Circulating proinsulin in patients with maturity onset diabetes

Area of Science:

• Endocrinology
• Metabolic Disorders
• Diabetes Research

Background:

• Maturity onset diabetes is characterized by impaired insulin secretion and action.
• Proinsulin is a precursor to insulin, and its proportion in circulation can reflect pancreatic beta-cell function.
• Elevated proinsulin levels have been observed in diabetes, but the relationship with hyperglycemia and treatment is not fully elucidated.

Purpose of the Study:

• To quantify the contribution of proinsulin to total serum immunoreactive insulin (IRI) in patients with maturity onset diabetes.
• To compare proinsulin levels in diabetic patients (on diet or sulfonylurea agents) with healthy controls.
• To investigate the correlation between proinsulin percentage, plasma glucose, and IRI in diabetic individuals.

Main Methods:

• Serum samples were collected from 59 maturity onset diabetes patients and 44 control subjects.
• Proinsulin percentage was measured and compared between groups.
• Statistical analysis was performed to correlate proinsulin levels with plasma glucose and IRI.

Main Results:

• The percentage of proinsulin was significantly increased in 11 diabetic patients compared to controls.
• Increased proinsulin levels correlated with plasma glucose but not with total IRI.
• No significant differences in proinsulin levels were found between diet-treated and sulfonylurea-treated groups, or across different sulfonylurea agents.
• One patient showed normalization of proinsulin proportion after plasma glucose reduction.

Conclusions:

• Hyperglycemic diabetic patients exhibit an increased circulating proportion of proinsulin.
• This elevation is likely secondary to pancreatic beta-cell exhaustion, leading to the release of less mature insulin granules.
• Proinsulin levels may serve as an indicator of beta-cell stress in hyperglycemia.