Treatment with recombinant human insulin-like growth factor (rhIGF)-I/rhIGF binding protein-3 complex improves metabolic control in subjects with severe insulin resistance.

Abstract

Diabetes in the context of severe insulin resistance (SIR) presents a major therapeutic challenge because conventional therapies including insulin and insulin sensitizers often fail to achieve adequate metabolic control. Adjunctive therapy with recombinant human IGF-I (rhIGF-I)/recombinant human IGF binding protein-3 (rhIGFBP-3) has been shown to improve insulin sensitivity in both type 1 and type 2 diabetes and may have a role in the treatment of SIR. We report clinical and physiological outcomes after adjunctive therapy with rhIGF-I/rhIGFBP-3 in five subjects with SIR. Five females (median age, 17 yr; range, 5-37) with SIR (two with pathogenic insulin receptor mutations) were treated with 0.5-2.0 mg/kg rhIGF-I/rhIGFBP-3 using a 16-wk dose escalation protocol. Glycosylated hemoglobin was recorded monthly. At baseline and end of treatment all patients were evaluated using continuous glucose monitoring sensing and admitted for overnight GH profiling and insulin-modified stable-label iv glucose tolerance test. Changes in body composition were assessed using dual-energy x-ray absorptiometry and magnetic resonance imaging. Treatment with rhIGF-I/rhIGFBP-3 was well tolerated, and all subjects reported clinical improvements with reduction in acanthosis nigricans. Glycosylated hemoglobin was reduced (8.5% pretreatment to 7.1%; P < 0.03) with a trend toward reduction in mean continuous glucose monitoring sensing glucose (10.7 vs. 8.5 mmol/liter; P = 0.08). Effects of treatment on other biochemical measures were variable, but there was a trend toward improved C-peptide responses during the iv glucose tolerance test. rhIGF-I/rhIGFBP-3 is well tolerated and clinically effective in subjects with SIR.