ß2-Adrenergic receptor agonists as a treatment for diabetic kidney disease.

We have previously shown that the long-acting ß2-adrenergic receptor (ß2-AR) agonist formoterol induced recovery from acute kidney injury in mice. To determine whether formoterol protected against diabetic nephropathy, the most common cause of end-stage kidney disease (ESKD), we used a high-fat diet (HFD), a murine type 2 diabetes model, and streptozotocin, a murine type 1 diabetes model. Following formoterol treatment, there was a marked recovery from and reversal of diabetic nephropathy in HFD mice compared with those treated with vehicle alone at the ultrastructural, histological, and functional levels. Similar results were seen after formoterol treatment in mice receiving streptozotocin. To investigate effects in humans, we performed a competing risk regression analysis with death as a competing risk to examine the association between Veterans with chronic kidney disease (CKD) and chronic obstructive pulmonary disease (COPD), who use ß2-AR agonists, and Veterans with CKD but no COPD, and progression to ESKD in a large national cohort of Veterans with stage 4 CKD between 2011 and 2013. Veterans were followed until 2016 or death. ESKD was defined as the initiation of dialysis and/or receipt of kidney transplant. We found that COPD was associated with a 25.6% reduction in progression from stage 4 CKD to ESKD compared with no COPD after adjusting for age, diabetes, sex, race-ethnicity, comorbidities, and medication use. Sensitivity analysis showed a 33.2% reduction in ESKD in Veterans with COPD taking long-acting formoterol and a 20.8% reduction in ESKD in Veterans taking other ß2-AR agonists compared with those with no COPD. These data indicate that ß2-AR agonists, especially formoterol, could be a treatment for diabetic nephropathy and perhaps other forms of CKD.NEW & NOTEWORTHY Diabetic nephropathy is the most common cause of ESKD. Formoterol, a long-acting ß2-adrenergic receptor (ß2-AR) agonist, reversed diabetic nephropathy in murine models of type 1 and 2 diabetes. In humans, there was an association with protection from progression of CKD in patients with COPD, by means of ß2-AR agonist intake, compared with those without COPD. These data indicate that ß2-AR agonists, especially formoterol, could be a new treatment for diabetic nephropathy and other forms of CKD.

The effects of resistance exercise on appetite sensations, appetite related hormones and energy intake in hormone receptor-positive breast cancer survivors.

Appetite is a determinant of dietary intake and is impacted by sex hormones, exercise, and body composition among individuals without chronic conditions. Whether appetite is altered by exercise in the context of estrogen suppression and cancer survivorship is unknown. This randomized cross-over study compared appetite and ad libitum energy intake (EI) after acute resistance exercise (REx) versus sedentary (SED) conditions and in relation to body composition and resting metabolic rate (RMR) in breast cancer survivors (BCS). Physically inactive premenopausal females with previous stage I-III estrogen receptor-positive breast cancer completed a single bout of REx or SED 35 minutes after a standardized breakfast meal. Appetite visual analog scales and hormones (total ghrelin and peptide-YY [PYY]) were measured before and 30, 90, 120, 150, and 180 minutes post-meal and expressed as area under the curve (AUC). Participants were offered a buffet-type meal 180 minutes after breakfast to assess ad libitum EI. Body composition (dual X-ray absorptiometry) and RMR (indirect calorimetry) were measured during a separate visit. Sixteen BCS were included (age: 46 ± 2 y, BMI: 24.9 ± 1.0 kg/m2). There were no differences in appetite ratings or EI between conditions. There were no differences in appetite hormone AUC, but REx resulted in lower ghrelin 120 (-85 ± 39 pg/mL, p = 0.031) and 180 (-114 ± 43 pg/mL, p = 0.018) minutes post-breakfast and higher PYY 90 (21 ± 10 pg/mL, p = 0.028) and 120 (14 ± 7 pg/mL, p = 0.041) minutes post-breakfast. Fat-free mass and RMR negatively correlated with hunger and prospective food consumption AUC after SED, but not REx. In sum, a single REx bout temporarily reduces orexigenic and increases anorexic appetite hormones, but not acute subjective appetite sensations or EI.

Obesity Management in Cardiometabolic Disease: State of the Art.

PURPOSE OF REVIEW: To summarize research from the last 5 years on the effects of weight loss treatments, including lifestyle changes, anti-obesity medications, and bariatric procedures on cardiovascular disease (CVD) risk factors and CVD outcomes in adults. RECENT FINDINGS: This narrative review includes and summarizes the contemporary evidence of the effects of these different weight loss approaches individually. A literature search was performed using the key words obesity, weight loss, CVD, cardiometabolic, and risk factors and included key clinical trials from the past 5 years. Obesity management through weight loss is associated with improvements in CVD risk factors, such as improved blood pressure, lipid profiles, and glycemic control, with greater weight loss leading to greater improvements in CVD risk factors. Bariatric surgery is associated with greater weight loss than the other procedures and treatments for obesity, and for this, and possibly for other reasons, it is associated with greater reductions in CVD outcomes and mortality. Obesity is an independent risk factor and modulator of other CVD risk factors, and thus, treatment of obesity should be an integral part of management strategies to reduce CVD risk. Future trials and real-world studies of longer duration are needed to inform providers and patients on how to individualize the approach to modifying risks of cardiometabolic disorders through obesity management.

Mindfulness-based group intervention in adolescents at-risk for excess weight gain: A randomized controlled pilot study.

OBJECTIVES: To assess feasibility/acceptability of a mindfulness-based approach to excess weight prevention in adolescents at-risk for excess weight gain. To pilot test efficacy of a mindfulness-based intervention for improving food reward sensitivity, stress-eating, executive function (EF), and BMI/adiposity. METHODS: A pilot randomized controlled trial was conducted with 12-17y adolescents at-risk for excess weight gain based on above-average weight (body mass index [BMI]≥70%ile) or parental history of obesity (BMI≥30 kg/m2). Adolescents were randomized to a mindfulness-based (n = 29) or health education control group (n = 25) that met for six weekly one-hour sessions. Feasibility/acceptability were determined from attendance and acceptability survey ratings. At baseline, six-week and six-month follow-up, adolescents' perceived stress was measured with the Perceived Stress Scale, food reward sensitivity with a behavioral task, stress-eating during a laboratory test meal, and EF with the parent-reported Behavior Rating Inventory of Executive Function and NIH Toolbox. At the same intervals, BMI indices and body fat by air displacement plethysmography were assessed in a fasted state. RESULTS: Median session attendance was 6:6 sessions in both conditions; program acceptability ratings were above-average. Compared to health education, adolescents in mindfulness had lower food reward sensitivity at six-months (Cohen's d = 0.64, p = .01). There were no between-condition differences in BMI (mindfulness vs. health educationΔsix-months 95%CI 0.20, 1.52 kg/m2 vs. 0.21, 1.62 kg/m2) or adiposity (-3.64, -0.61% vs. -4.31, -1.04%) changes. CONCLUSIONS: A mindfulness-based group intervention is feasible/acceptable among adolescents at-risk for excess weight. In this pilot sample, mindfulness and health education were equivocal for BMI/adiposity outcomes. Future trials with a larger, adequately-powered sample and longer-term follow-up are necessary to test efficacy of a mindfulness-based intervention for food reward sensitivity, stress-eating, EF, and stabilizing growth trajectories in youth at-risk for adult obesity.

Alirocumab in patients with heterozygous familial hypercholesterolaemia undergoing lipoprotein apheresis: the ODYSSEY ESCAPE trial.

AIM: To evaluate the effect of alirocumab on frequency of standard apheresis treatments [weekly or every 2 weeks (Q2W)] in heterozygous familial hypercholesterolaemia (HeFH). METHODS AND RESULTS: ODYSSEY ESCAPE (NCT02326220) was a double-blind study in 62 HeFH patients undergoing regular weekly or Q2W lipoprotein apheresis. Patients were randomly assigned (2:1, respectively) to receive alirocumab 150 mg (n = 41) or placebo (n = 21) Q2W subcutaneously for 18 weeks. From day 1 to week 6, apheresis rate was fixed according to the patient's established schedule; from weeks 7 to 18, apheresis rate was adjusted based on the patient's low-density lipoprotein cholesterol (LDL-C) response in a blinded fashion. Apheresis was not performed when the LDL-C value was ≥30% lower than the baseline (pre-apheresis) value. The primary efficacy endpoint was the rate of apheresis treatments over 12 weeks (weeks 7-18), standardized to number of planned treatments. In the alirocumab group the least square (LS) mean ± SE (95% confidence interval [CI]) per cent change in pre-apheresis LDL-C from baseline at week 6 was -53.7 ± 2.3 (-58.2 to - 49.2) compared with 1.6 ± 3.1 (-4.7 to 7.9) in the placebo group. The primary efficacy endpoint showed statistically significant benefit in favour of alirocumab (Hodges-Lehmann median estimate of treatment difference: 0.75; 95% CI 0.67-0.83; P < 0.0001). Therefore, alirocumab-treated patients had a 0.75 (75%) additional reduction in the standardized rate of apheresis treatments vs. placebo-treated patients. During this period, 63.4% of patients on alirocumab avoided all and 92.7% avoided at least half of the apheresis treatments. Adverse event rates were similar (75.6% of patients on alirocumab vs. 76.2% on placebo). CONCLUSIONS: Lipoprotein apheresis was discontinued in 63.4% of patients on alirocumab who were previously undergoing regular apheresis, and the rate was at least halved in 92.7% of patients. Alirocumab was generally safe and well tolerated.

Extremes of eating are associated with reduced neural taste discrimination.

OBJECTIVE: Eating disorders are severe psychiatric disorders of unknown etiology. Understanding how neuronal function affects food choices could help personalize treatment based on brain function. Here we wanted to determine whether disordered eating behavior is associated with alterations in the primary taste cortex's ability to classify taste stimuli, which could interfere with taste reward processing. METHOD: One-hundred and six women, 27 healthy comparison (age 26.15 ± 6.95 years), 21 with restricting-type anorexia nervosa (AN; age 23.10 ± 6.14 years), 19 recovered from restricting-type AN (recovered AN; age 26.95 ± 5.31 years), 20 with bulimia nervosa (BN; age 25.15 ± 5.31 years), and 19 with obesity (age 28.16 ± 8.13 years), received sucrose, control solution or no taste stimulation during functional magnetic resonance brain imaging. Multivariate Bayesian pattern analysis (decoding) and cross-validation tested taste classification accuracy (adjusted for comorbidity, medication use, taste perception, interoception, and brain activation volume). RESULTS: For sucrose versus control solution, classification accuracy differed (F = 2.53, P < 0.041). Post hoc tests indicated higher classification accuracy in healthy comparison compared to women with AN (P < 0.016) or obesity (P < 0.027), and in recovered AN as compared to AN (P < 0.016) or obesity (P < 0.047) groups. Taste stimulation resulted in sparse insula voxel activation across all groups. DISCUSSION: Reduced classification accuracy across stimuli in women with AN or obesity could indicate low brain encoding discrimination of stimulus quality, which could contribute to altered reward activation and eating drive that is not adjusted to nutritional needs. This deficit appears to normalize with recovery from AN, but adjusting food flavor intensity could aid in the treatment of individuals with AN or obesity. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2016; 49:603-612).

Between-network connectivity occurs in brain regions lacking layer IV input.

To better understand the cortical circuitry underlying connectivity between large-scale neural networks, we develop a novel, data-driven approach to identify potential integration subregions. Between-network connectivity (BNC) associated with any anatomical region is the amount of connectivity between that point and all large-scale networks, as measured using simple and multiple correlations. It is straightforward to calculate and applicable to functional networks identified using independent components analysis. We calculated BNC for all fMRI voxels within the brain and compared the results to known regional cytoarchitectural patterns. Based on previous observations of the relationship between macroscopic connectivity and microscopic cytoarchitecture, we predicted that areas with high BNC will be located in paralimbic subregions with an undifferentiated laminar structure. Results suggest that the anterior insula and dorsal posterior cingulate cortices play prominent roles in information integration. Cytoarchitecturely, these areas show agranular or dysgranular cytologies with absent or disrupted cortical layer IV. Since layer IV is the primary recipient of feed-forward thalamocortical connections, and due to the exclusive nature of driving connections to this layer, we suggest that the absence of cortical layer IV might allow for information to be exchanged across networks, and is an organizational characteristic of brain-subregions serving as inter-network communication hubs.

Non-traditional dosing of statins in statin-intolerant patients-is it worth a try?

In this manuscript, three manifestations of statin intolerance will be covered. The first, myopathy, is mostly subjective with variable complaints of myalgias often worsened by exercise, muscle cramping or weakness, and at times associated with a biomarker, elevations in creatine kinase (CK). A rare but serious manifestation can be rhabdomyolysis. The second, liver toxicity, is associated with reversible biochemical increases in transaminases and rarely other liver function tests. Finally, statin-related central nervous system (CNS) toxicity typically defined as cognitive impairment is quite rare and appears to be idiosyncratic. Statin dose alternatives will then be discussed and highlighted in the setting of the new cholesterol-lowering guidelines. Non-statin lipid-altering therapies as well as other alternative therapies will also be reviewed.

Update on the NCEP ATP-III emerging cardiometabolic risk factors.

The intent of this review is to update the science of emerging cardiometabolic risk factors that were listed in the National Cholesterol Education Program (NCEP) Adult Treatment Panel-III (ATP-III) report of 2001 (updated in 2004). At the time these guidelines were published, the evidence was felt to be insufficient to recommend these risk factors for routine screening of cardiovascular disease risk. However, the panel felt that prudent use of these biomarkers for patients at intermediate risk of a major cardiovascular event over the subsequent 10 years might help identify patients who needed more aggressive low density lipoprotein (LDL) or non-high density lipoprotein (HDL) cholesterol lowering therapy. While a number of other emerging risk factors have been identified, this review will be limited to assessing the data and recommendations for the use of apolipoprotein B, lipoprotein (a), homocysteine, pro-thrombotic factors, inflammatory factors, impaired glucose metabolism, and measures of subclinical atherosclerotic cardiovascular disease for further cardiovascular disease risk stratification.

The effects of early time restricted eating plus daily caloric restriction compared to daily caloric restriction alone on continuous glucose levels.

Background: The median eating duration in the U.S. is 14.75 h, spread throughout the period of wakefulness and ending before sleep. Food intake at an inappropriate circadian time may lead to adverse metabolic outcomes. Emerging literature suggests that time restricted eating (TRE) may improve glucose tolerance and insulin sensitivity. The aim was to compare 24-h glucose profiles and insulin sensitivity in participants after completing 12 weeks of a behavioral weight loss intervention based on early TRE plus daily caloric restriction (E-TRE+DCR) or DCR alone. Methods: Eighty-one adults with overweight or obesity (age 18-50 years, BMI 25-45 kg/m2) were randomized to either E-TRE+DCR or DCR alone. Each participant wore a continuous glucose monitor (CGM) for 7 days and insulin sensitivity was estimated using the homeostatic model assessment of insulin resistance (HOMA-IR) at Baseline and Week 12. Changes in CGM-derived measures and HOMA-IR from Baseline to Week 12 were assessed within and between groups using random intercept mixed models. Results: Forty-four participants had valid CGM data at both time points, while 38 had valid glucose, insulin, HOMA-IR, and hemoglobin A1c (A1c) data at both timepoints. There were no significant differences in sex, age, BMI, or the percentage of participants with prediabetes between the groups (28% female, age 39.2 ± 6.9 years, BMI 33.8 ± 5.7 kg/m2, 16% with prediabetes). After adjusting for weight, there were no between-group differences in changes in overall average sensor glucose, standard deviation of glucose levels, the coefficient of variation of glucose levels, daytime or nighttime average sensor glucose, fasting glucose, insulin, HOMA-IR, or A1c. However, mean amplitude of glycemic excursions changed differently over time between the two groups, with a greater reduction found in the DCR as compared to E-TRE+DCR (p = 0.03). Conclusion: There were no major differences between E-TRE+DCR and DCR groups in continuous glucose profiles or insulin sensitivity 12 weeks after the intervention. Because the study sample included participants with normal baseline mean glucose profiles and insulin sensitivity, the ability to detect changes in these outcomes may have been limited.

Relationship between functional connectivity and weight-gain risk of antipsychotics in schizophrenia.

BACKGROUND: The mechanisms by which antipsychotic medications (APs) contribute to obesity in schizophrenia are not well understood. Because AP effects on functional brain connectivity may contribute to weight effects, the current study investigated how AP-associated weight-gain risk relates to functional connectivity in schizophrenia. METHODS: Fifty-five individuals with schizophrenia (final N = 54) were divided into groups based on previously reported AP weight-gain risk (no APs/low risk [N = 19]; moderate risk [N = 17]; high risk [N = 18]). Resting-state functional magnetic resonance imaging (fMRI) was completed after an overnight fast ("fasted") and post-meal ("fed"). Correlations between AP weight-gain risk and functional connectivity were assessed at the whole-brain level and in reward- and eating-related brain regions (anterior insula, caudate, nucleus accumbens). RESULTS: When fasted, greater AP weight-gain risk was associated with increased connectivity between thalamus and sensorimotor cortex (pFDR = 0.021). When fed, greater AP weight-gain risk was associated with increased connectivity between left caudate and left precentral/postcentral gyri (pFDR = 0.048) and between right caudate and multiple regions, including the left precentral/postcentral gyri (pFDR = 0.001), intracalcarine/precuneal/cuneal cortices (pFDR < 0.001), and fusiform gyrus (pFDR = 0.008). When fed, greater AP weight-gain risk was also associated with decreased connectivity between right anterior insula and ventromedial prefrontal cortex (pFDR = 0.002). CONCLUSIONS: APs with higher weight-gain risk were associated with greater connectivity between reward-related regions and sensorimotor regions when fasted, perhaps relating to motor anticipation for consumption. Higher weight-gain risk APs were also associated with increased connectivity between reward, salience, and visual regions when fed, potentially reflecting greater desire for consumption following satiety.

The association of gender-affirming hormone therapy duration and body mass index on bone mineral density in gender diverse adults.

Introduction: Feminizing and masculinizing gender-affirming hormone therapy (fGAHT, mGAHT) results in bone mineral density (BMD) maintenance or improvement over time in transgender and gender diverse (TGD) adults. Mostly European TGD studies have explored GAHT's impact on BMD, but the association of BMI and BMD in TGD adults deserves further study. Objective: To determine whether GAHT duration or BMI are associated with BMD and Z-scores among TGD young adults. Methods: Cross-sectional study of nonsmoking TGD adults aged 18-40 years without prior gonadectomy or gonadotropin-releasing hormone agonist (GnRHa) therapy taking GAHT for > 1 year. BMD and Z-scores were collected from dual-energy x-ray absorptiometry. Associations between femoral neck, total hip, and lumbar spine BMDs and Z-scores and the predictors, GAHT duration and BMI, were estimated using linear regression. Results: Among 15 fGAHT and 15 mGAHT, mean BMIs were 27.6 +/- standard deviation (SD) 6.4 kg/m2 and 25.3 +/- 5.9 kg/m2, respectively. Both groups had mean BMDs and Z-scores within expected male and female reference ranges at all three sites. Higher BMI among mGAHT was associated with higher femoral neck and total hip BMDs (femoral neck: ß = 0.019 +/- standard error [SE] 0.007 g/cm2, total hip: ß = 0.017 +/- 0.006 g/cm2; both p < 0.05) and Z-scores using male and female references. GAHT duration was not associated with BMDs or Z-scores for either group. Conclusions: Z-scores in young, nonsmoking TGD adults taking GAHT for > 1 year, without prior gonadectomy or GnRHa, and with mean BMIs in the overweight range, were reassuringly within the expected ranges for age based on male and female references. Higher BMI, but not longer GAHT duration, was associated with higher femoral neck and total hip BMDs and Z-scores among mGAHT. Larger, prospective studies are needed to understand how body composition changes, normal or low BMIs, and gonadectomy affect bone density in TGD adults.

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.

Evaluation and treatment of metabolic syndrome and cardiovascular disease in adult patients with psoriasis.

Psoriasis is strongly associated with cardiovascular disease (CVD) and metabolic syndrome, with patients having an approximately twofold increased risk of each compared to the general population. This increased risk is based on shared underlying genetic and cytokine profiles, as well as similar environmental risks. Many screening guidelines do not address the development of CVD and metabolic syndrome in these predisposed patients. These deficits are evidenced by the exclusion of psoriasis as a risk factor in validated 10-year CVD risk calculators for adult patients with chronic inflammatory diseases, as well as insufficient screening guidelines for insulin resistance in patients with psoriasis. This manuscript aims to discuss and propose allopathic and lifestyle recommendations for the screening and management of the aforementioned comorbidities in adult patients with psoriasis.

Sex Differences in Effects of Mood, Eating-Related Behaviors, and BMI on Food Appeal and Desire to Eat: A Cross-Sectional Survey Study.

Although sex differences in food intake have been observed consistently, contributing factors are not well understood. Using a cross-sectional online survey (n = 306; 151 men, 155 women), this study aimed to assess how sex impacts relationships between food ratings (appeal/desire to eat for high-calorie (HC) and low-calorie (LC) food images) and eating-related attitudes/behaviors, body mass index (BMI), and mood. Across participants, increased state- and trait-based hunger, disinhibition, and cravings were associated with both increased HC appeal and desire (p < 0.001). Increased state-based hunger and cravings were associated with greater LC desire (p < 0.001). Greater satiety was associated with decreased desire for both HC and LC (p < 0.001), while greater anxiety was associated with increased desire for both HC and LC (p < 0.001). Significant associations between BMI and food ratings were not observed. Women reported greater dietary restraint, trait-based hunger, disinhibition, eating disorder-related behaviors, depression, and stress compared to men, in addition to greater appeal and familiarity with LC foods (all p < 0.05). Significant effects of sex on the associations between food ratings and eating-related attitudes/behaviors, BMI, and mood were not observed, however. Findings support the importance of considering mood and eating-related attitudes/behaviors in investigations of food cue responsivity.

The Effects of an Acute Bout of Aerobic or Resistance Exercise on Nonexercise Physical Activity.

Introduction/Purpose: A reduction in nonexercise physical activity (NEPA) after exercise may reduce the effectiveness of exercise interventions on weight loss in adults with overweight or obesity. Aerobic exercise (AEx) and resistance exercise (REx) may have different effects on NEPA. The purpose of this secondary analysis was to examine the effect of a single bout of AEx or REx on NEPA and sedentary behavior in inactive adults with overweight or obesity. Methods: Adults with overweight or obesity (n = 24; 50% male; age, 34.5 ± 1.5 yr; body mass index, 28.5 ± 0.9 kg·m-2) not meeting current physical activity guidelines completed a single 45-min bout of AEx, REx, or a sedentary control on different days in random order. After each condition, participants' NEPA was recorded for 84 h by accelerometer. Time spent sedentary and in light, moderate, and vigorous physical activity; steps; metabolic equivalent of task (MET)-hours; and sit-to-stand transitions were calculated using activity count data. Results: No differences were observed in the percent of waking time spent sedentary and in light, moderate, and vigorous activity between conditions (P > 0.05). No differences were observed in steps, MET-hours, or sit-to-stand transitions between conditions (P > 0.05). NEPA responses were variable among individuals, with approximately half of participants reducing and half increasing NEPA over the 84 h after each exercise condition. Conclusion: NEPA was not reduced after an acute bout of AEx or REx in a sample of inactive adults with overweight or obesity.

The metabolic syndrome.

The "metabolic syndrome" (MetS) is a clustering of components that reflect overnutrition, sedentary lifestyles, and resultant excess adiposity. The MetS includes the clustering of abdominal obesity, insulin resistance, dyslipidemia, and elevated blood pressure and is associated with other comorbidities including the prothrombotic state, proinflammatory state, nonalcoholic fatty liver disease, and reproductive disorders. Because the MetS is a cluster of different conditions, and not a single disease, the development of multiple concurrent definitions has resulted. The prevalence of the MetS is increasing to epidemic proportions not only in the United States and the remainder of the urbanized world but also in developing nations. Most studies show that the MetS is associated with an approximate doubling of cardiovascular disease risk and a 5-fold increased risk for incident type 2 diabetes mellitus. Although it is unclear whether there is a unifying pathophysiological mechanism resulting in the MetS, abdominal adiposity and insulin resistance appear to be central to the MetS and its individual components. Lifestyle modification and weight loss should, therefore, be at the core of treating or preventing the MetS and its components. In addition, there is a general consensus that other cardiac risk factors should be aggressively managed in individuals with the MetS. Finally, in 2008 the MetS is an evolving concept that continues to be data driven and evidence based with revisions forthcoming.

Brain structure predicts risk for obesity.

The neurobiology of obesity is poorly understood. Here we report findings of a study designed to examine the differences in brain regional gray matter volume in adults recruited as either Obese Prone or Obese Resistant based on self-identification, body mass index, and personal/family weight history. Magnetic resonance imaging was performed in 28 Obese Prone (14 male, 14 female) and 25 Obese Resistant (13 male, 12 female) healthy adults. Voxel-based morphometry was used to identify gray matter volume differences between groups. Gray matter volume was found to be lower in the insula, medial orbitofrontal cortex and cerebellum in Obese Prone, as compared to Obese Resistant individuals. Adjusting for body fat mass did not impact these results. Insula gray matter volume was negatively correlated with leptin concentration and measures of hunger. These findings suggest that individuals at risk for weight gain have structural differences in brain regions known to be important in energy intake regulation, and that these differences, particularly in the insula, may be related to leptin.

A review of current guidelines for the treatment of obesity.

Two guidelines-one by the American College of Cardiology (ACC)/American Heart Association (AHA)/The Obesity Society (TOS), and the other by the American Association of Clinical Endocrinologists (AACE)/American College of Endocrinology (ACE)-remain the standard of care in the management of overweight and obesity in adults. However, since the publication of the ACC/AHA/TOS document, several relevant pharmacotherapies have been approved by the FDA, a medication was withdrawn from the market, and several procedures and device types for weight loss have been recommended or FDA-approved. Simultaneously, research in obesity treatment has advanced, and leaders in the field have issued complementary guidance. This article summarizes and synthesizes the 2013 ACC/AHA/TOS and the 2016 AACE/ACE guidelines and includes updates from more recent professional association guidance. Measurement of body mass index is recommended to initiate evaluation for overweight and obesity and determine disease classification. To stage disease severity, weight-related conditions should be assessed. Although lifestyle therapy remains the cornerstone of treatment for this disease, both pharmacotherapy and metabolic and bariatric surgery produce greater and more sustained weight loss in treatment-approved populations as compared with lifestyle modifications alone. An ongoing partnership between the patient and clinician is highly recommended to manage this serious, progressive, chronic disease.

Early time-restricted eating compared with daily caloric restriction: A randomized trial in adults with obesity.

OBJECTIVE: This trial aimed to evaluate the acceptability and efficacy of early time-restricted eating plus daily caloric restriction (E-TRE+DCR) compared with DCR alone within a behavioral weight-loss intervention. METHODS: Participants (n = 81, 69 women, mean [SD] age: 38.0 [7.8] years, BMI: 34.1 [5.7] kg/m2 ) were randomized to E-TRE (10-hour eating window starting within 3 hours of waking) plus DCR or DCR alone (~35% DCR) for 39 weeks. The primary outcome was body weight (measured with digital scale) at week 12. Secondary outcomes measured at week 12 included hemoglobin A1c, lipids, energy intake (photographic food records), physical activity (accelerometry), dietary adherence (questionnaires), and body composition (dual-energy x-ray absorptiometry). Weight and body composition were also assessed at week 39. RESULTS: Mean [SD] weight loss was not different between groups at week 12 (E-TRE+DCR: -6.2 [4.1] kg vs. DCR: -5.1 [3.2] kg) or at week 39 (E-TRE: -4.9 [5.3] kg vs. DCR: -4.3 [5.3] kg). There were no between-group differences in changes in body composition, dietary adherence, energy intake, physical activity, hemoglobin A1c, or lipids at week 12. CONCLUSIONS: E-TRE+DCR was found to be an acceptable dietary strategy, resulting in similar levels of adherence and weight loss compared with DCR alone.