Leg length and type 2 diabetes

Noel T. Mueller, Mark A. Pereira

Human leg length is determined by a complex interplay of genetics and environmental exposures during development, which may be associated with long-term metabolic disease risk. Here, we review recent literature on the link between relative leg length and type 2 diabetes in more and less economically developed societies, wherein the contextual influences on relative leg length are unique. We also hypothesize mechanisms underlying and mediating this association. Evidence from more economically prosperous Western populations and contemporary adult populations in China and Brazil indicates that lower relative leg length is associated with greater risk for impaired glucose homeostasis and type 2 diabetes. In Brazil, this association was stronger among women with early menarche. Although still poorly defined and in need of further research, the potential mechanisms likely involve suboptimal early-life net nutrition that simultaneously leads to retarded growth and impaired glucose regulation. An untested hypothesis is that the association is mediated by differences in skeletal muscle mass. Epidemiologic evidence from diverse settings points to humans with shorter legs relative to their stature having higher risk for type 2 diabetes. Although research is needed to test mechanistic hypotheses, the greatest potential for improving public health will come through identification of, and intervention upon, the upstream modifiable determinants of inadequate leg growth.