Association of type 2 diabetes according to the number of risk factors within the recommended range with incidence of major depression and clinically relevant depressive symptoms: a prospective analysis

Background: Type 2 diabetes is associated with an increased risk of depression, but the extent to which risk factor modification can mitigate this risk is unclear. We aimed to examine the association between the incidence of major depression and clinically relevant depressive symptoms among individuals with type 2 diabetes, according to the number of risk factors within the recommended target range, compared with individuals without diabetes. Methods: We did a prospective analysis of population-based data from the UK Biobank and the Maastricht Study. Individuals with type 2 diabetes were categorised according to the number of risk factors within the recommended target range (non-smoking, guideline-recommended levels of glycated haemoglobin (HbA _1c), blood pressure, BMI, albuminuria, physical activity, and diet). The primary outcome, based on data from the UK Biobank, was the incidence of major depression ascertained from hospital records; the secondary outcome, based on data from the UK Biobank and the Maastricht Study, was clinically relevant depressive symptoms based on a score of 10 or higher on the Patient Health Questionnaire (PHQ-9). Findings: The study population of the UK Biobank comprised 77 786 individuals (9047 with type 2 diabetes and 68 739 without diabetes; median age 59 years [IQR 51–64]; 34 136 [43·9%] women and 43 650 [56·1%] men). A median of 12·7 years (IQR 11·8–13·4) after recruitment (between March 13, 2006, and Oct 1, 2010), 493 (5·5%) of 9047 individuals with type 2 diabetes and 2574 (3·7%) of 68 739 individuals without diabetes developed major depression. Compared with individuals without diabetes, those with type 2 diabetes had a higher risk of major depression (hazard ratio [HR] 1·61 [95% CI 1·49–1·77]). Among individuals with type 2 diabetes, the excess risk of depression decreased stepwise with an increasing number of risk factors within the recommended target range (HR 2·04 [95% CI 1·65–2·52] for up to two risk factors within the recommended target range; 1·95 [1·65–2·30] for three risk factors within the recommended target range; 1·38 [1·16–1·65] for four risk factors within the recommended target range; and 1·34 [1·12–1·62] for five to seven risk factors within the recommended target range). In the UK Biobank dataset, a median of 7·5 years (IQR 6·8–8·2) after the baseline examination, 147 (7·5%) of 1953 individuals with type 2 diabetes and 954 (4·5%) of 21 413 individuals without diabetes had developed clinically relevant depressive symptoms. The study population of the Maastricht Study comprised 4530 individuals (1158 with type 2 diabetes and 3372 without diabetes; median age 60 years [IQR 53–66]; 2244 [49·5%] women and 2286 [50·1%] men). A median of 5·1 years (IQR 4·1–6·1) after recruitment (between Sept 1, 2010, and Dec 7, 2017), 170 (14·7%) of 1158 individuals with type 2 diabetes and 227 (6·7%) of 3372 individuals without diabetes developed clinically relevant depressive symptoms. Similarly, in both the UK Biobank dataset and the Maastricht Study cohort, among individuals with type 2 diabetes, the excess risk of clinically relevant depressive symptoms decreased stepwise with an increasing number of risk factors within the recommended target range. Interpretation: Among individuals with type 2 diabetes, the excess risk of major depression and clinically relevant depressive symptoms decreased stepwise with an increasing number of risk factors within the recommended target range. This study provides further evidence to promote risk factor modification strategies in individuals with type 2 diabetes and to encourage the adoption of a healthy lifestyle. Funding: ZonMW, Hartstichting, and Diabetes Fonds.