2D: 4D digit ratio, bilateral asymmetry, and insulin resistance in women with obesity

The second-to-fourth digit ratio (2D:4D) has been proposed as a marker of the prenatal hormonal environment, while right (R)-left (L) asymmetry is considered an indicator of developmental instability. In individuals exposed to the increased metabolic burden of obesity, the role of these early developmental markers in determining the presence of insulin resistance (IR) remains insufficiently understood. The aim of this study was to examine the associations of R and L 2D:4D ratios, R-L 2D:4D (Dr-l) and |Dr-l| with IR in women with obesity.

This single-center cross-sectional study included women aged ≥18 years with a body mass index (BMI) ≥30 kg/m². The lengths of the second and fourth digits were measured, and R and L 2D:4D ratios as well as Dr-l and |Dr-l| were calculated. IR was defined using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), with values ≥2.5 considered indicative of IR. Sociodemographic characteristics, comorbidities, body fat percentage, and glycemic status were included as covariates in multivariable analyses.

Among 124 women, the R 2D:4D was not associated with IR, whereas the L 2D:4D remained independently associated with IR after multivariable adjustment (OR = 1.13 [1.02-1.26]). |Dr-l| was a strong independent predictor of IR (OR = 1.26 [1.11-1.44]). In direction-specific piecewise regression analyses, leftward asymmetry was more strongly associated with IR (OR = 1.50 [1.19-1.90]) than rightward asymmetry (OR = 1.16 [1.02-1.33]).

Bilateral 2D:4D asymmetry, especially leftward asymmetry, may capture developmental instability contributing to IR among women with obesity.