TY - JOUR
T1 - Galantamine alleviates inflammation and insulin resistance in patients with metabolic syndrome in a randomized trial
AU - Consolim-Colombo, Fernanda M.
AU - Sangaleti, Carine T.
AU - Costa, Fernando O.
AU - Morais, Tercio L.
AU - Lopes, Heno F.
AU - Motta, Josiane M.
AU - Irigoyen, Maria C.
AU - Bortoloto, Luiz A.
AU - Rochitte, Carlos Eduardo
AU - Harris, Yael Tobi
AU - Satapathy, Sanjaya K.
AU - Olofsson, Peder S.
AU - Akerman, Meredith
AU - Chavan, Sangeeta S.
AU - MacKay, Meggan
AU - Barnaby, Douglas P.
AU - Lesser, Martin L.
AU - Roth, Jesse
AU - Tracey, Kevin J.
AU - Pavlov, Valentin A.
N1 - Funding Information:
This study was supported by Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP: 2013/22250-9 (to FMCC) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brazil, and the following grants from the National Institute of General Medical Sciences, NIH: R01GM057226 (to KJT) and R01GM089807 (to KJT and VAP).
Funding Information:
This study was supported by Funda??o de Amparo a Pesquisa do Estado de S?o Paulo (FAPESP: 2013/22250-9 (to FMCC) and Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico (CNPq), Brazil, and the following grants from the National Institute of General Medical Sciences, NIH: R01GM057226 (to KJT) and R01GM089807 (to KJT and VAP).
Funding Information:
was funded by Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and the NIH, National Institute of General Medical Sciences. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing the report.
Funding Information:
FUNDING. Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brazil, and the NIH.
Publisher Copyright:
© 2017 American Society for Clinical Investigation. All rights reserved.
PY - 2017/7/20
Y1 - 2017/7/20
N2 - BACKGROUND. Metabolic syndrome (MetS) is an obesity-driven condition of pandemic proportions that increases the risk of type 2 diabetes and cardiovascular disease. Pathophysiological mechanisms are poorly understood, though inflammation has been implicated in MetS pathogenesis. The aim of this study was to assess the effects of galantamine, a centrally acting acetylcholinesterase inhibitor with antiinflammatory properties, on markers of inflammation implicated in insulin resistance and cardiovascular risk, and other metabolic and cardiovascular indices in subjects with MetS. METHODS. In this randomized, double-blind, placebo-controlled trial, subjects with MetS (30 per group) received oral galantamine 8 mg daily for 4 weeks, followed by 16 mg daily for 8 weeks or placebo. The primary outcome was inflammation assessed through plasma levels of cytokines and adipokines associated with MetS. Secondary endpoints included body weight, fat tissue depots, plasma glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), cholesterol (total, HDL, LDL), triglycerides, BP, heart rate, and heart rate variability (HRV). RESULTS. Galantamine resulted in lower plasma levels of proinflammatory molecules TNF (–2.57 pg/ml [95% CI –4.96 to –0.19]; P = 0.035) and leptin (–12.02 ng/ml [95% CI –17.71 to –6.33]; P < 0.0001), and higher levels of the antiinflammatory molecules adiponectin (2.71 μg/ml [95% CI 1.93 to 3.49]; P < 0.0001) and IL-10 (1.32 pg/ml, [95% CI 0.29 to 2.38]; P = 0.002) as compared with placebo. Galantamine also significantly lowered plasma insulin and HOMA-IR values, and altered HRV. CONCLUSION. Low-dose galantamine alleviates inflammation and insulin resistance in MetS subjects. These findings support further study of galantamine in MetS therapy.
AB - BACKGROUND. Metabolic syndrome (MetS) is an obesity-driven condition of pandemic proportions that increases the risk of type 2 diabetes and cardiovascular disease. Pathophysiological mechanisms are poorly understood, though inflammation has been implicated in MetS pathogenesis. The aim of this study was to assess the effects of galantamine, a centrally acting acetylcholinesterase inhibitor with antiinflammatory properties, on markers of inflammation implicated in insulin resistance and cardiovascular risk, and other metabolic and cardiovascular indices in subjects with MetS. METHODS. In this randomized, double-blind, placebo-controlled trial, subjects with MetS (30 per group) received oral galantamine 8 mg daily for 4 weeks, followed by 16 mg daily for 8 weeks or placebo. The primary outcome was inflammation assessed through plasma levels of cytokines and adipokines associated with MetS. Secondary endpoints included body weight, fat tissue depots, plasma glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), cholesterol (total, HDL, LDL), triglycerides, BP, heart rate, and heart rate variability (HRV). RESULTS. Galantamine resulted in lower plasma levels of proinflammatory molecules TNF (–2.57 pg/ml [95% CI –4.96 to –0.19]; P = 0.035) and leptin (–12.02 ng/ml [95% CI –17.71 to –6.33]; P < 0.0001), and higher levels of the antiinflammatory molecules adiponectin (2.71 μg/ml [95% CI 1.93 to 3.49]; P < 0.0001) and IL-10 (1.32 pg/ml, [95% CI 0.29 to 2.38]; P = 0.002) as compared with placebo. Galantamine also significantly lowered plasma insulin and HOMA-IR values, and altered HRV. CONCLUSION. Low-dose galantamine alleviates inflammation and insulin resistance in MetS subjects. These findings support further study of galantamine in MetS therapy.
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U2 - 10.1172/JCI.INSIGHT.93340
DO - 10.1172/JCI.INSIGHT.93340
M3 - Article
C2 - 28724799
AN - SCOPUS:85042674247
SN - 2379-3708
VL - 2
JO - JCI insight
JF - JCI insight
IS - 14
M1 - e93340
ER -
