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Short-Term Effects of the Long-Acting Insulin Analog Detemir and Human Insulin on Plasma Levels of Insulin-Like Growth Factor-I and Its Binding Proteins in Humans

Department of Internal Medicine (F.P., P.R., P.Ca., P.L., P.Ci., A.M.A., G.B.B., C.G.F.), Section of Internal Medicine, Endocrinology and Metabolism, University of Perugia, 06126 Perugia, Italy; and Division of Endocrinology and Metabolism (E.G.), Department of Internal Medicine, University of Torino, 10126 Torino, Italy

Address all correspondence and requests for reprints to: Prof. Geremia B. Bolli, University of Perugia, Department of Internal Medicine, Via E. Dal Pozzo, 06126 Perugia, Italy. E-mail: gbolli{at}unipg.it.

Objective: The objective of the study was to compare responses of plasma levels of IGF-I and IGF binding proteins (IGFBP-1 and IGFBP-3) induced by human regular insulin (HI) and the long-acting insulin analog detemir (IDet) at doses equivalent with respect to the glucose-lowering effect.

Experimental Design: Ten nondiabetic subjects (six males, four females; age, 36 ± 7 yr; body mass index, 22.9 ± 2.6 kg/m²) were studied on four randomized occasions with iv infusion of IDet (2 mU/kg · min for 4 h, followed by 4 mU/kg · min for 1 h) or HI (1 mU/kg · min for 4 h, followed by 2 mU/kg · min for 1 h) in euglycemia [plasma glucose (PG), 90 mg/dl] or during stepped hypoglycemia (PG, 90, 78, 66, 54, and 42 mg/dl).

Results: PG was maintained at preselected plateaus, without any significant difference between IDet and HI (P > 0.2). Plasma insulin concentrations were on average approximately nine times greater with IDet than HI (749 ± 52 vs. 83 ± 19 µU/ml, respectively). Plasma IGF-I concentrations did not change from baseline during insulin infusion in euglycemia (IDet, 147 ± 16 ng/ml; HI, 155 ± 15 ng/ml) and hypoglycemia (IDet, 163 ± 14 ng/ml; HI, 165 ± 14 ng/ml) with no differences between the two insulins (P > 0.2). A similar pattern was observed for plasma IGFBP-3 levels. Insulin infusion resulted in a suppression of plasma IGFBP-1 concentrations with no differences between IDet (baseline, 16.6 ± 3.8 ng/ml; endpoint, 2.0 ± 0.6 ng/ml) and HI (baseline, 16.6 ± 4.1 ng/ml; endpoint, 2.6 ± 1.4 ng/ml) (P > 0.2) and study conditions (P > 0.2).

Conclusions: The greater plasma insulin concentrations obtained with IDet exert effects on plasma levels of IGF-I, IGFBP-1, and IGFBP-3 similar to those of HI. Additional studies are needed to confirm these short-term results in patients with diabetes mellitus on long-term treatment with IDet.