Visceral Adipose Tissue Loss Research Articles

Abstract 2425: Moderate to vigorous physical activity reduces visceral adipose tissue in obese breast cancer survivors undergoing a weight loss intervention

Abstract Background: Body composition, adipose distribution, and fitness are likely superior to BMI alone in predicting outcomes in obese breast cancer survivors. Visceral adipose tissue (VAT) is thought to be disproportionately responsible for the metabolic and inflammatory changes linking obesity and breast cancer recurrence. Purpose: Feasibility of achievement of high volume moderate-to-vigorous physical activity (MVPA) and its effect on body composition including VAT and other risk biomarkers in older sedentary, obese breast cancer survivors participating in a behavioral weight loss intervention. Methods: Modest caloric restriction (350-500 kcal per day) was combined with a study provided YMCA membership and twice weekly personal trainer sessions. MVPA (40-80% of heart rate reserve in older women) was assessed by Garmin Vivoactive smart watches linked to GarminConnect. Total activity was escalated from 100 minutes week 1 to a total of 300 minutes per week by week 9 with a goal of > 200 min/wk as MVPA. Women were evaluated pre- and post-intervention for peak oxygen consumption (VO2peak), body composition by dual energy x-ray absorptiometry (GE Lunar iDXA), and serum levels of adipokines, cytokines, and hormones. Results: 18 breast cancer survivors were enrolled and completed the 3 months of the behavioral weight loss intervention which included the YMCA membership and twice weekly personal trainer. Median age was 60, 11 had received prior chemotherapy, and 13 were currently taking aromatase inhibitors. Median (and range) baseline anthropomorphic values were BMI 37 (31-43) kg/m2, total mass 95 (76-125) kg, total fat 46 (34-66) kg, and VAT 1.7 (1.0-3.0) kg. All but one had a baseline VAT > 1.17 kg, consistent with elevated risk of metabolic syndrome. 17/18 achieved at least 150 min/wk of MVPA, with a median of 176 (range 55-291) min/wk for weeks 9-12. Fitness measured as VO2peak increased from 18.9 (13.7-25.3) to 21.1 (17.1-31.4) ml/kg/min (p=0.0003; Wilcoxon signed rank test). At 3 months, significant reductions were observed for total mass (median 7%), fat mass (median 13%), and VAT (median 20%, range 1-41%)(p<0.0003); as well as serum leptin, insulin, and leptin: adiponectin ratio (p<0.01). A strong correlation was observed between week 9-12 MVPA and leptin: adiponectin ratio (p=0.001) with more modest correlations between week 9-12 MVPA and VAT loss (p=0.043), and leptin: adiponectin ratio and VAT loss (p=0.013). Conclusion: High volume moderate-to-vigorous physical activity can be achieved by older, sedentary, obese breast cancer survivors; and this translates to favorable modulation of body composition including VAT measures and serum risk biomarkers. Citation Format: Carol J. Fabian, Jennifer R. Klemp, Jeffrey M. Burns, Eric D. Vidoni, Lauren Nye, Christie A. Befort, Jill M. Hamilton-Reeves, Debra K. Sullivan, Teresa A. Phillips, Stephen D. Hursting, Bruce F. Kimler. Moderate to vigorous physical activity reduces visceral adipose tissue in obese breast cancer survivors undergoing a weight loss intervention [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 2425.

Skeletal muscle mass and adipose tissue alteration in critically ill patients.

BackgroundIncreasing numbers of studies in chronic diseases have been published showing the relationship between body composition (BC) parameters (i.e. skeletal muscle mass (SMM) and adipose tissue (AT)) and outcomes. For patients admitted to intensive care unit (ICU), BC parameters have rarely been described as a prognostic marker of outcome. The primary objective was to evaluate the relationship between body composition at ICU admission and major clinical outcomes. Secondary objectives were to assess the relationship between BC parameters and other parameters (systemic inflammatory markers, Sequential Organ Failure Assessment (SOFA) score, albumin level) at ICU admission, and between BC alterations during ICU stay and outcomes.Patients and methodsThis retrospective study enrolled 25 adult patients who had two abdominal CT scans for clinical indication: first, within 48 hours of ICU admission (initial assessment), and second, 7 to 14 days later (late assessment). Skeletal Muscle radiodensity (SMD), cross-sectional area of SMM, Visceral Adipose Tissue (VAT) and Subcutaneous Adipose Tissue (SAT) were measured at the third lumbar vertebra. Cox regression analysis was used to determine the association between these parameters and mortality.ResultsPatients’ mean age was 64.6 years. Their mean BMI was 27.7 kg/m2 (SD = 6.0). ICU mortality was 36%. There was no correlation between BC parameters at initial assessment and ICU outcomes. We observed a negative correlation between SMM index and SOFA score at initial assessment (r = -0.458, p = 0.037). There was a significant loss of VAT between two CT assessments which was associated with mortality (-22.34cm2 / m2 in non-survivors versus -6.22 cm2 / m2 in survivors, p = 0.039). Loss of SMD was greater with the occurrence of an infection than without (Delta SMD = -5.642 vs +1.957, p = 0.04).ConclusionsOur results show alterations in body composition during ICU stay with a loss of muscle quality (decreased SMD) and adipose tissue. These findings require confirmation in future studies but already show that BC assessments at ICU admission and BC alterations during ICU stay are important factors for outcome in critically ill patients.

Does Intermittent Energy Restriction Plus Mediterranean Diet Reduce Visceral Adipose Tissue and Minimize Adaptive Responses of Energy Restriction? A Randomized Pilot Study (P21-016-19)

ObjectivesTest if an intermittent energy restriction with a Mediterranean diet (IER + MED) preferentially promotes loss of visceral adipose tissue (VAT) over subcutaneous adipose tissue (SAT), with minimal changes to resting energy expenditure (REE) and physical activity level (PAL), compared to an active control, the Dietary Approaches to Stop Hypertension (DASH) diet, in an East Asian adult population. MethodsMen and women in Hawai’i (n = 60, aged 35–55, BMI 25–40, VAT ≥ 90cm2 for men and ≥ 80cm2 for women) of East Asian origin, were randomized equally to IER + MED (2 days with 70% energy restriction and 5 days euenergetic MED) or a 7 day euenergetic DASH diet for 12 weeks. Dual energy X-ray absorptiometry (DXA) for estimation of VAT and abdominal SAT, REE through indirect calorimetry, and physical activity questionnaires were collected at baseline and week 12. Four-days mobile food records were completed at baseline, weeks 5–6 and 11. ResultsAt week 12, participants in the IER + MED group lost greater amounts of VAT (−22.6 ± 3.6 cm2 vs. −10.7 ± 3.5 cm2 in DASH, P = 0.022) and SAT (−48.2 ± 6.4 cm2 vs. −15.0 ± 6.1 cm2 in DASH, P < 0.001). The IER + MED diet did not preferentially promote loss of VAT over SAT compared to DASH. Changes in VAT: SAT were 0.01 ± 0.01 for both groups (IER + MED vs. DASH, P = 0.825). Mean daily energy intake reductions at week 11 were larger in IER + MED (27%) than DASH (16%); and mean loss of weight at week 12 was higher in the IER + MED group (−5.9 ± 0.7 kg vs. −3.3 ± 0.6 kg in DASH, P = 0.007). Despite the significant drop in energy and weight for IER + MED, there was a non-significant change in REE of −105 ± 56 kcal/day for IER + MED (P = 0.068) and −25 ± 57 kcal/day for DASH (P = 0.663). Hours of moderate-to-vigorous physical activity per day were 1.6 ± 0.2 for IER + MED and 1.4 ± 0.3 for DASH at baseline and did not change significantly over 12 weeks. ConclusionsIn this short-term pilot study, the IER + MED diet was more effective at reducing VAT, SAT and weight; however, it did not preferentially promote loss of VAT over SAT, as compared to the active control DASH group. Loss of VAT, SAT and weight from the IER + MED diet may be sustainable long term as REE and PAL, which commonly decrease with large energy restriction, did not significantly change over 12 weeks. Funding SourcesThe William & Ellen Melohn Endowed Research Fund, University of Hawaii; National Institutes of Health, National Cancer Institute.

The beneficial effects of Mediterranean diet over low-fat diet may be mediated by decreasing hepatic fat content

It is unclear if a reduction in hepatic fat content (HFC) is a major mediator of the cardiometabolic benefit of lifestyle intervention, and whether it has prognostic significance beyond the loss of visceral adipose tissue (VAT). In the present sub-study, we hypothesized that HFC loss in response to dietary interventions induces specific beneficial effects independently of VAT changes. In an 18-month weight-loss trial, 278 participants with abdominal obesity/dyslipidemia were randomized to low-fat (LF) or Mediterranean/low-carbohydrate (MED/LC + 28 g walnuts/day) diets with/without moderate physical activity. HFC and abdominal fat-depots were measured using magnetic resonance imaging at baseline, after 6 (sub-study, n = 158) and 18 months. Of 278 participants (mean HFC 10.2% [range: 0.01%-50.4%]), the retention rate was 86.3%. The %HFC substantially decreased after 6 months (-6.6% absolute units [-41% relatively]) and 18 months (-4.0% absolute units [-29% relatively]; p <0.001 vs. baseline). Reductions of HFC were associated with decreases in VAT beyond weight loss. After controlling for VAT loss, decreased %HFC remained independently associated with reductions in serum gamma glutamyltransferase and alanine aminotransferase, circulating chemerin, and glycated hemoglobin (p <0.05). While the reduction in HFC was similar between physical activity groups, MED/LC induced a greater %HFC decrease (p = 0.036) and greater improvements in cardiometabolic risk parameters (p <0.05) than the LF diet, even after controlling for VAT changes. Yet, the greater improvements in cardiometabolic risk parameters induced by MED/LC were all markedly attenuated when controlling for HFC changes. %HFC is substantially reduced by diet-induced moderate weight loss and is more effectively reduced by the MED/LC diet than the LF diet, independently of VAT changes. The beneficial effects of the MED/LC diet on specific cardiometabolic parameters appear to be mediated more by decreases in %HFC than VAT loss. High hepatic fat content is associated with metabolic syndrome, type 2 diabetes mellitus, and coronary heart disease. In the CENTRAL 18-month intervention trial, a Mediterranean/low-carbohydrate diet induced a greater decrease in hepatic fat content than a low-fat diet, conferring beneficial health effects that were beyond the favorable effects of visceral fat loss. ClinicalTrials.gov Identifier: NCT01530724.

Effect of Exercise and Pharmacological Interventions on Visceral Adiposity: A Systematic Review and Meta-analysis of Long-term Randomized Controlled Trials

ObjectiveTo assess the effectiveness of exercise and pharmacotherapy interventions in reducing visceral adipose tissue (VAT). Patients and MethodsA systematic search of Ovid MEDLINE, Scopus, Web of Science, Cochrane Library, ClinicalTrials.gov, New York Academy of Science Grey Literature Report, and OpenGrey was combined with hand searches of existing literature. A total of 2515 titles and abstracts were reviewed. Only randomized controlled trials evaluating the effectiveness of monitored exercise or pharmacological interventions in reducing VAT by using computed tomography or magnetic resonance imaging during a sustained intervention period (≥6 months) were included. Data were independently extracted by reviewers according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and assessed for quality and risk of bias. Separate analyses for each intervention were performed using random effect models, with pooled estimates of the change in VAT area (in centimeters squared) from baseline to follow-up reported as standardized mean difference (SMD; with 95% CI). ResultsA total of 3602 participants from 17 randomized controlled trials were included in the final analysis. Both exercise and pharmacological interventions were associated with significant reductions in VAT: small reduction with pharmacological interventions (SMD, −0.27; 95% CI, −0.47 to −0.07; P=.02) and more substantial reductions with exercise interventions (SMD, −0.54; 95% CI, −0.63 to −0.46; P<.001). The mean absolute VAT reduction was greater in pharmacological trials than in exercise trials. Meta-regression exhibited a linear correlation between VAT and weight loss (R2=0.52 for exercise and R2=0.88 for pharmacological interventions), but VAT reduction relative to weight loss differed by intervention type. ConclusionExercise interventions resulted in greater reduction in VAT relative to weight loss than did pharmacological interventions. A preferential reduction in VAT may be clinically meaningful when monitoring success of interventions because weight loss alone may underestimate benefits.

Pleiotropic Impacts of Macrophage and Microglial Deficiency on Development in Rats with Targeted Mutation of the Csf1r Locus.

We have produced Csf1r-deficient rats by homologous recombination in embryonic stem cells. Consistent with the role of Csf1r in macrophage differentiation, there was a loss of peripheral blood monocytes, microglia in the brain, epidermal Langerhans cells, splenic marginal zone macrophages, bone-associated macrophages and osteoclasts, and peritoneal macrophages. Macrophages of splenic red pulp, liver, lung, and gut were less affected. The pleiotropic impacts of the loss of macrophages on development of multiple organ systems in rats were distinct from those reported in mice. Csf1r−/− rats survived well into adulthood with postnatal growth retardation, distinct skeletal and bone marrow abnormalities, infertility, and loss of visceral adipose tissue. Gene expression analysis in spleen revealed selective loss of transcripts associated with the marginal zone and, in brain regions, the loss of known and candidate novel microglia-associated transcripts. Despite the complete absence of microglia, there was little overt phenotype in brain, aside from reduced myelination and increased expression of dopamine receptor-associated transcripts in striatum. The results highlight the redundant and nonredundant functions of CSF1R signaling and of macrophages in development, organogenesis, and homeostasis.

Laparoscopic sleeve gastrectomy improves body composition and alleviates insulin resistance in obesity related acanthosis nigricans

BackgroundAcanthosis nigricans (AN) has a close relationship with obesity. It is believed that obesity and AN have the common pathophysiological basis such as hyperinsulinism. This study is aimed to observe the effect of laparoscopic sleeve gastrectomy (LSG) on body composition and insulin resistance in Chinese obese patients with acanthosis nigricans.MethodsA total of 37 obese patients who underwent LSG in our hospital were selected for analysis. They were divided into simple obesity (OB n = 14) and obesity with acanthosis nigricans (AN n = 23) group respectively. Body composition was measured by dual-energy X-ray absorptiometry (DEXA). Anthropometric measurements and glucolipid metabolism before and 3 months post LSG were collected for analysis.ResultsPatients with AN got noticeable improvement in skin condition and their AN score was significantly decreased (3.52 ± 0.79 vs. 1.48 ± 0.73, P < 0.001).Alleviated insulin resistance and more trunk fat loss than limbs’ were observed in both groups (P value < 0.01). In AN group, preoperative android fat mass (FM) was positively correlated with fasting insulin and natural logarithm of HOMA-IR (LNIR) (r = 0.622, 0.608, respectively; all P < 0.01). Besides, changes in android FM and visceral adipose tissue (VAT) also showed significantly positive correlation with changes in LNIR (r = 0.588, r = 0.598, respectively; all P < 0.01).ConclusionsLSG had a positive impact on body composition and skin condition in Chinese obese patients with AN. Loss of android FM and VAT might result in the alleviation of insulin resistance in AN patients. Android fat distribution seems to be a potential indicator of postoperative metabolic benefits for obese patients with AN.

Differential Impact of Weight Loss on Nonalcoholic Fatty Liver Resolution in a North American Cohort with Obesity.

Nonalcoholic fatty liver disease (NAFLD) is closely associated with obesity. In this study, a North American cohort with obesity enrolled in a lifestyle modification program was examined to determine the impact of weight loss on NAFLD resolution and sarcopenia. Nondiabetic individuals with World Health Organization Class II/III obesity enrolled in a 6-month weight loss intervention were included. Steatosis was measured using computed tomography (CT)-derived liver:spleen attenuation ratio. Body composition was assessed using dual X-ray absorptiometry, air-displacement plethysmography, and CT anthropometry. At baseline, participants with NAFLD had greater visceral adipose tissue (VAT) but similar skeletal muscle area compared to those without NAFLD. After intervention, weight loss was similar in the two groups, but participants with NAFLD lost more VAT than those without NAFLD (-38.81 [-55.98 to -21.63] cm2 vs. -13.82 [-29.65 to -2.02] cm2 ; P = 0.017). In the subset with NAFLD at baseline, participants with NAFLD resolution after intervention lost more VAT than those with persistent NAFLD (-57.23 [-88.63 to -25.84) cm2 vs. -26.92 [-52.14 to -26.92] cm2 , P = 0.039). In a Western cohort with obesity, NAFLD was not associated with sarcopenia. After lifestyle modification, there was a differential impact on NAFLD resolution, with twofold greater VAT loss in participants who resolved NAFLD compared with those with persistent NAFLD despite similar weight loss.

Clinical impact of sarcopenia on prognosis in pancreatic ductal adenocarcinoma.

259 Background: In the past, various prognostic factors in pancreatic ductal carcinoma (PDAC) have been identified, and there found to be not only tumor-specific clinicopathological factors but also individual patient characteristics. In particular, weight loss, muscle wasting and cachexia are hallmarks of PDAC that may be associated with depletion of both skeletal muscle and adipose tissue. Most notably, sarcopenia is defined to be degenerative loss of skeletal muscle mass that is quantifiable using cross sectional imaging computed tomography (CT) by measurement of psoas area and the muscle’s density. Furthermore, visceral adipose tissue loss also has been reported to associate with a poor survival among patients with PDAC. Methods: A total of 265 patients who underwent curative surgery for PDAC were examined in this study. The total skeletal muscle and fat tissue areas were evaluated in a single image obtained at the third lumber vertebra during a preoperative computed tomography (CT) scan. The patients were assigned to either the sarcopenia or non-sarcopenia group based on their skeletal muscle index (SMI) and classified into high visceral fat area (H-VFA) or low VFA (L-VFA) groups. The association of clinicopathological features and prognosis with the body composition were statistically analyzed. Results: There were 170 patients (64.2%) with sarcopenia. The median survival time (MST) was 23.7 months for sarcopenia patients and 25.8 months for patients without sarcopenia. The MST was 24.4 months for H-VFA patients and 25.8 months for L-VFA patients. However, sarcopenia patients with BMI ≥ 22 exhibited significantly poorer survival than patients without sarcopenia (MST: 19.2 vs. 35.4 months, P = 0.025). There was a significant difference between patients with and without sarcopenia who did not receive chemotherapy (5-year survival rate: 0% vs. 68.3%, P = 0.003). The multivariate analysis revealed that tumor size, positive dissected peripancreatic tissue margin, and sarcopenia were independent prognostic factors. Conclusions: Sarcopenia is an independent prognostic factor in PDAC patients with a BMI ≥ 22. Therefore, evaluating skeletal muscle mass may be a simple and useful approach for predicting patient prognosis.

Effects of Calorie Restriction in Obese Older Adults: The CROSSROADS Randomized Controlled Trial.

We lack a comprehensive assessment of the risks and benefits of calorie restriction in older adults at high risk for cardiometabolic disease. Calorie restriction may reduce visceral adipose tissue (VAT) but also have negative effects on lean mass and quality of life. We conducted a 52-week, randomized controlled trial involving 164 older adults with obesity taking at least one medication for hyperlipidemia, hypertension, or diabetes. Interventions included an exercise intervention alone (Exercise), or with diet modification and body weight maintenance (Maintenance), or with diet modification and energy restriction (Weight Loss). The primary outcome was change in VAT at 12 months. Secondary outcomes included cardiometabolic risk factors, functional status, and quality of life. A total of 148 participants had measured weight at 12 months. Despite loss of -1.6% ± 0.3% body fat and 4.1% ± 0.7% initial body weight, Weight Loss did not have statistically greater loss of VAT (-192.6 ± 185.2 cm3) or lean mass (-0.4 ± 0.3 kg) compared with Exercise (VAT = -21.9 ± 173.7 cm3; lean mass = 0.3 ± 0.3 kg). Quality of life improved in all groups with no differences between groups. No significant changes in physical function were observed. Weight Loss had significantly greater improvements in blood glucose (-8.3 ± 3.6 mg/dL, p < .05) and HDL-cholesterol (5.3 ± 1.9, p < .01) compared with Exercise. There were no group differences in the frequency of adverse events. While moderate calorie restriction did not significantly decrease VAT in older adults at high risk for cardiometabolic disease, it did reduce total body fat and cardiometabolic risk factors without significantly more adverse events and lean mass loss.

Automatic segmentation of abdominal organs and adipose tissue compartments in water-fat MRI: Application to weight-loss in obesity

PurposeTo develop a fully automatic algorithm for abdominal organs and adipose tissue compartments segmentation and to assess organ and adipose tissue volume changes in longitudinal water-fat magnetic resonance imaging (MRI) data. Materials and methodsAxial two-point Dixon images were acquired in 20 obese women (age range 24–65, BMI 34.9±3.8kg/m2) before and after a four-week calorie restriction. Abdominal organs, subcutaneous adipose tissue (SAT) compartments (abdominal, anterior, posterior), SAT regions along the feet-head direction and regional visceral adipose tissue (VAT) were assessed by a fully automatic algorithm using morphological operations and a multi-atlas-based segmentation method. ResultsThe accuracy of organ segmentation represented by Dice coefficients ranged from 0.672±0.155 for the pancreas to 0.943±0.023 for the liver. Abdominal SAT changes were significantly greater in the posterior than the anterior SAT compartment (−11.4%±5.1% versus −9.5%±6.3%, p<0.001). The loss of VAT that was not located around any organ (−16.1%±8.9%) was significantly greater than the loss of VAT 5cm around liver, left and right kidney, spleen, and pancreas (p<0.05). ConclusionThe presented fully automatic algorithm showed good performance in abdominal adipose tissue and organ segmentation, and allowed the detection of SAT and VAT subcompartments changes during weight loss.

Effects of an Almond‐Enriched Energy Restricted Diet on Body Composition, Visceral Adipose Tissue and Blood Pressure in Obese Adults

BACKGROUNDAlmonds are a good source of protein and monounsaturated fats and their effects on differential rates of visceral and subcutaneous body fat loss, in conjunction with energy restriction, have not been widely examined. Increasing the proportion of protein in an energy‐restricted diet enhances satiety, energy expenditure and greater relative fat mass loss. In addition, monounsaturated fats are oxidized preferentially and a diet higher in the unsaturated: saturated fat ratio may reduce subcutaneous adipose tissue (SAT) but more importantly, visceral adipose tissue (VAT) during weight loss. The promotion of VAT loss is important clinically as this may translate into a reduction in the risk for metabolic diseases. In addition, emerging evidence indicates food‐derived peptides such as arginine reduce the risk of cardiovascular disease. Almonds contain a high level of arginine, a peptide that helps to reduce blood pressure (BP).METHODSObese adults (n=28, age: 35.7±11.4 yr, body mass index: 33.1±2.7 kg/m2) were randomly assigned to a 12 week energy restricted (500 kcal deficit) almond‐enriched diet (AED) (n=14) or an energy restricted nut‐free diet (NFD) (n=14). Participants in the AED group were asked to consume dry‐roasted, lightly salted almonds comprising of 15% energy in the individualized energy‐restricted diet. Participants in the NFD group were asked to avoid all nuts during the intervention period. The primary outcomes for this analysis were changes in weight, body composition, VAT and BP pre‐ and post‐study. Body composition was assessed using DEXA. VAT was predicted using multivariate anthropometric models. Resting BP was assessed using automated instruments.RESULTSBody weight, trunk fat percent, total fat percent, VAT and systolic BP decreased after 12 weeks on energy restriction (p&lt;0.05). Diastolic BP remained unchanged with weight loss. Both groups lost similar amounts of body weight over time. The AED group lost more trunk fat percent and total fat percent over time compared to the NFD group (p&lt;0.05). The AED group also had a greater trend for VAT loss over time compared to the NFD group. Both groups had similar reductions in systolic BP with weight loss.CONCLUSIONConsumption of almonds during a weight loss regimen resulted in greater improvements in trunk and total body composition compared to the nut‐free weight loss regimen. The overall improvements in body composition with almond consumption coupled with greater trend for VAT loss may help to reduce metabolic disease risk. In addition, consumption of lightly salted almonds had similar blood pressure reducing effects as the nut‐free intervention.Support or Funding InformationAlmond Board of California

Loss of visceral adipose tissue precedes subcutaneous adipose tissue and associates with n-6 fatty acid content

During cancer development, fat loss occurs in most cancer patients. Characterization of the behavior of fat loss from visceral (VAT) and subcutaneous adipose tissue (SAT) depots has not been established. The first objective of this study was to assess the intensity and time course of changes in VAT and SAT depots of advanced cancer patients in the year preceding death. Secondly, this study explored the differences in adipokine content and fatty acid composition between VAT and SAT depots and in relation to changes in fat mass. Longitudinal quantitative analyses of computed tomography images was conducted to define changes in adipose tissue cross sectional areas in fat depots in advanced colorectal and cholangiocarcinoma cancer patients (n=46) at mean time points corresponding to 9, 6, 3 and 1 month before death. Proportions of adipose tissue fatty acid and adipokine content were characterized in a second cohort of advanced colorectal cancer patients (n=16). On average, loss of total adipose tissue (TAT) happens at all time intervals but there is an elevation in the intensity of loss close to death. Nine months from death, 42% of patients were losing fat (Mean TAT cross sectional area change=-0.2±13cm2) whereas within one month from death, fat wasting was observed in 78% of patients (-60.1±9.2cm2, P=0.001). However, loss of TAT did not reflect changes in VAT and SAT in the same direction or intensity. Intensity of VAT loss remains constant throughout the disease progression whereas SAT is more likely to be gained further way from death. Nine month prior to death, mean change in cross sectional area of VAT was-7.9±6.8cm2 whereas, mean change in CSA of SAT was 7.4±7.7cm2 (p=0.03). One month before death, mean VAT and SAT absolute changes were-24.5±4.9cm2 and -34.5±5.2cm2, respectively (p=0.05). Moreover, fat losing patients had higher proportions of polyunsaturated fatty acids, especially n-6 fatty acids, in VAT compared to patients who were gaining fat (mean=15.4% in losing group vs. 13.4% in gaining group; p=0.03). VAT contained more monocyte chemoattractant protein-1 than SAT, whereas leptin levels were higher in SAT. Further from death, VAT and SAT behave differently whereas close to death, accelerated loss occurs in both depots. These differences are further characterized by differences in fatty acid composition and adipokine levels.

Is There a Role for Visceral Adiposity in Inducing Type 2 Diabetes Remission in Severely Obese Patients Following Biliopancreatic Diversion with Duodenal Switch Surgery?

Severe obesity is often characterized by ectopic fat deposition, which is related to development of type 2 diabetes (T2D). Thus, resolution of T2D may not be linearly associated with weight loss. The importance of ectopic fat reduction after bariatric surgery and T2D resolution is uncertain. The aim of this pilot study is to compare body composition and body fat distribution in severely obese patients with or without T2D after biliopancreatic diversion with duodenal switch (BPD-DS) surgery in relation to diabetes resolution. Sixty-two severely obese patients were evaluated at baseline, 6, and 12months. Of these, 40 patients underwent BPD-DS surgery. Anthropometric measurements and abdominal and mid-thigh computed tomography scans were performed at each visit. Before BPD-DS surgery, obese patients with T2D had higher weight as well as greater ectopic fat deposition in the abdomen and mid-thigh level than obese patients without T2D (p < 0.05). Resolution of T2D was 65 and 90% at 6 and 12months, respectively. No difference in body composition changes at 6 and 12months could be found between patients without T2D, patients with T2D resolution, and patients who remained T2D. Resolution of T2D was associated with a greater absolute loss of visceral adipose tissue (VAT) in comparison to patients without T2D (-1175 ± 570cm(3) vs. -729 ± 394cm(3) at 6months and -1647 ± 816cm(3) vs. -1103 ± 422cm(3) at 12months; all p ≤ 0.05). Ectopic fat mobilization, particularly the absolute loss of VAT, may play a major role in T2D resolution following BPD-DS surgery, regardless of the amount of weight loss.

Association of decrease in carbohydrate intake with reduction in abdominal fat during 3-month moderate low-carbohydrate diet among non-obese Japanese patients with type 2 diabetes

ObjectiveThe effectiveness of a moderate low-carbohydrate diet (M-LCD) has been demonstrated in terms of glycemic control, body weight and serum lipid profiles. We investigated the effect of a 3-monthM-LCD on visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), and examined an association between decrease in carbohydrate intake and reduction in abdominal fat among patients with Type 2 diabetes mellitus (T2DM). MethodsSeventy-six patients (45 men and 31 women; mean age±SD: 59.5±11.1years) with T2DM were instructed to follow an M-LCD for 3months. We assessed abdominal fat distribution using computed tomography and macronutrient intakes from 3-day dietary records at baseline and after 3months. ResultsThe patients complied well with the M-LCD – %carbohydrate: %fat: %protein at baseline and after 3months were 51:27:15 and 41:33:18 in men and 54:27:16 and 42:37:19 in women, respectively. VAT and SAT significantly decreased during the 3months (P for time <0.001 for both). Decrease in carbohydrate intake (g/day) and %carbohydrate were correlated with decrease (%) in VAT. The correlations were significant in men (Spearman correlation coefficient r=0.469 for carbohydrate intake (g) and r=0.402 for %carbohydrate) but not in women (r=0.269 and 0.278, respectively). The correlations in men remained significant in multiple regression analysis adjusted for age and changes in energy intake. ConclusionsIn men, decrease in carbohydrate intake was significantly correlated with VAT loss during a 3-monthM-LCD, independently of reduction in energy intake.

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...

Accelerated muscle and adipose tissue loss may predict survival in pancreatic cancer patients: the relationship with diabetes and anaemia

Weight loss leading to cachexia is associated with poor treatment response and reduced survival in pancreatic cancer patients. We aim to identify indicators that allow for early detection that will advance our understanding of cachexia and will support targeted anti-cachexia therapies. A total of fifty pancreatic cancer patients were analysed for skeletal muscle and visceral adipose tissue (VAT) changes using computed tomography (CT) scans. These changes were related to physical characteristics, secondary disease states and treatment parameters. Overall, patients lost 1.72 (SD 3.29) kg of muscle and 1.04 (SD 1.08) kg of VAT during the disease trajectory (413 (SD 213) d). After sorting patients into tertiles by rate of VAT and muscle loss, patients losing VAT at > -0.40 kg/100 d had poorer survival outcomes compared with patients with < -0.10 kg/100 d of VAT loss (P= 0.020). Patients presenting with diabetes at diagnosis demonstrated significantly more and accelerated VAT loss compared with non-diabetic patients. In contrast, patients who were anaemic at the first CT scan lost significantly more muscle tissue and at accelerated rates compared with non-anaemic patients. Accelerated rates of VAT loss are associated with reduced survival. Identifying associated features of cachexia, such as diabetes and anaemia, is essential for the early detection of cachexia and may facilitate the attenuation of complications associated with cachexia.

Relationships Among Body Mass Index, Longitudinal Body Composition Alterations, and Survival in Patients With Locally Advanced Pancreatic Cancer Receiving Chemoradiation: A Pilot Study

ContextIn pancreatic cancer, the presence of obesity or weight loss is associated with higher mortality. ObjectivesTo explore the relationships among body mass index, longitudinal body composition alterations, and clinical outcomes in pancreatic cancer patients. MethodsRecords of 41 patients with inoperable locally advanced pancreatic cancer who participated in a prospective chemoradiation study were reviewed. Body composition was analyzed from two sets of computed tomography images obtained before and after radiation treatment (median interval 104 days). ResultsMedian age was 59 years and 56% of patients were female. Twenty-four (59%) patients were either overweight (22%) or obese (37%). Sarcopenia was present in 26 (63%) patients. At follow-up, weight loss was experienced by 33 (81%) patients. The median losses (%) before and after treatment were weight 5% (P<0.001), skeletal muscle (SKM) 4% (P=0.003), visceral adipose tissue (VAT) 13% (P<0.001), and subcutaneous adipose tissue 11% (P=0.002). SKM loss positively correlated with age (P=0.03), baseline body mass index (P<0.001), and VAT (P=0.04) index. Obese patients experienced higher losses in weight (P=0.009), SKM (P=0.02), and VAT (P=0.02). Median survival was 12 months. In univariate analysis, age, baseline obesity, sarcopenic obesity, and losses (%) in weight, SKM, and VAT were associated with worse survival. In multivariate analysis, only age (hazard ratio=1.033, P=0.04) and higher VAT loss (hazard ratio=2.6 and P=0.03) remained significant. ConclusionOur preliminary findings suggest that obese patients experience higher losses in weight, SKM, and VAT, which may contribute to poorer survival in these patients.

Effects of diet macronutrient composition on visceral adiposity during weight maintenance

Macronutrient composition of the diet may affect propensity to distribute fat centripetally, and thus influence risk of cardiovascular disease and type 2 diabetes. The objective of this study was to determine if consumption of a relatively low glycemic load (GL) diet would result in preferential loss of visceral adipose tissue under eucaloric conditions and to determine if these effects were gender‐specific. Participants were 69 healthy overweight men and women. Body composition was assessed by DXA and fat distribution by CT scan at baseline and after 8 weeks of a eucaloric diet intervention. Participants were provided all food for the intervention period, and randomized to either a low GL diet (&lt;45 points per 1000 kcal; n=40) or high GL diet (&gt;75 points per 1000 kcal, n=29). Results indicated women in the low GL group lost 15.1% (P=0.001) IAAT, while women in the high GL diet group lost 1% (P=0.82), men in the high GL diet group gained 4.2% (P=0.55), and men in the low GL diet group lost 4.3% (P=0.44). Women on the low GL diet had a significant reduction in SHBG (p=0.01) after 8 wks and loss of IAAT was significantly associated with 8‐wk estradiol (p=0.02). Consumption of a relatively low GL diet may induce reduction in IAAT independent of weight change, specifically among women. These affects may be mediated by diet‐induced alterations in the sex hormone environment.

Abstract P198: Does Cetp Mass Contribute to the Response of LDL Particle Size to a 1-yr Lifestyle Modification Program in Viscerally Obese Dyslipidemic Men?

Numerous studies have demonstrated improvements in lipid and lipoprotein levels with endurance exercise training and weight loss. However, less is known about the contribution of the enzyme cholesteryl ester transfer protein (CETP) to the response of lipoprotein levels to a physical activity/healthy eating lifestyle modification program. Objective: To examine the effect of a 1-year lifestyle modification program inducing loss of visceral adipose tissue on plasma CETP mass in abdominally obese dyslipidemic men. Methods: Plasma CETP mass concentration was measured by ELISA at baseline and after a 1-year lifestyle modification program in 116 abdominally obese men aged 30 to 65 years without diabetes. Visceral adiposity was assessed by computed tomography and a complete fasting plasma lipoprotein-lipid profile was also obtained at baseline and after the intervention. Results: After 1 year, no significant changes were observed in CETP mass (1.91±0.45 vs.1.93±0.49 mg/l, ns). However, both HDL (81.7±2.1 vs. 83.8±3.1 Å, p&lt;0.0001) and LDL (252.1±3.9 vs. 253.6±3.7 Å, p&lt;0.0001) particle sizes assessed by gradient gel electrophoresis were increased. Whereas no significant correlation between change in HDL size and CETP mass was observed, change in LDL size was significantly correlated with change in CETP mass (r=−0.30, p=0.001). We also divided men into two groups: men who showed no change or an increase in their CETP mass (ΔCETP≥0) and men who decreased their CETP mass (ΔCETP&lt;0). Men who reduced their CETP mass after one year showed a greater increase in LDL size (Δ 2.37±3.18 vs.0.32±3.04 Å, p=0.0006) and a greater decrease in triglyceride levels (Δ-0.70±0.86 vs. −0.34±0.80 mmol/l, p=0.03) than men who showed no change or an increase in CETP mass. A Multivariate analysis revealed that 19% of the variance in the response of LDL size could be attributed to changes in triglyceride levels (15%) and in CETP mass (4%) (p=0.02). Conclusion: Whereas no significant change in CETP mass was observed, our results showed that individual variation in the response of CETP mass contributed to the response of LDL particle size to a 1-yr lifestyle modification program in viscerally obese dyslipidemic men.