Prediabetes and the risk of type 2 diabetes: investigating the roles of depressive and anxiety symptoms in the Lifelines Cohort Study

Background: Depression and anxiety may increase the risk of progressing from prediabetes to type 2 diabetes. The present study examined the interactions between prediabetes status and elevated depressive and anxiety symptoms with the risk of type 2 diabetes.

Methods: Participants (N=72,428) were adults aged 40 years and above without diabetes at baseline from the Lifelines Cohort Study (58% female; mean age=51.4 years). The Mini-International Neuropsychiatric Interview screened for elevated symptoms of major depressive disorder and generalized anxiety disorder. Glycated hemoglobin A1c (HbA1c) levels determined prediabetes status at baseline (2007-2013), and HbA1c and self-reported diabetes diagnoses determined diabetes status at follow-up (2014-2017). Groups were formed for elevated depressive and anxiety symptoms, respectively, and prediabetes status at baseline (elevated depressive/anxiety symptoms with prediabetes, elevated depressive/anxiety symptoms alone, and prediabetes alone), and compared to a reference group (no prediabetes or anxiety/depression) on the likelihood of developing diabetes during the follow-up period.

Findings: N=1,300 (1.8%) participants developed diabetes. While prediabetes alone was associated with incident diabetes (OR=5.94; 95% CI=5.10-6.90, p<.001), the group with combined prediabetes and depressive symptoms had the highest likelihood of developing diabetes over follow-up (OR=8.29; 95% CI=5.58-12.32, p<.001). Similar results were found for prediabetes and anxiety symptoms (OR=6.57; 95% CI=4.62-9.33, p<.001), compared to prediabetes alone (OR=6.09; 95% CI=5.23-7.11, p<.001), though with a smaller effect. The interaction between depressive symptoms and prediabetes was synergistic in age-and-sex adjusted analyses.

Conclusion: Individuals with elevated depressive, and to some extent anxiety, symptoms in combination with prediabetes may represent a high-risk subgroup for type 2 diabetes.