Model-based subcutaneous insulin for glycemic control of pre-term infants in the neonatal intensive care unit

Zhou, Tony; Boettger, Merle H.; Knopp, Jennifer L.; Lange, Marc; Heep, A.; Chase, J. Geoffrey

doi:10.1016/j.compbiomed.2023.106808

Cited by 4 publications

(2 citation statements)

References 62 publications

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“…It has to be acknowledged that comparison has been limited to methods relying on C-peptide, although other methods based on “glucose correction” have been proposed 11 . The reason for this choice relies on the fact that methods based on glucose were developed in applications devoted to glucose control, thus in conditions in which additional simplifying assumptions are needed.…”

Section: Discussionmentioning

confidence: 99%

“…However, issues related to the quantification of endogenous insulin secretion were often ignored since suppression of this component can be obtained through experimental procedures (e.g., hyper-insulinemic clamp or somatostatin administration), which, however, are complex to perform, present drawbacks for the individual and may be not fully effective in achieving adequate suppression 10 . When experimental conditions are more physiological and thus do not involve endogenous insulin suppression (as in mixed meal tolerance test), simple “baseline correction” methods are exploited that assume a single value of plasma glucose, insulin or C-peptide reflecting the endogenous component and correct the total plasma insulin for this constant quantity 11 – 13 . Plasma C-peptide is commonly considered a more reliable marker with respect to insulin since it is co-secreted with insulin in equimolar amount, but it is not extracted to a significant extent by the liver.…”

Section: Introductionmentioning

confidence: 99%

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An in-silico modeling approach to separate exogenous and endogenous plasma insulin appearance, with application to inhaled insulin

Piersanti,

Pacini,

Tura

et al. 2024

Sci Rep

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The aim of this study was to develop a dynamic model-based approach to separately quantify the exogenous and endogenous contributions to total plasma insulin concentration and to apply it to assess the effects of inhaled-insulin administration on endogenous insulin secretion during a meal test. A three-step dynamic in-silico modeling approach was developed to estimate the two insulin contributions of total plasma insulin in a group of 21 healthy subjects who underwent two equivalent standardized meal tests on separate days, one of which preceded by inhalation of a Technosphere® Insulin dose (22U or 20U). In the 30–120 min test interval, the calculated endogenous insulin component showed a divergence in the time course between the test with and without inhaled insulin. Moreover, the supra-basal area-under-the-curve of endogenous insulin in the test with inhaled insulin was significantly lower than that in the test without (2.1 ± 1.7 × 104 pmol·min/L vs 4.2 ± 1.8 × 104 pmol·min/L, p < 0.01). The percentage of exogenous insulin reaching the plasma, relative to the inhaled dose, was 42 ± 21%. The proposed in-silico approach separates exogenous and endogenous insulin contributions to total plasma insulin, provides individual bioavailability estimates, and can be used to assess the effect of inhaled insulin on endogenous insulin secretion during a meal.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

An in-silico modeling approach to separate exogenous and endogenous plasma insulin appearance, with application to inhaled insulin

Piersanti,

Pacini,

Tura

et al. 2024

Sci Rep

View full text Add to dashboard Cite

show abstract

Assessment of food supplements for the prevention of necrotizing enterocolitis in preterm neonates: A systematic review and network meta-analysis

Zhou,

Yang,

Wang

et al. 2023

Computers in Biology and Medicine

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A stochastic model-based control methodology for glycemic management in the intensive care unit

Sirlanci,

Hripcsak,

Low Wang

et al. 2024

Front. Med. Eng.

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Introduction: Intensive care unit (ICU) patients exhibit erratic blood glucose (BG) fluctuations, including hypoglycemic and hyperglycemic episodes, and require exogenous insulin delivery to keep their BG in healthy ranges. Glycemic control via glycemic management (GM) is associated with reduced mortality and morbidity in the ICU, but GM increases the cognitive load on clinicians. The availability of robust, accurate, and actionable clinical decision support (CDS) tools reduces this burden and assists in the decision-making process to improve health outcomes. Clinicians currently follow GM protocol flow charts for patient intravenous insulin delivery rate computations.Methods: We present a mechanistic model-based control algorithm that estimates the optimal intravenous insulin rate to keep BG within a target range; the goal is to develop this approach for eventual use within CDS systems. In this control framework, we employed a stochastic model representing BG dynamics in the ICU setting and used the linear quadratic Gaussian control methodology to develop a controller.Results: We designed two experiments, one using virtual (simulated) patients and one using a real-world retrospective dataset. Using these, we evaluated the safety and efficacy of this model-based glycemic control methodology. The presented controller avoids hypoglycemia and hyperglycemia in virtual patients, maintaining BG levels in the target range more consistently than two existing GM protocols. Moreover, this methodology could theoretically prevent a large proportion of hypoglycemic and hyperglycemic events recorded in a real-world retrospective dataset.Discussion: The current version of the methodology shows potential usefulness in GM of ICU patients. However, it is limited to a subgroup of the ICU patient population, who are fed through and enteral tube and delivered intravenous insulin. After extending to a broader ICU patient population who can consume oral nutrition and are delivered subcutaneous insulin for GM, the methodology could be tested with pilot studies and clinical trials for eventual use as a CDS tool.

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Model-based subcutaneous insulin for glycemic control of pre-term infants in the neonatal intensive care unit

Cited by 4 publications

References 62 publications

An in-silico modeling approach to separate exogenous and endogenous plasma insulin appearance, with application to inhaled insulin

An in-silico modeling approach to separate exogenous and endogenous plasma insulin appearance, with application to inhaled insulin

Assessment of food supplements for the prevention of necrotizing enterocolitis in preterm neonates: A systematic review and network meta-analysis

A stochastic model-based control methodology for glycemic management in the intensive care unit

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