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.
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.


METHODS
Ten nondiabetic subjects (six males, four females; age, 36 +/- 7 yr; body mass index, 22.9 +/- 2.6 kg/m(2)) 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 muU/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.
Porcellati
Francesca
F
University of Perugia, Department of Internal Medicine, Via E. Dal Pozzo, Perugia, Italy.
Rossetti
Paolo
P
Candeloro
Paola
P
Lucidi
Paola
P
Cioli
Patrizia
P
Andreoli
Anna Marinelli
AM
Ghigo
Ezio
E
Bolli
Geremia B
GB
Fanelli
Carmine G
CG
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D002096:C-Peptide / Q000032:analysis; D005260:Female; D006801:Humans; D007328:Insulin / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology*; D000069057:Insulin Detemir; D049528:Insulin, Long-Acting; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D008297:Male
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D049528:Insulin, Long-Acting; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D000069057:Insulin Detemir; D007334:Insulin-Like Growth Factor I