Fat infiltration in muscle: new evidence for familial clustering and associations with diabetes.
OBJECTIVE
Increased fat infiltration in skeletal muscle has been associated with diabetes. Quantitative computed tomography (QCT) can be used to measure muscle density, which reflects the lipid content of skeletal muscle such that greater fat infiltration in skeletal muscle is associated with lower muscle density. The relative contribution of genetic and environmental factors to fat infiltration in skeletal muscle has not been assessed. Therefore, our aim is to determine genetic and environmental contributions to measures of skeletal muscle composition, and describe their associations with type 2 diabetes in multigenerational families of African ancestry.


METHODS
Peripheral QCT (pQCT) measures of skeletal muscle density were obtained for the calf in 471 individuals (60% women; mean 43 years) belonging to eight large, multigenerational Afro-Caribbean families (mean family size 51 individuals; 3,535 relative pairs).


RESULTS
The proportion of variance in muscle density due to additive genetic effects (residual heritability) was 35.0% (P < 0.001) and significant covariates (age, gender, BMI, and parity) explained 55.0% of the total phenotypic variation in muscle density. Muscle density was lower (P < 0.001) in 62 diabetics (69.5 mg/cm(3)) than in 339 nondiabetics (74.3 mg/cm(3)) and remained significant after adjusting for age, gender, and BMI (P = 0.005) or age, gender, and waist circumference (P = 0.01).


CONCLUSIONS
Our results provide new evidence that ectopic lipid deposition in skeletal muscle is a heritable trait and is associated with diabetes, independent of overall and central obesity in families of African heritage. Genome-wide screens and candidate gene studies are warranted to identify the genetic factors contributing to ectopic deposition of skeletal muscle fat.
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. ivm1@pitt.edu
Iva
I
Miljkovic-Gacic
Xiaojing
X
Wang
Candace M
CM
Kammerer
Christopher L
CL
Gordon
Clareann H
CH
Bunker
Lewis H
LH
Kuller
Alan L
AL
Patrick
Victor W
VW
Wheeler
Rhobert W
RW
Evans
Joseph M
JM
Zmuda
D000273:Adipose Tissue / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000208:ethnology / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D050218:Body Fat Distribution; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism*; D004777:Environment; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008019:Life Style; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D018482:Muscle, Skeletal / Q000378:metabolism*; D009765:Obesity / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism*