Elevated plasma proinsulin/insulin ratio is a marker of reduced insulin secretory capacity in healthy young men

Aim: To examine whether reduced insulin secretory capacity or increased insulin secretory demand is associated with elevated ratio of plasma proinsulin to immunoreactive insulin (PI/IRI ratio) in non-diabetic subjects. Subjects and Methods: We measured various indices of insulin secretory function and insulin sensitivity by frequently sampled intravenous glucose tolerance test (FSIGT) and hyerglycemic glucose clamp in 21 healthy young men. We then examined the relationships between these indices and PI, IRI, or PI/IRI ratio in the fasting state. Results: Insulin sensitivity index (S-1) measured by FSIGT correlated inversely with basal IRI (r=-0.53, P<0.01) and Pi levels (r=-0.57, P<0.01), but there was no significant correlation between S-1 and Pl/IRI ratio (r = 0.26, NS). On the other hand, PI/IRI ratio correlated inversely with insulin secretory indices, such as acute insulin responses during FSIGT(r = - 0.46, P < 0.01) and hyperglycemic glucose clamp (r=-0.54, P<0.01) and submaximum insulin response during hyperglycemic glucose clamp (r=-0.59, P(0.01). Conclusions: These results indicate that elevated PI/IRI ratio may serve as a marker of reduced insulin secretory function in non-diabetic subjects.