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BACKGROUND. Recombinant leptin (metreleptin) ameliorates hyperphagia and metabolic abnormalities in leptin-deficient humans with lipodystrophy. We aimed to determine whether metreleptin improves glucose and lipid metabolism in humans when food intake is held constant. METHODS. Patients with lipodystrophy were hospitalized for 19 days, with food intake held constant by a controlled diet in an inpatient metabolic ward. In a nonrandomized, crossover design, patients previously treated with metreleptin (n = 8) were continued on metreleptin for 5 days and then taken off metreleptin for the next 14 days (withdrawal cohort). This order was reversed in metreleptin-naive patients (n = 14), who were reevaluated after 6 months of metreleptin treatment on an ad libitum diet (initiation cohort). Outcome measurements included insulin sensitivity by hyperinsulinemic-euglycemic clamp, fasting glucose and triglyceride levels, lipolysis measured using isotopic tracers, and liver fat by magnetic resonance spectroscopy. RESULTS. With food intake constant, peripheral insulin sensitivity decreased by 41% after stopping metreleptin for 14 days (withdrawal cohort) and increased by 32% after treatment with metreleptin for 14 days (initiation cohort). In the initiation cohort only, metreleptin decreased fasting glucose by 11% and triglycerides by 41% and increased hepatic insulin sensitivity. Liver fat decreased from 21.8% to 18.7%. In the initiation cohort, changes in lipolysis were not independent of food intake, but after 6 months of metreleptin treatment on an ad libitum diet, lipolysis decreased by 30% (palmitate turnover) to 35% (glycerol turnover). CONCLUSION. Using lipodystrophy as a human model of leptin deficiency and replacement, we show that metreleptin improves insulin sensitivity and decreases hepatic and circulating triglycerides and that these improvements are independent of its effects on food intake. TRIAL REGISTRATION. ClinicalTrials.gov NCT01778556 FUNDING. This research was supported by the intramural research program of the NIDDK., Introduction Leptin is an adipocyte-derived hormone that signals overall body energy sufficiency (1) and acute energy balance (2). Leptin-deficient states, such as starvation or mutations in the leptin gene, lead [...]

The paper evaluates the effectiveness of citizen participation in environmental management, specifically, in relation to the process of evaluation of environmental impact assessment studies of large-scale mining projects in Peru. It is analysed if these mechanisms are equally inclusive of female and male voices; identifies the barriers that women face in these deliberative spaces and assess what the government is doing to reduce gender based exclusions. The paper argues that, although according to Peruvian environmental and mining law, participatory spaces are aimed to include citizens' voices; they end up reinforcing domination and control as they mainly operate to facilitate a rapid expedition of environmental licenses in mining projects rather than truly foster spaces of dialogue, consensus and political inclusion. For the most part, such mechanisms have also been blind to the gendered impacts of extractivism. [ABSTRACT FROM AUTHOR]

Context: Leptin is an adipokine that signals energy sufficiency. In rodents, leptin deficiency decreases energy expenditure (EE), which is corrected following leptin replacement. In humans, data are mixed regarding leptin-mediated effects on EE. Objective: To determine the effects of metreleptin on EE in patients with lipodystrophy. Design, setting, and patients: Nonrandomized crossover study of 25 patients with lipodystrophy (National Institutes of Health, 2013-2018). Intervention: The initiation cohort consisted of 17 patients without prior exposure to metreleptin, studied before and after 14 days of metreleptin. The withdrawal cohort consisted of 8 previously metreleptin-treated patients, studied before and after 14 days of metreleptin withdrawal. Main outcomes: 24-h total energy expenditure (TEE), resting energy expenditure (REE), autonomic nervous system activity [heart rate variability (HrV)], plasma-free triiodothyronine (T3), free thyroxine (T4), epinephrine, norepinephrine, and dopamine. Results: In the initiation cohort, TEE and REE decreased by 5.0% (121 ± 152 kcal/day; P = 0.006) and 5.9% (120 ± 175 kcal/day; P = 0.02). Free T3 increased by 19.4% (40 ± 49 pg/dL; P = 0.01). No changes in catecholamines or HrV were observed. In the withdrawal cohort, free T3 decreased by 8.0% (P = 0.04), free T4 decreased by 11.9% (P = 0.002), and norepinephrine decreased by 34.2% (P = 0.03), but no changes in EE, epinephrine, dopamine, or HrV were observed. Conclusions: Metreleptin initiation decreased EE in patients with lipodystrophy, but no changes were observed after metreleptin withdrawal. Thyroid hormone was higher on metreleptin in both initiation and withdrawal cohorts. Decreased EE after metreleptin in lipodystrophy may result from reductions in energy-requiring metabolic processes that counteract increases in EE via adipose tissue-specific neuroendocrine and adrenergic signaling. [ABSTRACT FROM AUTHOR]

Objective: The percentage of Hispanics in a county has a negative association with prevalence of obesity. Because Hispanic individuals are unevenly distributed in the United States, this study examined whether this protective association persists when stratifying counties into quartiles based on the size of the Hispanic population and after adjusting for county‐level demographic, socioeconomic, healthcare, and environmental factors. Methods: Data were extracted from the 2018 Robert Wood Johnson Foundation County Health Rankings. Counties were categorized into quartiles based on their percentage of Hispanics, 0%–5% (n = 1794), 5%–20% (n = 962), 20%–50% (n = 283), and >50% (n = 99). For each quartile, univariate and multivariate regression models were used to evaluate the association between prevalence of obesity and demographic, socioeconomic, healthcare, and environmental factors. Results: Counties with the top quartile of Hispanic individuals had the lowest prevalence of obesity compared to counties at the bottom quartile (28.4 ± 3.6% vs. 32.7 ± 4.0%). There was a negative association between county‐level percentage of Hispanics and prevalence of obesity in unadjusted analyses that persisted after adjusting for all county‐level factors. Conclusions: Counties with a higher percentage of Hispanics have lower levels of obesity, even after controlling for demographic, socioeconomic, healthcare, and environmental factors. More research is needed to elucidate why having more Hispanics in a county may be protective against county‐level obesity. [ABSTRACT FROM AUTHOR]

Abstract Background Previous studies have demonstrated that ethnic minority patients experience significant metabolic improvements after bariatric surgery but less so than non-Hispanic whites. Previous research has primarily investigated differences between non-Hispanic white and black patients. Thus, there remains a need to assess differences in diabetic outcomes among other ethnic groups, including Hispanic and Asian patient populations. Materials and methods A retrospective analysis including 650 patients with type II diabetes mellitus (T2DM), who underwent either laparoscopic Roux-en-Y gastric bypass or laparoscopic sleeve gastrectomy (LSG) procedures, was conducted to understand ethnic disparities in diabetic metabolic outcomes, including weight loss, serum concentrations of glucose, fasting insulin, and hemoglobin A1c (HbA1c). Data were from a single academic institution in northern California. Ethnicity data were self reported. T2DM was defined as having one or more of the following criteria: a fasting glucose concentration >125 mg/dL, HbA1c >6.5%, or taking one or more diabetic oral medications. Diabetes resolution was defined as having a fasting glucose <125 mg/dL, a HbA1c <6.5%, and discontinuation of diabetic oral medications. Results Within-group comparisons in all ethnic groups showed significant reductions in body mass index, body weight, fasting insulin, fasting glucose, and HbA1c by 6 mo, but Asian patients did not experience further improvement in body mass index or diabetic outcomes at the 12-mo visit. Black patients did not experience additional reductions in fasting insulin or glucose between the 6- and 12-mo visit and their HbA1c significantly increased. Nevertheless, the majority of patients had diabetes remission by the 12-mo postoperative visit (98%, 97%, 98%, and 92% in Non-Hispanic, Hispanic, black, and Asian, respectively). Conclusions The results of this study demonstrate that bariatric surgery serves as an effective treatment for normalizing glucose metabolism among patients with T2DM. However, this study suggests that additional interventions that support black and Asian patients with achieving similar metabolic outcomes as non-Hispanic white and Hispanic patients warrant further consideration. [ABSTRACT FROM AUTHOR]

Introduction: Population-level and individual-level analyses have strengths and limitations as do 'blackbox' machine learning (ML) and traditional, interpretable models. Diabetes mellitus (DM) is a leading cause of morbidity and mortality with complex sociodemographic dynamics that have not been analyzed in a way that leverages population-level and individual-level data as well as traditional epidemiological and ML models. We analyzed complementary individual-level and county-level datasets with both regression and ML methods to study the association between sociodemographic factors and DM., Research Design and Methods: County-level DM prevalence, demographics, and socioeconomic status (SES) factors were extracted from the 2018 Robert Wood Johnson Foundation County Health Rankings and merged with US Census data. Analogous individual-level data were extracted from 2007 to 2016 National Health and Nutrition Examination Survey studies and corrected for oversampling with survey weights. We used multivariate linear (logistic) regression and ML regression (classification) models for county (individual) data. Regression and ML models were compared using measures of explained variation (area under the receiver operating characteristic curve (AUC) and R 2 )., Results: Among the 3138 counties assessed, the mean DM prevalence was 11.4% (range: 3.0%-21.1%). Among the 12 824 individuals assessed, 1688 met DM criteria (13.2% unweighted; 10.2% weighted). Age, gender, race/ethnicity, income, and education were associated with DM at the county and individual levels. Higher county Hispanic ethnic density was negatively associated with county DM prevalence, while Hispanic ethnicity was positively associated with individual DM. ML outperformed regression in both datasets (mean R 2 of 0.679 vs 0.610, respectively (p<0.001) for county-level data; mean AUC of 0.737 vs 0.727 (p<0.0427) for individual-level data)., Conclusions: Hispanic individuals are at higher risk of DM, while counties with larger Hispanic populations have lower DM prevalence. Analyses of population-level and individual-level data with multiple methods may afford more confidence in results and identify areas for further study., Competing Interests: Competing interests: DMM acts as an advisor for Sanofi-Aventis US LLC, Novo Nordisk Inc, WL Gore and Associates, Inc, and Medtronic Minimed, Inc. DS acts as an advisor for Carta Healthcare. No other potential conflicts of interest relevant to this article were reported., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The percentage of Hispanics in a county has a negative association with prevalence of obesity. Because Hispanic individuals are unevenly distributed in the United States, this study examined whether this protective association persists when stratifying counties into quartiles based on the size of the Hispanic population and after adjusting for county-level demographic, socioeconomic, healthcare, and environmental factors., Methods: Data were extracted from the 2018 Robert Wood Johnson Foundation County Health Rankings. Counties were categorized into quartiles based on their percentage of Hispanics, 0%-5% ( n = 1794), 5%-20% ( n = 962), 20%-50% ( n = 283), and >50% ( n = 99). For each quartile, univariate and multivariate regression models were used to evaluate the association between prevalence of obesity and demographic, socioeconomic, healthcare, and environmental factors., Results: Counties with the top quartile of Hispanic individuals had the lowest prevalence of obesity compared to counties at the bottom quartile (28.4 ± 3.6% vs. 32.7 ± 4.0%). There was a negative association between county-level percentage of Hispanics and prevalence of obesity in unadjusted analyses that persisted after adjusting for all county-level factors., Conclusions: Counties with a higher percentage of Hispanics have lower levels of obesity, even after controlling for demographic, socioeconomic, healthcare, and environmental factors. More research is needed to elucidate why having more Hispanics in a county may be protective against county-level obesity., (© 2020 The Authors. Obesity Science & Practice published by World Obesity and The Obesity Society and John Wiley & Sons Ltd.)