Tissue IGF-I measured by microdialysis reflects body glucose utilization after rhIGF-I injection in type 1 diabetes

Abstract

Context: Type 1 diabetes is associated with portal insulin deficiency and disturbances in the GH-IGF axis including low circulating IGF-I and GH hypersecretion. Whether peripheral hyperinsulinemia and GH hypersecretion, which are relevant to the development of vascular complications, result in elevated tissue IGF-I remains unknown. Objective: The purpose of this study was to determine the relationship between whole-body glucose uptake and tissue IGF-I measured by microdialysis. Design: This was a single-blind placebo-controlled crossover study. Setting: The setting was a tertiary pediatric endocrine referral center. Participants: The participants were seven young male adults with type 1 diabetes. Intervention: After an overnight fast, a 6-h lasting euglycemic clamp was performed (constant insulin infusion at 0.5mU/kg×minute and variable glucose infusion rate [GIR]) and a subcutaneous injection of recombinant human (rh) IGF-I (120-g/kg) or saline was given after 2 hours. In parallel, tissue IGF-I levels were determined by microdialysis (md-IGF-I). Main Outcome Measures: md-IGF-I levels in muscle and subcutaneous fat, and GIR were determined. Results: md-IGF-I levels were detectable but unchanged after saline. After rhIGF-I, muscle and subcutaneous fat md-IGF-I increased during the second and third hour and then reached a plateau up to 10-fold higher than baseline (P-.001). GIR was unchanged after saline, whereas it increased 2.5-fold concomitantly with the increase in md-IGF-I (P < .0001). Conclusion:Wedemonstrate that md-IGF-I measurements are valid and physiologically relevant by reflecting rhIGF-I-induced glucose uptake. Future studies should be conducted to elucidate the role of local tissue IGF-I in diabetic vascular complications.