The moderating role of diet and physical activity in insulin resistance and immunometabolic depression

Insulin resistance (IR) and atypical depression share an immunometabolic pathway and present major health risks. Although IR has been associated with atypical depression, its link to immunometabolic depression (IMD) symptoms is less understood. Lifestyle factors like physical activity (PA) and diet may mitigate these conditions through anti-inflammatory and antidiabetic effects. This study examines how lifestyle factors moderate the IR-IMD relationship. We conducted a cross-sectional analysis using baseline data from the mPRIME study (n = 124). IR was measured via HOMA-IR, and IMD symptoms (hypersomnia, hyperphagia, loss of energy, tiredness) were assessed using a composite score derived from four Beck Depression Inventory-II items that have been previously linked to immunometabolic alterations. PA was tracked using accelerometers; diet via the empirical dietary inflammatory pattern (EDIP). Multiple linear regression and moderation analyses were applied. Ninety-four individuals (M(age) = 49.43, SD = 13.93; 48% IR) were analyzed. IR was significantly associated with the IMD-score (β = 0.817, p = 0.001). PA showed no direct or moderating effect (p > 0.05). A proinflammatory diet moderated the IR-IMD link in men (β = 0.718, p < 0.001), but not women (p > 0.05). Findings indicate an IR-IMD association, suggesting symptom monitoring in IR patients may aid early IMD detection and prevention.Trial registration Registered at https://www.drks.de/search/de/trial/DRKS00022774 Identifier no. DRKS00022774 (Registration date: 2021-03-08).