity of obstructive sleep apnea (OSA) in rapid-eye movement (REM) sleep, and to determine if longitudinal changes in glycaemic control are related to changes in OSA severity during REM sleep over a 4-year follow-up. This was a randomized controlled trial including 264 overweight/obese adults with type 2 diabetes (T2D) and OSA. Participants were randomized to an ILI targeted to weight loss or a diabetes support and education (DSE) control group. Measures included anthropometry, apnea-hypopnea index (AHI) during REM sleep (REM-AHI) and non-REM sleep (NREM-AHI) and glycated haemoglobin (HbA1c) at baseline and year 1, year 2 and year 4 follow-ups. Mean baseline values of REM-AHI were significantly higher than NREM-AHI in both groups. Both REM-AHI and NREM-AHI were reduced significantly more in ILI versus DSE, but these differences were attenuated slightly after adjustment for weight changes. Repeated-measure mixed-model analyses including data to year 4 demonstrated that changes in HbA1c were related significantly to changes in weight, but not to changes in REM-AHI and NREM-AHI. Compared to control, the ILI reduced REM-AHI and NREM-AHI during the 4-year follow-up. Weight, as opposed to REM-AHI and NREM-AHI, was related to changes in HbA1c. The findings imply that weight loss from a lifestyle intervention is more important than reductions in AHI for improving glycaemic control in T2D patients with OSA.

Dynamics of intrapericardial and extrapericardial fat tissues during long-term, dietary-induced, moderate weight loss

Background: In view of evidence linking pericardial fat accumulation with increased cardiovascular disease risk, strategies to reduce its burden are needed. Data comparing the effects of specific long-term dietary interventions on pericardial fat tissue mobilization are sparse.Objective: We sought to evaluate intrapericardial-fat (IPF) and extrapericardial-fat (EPF) changes during weight-loss interventions by different dietary regimens.Design: During 18 mo of a randomized controlled trial, we compared a Mediterranean/low-carbohydrate (MED/LC) diet plus 28 g walnuts/d with a calorically equal low-fat (LF) diet among randomly assigned participants with moderate abdominal obesity. We performed whole-body MRI and volumetrically quantified IPF and EPF among 80 participants to follow the 18-mo changes.Results: The participants [mean age: 48.6 y; mean body mass index (BMI; in kg/m2); 31.7; 90% men] had baseline IPF and EPF (mean ± SD) volumes of 172.4 ± 53.3 mL and 194.9 ± 71.5 mL, respectively. The 18-mo moderate weight loss of 3.7 kg was similar in both groups, but the reduction in waist circumference was higher in the MED/LC group (-6.9 ± 6.6 cm) than in the LF diet group (-2.3 ± 6.5 cm; P = 0.01). After 18 mo, the IPF volume had reduced twice as much in the MED/LC group compared with the LF group [-37 ± 26.2 mL (-22% ± 15%) compared with -15.5 ± 26.2 mL (-8% ± 15%), respectively; P < 0.05, after adjustment for changes in weight or visceral adipose tissue]. The EPF volume had reduced similarly in both groups [-41.6 ± 30.2 mL (-23% ± 16%) in the MED/LC group compared with -37.9 ± 28.3 mL (-19% ± 14%) in the LF group; P > 0.1]. After controlling for weight loss, IPF and EPF volume reduction paralleled changes in lipid profile but not with improved glycemic profile variables: the IPF relative reduction was associated with a decrease in triglycerides (TGs) (β = 0.090; 95% CI: 0.026, 0.154; P = 0.007) and the ratio of TGs to high-density lipoprotein (HDL) cholesterol (β = 2.689; 95% CI: 0.373, 5.003; P = 0.024), and the EPF relative reduction was associated with an increase in HDL cholesterol (β = -0.452; 95% CI: -0.880, -0.023; P = 0.039) and a decrease in total cholesterol and HDL cholesterol (β = 3.766; 95% CI: 1.092, 6.440; P = 0.007).Conclusions: Moderate but persistent dietary-induced weight loss substantially decreased both IPF and EPF volumes. Reduction of pericardial adipose tissues is independently associated with an improved lipid profile. The Mediterranean diet, rich in unsaturated fats and restricted carbohydrates, is superior to an LF diet in terms of the IPF burden reduction. This trial was registered at clinicaltrials.gov as NCT01530724.

Poly is more effective than monounsaturated fat for dietary management in the metabolic syndrome: The muffin study

The metabolic syndrome (MetS) is highly prevalent and associated with an increased risk for type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Lifestyle recommendations to treat MetS often include the replacement of saturated fats (SFAs) and monosaccharides with unsaturated fat. However, it is unclear whether metabolic parameters will improve more when the saturated fat in American Heart Association (AHA) diets is replaced with higher concentrations of monounsaturated or polyunsaturated fatty acids (MUFA or PUFA). To test the hypothesis that an AHA diet enriched in MUFA improves lipoprotein lipids, insulin resistance, inflammation, and endothelial function to a greater extent than a diet enriched in PUFA in middle-aged men and women with MetS. A prospective, open-label, parallel group design with randomization to a hypocaloric MUFA or PUFA-enriched diet after weight stabilization on an AHA step I diet. Participants consumed 3 MUFA-enriched or PUFA-enriched muffins daily with additional supplementation as required to ensure 25%-50% increases in dietary fat intake from these sources at the expense of SFA and the opposing unsaturated fat. Changes in MetS components were measured at baseline and after 6months of dietary intervention. Thirty-nine participants (mean age, 60.8years; 79% African-American, 60% women) with MetS completed the 6-month study. Compared to baseline, assignment to either MUFA (n=23) or PUFA (n=16) both were associated with weight loss (MUFA: -2.3±1kg, P=.06; PUFA: -4.6±2kg; P=.002), but PUFA was also associated with reductions in triglycerides (TG) (-30±18mg/dL, P=.02), systolic blood pressure (BP) (-7 ± 3mm Hg, P=.01), diastolic BP (DBP) (-4 ± 2mm Hg, P=.01) and improved flow mediated dilation (FMD) (7.1%±1.8% vs 13.6%±2%, absolute increase; P=.0001). When compared to MUFA treatment, PUFA intervention was associated with reduced TG (P=.04) and DBP (P=.07) as well as increased FMD (P=.04) even after adjustment for changes in weight. There was no effect on total cholesterol, low-density lipoprotein cholesterol, glucose, high-sensitivity C-reactive protein (hs-CRP), or other inflammatory proteins. Overall, 25% (4 of 16) assigned to PUFA and 13% (3 of 23) to MUFA converted to non-MetS status. Substitution of SFA with PUFA in patients with MetS is associated with greater reductions in TG and improvement in endothelial function than MUFA that is independent of weight loss. These preliminary findings raise the possibility that PUFA may be the unsaturated fat of choice to reduce cardiometabolic risk in patients with MetS.

Abstract P315: Three-year Progression of Sleep-disordered Breathing is Associated with Cardiovascular Disease Risk Factors in Young Adults

Introduction: Sleep-disordered breathing (SDB) is a common sleep disorder that is significantly associated with cardiovascular disease (CVD) risk. Less is known about the short-term cardiovascular implications of mild-severity SDB progression, as mild SDB is less commonly associated with CVD but often develops into more severe SDB over time if left untreated. Hypothesis: We hypothesized that worsening of SDB severity over 3 years would be associated with greater changes in common CVD risk factors (body weight, heart rate [HR], blood pressure [BP], insulin resistance, and C-reactive protein [CRP]). Methods: A sample of 32 adults (38.6±6.4 y; 31.9±4.0 kg/m2; 72% female) who previously had participated in a 1-year lifestyle intervention were followed from 1-year post-intervention (2Y) for an additional 3 years (5Y). At 2Y and 5Y, SDB was assessed with an ambulatory monitor (ResMed ApneaLink); the oxygen desaturation index (ODI; the number of times per hour of recording that the blood oxygen saturation [SaO2] level was reduced by ≥4%) and mean SaO2 served as the primary indices of SDB severity. At 2Y and 5Y, body weight and resting BP and HR were assessed using standard procedures and fasting blood samples were obtained and measured for glucose, insulin, and CRP. Insulin resistance was measured via the Homeostatic Model Assessment method. Multiple linear regression and analysis of covariance were used to examine the associations between changes in SDB severity and changes in CVD risk factors, adjusting for 2Y values of CVD risk factors. Results: ODI at 2Y was 5.3±6.6. At 5Y, ODI had changed (i.e., improved) by -0.2±4.9, with ODI worsening by ≥2 in 7 adults and improving by ≥2 in 11 adults. Mean SaO2 at 2Y was 95.5±1.6% and changed (i.e., improved) by +0.1±1.1% at 5Y; mean SaO2 worsened in 10 adults and improved in 12 adults. Three-year change in ODI, but not SaO2, was significantly associated with weight change (β=.42, P=.02). Compared to those whose ODI worsened or did not change, improved ODI was associated with more favorable changes in CRP (-1.8 vs. +0.8 mg/L; P=.04) and heart rate (-5.0 vs. +0.2 beats/min; P=.05); however, these associations were weakened after further adjustment for weight change (P=.16 and P=.07, respectively). Compared to those whose SaO2 remained unchanged or improved, worsened SaO2 was associated with increased insulin resistance (+1.1 vs. -0.4; P&lt;.01); results were unchanged following adjustment for weight change (P=.01). Changes in ODI and SaO2 were not related to changes in BP. Conclusions: Even marginal worsening of SDB severity over 3 years is associated with elevation in some CVD risk markers. Treatment of mild SDB in young- to middle-aged adults may reduce risk for CVD.

Abstract P145: The Effects of Phosphorus Additives on Albuminuria and Fibroblast Growth Factor-23

Background: Phosphorus-based additives are prevalent in processed foods. Their effects on cardiovascular and renal health are unknown. Methods: We conducted a randomized, double-blind, cross-over study to examine the effects of phosphorus additives on albuminuria and fibroblast growth factor-23 (FGF-23) in adults with microalbuminuria and estimated glomerular filtration rate (eGFR) ≥ 45 ml/min/1.73m2. Participants (n=31) received unaltered beverages and breakfast bars (with or without phosphorus additives; 941 mg/d contrast in phosphorus) for 3 week periods, separated by a 2-4 week washout period. Diet was assessed by 24-hour recalls bi-weekly. Primary outcomes were albuminuria and FGF-23 assessed by two 24-hour urine collections and a single fasting blood draw at the end of each period. Results: We included 31 participants (32% female, 90% black, 87% hypertension, 48% diabetes) with mean age, eGFR, and 24-hour urine albumin excretion of 66 years, 68 ml/min/1.73m2, and 74.4 mg/d, respectively. Mean self-reported phosphorus intake and 24-hour urine phosphorus excretion was 1113 mg/d and 687.9 mg/d at baseline. Self-reported phosphorus intake (excluding intervention products) decreased by 151 mg/d (p=0.004) during the phosphorus additive period compared to the non-phosphorus additive period as did protein intake (8.0 g/d lower, p=0.02). In unadjusted analyses, consumption of phosphorus additives increased 24-hour urine phosphorus excretion by a mean of 505 mg/d, non-significantly increased albuminuria by 14.3% (95% CI: -2.5% to 34.0%, p=0.1), but had no effect on FGF-23 (3.0%, 95% CI: -9.3% to 16.8%). After adjustment for changes in weight and self-reported dietary intake (sodium, phosphorus, and protein intake), consumption of phosphorus additives increased albuminuria by 22.5% (95% CI: 3.1% to 45.6%, p=0.02). In unadjusted analysis excluding two patients non-compliant with the intervention, consumption of phosphorus additives increased albuminuria by 17.3% (95% CI: 0.08% to 37.5%, p=0.049). Neither sensitivity analysis showed an effect on FGF-23. Conclusion: High consumption of phosphorus-based additives may increase albuminuria. Further studies are needed to confirm this finding and determine the long-term effects on cardiovascular and renal health.

The Effect of Changes in Cardiorespiratory Fitness and Weight on Obstructive Sleep Apnea Severity in Overweight Adults with Type 2 Diabetes

To examine the effect of changes in cardiorespiratory fitness on obstructive sleep apnea (OSA) severity prior to and following adjustment for changes in weight over the course of a 4-y weight loss intervention. As secondary analyses of a randomized controlled trial, 263 overweight/obese adults with type 2 diabetes and OSA participated in an intensive lifestyle intervention or education control condition. Measures of OSA severity, cardiorespiratory fitness, and body weight were obtained at baseline, year 1, and year 4. Change in the apnea-hypopnea index (AHI) served as the primary outcome. The percentage change in fitness (submaximal metabolic equivalents [METs]) and change in weight (kg) were the primary independent variables. Primary analyses collapsed intervention conditions with statistical adjustment for treatment group and baseline METs, weight, and AHI among other relevant covariates. At baseline, greater METs were associated with lower AHI (B [SE] = -1.48 [0.71], P = 0.038), but this relationship no longer existed (B [SE] = -0.24 [0.73], P = 0.75) after adjustment for weight (B [SE] = 0.31 [0.07], P < 0.0001). Fitness significantly increased at year 1 (+16.53 ± 28.71% relative to baseline), but returned to near-baseline levels by year 4 (+1.81 ± 24.48%). In mixed-model analyses of AHI change over time without consideration of weight change, increased fitness at year 1 (B [SE] = -0.15 [0.04], P < 0.0001), but not at year 4 (B [SE] = 0.04 [0.05], P = 0.48), was associated with AHI reduction. However, with weight change in the model, greater weight loss was associated with AHI reduction at years 1 and 4 (B [SE] = 0.81 [0.16] and 0.60 [0.16], both P < 0.0001), rendering the association between fitness and AHI change at year 1 nonsignificant (B [SE] = -0.04 [0.04], P = 0.31). Among overweight/obese adults with type 2 diabetes, fitness change did not influence OSA severity change when weight change was taken into account. ClinicalTrials.gov identification number NCT00194259.

The Dietary Approaches to Stop Hypertension (DASH) Diet Affects Inflammation in Childhood Metabolic Syndrome: A Randomized Cross-Over Clinical Trial

Background: The effects of the DASH (Dietary Approaches to Stop Hypertension) diet on inflammation in childhood metabolic syndrome (MetS) have still to be identified. Objective: To examine the effects of the DASH diet on markers of systemic inflammation in adolescents with MetS. Methods: In this randomized, cross-over clinical trial, 60 postpubescent girls with MetS were randomly assigned to receive either the DASH diet menu cycles or usual dietary advice (UDA) for 6 weeks. After a 4-week washout period, participants were crossed over to the alternate arm. The DASH diet was designed to maintain the current body weight. This diet contained high amounts of fruit, vegetables and low-fat dairy products and was low in saturated fats and cholesterol. UDA consisted of general oral advice and written information about healthy food choices based on the Healthy Eating Plate. Compliance to the DASH diet was assessed through quantification of plasma vitamin C levels. Fasting venous blood samples were taken 4 times from each participant: at baseline and at the end of each study arm. Circulating levels of biomarkers of systemic inflammation were quantified according to standard protocols. Results: Mean (SD) age and weight of participants was 14.2 years (1.7) and 69 kg (14.5), respectively. Serum vitamin C levels tended to increase during the DASH phase compared with the UDA phase (16.8 ± 12.9 vs. -13.8 ± 9.7 ng/dl, respectively, p = 0.06) indicating a relatively good compliance to the DASH diet. Adherence to the DASH diet, compared to the UDA, had a significant effect on serum high-sensitivity C-reactive protein levels (p = 0.002). This effect remained significant even after adjustment for weight changes and after further controlling for changes in lipid profiles. We did not observe any significant effect of intervention on levels of serum tumor necrosis factor-alpha, interleukin (IL)-2, IL-6 and adiponectin, in either the crude or adjusted models. There were no significant group*time interactions for any dependent variable, except for IL-6; this was close to the significant level. Conclusion: In summary, consumption of the DASH eating pattern for 6 weeks may reduce circulating levels of hs-CRP among adolescents with MetS. Other inflammatory markers were not affected by the DASH diet.

Effect of exercise on abdominal fat loss in men and women with and without type 2 diabetes

ObjectiveTo examine the effect of exercise on abdominal adipose tissue in adults with and without type 2 diabetes mellitus (T2DM).DesignPost hoc analysis of two randomised controlled trials.SettingOutpatient secondary prevention programme...

N3 PUFAs Do Not Affect Adipose Tissue Inflammation in Overweight to Moderately Obese Men and Women1–3

Recent studies have indicated that omega-3 (n3) polyunsaturated fatty acids (PUFAs) decrease adipose tissue inflammation in rodents and in morbidly obese humans. We investigated whether a diet rich in n3 PUFAs from both marine and plant sources reduces adipose tissue and systemic inflammation in overweight to moderately obese adults. We conducted a randomized, single-blind, parallel-design, placebo-controlled feeding trial. Healthy men and women with a body mass index between 28 and 33 kg/m2 consumed a diet rich in n3 PUFAs (3.5% of energy intake; n = 11) from plant and marine sources or a control diet (0.5% of energy intake from n3 PUFAs; n = 13). These diets were consumed for 14 wk (ad libitum for 12 wk). All foods were provided for the entire study period. Subcutaneous abdominal adipose tissue and fasting plasma were collected after the first 2 wk with the control diet and again at the end of the 14-wk dietary period. The primary outcome of this ex post analysis was the adipose tissue gene expression of 13 key mediators of inflammation. Adipose tissue gene expression of inflammatory mediators did not differ between the 2 groups, after adjustment for weight change. Furthermore, none of the 5 plasma markers of systemic inflammation differed significantly as an effect of diet treatment. We conclude that a relatively high dose of n3 PUFAs from plant and marine sources did not significantly lower adipose tissue or systemic inflammation in overweight to moderately obese healthy men and women over 14 wk.