[Decrease of early insulin secretion, risk factor of insulin-dependent diabetes. Prospective study in families with...

Area of Science:

• Endocrinology
• Immunology
• Genetics

Background:

• Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease with genetic and immunological components.
• Predictive markers for IDDM onset are crucial for early intervention and understanding disease progression.

Purpose of the Study:

• To evaluate the predictive capacity of the first phase insulin response (FPIR) for the development of IDDM.
• To assess the utility of FPIR in conjunction with islet-cell antibodies (ICA) and HLA-typing for risk stratification.

Main Methods:

• Prospective study of 220 first-degree relatives of IDDM patients (aged 2-29 years).
• Intravenous glucose tolerance tests (IVGTT) to measure FPIR, ICA determination, and HLA-typing.
• Follow-up for 18 months to 8 years to monitor disease development.

Main Results:

• Mean FPIR was significantly lower in ICA-positive subjects compared to ICA-negative subjects.
• A single low FPIR measurement did not predict individual IDDM development.
• ICA-positive subjects showed persistently low or decreasing FPIR over time, unlike ICA-negative subjects.
• Among 9 subjects who developed IDDM, most had persisting ICA and specific HLA types; FPIR was consistently low in only 3.

Conclusions:

• FPIR is a less reliable individual predictor of IDDM compared to persisting ICA and specific HLA genotypes.
• Changes in FPIR over time may reflect distinct disease trajectories in ICA-positive versus ICA-negative individuals.
• Combined immunological and genetic factors offer better risk assessment for IDDM than FPIR alone.