A Cross-Sectional Study of Food Insecurity, Mediterranean Diet Adherence, and Gut-Derived Metabolites and Their Associations with Glycemic Control and Macrovascular Complications in Adults with Type 2 Diabetes

Objective: This study aimed to investigate the combined associations of food insecurity and Mediterranean diet adherence with glycemic control and to determine whether gut-derived metabolites differ according to food insecurity and macrovascular complication status in adults with type 2 diabetes mellitus (T2DM). Methods: In this cross-sectional study, food insecurity was assessed using the Food Insecurity Experience Scale, and Mediterranean diet adherence was evaluated with the 14-item Mediterranean Diet Adherence (MDA) Scale. Serum trimethylamine N-oxide (TMAO) and L-carnitine concentrations were quantified using enzyme-linked immunosorbent assay (ELISA). Multinomial logistic regression was used as the primary analysis of data-derived HbA1c tertiles, and separate binary logistic regression models were performed as sensitivity analyses. ANCOVA was used for adjusted comparisons of continuous outcomes. Results: In the primary multinomial analysis, none of the combined food insecurity–MDA patterns were significantly associated with the intermediate or highest HbA1c tertiles after multivariable adjustment. However, point estimates suggested higher odds of the intermediate HbA1c tertile among participants with food insecurity and high MDA adherence (AOR = 3.41, 95% CI: 0.76–15.25) and of the highest HbA1c tertile among those with food insecurity and low MDA adherence (AOR = 4.74, 95% CI: 0.66–34.16); these estimates were imprecise. Sensitivity analyses using separate binary logistic regression models yielded stronger associations, but these findings should also be interpreted cautiously. Participants with macrovascular complications exhibited significantly higher serum TMAO and L-carnitine concentrations (p = 0.026 and p = 0.039, respectively), whereas food-insecure participants had significantly lower concentrations of both metabolites (p = 0.009 and p = 0.018, respectively). Higher dietary fiber and plant protein intakes were cross-sectionally associated with lower TMAO concentrations, while L-carnitine concentrations were positively associated with dietary fiber intake and inversely associated with plant protein intake. Conclusions: Combined food insecurity–MDA patterns showed suggestive but imprecise differences in HbA1c category membership that require confirmation in larger prospective studies. Serum TMAO and L-carnitine concentrations differed according to food insecurity and macrovascular complication status and were associated with selected dietary components. These findings should be interpreted as exploratory cross-sectional associations rather than evidence of causal or mechanistic effects.