Oral Disposition Index Predicts the Development of Future Diabetes Above and Beyond Fasting and 2-h Glucose Levels

OBJECTIVE—We sought to determine whether an oral disposition index (DIO) predicts the development of diabetes over a 10-year period. First, we assessed the validity of the DIO by demonstrating that a hyperbolic relationship exists between oral indexes of insulin sensitivity and β-cell function

Oral Disposition Index Predicts the Development of Future Diabetes Above and Beyond Fasting and 2-h Glucose Levels

OBJECTIVE—We sought to determine whether an oral disposition index (DIO) predicts the development of diabetes over a 10-year period. First, we assessed the validity of the DIO by demonstrating that a hyperbolic relationship exists between oral indexes of insulin sensitivity and β-cell function

Insulin Response in Relation to Insulin Sensitivity An appropriate beta-cell response in black South African women

OBJECTIVE - The purpose of this study was to characterize differences in the acute insulin response to glucose (AIRg) relative to insulin sensitivity (SI) in black and white premenopausal normoglycemic South African women matched for body fatness. RESEARCH DESIGN AND METHODS - Cross-sectional analysis including 57 black and white South African women matched for BMI, SI, AIRg, and the disposition index (AIRg X SI) were performed using a frequently sampled intravenous glucose tolerance test with minimal model analysis, and similar measures were analyzed using an oral glucose tolerance test (OGTT). Body composition was assessed by dual-energy X-ray absorptiometry and computed tomography. RESULTS - SI was significantly lower (4.4 ± 0.8 vs. 9.4 ± 0.8 and 2.9 ± 0.8 vs. 6.0 ± 0. 8 × 10 -5 min-1/[pmol/l], P < 0.001) and AIRg was significantly higher (1,028 ± 255 vs. 352 ± 246 and 1,968 ± 229 vs. 469 ± 246 pmol/l, P < 0.001), despite similar body fatness (30.9 ± 1.4 vs. 29.7 ± 1.3 and 46.8 ± 1.2 vs. 44.4 ± 1.3%) in the normal-weight and obese black women compared with their white counterparts, respectively. Disposition index, a marker of β-cell function, was not different between ethnic groups (3,811 ± 538 vs. 2,966 ± 518 and 3,646 ± 485 vs. 2,353 ± 518 × 10-5 min, P = 0.10). Similar results were obtained for the OGTT-derived measures. CONCLUSIONS - Black South African women are more insulin resistant than their white counterparts but compensate by increasing their insulin response to maintain normal glucose levels, suggesting an appropriate β-cell response for the level of insulin sensitivity

Stratification of asthma phenotypes by airway proteomic signatures

© 2019 Background: Stratification by eosinophil and neutrophil counts increases our understanding of asthma and helps target therapy, but there is room for improvement in our accuracy in prediction of treatment responses and a need for better understanding of the underlying mechanisms. Objective: We sought to identify molecular subphenotypes of asthma defined by proteomic signatures for improved stratification. Methods: Unbiased label-free quantitative mass spectrometry and topological data analysis were used to analyze the proteomes of sputum supernatants from 246 participants (206 asthmatic patients) as a novel means of asthma stratification. Microarray analysis of sputum cells provided transcriptomics data additionally to inform on underlying mechanisms. Results: Analysis of the sputum proteome resulted in 10 clusters (ie, proteotypes) based on similarity in proteomic features, representing discrete molecular subphenotypes of asthma. Overlaying granulocyte counts onto the 10 clusters as metadata further defined 3 of these as highly eosinophilic, 3 as highly neutrophilic, and 2 as highly atopic with relatively low granulocytic inflammation. For each of these 3 phenotypes, logistic regression analysis identified candidate protein biomarkers, and matched transcriptomic data pointed to differentially activated underlying mechanisms. Conclusion: This study provides further stratification of asthma currently classified based on quantification of granulocytic inflammation and provided additional insight into their underlying mechanisms, which could become targets for novel therapies