Relationship between proinsulin-to-insulin ratio and advanced glycation endproducts in Japanese type 2 diabetic subjects.

OBJECTIVE

Type 2 diabetes (T2DM) is characterized by increased proinsulin-to-insulin ratio (P/I ratio), increased glycation and oxidative stress, and beta-cell dysfunction. Previous reports implicated that increased P/I ratio, glycation and oxidative stress constitute markers of beta-cell dysfunction in T2DM. However, its clinical relevance remains to be elucidated. Therefore, in the present study we investigated the relationship between the P/I ratio, glycation and oxidative stress markers in patients with T2DM, using newly developed intact chemiluminescent immunoassay for proinsulin.

METHODS

Fasting intact proinsulin, insulin, advanced glycation endproducts (AGEs), pentosidine, lipid peroxide and urine 8-isoprostane as well as other metabolic parameters were measured in 64 T2DM subjects.

RESULTS

Using univariate analysis, P/I ratio showed significant positive correlations with plasma glucose (r=0.465), HbA1c (r=0.434) and AGEs (r=0.282), and significant negative correlations with insulin (r=-0.330) and HOMA-beta (r=-0.520) even after adjustment for age, sex, duration of diabetes, family history of diabetes, use of sulfonylureas, smoking and body mass index. Additionally, stepwise multiple regression analysis revealed that HOMA-beta, HbA1c and AGEs were independently and significantly correlated with P/I ratio.

CONCLUSION

These findings suggest that not only hyperglycemia per se but also glycation is involved in beta-cell dysfunction in T2DM subjects.