Galantamine alleviates inflammation and insulin resistance in patients with metabolic syndrome in a randomized trial.

Autor:	Consolim-Colombo FM; University of Sao Paulo, Hypertension Unit, Sao Paulo, Brazil.; Nove de Julho University (UNINOVE), PPG, Sao Paulo, Brazil., Sangaleti CT; University of Sao Paulo, Hypertension Unit, Sao Paulo, Brazil.; Midwestern State University (UNICENTRO), Paraná, Brazil., Costa FO; Nove de Julho University (UNINOVE), PPG, Sao Paulo, Brazil., Morais TL; Nove de Julho University (UNINOVE), PPG, Sao Paulo, Brazil., Lopes HF; University of Sao Paulo, Hypertension Unit, Sao Paulo, Brazil.; Nove de Julho University (UNINOVE), PPG, Sao Paulo, Brazil., Motta JM; Nove de Julho University (UNINOVE), PPG, Sao Paulo, Brazil., Irigoyen MC; University of Sao Paulo, Hypertension Unit, Sao Paulo, Brazil., Bortoloto LA; University of Sao Paulo, Hypertension Unit, Sao Paulo, Brazil., Rochitte CE; University of Sao Paulo, Hypertension Unit, Sao Paulo, Brazil., Harris YT; Hofstra Northwell School of Medicine at Hofstra University, Division of Endocrinology, Diabetes and Metabolism, Hempstead, New York, USA., Satapathy SK; Methodist University Hospital, University of Tennessee Health Sciences Center, Memphis, Tennessee, USA., Olofsson PS; Center for Biomedical Science, and.; Center for Bioelectronic Medicine, Department of Medicine, Center for Molecular Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden., Akerman M; Biostatistics Unit, and., Chavan SS; Center for Biomedical Science, and.; Center for Bioelectronic Medicine, The Feinstein Institute for Medical Research, Northwell Health, Manhasset, New York, USA., MacKay M; Center for Autoimmune & Musculoskeletal Disease, The Feinstein Institute for Medical Research, Northwell Health, Manhasset, New York, USA., Barnaby DP; Department of Emergency Medicine of Albert Einstein College of Medicine, Bronx, New York, USA., Lesser ML; Biostatistics Unit, and., Roth J; Laboratory of Diabetes and Diabetes-related Research, The Feinstein Institute for Medical Research, Northwell Health, Manhasset, New York, USA., Tracey KJ; Center for Biomedical Science, and.; Center for Bioelectronic Medicine, The Feinstein Institute for Medical Research, Northwell Health, Manhasset, New York, USA., Pavlov VA; Center for Biomedical Science, and.; Center for Bioelectronic Medicine, The Feinstein Institute for Medical Research, Northwell Health, Manhasset, New York, USA.
Jazyk:	angličtina
Zdroj:	JCI insight [JCI Insight] 2017 Jul 20; Vol. 2 (14). Date of Electronic Publication: 2017 Jul 20 (Print Publication: 2017).
DOI:	10.1172/jci.insight.93340
Abstrakt:	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. Trial Registration: ClinicalTrials.gov, number NCT02283242. 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.
Databáze:	MEDLINE
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