With an estimated prevalence of 463
million affected, type 2 diabetes represents a major challenge to health
care systems worldwide. Analyzing the plasma proteomes of individuals with type
2 diabetes may illuminate hitherto unknown functional mechanisms underlying
disease pathology. We assessed the associations between type 2 diabetes and >1000
plasma proteins in the KORA (Cooperative health research in the Region of
Augsburg) F4 cohort (n=993, 110 cases), with subsequent replication in the
HUNT3 (Third wave of the Nord-Trøndelag Health Study) cohort (n=940, 149
cases). We computed logistic regression models adjusted for age, sex, BMI,
smoking status and hypertension. Additionally, we investigated associations
with incident type 2 diabetes and performed two-sample bi-directional Mendelian
randomization (MR) analysis to prioritize our results. Association analysis of
prevalent type 2 diabetes revealed 24 replicated proteins, of which eight are
novel. Proteins showing association with incident type 2 diabetes were
aminoacylase-1, growth hormone receptor, and insulin-like growth factor binding
protein-2. Aminoacylase-1 was associated with both prevalent and incident type
2 diabetes. MR analysis yielded nominally significant causal effects of type 2
diabetes on cathepsin Z and rennin, both known to have roles in the
pathophysiological pathways of cardiovascular disease, and of sex
hormone-binding globulin on type 2 diabetes. In conclusion, our high-throughput
proteomics study replicated previously reported type 2 diabetes-protein
associations, and identified new candidate proteins possibly involved in the
pathogenesis of type 2 diabetes.
Prospective Study of Ambient Particulate Matter Exposure and Risk of Pulmonary Embolism in the Nurses’ Health Study Cohort
