The relationship of life-course patterns of adiposity with type 2 diabetes, depression, and their comorbidity in the Northern Finland Birth Cohort 1966

Objectives Type 2 diabetes (T2D) and comorbid depression challenges clinical management particularly in individuals with overweight. We aim to explore the shared etiology, via lifecourse adiposity, between T2D and depression. Methods We used data from birth until 46years from Northern Finland Birth Cohort 1966 (n = 6,372; 53.8% females). We conducted multivariate analyses on three outcomes: T2D (4.2%), depression (19.2%) and as comorbidity (1.8%). We conducted (i) Path analysis to clarify time-dependent body mass index (BMI) related pathways, including BMI polygenic risk scores (PRS); and (ii) Cox regression models to assess whether reduction of overweight between 7years and 31years influence T2D, depression and/or comorbidity. The models were tested for covariation with sex, education, smoking, physical activity, and diet score. Results The odd ratios (OR) of T2D in individuals with depression was 1.68 [95% confidence interval (CI): 1.34-2.11], and no change in estimate was observed when adjusted for covariates. T2D and comorbidity showed similar patterns of relationships in the path analyses (P < 0.001). The genetic risk for obesity (PRS BMI) did not show direct effect on T2D or comorbidity in adulthood but indirectly through measures of adiposity in early childhood and mid-adulthood in the path analysis (P < 0.001). Having early-onset of overweight at 7years and 31years showed highest risk of T2D (OR 3.8, 95%CI 2.4-6.1) and comorbidity (OR 5.0, 95%CI 2.7-9.5), with mild-to-moderate attenuation with adjustments. Depression showed no significant associations. Conclusions We found evidence for overweight since childhood as a risk factor for T2D and co-morbidity between T2D and depression, influenced moderately by lifestyle factors in later life. However, no shared early life adiposity related risk factors were observed between T2D and depression when assessed independently in this Finnish setting.