Depression in Type 2 Diabetes: Association with Higher Insulin Resistance and Increased Low Grade Inflammation

Background: Depression is approximately twice as prevalent in type 2 diabetes (T2D) compared to non-diabetic individuals, but its underlying mechanisms remain unclear. Insulin resistance (IR) and low-grade inflammation have been proposed as potential contributors. This study investigated whether IR and inflammatory markers are associated with depression in people with T2D. Methods: This cross-sectional study included 189 participants divided into four groups: T2D with depression (A, n = 38), T2D without depression (B, n = 60), depression without T2D (C, n = 44), and healthy controls (D, n = 47). Depression was diagnosed using the MINI-6 and HAMD scale. IR was assessed using the Matsuda index and HOMA-IR, while low-grade inflammation was evaluated by high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6). Results: The Matsuda index was significantly lower in group A compared with B, C and D groups (p < 0.001). HOMA-IR was higher in A than in C and D groups, though not significantly different from group B. Hs-CRP was highest in group A (p < 0.001), with no differences among B, C and D. IL-6 was significantly higher in A than B and D (p < 0.001), and similar between A and C. In multivariable analysis younger age, lower Matsuda index, and higher IL-6 independently predicted depression in people with T2D. ROC analysis detected an AUC of 0.75 (p < 0.001) for IL-6, with a sensitivity of 57% and specificity of 82% at the cutoff of 5.29 pg/mL. Conclusions: Our findings suggest that people with T2D and depression exhibit higher IR and elevated IL-6 and hs-CRP levels as parameters of low-grade inflammation. Depression in T2D was associated with younger age, lower Matsuda ISI, and higher IL-6, highlighting the potential relevance of those metabolic and inflammatory biomarkers in this co-occurrence. Further longitudinal studies are needed to clarify causal relationships.