TY - JOUR
T1 - Metabolic Dysregulation in Adult Survivors of Pediatric Hematopoietic Stem Cell Transplantation
T2 - The Role of Incretins
AU - Vadmand, Amalia Christina
AU - Nissen, Anne Anker
AU - Mathiesen, Sidsel
AU - Ebbesen, Maria Schou
AU - Gerbek, Tina
AU - Fridh, Martin Kaj
AU - Sørensen, Kaspar
AU - Hartmann, Bolette
AU - Holst, Jens Juul
AU - Müller, Klaus
N1 - © The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: [email protected].
PY - 2023
Y1 - 2023
N2 - 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.INTERVENTION: None.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.
AB - 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.INTERVENTION: None.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.
U2 - 10.1210/clinem/dgac561
DO - 10.1210/clinem/dgac561
M3 - Journal article
C2 - 36181459
VL - 108
SP - 453
EP - 462
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 2
ER -