(P20-027-25) Normal Weight Obesity Is Associated With Serum Lipid, Hormone, and Liver Enzyme Differences in the UK Biobank Cohort

Objectives: Normal weight obesity (NWO) – those with a normal body mass index (BMI), yet high body fat percent (BF%) – is an understudied at-risk group for cardiovascular disease (CVD). We hypothesized that subjects with NWO will display alterations in CVD biomarkers, hormones, and liver enzymes versus normal-weight lean (NWL) counterparts.

Methods: \We conducted a cross-sectional analysis using quantile regression in the UK Biobank cohort (40-69 years of age). NWO was defined as a BMI of 18.5-25 & BF% ≥25% males or ≥35% females while NWL was defined as those with a BMI of 18.5-25 but below the aforementioned BF% cutoffs. Sex-specific analyses were conducted by splitting males (M) and females (F) into separate analyses. Study groups included NWL (M=23,653, F=35,518) NWO (M=1,876, F=7,297) and those with overweight (M=42,302, F=34,176) or obese (M=14,391, F=15,966) BMIs. Outcomes included serum biomarkers such as high-density lipoprotein cholesterol (HDL-C), triglycerides, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), apolipoproteins A and B (ApoA, ApoB), lipoprotein A, Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma-glutamyl transferase (GGT), Alkaline Phosphatase (ALP), C-reactive protein (CRP), Testosterone, and Sex Hormone Binding Globulin (SHBG). Covariates included age, sex, smoking status, townsend deprivation index, education, income, genetic principal components, fasting time, and menopause status for females. Data were analyzed in Stata and an FDR < 0.05 after a Bonferroni correction was used to account for multiple comparisons.

Results: In both sexes, NWO was associated with decreased HDL-C, Apo A, and SHBG and increased triglycerides, TC, LDL-C, ApoB, ALT, GGT, ALP, and CRP versus NWL (FDR < 1.0x10^-8). Males with NWO have decreased testosterone, whereas females with NWO have increased testosterone compared to NWL (FDR < 1.0x10^-8). Women with NWO had lower AST than NWL (FDR < 0.0001). Males with NWO also had higher TC and LDL-C than those with overweight/obesity.

Conclusions: NWO was associated with differences in lipid, hormone, and liver enzyme biomarkers that are generally consistent with unfavorable cardiometabolic risk profiles found in people with overweight and obese BMIs, which may indicate an increased risk of CVD.

Funding Sources: Oklahoma State University President’s Faculty Fellows Research Award