Metabolic Dysregulation in Adult Survivors of Pediatric Hematopoietic Stem Cell Transplantation: The Role of Incretins

Amalia Christina Vadmand, Anne Anker Nissen, Sidsel Mathiesen, Maria Ebbesen Sørum, Tina Gerbek, Martin Kaj Fridh, Kaspar Sørensen, Bolette Hartmann, Jens Juul Holst, Klaus Müller*

*Corresponding author for this work

Abstract

CONTEXT: Survivors of pediatric hematopoietic stem cell transplantation (HSCT) have increased risk of developing metabolic syndrome (MetS), but the mechanisms are poorly understood.

OBJECTIVE: We aimed to test the hypothesis that insufficient secretion of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) plays a pathogenetic role in HSCT survivors with MetS.

METHODS: This cross-sectional cohort study, conducted at the Danish national referral center for HSCT, studied 42 male HSCT survivors (median age 28.9 years) for a median 21.2 years from HSCT, along with 15 age- and sex-matched healthy controls. Main outcome measures were glucose metabolism and incretin hormones (by oral glucose tolerance test [OGTT]) and MetS criteria. The hypothesis was formulated before data collection.

RESULTS: GLP-1, GIP, and glucagon during an OGTT were similar in patients and controls, with no overall difference between survivors with (24%) and without MetS. However, fasting glucagon was significantly higher in patients with hypertriglyceridemia (mean difference [MD]: 6.1 pmol/L; 95% CI, 1.5-10.8; P = 0.01), and correlated with HDL (MD: 4.7 mmol/L; 95% CI, -0.6 to 9.9; P = 0.08), android-gynoid ratio (correlation coefficient [r] = 0.6, P = 0.0001) and waist-hip ratio (r = 0.5, P = 0.002). A similar pattern was seen for GIP, correlating positively with triglyceride (MD: 60%; 95% CI, 44-82; P = 0.002). GIP levels were significantly increased in patients treated with total body irradiation (TBI) (MD: 165%; 95% CI, 118-230; P = 0.004), which was found to be a significant risk factor for MetS.

CONCLUSION: This study demonstrates an altered production of incretin hormones in HSCT survivors previously treated with TBI, developing dyslipidemia and abdominal adiposity.

Original languageEnglish
JournalThe Journal of clinical endocrinology and metabolism
Volume108
Issue number2
Pages (from-to)453-462
Number of pages10
ISSN0021-972X
DOIs
Publication statusPublished - 17 Jan 2023

Keywords

  • Adult
  • Blood Glucose/metabolism
  • Child
  • Cross-Sectional Studies
  • Gastric Inhibitory Polypeptide
  • Glucagon
  • Glucagon-Like Peptide 1
  • Hematopoietic Stem Cell Transplantation/adverse effects
  • Humans
  • Incretins/metabolism
  • Insulin/metabolism
  • Male
  • Metabolic Syndrome/epidemiology
  • Survivors

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