Circulating FTO Protein Levels and β-Cell Function in Individuals with Different Metabolic Profiles: A Cross- Sectional Study

Hadil Shams Aldeen Alsagher, Shaden HaddadDepartment of Biochemistry and Microbiology, Faculty of Pharmacy, Damascus University, Damascus, SyriaCorrespondence: Hadil Shams Aldeen Alsagher, Email pharmacyainminen@gmail.comBackground: Obesity and type 2 diabetes mellitus are characterized by insulin resistance and progressive impairment of β-cell function. Fat mass and obesity-associated (FTO) protein, an m6A demethylase involved in metabolic regulation, has been linked to obesity. However, the relationship between circulating FTO protein levels and β-cell function among individuals with different metabolic profiles remains unclear. This study aimed to investigate circulating FTO levels and their relationship with β-cell function, assessed by (HOMA-β), in individuals with newly diagnosed T2D, obese individuals without diabetes, and normal-weight individuals without diabetes.Patients and Methods: This cross-sectional observational study included 82 participants: 39 individuals newly diagnosed with T2D, 23 obese individuals without diabetes, and 20 normal-weight individuals without diabetes. Anthropometric and biochemical parameters, including fasting blood glucose, glycated hemoglobin, fasting insulin, HOMA-IR, and HOMA-β, were assessed. Serum FTO levels were measured using ELISA. Correlation and multiple linear regression analyses were performed to examine the relationship between circulating FTO levels and (HOMA-β).Results: Serum FTO protein levels differed significantly among the three groups (P = 0.002), with the highest levels observed in obese individuals without diabetes. In this group, FTO protein levels were positively correlated with body mass index, fasting insulin, and HOMA-β (P = 0.018, P = 0.040, and P = 0.033, respectively). HOMA-β was also positively correlated with FTO, fasting insulin, and HOMA-IR. However, the positive association between FTO levels and HOMA-β was not statistically significant after adjustment for age, sex, and metabolic status.Conclusions: Circulating FTO levels were highest in obese individuals without diabetes and were positively correlated with HOMA-β in this group. However, this relationship was not independently significant after adjustment for potential confounders. These findings provide preliminary evidence of a relationship between circulating FTO and β-cell function in the context of obesity, while the cross-sectional design precludes causal or temporal inferences.Keywords: FTO protein, obesity, type 2 diabetes mellitus, β-cell function, HOMA-β, insulin resistance