Validation of a Deconvolution Procedure (AutoDecon) for Identification and Characterization of Fasting Insulin Secretory Bursts

Johnson, Michael L.; Veldhuis, Paula P.; Grimmichova, Tereza; Farhy, Leon S.; Evans, William S.

doi:10.1177/193229681000400521

Cited by 7 publications

(4 citation statements)

References 32 publications

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“…Across testing days, there were no significant differences in body weight in any of the subjects. According to self-report dietary logs and physical activity questionnaires, subjects consumed meals an average of 4.7±0.38 times/day, and participated in walking activity 3.3±0.57 times/wk at a Borg RPE (6–20) level of 13.4±0.5.…”

Section: Resultsmentioning

confidence: 99%

“…The c-peptide pulse profile was analyzed using a multi-parameter deconvolution technique (AutoDecon, Pulse_XP software; University of Virginia) designed to derive quantitative estimates of attributes of c-peptide secretory pulses and half-life from measured c-peptide concentrations (19, 20). Basal secretion was estimated for each condition, and assumed not to change during the exercise days (19).…”

Section: Methodsmentioning

confidence: 99%

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Multiple short bouts of exercise over 12-h period reduce glucose excursions more than an energy-matched single bout of exercise

et al. 2014

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Objective Long, uninterrupted bouts of sedentary behavior are thought to negatively influence postprandial glucose and insulin concentrations. We examined the effects of a 1-h bout of morning exercise versus intermittent walking bouts of short duration on glucose excursions and insulin secretion over 12-h. Materials/Methods Eleven young, obese individuals (18–35y, BMI>30kg/m2) with impaired glucose tolerance were studied on three 12-h study days: 1) sedentary behavior (SED); 2) sedentary behavior with 1-h morning exercise (EX) at 60–65% VO2peak; and 3) sedentary behavior with 12-hourly, 5-min intervals of exercise (INT) at 60–65% VO2peak. Meals (1046 kJ/meal) were provided every 2-h. Blood samples were collected every 10 min and measured for glucose, insulin, and c-peptide concentrations. Results Glucose iAUC (12-h) was attenuated in the INT and SED conditions compared to the EX condition (P<0.05). Glucose concentrations were higher in the EX compared to the SED condition for ~150 min (20% of the study day), and comparison of the EX-INT study days revealed that glucose concentrations were greater for ~ 240 minutes (~1/3 of the 12-h day). In the SED condition, the 12-h insulin iAUC was ~15% higher (P<0.05) compared to the INT and EX conditions. Insulin production rate was found to increase ~20% with INT exercise vs. the SED and EX condition (P<0.05). Conclusions Short, frequent periods of exercise attenuated glucose excursions and insulin concentrations in obese individuals to a greater degree than an equal amount of exercise performed continuously in the morning.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Multiple short bouts of exercise over 12-h period reduce glucose excursions more than an energy-matched single bout of exercise

et al. 2014

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“…Insulin secretion was determined using the C-peptide data. A pulse profile was analysed using a multi-parameter deconvolution technique (AutoDecon, Pulse_XP software; University of Virginia) that derives quantitative estimates of attributes of C-peptide secretory pulses and half-life from measured C-peptide concentrations ( 22 , 23 ) . A Gaussian distribution of secretory rate was assumed using the serum C-peptide concentration value and it was assumed to match insulin concentration at a 1:1 ratio.…”

Section: Experimental Methodsmentioning

confidence: 99%

Alteration of postprandial glucose and insulin concentrations with meal frequency and composition

et al. 2014

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A frequent eating pattern may alter glycaemic control and augment postprandial insulin concentrations in some individuals due to the truncation of the previous postprandial period by a subsequent meal. The present study examined glucose, insulin, C-peptide and glucose-dependent insulinotropic peptide (GIP) responses in obese individuals when meals were ingested in a high-frequency pattern (every 2 h, 6M) or in a low-frequency pattern (every 4 h, 3M) over 12 h. It also examined these postprandial responses to high-frequency, high-protein meals (6M HP ). In total, thirteen obese subjects completed three 12 h study days during which they consumed 6276 kJ (1500 kcal): (1) 3M -15 % protein and 65 % carbohydrate; (2) 6M -15 % protein and 65 % carbohydrate; (3) 6M HP -45 % protein and 35 % carbohydrate. Blood samples were collected every 10 min and analysed for glucose, insulin, C-peptide and GIP. Insulin total AUC (tAUC) and peak insulin concentrations (P,0·05) were higher in the 3M condition than in the 6M condition, but there were no differences in glucose tAUC between the conditions. The 6M HP regimen (glucose: 3569 (SE 83) mmol/l £ min (64·3 (SE 1·5) g/dl £ min), insulin: 1·577 (SE 0·146) pmol/l (22·7 (SE 2·1) mIU/dl) for 12 h) lowered glucose and insulin excursions more so over 12 h than either the 3M regimen (glucose: 3913 (SE 78) mmol/l £ min (70·5 (SE 1·4) g/dl £ min), insulin: 2·195 (SE 0·146) pmol/l £ min (31·6 (SE 2·1) mIU/dl £ min) for 12 h) or the 6M regimen (glucose: 3902 (SE 83) mmol/l £ min (70·3 (SE 1·5) g/dl £ min), insulin: 1·861 (SE 0·174) pmol/l £ min (26·8 (SE 2·5) mIU/dl £ min) for 12 h; P, 0·01). Insulin secretion, GIP concentrations and the glucose:insulin ratio were not altered by meal frequency or composition. In obese subjects, ingestion of meals in a low-frequency pattern does not alter glucose tAUC, but increases postprandial insulin responses. The substitution of carbohydrates with protein in a frequent meal pattern results in tighter glycaemic control and reduced postprandial insulin responses.

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“…The Gaussian shaped events that are fitted in deconvolution analysis have the advantage to be applicable on a wide range of pulsatile compounds [ 31 , 32 ]. However, this generalization inherently brings the disadvantage that no mechanistic information of the biological regulation of the compound is incorporated in the structural model.…”

Section: Discussionmentioning

confidence: 99%

A two-step deconvolution-analysis-informed population pharmacodynamic modeling approach for drugs targeting pulsatile endogenous compounds

Esdonk

Burggraaf

Graaf

et al. 2017

J Pharmacokinet Pharmacodyn

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Pharmacodynamic modeling of pulsatile endogenous compounds (e.g. growth hormone [GH]) is currently limited to the identification of a low number of pulses. Commonly used pharmacodynamic models are not able to capture the complexity of pulsatile secretion and therefore non-compartmental analyses are performed to extract summary statistics (mean, AUC, Cmax). The aim of this study was to develop a new quantification method that deals with highly variable pulsatile data by using a deconvolution-analysis-informed population pharmacodynamic modeling approach. Pulse frequency and pulse times were obtained by deconvolution analysis of 24 h GH profiles. The estimated pulse times then informed a non-linear mixed effects population pharmacodynamic model in NONMEM V7.3. The population parameter estimates were used to perform simulations that show agonistic and antagonistic drug effects on the secretion of GH. Additionally, a clinical trial simulation shows the application of this method in the quantification of a hypothetical drug effect that inhibits GH secretion. The GH profiles were modeled using a turnover compartment in which the baseline secretion, kout, pulse secretion width, amount at time point 0 and pulse amplitude were estimated as population parameters. Population parameters were estimated with low relative standard errors (ranging from 2 to 5%). Total body water (%) was identified as a covariate for pulse amplitude, baseline secretion and the pulse secretion width following a power relationship. Simulations visualized multiple gradients of a hypothetical drug that influenced the endogenous secretion of GH. The established model was able to fit and quantify the highly variable individual 24 h GH profiles over time. This pharmacodynamic model can be used to quantify drug effects that target other endogenous pulsatile compounds.Electronic supplementary materialThe online version of this article (doi:10.1007/s10928-017-9526-0) contains supplementary material, which is available to authorized users.

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Validation of a Deconvolution Procedure (AutoDecon) for Identification and Characterization of Fasting Insulin Secretory Bursts

Cited by 7 publications

References 32 publications

Multiple short bouts of exercise over 12-h period reduce glucose excursions more than an energy-matched single bout of exercise

Multiple short bouts of exercise over 12-h period reduce glucose excursions more than an energy-matched single bout of exercise

Alteration of postprandial glucose and insulin concentrations with meal frequency and composition

A two-step deconvolution-analysis-informed population pharmacodynamic modeling approach for drugs targeting pulsatile endogenous compounds

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