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Updated: Aug 26, 2026

Hyperinsulinemic-euglycemic Clamps in Conscious, Unrestrained Mice
Published on: November 16, 2011
Both relative insulin resistance and defective islet beta-cell processing of proinsulin are responsible for transient
Delphine Mitanchez-Mokhtari1, Najiba Lahlou, François Kieffer
1Service de Réanimation Pédiatrique et Néonatale, Hôpital Necker-Enfants Malades, Paris, France. delphine.mitanchez@nck.ap-hop-paris.fr
Insights
Extremely preterm infants with hyperglycemia show defective proinsulin processing and insulin resistance. Insulin infusion effectively lowers glucose levels in these neonates.
Area of Science:
- Neonatalogy
- Endocrinology
- Metabolic Disorders
Background:
- Extremely preterm infants frequently experience hyperglycemia during neonatal intensive care.
- The underlying mechanisms of transient hyperglycemia in this population are not fully understood.
Purpose of the Study:
- To investigate whether defective insulin secretion or insulin resistance is the primary cause of transient hyperglycemia in extremely preterm infants.
- To evaluate beta-cell peptide levels and insulin sensitivity in hyperglycemic preterm neonates.
Main Methods:
- A prospective comparative study involving three groups: hyperglycemic preterm infants, normoglycemic preterm infants, and term neonates.
- Serum proinsulin, insulin, and C-peptide levels were measured using specific immunoassays.
- Changes in beta-cell peptide levels were analyzed during and after intravenous insulin infusion in hyperglycemic infants.
Main Results:
- Hyperglycemic preterm infants had significantly higher proinsulin concentrations compared to controls.
- Proinsulin and C-peptide levels were elevated in normoglycemic preterm infants versus term neonates.
- Insulin infusion in hyperglycemic neonates led to decreased plasma glucose, proinsulin, and C-peptide levels.
Conclusions:
- Preterm neonates exhibit impaired proinsulin processing to insulin during hyperglycemia.
- Hyperglycemic preterm infants demonstrate relative insulin resistance, requiring higher insulin levels for euglycemia.
- Intravenous insulin infusion is a beneficial treatment for transient hyperglycemia in extremely preterm infants.
Objective:
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.
Methods:
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.
Results:
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).
Conclusion:
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.
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