Higher metabolic variability increases the risk of depressive disorder in type 2 diabetes mellitus: a longitudinal nationwide cohort study

Background and objectives: While variabilities in metabolic parameters (METv) have been linked to adverse health outcomes in type 2 DM, their association with depression is yet to be studied. This research aimed to investigate the association between METv and depressive disorder in patients with type 2 DM. Methods: The study involved a nationwide cohort of 1,119,631 type 2 DM patients who had undergone three or more serial health examinations between 2005 and 2012. At each visit, body mass index (BMI), fasting glucose (FG), systolic blood pressure (BP), and total cholesterol (TC) were measured and stratified into quartiles, with Q4 being the highest and Q1 the lowest. The risk of depressive disorder was evaluated using Cox proportional hazard regression models, which accounted for METs in the indexes, after adjusting for sex, income status, lifestyle habits, medical comorbidities, DM severity, and baseline levels of BMI, FG, BP, and TC. Results: During a mean follow-up period of 6.00 ± 2.42 years, 239,477 (21.4%) cases of type 2 DM patients developed depressive disorder. The risk of developing depressive disorder was gradually increased as the number of METv increased (HR 1.18; 95% CI 1.13, 1.23 for the group with the highest METv in all parameters compared to those with the lowest METv in all parameters). In the subgroup analysis, the risk of developing depressive disorder was 43% higher in men (HR 1.43; 95% CI 1.34, 1.51), and 31% higher in those younger than 65 years of age (HR 1.31; 95% CI 1.23, 1.39) in the group with the highest number of METv compared to the group with the lowest number of METv. Conclusion: In type 2 DM, higher METv was an independent risk factor for depressive disorder. This risk is notably elevated in men and individuals under the age of 65 years.