title: Adipose depots, not disease-related factors, account for skeletal muscle insulin sensitivity in established and treated rheumatoid arthritis.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Hiba
authors.initials: H
authors.lastname: AbouAssi
authors.affiliation: 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.
authors.forename: K Noelle
authors.initials: KN
authors.lastname: Tune
authors.affiliation: 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.
authors.forename: Brian
authors.initials: B
authors.lastname: Gilmore
authors.affiliation: 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.
authors.forename: Lori A
authors.initials: LA
authors.lastname: Bateman
authors.affiliation: 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.
authors.forename: Gary
authors.initials: G
authors.lastname: McDaniel
authors.affiliation: 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.
authors.forename: Michael
authors.initials: M
authors.lastname: Muehlbauer
authors.affiliation: 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.
authors.forename: Janet L
authors.initials: JL
authors.lastname: Huebner
authors.affiliation: 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.
authors.forename: Helen M
authors.initials: HM
authors.lastname: Hoenig
authors.affiliation: 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.
authors.forename: Virginia B
authors.initials: VB
authors.lastname: Kraus
authors.affiliation: 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.
authors.forename: E William
authors.initials: EW
authors.lastname: St Clair
authors.affiliation: 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.
authors.forename: William E
authors.initials: WE
authors.lastname: Kraus
authors.affiliation: 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.
authors.forename: Kim M
authors.initials: KM
authors.lastname: Huffman
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D050154:Adiposity / Q000502:physiology; D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000378:metabolism*; D003430:Cross-Sectional Studies; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D020382:Interleukin-18 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D018501:Antirheumatic Agents; D020382:Interleukin-18; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha
keywords: BODY COMPOSITION; INSULIN RESISTANCE; PHYSICAL ACTIVITY; SKELETAL MUSCLE