Early-Onset Type 2 Diabetes and Mood, Anxiety, and Stress-Related Disorders: A Genetically Informative Register-Based Cohort Study

Abstract

OBJECTIVE To assess the association and familial coaggregation between early-onset type 2 diabetes (diagnosed before age 45 years) 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 during 1968–1998, from whom pairs of full siblings, half-siblings, and cousins were identified. Information on diagnoses of early-onset type 2 diabetes and mood (including unipolar depression and bipolar disorder), anxiety, and stress-related disorders was obtained from the National Patient Register. Logistic and Cox regression models were used to assess the phenotypic association and familial coaggregation 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 had higher risks of any diagnosis (odds ratio [OR] 3.62 [95% CI 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 nonshared environmental factors. CONCLUSIONS 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 in future research investigators should aim to identify shared risk factors and ultimately refine preventive and intervention strategies.

Shared familial risk for type 2 diabetes mellitus and psychiatric disorders: a nationwide multigenerational genetics study

“…Our findings of stronger associations for first-than seconddegree relatives for MDD and anxiety disorders are in line with the findings of a Swedish familial co-aggregation study of early-onset T2DM and these disorders, where they similarly found a stronger association in full-siblings (sharing 50% of their segregating genes) than in cousins (sharing 25% of their segregating genes), the latter not reaching statistical significance for MDD (Liu et al, 2022). A Taiwanese study found that a family history of T2DM was correlated with a family history of major psychiatric disorders with ORs around 1.2 for schizophrenia, MDD, and bipolar disorder, but found no evidence of association between T2DM-PRS and these disorders (Su et al, 2022).…”

“…Since GWAS-based genetic correlations do not always reflect phenotypic association patterns, using other genetically informative study designs, such as family designs, can help triangulate evidence of how genetic as well as environmental factors contribute to the associations between T2DM and psychiatric disorders. One recently published study showed an association between early-onset T2DM and mood, anxiety, and stress-related disorders within individuals and by investigating pairs of siblings and cousins (Liu et al, 2022). In addition to GWAS correlation and epidemiological familial risk studies, genetic cross-disorder association can be studied using polygenic risk scores (PRSs), which capture an individual's genetic risk for a specific condition by summarizing the effect of risk variants across the genome.…”

Changing landscape of diabetes in Asia – What are the unmet needs?

“…Mental health disorders including schizophrenia, bipolar affective disorder, and depression accounted for 38% of hospital bed‐days in the youngest age group 44 . Co‐occurrence of young‐onset type 2 diabetes and mental health disorders has been reported previously 45 , and reflects a shared lifestyle and other environmental factors, effects of psychotropic drugs on metabolic health, and challenges in coping with diabetes self‐management from an early age contributing to distress and other negative emotions.…”

Type 2 diabetes in children and adolescents: Exploring the disease heterogeneity and research gaps to optimum management

“…Notably, in another registry-based study, about 40% of hospitalizations among young individuals with T2DM were attributable to mental health issues[ 78 ]. In a study on Swedish people with young-onset T2DM, the risk of bipolar disorder, anxiety, depression or stress-related events was higher by up to 4-fold[ 79 ]. Among youth with T2DM, younger age at diagnosis was found to be an independent predictor for depression[ 80 ].…”