Porcellati F, Rossetti P, Candeloro P, Lucidi P, Cioli P, Andreoli AM, Ghigo E, Bolli GB, Fanelli CG
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. [JOURNAL ARTICLE]
J Clin Endocrinol Metab 2009 May 26.
Objective: The objective of the study was to compare responses of plasma levels of IGF-I and IGF- binding proteins (IGFBP-1, -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 non-diabetic subjects (6 males, age 36+/-7 years, BMI 22.9+/-2.6 kg/m(2)) were studied on 4 randomized occasions, with i.v. infusion of IDet (2 mU/kg/min for 4h, followed by 4 mU/kg/min for 1h) or HI (1 mU/kg/min for 4h, followed by 2 mU/kg/min for 1h) 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 pre-selected plateaus, without any significant difference between IDet and HI (p>0.2). Plasma insulin concentrations were on average approximately 9 times greater with IDet than HI (749+/-52 microU/ml vs 83+/-19 microU/ml, respectively). Plasma IGF-I concentrations did not change from baseline during insulin infusion in euglycemia (IDet 147+/-16, HI 155+/-15 ng/ml) and hypoglycemia (IDet 163+/-14, HI 165+/-14 ng/ml) with no differences between the two insulins (p>0.2). 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, endpoint 2.0+/-0.6 ng/ml) and HI (baseline 16.6+/-4.1, 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 and IGFIBP-1 and IGFIBP-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.
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