Associations of serum adiponectin with skeletal muscle morphology and insulin sensitivity.

CONTEXT Skeletal muscle morphology and function are strongly associated with insulin sensitivity. OBJECTIVE The objective of the study was to test the hypothesis that circulating adiponectin is associated with skeletal muscle morphology and that adiponectin mediates the relation of muscle morphology to insulin sensitivity. DESIGN, SETTINGS, AND PARTICIPANTS This was a cross-sectional investigation of 461 men aged 71 yr, participants of the community-based Uppsala Longitudinal Study of Adult Men study. MAIN OUTCOME MEASURES Measures included serum adiponectin, insulin sensitivity measured with euglycemic insulin clamp technique, and capillary density and muscle fiber composition determined from vastus lateralis muscle biopsies. RESULTS In multivariable linear regression models (adjusting for age, physical activity, fasting glucose, and pharmacological treatment for diabetes), serum adiponectin levels rose with increasing capillary density (beta, 0.30 per 50 capillaries per square millimeter increase; P = 0.041) and higher proportion of type I muscle fibers (beta, 0.27 per 10% increase; P = 0.036) but declined with a higher proportion of type IIb fibers (beta, -0.39 per 10% increase; P = 0.014). Using bootstrap methods to examine the potential role of adiponectin in associations between muscle morphology and insulin sensitivity and the associations of capillary density (beta difference, 0.041; 95% confidence interval 0.001, 0.085) and proportion of type IIb muscle fibers (beta difference, -0.053; 95% confidence interval -0.107, -0.002) with insulin sensitivity were significantly attenuated when adiponectin was included in the models. CONCLUSIONS Circulating adiponectin concentrations were higher with increasing skeletal muscle capillary density and in individuals with higher proportion of slow oxidative muscle fibers. Furthermore, our results indicate that adiponectin could be a partial mediator of the relations between skeletal muscle morphology and insulin sensitivity.

[1]  Y. Liu,et al.  Adiponectin is expressed by skeletal muscle fibers and influences muscle phenotype and function. , 2008, American journal of physiology. Cell physiology.

[2]  S. Kihara,et al.  Adiponectin protects against the development of systolic dysfunction following myocardial infarction. , 2007, Journal of molecular and cellular cardiology.

[3]  M. Quon,et al.  Adiponectin and cardiovascular disease: response to therapeutic interventions. , 2007, Journal of the American College of Cardiology.

[4]  Patrick Royston,et al.  Multivariable Modeling with Cubic Regression Splines: A Principled Approach , 2007 .

[5]  C. Berne,et al.  Serum adiponectin is a predictor of coronary heart disease: a population-based 10-year follow-up study in elderly men. , 2007, The Journal of clinical endocrinology and metabolism.

[6]  J. Layne,et al.  Strength training improves muscle quality and insulin sensitivity in Hispanic older adults with type 2 diabetes , 2006, International journal of medical sciences.

[7]  Herbert Tilg,et al.  Adipocytokines: mediators linking adipose tissue, inflammation and immunity , 2006, Nature Reviews Immunology.

[8]  C. Mantzoros,et al.  Circulating adiponectin and expression of adiponectin receptors in human skeletal muscle: associations with metabolic parameters and insulin resistance and regulation by physical training. , 2006, The Journal of clinical endocrinology and metabolism.

[9]  Jan Frystyk,et al.  Plasma Adiponectin, Body Mass Index, and Mortality in Patients With Chronic Heart Failure , 2005, Circulation.

[10]  E. Ingelsson,et al.  Insulin resistance and risk of congestive heart failure. , 2005, JAMA.

[11]  S. Kihara,et al.  Adiponectin Stimulates Angiogenesis in Response to Tissue Ischemia through Stimulation of AMP-activated Protein Kinase Signaling* , 2004, Journal of Biological Chemistry.

[12]  L. Byberg,et al.  Muscle morphology, self-reported physical activity and insulin resistance syndrome. , 2002, Acta physiologica Scandinavica.

[13]  G. Dohm,et al.  Muscle fiber type is associated with obesity and weight loss. , 2002, American journal of physiology. Endocrinology and metabolism.

[14]  L. Berglund,et al.  Relationships between muscle morphology and insulin sensitivity are improved after adjustment for intra-individual variability in 70-year-old men. , 2000, Acta physiologica Scandinavica.

[15]  P. Raskin,et al.  Report of the expert committee on the diagnosis and classification of diabetes mellitus. , 1999, Diabetes care.

[16]  K. Bønaa,et al.  Insulin kinetics, insulin action, and muscle morphology in lean or slightly overweight persons with impaired glucose tolerance. , 1998, Metabolism: clinical and experimental.

[17]  S. Lillioja,et al.  Interrelationships between muscle morphology, insulin action, and adiposity. , 1996, The American journal of physiology.

[18]  B. Spiegelman,et al.  AdipoQ Is a Novel Adipose-specific Gene Dysregulated in Obesity (*) , 1996, The Journal of Biological Chemistry.

[19]  Philipp E. Scherer,et al.  A Novel Serum Protein Similar to C1q, Produced Exclusively in Adipocytes (*) , 1995, The Journal of Biological Chemistry.

[20]  H. Lithell,et al.  Lipoprotein lipase activity in skeletal muscle is related to insulin sensitivity. , 1991, Arteriosclerosis and thrombosis : a journal of vascular biology.

[21]  R. DeFronzo,et al.  The Effect of Insulin on the Disposal of Intravenous Glucose: Results from Indirect Calorimetry and Hepatic and Femoral Venous Catheterization , 1981, Diabetes.

[22]  R. DeFronzo,et al.  Glucose clamp technique: a method for quantifying insulin secretion and resistance. , 1979, The American journal of physiology.

[23]  Peter Lindgren,et al.  Guidelines on diabetes, pre-diabetes, and cardiovascular diseases: executive summary , 2007 .

[24]  Y. Matsuzawa.  Therapy Insight: adipocytokines in metabolic syndrome and related cardiovascular disease , 2006, Nature Clinical Practice Cardiovascular Medicine.

[25]  B. Efron.  The jackknife, the bootstrap, and other resampling plans , 1987 .

[26]  Response to Therapeutic Interventions , 2022 .