Insulin Sensitivity Modulates the Growth Response during the First Year of High-Dose Growth Hormone Treatment in Short Prepubertal Children Born Small for Gestational Age

Abstract

Aim: To study the relationship between insulin sensitivity and growth response in short children born small for gestational age (SGA) treated with growth hormone (GH). Methods: Randomized, open-label, 24-month intervention study in 40 short prepubertal SGA children [age (mean ± SD) 5.3 ± 1.5 years], who either remained untreated (n = 20) or were treated with GH (66 µg/kg/day; n = 20). Changes in fasting glucose, insulin, quantitative insulin sensitivity check index (QUICKI), IGF-1 and leptin after 1 and 2 years were studied. Results: Mean height SDS increased from –3.3 ± 0.7 to –2.3 ± 0.7 after 1 year, and to –1.9 ± 0.7 after 2 years of treatment. QUICKI decreased significantly (p = 0.008) in the first year of GH treatment and stabilized in the second year. Baseline QUICKI was positively associated (r = 0.40; p < 0.05) with the change in height SDS in the first year. Conclusion: Higher insulin sensitivity at the start of GH therapy is associated with greater first-year growth response to GH, and could be a promising parameter in selecting prepubertal short SGA children for GH treatment. However, this finding needs to be confirmed in larger studies.

Evaluation of changes in insulin sensitivity in prepubertal small for gestational age children treated with growth hormone

“…It is therefore questionable if these temporary changes are relevant. Like others,[383940] we are also unable to detect a tendency to deterioration with a longer period of GH treatment. However, puberty might have an influence, as a relatively large number of abnormal values were found in the individual last prepubertal year of these children.…”

“…In line with the findings in all other studies,[69172337] in our group none of the children developed diabetes. The significant rise of insulin levels in oGTT has also been reported before, but the results differ in detail: some studies find changes in insulin levels only after 6 months[38] or the first year,[3940] others see a continuous rise throughout their follow-up period. [6841] In our cohort of prepubertal children, apart from fasting values, we could demonstrate a stabilization of insulin levels after the first year of treatment.…”

Genetic Markers of Insulin Sensitivity and Insulin Secretion Are Associated With Spontaneous Postnatal Growth and Response to Growth Hormone Treatment in Short SGA Children: the North European SGA Study (NESGAS)

“…We and others have reported that the growth response to GH therapy in short SGA children is associated with baseline insulin sensitivity and IGF-1 levels (2,3). Children with the highest baseline IGF-1 levels had lower insulin sensitivity, lower height velocity, and lower IGF-1 responses after 1 year of GH therapy (3).…”

Baseline IGF-I Levels Determine Insulin Secretion and Insulin Sensitivity during the First Year on Growth Hormone Therapy in Children Born Small for Gestational Age. Results from a North European Multicentre Study (NESGAS)

“…Insulin sensitivity (IS) at baseline has been associated with baseline IGF-I levels, and may predict growth response [16,17]. These findings suggest that variations in baseline IGF-I levels may be related to both growth and metabolic response to GH treatment.…”