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

Effect of psychological stress on glucose control in patients with Type 2 diabetes

AIM: To investigate the effect of acute psychological stress on glucose concentrations in patients with Type 2 diabetes, in the fasting state as well as in the postprandial state. METHODS: Thirty patients (12 female) with Type 2 diabetes were included. Mean ± SD age was 60 ± 12 years, BMI 28.8 ± 4.2 kg/m(2), diabetes duration 8.9 ± 6.7 years and HbA(1c) 51 ± 9 mmol/mol (6.8 ± 0.8%). Using a non-randomized approach, all participants were exposed to moderate psychological stress by means of the Trier Social Stress Test: 10 participants in the fasting state and 20 participants 75 min after intake of a standard meal. Blood pressure, heart rate and salivary cortisol were monitored on the control day and the stress-test day. Glucose concentrations were assessed using a continuous glucose monitoring system. RESULTS: On the stress-test day, blood pressure rose from 117/73 ± 13/12 to 155/92 ± 22/14 mmHg, heart rate from 77 ± 11 to 91 ± 25 b min(-1) and salivary cortisol concentrations from 8.5 ± 3.7 to 26.4 ± 12.1 nmol/l (P < 0.001); these measurements remained unchanged on the control day. On the stress-test day, when the Trier Social Stress Test was applied 75 min after the intake of a standard meal, the glucose concentrations were significantly higher compared with the control day (mean difference 1.5 mmol/l, 95% CI 0.5-2.4, P = 0.003). In the fasting state, glucose concentrations slightly decreased during the control day but remained stable on the stress-test day (mean difference compared with the control day 0.7 mmol/l, 95% CI -0.7 to 2.0, P = 0.31). CONCLUSIONS: When stress is experienced in the postprandial period, acute psychological stress significantly increases glucose concentrations in patients with Type 2 diabetes