Short Leg Length, a Marker of Early Childhood Deprivation, Is Associated With Metabolic Disorders Underlying Type 2 Diabetes: The PROMISE cohort study

Short leg length, a marker of early childhood deprivation, has been used in studies of the association of early life conditions with adult chronic disease risk. The objective of this study was to determine the cross-sectional associations of leg length with measures of insulin sensitivity and β-cell function. Subjects (n = 462) at risk for type 2 diabetes were recruited into the PROspective Metabolism and ISlet cell Evaluation (PROMISE) longitudinal cohort. Leg length was calculated from sitting and standing height at the 3-year clinical examination. Glucose tolerance status was determined using an oral glucose tolerance test. Insulin sensitivity was assessed using homeostasis model assessment of insulin resistance (HOMA-IR) and the Matsuda insulin sensitivity index (ISI), while the insulinogenic index over HOMA-IR (IGI/IR) and the insulin secretion sensitivity index 2 (ISSI-2) determined β-cell function. Multiple linear regression analysis was conducted, adjusting for covariates including age, sex, ethnicity, family history of diabetes, waist, and weight. Leg length and leg-to-height ratio were significantly associated with HOMA-IR (β = -0.037, β = -10.49, respectively; P < 0.0001), ISI (β = 0.035, β = 8.83, respectively; P < 0.0001), IGI/IR (β = 0.021, P < 0.05; β = 7.60, P < 0.01, respectively), and ISSI-2 (β = 0.01, P < 0.03; β = 3.34, P < 0.01, respectively) after adjustment for covariates. The association of shorter leg length with lower insulin sensitivity was most evident for those with high waist circumferences. Shorter legs were independently associated with lower insulin sensitivity and β-cell function, suggesting that early childhood deprivation may increase the risk of developing diabetes.