High adherence to the Mediterranean Diet (MD) is associated with a lower risk of type 2 diabetes. However, it is less clear whether the different MD food items might influence specific biological functions related to glucose tolerance, i.e., insulin resistance (IR) and/or secretion (IS). Thus, this cross-sectional study aimed to investigate the relationship between adherence to MD and IR, insulin sensitivity, and IS in individuals with overweight/obesity. Participants (62 individuals; 7M/55F; mean age 49 ± 15 years; mean BMI 35.8 ± 6.7 kg/m²) underwent a 75 g oral glucose tolerance test (OGTT) to assess plasma glucose and insulin concentrations. These parameters were used for the calculation of validated IR indices (Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), Homeostatic Model Assessment for β-cell function (HOMA-β)), as well as insulin sensitivity indices (insulin sensitivity index (ISI), oral glucose insulin sensitivity (OGIS)). MD adherence was gauged using the PREDIMED questionnaire. Bivariate correlations were used to highlight the association between OGTT-derived indices and MD adherence (PREDIMED score) or specific foodstuffs related to MD. Despite there being no significant differences in BMI, impaired fasting glucose (IFG), and impaired glucose tolerance (IGT), the high MD adherence group presented lower HOMA-IR (p = 0.022) and higher ISI (p = 0.033) compared to other groups. High MD adherence was inversely correlated with HOMA-IR (r = -0.400; p = 0.004) and directly correlated with ISI (r = 0.296, p = 0.039). Fish consumption, a key component of MD, exhibited significant associations: it was directly correlated to ISI (r = 0.394, p = 0.005) and inversely related to HOMA-IR (r = -0.327, p = 0.019) and β-cell function (r = -0.489, p < 0.001). In conclusion, a high MD adherence, and in particular the consumption of fish, is associated with a decreased IR in individuals with overweight/obesity.
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