Despite the frequent co-occurrence of depression and diabetes, gender differences in their relationship remain unclear.

This exploratory study examined if gender modifies the association between depressive symptoms, prediabetes and diabetes with cognitive-affective and somatic depressive symptom clusters.

Cross-sectional analyses were conducted on 29 619 participants from the 2007–2018 National Health and Nutrition Examination Survey. Depressive symptoms were measured by the nine-item Patient Health Questionnaire. Multiple logistic regression was used to analyse the relationship between depressive symptoms and diabetes. Multiple linear regression was used to analyse the relationship between depressive symptom clusters and diabetes.

The odds of having depressive symptoms were greater in those with diabetes compared to those without. Similarly, total symptom cluster scores were higher in participants with diabetes. Statistically significant diabetes–gender interactions were found in the cognitive-affective symptom cluster model. Mean cognitive-affective symptom scores were higher for females with diabetes (coefficient = 0.23, CI: 0.10, 0.36, P = 0.001) than males with diabetes (coefficient = −0.05, CI: −0.16, 0.07, P = 0.434) when compared to the non-diabetic groups.

Diabetes was associated with higher cognitive-affective symptom scores in females than in males. Future studies should examine gender differences in causal pathways and how diabetic states interact with gender and influence symptom profiles.