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

Research output: Contribution to journalJournal articlepeer-review

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

OBJECTIVE: 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.

DESIGN: Cross-sectional cohort study.

SETTING: The Danish national referral center for HSCT.

PATIENTS OR OTHER PARTICIPANTS: Forty-two male HSCT survivors (median age of 28.9 years) studied median 21.2 years from HSCT. Fifteen age- and sex-matched healthy controls.


MAIN OUTCOME MEASURES: Glucose metabolism and incretin hormones (measured in an 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%Confidence Interval (CI): 1.5 to 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 to 82, p = 0.002).GIP levels were significantly increased in patients treated with total body irradiation (TBI) (MD: 165%, 95%CI: 118 to 230, p = 0.004), that 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
JournalJournal of Clinical Endocrinology and Metabolism
Issue number2
Pages (from-to)453–462
Publication statusPublished - 2023

Bibliographical note

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