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Muscle microvascular dysfunction in central obesity is related to muscle insulin insensitivity but Is not reversed by high-dose statin treatment

Muscle microvascular dysfunction in central obesity is related to muscle insulin insensitivity but Is not reversed by high-dose statin treatment
Muscle microvascular dysfunction in central obesity is related to muscle insulin insensitivity but Is not reversed by high-dose statin treatment
Objective: to test the hypotheses that decreased insulin-mediated glucose disposal in muscle is associated with a reduced muscle microvascular exchange capacity (Kf) and that 6 months of high-dose statin therapy would improve microvascular function in people with central obesity.
Research design and methods: we assessed skeletal muscle microvascular function, visceral fat mass, physical activity levels, fitness, and insulin sensitivity in skeletal muscle in 22 female and 17 male volunteers with central obesity whose age (mean ± SD) was 51 ± 9 years. We tested the effect of atorvastatin (40 mg daily) on muscle microvascular function in a randomized, double-blind, placebo-controlled trial lasting 6 months.
Results: Kf was negatively associated with a measure of glycemia (A1C; r = ?0.44, P = 0.006) and positively associated with insulin sensitivity (the ratio of insulin-stimulated glucose effectiveness, or M value, to the mean insulin concentration, or I value; r = 0.39, P = 0.02). In regression modeling, A1C, visceral fat mass, and M:I explained 38% of the variance in Kf (in a linear regression model with Kf as the outcome [R2 = 0.38, P = 0.005]). M:I was associated with Kf independently of visceral fat mass (B coefficient 3.13 [95% CI 0.22–6.02], P = 0.036). Although 6 months' treatment with atorvastatin decreased LDL cholesterol by 51% (P < 0.001) and plasma high-sensitivity C-reactive protein by 75% (P = 0.02), microvascular function was unchanged.
Conclusions: decreased insulin-mediated glucose uptake in skeletal muscle is associated with impaired muscle microvascular exchange capacity (Kf), independently of visceral fat mass. Muscle microvascular function is not improved by 6 months of high-dose statin treatment, despite marked statin-mediated improvements in lipid metabolism and decreased inflammation.
obesity, diabetes, statins, insulin sensitivity
0012-1797
1185-1191
Clough, Geraldine F.
9f19639e-a929-4976-ac35-259f9011c494
Turzyniecka, Magdalena
8368c46e-6803-4750-b56c-518ea1fbf871
Walter, Lara
eaf77899-5915-4f62-9996-bab7676069ae
Krentz, Andrew J.
e2c541b2-1292-4cf1-bc0c-d06f3242156d
Wild, Sarah H.
b790195a-4aae-421b-81f7-2c18c96e6870
Chipperfield, Andrew J.
524269cd-5f30-4356-92d4-891c14c09340
Gamble, John
2e45ff40-aab3-4fca-b553-1f5bcff68ffe
Byrne, Christopher D.
1370b997-cead-4229-83a7-53301ed2a43c
Clough, Geraldine F.
9f19639e-a929-4976-ac35-259f9011c494
Turzyniecka, Magdalena
8368c46e-6803-4750-b56c-518ea1fbf871
Walter, Lara
eaf77899-5915-4f62-9996-bab7676069ae
Krentz, Andrew J.
e2c541b2-1292-4cf1-bc0c-d06f3242156d
Wild, Sarah H.
b790195a-4aae-421b-81f7-2c18c96e6870
Chipperfield, Andrew J.
524269cd-5f30-4356-92d4-891c14c09340
Gamble, John
2e45ff40-aab3-4fca-b553-1f5bcff68ffe
Byrne, Christopher D.
1370b997-cead-4229-83a7-53301ed2a43c

Clough, Geraldine F., Turzyniecka, Magdalena, Walter, Lara, Krentz, Andrew J., Wild, Sarah H., Chipperfield, Andrew J., Gamble, John and Byrne, Christopher D. (2009) Muscle microvascular dysfunction in central obesity is related to muscle insulin insensitivity but Is not reversed by high-dose statin treatment. Diabetes, 58 (5), 1185-1191. (doi:10.2337/db08-1688).

Record type: Article

Abstract

Objective: to test the hypotheses that decreased insulin-mediated glucose disposal in muscle is associated with a reduced muscle microvascular exchange capacity (Kf) and that 6 months of high-dose statin therapy would improve microvascular function in people with central obesity.
Research design and methods: we assessed skeletal muscle microvascular function, visceral fat mass, physical activity levels, fitness, and insulin sensitivity in skeletal muscle in 22 female and 17 male volunteers with central obesity whose age (mean ± SD) was 51 ± 9 years. We tested the effect of atorvastatin (40 mg daily) on muscle microvascular function in a randomized, double-blind, placebo-controlled trial lasting 6 months.
Results: Kf was negatively associated with a measure of glycemia (A1C; r = ?0.44, P = 0.006) and positively associated with insulin sensitivity (the ratio of insulin-stimulated glucose effectiveness, or M value, to the mean insulin concentration, or I value; r = 0.39, P = 0.02). In regression modeling, A1C, visceral fat mass, and M:I explained 38% of the variance in Kf (in a linear regression model with Kf as the outcome [R2 = 0.38, P = 0.005]). M:I was associated with Kf independently of visceral fat mass (B coefficient 3.13 [95% CI 0.22–6.02], P = 0.036). Although 6 months' treatment with atorvastatin decreased LDL cholesterol by 51% (P < 0.001) and plasma high-sensitivity C-reactive protein by 75% (P = 0.02), microvascular function was unchanged.
Conclusions: decreased insulin-mediated glucose uptake in skeletal muscle is associated with impaired muscle microvascular exchange capacity (Kf), independently of visceral fat mass. Muscle microvascular function is not improved by 6 months of high-dose statin treatment, despite marked statin-mediated improvements in lipid metabolism and decreased inflammation.

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Submitted date: 5 December 2008
Published date: 10 February 2009
Keywords: obesity, diabetes, statins, insulin sensitivity
Organisations: Computational Engineering and Design, Dev Origins of Health & Disease

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Local EPrints ID: 66623
URI: http://eprints.soton.ac.uk/id/eprint/66623
ISSN: 0012-1797
PURE UUID: ff52a48d-1d6a-43e8-ace6-b7eb075064af
ORCID for Geraldine F. Clough: ORCID iD orcid.org/0000-0002-6226-8964
ORCID for Andrew J. Chipperfield: ORCID iD orcid.org/0000-0002-3026-9890
ORCID for Christopher D. Byrne: ORCID iD orcid.org/0000-0001-6322-7753

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Date deposited: 25 Aug 2009
Last modified: 14 Mar 2024 02:47

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Contributors

Author: Magdalena Turzyniecka
Author: Lara Walter
Author: Andrew J. Krentz
Author: Sarah H. Wild
Author: John Gamble

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