A C-Peptide-Based Model of Pancreatic Insulin Secretion in Extremely Preterm Neonates in Intensive Care

Abstract

Background: Model-based glycemic control relies on sufficiency of underlying models to describe underlying patient physiology. In particular, very preterm infant glucose-insulin metabolism can differ significantly from adults, and is relatively unstudied. In this study, C-peptide concentrations are used to develop insulin-secretion models for the purposes of glycemic control in neonatal intensive care.

Methods: Plasma C-peptide, insulin, and blood glucose concentrations (BGC) were retrospectively analyzed from a cohort of 41 hyperglycemic very preterm (median age 27.2 [26.2-28.7] weeks) and very low birth-weight infants (median birth weight 839 [735-1000] g). A 2-compartment model of C-peptide kinetics was used to estimate insulin secretion. Insulin secretion was examined with respect to nutritional intake, exogenous and plasma insulin concentration, and BGC.

Results: Insulin secretion was found to be highly variable between patients and over time, and could not be modeled with respect to age, weight, or protein or dextrose intake. In 13 of 54 samples exogenous insulin was being administered, and insulin secretion was lower. However, low data numbers make this result inconclusive. Insulin secretion was found to increase with BG, with a stronger association in female infants than males (R(2) = .51 vs R(2) = .13, and R(2) = .26 for the combined cohort).

Conclusions: A sex-based insulin secretion model was created and incorporated into a model-based glycemic control framework. Nutritional intake did not predict insulin secretion, indicating that insulin secretion is a complex function of a number of metabolic factors.

Keywords: glycemic control; insulin secretion; insulin therapy; physiological modeling; very preterm infants.

Figure 1.

Insulin secretion is highly variable with birth weight.

Figure 2.

Endogenous insulin secretion and blood glucose concentration (BGC) with respect to protein (a and b) and total dextrose intake (c and d) on the day the sample was taken. In (a) and (c) data points are scaled in size by the magnitude of nutritional intake, with data points from infants with a larger mass of intake being larger in size.

Figure 3.

Endogenous insulin secretion with (a) blood glucose concentration (BGC) and plasma insulin concentration, and (b) plasma insulin. In (a) data points are scaled in size by the magnitude of plasma insulin, with larger data points representing samples with higher plasma insulin concentration. Open (o) and closed (●) circles denote results from infants not receiving and receiving exogenous insulin at the time of sampling, respectively.

Figure 4.

Models of endogenous insulin secretion as a function of blood glucose concentration (BGC) over the whole cohort and male and female subcohorts. A total of 5 data points from 54 total (9%) were excluded from the analysis as outliers based on a 2- to 3-fold difference with other data points of similar BGC. Of these data points, 3/5 were from heavier and older patients of GA > 29 weeks. However, 2 were from male and female babies with a GA of 26 weeks.