Supplemental material for the publication "Children born SGA receiving growth hormone have similarly impaired glucose-insulin metabolism as children with obesity"

Background and Objectives: Being born small for gestational age (SGA) and growth hormone (GH) treatment are linked to disturbed glucose-insulin metabolism. We investigated how GH treatment affects glucose-insulin metabolism in children born SGA compared to children with isolated growth-hormone deficiency (iGHD), obesity and lean controls.

Methods: We analyzed glucose-insulin metabolism indices derived from OGTTs (Matsuda index, AUC insulin) and fasting parameters (fasting glucose, HOMA-IR) in 134 SGA patients without catch-up growth (CUG) receiving GH therapy (SGA-GHT), 27 untreated SGA patients with catch-up growth (SGA-CUG), 308 iGHD patients under GH treatment, 427 children with obesity and 356 lean controls. We adjusted for sex, age and BMI through matching and multivariable regression.

Results: Treatment-naïve SGA-GHT patients were more insulin-resistant than iGHD patients (higher insulin AUC (p=0.002) and HOMA-IR (p<0.001), lower Matsuda index (p<0.001)) with levels approaching those of the obesity cohort. Under GH therapy, HbA1c was higher in SGA-GHT and iGHD patients (5.26%±0.35 vs. 5.25%±0.25) than in lean controls (5.09%±0.27). Insulin resistance in SGA-GHT patients approached levels seen in obesity. The prevalence of prediabetes was highest in SGA-GHT children (11.11%) compared to those with iGHD (1.59%) or obesity (3.13%). After stopping GH therapy, SGA-GHT patients retained elevated markers of prediabetes (4.65%) and insulin resistance compared to controls and iGHD patients, similar to children with obesity (6.38%). No overt type 2 diabetes was observed.

Conclusion: SGA patients have an impaired glucose-insulin metabolism similar to that of children with obesity, which worsens under GH therapy. Close metabolic monitoring of GH-treated SGA patients is recommended.