Kaiser Wani ^1* Balvir Kumar ² Nasser Al-Daghri ¹ Shaun Sabico ^3*

• ¹ King Saud University, Riyadh, Riyadh, Saudi Arabia
• ² Chandigarh University, Mohali, Punjab, India
• ³ Chair for Biomarkers of Chronic Diseases, Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia

The metabolically healthy obesity (MHO) phenotype represents a complex and distinctive trait, the trends and characteristics of which remain unknown in the Saudi Arabian adult population. The present study aims to fill that gap. A combined total of 10220 Saudi adults from 2 independent cohorts [2008-2019, N = 7896 (2903 males and 4993 females), and 2021-2023, N = 2324 (830 males and 1494 females)] aged 19-70 years old was screened, of whom 9631 (3428 males and 6203 females) were included. Anthropometric data were measured, and fasting blood samples were collected to assess glucose, lipids, adipocytokines and inflammatory markers using routine methods and commercially available assays. Obesity was defined as a body mass index (BMI) ≥30kg/m 2 . Screening for MHO was done using the empiric definition proposed by Zembic and colleagues and the by the National Cholesterol Education Program's Adult Treatment Panel III (NCEP ATPIII). Of the 3949 (41.0%) participants with obesity, 33.4% (95% confidence interval, CI, 32-35) were considered MHO using the empiric definition, and 32.8% (95% CI, 31-34) using NCEP-ATPIII. The overall age and gender adjusted prevalence of MHO in the Saudi adult population was 31.6% (95% CI, 30-33) and 30.1% (29-31) by the two definitions respectively. Females had a higher age-adjusted prevalence of MHO than males (OR=1.22, 95% CI 1.1 -1.4), p=0.009) as per the ATPIII criteria. MHO prevalence substantially increased over time from 2008-2023 (p<0.001) for both definitions. Circulating leptin levels and insulin resistance were significantly higher in the MUO group than the MHO group independent of the definition used, suggesting the presence of a more severe form of leptin resistance in the MUO group which may explain the worse cardiometabolic profile as compared to the MHO group. In summary, the study highlights the first time the characteristics and trends of the MHO phenotype among Saudi Arabian adults. The pluripotent effects of leptin and its resistance may be central to MHO's progression, or lack thereof, to the MUO phenotype, and this needs further investigation.