Skeletal muscle fat accumulation, independent of overall body fat, may contribute to hyperglycemia and insulin resistance, disorders that are highly prevalent in populations of African origin. A few studies conducted mainly in women or in small samples, also suggest that individuals of African ancestry may have increased skeletal muscle fat compared to Caucasians, independent of overall body fat. However, much remains to be learned about the epidemiology of skeletal muscle composition and its relationship to metabolic disorders, particularly in populations of African ancestry. The goal of the proposed application is to characterize the epidemiology of ectopic skeletal muscle fat. Components of skeletal muscle composition including muscle cross-sectional area, total, subcutaneous, and intermuscular adipose tissue areas, and skeletal muscle density will be measured from existing quantitative computed tomography (pQCT) scans in 2200 men of Caucasian and African descent.
The specific aims are to: (1) determine if there are ethnic differences in the distribution of skeletal muscle fat;(2) evaluate if genetic variations in the fatty-acid binding protein 4 gene contribute to skeletal muscle composition in men of African and Caucasian ancestry;and (3) to test the hypothesis that skeletal muscle fat increases with advancing age. The candidate's goals are to: (1) acquire new skills in quantitative computed tomography imaging of skeletal muscle composition;(2) become proficient in high-throughput genotyping and DMA sequence analysis;(3) obtain field experience in conducting longitudinal studies of skeletal muscle composition.

Public Health Relevance

The accomplishment of the proposed aims will greatly enhance our understanding of the epidemiology and genetics of ectopic fat infiltration in skeletal muscle and its relationship to diabetes.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Scientist Development Award - Research & Training (K01)
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Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
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Hyde, James F
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University of Pittsburgh
Public Health & Prev Medicine
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United States
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Zhao, Qian; Zmuda, Joseph M; Kuipers, Allison L et al. (2017) Muscle Attenuation Is Associated With Newly Developed Hypertension in Men of African Ancestry. Hypertension 69:957-963
Kuipers, A L; Miljkovic, I; Evans, R et al. (2016) Optimal serum cholesterol concentrations are associated with accelerated bone loss in African ancestry men. Osteoporos Int 27:1577-1584
Liu, Ching-Ti; Raghavan, Sridharan; Maruthur, Nisa et al. (2016) Trans-ethnic Meta-analysis and Functional Annotation Illuminates theĀ Genetic Architecture of Fasting Glucose and Insulin. Am J Hum Genet 99:56-75
Miljkovic, Iva; Kuipers, Allison L; Cvejkus, Ryan et al. (2016) Myosteatosis increases with aging and is associated with incident diabetes in African ancestry men. Obesity (Silver Spring) 24:476-82
Tilves, Curtis M; Zmuda, Joseph M; Kuipers, Allison L et al. (2016) Association of Lipopolysaccharide-Binding Protein With Aging-Related Adiposity Change and Prediabetes Among African Ancestry Men. Diabetes Care 39:385-91
Miljkovic, Iva; Kuipers, Allison L; Cauley, Jane A et al. (2015) Greater Skeletal Muscle Fat Infiltration Is Associated With Higher All-Cause and Cardiovascular Mortality in Older Men. J Gerontol A Biol Sci Med Sci 70:1133-40
Kuipers, A L; Zmuda, J M; Carr, J J et al. (2014) Association of volumetric bone mineral density with abdominal aortic calcification in African ancestry men. Osteoporos Int 25:1063-9
Kuipers, Allison L; Miljkovic, Iva; Kammerer, Candace M et al. (2013) Evidence for a genetic link between bone and vascular measures in African ancestry families. J Bone Miner Res 28:1804-10
Miljkovic, Iva; Cauley, Jane A; Wang, Patty Y et al. (2013) Abdominal myosteatosis is independently associated with hyperinsulinemia and insulin resistance among older men without diabetes. Obesity (Silver Spring) 21:2118-25
Li, Hu; Kuipers, Allison; Kammerer, Candace M et al. (2013) The association between renal function biomarkers and subclinical cardiovascular measures in African Caribbean families. Ethn Dis 23:492-8

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