Early-onset type 2 diabetes and mood, anxiety, and stress-related disorders: a genetically informative register-based cohort study
Objective
To assess the association and familial co-aggregation between early-onset type 2 diabetes (diagnosed before age 45) and mood, anxiety, and stress-related disorders, and estimate the contribution of genetic and environmental factors to their co-occurrence.
Research Design and Methods
This population-based cohort study included individuals born in Sweden 1968-1998, from whom pairs of full-siblings, half-siblings, and cousins were identified. Diagnoses of early-onset type 2 diabetes and mood (including unipolar depression and bipolar disorder), anxiety, and stress-related disorders were obtained from the National Patient Register. Logistic and Cox regression models were used to assess the phenotypic association and familial co-aggregation between type 2 diabetes and psychiatric disorders. Quantitative genetic modeling was conducted in full- and maternal half-sibling pairs to estimate the relative contributions of genetic and environmental factors to the association.
Results
Among a total of 3,061,192 individuals, 7,896(0.3%) were diagnosed with early-onset type 2 diabetes. These individuals showed higher risks of any diagnosis (Odds Ratio [OR][95%CI]: 3.62[3.44,3.80]) and specific diagnosis of unipolar depression (3.97[3.75,4.22]), bipolar disorder (4.17[3.68,4.73]), anxiety (3.76[3.54,3.99]) and stress-related disorders (3.35[3.11,3.61]). Relatives of individuals with early-onset type 2 diabetes also had higher overall risks of the examined psychiatric disorders (ORs:1.03-1.57). These associations are largely explained by genetic factors (51%-78%), with the rest explained by non-shared environmental factors.
Conclusion
Our findings highlight the burden of mood, anxiety, and stress-related disorders in early-onset type 2 diabetes and demonstrate that shared familial liability may contribute to their co-occurrence, suggesting that future research should aim to identify shared risk factors and ultimately refine preventive and intervention strategies.