Normalization of the IGF-IGFBP axis by sustained nightly insulinization in type 1 diabetes.
OBJECTIVE
We sought to test the hypothesis that start of insulin glargine with sustained nightly insulin action results in changes in circulating concentrations of IGF-I and IGF binding proteins (IGFBPs) in adolescents with type 1 diabetes-changes that may support improvement of A1C.


METHODS
Twelve pubertal adolescents with type 1 diabetes and initially on NPH insulin were studied during 12 weeks of intensified treatment with glargine.


RESULTS
Subnormal IGF-I SD scores on NPH (-1.8 +/- 0.4) rapidly increased and remained 54 +/- 9% elevated (P < 0.001) after 12 weeks on glargine. A1C decreased from 8.3 +/- 0.6% to a nadir of 6.9 +/- 0.3% (P = 0.002) at 6 weeks and correlated with changes in IGF-I (r = -0.64, P < 0.05). The increase in IGF-I did not suppress the mean overnight growth hormone (GH) secretion at 6 weeks. The mean overnight IGFBP-1 levels decreased (P = 0.035), supporting the hypothesis that the nightly hepatic insulin action was increased. Circulating IGF-I increased in the absence of changes in both GH secretion and GH receptor numbers (assessed by growth hormone binding protein), indicating that postreceptor mechanisms are involved. IGFBP-3 proteolysis was decreased.


CONCLUSIONS
Increased hepatic insulin action after start of glargine was evident from a decrease in night time IGFBP-1 concentrations. This may improve GH postreceptor signaling, resulting in increased circulating IGF-I. We suggest that even in the absence of changes in GH, increased IGF-I and decreased IGFBP-1 support the improvement of metabolic control.
Ekström
Klas
K
Pediatric Endocrinology Unit, Department of Woman and Child Health, Karolinska Institute, Stockholm, Sweden.
Salemyr
Jenny
J
Zachrisson
Ingmar
I
Carlsson-Skwirut
Christine
C
Ortqvist
Eva
E
Bang
Peter
P
D000293:Adolescent; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy; D004334:Drug Administration Schedule; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007336:Insulin, Isophane / Q000008:administration & dosage / Q000627:therapeutic use*; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D011627:Puberty
D007004:Hypoglycemic Agents; D018969:Insulin-Like Growth Factor Binding Proteins; D019382:Human Growth Hormone; D007336:Insulin, Isophane; D007334:Insulin-Like Growth Factor I