High proinsulin levels in late PRE-IDDM stage

Area of Science:

• Endocrinology
• Diabetes Research
• Immunology

Background:

• Insulin-dependent diabetes mellitus (IDDM) has a significant genetic component, with first-degree relatives exhibiting varying risks.
• Early identification of individuals at high risk for IDDM is crucial for potential interventions.

Purpose of the Study:

• To analyze fasting proinsulin levels in first-degree relatives of IDDM patients.
• To assess the predictive value of proinsulin and proinsulin/insulin ratio for IDDM development.

Main Methods:

• Studied 33 first-degree relatives of IDDM patients, stratified by risk based on first-phase insulin release (FPIR) and islet cell antibodies (ICA).
• Measured fasting proinsulin (PRO) and insulin (IRI) levels using radioimmunoassay (RIA), calculating the PRO/IRI ratio.
• Monitored development of IDDM over 2-32 months.

Main Results:

• Four individuals in the highest-risk group (diminished FPIR, ICA > 20 JDF U) developed IDDM.
• While no significant differences in fasting PRO or PRO/IRI ratio were found between risk groups initially, subjects who developed IDDM had significantly higher PRO and PRO/IRI ratio levels.
• Elevated fasting PRO and PRO/IRI ratio were associated with subsequent IDDM development.

Conclusions:

• Fasting proinsulin levels and the PRO/IRI ratio serve as potential additional markers for IDDM risk.
• These markers are particularly relevant in post-pubertal first-degree relatives with immunological and metabolic indicators of high risk.
• This finding aids in identifying individuals who may benefit from closer monitoring or early intervention strategies.