scholarly journals The Linearized Disposition Index Augments Understanding of Treatment Effects in Diabetes

2020 ◽  
Author(s):  
Amanda J Kile ◽  
Clarissa Hanna ◽  
Tamara S Hannon ◽  
Marian Sue Kirkman ◽  
Robert V Considine ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Repeated Measures ◽  
Treatment Effects ◽  
Mixed Model ◽  
Disposition Index ◽  
Coupling Relationship ◽  
Novel Approach ◽  
Induced Changes ◽  
Relationship Of

The Disposition Index, calculated by multiplying measures of insulin secretion and insulin sensitivity, is widely applied as a sensitivity-adjusted measure of insulin secretion. We have recently shown that linearizing the underlying relationship uniquely permits identification of terms relating to maximal insulin secretion capacity and the secretion-coupling relationship, with both terms separately contributing to differences in the secretion-sensitivity relationship across gradations of glycemia. Here we demonstrate the application of this linearized equation to the evaluation of treatment-induced changes in the insulin secretion-sensitivity relationship. We applied a combination of repeated measures multivariable linear regression (evaluating treatment-induced changes in the joint relationship of insulin sensitivity and secretion) plus mixed model repeated measures (evaluating treatment effects on maximal secretion capacity and on the secretion-sensitivity coupling slope), and compared against a usual application of the disposition index calculated from the same measurements. This novel approach allows a more informative description of treatment-induced changes compared to the usual disposition index, including isolating the source of change within the mutually adjusted relationship, and identifying treatment-induced changes in the secretion-sensitivity coupling slope and in maximal insulin secretion. Application of this linearized approach provides an expanded understanding of treatment-induced changes in the insulin sensitivity-secretion relationship.

scholarly journals Evaluating the Effect of Acarbose Treatment on Insulin Secretion and Sensitivity in Early Diabetes Using a Novel Interpretation of the Disposition Index Equation

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Clarissa Hanna ◽  
Tamara Hannon ◽  
Robert V. Considine ◽  
Kieren J. Mather
Keyword(s):  
Insulin Resistance ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Inverse Relationship ◽  
Treatment Effects ◽  
Cell Function ◽  
Disposition Index ◽  
Β Cell ◽  
Progressive Decline ◽  
Analytic Methods

Background and Hypothesis: In pathologic states such as obesity and insulin resistance, there is a progressive decline in insulin sensitivity requiring greater insulin secretion to maintain normoglycemia. The inverse relationship between insulin sensitivity and secretion is mathematically defined by the Disposition Index (DI), a measure of βcell function adjusted for insulin sensitivity. We are working to generalize the DI equation to allow direct physiologic interpretation of the DI term, and of the slope relating insulin secretion with insulin sensitivity. We tested study treatment effects hypotheses using these new analytic methods. Background and Hypothesis: In pathologic states such as obesity and insulin resistance, there is a progressive decline in insulin sensitivity requiring greater insulin secretion to maintain normoglycemia. The inverse relationship between insulin sensitivity and secretion is mathematically defined by the Disposition Index (DI), a measure of βcell function adjusted for insulin sensitivity. We are working to generalize the DI equation to allow direct physiologic interpretation of the DI term, and of the slope relating insulin secretion with insulin sensitivity. We tested study treatment effects hypotheses using these new analytic methods. Results: These analyses revealed statistically significant 1-year changes in DI, in secretion-sensitivity coupling slopes, and in the joint changes in secretion and sensitivity. However, these treatment effects did not differ by randomized treatment group, suggesting an on-study effect beyond the randomized treatments. Conclusion and Potential Impact:  We have applied a novel analytic approach to evaluate the secretion-sensitivity relationship modeled by the disposition index equation to investigate the effect of randomized therapy on β-cell function in a placebo-controlled randomized clinical trial. These analyses revealed study effects on the secretion-sensitivity relationship that have not been previously described, suggesting that this novel approach will have value in clinical studies of β-cell dysfunction and treatment effects.  

scholarly journals Relationship Between Insulin Secretion and Insulin Sensitivity and its Role in Development of Type 2 Diabetes Mellitus: Beyond the Disposition Index

2021 ◽  
Author(s):  
Elsa Vazquez Arreola ◽  
Robert L. Hanson ◽  
Clifton Bogardus ◽  
William C. Knowler
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Allostatic Load ◽  
Regression Line ◽  
Epidemiologic Study ◽  
Disposition Index ◽  
Lower Sensitivity ◽  
The Relationship

We assessed whether the relationship between insulin secretion and sensitivity predicted development of type 2 diabetes in American Indians participating in a longitudinal epidemiologic study. At baseline, when all subjects did not have diabetes, 1566 participants underwent oral tests and 420 had intravenous measures of glucose regulation with estimates of insulin secretion and sensitivity. Standardized major axis regression was used to study the relationship of secretion and sensitivity. Distances away from and along the regression line estimated compensatory insulin secretion and secretory demand, respectively. This relationship differed according to glucose tolerance and BMI categories. The distance away from the line is similar to the disposition index (DI) defined as the product of estimated secretion and sensitivity, but the regression line may differ from a line with constant DI (i.e., it is not necessarily hyperbolic). Subjects with the same DI but different levels of insulin secretion and sensitivity had different incidence rates of diabetes; lower sensitivity with higher secretory demand was associated with greater diabetes risk. Insulin secretion and insulin sensitivity, analyzed together, predict diabetes better than DI alone. Physiologically, this may reflect long-term risk associated with increased allostatic load resulting from the stimulation of insulin hypersecretion by increased glycemia.

scholarly journals Relationship Between Insulin Secretion and Insulin Sensitivity and its Role in Development of Type 2 Diabetes Mellitus: Beyond the Disposition Index

2021 ◽  
Author(s):  
Elsa Vazquez Arreola ◽  
Robert L. Hanson ◽  
Clifton Bogardus ◽  
William C. Knowler
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Allostatic Load ◽  
Regression Line ◽  
Epidemiologic Study ◽  
Disposition Index ◽  
Lower Sensitivity ◽  
The Relationship

We assessed whether the relationship between insulin secretion and sensitivity predicted development of type 2 diabetes in American Indians participating in a longitudinal epidemiologic study. At baseline, when all subjects did not have diabetes, 1566 participants underwent oral tests and 420 had intravenous measures of glucose regulation with estimates of insulin secretion and sensitivity. Standardized major axis regression was used to study the relationship of secretion and sensitivity. Distances away from and along the regression line estimated compensatory insulin secretion and secretory demand, respectively. This relationship differed according to glucose tolerance and BMI categories. The distance away from the line is similar to the disposition index (DI) defined as the product of estimated secretion and sensitivity, but the regression line may differ from a line with constant DI (i.e., it is not necessarily hyperbolic). Subjects with the same DI but different levels of insulin secretion and sensitivity had different incidence rates of diabetes; lower sensitivity with higher secretory demand was associated with greater diabetes risk. Insulin secretion and insulin sensitivity, analyzed together, predict diabetes better than DI alone. Physiologically, this may reflect long-term risk associated with increased allostatic load resulting from the stimulation of insulin hypersecretion by increased glycemia.

scholarly journals Influence of motivational placebo-related factors on the effects of exercise treatment in depressive adolescents

2021 ◽  
Author(s):  
Heidrun Lioba Wunram ◽  
Stefanie Hamacher ◽  
Max Oberste ◽  
Susanne Neufang ◽  
Luisa Belke ◽  
...  
Keyword(s):  
Repeated Measures ◽  
Adolescent Depression ◽  
Protective Factor ◽  
Mixed Model ◽  
Rating Scale ◽  
Motivational Factors ◽  
Related Factors ◽  
Exercise Treatment ◽  
Meta Analyses ◽  
Induced Changes

AbstractRecent meta-analyses reveal a moderate effect of physical activity (PA) in the treatment of adolescent depression. However, not only the underlying neurobiological mechanisms, also the influences of placebo-related motivational factors (beliefs and expectancies in sporting, enjoyment and prior sports experiences), are still unclear. Based on the data of our prior study “Mood Vibes”, we hypothesized that placebo-inherent factors like positive prior sports experiences and motivational factors, (positive beliefs, expectancies, and enjoyment related to PA), would increase the effects of an add-on exercise-therapy in juvenile depression. From 64 included depressed adolescents, 41 underwent an intensive add-on PA-therapy. Motivational factors were assessed using sport-specific scales. The changes in depression scores under treatment were rated by self-rating scale (German “Childhood Depression Inventory”, (DIKJ)). A mixed model for repeated measures (MMRM) was used to analyze the effects of the different motivational variates on DIKJ. While prior sports experiences had no impact, motivational factors showed a significant effect on PA-induced changes in DIKJ scores (p = 0.002). The demotivated participants improved less, whereas it was sufficient to be neutral towards sporting to benefit significantly more. Motivational placebo-related factors (beliefs, expectancies and enjoyment regarding PA) affected the outcomes of an exercise treatment in depressed adolescents. Yet, a neutral mindset was sufficient to profit more from PA. Prior sporting in the sense of positive conditioning and as a protective factor did not play a role. Knowledge about these influences could in a second step help to develop tailored therapies.

scholarly journals Diet, insulin secretion and insulin sensitivity – the Dose–Responses to Exercise Training (DR's EXTRA) Study (ISRCTN45977199)

2014 ◽  
Vol 112 (9) ◽  
pp. 1530-1541 ◽  
Author(s):  
Harri M. Heikkilä ◽  
Benno Krachler ◽  
Rainer Rauramaa ◽  
Ursula S. Schwab
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Metabolism ◽  
Cardiorespiratory Fitness ◽  
Dietary Fibre ◽  
Linear Models ◽  
Disposition Index ◽  
Oral Glucose ◽  
Dietary Intakes ◽  
Normal Glucose

Intakes of saturated fat (SF) and dietary fibre, body mass and physical activity are all associated with the incidence of type 2 diabetes mellitus. Their relative importance for the maintenance of normal glucose metabolism is not fully known. In a population-based sample of 1114 individuals, aged 58–78 years, dietary intakes were assessed by 4 d food records and cardiorespiratory fitness as maximal oxygen uptake. Insulin secretion, insulin sensitivity, the early-phase disposition index (DI30) and the total disposition index (DI120) were assessed based on an oral glucose tolerance test. Linear associations were modelled using linear regression. Combined effects were studied by introducing SF and fibre intakes, as well as cardiorespiratory fitness and waist circumference (WC) as dichotomised variables in general linear models. Intakes of dietary fibre and whole-grain bread were positively associated with insulin sensitivity, independent of physical fitness and WC. In women, dietary fibre intake was also positively associated with DI30. The negative association of high WC with DI30 was attenuated by a combination of low SF intake and high cardiorespiratory fitness. In conclusion, dietary fibre and a combination of low SF intake and high cardiorespiratory fitness may contribute to the maintenance of normal glucose metabolism, independent of WC.

scholarly journals Simultaneous Measurement of Insulin Sensitivity, Insulin Secretion, and the Disposition Index in Conscious Unhandled Mice

Obesity ◽  
2012 ◽  
Vol 20 (7) ◽  
pp. 1403-1412 ◽  
Author(s):  
Laura C. Alonso ◽  
Yoshio Watanabe ◽  
Darko Stefanovski ◽  
Euhan J. Lee ◽  
Srikanth Singamsetty ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Simultaneous Measurement ◽  
Disposition Index

scholarly journals The increase in serum 25-hydroxyvitamin D following weight loss does not contribute to the improvement in insulin sensitivity, insulin secretion and β-cell function

2015 ◽  
Vol 114 (2) ◽  
pp. 161-168 ◽  
Author(s):  
Véronique Thibault ◽  
Anne-Sophie Morisset ◽  
Christine Brown ◽  
André C. Carpentier ◽  
Jean-Patrice Baillargeon ◽  
...  
Keyword(s):  
Weight Loss ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Cell Function ◽  
Disposition Index ◽  
Model Assessment ◽  
Β Cell ◽  
Hydroxyvitamin D ◽  
Β Cell Function ◽  
25 Hydroxyvitamin D

Serum 25-hydroxyvitamin D (25(OH)D) concentrations have been reported to increase following weight loss. Moreover, both weight loss and higher serum 25(OH)D concentrations have been associated with a lower risk of developing type 2 diabetes. The objective of the present study was to determine whether the increase in serum 25(OH)D concentration following weight loss is associated with improved insulin sensitivity, insulin secretion and disposition index (β-cell function). Data from two prospective lifestyle modification studies had been combined. Following a lifestyle-modifying weight loss intervention for 1 year, eighty-four men and women with prediabetes and a BMI ≥ 27 kg/m2 were divided based on weight loss at 1 year: < 5 % (non-responders, n 56) and ≥ 5 % (responders, n 28). The association between the change in serum 25(OH)D concentration and changes in insulin sensitivity (homeostasis model assessment of insulin sensitivity (HOMA%S) and Matsuda), insulin secretion (AUC of C-peptide) and disposition index after adjustment for weight loss was examined. Participants in the responders' group lost on average 9·5 % of their weight when compared with non-responders who lost only 0·8 % of weight. Weight loss in responders resulted in improved insulin sensitivity (HOMA%S, P= 0·0003) and disposition index (P= 0·02); however, insulin secretion remained unchanged. The rise in serum 25(OH)D concentration following weight loss in responders was significantly higher than that in non-responders (8·9 (sd 12·5) v. 3·6 (sd 10·7) nmol/l, P= 0·05). However, it had not been associated with amelioration of insulin sensitivity and β-cell function, even after adjustment for weight loss and several confounders. In conclusion, the increase in serum 25(OH)D concentration following weight loss does not contribute to the improvement in insulin sensitivity or β-cell function.

scholarly journals Anti-Fel d1 immunoglobulin Y antibody-containing egg ingredient lowers allergen levels in cat saliva

2019 ◽  
Vol 21 (10) ◽  
pp. 875-881 ◽  
Author(s):  
Ebenezer Satyaraj ◽  
Qinghong Li ◽  
Peichuan Sun ◽  
Scott Sherrill
Keyword(s):  
Treatment Group ◽  
Treatment Period ◽  
Repeated Measures ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Control Diet ◽  
Baseline Period ◽  
Daily Trial ◽  
Mixed Model Analysis ◽  
Novel Approach

Objectives Fel d1 is the major cat allergen, causing IgE reactions in up to 90% of cat-allergic adults. Fel d1 secreted in saliva is spread to the haircoat during grooming. Current management includes attempts to reduce or eliminate exposure to Fel d1. A novel approach to reducing immunologically active Fel d1 (aFel d1) exposure, which involves binding the Fel d1 with an anti-Fel d1-specific polyclonal egg IgY antibody (sIgY), was evaluated. The hypothesis was that saliva from cats fed diets containing this sIgY would show a significant reduction in aFel d1. Methods Two trials in cats were completed. In trial 1, saliva was collected 0, 1, 3 and 5 h post-feeding during a 2 week baseline and subsequent 6 week treatment period. Trial 2 included a control and treatment group, and saliva was collected once daily. Trial 2 cats were fed the control diet during a 1 week baseline period, and then fed either control or sIgY diet during the 4 week treatment period. Fel d1-specific ELISA was used to measure salivary aFel d1. Data were analysed using repeated-measures ANOVA and a linear mixed-model analysis. Results Salivary aFel d1 decreased post-treatment in both trials. There were no differences in aFel d1 based on time of collection relative to feeding in trial 1. In trial 2, 82% of treatment group cats showed a decrease in aFel d1 of at least 20% from baseline vs just 38% of control cats. Only one (9%) treatment cat showed an increase in aFel d1 vs 63% of control cats. Conclusions and relevance Feeding sIgY significantly reduced aFel d1 in the saliva of cats within 3 weeks. Although additional research is needed, these findings show promise for an alternative approach to the management of allergies to cats.

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