SAT-669 - Sex Hormone Binding Globulin Is Inversely Associated with Insulin Resistance Among Normal Weight Adults in A Nationally Representative U.S. Sample

Background: Body mass index (BMI) incompletely captures metabolic health, as insulin resistance can be present even among individuals with normal body weight. Sex hormone–binding globulin (SHBG) is a hepatically synthesized glycoprotein regulated by insulin signaling and metabolic status, but its relationship with insulin resistance among normal-weight adults remains poorly characterized.

Objective: To evaluate the association between SHBG and insulin resistance among normal-weight U.S. adults using nationally representative data and to assess whether this relationship is independent of demographic, socioeconomic, and dietary factors.

Methods: We conducted a cross-sectional analysis of adults aged ≥18 years from the 2017–2018 National Health and Nutrition Examination Survey (NHANES), the most recent cycle preceding COVID-19–related disruptions. Among 1,717 adults with available SHBG measurements, 473 had a normal BMI ( < 25 kg/m²) and complete metabolic data and were included in the analytic cohort. Insulin resistance was assessed continuously using the homeostasis model assessment of insulin resistance (HOMA-IR). Serum SHBG was log-transformed and standardized. Survey-weighted linear regression models were used to evaluate the association between SHBG and HOMA-IR, adjusting for age, sex, race/ethnicity, socioeconomic status, smoking status, and self-reported dietary behaviors (fast food consumption and meals prepared away from home).

Results: Among normal-weight adults, higher SHBG levels were independently associated with lower insulin resistance. Each standard deviation increase in log-transformed SHBG corresponded to a 2.29-unit lower HOMA-IR after multivariable adjustment. Although mean SHBG and insulin resistance differed by sex and race, neither was independently associated with insulin resistance after adjustment. The inverse relationship between SHBG and insulin resistance was consistent across sexes. Dietary behaviors were not independently associated with insulin resistance.

Conclusion: In a nationally representative U.S. population, SHBG was strongly and inversely associated with insulin resistance among normal-weight adults, independent of dietary behaviors. These findings suggest that SHBG may reflect underlying metabolic dysfunction not captured by BMI alone and could serve as an endocrine marker of metabolic risk in individuals who appear healthy by traditional anthropometric screening.

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