Endogenous Leptin Concentrations Poorly Predict Metreleptin Response in Patients with Partial Lipodystrophy

2021 ◽  
Author(s):  
Rasimcan Meral ◽  
Noemi Malandrino ◽  
Mary Walter ◽  
Adam H Neidert ◽  
Ranganath Muniyappa ◽  
...  
Keyword(s):  
Predictive Power ◽  
National Institutes Of Health ◽  
Sensitivity Analyses ◽  
University Of Michigan ◽  
Serum Triglycerides ◽  
Cross Sectional ◽  
Partial Lipodystrophy ◽  
Cut Points ◽  
Cut Point ◽  
Sectional Analysis

Abstract Context Leptin replacement with metreleptin improves glycemia and hypertriglyceridemia in severely hypoleptinemic patients with Generalized Lipodystrophy (GLD), but its effects are variable in partially leptin-deficient patients with Partial Lipodystrophy (PLD). Objective Compare three leptin assays (Study I); identify diagnostic performance of leptin assays to detect responders to metreleptin for each assay (Study II). Design Study I: cross-sectional analysis of average bias between leptin assays. Study II: retrospective analysis of diagnostic accuracy of potential leptin cut-points to detect clinical responders to metreleptin. Setting National Institutes of Health (NIH); University of Michigan. Participants and Interventions Study I: Metreleptin-naïve patients with lipodystrophy (GLD, n=33, PLD, n=67) and healthy volunteers (n=239). Study II: GLD (n=66) and PLD (n=84) patients treated with metreleptin for 12 months. Outcome Measures Leptin concentrations by Millipore RIA; Millipore ELISA (MELISA); R&D systems ELISA, (RDELISA). Response to metreleptin therapy was defined as either reduction ≥1.0% in A1c or ≥30% in serum triglycerides. Results RDELISA measured 3.0±9.5 ng/mL higher than RIA; MELISA measured 11.0±17.8 and 14.0±19.2 less than RIA and RDELISA, respectively. Leptin by RIA, MELISA, and RDELISA modestly predicted metreleptin response in GLD+PLD (ROC AUC 0.74, 0.69, and 0.71, respectively; p<0.01 for all) with lower predictive power in PLD (ROC AUC 0.63, 0.61 and 0.65, respectively; p>0.05 for all). The only reproducible cut-point identified on sensitivity analyses was RIA leptin 7.2 ng/mL (sensitivity 56%; specificity 78%). Conclusions Three common leptin assays are not interchangeable, and a reliable cut-point to select responders to metreleptin was not identified.

scholarly journals Apolipoprotein CIII and Angiopoietin-like Protein 8 are Elevated in Lipodystrophy and Decrease after Metreleptin

2020 ◽  
Vol 5 (2) ◽  
Author(s):  
Marissa Lightbourne ◽  
Anna Wolska ◽  
Brent S Abel ◽  
Kristina I Rother ◽  
Mary Walter ◽  
...  
Keyword(s):  
Ex Vivo ◽  
National Institutes Of Health ◽  
Healthy Controls ◽  
Longitudinal Analyses ◽  
Cross Sectional ◽  
Partial Lipodystrophy ◽  
Apolipoprotein Ciii ◽  
Before And After ◽  
Relationship Of ◽  
Control Plasma

Abstract Context Lipodystrophy syndromes cause hypertriglyceridemia that improves with leptin treatment using metreleptin. Mechanisms causing hypertriglyceridemia and improvements after metreleptin are incompletely understood. Objective Determine relationship of circulating lipoprotein lipase (LPL) modulators with hypertriglyceridemia in healthy controls and in patients with lipodystrophy before and after metreleptin. Methods Cross-sectional comparison of patients with lipodystrophy (generalized lipodystrophy n = 3; partial lipodystrophy n = 11) vs age/sex-matched healthy controls (n = 28), and longitudinal analyses in patients before and after 2 weeks and 6 months of metreleptin. The study was carried out at the National Institutes of Health, Bethesda, Maryland. Outcomes were LPL stimulators apolipoprotein (apo) C-II and apoA-V and inhibitors apoC-III and angiopoietin-like proteins (ANGPTLs) 3, 4, and 8; ex vivo activation of LPL by plasma. Results Patients with lipodystrophy were hypertriglyceridemic and had higher levels of all LPL stimulators and inhibitors vs controls except for ANGPTL4, with >300-fold higher ANGPTL8, 4-fold higher apoC-III, 3.5-fold higher apoC-II, 1.9-fold higher apoA-V, 1.6-fold higher ANGPTL3 (P < .05 for all). At baseline, all LPL modulators except ANGPLT4 positively correlated with triglycerides. Metreleptin decreased apoC-II and apoC-III after 2 weeks and 6 months, and decreased ANGPTL8 after 6 months (P < 0.05 for all). Plasma from patients with lipodystrophy caused higher ex vivo LPL activation vs hypertriglyceridemic control plasma (P < .0001), which did not change after metreleptin. Conclusion Elevations in LPL inhibitors apoC-III and ANGPTL8 may contribute to hypertriglyceridemia in lipodystrophy, and may mediate reductions in circulating and hepatic triglycerides after metreleptin. These therefore are strong candidates for therapies to lower triglycerides in these patients.

Screening Screeners: Calculating Classification Indices Using Correlations and Cut-points

2020 ◽  
Author(s):  
Ashley Edwards ◽  
Wilhelmina van Dijk ◽  
Chris Schatschneider
Keyword(s):  
Predictive Power ◽  
Bivariate Normal Distribution ◽  
Base Rate ◽  
Online Tool ◽  
Cut Points ◽  
Cut Point ◽  
Good Classification ◽  
Classification Information ◽  
The Impact ◽  
Very High

Given the recent push for universal screening, it is important to take into account how well the screener identifies children as well as what contributes to this classification based on screener and sample information. If we assume a bivariate normal distribution, we can calculate all of the classification information for a screener based on the correlation between the screener and outcome, the cut-point on the outcome (base rate in sample), and the cut-point on the screener. This information is put together in a free online tool that provides classification information for a given correlation between screener and outcome and cut-points on each. Through this we can see that the correlation between the screener and outcome needs to be very high, greater than .9 (higher than observed in practice) to obtain good classification. These findings are important for researchers, administrators, and practitioners because our current screeners don’t meet these requirements. Since a correlation is dependent on the reliability of the measures involved, we need screeners with better reliability and the use of multiple measures to increase reliability. Additionally, we demonstrate the impact of base rate on positive predictive power and discuss how gated screening can be useful in samples with low base rates.

Association of dietary patterns with obesity and metabolically healthy obesity phenotype in Chinese population: a cross-sectional analysis of China Multi-Ethnic Cohort Study

2022 ◽  
pp. 1-29
Author(s):  
Dan Tang ◽  
Xiong Xiao ◽  
Liling Chen ◽  
Yixi kangzhu ◽  
Wei Deng ◽  
...  
Keyword(s):  
Chinese Population ◽  
Large Population ◽  
Sensitivity Analyses ◽  
Reverse Causality ◽  
Metabolically Healthy Obesity ◽  
Cross Sectional ◽  
Dash Diet ◽  
Cross Sectional Analysis ◽  
Metabolically Healthy ◽  
Sectional Analysis

Abstract Metabolically healthy obesity (MHO) might be an alternative valuable target in obesity treatment. We aimed to assess whether alternative Mediterranean (aMED) diet and Dietary Approaches to Stop Hypertension (DASH) diet were favorably associated with obesity and MHO phenotype in a Chinese Multi-Ethnic population. We conducted this cross-sectional analysis using the baseline data of the China Multi-Ethnic Cohort (CMEC) study that enrolled 99 556 participants from seven diverse ethnic groups. Participants with self-reported cardiometabolic diseases were excluded to eliminate possible reverse causality. Marginal structural logistic models were used to estimate the associations, with confounders determined by directed acyclic graph (DAG). Among 65 699 included participants, 11.2% were with obesity. MHO phenotype was present in 5.7% of total population and 52.7% of population with obesity. Compared with the lowest quintile, the highest quintile of DASH diet score had 23% decreased odds of obesity (OR = 0.77, 95% CI: 0.71-0.83, Ptrend <0.001), and 27% increased odds of MHO (OR = 1.27, 95% CI: 1.10-1.48, Ptrend =0.001) in population with obesity. However, aMED diet showed no obvious favorable associations. Further adjusting for BMI did not change the associations between diet scores and MHO. Results were robust to various sensitivity analyses. In conclusion, DASH diet rather than aMED diet is associated with reduced risk of obesity and presents BMI-independent metabolic benefits in this large population-based study. Recommendation for adhering to DASH diet may benefit the prevention of obesity and related metabolic disorders in Chinese population.

scholarly journals Defining the optimal cut-point of self-reported ART adherence to achieve viral suppression in the era of contemporary HIV therapy: a cross-sectional study

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Emma O’Halloran Leach ◽  
Huiyin Lu ◽  
Joshua Caballero ◽  
Jennifer E. Thomas ◽  
Emma C. Spencer ◽  
...  
Keyword(s):  
Medication Adherence ◽  
Viral Suppression ◽  
Youden Index ◽  
Art Adherence ◽  
Item Score ◽  
Cross Sectional ◽  
Single Item ◽  
Cut Points ◽  
Cut Point ◽  
Hiv Viral Suppression

Abstract Background When considering adherence to antiretroviral therapy (ART) for HIV, many different cut-points are used. The primary goals of this study were to identify a level of self-reported medication adherence that best distinguished HIV viral suppression from non-suppression, and to compare the ability of a single-item and a 3-item adherence questionnaire to predict HIV viral suppression. Methods This cross-sectional analysis included 380 persons with HIV (PWH) from the Florida Cohort study who completed a self-reported ART adherence measure within 30-days of having an HIV viral load test. We used Receiver Operating Characteristic (ROC) curve analyses and ROCContrast to compare the ability of a single-item and a 3-item self-reported adherence measure to predict HIV viral suppression (defined as ≤ 200 copies/mL). We used the Youden index and chi square statistics to assess specific cut-points, and repeated the analysis with a different definition of HIV viral suppression (≤ 1000 copies/mL). Results The mean percent adherence was 92.4% using the single-item score and 90.4% using the 3-item score; 81.6% had viral suppression. The areas under the curve for the single-item and 3-item adherence measures were generally poor overall and not significantly different from each other (0.589 and 0.580, p = 0.67). The Youden index identified cut-points of 93% and 89% as maximizing the sensitivity and specificity for the single-item and 3-item measures, respectively, whereas a cut-point of 80% on the single-item measure was best able to discriminate those with viral suppression (58% vs. 84%, p < 0.001). Results were similar with viral suppression defined as ≤ 1000 copies/mL. Conclusions In this sample of PWH, a single question on medication adherence was as good as a 3-item questionnaire in predicting HIV viral suppression, although neither had good discriminatory ability. A cut-point close to 90% adherence maximized sensitivity and specificity, although viral suppression was very similar for nearly all measures above 80%.

scholarly journals Tri-Ponderal Mass Index Reference Values for Screening Metabolic Syndrome in Children and Adolescents: Results From Two National-Representative Cross-Sectional Studies in China and America

2021 ◽  
Vol 12 ◽  
Author(s):  
Xijie Wang ◽  
Yanjun Chen ◽  
Jun Ma ◽  
Bin Dong ◽  
Yanhui Dong ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Children And Adolescents ◽  
Misclassification Rate ◽  
Cross Sectional ◽  
Cut Points ◽  
Cut Point ◽  
Health And Nutrition ◽  
Misclassification Rates ◽  
American Children ◽  
Validation Set

IntroductionTo ascertain the possible cut point of tri-ponderal mass index (TMI) in discriminating metabolic syndrome (MetS) and related cardio-metabolic risk factors in Chinese and American children and adolescents.MethodsA total of 57,201 Chinese children aged 7-18 recruited in 2012 and and 10,441 American children aged 12-18 from National Health and Nutrition Examination Survey (NHANES 2001-2014) were included to fit TMI percentiles. Participants were randomly assigned to a derivation set (75%) and validation set (25%). The cut points of TMI with the lowest misclassification rate under the premise of the highest area under curves (AUC) were selected for each sex, which were additionally examined in the validation set. All of data analysis was conducted between September and December in 2019.ResultsTMI showed good capacity on discriminating MetS, with AUC of 0.7658 (95% CI: 0.7544-0.7770) to 0.8445 (95% CI: 0.8349-0.8537) in Chinese and 0.8871 (95% CI: 0.8663-0.9056) to 0.9329 (95% CI: 0.9166-0.9469) in American children. The optimal cut points were 14.46 kg/m3 and 13.91 kg/m3 for Chinese boys and girls, and 17.08 kg/m3 and 18.89 kg/m3 for American boys and girls, respectively. The corresponding misclassification rates were 17.1% (95% CI: 16.4-17.8) and 11.2% (95% CI: 9.9-12.6), respectively. Performance of these cut points were also examined in the validation set (sensitivity 67.7%, specificity 82.4% in Chinese; sensitivity 84.4%, specificity 88.7% in American children).ConclusionsA sex- and ethnicity- specific single cut point of TMI could be used to distinguish MetS and elevated risk of cardio-metabolic factors in children and adolescents.

Accruals, Investment, and the Accrual Anomaly

2007 ◽  
Vol 82 (5) ◽  
pp. 1333-1363 ◽  
Author(s):  
X. Frank Zhang
Keyword(s):  
Stock Returns ◽  
Business Model ◽  
Predictive Power ◽  
Accrual Anomaly ◽  
Cross Sectional ◽  
Earnings Growth ◽  
Competing Hypotheses ◽  
One Year ◽  
Sectional Analysis ◽  
Investment Growth

This paper investigates two competing hypotheses for the accrual anomaly: investment/growth and persistence. Both investment/growth and persistence information in accruals are likely to vary cross-sectionally, depending on a firm's business model, a fact that generates different cross-sectional implications for the accrual anomaly. I find that the magnitude of the accrual anomaly monotonically increases with the investment information contained in accruals, as measured by the co-variation between accruals and employee growth. In industries/firms in which accruals co-vary with employee growth, accruals show strong predictive power for future stock returns. In industries/firms in which accruals show little correlations with employee growth, the accrual anomaly is much weaker. In contrast, the evidence from the cross-sectional analysis is inconsistent with the persistence argument. From the earnings perspective, the evidence on one-year-ahead earnings growth is inconclusive, but the results on longer-term earnings growth support the investment argument but not the persistence argument. Collectively, I conclude that these results support the view that the accrual anomaly is attributable to the fundamental investment information contained in accruals.

scholarly journals Health as an independent predictor of the 2017 French presidential voting behaviour: a cross-sectional analysis

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Jean-David Zeitoun ◽  
Matthieu Faron ◽  
Sophie de Vaugrigneuse ◽  
Jérémie H. Lefèvre
Keyword(s):  
Presidential Election ◽  
Health Indicators ◽  
Analysis Data ◽  
Sensitivity Analyses ◽  
Far Right ◽  
Cross Sectional ◽  
Cross Sectional Analysis ◽  
The Us ◽  
Marine Le Pen ◽  
Sectional Analysis

Abstract Background It has been suggested that poor health has influenced vote for Brexit and the US presidential election. No such research has been published regarding the 2017 French presidential election. Methods We performed a cross-sectional analysis using a comprehensive set of socioeconomic and health indicators, to be compared with voting outcome at the first round of the 2017 French presidential election. The 95 French departments were selected as the unit of analysis. Data were obtained from publicly available sources. The linear model was used for both univariate and multivariate analysis to investigate the relation between voting patterns and predictors. Sensitivity analyses were done using the elastic-net regularisation. Results Emmanuel Macron and Marine Le Pen arrived ahead. When projected on the first factorial plane (~ 60% of the total inertia), Emmanuel Macron and Marine Le Pen tended to be in opposite directions regarding both socioeconomic and health factors. In the respective multivariate analyses of the two candidates, both socio-economic and health variables were significantly associated with voting patterns, with wealthier and healthier departments more likely to vote for Emmanuel Macron, and opposite departments more likely to vote for Marine Le Pen. Mortality (p = 0.03), severe chronic conditions (p = 0.014), and diabetes mellitus (p < 0.0001) were among the strongest predictors of voting pattern for Marine Le Pen. Sensitivity analyses did not substantially change those findings. Conclusions We found that areas associated with poorer health status were significantly more likely to vote for the far-right candidate at the French presidential election, even after adjustment on socioeconomic criteria.

scholarly journals Establishing modified Canadian Aerobic Fitness Test (mCAFT) cut-points to detect clustered cardiometabolic risk among Canadian children and youth aged 9 to 17 years

2020 ◽  
Vol 45 (3) ◽  
pp. 311-317 ◽  
Author(s):  
Justin J. Lang ◽  
Emily Wolfe Phillips ◽  
Matt D. Hoffmann ◽  
Stephanie A. Prince
Keyword(s):  
Aerobic Fitness ◽  
Cardiometabolic Risk ◽  
Health Surveillance ◽  
Children And Youth ◽  
Peak Oxygen Consumption ◽  
Cardiometabolic Health ◽  
Cross Sectional ◽  
Cut Points ◽  
Fitness Test ◽  
Cut Point

The objective of this study was to establish cut-points to identify potential clustered cardiometabolic risk among children (aged 9–13 years) and youth (aged 14–17 years) using the modified Canadian Aerobic Fitness Test (mCAFT). Nationally representative cross-sectional data were obtained from cycles 1 and 2 (2007–2011) of the Canadian Health Measures Survey. Cardiorespiratory fitness was measured using the mCAFT, which was used to estimate peak oxygen consumption. Clustered cardiometabolic health was identified as the mean of 4 standardized variables: sum of 4 skinfolds; total cholesterol–to–high-density lipoprotein ratio; and systolic and diastolic blood pressure. In total, 2106 (49% female) participants were retained for this analysis. The optimal mCAFT cut-point for males was 49 and 46 mL·kg–1·min–1 among children and youth, respectively. Among females, the mCAFT cut-point was 46 and 37 mL·kg–1·min–1 among children and youth, respectively. In 2016–2017, 83% of females and 71% of males met the new mCAFT cut-points. The mCAFT cut-points can help identify children and youth at potential risk of poor cardiometabolic health in public health surveillance, clinical, and school-based settings. Novelty We developed new mCAFT cut-points to identify potential clustered cardiometabolic risk among Canadian children and youth. These mCAFT cut-points can be used to inform national health surveillance efforts.

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