Leptin Serum Levels are Associated With GLP-1 Receptor Agonist-Mediated Effects on Glucose Metabolism in Clozapine-or Olanzapine-Treated, Prediabetic, Schizophrenia Patients
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Leptin Serum Levels are Associated With GLP-1 Receptor Agonist-Mediated Effects on Glucose Metabolism in Clozapine-or Olanzapine-Treated, Prediabetic, Schizophrenia Patients. / Tomasik, Jakub; Rustogi, Nitin; Larsen, Julie R.; Jakobsen, Michelle I.; Svensson, Camilla K.; Vedtofte, Louise; Jakobsen, Mathilde S.L.; Jespersen, Hans R.; Koyuncu, Kamuran; Schjerning, Ole; Nielsen, Jimmi; Ekstrøm, Claus T.; Correll, Christoph U.; Holst, Jens J.; Vilsbøll, Tina; Bahn, Sabine; Fink-Jensen, Anders.
In: Schizophrenia Bulletin Open, Vol. 1, No. 1, sgaa044, 2020.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Leptin Serum Levels are Associated With GLP-1 Receptor Agonist-Mediated Effects on Glucose Metabolism in Clozapine-or Olanzapine-Treated, Prediabetic, Schizophrenia Patients
AU - Tomasik, Jakub
AU - Rustogi, Nitin
AU - Larsen, Julie R.
AU - Jakobsen, Michelle I.
AU - Svensson, Camilla K.
AU - Vedtofte, Louise
AU - Jakobsen, Mathilde S.L.
AU - Jespersen, Hans R.
AU - Koyuncu, Kamuran
AU - Schjerning, Ole
AU - Nielsen, Jimmi
AU - Ekstrøm, Claus T.
AU - Correll, Christoph U.
AU - Holst, Jens J.
AU - Vilsbøll, Tina
AU - Bahn, Sabine
AU - Fink-Jensen, Anders
N1 - Publisher Copyright: © 2020 The Author(s). Published by Oxford University Press on behalf of the University of Maryland's school of medicine, Maryland Psychiatric Research Center.
PY - 2020
Y1 - 2020
N2 - Background: We previously demonstrated that the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide significantly reduced glucometabolic disturbances and body weight vs placebo in prediabetic, overweight, or obese schizophrenia-spectrum disorder patients treated with clozapine or olanzapine. Here, we aimed to identify potential biomarkers of prediabetes and the GLP-1RA-induced effects on glucose tolerance in schizophrenia patients treated with clozapine or olanzapine. Methods: Multiplexed immunoassays were used to measure 8 proteins (adiponectin, C-reactive protein, interleukin-1 receptor antagonist, leptin, macrophage migration inhibitory factor, prolactin, receptor for advanced glycation end products, and vascular endothelial growth factor [VEGF]) in fasting prediabetic and non-prediabetic patients with schizophrenia-spectrum disorder, the prediabetic patients receiving 16-week randomized treatment with liraglutide or placebo. Results: Serum adiponectin (P =. 004) and VEGF (P =. 019) levels were significantly lower in prediabetic (n = 81) than non-prediabetic schizophrenia-spectrum disorder patients (n = 32). Adiponectin levels increased significantly (P =. 022) and leptin levels decreased significantly (P =. 017) following treatment with liraglutide (n = 39) vs placebo (n = 42). Importantly, patients receiving liraglutide who had higher baseline leptin levels showed significantly larger reductions in the primary endpoint, the 75-g oral glucose tolerance test value, than patients with lower baseline leptin levels (P =. 009). Conclusion: These results provide new evidence for metabolic alterations associated with prediabetes and GLP-1RA treatment in the context of schizophrenia. They suggest that leptin may be a valuable biomarker predicting GLP-1RA-induced improvement in glucose tolerance in overweight or obese schizophrenia-spectrum disorder patients with prediabetes treated with clozapine or olanzapine. These findings require further validation in larger numbers of individuals.
AB - Background: We previously demonstrated that the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide significantly reduced glucometabolic disturbances and body weight vs placebo in prediabetic, overweight, or obese schizophrenia-spectrum disorder patients treated with clozapine or olanzapine. Here, we aimed to identify potential biomarkers of prediabetes and the GLP-1RA-induced effects on glucose tolerance in schizophrenia patients treated with clozapine or olanzapine. Methods: Multiplexed immunoassays were used to measure 8 proteins (adiponectin, C-reactive protein, interleukin-1 receptor antagonist, leptin, macrophage migration inhibitory factor, prolactin, receptor for advanced glycation end products, and vascular endothelial growth factor [VEGF]) in fasting prediabetic and non-prediabetic patients with schizophrenia-spectrum disorder, the prediabetic patients receiving 16-week randomized treatment with liraglutide or placebo. Results: Serum adiponectin (P =. 004) and VEGF (P =. 019) levels were significantly lower in prediabetic (n = 81) than non-prediabetic schizophrenia-spectrum disorder patients (n = 32). Adiponectin levels increased significantly (P =. 022) and leptin levels decreased significantly (P =. 017) following treatment with liraglutide (n = 39) vs placebo (n = 42). Importantly, patients receiving liraglutide who had higher baseline leptin levels showed significantly larger reductions in the primary endpoint, the 75-g oral glucose tolerance test value, than patients with lower baseline leptin levels (P =. 009). Conclusion: These results provide new evidence for metabolic alterations associated with prediabetes and GLP-1RA treatment in the context of schizophrenia. They suggest that leptin may be a valuable biomarker predicting GLP-1RA-induced improvement in glucose tolerance in overweight or obese schizophrenia-spectrum disorder patients with prediabetes treated with clozapine or olanzapine. These findings require further validation in larger numbers of individuals.
KW - adiponectin
KW - biomarker
KW - GLP-1RA
KW - liraglutide
KW - OGTT
KW - prediabetes
U2 - 10.1093/schizbullopen/sgaa044
DO - 10.1093/schizbullopen/sgaa044
M3 - Journal article
AN - SCOPUS:85117504217
VL - 1
JO - Schizophrenia Bulletin Open
JF - Schizophrenia Bulletin Open
SN - 2632-7899
IS - 1
M1 - sgaa044
ER -
ID: 340119019