Pharmacokinetics, safety, and tolerability of BMS-986263, a lipid nanoparticle containing HSP47 siRNA, in participants with hepatic impairment.

BMS-986263 is a retinoid-conjugated lipid nanoparticle delivering small interfering RNA designed to inhibit synthesis of HSP47 protein, a collagen-specific chaperone protein involved in fibrosis development. This is a phase I, open-label, two-part study evaluating pharmacokinetics and safety of BMS-986263 in participants with hepatic impairment (HI). Part 1 (n = 24) of this study enrolled two cohorts with mild and moderate HI and a separate cohort of age- and body mass index (BMI)-matched participants with normal hepatic function.

Effect of pegbelfermin on NASH and fibrosis-related biomarkers and correlation with histological response in the FALCON 1 trial.

Background & Aims: FALCON 1 was a phase IIb study of pegbelfermin in patients with non-alcoholic steatohepatitis (NASH) and stage 3 fibrosis. This FALCON 1 analysis aimed to further assess the effect of pegbelfermin on NASH-related biomarkers, correlations between histological assessments and non-invasive biomarkers, and concordance between the week 24 histologically assessed primary endpoint response and biomarkers.

Methods: Blood-based composite fibrosis scores, blood-based biomarkers, and imaging biomarkers were evaluated for patients with available data from FALCON 1 at baseline through week 24.

Liver Enlargement Predicts Obstructive Sleep Apnea-Hypopnea Syndrome in Morbidly Obese Women.

Obstructive sleep apnea-hypopnea syndrome (OSAHS) is frequently present in patients with severe obesity, but its prevalence especially in women is not well defined. OSAHS and non-alcoholic fatty liver disease are common conditions, frequently associated in patients with central obesity and metabolic syndrome and are both the result of the accumulation of ectopic fat mass. Identifying predictors of risk of OSAHS may be useful to select the subjects requiring instrumental sleep evaluation.

Cytokine Patterns in Healthy Adolescent Girls: Heterogeneity Captured by Variable and Person-Centered Statistical Strategies.

Background: Little is known about variation in individual cytokines/cytokine profiles for a large healthy, pediatric population. When cytokines in a healthy group are not abnormally high as in a disease state, it is challenging to determine appropriate statistical strategies. The aims of the study were (1) to describe variation among cytokine concentrations and profiles in healthy adolescent girls, (2) to illustrate utility of data reduction approaches novel to cytokine research, (variable-centered [principal factor analysis, PFA], person-centered [latent profile analysis, LPA]), and (3) to demonstrate utility of such methods in linking cytokine profiles to health outcomes (e.

Hawthorne effect with transient behavioral and biochemical changes in a randomized controlled sleep extension trial of chronically short-sleeping obese adults: implications for the design and interpretation of clinical studies.

Objective: To evaluate the effects of study participation per se at the beginning of a sleep extension trial between screening, randomization, and the run-in visit.

Design: Subjects were screened, returned for randomization (Comparison vs. Intervention) after 81 days (median), and attended run-in visit 121 days later.

Neck circumference is a predictor of metabolic syndrome and obstructive sleep apnea in short-sleeping obese men and women.

Background: The constellation of metabolic syndrome, although controversial with regard to its clinical usefulness, is epidemiologically related to increased diabetes risk and cardiovascular mortality. Our goal was to investigate the associations among neck circumference (NC), obstructive sleep apnea syndromes (OSAS), and metabolic syndrome in obese men and women sleeping less than 6.5 hr per night.

Sleep extension improves neurocognitive functions in chronically sleep-deprived obese individuals.

Background: Sleep deprivation and obesity, are associated with neurocognitive impairments. Effects of sleep deprivation and obesity on cognition are unknown, and the cognitive long-term effects of improvement of sleep have not been prospectively assessed in short sleeping, obese individuals.

Objective: To characterize neurocognitive functions and assess its reversibility.

Challenging recruitment of youth with type 2 diabetes into clinical trials.

Purpose: To better understand and overcome difficulties with recruitment of adolescents with type 2 diabetes into clinical trials at three United States institutions, we reviewed recruitment and retention strategies in clinical trials of youth with various chronic conditions. We explored whether similar strategies might be applicable to pediatric patients with type 2 diabetes.

Methods: We compiled data on recruitment and retention of adolescents with type 2 diabetes at three centers (National Institutes of Health, Bethesda, Maryland; Baylor College of Medicine, Houston, Texas; and Children's National Medical Center, Washington, DC) from January 2009 to December 2011.

Obstructive sleep apnea is a predictor of abnormal glucose metabolism in chronically sleep deprived obese adults.

Context: Sleep abnormalities, including obstructive sleep apnea (OSA), have been associated with insulin resistance.

Objective: To determine the relationship between sleep, including OSA, and glucose parameters in a prospectively assembled cohort of chronically sleep-deprived obese subjects.

Design: Cross-sectional evaluation of a prospective cohort study.

Evening chronotype is associated with changes in eating behavior, more sleep apnea, and increased stress hormones in short sleeping obese individuals.

Background: Short sleep duration and decreased sleep quality are emerging risk factors for obesity and its associated morbidities. Chronotype, an attribute that reflects individual preferences in the timing of sleep and other behaviors, is a continuum from morningness to eveningness. The importance of chronotype in relation to obesity is mostly unknown.

Inverse relationship of food and alcohol intake to sleep measures in obesity.

Background: Short sleep and weight gain are inversely related. Sleep deprivation acutely increases food intake but little is known about eating behavior in chronically sleep-deprived, obese individuals.

Objective: To characterize the relationship between sleep, food intake and alcohol consumption under free-living conditions in obese, chronically sleep-deprived individuals.

The Hypothalamic-Pituitary-Adrenal Axis, Obesity, and Chronic Stress Exposure: Sleep and the HPA Axis in Obesity.

Obesity, exposure to stress and inadequate sleep are prevalent phenomena in modern society. In this review we focus on their relationships and critically evaluate causality. In obese individuals, one of the main stress systems, the hypothalamic-pituitary-adrenal axis, is altered, and concentrations of cortisol are elevated in adipose tissue due to elevated local activity of 11β-hydroxysteroid dehydrogenase (HSD) type 1.

Do premenopausal women with major depression have low bone mineral density? A 36-month prospective study.

Background: An inverse relationship between major depressive disorder (MDD) and bone mineral density (BMD) has been suggested, but prospective evaluation in premenopausal women is lacking.

Methods: Participants of this prospective study were 21 to 45 year-old premenopausal women with MDD (n = 92) and healthy controls (n = 44). We measured BMD at the anteroposterior lumbar spine, femoral neck, total hip, mid-distal radius, trochanter, and Ward's triangle, as well as serum intact parathyroid hormone (iPTH), ionized calcium, plasma adrenocorticotropic hormone (ACTH), serum cortisol, and 24-hour urinary-free cortisol levels at 0, 6, 12, 24, and 36 months.

Interacting epidemics? Sleep curtailment, insulin resistance, and obesity.

In the last 50 years, the average self-reported sleep duration in the United States has decreased by 1.5-2 hours in parallel with an increasing prevalence of obesity and diabetes. Epidemiological studies and meta-analyses report a strong relationship between short or disturbed sleep, obesity, and abnormalities in glucose metabolism.

Poor sleep quality and sleep apnea are associated with higher resting energy expenditure in obese individuals with short sleep duration.

Context: Epidemiological studies reported an inverse or U-shaped relationship between sleep duration and weight. The relationship between sleep and resting energy expenditure (REE) has not been well characterized.

Objective: The aim of the study was to determine the relationship between sleep, REE, and stress hormones.

Rising incidence and challenges of childhood diabetes. A mini review.

Approximately 215,000 people younger than 20 yr of age, or 1 in 500 children and adolescents, had diabetes in the United States in 2010--and the incidence is rising. We still have insufficient knowledge about the precise mechanisms leading to the autoimmune mediated β-cell destruction in Type 1 diabetes, and the β-cell failure associated with insulin resistance in Type 2 diabetes. Long-term complications are similar: micro- and macrovascular disease occurs prematurely and presents an enormous burden on affected individuals, often as early as in middle age.

Predictors of sleep-disordered breathing in obese adults who are chronic short sleepers.

Background: Sleep disordered breathing (SDB) is common in obese adults, but not all obese adults have SDB. The aim of these analyses was to determine what predicted SDB in a sample of obese adults.

Methods: We conducted cross-sectional analysis of 139 obese men and women aged 18-50 years who are chronic short sleepers.

Clinical subtypes of depression are associated with specific metabolic parameters and circadian endocrine profiles in women: the power study.

Background: Major depressive disorder (MDD) has been associated with adverse medical consequences, including cardiovascular disease and osteoporosis. Patients with MDD may be classified as having melancholic, atypical, or undifferentiated features. The goal of the present study was to assess whether these clinical subtypes of depression have different endocrine and metabolic features and consequently, varying medical outcomes.

Beyond fast food and slow motion: weighty contributors to the obesity epidemic.

Decreased physical activity and marketing-driven increased consumption of "junk" food, dubbed "The Big Two", are generally regarded as the most important contributors to the obesity epidemic. However, the full picture contains many more pieces of the puzzle. We address several additional issues and review current clinical developments in obesity research.

No association between leptin levels and sleep duration or quality in obese adults.

Previous research in lean subjects has found lower leptin levels associated with shorter sleep duration. Since leptin levels are higher and some of the actions of leptin are impaired in obese individuals, one cannot assume that sleep will be similarly associated with leptin in obese individuals. The aim of this paper was to examine the cross-sectional association between habitual sleep duration and quality and plasma leptin levels in a sample of 80 obese men and premenopausal women aged 18-50 years.

Clinical manifestations of highly prevalent corticosteroid-binding globulin mutations in a village in southern Italy.

Context: Corticosteroid-binding globulin (CBG) is the binding protein for cortisol. Rare kindreds with CBG mutations reducing CBG levels or altering binding affinity have been described, along with clinical manifestations encompassing fatigue, chronic pain, and hypotension. The largest kindred, exhibiting two mutations (null and Lyon) were Australian immigrants from Italy.