Plasma proinsulin in recently diagnosed type 2 diabetes mellitus

We measured levels of immunoreactive insulin (IRI) and proinsulin using a sensitive and specific immunoradiometric assay (IRMA), in non-obese recently diagnosed type 2 diabetic subjects. The proinsulin IRMA showed full cross reaction with intact proinsulin, des 31-32 proinsulin and des 64-65 proinsulin, but no reaction with insulin or C-peptide. In a group of 41 recently diagnosed non-obese Caucasian type 2 diabetic subjects (study group), mean fasting proinsulin levels were greater than that of 40 age and body mass index (BMI) matched controls (study group 17.4 +/- 2.0, controls 10.1 +/- 0.9 pmol-1, P < 0.001). Following a standard test meal, 30 and 60 min levels were not significantly different between groups but 90- and 120-min proinsulin levels were elevated in the study group. The maximum proinsulin to IRI ratio was 20% in the fasting state and did not differ between study and control groups. Proinsulin profiles were similar in subjects receiving oral hypoglycaemic agents and those on dietary treatment alone. Proinsulin did not correlate with indices of glycaemic control, total cholesterol, triglycerides or HDL cholesterol, but a relationship was observed with IRI before and after the meal. These results suggest that increased secretion of insulin precursors of low biological activity occurs in non obese recently diagnosed type 2 diabetic subjects under reasonably good glycaemic control; in such individuals the elevated levels of these precursors are approximately in proportion to the increase in IRI and are less than those reported in some previous studies.