Metabolic effects of biosynthetic human proinsulin in type 2 diabetes mellitus

Abstract. Due to a longer plasma half‐life and half‐time of action on glucose metabolism biosynthetic human proinsulin was thought to be an alternative to long‐acting insulin preparations. To test this hypothesis we studied 23 type 2 diabetic patients who could no longer be treated sufficiently with oral hypoglycaemic agents. After an initial 1 week phase during which all patients received protamine bound insulin twice daily, the patients either continued on NPH insulin (Group A, n= 11) or were randomly switched to human proinsulin (Group B, n= 12). Glucose profiles and peripheral and hepatic insulin sensitivity (euglycaemic clamp: 120 mU m‐2 min‐1) were measured at the end of the initial period (Time 1) and 1 week later (Time 2). The insulin‐mediated glucose disposal (RD) was not changed after either treatment (group A: 176±18 vs. 192±19 mg m‐2 min‐1; group B: 175 ± 15 vs.174±12 mg m‐2 min‐1 for times 1 and 2, respectively, NS). Suppression of hepatic glucose output (HGO) was complete in both groups at both times. Fasting blood glucose levels (FBG) and basal HGO were equally low at times 1 and 2 (group A: FBG 118 vs. 123 mg dl‐1, BHGO 81 vs. 79 mg m‐2 min‐1; group B: FBG 118 vs. 106 mg dl‐1, BHGO 87 vs. 84 mg m‐2 min‐1; NS). Mean blood glucose levels (MBG) were unchanged in the group receiving NPH insulin (164 vs. 162 mg dl‐1; NS) but improved in group B (182 vs. 142 mg dl‐1; P < 0.001). Blood glucose levels were lower in group B, expecially during the afternoon (from 12.00 to 19.00 h). Insulin requirement was the same in group A at times 1 and 2; in group B the proinsulin dosage was reduced significantly to 33 U day‐1 at time 2 as compared to an insulin dose of 41 U day‐1 at time 1 (P < 0.01). In summary, equal metabolic control can be achieved with proinsulin compared to protamine bound insulin with a lower dose on a unit base for proinsulin. Peripheral and hepatic insulin sensitivity remain unchanged during proinsulin therapy compared to NPH insulin treatment.