Obesity-related Morbidity Research Articles

Epidemiology of Obesity and Pharmacologic Treatment Options.

Prevalence of obesity and its related morbidity have increased to alarming levels in adults and children in the United States and globally. Weight loss results in improvement of much of the obesity-related morbidity. Lifestyle changes such as dietary modifications, increased physical activity, and behavioral therapy form the crux of weight management. However, many individuals need additional assistance (pharmacologic or surgical) to initiate or sustain weight loss. Pharmacologic therapy consists of a number of agents that work by decreasing appetite, gastric emptying, or nutrient absorption or by increasing satiety. Five classes of drug are currently approved for adults, including sympathomimetics (with and without an antiepileptic agent topiramate), gastrointestinal lipase inhibitors, serotonin agonists, glucagon-like peptide 1 agonists, and antidepressant/opioid antagonist combination. Pharmacologic options for children with obesity are minimal (lipase inhibitor orlistat is the only approved medication for children aged >12 years); however, all adult medications are approved by the Food and Drug Administration for children aged >16 years old. While side effect profiles of these medications are far superior to older medications, their use is limited by lack of long-term cardiovascular safety data, costs of medications and variable insurance coverages, and the need for continued usage for sustainable benefits. Weight loss medications may induce complacence, on part of both the patient and the provider, regarding lifestyle modifications, without which the drug therapy is almost certain to be of minimal benefit. Several novel drugs are in the pipeline targeting brown fat, energy expenditure, appetite suppression, and satiety.

The kynurenine:tryptophan ratio as a predictor of incident type 2 diabetes mellitus in individuals with coronary artery disease

Aims/hypothesisThe tryptophan metabolite kynurenine has potent immune modulatory and vasoactive properties. Experimental data implicate kynurenine in obesity-related morbidities. Epidemiological studies are, however, sparse. We evaluated associations of the plasma and urine kynurenine:tryptophan ratio (KTR) to incident type 2 diabetes.MethodsWe followed 2519 individuals with coronary artery disease (CAD; 73.1% men) without diabetes at baseline for a median of 7.6 years, during which 173 (6.9%) new incidences of type 2 diabetes were identified. Multivariate Cox regression analyses were applied to investigate the prospective relationships of plasma and urine KTR with new onset type 2 diabetes.ResultsAt inclusion, mean (SD) age was 61.3 (10.4) years, BMI was 25.9 (3.71) kg/m2 and median (interquartile range) HbA1c was 5.6% (5.0%–6.0%) (38 [31–42] mmol/mol). Plasma KTR was not significantly related to type 2 diabetes risk. By contrast, urine KTR showed a strong positive association. Comparing quartile 4 with quartile 1, the HRs (95% CIs) were 2.59 (1.56, 4.30) and 2.35 (1.39, 3.96) in the age- and sex-adjusted and multivariate models, respectively.Conclusions/interpretationUrine KTR is a strong predictor of incident type 2 diabetes in individuals with CAD. Potential clinical implications and possible pathogenic roles of renal kynurenine excretion in type 2 diabetes development should be further elucidated.

Twenty-year progression of body mass index in a county-wide cohort of people with schizophrenia and bipolar disorder identified at their first episode of psychosis.

There is an increased prevalence of obesity in schizophrenia and bipolar disorder, leading to a disproportionate risk of adverse health conditions. Prospective, long-term weight gain data, however, are scarce. We analyzed data from the Suffolk County Mental Health Project cohort of consecutive first admissions with psychosis recruited from September 1989 to December 1995 and subsequently followed for 20years, focusing on people with schizophrenia (n=146) and bipolar disorder (n=87). The time course of weight gain was examined using a 2 (group)×5 (time) mixed-model repeated measures ANOVA, and body mass index (BMI) scores at the first (6months) and second (2years) assessments were compared to examine whether early overweight predicted later obesity. There was a statistically significant effect of time (F(1,210)=68.06, P<.001) and diagnosis (F(1,210)=29.18, P<.001) on BMI, but not the interaction of time×diagnosis (F(1,210)=0.88, P=.48). Most participants had normal BMIs at the first two assessments. Early overweight was a predictor of eventual obesity for both groups. At the 20-year follow-ups, approximately 50% of the bipolar and 62% of the schizophrenia sample were obese, with a greater prevalence of obesity in schizophrenia at each assessment (all P<.02), except for years 4 (P=.12) and 20 (P=.27). Nearly two-thirds of the participants with schizophrenia and over half of those with bipolar disorder were obese 20years after first hospitalization for psychosis, considerably higher than the rate for adults in New York State (27%). Early intervention may be required to prevent long-term consequences of obesity-related morbidity and mortality.

ASK1 (MAP3K5) is transcriptionally upregulated by E2F1 in adipose tissue in obesity, molecularly defining a human dys-metabolic obese phenotype

ObjectiveObesity variably disrupts human health, but molecular-based patients' health-risk stratification is limited. Adipose tissue (AT) stresses may link obesity with metabolic dysfunction, but how they signal in humans remains poorly-characterized. We hypothesized that a transcriptional AT stress-signaling cascade involving E2F1 and ASK1 (MAP3K5) molecularly defines high-risk obese subtype. MethodsASK1 expression in human AT biopsies was determined by real-time PCR analysis, and chromatin immunoprecipitation (ChIP) adopted to AT explants was used to evaluate the binding of E2F1 to the ASK1 promoter. Dual luciferase assay was used to measure ASK1 promoter activity in HEK293 cells. Effects of E2F1 knockout/knockdown in adipocytes was assessed utilizing mouse-embryonal-fibroblasts (MEF)-derived adipocyte-like cells from WT and E2F1−/− mice and by siRNA, respectively. ASK1 depletion in adipocytes was studied in MEF-derived adipocyte-like cells from WT and adipose tissue-specific ASK1 knockout mice (ASK1-ATKO). ResultsHuman visceral-AT ASK1 mRNA (N = 436) was associated with parameters of obesity-related cardio-metabolic morbidity. Adjustment for E2F1 expression attenuated the association of ASK1 with fasting glucose, insulin resistance, circulating IL-6, and lipids (triglycerides, HDL-cholesterol), even after adjusting for BMI. Chromatin-immunoprecipitation in human-AT explants revealed BMI-associated increased occupancy of the ASK1 promoter by E2F1 (r2 = 0.847, p < 0.01). In adipocytes, siRNA-mediated E2F1-knockdown, and MEF-derived adipocytes of E2F1-knockout mice, demonstrated decreased ASK1 expression and signaling to JNK. Mutation/truncation of an E2F1 binding site in hASK1 promoter decreased E2F1-induced ASK1 promoter activity, whereas E2F1-mediated sensitization of ASK1 promoter to further activation by TNFα was inhibited by JNK-inhibitor. Finally, MEF-derived adipocytes from adipocyte-specific ASK1-knockout mice exhibited lower leptin and higher adiponectin expression and secretion, and resistance to the effects of TNFα. ConclusionsAT E2F1 –ASK1 molecularly defines a metabolically-detrimental obese sub-phenotype. Functionally, it may negatively affect AT endocrine function, linking AT stress to whole-body metabolic dysfunction.

Associations between gender and obesity among adults psychiatric outpatients in the town of Gabes (Tunisia)

BackgroundPatients with severe mental illness (SMI) suffer from two to three times higher rates of obesity, and this has translated into much higher rates of obesity-related morbidity and premature mortality in this population.AimsMeasuring the frequency of obesity and its associations with gender, and others socio-demographics factors among 115 adults psychiatric outpatients.MethodsA cross-sectional study, was conducted to assess frequency of obesity among 115 adults attending public mental health department in the regional hospital of Gabes (south of Tunisia). For the diagnosis of mental disorders, we used the diagnostic and statistical manual of mental disorders (DSM-V). Obesity was estimated by body mass index (BMI). This index is defined as the ratio of weight (kg) to squared size (m2). Overweight is defined as a BMI between 25 and 29.9 kg/m2 and obesity by a BMI ≥30 kg/m2. BMI was measured directly and other information was gathered by interview.ResultsThe mean BMI was 25. In our patients, 40.9% were overweight, 49.6% (n = 57) were obese including 8.7% (n = 10) who were morbidly obese. Obesity was significantly more frequent in women (63.8% vs 39.7%, P = 0.009), living in a couple (60.9% vs 42%, P = 0.03) and having a medium or high socioeconomic level (53.3% vs 30.4%, P = 0.03). There were no differences between obese and non-obese regarding age, level of education and professional status.ConclusionThe high prevalence of obesity among women suggests that targeted approaches are needed to promote optimal physical health in this population.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Mortality, hospital days and treatment costs of current and reduced sugar consumption in Israel

BackgroundConsumption of sugar causes tooth decay, overweight and obesity related morbidities. This paper in response to the Minister of Health’s request, provides estimates of the mortality, morbidity and health care costs attributable to sugar consumption in Israel along with the effects of reducing sugar consumption.MethodsGender specific relative risks of many diseases from overweight (25 < =BMI < 30) and obesity (BMI > =30) were applied to the national gender specific prevalence rates of overweight and obesity in order to calculate the population attributable fraction (PAF) from overweight and obesity. National expenditure on these related diseases was calculated by applying disease-specific data from a recent Canadian study to estimates of disease specific general hospital expenditures in Israel. Disease specific costs attributable to overweight and obesity were estimated from the product of these expenditures and PAF. In addition national costs of treating caries in persons under 18 years of age from sugar were calculated. Similar calculations were made to estimate the burden from sugar in terms of mortality and hospital utilisation. A recent UK modelling study was used to estimate the effect of a national program to reduce calorific consumption of sugar from 12.45 to 10% in 5 years.ResultsConditions associated with overweight or obesity accounted annually for 6402 deaths (95% CI 3296–8760) and 268,009 hospital days. Dental costs attributable to sugar consumption were 264 million NIS. In total, obesity, overweight and sugar consumption accounted for 2449 million in direct treatment costs (0.21% of GDP), rising to 4027 million (0.35% of GDP) when indirect costs were included. A national program of reducing energy from sugar consumption from 12.45 to 10% over 5 years is considered have a very feasible short-term goal. Even if the program does not impose taxes on sugar consumption, this would save 778 million NIS as well as 1184 lives.ConclusionSugar consumption causes a huge monetary and mortality burden. Estimates of potential decreases in this burden justify the current prioritisation given by the health minister of creating and implementing a national program to reduce sugar consumption, which is likely to be cost-saving (ie: averted treatment costs will exceed intervention costs).

Laparoscopic sleeve gastrectomy: gateway to kidney transplantation

BackgroundThe prevalence of obesity and obesity-related morbidity in end-stage renal disease patients is rising. Although it is established that obesity does not abrogate the transplant benefit with respect to lower long-term mortality and cardiovascular risk, it is associated with increased graft failure, delayed graft function, surgical complications, prolonged hospital stay, and costs. ObjectivesTo examine the safety and efficacy of LSG (laparoscopic sleeve gastrectomy) in renal transplant candidates and evaluate transplant outcomes. SettingSingle-center prospective nonrandomized trial MethodsWe here report on a prospective single-center trial establishing a 2-step approach for obese renal transplant candidates. Patients with end-stage renal disease and a BMI (body mass index) of 35 kg/m2 or higher underwent laparoscopic sleeve gastrectomy. After reaching a BMI of<35 kg/m2, patients were waitlisted for kidney transplantation. Age, gender, body mass index (BMI), associated co-morbidities, cause of end-stage renal disease, surgical complications, and outcome after kidney transplantation (graft survival, incidence of delayed graft function, incidence of rejection, serum creatinine) were collected. ResultsLSG was performed in 8 renal transplant candidates with a mean BMI of 38.8 kg/m2 each. BMI dropped to below 35 kg/m2 within a median of 3 months. Percent excess body mass index loss (%EBMIL) was 62.7% at 1 year after LSG. Within 17 months (mean) after metabolic surgery, 7 patients underwent kidney transplantation. All transplants were successful with a serum creatinine of 1.9±.8 mg/dL at discharge and stable allograft function thereafter. Mean follow-up was 3.2±1.4 years; no patient was lost to follow-up. ConclusionLSG is safe and efficacious for treatment of obesity in renal transplant candidates. Rapid and sustained weight loss and subsequent waitlisting for kidney transplantation may reduce overall and in particular posttransplant patient morbidity.

Diet-induced weight loss improves not only cardiometabolic risk markers but also markers of vascular function: a randomized controlled trial in abdominally obese men

Background: Many trials assessing effects of dietary weight loss on vascular function have been performed without no–weight loss control groups and in individuals with obesity-related morbidities. Usually a limited set of vascular function markers has been investigated.Objective: The objective of this study was to examine effects of diet-induced weight loss on various vascular function markers and differences between normal-weight and abdominally obese men at baseline and after weight reduction.Design: Twenty-five healthy, normal-weight men (waist circumference: <94 cm) and 54 abdominally obese men (waist circumference: 102–110 cm) participated. Abdominally obese participants were randomly allocated to a dietary weight-loss or a no–weight loss control group. Individuals from the weight-loss group followed a calorie-restricted diet for 6 wk to obtain a waist circumference <102 cm followed by a weight-maintenance period of 2 wk. The control group maintained their habitual diet and physical activity levels. The primary outcome was the change in brachial artery flow-mediated vasodilation (FMD).Results: Compared with the control group, FMD did not change in the weight-loss group, but carotid-to-femoral pulse wave velocity tended to decrease by 0.5 m/s (P = 0.065). The retinal arteriolar caliber increased by 5 μm (P < 0.001) and the arteriolar-to-venular ratio by 0.02 (P < 0.01). Soluble endothelial selectin and soluble intercellular adhesion molecule concentrations decreased (P < 0.001). Also, total cholesterol, low–density lipoprotein cholesterol, triacylglycerol, glucose, insulin, C-peptide, homeostasis model assessment of insulin resistance, and blood pressure improved (P < 0.05 for all variables). Except for FMD, these markers differed at baseline between normal-weight and abdominally obese men but became comparable after weight loss.Conclusions: In abdominally obese men, dietary weight loss targeting a waist circumference of <102 cm improved retinal microvascular caliber, plasma biomarkers of microvascular endothelial function, and the more conventional cardiometabolic risk markers. Aortic stiffness tended to decrease, but FMD was not changed. This trial was registered at clinicaltrials.gov as NCT01675401.

Prevention of type 2 diabetes mellitus in women with previous gestational diabetes mellitus.

Gestational diabetes mellitus (GDM), defined as any degree of glucose intolerance with onset or first recognition during pregnancy, is characterized by underlying maternal defects in the β-cell response to insulin during pregnancy. Women with a previous history of GDM have a greater than 7-fold higher risk of developing postpartum diabetes compared with women without GDM. Various risk factors for postpartum diabetes have been identified, including maternal age, glucose levels in pregnancy, family history of diabetes, pre-pregnancy and postpartum body mass index, dietary patterns, physical activity, and breastfeeding. Genetic studies revealed that GDM shares common genetic variants with type 2 diabetes. A number of lifestyle interventional trials that aimed to ameliorate modifiable risk factors, including diet, exercise, and breastfeeding, succeeded in reducing the incidence of postpartum diabetes, weight retention, and other obesity-related morbidities. The present review summarizes the findings of previous studies on the incidence and risk factors of postpartum diabetes and discusses recent lifestyle interventional trials that attempted to prevent postpartum diabetes.

The Role of Sleeve Gastrectomy in Reducing Cardiovascular Risk.

Obesity is an independent cardiovascular risk factor and a catalyst of other cardiovascular risk factors, such as hypertension, dyslipidemia, type 2 diabetes mellitus (DM2) and metabolic syndrome. We analyzed cardiovascular risk in obese patients before and after sleeve gastrectomy (SG). To this end, we studied changes in body mass index (BMI), blood chemistry parameters that characterize the risk of atherosclerosis and instrumental parameters (objective markers of this risk), namely intima-media thickness (IMT) and flow-mediated dilation (FMD), the latter reflecting endothelial function. We also considered purely cardiac parameters-mitral annular plane systolic excursion (MAPSE) and tricuspid annular plane systolic excursion (TAPSE)-which describe cardiac risk more specifically than the ejection fraction. Alteration of one or more of these parameters determines an increase in cardiovascular morbidity and mortality. The results showed that weight loss, in patients undergoing SG, is accompanied by a reduced BMI and a marked improvement in blood chemistry, confirming what has already been shown in many other studies, but the most interesting finding was the effect of SG on the instrumental markers of atherosclerosis. In particular, carotid IMT was significantly reduced (p<0.001) and FMD significantly improved. MAPSE and TAPSE also improved significantly at both follow-up assessments (p<0.001). This study suggests that SG should be considered from a broader perspective, i.e. as a weight loss treatment that also improves obesity-related morbidity and mortality, benefitting both the patient and, in an economic sense, the society as a whole.

Perceived Weight Discrimination and 10-Year Risk of Allostatic Load Among US Adults.

Discrimination promotes multisystem physiological dysregulation termed allostatic load, which predicts morbidity and mortality. It remains unclear whether weight-related discrimination influences allostatic load. The aim of this study was to prospectively examine 10-year associations between weight discrimination, allostatic load, and its components among adults 25-75years in the Midlife Development in the US Biomarker Substudy. Participants with information on weight discrimination were analyzed (n=986). At both timepoints, participants self-reported the frequency of perceived weight discrimination across nine scenarios as "never/rarely" (scored as 0), "sometimes" (1), or "often" (2). The two scores were averaged and then dichotomized as "experienced" versus "not experienced" discrimination. High allostatic load was defined as having ≥3 out of 7 dysregulated systems (cardiovascular, sympathetic/parasympathetic nervous systems, hypothalamic pituitary axis, inflammatory, lipid/metabolic, and glucose metabolism), which collectively included 24 biomarkers. Relative risks (RR) were estimated from multivariate models adjusted for sociodemographic and health characteristics, other forms of discrimination, and BMI. Over 41% of the sample had obesity, and 6% reported weight discrimination at follow-up. In multivariable-adjusted analyses, individuals who experienced (versus did not experience) weight discrimination had twice the risk of high allostatic load (RR, 2.07; 95% CI, 1.21; 3.55 for baseline discrimination; 2.16, 95% CI, 1.39; 3.36 for long-term discrimination). Weight discrimination was associated with lipid/metabolic dysregulation (1.56; 95% CI 1.02, 2.40), glucose metabolism (1.99; 95% CI 1.34, 2.95), and inflammation (1.76; 95% CI 1.22, 2.54), but no other systems. Perceived weight discrimination doubles the 10-year risk of high allostatic load. Eliminating weight stigma may reduce physiological dysregulation, improving obesity-related morbidity and mortality.

SILAC-MS Based Characterization of LPS and Resveratrol Induced Changes in Adipocyte Proteomics - Resveratrol as Ameliorating Factor on LPS Induced Changes.

Adipose tissue inflammation is believed to play a pivotal role in the development obesity-related morbidities such as insulin resistance. However, it is not known how this (low-grade) inflammatory state develops. It has been proposed that the leakage of lipopolysaccharides (LPS), originating from the gut microbiota, through the gut epithelium could drive initiation of inflammation. To get a better understanding of which proteins and intracellular pathways are affected by LPS in adipocytes, we performed SILAC proteomic analysis and identified proteins that were altered in expression. Furthermore, we tested the anti-inflammatory compound resveratrol. A total of 927 proteins were quantified by the SILAC method and of these 57- and 64 were significantly up- and downregulated by LPS, respectively. Bioinformatic analysis (GO analysis) revealed that the upregulated proteins were especially involved in the pathways of respiratory electron transport chain and inflammation. The downregulated proteins were especially involved in protein glycosylation. One of the latter proteins, GALNT2, has previously been described to regulate the expression of liver lipases such as ANGPTL3 and apoC-III affecting lipid metabolism. Furthermore, LPS treatment reduced the protein levels of the insulin sensitizing adipokine, adiponectin, and proteins participating in the final steps of triglyceride- and cholesterol synthesis. Generally, resveratrol opposed the effect induced by LPS and, as such, functioning as an ameliorating factor in disease state. Using an unbiased proteomic approach, we present novel insight of how the proteome is altered in adipocytes in response to LPS as seen in obesity. We suggest that LPS partly exerts its detrimental effects by altering glycosylation processes of the cell, which is starting to emerge as important posttranscriptional regulators of protein expression. Furthermore, resveratrol could be a prime candidate in ameliorating dysfunctioning adipose tissue induced by inflammatory stimulation.

Comparing the risk of obesity-related morbidity and mortality in different ethnic groups

Comparing the risk of obesity-related morbidity and mortality in different ethnic groups

A Rat Model to Study the Effects of Diet-Induced Obesity on Radiation-Induced Mammary Carcinogenesis.

A detailed understanding of the relationship between radiation-induced breast cancer and obesity is needed for appropriate risk management and to prevent the development of a secondary cancer in patients who have been treated with radiation. Our goal was to develop an animal model to study the relationship by combining two existing Sprague-Dawley rat models of radiation-induced mammary carcinogenesis and diet-induced obesity. Female rats were fed a high-fat diet for 4 weeks and categorized as obesity prone or obesity resistant based on their body weight at 7 weeks of age, at which time the rats were irradiated with 4 Gy. Control rats were fed a standard diet and irradiated at the same time and in the same manner. All rats were maintained on their initial diets and assessed for palpable mammary cancers once a week for the next 30 weeks. The obesity-prone rats were heavier than those in the other groups. The obesity-prone rats were also younger than the other animals at the first detection of mammary carcinomas and their carcinoma weights were greater. A tendency toward higher insulin and leptin blood levels were observed in the obesity-prone rats compared to the other two groups. Blood angiotensin II levels were elevated in the obesity-prone and obesity-resistant rats. Genes related to translation and oxidative phosphorylation were upregulated in the carcinomas of obesity-prone rats. Expression profiles from human breast cancers were used to validate this animal model. As angiotensin is potentially an important factor in obesity-related morbidities and breast cancer, a second set of rats was fed in a similar manner, irradiated and then treated with an angiotensin-receptor blocker, losartan and candesartan. Neither blocker altered mammary carcinogenesis; analyses of losartan-treated animals indicated that expression of renin in the renal cortex and of Agtr1a (angiotensin II receptor, type 1) in cancer tissue was significantly upregulated, suggesting the presence of compensating mechanisms for blocking angiotensin-receptor signaling. Thus, obesity-related elevation of insulin and leptin blood levels and an increase in available energy may facilitate sustained protein synthesis in cancer cells, which is required for rapid cancer development.

“Are you eating healthy?” Nutrition discourse in Midwestern clinics for the underserved

ObjectiveTo investigate nutrition information provided and exchanged between patients and health providers in Midwestern clinics for underserved populations. MethodsForty-six clinic visits were observed to determine content and direction of nutrition information. In-depth data were collected with clinicians and clinic administrators regarding nutrition education provided to patients. ResultsAll patients were diagnosed with multiple obesity-related morbidities. Although women more often posed nutrition questions, few patients asked about dietary intake. Two-thirds of healthcare professionals initiated discussion about dietary intake; however, nutrition education was not provided regardless of clinician’s profession. ConclusionsPatients did not appear to link morbidity with diet. Providers did not share comprehensive nutrition knowledge during clinic visits. Dietitians, who specialize in nutrition education, rarely had access to patients. ImplicationsNutrition education during clinic visits is essential for reducing obesity rates. Nutrition students need clinic experience and could provide important patient education at low cost.

Abstract 45: Weight-related Discrimination Increases the Risk of Multi-system Physiological Dysregulation Among US Adults

Background: Obesity stigma is prevalent in the US. General discrimination has been shown to trigger a multi-system physiological dysregulation collectively referred to as allostatic load (AL), which independently predicts cardiovascular disease morbidity and mortality. However, it remains unclear whether weight-related discrimination influences AL. We aimed to examine the prospective associations between weight-related discrimination and AL and its individual systems among adults aged 25-75y participating in the national Midlife Development in the US (MIDUS) study over 10-years. Methods: Participants from the MIDUS Biomarker Substudy with self-reported information on weight discrimination were analyzed (n=986). At baseline and at 10-years follow-up, participants were asked about the frequency (never, rarely, sometimes, often) of perceived weight discrimination across nine scenarios. A continuous score assigned 1-2 points for discrimination experienced ‘sometimes’ or ‘often’, and an average of the two values at baseline and 10-years were used to estimate long-term discrimination. An AL score (range 0-7) represented the sum of the proportion of 24 dysregulated biomarkers or corresponding medication use within each of 7 systems (cardiovascular, sympathetic and parasympathetic nervous systems, hypothalamic pituitary axis, inflammatory, lipid and general metabolic activity, and glucose metabolism). Estimated relative risks (RR) were obtained from multivariable models adjusted for age, sex, race, education, household income, smoking, physical activity, race and sex discrimination, and baseline BMI. Results: Over 41% of the sample was obese, and 6% reported weight discrimination at 10-year follow-up. Both baseline and long-term perceived weight discrimination were associated with more than double the risk of high AL in final multivariable models (RR: 2.06, 95%CI: 1.20, 3.52 for baseline; 2.16, 95%CI: 1.39, 3.36 for long-term discrimination). The associations remained significant when the continuous weight discrimination score was assessed (β=0.11, p=0.01 for baseline; β=0.19, p=0.0001 for long-term discrimination). In sensitivity analyses, when BMI and waist:hip ratio were excluded from the AL definition, long-term weight discrimination remained associated with a 62% greater risk of high AL (1.62, 95%CI: 1.01, 2.62). Weight discrimination was significantly associated with metabolic/lipid dysregulation (1.56, 95%CI: 1.03, 2.41), glucose metabolism (1.99, 95% CI: 1.34, 2.96), and inflammatory parameters (1.76. 95% CI: 1.22, 2.54), but not with the other systems. Conclusions: Perceived weight discrimination doubles the risk of high AL. Public health campaigns and individual patient counseling that avoid obesity stigma may help improve obesity-related morbidity and mortality by modulating multi-system physiological dysregulation.

Iraq and Afghanistan veterans with PTSD participate less in VA's weight loss program than those without PTSD

BackgroundThree-quarters of Iraq and Afghanistan veterans enrolled in Veterans Health Administration (VHA) care are overweight or obese. The VHA MOVE!® weight management program can mitigate the risks of obesity-related morbidity. However, many Iraq and Afghanistan veterans experience barriers to VHA services, which may affect participation, especially among those with posttraumatic stress disorder (PTSD) and/or depression. Little is known about MOVE! engagement among recent veterans. We describe a retrospective evaluation of MOVE! participation among Iraq and Afghanistan veterans with and without mental health problems. MethodsAs part of a national VHA mental health evaluation study, we accessed VHA patient care databases to identify Iraq and Afghanistan veterans receiving care from 2008–2013 who had ≥1 MOVE! visit(s) and ≥1 weight measurements (N=24,899). We used logistic regression to determine whether mental health conditions were associated with having 12 visits/year (desirable dose of care), adjusting for demographic, health, and utilization factors. ResultsAmong Iraq and Afghanistan veterans enrolled in MOVE!, 4% had a desirable dose of participation. In adjusted models, desirable MOVE! participation was more likely among those without PTSD; those who were older, female, and unmarried; and those who had higher baseline weight, more medical comorbidities, no pain, psychotropic medication use, higher disability ratings, and more mental health visits. LimitationsWe used administrative ICD-9 codes. Sample only included veterans in VHA care. ConclusionsIraq and Afghanistan veterans, particularly those with PTSD, had low participation in VHA weight management programming. Correlates of MOVE! participation were identified, highlighting opportunities to tailor MOVE! to improve participation for these veterans.

Perceived Physician-informed Weight Status Predicts Accurate Weight Self-Perception and Weight Self-Regulation in Low-income, African American Women

Obese African American women under-appraise their body mass index (BMI) classification and report fewer weight loss attempts than women who accurately appraise their weight status. This cross-sectional study examined whether physician-informed weight status could predict weight self-perception and weight self-regulation strategies in obese women. A convenience sample of 118 low-income women completed a survey assessing demographic characteristics, comorbidities, weight self-perception, and weight self-regulation strategies. BMI was calculated during nurse triage. Binary logistic regression models were performed to test hypotheses. The odds of obese accurate appraisers having been informed about their weight status were six times greater than those of under-appraisers. The odds of those using an "approach" self-regulation strategy having been physician-informed were four times greater compared with those using an "avoidance" strategy. Physicians are uniquely positioned to influence accurate weight self-perception and adaptive weight self-regulation strategies in underserved women, reducing their risk for obesity-related morbidity.

Hypoxia Promotes the Inflammatory Response and Stemness Features in Visceral Fat Stem Cells From Obese Subjects.

Low-grade chronic inflammation is a salient feature of obesity and many associated disorders. This condition frequently occurs in central obesity and is connected to alterations of the visceral adipose tissue (AT) microenvironment. Understanding how obesity is related to inflammation may allow the development of therapeutics aimed at improving metabolic parameters in obese patients. To achieve this aim, we compared the features of two subpopulations of adipose-derived stem cells (ASC) isolated from both subcutaneous and visceral AT of obese patients with the features of two subpopulations of ASC from the same isolation sites of non-obese individuals. In particular, the behavior of ASC of obese versus non-obese subjects during hypoxia, which occurs in obese AT and is an inducer of the inflammatory response, was evaluated. Obesity deeply influenced ASC from visceral AT (obV-ASC); these cells appeared to exhibit clearly distinguishable morphology and ultrastructure as well as reduced proliferation, clonogenicity and expression of stemness, differentiation and inflammation-related genes. These cells also exhibited a deregulated response to hypoxia, which induced strong tissue-specific NF-kB activation and an NF-kB-mediated increase in inflammatory and fibrogenic responses. Moreover, obV-ASC, which showed a less stem-like phenotype, recovered stemness features after hypoxia. Our findings demonstrated the peculiar behavior of obV-ASC, their influence on the obese visceral AT microenvironment and the therapeutic potential of NF-kB inhibitors. These novel findings suggest that the deregulated hyper-responsiveness to hypoxic stimulus of ASC from visceral AT of obese subjects may contribute via paracrine mechanisms to low-grade chronic inflammation, which has been implicated in obesity-related morbidity.

Understanding Academic Clinicians' Decision Making for the Treatment of Childhood Obesity.

Although most clinicians agree that obesity is a major problem, treatment rates remain low. We conducted this discrete choice experiment (DCE) to understand academic clinicians' decisions in treating childhood obesity. A total of 198 academic pediatric surgeons, pediatricians, family physicians, and allied health professionals were recruited from 15 teaching hospitals across Canada to participate in this DCE. Participants completed 15 tasks choosing between three obesity treatment scenarios to identify the scenario in which they would most likely treat pediatric obesity. Latent class analysis revealed two classes with early intervention and late intervention preferences. Participants in the early intervention group (30%) were sensitive to variations in patient and family support. They would likely intervene if patients were obese, with normal lipid levels, were prediabetic, had high blood pressure, and when obesity was lifestyle associated. Late intervention clinicians (70%) were more likely to intervene if patients were morbidly obese, had abnormal lipid levels, required insulin for diabetes, had very high blood pressure, or when obesity impacted the patient's mental health. Simulations predicted that increasing colleague support for intervention, providing expert consultation, and mobilizing multidisciplinary support would increase the likelihood of treating pediatric obesity earlier from 16.1% to 81.5%. This DCE was implemented to understand the factors clinicians use in making decisions. Most academic clinicians choose to intervene late in the clinical course when more-severe obesity-related morbidities are present. Increased support from colleagues, expert consultation, and multidisciplinary support are likely to lead to earlier treatment of obesity among academic clinicians caring for children.