c-peptide and Infant--Premature--Diseases

The aim of the study was to characterize factors that may serve as clinical tools to identify neonates with transient neonatal hyperinsulinism hypoglycemia (HH) who may benefit from diazoxide treatment. This retrospective study included 141 neonates with transient HH (93 males) of whom 34 (24%) were treated with diazoxide. Diazoxide treatment was started at median age of 13 days (range 5-35) and discontinued at median age of 42 days (range 14-224). The maximal dose was 7.1 ± 2.3 mg/kg/day. Diazoxide-treated neonates required a higher glucose infusion rate (GIR) compared with non-treated neonates (16.6 ± 3.4 vs. 10.4 ± 4.0 mg/kg/min, respectively, P < .01), had a longer duration of intravenous fluids (15.9 ± 9.3 vs. 7.8 ± 6.5 days, P < .01), a longer hospitalization (32.8 ± 22.7 vs. 20.4 ± 13.4 days, P < .01), a longer duration of carbohydrate supplementation (38.9 ± 40.4 vs. 17.8 ± 21.4 days, P < .01), and higher mean C-peptide levels on "critical sample" (1.4 ± 0.9 vs. 0.8 ± 0.5 ng/ml, P < .01). Their insulin levels also tended to be higher (3.5 ± 2.9 vs. 2.2 ± 3.8 μU/ml, P = .07). A stepwise logistic regression model revealed that significant predictors of prolonged HH were maximal GIRs (odds ratio (OR) 1.56, 95%; confidence interval (CI) 1.3-1.88, P < .001) and C-peptide levels (OR 3.57, 95%; CI 1.3-12.1, P = .005).Conclusion: Higher C-peptide levels and higher GIR requirements may serve as clinical tools to identify neonates with transient HH who may benefit from diazoxide treatment.What is Known:• Neonates with transient hyperinsulinism usually do not require treatment beyond glucose supplementation due to its self-limited clinical course, but some may benefit from diazoxide treatment.What is New:• Higher C-peptide levels and higher GIR requirements may serve as clinical tools to identify neonates with transient HH who may benefit from diazoxide treatment.• The incidence of prolonged neonatal HH is higher than the currently accepted figures.

Topics: Adult; Blood Glucose; C-Peptide; Case-Control Studies; Diazoxide; Female; Gestational Age; Humans; Hyperinsulinism; Hypoglycemia; Infant; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Pregnancy; Retrospective Studies

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.. 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.. 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).. 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.

Topics: Blood Glucose; C-Peptide; Decision Support Techniques; Female; Humans; Infant, Extremely Premature; Infant, Newborn; Infant, Premature, Diseases; Insulin; Insulin Secretion; Intensive Care, Neonatal; Male; Pancreas; Retrospective Studies

Many extremely preterm infants develop hyperglycemia in the first week of life during continuous glucose infusion. The objective of this study was to determine whether defective insulin secretion or resistance to insulin was the primary factor involved in transient hyperglycemia of extremely preterm infants.. A prospective comparative study was conducted in appropriate-for-gestational-age preterm infants <30 weeks of gestational age with the aim specifically to evaluate the serum levels of proinsulin, insulin, and C-peptide secreted during transient hyperglycemia by specific immunoassays. Three groups of infants were investigated hyperglycemic (n = 15) and normoglycemic preterm neonates (n = 12) and normal, term neonates (n = 21). In addition, the changes in beta-cell peptide levels were analyzed during and after intravenous insulin infusion in the hyperglycemic group. Data were analyzed using analysis of variance and analysis of variance for repeated measures.. At inclusion, insulin and C-peptide levels did not differ in hyperglycemic subjects and in preterm controls. Proinsulin concentration was significantly higher in the hyperglycemic group (36.5 +/- 3.9 vs 23.2 +/- 0.9 pmol/L). Compared with term neonates, proinsulin and C-peptide levels were higher in normoglycemic preterm infants (23.2 +/- 0.9 vs 18.9 +/- 2.71 pmol/L and 1.67 +/- 0.3 vs 0.62 +/- 0.12 nmol/L, respectively). During and after insulin infusion in hyperglycemic neonates, plasma glucose concentration fell and proinsulin and C-peptide levels were lowered (18.4 +/- 7.6 and 20.7 +/- 4.5 pmol/L, respectively).. These data suggest that 1) preterm neonates are sensitive to changes in plasma glucose concentration, but proinsulin processing to insulin is partially defective in hyperglycemic preterm neonates; 2) hyperglycemic neonates are relatively resistant to insulin because higher insulin levels are needed to achieve euglycemia in this group compared with normoglycemic neonates. These results also show that insulin infusion is beneficial in extremely preterm infants with transient hyperglycemia.

Topics: Blood Glucose; C-Peptide; Female; Humans; Hyperglycemia; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Insulin; Insulin Resistance; Islets of Langerhans; Male; Proinsulin; Prospective Studies

Polycythaemia in the neonate is a serious pathologic entity which occurs particularly in infants of diabetic mothers (IDM) and small-for-gestational age (SGA) infants. Both of these conditions are associated with fetal hyperinsulinaemia. Cultures of cord blood mononuclear cells from polycythaemic IDM showed increased growth of late erythroid progenitor colonies, compared to cord blood mononuclear cells from non-polycythaemic infants, reflecting a possible expansion of this progenitor population in the polycythaemic fetus. No changes were observed in early erythroid progenitor populations. Biosynthetic human insulin at physiological levels characteristic of IDM stimulated growth in culture of late erythroid progenitors in cord blood from premature, term and IDM infants. Three out of five polycythaemic infants had elevated cord blood plasma levels of insulin C-peptide at birth, whereas no infant with a haematocrit of less than 65% had high insulin C-peptide measurements. These data suggest that the polycythaemia noted in infants of diabetic mothers may be secondary, in large part, to a stimulatory effect on erythroid progenitor growth by the hyperinsulinaemic environment in which they develop in utero.

Topics: C-Peptide; Cell Division; Cells, Cultured; Colony-Forming Units Assay; Diabetes Complications; Diabetes Mellitus; Female; Fetal Blood; Hematopoietic Stem Cells; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Insulin; Polycythemia; Pregnancy; Pregnancy in Diabetics