Body mass index (BMI; kg·m−2) is a statistical construct that was designed as a proxy for adiposity in screening and surveillance of weight at the population level. However, since BMI reflects total mass rather than composition and distribution, BMI is a non-specific instrument that does not measure details of body composition or clinical phenotype necessary to assess individual risk.1, 2, 3., 4., 5, 6. The distribution of tissue types such as adipose and lean mass may provide more comprehensive information that may better explain the risk of cardiometabolic disease than BMI.7 The American Medical Association (AMA) recently adopted a new policy that no longer uses BMI in isolation for assessing the health of an individual based on weight.8

Both lean and adipose mass have been associated with cardiometabolic disease. Lower lean mass and higher adipose mass are jointly associated with a greater risk for type 2 diabetes mellitus (T2DM),9,10 atherosclerotic vascular diseases,10 and all-cause mortality.11,12 However, examining lean and adipose mass as independent factors ignores their biological interdependence and influence on one another through muscle-adipose tissue cross-talk.13, 14, 15, 16 Therefore, recent research has used lean-adipose mass ratios to evaluate the joint association of lean and adipose mass on measures of cardiometabolic health including metabolic syndrome,17, 18, 19 insulin resistance,17,20 and sarcopenic obesity.21

Healthy ranges of adipose tissue differ by sex, as women need more adipose tissue to maintain normal physiological processes.22 Despite the need for larger amounts of adipose tissue and increased adipogenesis,23 women have a lower prevalence of T2DM, hypertension, and dyslipidemia.24 BMI is a proxy for adiposity but cut-points do not account for sex differences in vital adiposity for physiological functions or location of adipose deposition. Therefore, sex may modify the association between measures of body composition and T2DM, hypertension, and dyslipidemia. The advantages of BMI are the low cost and ease of measurement. These advantages are not without limitations, which include a lack of distinguishing tissue types contributing to overall body composition and adiposity, particularly differences by sex, and subsequent health risk. Therefore, our goal is to assess the potential non-clinical value of a sex-standardized measure of adipose-to-lean ratio (ALR) in middle adulthood with incident T2DM, hypertension, and dyslipidemia over 10 years of follow-up. We hypothesized that ALR would be positively associated with risk for T2DM, hypertension, and dyslipidemia and these associations would not differ by sex.