Hiba AbouAssi1, K Noelle Tune1, Brian Gilmore1, Lori A Bateman1, Gary McDaniel1, Michael Muehlbauer1, Janet L Huebner1, Helen M Hoenig1, Virginia B Kraus1, E William St Clair1, William E Kraus1, Kim M Huffman2. 1. From the Divisions of Endocrinology, Rheumatology and Immunology, Cardiology, Geriatrics, Department of Medicine and Duke Molecular Physiology Institute, Duke University Medical Center; Durham Veterans Affairs Medical Center, Durham, North Carolina, USA.H. AbouAssi, MD, Division of Endocrinology; K.N. Tune, BA, Division of Rheumatology and Immunology; B. Gilmore, BS; L.A. Bateman, MS, Division of Cardiology; G. McDaniel, PA, Division of Rheumatology and Immunology, Department of Medicine, Duke University Medical Center; M. Muehlbauer, PhD; J.L. Huebner, MS, Duke Molecular Physiology Institute, Duke University Medical Center; H.M. Hoenig, MD, Division of Geriatrics, Department of Medicine, Duke University Medical Center, Veterans Affairs Medical Center; V.B. Kraus, MD, PhD, Division of Rheumatology and Immunology, Department of Medicine, Duke Molecular Physiology Institute, Duke University Medical Center; E.W. St. Clair, MD, Division of Rheumatology and Immunology, Department of Medicine, Duke University Medical Center; W.E. Kraus, MD, Division of Cardiology, Department of Medicine, Duke Molecular Physiology Institute, Duke University Medical Center; K.M. Huffman, MD, PhD, Division of Rheumatology and Immunology, Department of Medicine, Duke Molecular Physiology Institute, Duke University Medical Center, and Veterans Affairs Medical Center. 2. From the Divisions of Endocrinology, Rheumatology and Immunology, Cardiology, Geriatrics, Department of Medicine and Duke Molecular Physiology Institute, Duke University Medical Center; Durham Veterans Affairs Medical Center, Durham, North Carolina, USA.H. AbouAssi, MD, Division of Endocrinology; K.N. Tune, BA, Division of Rheumatology and Immunology; B. Gilmore, BS; L.A. Bateman, MS, Division of Cardiology; G. McDaniel, PA, Division of Rheumatology and Immunology, Department of Medicine, Duke University Medical Center; M. Muehlbauer, PhD; J.L. Huebner, MS, Duke Molecular Physiology Institute, Duke University Medical Center; H.M. Hoenig, MD, Division of Geriatrics, Department of Medicine, Duke University Medical Center, Veterans Affairs Medical Center; V.B. Kraus, MD, PhD, Division of Rheumatology and Immunology, Department of Medicine, Duke Molecular Physiology Institute, Duke University Medical Center; E.W. St. Clair, MD, Division of Rheumatology and Immunology, Department of Medicine, Duke University Medical Center; W.E. Kraus, MD, Division of Cardiology, Department of Medicine, Duke Molecular Physiology Institute, Duke University Medical Center; K.M. Huffman, MD, PhD, Division of Rheumatology and Immunology, Department of Medicine, Duke Molecular Physiology Institute, Duke University Medical Center, and Veterans Affairs Medical Center. kim.huffman@duke.edu.
Abstract
OBJECTIVE: In prior reports, individuals with rheumatoid arthritis (RA) exhibited increased insulin resistance. However, those studies were limited by either suboptimal assessment methods for insulin sensitivity or a failure to account for important determinants such as adiposity and lack of physical activity. Our objectives were to carefully assess, compare, and determine predictors of skeletal muscle insulin sensitivity in RA, accounting for adiposity and physical activity. METHODS: Thirty-nine individuals with established (seropositive or erosions) and treated RA and 39 controls matched for age, sex, race, body mass index, and physical activity underwent a frequently sampled intravenous glucose tolerance test to determine insulin sensitivity. Inflammation, body composition, and physical activity were assessed with systemic cytokine measurements, computed tomography scans, and accelerometry, respectively. Exclusions were diabetes, cardiovascular disease, medication changes within 3 months, and prednisone use over 5 mg/day. This investigation was powered to detect a clinically significant, moderate effect size for insulin sensitivity difference. RESULTS: Despite elevated systemic inflammation [interleukin (IL)-6, IL-18, tumor necrosis factor-α; p < 0.05 for all], persons with RA were not less insulin sensitive [SI geometric mean (SD): RA 4.0 (2.4) vs control 4.9 (2.1)*10(-5) min(-1)/(pmol/l); p = 0.39]. Except for visceral adiposity being slightly greater in controls (p = 0.03), there were no differences in body composition or physical activity. Lower insulin sensitivity was independently associated with increased abdominal and thigh adiposity, but not with cytokines, disease activity, duration, disability, or disease-modifying medication use. CONCLUSION: In established and treated RA, traditional risk factors, specifically excess adiposity, play more of a role in predicting skeletal muscle insulin sensitivity than do systemic inflammation or other disease-related factors.
OBJECTIVE: In prior reports, individuals with rheumatoid arthritis (RA) exhibited increased insulin resistance. However, those studies were limited by either suboptimal assessment methods for insulin sensitivity or a failure to account for important determinants such as adiposity and lack of physical activity. Our objectives were to carefully assess, compare, and determine predictors of skeletal muscle insulin sensitivity in RA, accounting for adiposity and physical activity. METHODS: Thirty-nine individuals with established (seropositive or erosions) and treated RA and 39 controls matched for age, sex, race, body mass index, and physical activity underwent a frequently sampled intravenous glucose tolerance test to determine insulin sensitivity. Inflammation, body composition, and physical activity were assessed with systemic cytokine measurements, computed tomography scans, and accelerometry, respectively. Exclusions were diabetes, cardiovascular disease, medication changes within 3 months, and prednisone use over 5 mg/day. This investigation was powered to detect a clinically significant, moderate effect size for insulin sensitivity difference. RESULTS: Despite elevated systemic inflammation [interleukin (IL)-6, IL-18, tumor necrosis factor-α; p < 0.05 for all], persons with RA were not less insulin sensitive [SI geometric mean (SD): RA 4.0 (2.4) vs control 4.9 (2.1)*10(-5) min(-1)/(pmol/l); p = 0.39]. Except for visceral adiposity being slightly greater in controls (p = 0.03), there were no differences in body composition or physical activity. Lower insulin sensitivity was independently associated with increased abdominal and thigh adiposity, but not with cytokines, disease activity, duration, disability, or disease-modifying medication use. CONCLUSION: In established and treated RA, traditional risk factors, specifically excess adiposity, play more of a role in predicting skeletal muscle insulin sensitivity than do systemic inflammation or other disease-related factors.
Entities:
Keywords:
BODY COMPOSITION; INSULIN RESISTANCE; PHYSICAL ACTIVITY; SKELETAL MUSCLE
Authors: Brian A Irving; Judy Y Weltman; David W Brock; Christopher K Davis; Glenn A Gaesser; Arthur Weltman Journal: Obesity (Silver Spring) Date: 2007-02 Impact factor: 5.002
Authors: Kitt Falk Petersen; Sylvie Dufour; David B Savage; Stefan Bilz; Gina Solomon; Shin Yonemitsu; Gary W Cline; Douglas Befroy; Laura Zemany; Barbara B Kahn; Xenophon Papademetris; Douglas L Rothman; Gerald I Shulman Journal: Proc Natl Acad Sci U S A Date: 2007-07-18 Impact factor: 11.205
Authors: Hilal Maradit-Kremers; Cynthia S Crowson; Paulo J Nicola; Karla V Ballman; Véronique L Roger; Steve J Jacobsen; Sherine E Gabriel Journal: Arthritis Rheum Date: 2005-02
Authors: Cecilia P Chung; Annette Oeser; Joseph F Solus; Tebeb Gebretsadik; Ayumi Shintani; Ingrid Avalos; Tuulikki Sokka; Paolo Raggi; Theodore Pincus; C Michael Stein Journal: Arthritis Rheum Date: 2008-07
Authors: Ruth E Taylor-Piliae; William L Haskell; Carlos Iribarren; Linda C Norton; Mohammed H Mahbouba; Joan M Fair; Mark A Hlatky; Alan S Go; Stephen P Fortmann Journal: J Cardiopulm Rehabil Prev Date: 2007 Jul-Aug Impact factor: 2.081
Authors: Samannaaz S Khoja; Charity G Moore; Bret H Goodpaster; Anthony Delitto; Sara R Piva Journal: Arthritis Care Res (Hoboken) Date: 2018-02-06 Impact factor: 4.794
Authors: Beatriz Y Hanaoka; Matthew P Ithurburn; Cody A Rigsbee; S Louis Bridges; Douglas R Moellering; Barbara Gower; Marcas Bamman Journal: Arthritis Care Res (Hoboken) Date: 2019-01-04 Impact factor: 4.794
Authors: Kim M Huffman; Ryan Jessee; Brian Andonian; Brittany N Davis; Rachel Narowski; Janet L Huebner; Virginia B Kraus; Julie McCracken; Brian F Gilmore; K Noelle Tune; Milton Campbell; Timothy R Koves; Deborah M Muoio; Monica J Hubal; William E Kraus Journal: Arthritis Res Ther Date: 2017-01-23 Impact factor: 5.156
Authors: Brian J Andonian; Ching-Heng Chou; Olga R Ilkayeva; Timothy R Koves; Margery A Connelly; William E Kraus; Virginia B Kraus; Kim M Huffman Journal: Front Immunol Date: 2019-06-27 Impact factor: 7.561
Authors: Brian J Andonian; Andrew Johannemann; Monica J Hubal; David M Pober; Alec Koss; William E Kraus; David B Bartlett; Kim M Huffman Journal: Arthritis Res Ther Date: 2021-07-10 Impact factor: 5.156
Authors: David B Bartlett; Margery A Connelly; Hiba AbouAssi; Lori A Bateman; K Noelle Tune; Janet L Huebner; Virginia B Kraus; Deborah A Winegar; James D Otvos; William E Kraus; Kim M Huffman Journal: Arthritis Res Ther Date: 2016-04-12 Impact factor: 5.156
Authors: Sara Manrique-Arija; Inmaculada Ureña; Pedro Valdivielso; José Rioja; Francisco G Jiménez-Núñez; María V Irigoyen; Antonio Fernández-Nebro Journal: Clin Rheumatol Date: 2015-11-03 Impact factor: 2.980
Authors: Hiba AbouAssi; Margery A Connelly; Lori A Bateman; K Noelle Tune; Janet L Huebner; Virginia B Kraus; Deborah A Winegar; James D Otvos; William E Kraus; Kim M Huffman Journal: Lipids Health Dis Date: 2017-02-10 Impact factor: 3.876