Normal proinsulin processing despite beta-cell dysfunction in persistent hyperinsulinaemic hypoglycaemia of infancy...

Area of Science:

• Endocrinology
• Genetics
• Metabolic Disorders

Background:

• Persistent hyperinsulinaemic hypoglycaemia of infancy (PHHI) is a genetic disorder characterized by severe neonatal hypoglycemia due to beta-cell dysfunction.
• PHHI can lead to NIDDM (non-insulin-dependent diabetes mellitus) later in life.
• Understanding proinsulin processing in PHHI is crucial for disease management and prognosis.

Purpose of the Study:

• To investigate proinsulin processing in PHHI patients with active disease, post-pancreatectomy, and in clinical remission.
• To compare proinsulin-like peptide levels between PHHI patients and age-matched control subjects.
• To determine if abnormal proinsulin processing is an intrinsic feature of PHHI.

Main Methods:

• Measurement of fasting insulin, intact proinsulin, and des 31,32 split proinsulin levels.
• Analysis of proinsulin-like peptide species and ratios in different PHHI patient groups and controls.
• Correlation analysis of peptide levels with age and BMI in healthy individuals.

Main Results:

• Des 31,32 split proinsulin levels and their proportion were significantly higher in pancreatectomized PHHI patients compared to non-pancreatectomized patients and controls.
• Proinsulin-like peptide levels were similar in PHHI patients with active disease and those in remission.
• Fasting insulin and proinsulin levels correlated with age and BMI in healthy subjects.

Conclusions:

• Relative hyperproinsulinaemia is observed in PHHI patients with increased secretory demand post-pancreatectomy, not in those with active disease or remission.
• Abnormal proinsulin processing is not an intrinsic feature of PHHI, despite severe beta-cell dysfunction.
• These findings highlight the adaptive response of beta cells to increased demand in PHHI.