Children born SGA receiving growth hormone have similarly impaired glucose-insulin metabolism as children with obesity

Lea Prengemann; Robert Stein; Ruth Gausche; Christoph Beger; Mandy Vogel; Eric Wenzel; Anette Stoltze; Wieland Kiess; Roland Pfäffle; Antje Körner

doi:10.1210/clinem/dgaf672

Children born SGA receiving growth hormone have similarly impaired glucose-insulin metabolism as children with obesity

J Clin Endocrinol Metab. 2026 Feb 10:dgaf672. doi: 10.1210/clinem/dgaf672. Online ahead of print.

Authors

Lea Prengemann¹, Robert Stein^{1

2

3

4}, Ruth Gausche¹, Christoph Beger¹, Mandy Vogel⁵, Eric Wenzel^{1

2

3}, Anette Stoltze¹, Wieland Kiess^{1

3

5}, Roland Pfäffle^{1

3}, Antje Körner^{1

2

3

4

5

6}

Affiliations

¹ Center for Pediatric Research, Medical Faculty, University of Leipzig, University Hospital for Children & Adolescents, 04103 Leipzig, Germany.
² Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG), Helmholtz Zentrum München at the University of Leipzig and University Hospital Leipzig, 04103 Leipzig, Germany.
³ German Center for Child and Adolescent Health (DZKG), Partner Site Leipzig/Dresden, 04103 Leipzig, Germany.
⁴ Leipzig Center of Metabolism (LeiCeM), Medical Faculty, University of Leipzig, 04103 Leipzig, Germany.
⁵ LIFE-Leipzig Research Center for Civilization Diseases, University of Leipzig, 04103 Leipzig, Germany.
⁶ Leipzig Reproductive Health Research Center (LE-REP), Leipzig University, 04103 Leipzig, Germany.

PMID: 41665939
DOI: 10.1210/clinem/dgaf672

Abstract

Context: Being born small for gestational age (SGA) and growth hormone (GH) treatment are linked to disturbed glucose-insulin metabolism.

Objective: 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 oral glucose tolerance tests (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 = .002] and HOMA-IR [P < .001], lower Matsuda index [P < .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. Prediabetes prevalence 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.

Keywords: diabetes; growth hormone deficiency; growth hormone therapy; insulin resistance; obesity; small for gestational age.

Abstract

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