Proteomics, dietary intake, and changes in cardiometabolic health within a behavioral weight-loss intervention: A pilot study.

OBJECTIVE: Identifying associations among circulating proteins, dietary intakes, and clinically relevant indicators of cardiometabolic health during weight loss may elucidate biologically relevant pathways affected by diet, allowing for an incorporation of precision nutrition approaches when designing future interventions. This study hypothesized that plasma proteins would be associated with diet and cardiometabolic health indicators within a behavioral weight-loss intervention. METHODS: This secondary data analysis included participants (n = 20, mean [SD], age: 40.1 [9.5] years, BMI: 34.2 [4.0] kg/m2 ) who completed a 1-year behavioral weight-loss intervention. Cardiovascular disease-related plasma proteins, diet, and cardiometabolic health indicators were evaluated at baseline and 3 months. Associations were determined via linear regression and integrated networks created using Visualization Of LineAr Regression Elements (VOLARE). RESULTS: A total of 16 plasma proteins were associated with ≥1 diet or health indicator at baseline (p < 0.001); changes in 42 proteins were associated with changes in diet or health indicators from baseline to 3 months (p < 0.005). Baseline tumor necrosis factor receptor superfamily member 10C (TNFRSF10C) was associated with intakes of dark green vegetables (r = -0.712), and fatty acid-binding protein 4 (FABP4) was associated with intakes of unsweetened coffee (r = -0.689). Changes in refined-grain intakes were associated with changes in scavenger receptor cysteine-rich type 1 protein M130 (CD163; r = 0.725), interleukin-1 receptor type 1 (IL1R-T1; r = 0.624), insulin (r = 0.656), and triglycerides (r = 0.648). CONCLUSIONS: Circulating cardiovascular disease-related proteins were associated with diet and cardiometabolic health indicators prior to and in response to weight loss.

Effect of sleep on weight loss and adherence to diet and physical activity recommendations during an 18-month behavioral weight loss intervention.

BACKGROUND/OBJECTIVES: To examine the association between indices of sleep quantity and quality with dietary adherence, physical activity adherence, and weight loss during a behavioral weight loss intervention. METHODS: Adults (n = 156) with overweight and obesity (40 ± 9 years, 84% female, BMI: 34.4 ± 4.2 kg/m2) participated in an 18-month behavioral weight loss intervention which prescribed a reduced calorie diet (1200-1800 kcal/d) and increased physical activity (300 min/wk). Body weight, indices of sleep (SenseWear armband; SWA), energy intake (EI, 3-day food records), and moderate-to-vigorous physical activity (SWA) were measured at baseline, 6, 12, and 18 months. Linear mixed effects models examined the association between sleep and weight change over time. Additional models were adjusted for covariates including age, BMI, sex, race, ethnicity, study completion, randomization, EI, and physical activity. Secondary analyses examined the association between sleep and adherence to diet and physical activity recommendations. RESULTS: Mean weight loss was 7.7 ± 5.4, 8.4 ± 7.9, and 7.1 ± 9.0 kg at 6, 12, and 18 months, respectively. Lower sleep efficiency, higher wake after sleep onset (WASO), more awakenings, and higher sleep onset latency (SOL) were significantly associated with attenuated weight loss (p < 0.05). Lower sleep efficiency, more awakenings, and higher SOL remained significantly associated with blunted weight loss after adjustment for covariates (p < 0.05). Later waketime, longer time in bed, longer sleep duration, higher WASO, more awakenings, and higher SOL were associated with lower odds of achieving ≥300 min/wk of moderate-to-vigorous physical activity, adjusted for covariates (FDR p < 0.05). CONCLUSIONS: Future studies should evaluate whether incorporating strategies to improve sleep health within a behavioral weight loss intervention leads to improved adherence to diet and physical activity recommendations and enhanced weight loss. CLINICAL TRIALS IDENTIFIER: NCT01985568.

Sex Differences in Adipose Tissue Function.

Regional adipose tissue distribution differs between men and women. Differences in the accumulation of adipose tissue as well as the regulation of secretion of a number of products from adipose tissue are under the control of sex steroids, which act through a wide variety of mechanisms, both direct and indirect, to tailor metabolism to the unique needs of each sex. A fuller understanding of sex-based differences in adipose tissue function may help with tailored strategies for disease prevention and treatment and provide insights into fundamental differences in the processes that regulate nutrient homeostasis and body weight.

Obesity.

The role of internists in evaluating obesity is to assess the burden of weight-related disease, mitigate secondary causes of weight gain (medications, sleep deprivation), and solicit patient motivation for weight loss. Internists should assess these factors and emphasize the importance of weight loss for the individual patient. All patients wishing to lose weight should be encouraged to monitor their diet and physical activity and should be referred to high-intensity behavioral programs. Some patients with obesity may also benefit from pharmacotherapy or bariatric surgery.

The Role of Weight Management in the Treatment of Adult Obstructive Sleep Apnea. An Official American Thoracic Society Clinical Practice Guideline.

BACKGROUND: Overweight/obesity is a common, reversible risk factor for obstructive sleep apnea severity (OSA). The purpose of this guideline is to provide evidence-based recommendations for the management of overweight/obesity in patients with OSA. METHODS: The Grading of Recommendations, Assessment, Development and Evaluation approach was used to evaluate the literature. Clinical recommendations were formulated by a panel of pulmonary, sleep medicine, weight management, and behavioral science specialists. RESULTS: Behavioral, pharmacological, and surgical treatments promote weight loss and can reduce OSA severity, reverse common comorbidities, and improve quality of life, although published studies have methodological limitations. After considering the quality of evidence, feasibility, and acceptability of these interventions, the panel made a strong recommendation that patients with OSA who are overweight or obese be treated with comprehensive lifestyle intervention consisting of 1) a reduced-calorie diet, 2) exercise or increased physical activity, and 3) behavioral guidance. Conditional recommendations were made regarding reduced-calorie diet and exercise/increased physical activity as separate management tools. Pharmacological therapy and bariatric surgery are appropriate for selected patients who require further assistance with weight loss. CONCLUSIONS: Weight-loss interventions, especially comprehensive lifestyle interventions, are associated with improvements in OSA severity, cardiometabolic comorbidities, and quality of life. The American Thoracic Society recommends that clinicians regularly assess weight and incorporate weight management strategies that are tailored to individual patient preferences into the routine treatment of adult patients with OSA who are overweight or obese.

Region-specific effects of oestradiol on adipose-derived stem cell differentiation in post-menopausal women.

The goal of this study was to determine the effect of acute transdermal 17ß-oestradiol (E2 ) on the adipogenic potential of subcutaneous adipose-derived stem cells (ASC) in post-menopausal women. Post-menopausal women (n = 11; mean age 57 ± 4.5 years) were treated for 2 weeks, in a randomized, cross-over design, with transdermal E2 (0.15 mg) or placebo patches. Biopsies of abdominal (AB) and femoral (FEM) subcutaneous adipose tissue (SAT) were obtained after each treatment and mature adipocytes were analysed for cell size and ASC for their capacity for proliferation (growth rate), differentiation (triglyceride accumulation) and susceptibility to tumour necrosis factor alpha-induced apoptosis. Gene expression of oestrogen receptors α and ß (ESR1 and ESR2), perilipin 1 and hormone-sensitive lipase (HSL), was also assessed. In FEM SAT, but not AB SAT, 2 weeks of E2 significantly (P = 0.03) increased ASC differentiation and whole SAT HSL mRNA expression (P = 0.03) compared to placebo. These changes were not associated with mRNA expression of oestrogen receptors α and ß, but HSL expression was significantly increased in FEM SAT with transdermal E2 treatment. Adipose-derived stem cells proliferation and apoptosis did not change in either SAT depot after E2 compared with placebo. Short-term E2 appeared to increase the adipogenic potential of FEM, but not AB, SAT in post-menopausal women with possible implications for metabolic disease. Future studies are needed to determine longer term impact of E2 on regional SAT accumulation in the context of positive energy imbalance.

Postprandial triglycerides and adipose tissue storage of dietary fatty acids: impact of menopause and estradiol.

OBJECTIVES: Postprandial lipemia worsens after menopause, but the mechanism remains unknown. The hypothesized menopause-related postprandial lipemia would be (1) associated with reduced storage of dietary fatty acids (FA) as triglyceride (TG) in subcutaneous adipose tissue (SAT) and (2) improved by short-term estradiol (E2 ). METHODS: Twenty-three pre- (mean ± SD: 42 ± 4 years) and 22 postmenopausal (55 ± 4 years) women with similar total adiposity were studied. A subset of postmenopausal women (n = 12) were studied following 2 weeks of E2 (0.15 mg) and matching placebo in a random, cross-over design. A liquid meal containing (14) C-oleic acid traced appearance of dietary FA in: serum (postprandial TG), breath (oxidation), and abdominal and femoral SAT (TG storage). RESULTS: Compared to premenopausal women, healthy, lean, postmenopausal women had increased postprandial glucose and insulin and trend for higher TG but had similar dietary FA oxidation and storage. Adipocytes were larger in post- compared to premenopausal women, particularly in femoral SAT. Short-term E2 reduced postprandial TG and insulin but had no effect on oxidation or storage of dietary FA. E2 increased the proportion of small adipocytes in femoral (but not abdominal) SAT. CONCLUSIONS: Short-term E2 attenuated menopause-related increases in postprandial TG and increased femoral adipocyte hyperplasia but not through increased net storage of dietary FA.

Eating-related behaviors and appetite during energy imbalance in obese-prone and obese-resistant individuals.

While the majority of Americans are now overweight, some individuals maintain their weight with minimal effort. This study investigated behavioral differences between 58 individuals recruited as either obese-resistant (OR) or obese-prone (OP) based on self-identification, BMI, and personal/family weight history. Subjects were studied during Eucaloric (EU), Overfed (OF), and Underfed (UF) phases which included a run-in diet, 1 day intervention diet, and a study day. At baseline, subjects completed the Three Factor Eating Questionnaire (TFEQ) and Power of Food Scale (PFS). On the study day, ratings of appetite, food appeal and desire, and food cravings were performed in response to a breakfast shake. OF resulted in reduced hunger and food desire while UF resulted in increased hunger and food appeal and desire. While hunger did not differ between groups, OP had higher scores for TFEQ measures (hunger, restraint and disinhibition), higher "hedonic hunger" as measured by the PFS, and greater food cravings and ratings of food appeal and desire. These results suggest that subjective hunger and desire for food change significantly after only one day of over- or underfeeding. Additionally, we found several behavioral differences between groups that are likely to promote weight gain over time in the OP.

Brown fat activity is not apparent in subjects with HIV lipodystrophy and increased resting energy expenditure.

The HIV lipodystrophy (LD) syndrome is associated with increased resting energy expenditure (REE), but the basis of this hypermetabolism has not been determined. The objective of this pilot study was to determine if brown fat is activated in subjects with HIV LD and increased REE. In this descriptive study of four subjects with HIV LD and marked hypermetabolism, REE was measured by indirect calorimetry and brown fat activity was determined by (18)F-fluorodeoxyglucose (FDG) positron-emission tomography (PET) combined with anatomic computed tomography (CT). Brown fat activity was not apparent in any subject with HIV LD and resting hypermetabolism. Therefore, brown fat activation is unlikely to be the principal cause of the increased REE associated with the HIV LD syndrome. Evidence of adaptive thermogenesis has been demonstrated in this syndrome, but this study suggests that tissues other than brown adipose tissue (BAT) are responsible. Further understanding of the chronic hypermetabolism associated with HIV LD could provide new insights into the regulation of energy balance.

Update on obesity.

Endocrinologists have unique skills in evaluating and caring for patients with metabolic diseases. As such, they have a special role to play within the organizations in which they work as leaders in the approach to managing obese patients. Recent epidemiological data demonstrate that the prevalence of obesity is beginning to plateau. However, the rate of severe obesity in adults and the prevalence of overweight among children continue to grow, suggesting that in the future there will be an increasing burden of obesity-related illnesses. A number of recent studies have identified a number of novel mechanisms that predispose to obesity including several newly identified genes, the role of intestinal microflora, and even social networks. The selection of treatment for obese patients remains a complex issue. Recent studies demonstrate that a range of dietary approaches including the Atkins diet can provide modest weight loss, although the key feature appears to be adherence in the dietary strategy. High levels of physical activity appear to be necessary to maintain a reduced state, although modest increases in activity improve fitness. Although the new understanding of biology of weight regulation has provided a wide range of potential drug targets, available pharmacotherapy options remain limited although a number of potential targets show promise. Recent data provides the most enthusiasm for surgical treatment of obesity. Several recent studies demonstrate a reduction in mortality and dramatic benefits in diabetes in obese patients treated surgically. Questions remain as to the best surgical approach and the cost effectiveness. Research advances in obesity continue to move at a rapid pace and raise hopes for more effective management strategies in the future.

Clinic-based support to help overweight patients with type 2 diabetes increase physical activity and lose weight.

BACKGROUND: Our objective was to test the effect of physicians providing brief health lifestyle counseling to patients with type 2 diabetes mellitus during usual care visits. METHODS: We conducted a randomized controlled trial of a 12-month intervention at 2 large community health centers, enrolling 310 patients with a body mass index (calculated as weight in kilograms divided by height in meters squared) of 25 or greater. In the intervention group, self-management goals for nutrition and physical activity were set using a tailored computer program. Goals were then reviewed at each clinic visit by physicians. The control group received only printed health education materials. The main outcome measures included change in physical activity and body weight. RESULTS: In the intervention group, recommended levels of physical activity increased from 26% at baseline to 53% at 12 months (P< .001) compared with controls (30% to 37%; P= .27), and 32% of patients in the intervention group lost 6 or more pounds at 12 months compared with 18.9% of controls (odds ratio, 2.2; P= .006). CONCLUSION: A brief intervention to increase the dialogue between patients and health care providers about behavioral goals can lead to increased physical activity and weight loss.

The effects of short-term overfeeding on insulin action in lean and reduced-obese individuals.

Insulin resistance is clearly associated with obesity. However, the role of excess energy intake per se as opposed to increased fat mass in the development of insulin resistance has not been clearly defined. It may be that the nutrient load provided by short-term overfeeding is sufficient to induce measurable changes in insulin action in skeletal muscle and the liver. We examined the effects of 3 days of overfeeding on insulin action and glucose kinetics in 13 lean (body mass index, 20.9 +/- 2.4 kg/m(2); 6 men, 7 women) and 9 reduced-obese (RO) (body mass index, 29.1 +/- 2.2 kg/m(2); 4 men, 5 women) individuals. A two-step euglycemic hyperinsulinemic clamp study (5 and 40 mU m(-2) min(-1)) with a primed, constant infusion of [6,6-(2)H(2)]glucose was performed after 3 days of a weight-maintenance diet and again after 3 days of overfeeding by 50% (50% carbohydrate, 30% fat, 20% protein). At baseline, lean individuals were more insulin sensitive, as measured by glucose infusion rate, than RO individuals (12.08 +/- 0.8 vs 7.62 +/- 1.0 mg x kg(-1) x min(-1), P < .01) with lean women being more insulin sensitive than lean men (P < .01). Overfeeding resulted in a reduction in glucose infusion rate in lean women (13.37 +/- 1.3 to 11.42 +/- 1.0 mg x kg(-1) x min(-1), P < .05), but no change was noted in lean men or RO individuals. Basal and insulin-stimulated glucose disposal remained unchanged with overfeeding in all groups. Low-dose insulin suppression of endogenous glucose production was impaired after overfeeding in lean women (euenergetic, 1.92 +/- 0.36 to 0.36 +/- 0.16 mg x kg(-1) x min(-1); overfeeding: 2.13 +/- 0.17 to 0.86 +/- 0.12 mg x kg(-1) x min(-1); P = .04) but remained unchanged in the other groups. These findings demonstrate that insulin action is reduced in lean, obese-resistant women after short-term overfeeding primarily because of an inhibition of insulin-mediated suppression of endogenous glucose production, whereas short-term overfeeding does not appear to effect insulin action in lean men and RO individuals. This response may be indirectly involved in the ability of lean women to maintain weight in the face of an obesigenic environment.

Relationship between waist circumference, body mass index, and medical care costs.

OBJECTIVE: Excessive visceral adiposity as measured by anthropomorphic measures may be more closely associated with adverse health consequences than body weight or body mass index (BMI), the more commonly obtained clinical measures. Waist circumference (WC) provides information about regional adiposity and may correlate with health care costs better than body weight or BMI. RESEARCH METHODS AND PROCEDURES: A total of 424 men (37%) and women (63%) were identified as they were seen in outpatient medical clinics at Denver Health, an integrated health care system serving a largely indigent population. Height, weight, and WC were measured by one examiner. Information on outpatient, laboratory, pharmacy, inpatient, and total charges attributable to each subject for the preceding year were obtained from computerized databases. Data on health care charges were divided into quartiles based on WC and BMI. RESULTS: Total annual health care charges were significantly greater in the highest WC quartile (WC < 83.3 cm: $6062 +/- $784; 83.3 to 93.5 cm: $5968 +/- $812; 93.7 to 103.5 cm: $6369 +/- $1015; >103.5 cm: $8699 +/- $1092; p = 0.047). Those with a WC >103.5 cm generated 85% more inpatient charges than the group with a WC <83.3 cm. Although there was a positive trend, BMI was not found to significantly correlate with total health care charges in this population sample. DISCUSSION: These results suggest that abdominal adiposity as assessed by WC is associated with increased total health care charges and may be a better predictor of health care charges than the more widely used BMI.