Depression occurs about twice as frequently in individuals with type 2 diabetes mellitus (T2DM) compared with those without diabetes. The biological pathways responsible for this association remain uncertain. A cross-sectional analysis published in Diabetology evaluated whether insulin resistance (IR) and markers of low-grade inflammation are related to depression in people with T2DM.

The study evaluated 189 participants assigned to four groups: T2DM with depression (n = 38), T2DM without depression (n = 60), depression without T2DM (n = 44), and healthy controls (n = 47). Depression assessment relied on the Mini International Neuropsychiatric Interview-6 (MINI-6) and the Hamilton Depression Rating Scale (HAMD). The analysis quantified IR using the Matsuda index and the homeostatic model assessment of insulin resistance (HOMA-IR). The study also measured high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6) to evaluate low-grade inflammation.

The Matsuda index reached its lowest values in participants with both T2DM and depression compared with the other three groups (p < 0.001). HOMA-IR values were higher in this group than in those with depression without T2DM and healthy controls, although values did not differ significantly from those observed in T2DM without depression. The analysis also identified the highest hs-CRP concentrations in T2DM with depression (p < 0.001). IL-6 levels exceeded those recorded in T2DM without depression and healthy controls (p < 0.001), while values remained similar to those observed in depression without T2DM.

Multivariable analysis showed that younger age, lower Matsuda index, and higher IL-6 levels independently predicted depression in individuals with T2DM. Receiver operating characteristic analysis produced an area under the curve of 0.75 for IL-6 (p < 0.001). At a 5.29 pg/mL threshold, IL-6 demonstrated 57% sensitivity and 82% specificity for identifying depression. 

These results indicate that greater IR and elevated inflammatory markers accompany depression in individuals with T2DM. The findings also link depression in T2DM with younger age, lower Matsuda index, and higher IL-6 levels. Further longitudinal research is required to clarify causal relationships.