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.