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Associations of Serum Adiponectin with Skeletal Muscle Morphology and Insulin Sensitivity

Department of Medical Epidemiology and Biostatistics (E.I.), Karolinska Institutet, SE-171 77 Stockholm, Sweden; Departments of Public Health and Caring Sciences (E.I., J.Ä., B.Z., A.H.) and Medical Sciences (C.B., L.L., J.S.), Uppsala University, SE-751 85 Uppsala, Sweden; Department of Health and Social Sciences (J.Ä.), Högskolan Dalarna, SE-791 88 Falun, Sweden; The Framingham Heart Study (R.S.V.), Boston University School of Medicine, Framingham, Massachusetts 01702; and The Medical Research Laboratories (A.F., J.F.), Clinical Institute, Aarhus University Hospital, DK-8000 Aarhus C, Denmark

Address all correspondence and requests for reprints to: Erik Ingelsson, M.D., Ph.D., Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Box 281, SE-171 77 Stockholm, Sweden. E-mail: erik.ingelsson{at}ki.se.

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 (β, 0.30 per 50 capillaries per square millimeter increase; P = 0.041) and higher proportion of type I muscle fibers (β, 0.27 per 10% increase; P = 0.036) but declined with a higher proportion of type IIb fibers (β, –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 (β difference, 0.041; 95% confidence interval 0.001, 0.085) and proportion of type IIb muscle fibers (β 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.