title: Insulin resistance is associated with skeletal muscle weakness in COPD.
abstract: OBJECTIVE
  Quadriceps weakness is seen across all GOLD stages of COPD and is associated with increased morbidity and mortality. As quadriceps weakness is only weakly associated with FEV1 , mechanisms other than airflow obstruction are implicated. We tested the hypothesis that insulin resistance contributes to skeletal muscle weakness in people with stable COPD.
  
  
  METHODS
  Fifty-one COPD patients (no exacerbations preceding 6 weeks, no rehabilitation preceding 3 months) without known diabetes mellitus underwent assessment of skeletal muscle, including measurement of quadriceps maximal voluntary contraction (QMVC). Physical activity was measured for 7 days using a multisensory biaxial accelerometer armband. Insulin resistance (HOMA2 IR) was calculated from fasting blood glucose and insulin concentrations.
  
  
  RESULTS
  QMVC was 30 ± 13 kg (74 ± 25% predicted) and 16 (31%) participants had quadriceps weakness. There was a negative univariate correlation between HOMA2 IR and QMVC (r = -0.446, P = 0.002). HOMA2 IR was greater in people with quadriceps weakness (1.59 ± 0.99) than in those without (1.11 ± 0.55, P = 0.032). On multivariate analysis, with age, sex, weight, BODE index and step count per day included in the model, a one-unit increase in insulin resistance was associated with a 5.9 (2.0-9.8)-kg decrease in QMVC (P = 0.004) and a 4.2 (1.3-14.3)-fold increased risk of quadriceps weakness (P = 0.02).
  
  
  CONCLUSIONS
  Insulin resistance is associated with skeletal muscle weakness in COPD, independent of potential confounders. Further studies are required to explore underlying mechanisms and determine whether insulin-sensitizing drugs could augment pulmonary rehabilitation in building skeletal muscle strength in COPD.
authors.affiliation: Institute of Infection and Immunity (mail point J1A), St George's, University of London, London, UK.
authors.forename: Claire E
authors.initials: CE
authors.lastname: Wells
authors.affiliation: NIHR Respiratory Biomedical Research Unit, Royal Brompton and Harefield NHS Foundation Trust and Imperial College, London, UK.
authors.forename: Michael I
authors.initials: MI
authors.lastname: Polkey
authors.affiliation: Institute of Infection and Immunity (mail point J1A), St George's, University of London, London, UK.
authors.forename: Emma H
authors.initials: EH
authors.lastname: Baker
mesh_terms: D061725:Accelerometry; D000368:Aged; D015444:Exercise; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction; D053580:Muscle Strength; D018908:Muscle Weakness / Q000209:etiology / Q000503:physiopathology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000503:physiopathology*; D052097:Quadriceps Muscle / Q000502:physiology
keywords: Exercise; insulin resistance; muscle; obstructive pulmonary disease; skeletal