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

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.

Abnormalities of Anthropometric, Hemodynamic, and Autonomic Variables in Offspring of Hypertensive Parents.

Young adult offspring of hypertensive parents (pHTN⊕) are a good model for assessing abnormalities of anthropometric, cardiometabolic, and autonomic variables prior to clinical hypertension. The objectives of this study were to determine whether these variables and autonomic responses to oral carbohydrates were altered in offspring of pHTN⊕. Two hundred consecutive patients, including 100 pHTN⊕, were evaluated, with 29 patients, including 14 pHTN⊕, given a 70-gram carbohydrate load. The pHTN⊕ group had higher blood pressure, pulse pressure, abdominal circumference (AC), weight, body mass index, and basal metabolic rate than offspring of normotensive parents (pHTN∅). At baseline, the low-frequency (LF, sympathetic) to high-frequency (HF, parasympathetic) ratio, assessed by spectral analysis of heart rate variability, was similar in both groups. After the carbohydrate load, the LF/HF ratio was greater in offspring of pHTN⊕. pHTN⊕ individuals have abnormalities of anthropometric and hemodynamic variables at baseline and autonomic responses to oral carbohydrates before developing hypertension.