Fluvastatin Reduces Glucose Tolerance in Healthy Young Individuals Independently of Cold Induced BAT Activity

BackgroundStatins are commonly prescribed for primary and secondary prevention of atherosclerotic disease. They reduce cholesterol biosynthesis by inhibiting hydroxymethylglutaryl-coenzyme A-reductase (HMG-CoA-reductase) and therefore mevalonate synthesis. Several studies reported a small, but signi...

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Autores principales:	Martina Felder, Claudia Irene Maushart, Gani Gashi, Jaël Rut Senn, Anton S. Becker, Julian Müller, Miroslav Balaz, Christian Wolfrum, Irene A. Burger, Matthias Johannes Betz
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	diabetes brown adipose tissue energy expenditure (EE) glucose tolerance fluvastatin statin Diseases of the endocrine glands. Clinical endocrinology RC648-665
Acceso en línea:	https://doaj.org/article/1da85f4685ec4a61a5d809db33327698
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spelling	oai:doaj.org-article:1da85f4685ec4a61a5d809db333276982021-11-10T08:07:32ZFluvastatin Reduces Glucose Tolerance in Healthy Young Individuals Independently of Cold Induced BAT Activity1664-239210.3389/fendo.2021.765807https://doaj.org/article/1da85f4685ec4a61a5d809db333276982021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fendo.2021.765807/fullhttps://doaj.org/toc/1664-2392BackgroundStatins are commonly prescribed for primary and secondary prevention of atherosclerotic disease. They reduce cholesterol biosynthesis by inhibiting hydroxymethylglutaryl-coenzyme A-reductase (HMG-CoA-reductase) and therefore mevalonate synthesis. Several studies reported a small, but significant increase in the diagnosis of diabetes mellitus with statin treatment. The molecular mechanisms behind this adverse effect are not yet fully understood. Brown adipose tissue (BAT), which plays a role in thermogenesis, has been associated with a reduced risk of insulin resistance. Statins inhibit adipose tissue browning and have been negatively linked to the presence of BAT in humans. We therefore speculated that inhibition of BAT by statins contributes to increased insulin resistance in humans.MethodsA prospective study was conducted in 17 young, healthy men. After screening whether significant cold-induced thermogenesis (CIT) was present, participants underwent glucose tolerance testing (oGTT) and assessment of BAT activity by FDG-PET/MRI after cold-exposure and treatment with a β3-agonist. Fluvastatin 2x40mg per day was then administered for two weeks and oGTT and FDG-PET/MRI were repeated.ResultsTwo weeks of fluvastatin treatment led to a significant increase in glucose area under the curve (AUC) during oGTT (p=0.02), reduction in total cholesterol and LDL cholesterol (both p<0.0001). Insulin AUC (p=0.26), resting energy expenditure (REE) (p=0.44) and diet induced thermogenesis (DIT) (p=0.27) did not change significantly. The Matsuda index, as an indicator of insulin sensitivity, was lower after fluvastatin intake, but the difference was not statistically significant (p=0.09). As parameters of BAT activity, mean standard uptake value (SUVmean) (p=0.12), volume (p=0.49) and total glycolysis (p=0.74) did not change significantly during the intervention. Matsuda index, was inversely related to SUVmean and the respiratory exchange ratio (RER) (both R2 = 0.44, p=0.005) at baseline, but not after administration of fluvastatin (R2 = 0.08, p=0.29, and R2 = 0.14, p=0.16, respectively).ConclusionsTreatment with fluvastatin for two weeks reduced serum lipid levels but increased glucose AUC in young, healthy men, indicating reduced glucose tolerance. This was not associated with changes in cold-induced BAT activity.Martina FelderClaudia Irene MaushartGani GashiJaël Rut SennAnton S. BeckerJulian MüllerMiroslav BalazChristian WolfrumIrene A. BurgerMatthias Johannes BetzFrontiers Media S.A.articlediabetesbrown adipose tissueenergy expenditure (EE)glucose tolerancefluvastatinstatinDiseases of the endocrine glands. Clinical endocrinologyRC648-665ENFrontiers in Endocrinology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	diabetes brown adipose tissue energy expenditure (EE) glucose tolerance fluvastatin statin Diseases of the endocrine glands. Clinical endocrinology RC648-665
spellingShingle	diabetes brown adipose tissue energy expenditure (EE) glucose tolerance fluvastatin statin Diseases of the endocrine glands. Clinical endocrinology RC648-665 Martina Felder Claudia Irene Maushart Gani Gashi Jaël Rut Senn Anton S. Becker Julian Müller Miroslav Balaz Christian Wolfrum Irene A. Burger Matthias Johannes Betz Fluvastatin Reduces Glucose Tolerance in Healthy Young Individuals Independently of Cold Induced BAT Activity
description	BackgroundStatins are commonly prescribed for primary and secondary prevention of atherosclerotic disease. They reduce cholesterol biosynthesis by inhibiting hydroxymethylglutaryl-coenzyme A-reductase (HMG-CoA-reductase) and therefore mevalonate synthesis. Several studies reported a small, but significant increase in the diagnosis of diabetes mellitus with statin treatment. The molecular mechanisms behind this adverse effect are not yet fully understood. Brown adipose tissue (BAT), which plays a role in thermogenesis, has been associated with a reduced risk of insulin resistance. Statins inhibit adipose tissue browning and have been negatively linked to the presence of BAT in humans. We therefore speculated that inhibition of BAT by statins contributes to increased insulin resistance in humans.MethodsA prospective study was conducted in 17 young, healthy men. After screening whether significant cold-induced thermogenesis (CIT) was present, participants underwent glucose tolerance testing (oGTT) and assessment of BAT activity by FDG-PET/MRI after cold-exposure and treatment with a β3-agonist. Fluvastatin 2x40mg per day was then administered for two weeks and oGTT and FDG-PET/MRI were repeated.ResultsTwo weeks of fluvastatin treatment led to a significant increase in glucose area under the curve (AUC) during oGTT (p=0.02), reduction in total cholesterol and LDL cholesterol (both p<0.0001). Insulin AUC (p=0.26), resting energy expenditure (REE) (p=0.44) and diet induced thermogenesis (DIT) (p=0.27) did not change significantly. The Matsuda index, as an indicator of insulin sensitivity, was lower after fluvastatin intake, but the difference was not statistically significant (p=0.09). As parameters of BAT activity, mean standard uptake value (SUVmean) (p=0.12), volume (p=0.49) and total glycolysis (p=0.74) did not change significantly during the intervention. Matsuda index, was inversely related to SUVmean and the respiratory exchange ratio (RER) (both R2 = 0.44, p=0.005) at baseline, but not after administration of fluvastatin (R2 = 0.08, p=0.29, and R2 = 0.14, p=0.16, respectively).ConclusionsTreatment with fluvastatin for two weeks reduced serum lipid levels but increased glucose AUC in young, healthy men, indicating reduced glucose tolerance. This was not associated with changes in cold-induced BAT activity.
format	article
author	Martina Felder Claudia Irene Maushart Gani Gashi Jaël Rut Senn Anton S. Becker Julian Müller Miroslav Balaz Christian Wolfrum Irene A. Burger Matthias Johannes Betz
author_facet	Martina Felder Claudia Irene Maushart Gani Gashi Jaël Rut Senn Anton S. Becker Julian Müller Miroslav Balaz Christian Wolfrum Irene A. Burger Matthias Johannes Betz
author_sort	Martina Felder
title	Fluvastatin Reduces Glucose Tolerance in Healthy Young Individuals Independently of Cold Induced BAT Activity
title_short	Fluvastatin Reduces Glucose Tolerance in Healthy Young Individuals Independently of Cold Induced BAT Activity
title_full	Fluvastatin Reduces Glucose Tolerance in Healthy Young Individuals Independently of Cold Induced BAT Activity
title_fullStr	Fluvastatin Reduces Glucose Tolerance in Healthy Young Individuals Independently of Cold Induced BAT Activity
title_full_unstemmed	Fluvastatin Reduces Glucose Tolerance in Healthy Young Individuals Independently of Cold Induced BAT Activity
title_sort	fluvastatin reduces glucose tolerance in healthy young individuals independently of cold induced bat activity
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/1da85f4685ec4a61a5d809db33327698
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Fluvastatin Reduces Glucose Tolerance in Healthy Young Individuals Independently of Cold Induced BAT Activity

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