ESPE Abstracts

Background and Objectives: Being born small for gestational age (SGA) as well as growth hormone (GH) treatment are associated with a disturbed glucose-insulin metabolism. We aimed to investigate whether SGA patients have a higher risk of developing an impaired glucose-insulin metabolism under GH treatment in comparison to children with an isolated growth-hormone deficiency (iGHD), to children with obesity and a healthy control group.

Methods: We compared indices of glucose-insulin metabolism derived from oral glucose tolerance testing (Matsuda index, area under the curve (AUC) insulin) or from fasting parameters (fasting insulin, HOMA-IR) between 134 SGA patients without catch-up growth (CUG) who received GH therapy (SGA-GHT), 27 SGA patients with CUG and thus no GH therapy (SGA-CUG), 308 iGHD patients under GH treatment, 427 children with obesity and 356 healthy controls born appropriate for gestational age (AGA). We corrected for sex-, age- and BMI-dependent bias through matching and/or multivariate linear regression.

Results: Treatment-naive SGA-GHT patients were more insulin resistant than iGHD patients as indicated by a higher insulin AUC (P = 0.002), higher HOMA-IR (P <0.001) and lower Matsuda index (P <0.001). They had higher (although not significant) insulin resistance than AGA controls but no difference to children with obesity. During treatment, SGA and iGHD patients showed higher HbA1c levels (SGA 5.26%, iGHD 5.25%) than controls (5.09%). Compared to iGHD, SGA patients developed elevated insulin resistance that nearly reached the levels of children with obesity. The prevalence of (pre)diabetic values was higher for all groups in comparison to controls (controls 0.8%, SGA 13.2%, iGHD 7.2%, obesity 8.5%). After cessation of GH therapy, SGA-GHT patients had sustained elevated markers of insulin resistance in comparison to controls and iGHD patients, that were on a similar level than among children with obesity. Prediabetic measures remained elevated for SGA-GHT patients (8.8% SGA-GHT, 0.8% controls, 9.2% obesity) with no overt type 2 diabetes among all study groups and time points. When comparing glucose-insulin metabolism of SGA-GHT and SGA-CUG, SGA-GHT tended to have a better insulin sensitivity before GH therapy and a worse one during and after treatment that remained non-significant.

Conclusion: SGA patients during and immediately after GH therapy have an impaired glucose-insulin-metabolism in comparison to iGHD and AGA children with levels comparable to those of children with obesity. We conclude that SGA patients should be monitored closely for changes in glucose-insulin metabolism especially under GH therapy.