LONG-TERM EFFECTS OF GH REPLACEMENT THERAPY ON GLUCOSE METABOLISM IN CHILDREN WITH GH DEFICIENCY

Objectives: The aim of our study was to evaluate the effects
of GH deficiency (GHD) and GH replacement therapy (GHRT)
on glucose metabolism in a large cohort of children with GHD
before and during GHRT.
Methods: We evaluated glucose, insulin, HOMA, QUICKI and
HbA1c levels in 100 GHD children aged 9.4±3.7 years at
diagnosis and 1 and 5 years after the start of GHRT. One
hundred healthy children age-, sex- and BMI-comparable to
patients were evaluated at baseline and after 1 and 5 years of
follow-up as controls.
Results: At baseline glucose metabolism parameters were
comparable between patients and controls. In GHD children
one year of GHRT was associated with a significant increase in
insulin (7.2±4.8 vs 4.5±3.3 mcU/ml, p<0.001) and HOMA
(1.32±0.98 vs 0.93±0.72, p<0.001) levels and a decrease of
QUICKI (0.39±0.06 vs 0.42±0.06 p<0.001) in absence of
significant modifications of glucose and HbA1c. Glucose
metabolism parameters remained stable during treatment
until the end of the study in GHD patients (insulin 7.5±4.0
mcU/ml, HOMA 1.34±0.79, QUICKI 0.38±0.06). In contrast,
healthy controls showed no significant changes in insulin
(4.6±3.0 vs 4.7±3.0 mcU/ml), HOMA (0.91±0.65 vs 0.89±0.63)
and QUICKI (0.41±0.04 vs 0.41±0.04) after the first year of
follow-up. At the fifth year of the study a significant increase
in insulin (6.4±3.6 vs 4.6±3.0 mcU/ml, p<0.001) and HOMA
(1.36±0.73 vs 0.91±0.65, p<0.001) and a decrease in QUICKI
(0.39±0.04 vs 0.41±0.04, p<0.001) levels were documented in
these children. Consequently, glucose metabolism
parameters resulted comparable between the two groups at
the end of the study.
Conclusions: Untreated GHD is not associated to insulinresistance
in childhood; GHRT determines a reduction in
insulin-sensitivity during the first year of therapy while
glucose parameters return to be similar to healthy children in
the subsequent years.