TOPLINE:

Children born small for gestational age (SGA) exhibited impaired glucose-insulin metabolism, similar to children with obesity, which worsened under growth hormone therapy. In contrast, children with isolated growth hormone deficiency (iGHD) showed better insulin sensitivity than those born SGA.

METHODOLOGY:

• Growth hormone therapy is approved for children born SGA without catch-up growth to improve height outcomes, but it may impair glucose-insulin metabolism.
• Researchers conducted a retrospective cohort analysis including participants treated at the University of Leipzig Medical Center and included data from the LIFE Child study, focusing on participants aged 0-21 years.
• They analyzed glucose-insulin metabolism in 134 patients born SGA who were receiving growth hormone therapy, 27 patients born SGA who did not receive growth hormone therapy, 308 patients with iGHD receiving growth hormone therapy, 427 children with obesity, and 356 lean control individuals. Children born SGA were defined by birth weight and/or length < -2 SD scores of the matched populational norm, with further stratification based on catch-up growth status.
• The study utilized oral glucose tolerance tests and fasting parameters to derive indices such as the Matsuda index, area under the curve (AUC) insulin, fasting glucose level, and homeostasis model assessment of insulin resistance (HOMA-IR).
• Patients born SGA were matched with children in the comparator groups (61 children in each of the four groups), and the analyses were adjusted for sex, age, and BMI. Analyses were performed in children who were treatment-naive, children on growth hormone therapy, and children after cessation of growth hormone therapy.

TAKEAWAY:

• Children born SGA who were treatment-naive and were on growth hormone therapy exhibited higher insulin resistance than those with iGHD, with significant differences in insulin AUC (P = .002), HOMA-IR (P < .001), and Matsuda index (P < .001).
• Children born SGA on growth hormone therapy had higher glucose AUC and 1-hour glucose levels than lean control individuals; A1c levels were also higher in children born SGA than in lean control children (P < .001) and in those with obesity (P < .05).
• After growth hormone therapy cessation, children born SGA continued to exhibit higher fasting glucose levels and 1-hour glucose levels than lean control individuals, similar to those with obesity. Children born SGA had C-peptide-based HOMA-IR comparable to that of children with obesity.
• In the matched analysis, children born SGA who were treatment-naive showed a higher prevalence of impaired fasting glucose levels (10.64%) and pathologic glucose tolerance (21.62%) than those with iGHD (2.5% and 20%, respectively). Children born SGA showed the highest prevalence of prediabetic fasting glucose and A1c levels during treatment among all cohorts, with comparable prevalence after treatment cessation vs those with obesity.

IN PRACTICE:

“We recommend that children born SGA treated with GH [growth hormone] should receive similar metabolic monitoring as children with obesity, which may comprise annual measures of [A1c], fasting glucose, fasting insulin, and lipid status. In cases with elevated fasting indices or additional risk factors (such as overweight or obesity, family history of diabetes, ethnicity at risk for diabetes, acanthosis nigricans), we recommend using OGTT [oral glucose tolerance testing],” the authors of the study wrote.

“We recommend similar treatment approaches for SGA patients who develop insulin resistance or prediabetes during GH therapy. Additionally, lowering the dose of GH should be considered first before initiating further pharmacotherapy,” they added.

SOURCE:

The study was led by Lea Prengemann and Robert Stein, Center for Pediatric Research, Medical Faculty, University of Leipzig, University Hospital for Children & Adolescents, Leipzig, Germany. It was published online in the Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

Consistent data from the same patients were lacking at different timepoints because many participants missed appointments or changed healthcare providers. The sample size for children born SGA with catch-up growth was small. The study relied on proxies for insulin sensitivity, rather than using the gold standard euglycemic hyperinsulinemic clamp. BMI was used as the sole measure of adiposity, without more precise assessments, which could overlook abdominal obesity in individuals born SGA.

DISCLOSURES:

The study was supported by grants from the German Research Foundation and the Federal Ministry of Research, Technology and Space. LIFE Child is supported by the Free State of Saxony, CrescNet is supported by unrestricted grants from various sources, and some authors reported being supported by various sources. The authors reported having no conflicts of interest to declare.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.