Endocrine Abstracts

Introduction: Proinsulin is a propeptide of insulin and C-peptide during physiological insulin production and is increased in patients with type 2 diabetes. Increased proinsulin in peripheral blood indicates impairment of cleavage capacity to process insulin within the beta cell. Recently, chemiluminescence assays have been developed that are able to specifically measure uncleaved intact proinsulin in peripheral blood. In this cross-sectional study, we investigated the relationship between intact proinsulin and insulin resistance and secretion in Korean adults.

Methods: We performed standard 75 g oral glucose tolerance test (OGTT) after an overnight fast in 388 subjects without history of diabetes. Glucose (0, 30, 60, 90, 120 min), insulin (0, 30, 60, 90, 120 min), C-peptide (0, 30 min), and fasting intact proinsulin were measured and insulin sensitivity and secretory indexes were calculated using the results of OGTT.

Results: Average age was 54.6±11.8 years and 41.5% of the subjects were male. Intact proinsulin level was positively correlated with homeostasis model assessment insulin resistance (HOMA-IR) (r=0.504, P<0.001) and was inversely correlated with insulin sensitivity indexes (Matsuda index: r=−0.445, P<0.001; OGIS: r=−0.399, P<0.001). However, there were no significant correlations between intact proinsulin and insulin secretory indexes (HOMA-beta).Total subjects were stratified by glucose tolerance status; normal glucose tolerance (NGT, n=33), prediabetes (impaired fasting glucose and/or impaired glucose tolerance, n=153), and diabetes mellitus (DM, n=202). Intact proinsulin level showed an increasing tendency with the deterioration of glucose tolerance (P<0.001). In the NGT group, intact proinsulin level was correlated with acute phase insulin secretion (insulinogenic index) but not with the indexes reflecting insulin sensitivity. However, in the prediabetes and DM groups, intact proinsulin levels were inversely correlated with insulin sensitivity indexes (Matsuda index and OGIS index).

Conclusions: Intact proinsulin level increases with the deterioration of glucose tolerance and is significantly correlated with insulin resistance indexes. Moreover, intact proinsulin partly reflects beta cell function.