Growth hormone treatment does not to lead to insulin resistance nor excessive rise in IGF‐1 levels, while improving height in patients small for gestational age A long‐term observational study

Abstract

Objective In children born small for gestational age (SGA), the relationship between growth hormone (GH) treatment and insulin resistance (IR) has only been investigated for a short period, necessitating a longer observation period. This study aimed to evaluate the long‐term (10 years) effect of GH to SGA‐children on IR and safety during treatment. Design This was a multicenter observational study. Patients: SGA‐children who received GH treatment in Spain (stratified by Tanner‐stage and age at GH onset [two groups: ≤6 years old or >6 years old]). Measurements: The analysed variables (yearly measures) included auxologic, metabolic (insulin‐like growth factor‐1 (IGF‐1), height velocity [HV], weight and homeostatic model assessment‐IR [HOMA‐IR]) and safety data. Data were collected prospectively (since the study approval: 2007) and retrospectively (since the initiation of GH treatment: 2005–2007). Results A total of 389 SGA children (369 Tanner‐I) were recruited from 27 centres. The mean age (standard deviation) of the children at GH treatment onset was 7.2 (2.8) years old. IGF‐1 (standard deviation score [SDS]) and HOMA‐IR values tended to increase until the sixth year of GH‐treatment, with significant differences being observed only during the first year, while these remained stable in the later years (within normal ranges). Height (SDS) increased significantly (basal: −3.0; tenth year: −1.13), and the maximum HV (SDS) occurred during the first year (2.75 ± 2.39). Conclusions HOMA‐IR values increased significantly in SGA‐children during the first year of GH‐treatment, remained stable and were within normal ranges in all cases. Our 10‐year data suggests that long‐term GH treatment does not promote IR and is well‐tolerated, safe and effective.

Response to Treatment with Recombinant Human Growth Hormone (rhGH) of Short Stature Children Born Too Small for Gestational Age (SGA) in Selected Centres in Poland

“…Our results for the whole observed group ΔHt12 SDS 0.57 and ΔHt24 SDS 0.38, as well as HV12 8.15 cm/year after the first and HV24 7.17 cm/year after the second year are consistent with the results obtained by Ranke et al or López-Siguero et al [ 16 , 17 ]. Both parameters indicate the benefit of treatment for SGA patients because they improve their centile position as well as maintain a relatively good HV.…”

“…The BA/CA ratio we obtained was comparable to those presented in the work of López-Siguero et al [ 17 ]. During the course of growth BA/CA ratio did not reach the value of 1.…”

Growth Hormone Dose Modulation and Final Height in Short Children Born Small for Gestational Age: French Real-Life Data

“…Several national and international studies have investigated the effect of growth hormone (GH) treatment on height outcomes in children born SGA [10][11][12][13][14]. All of the studies carried out in children who were prepubertal at start of treatment showed a significant increase in stature with GH treatment, which was inversely proportional to the child's age at the start of treatment [10][11][12].…”

“…Additionally, it has been demonstrated that individuals born SGA may have an increased risk of developing insulin resistance and metabolic syndrome in adulthood [8,16,17]. GH may temporarily reduce insulin sensitivity in these patients [18][19][20], although the only significant change appears to occur in the first year of treatment, with insulin resistance remaining within the normal range throughout longterm treatment [14]. Lastly, data concerning the effect of GH on bone maturation or the start of puberty are incomplete and contradictory [21][22][23].…”

The Exon 3-Deleted Growth Hormone Receptor (d3GHR) Polymorphism—A Favorable Backdoor Mechanism for the GHR Function

“…Small for gestational age (SGA) fetuses or newborns are those that are smaller than average for their gestational age. This is typically indicated by a weight that is below the 10th percentile [ 82 , 83 ] and affects approximately 3–10% of live births [ 84 , 85 ]. Compared with infants born with a normal length and weight for gestational age, SGA is linked to cardiovascular disease, T2DM, increased risk for insulin resistance, and adults short stature [ 86 , 87 ].…”