The immune response involved in each phase of
type 2 diabetes (T2D) development might be different. We
aimed to identify novel inflammatory markers that predict
progression from normoglycemia to pre-diabetes, incident
T2D and insulin therapy. We used plasma levels of 26
inflammatory markers in 971 subjects from the Rotterdam
Study. Among them 17 are novel and 9 previously studied.
Cox regression models were built to perform survival
analysis. Main Outcome Measures: During a follow-up of
up to 14.7 years (between April 1, 1997, and Jan 1, 2012)
139 cases of pre-diabetes, 110 cases of T2D and 26 cases of
insulin initiation were identified. In age and sex adjusted
Cox models, IL13 (HR = 0.78), EN-RAGE (1.30), CFH
(1.24), IL18 (1.22) and CRP (1.32) were associated with
incident pre-diabetes. IL13 (0.62), IL17 (0.75), EN-RAGE
(1.25), complement 3 (1.44), IL18 (1.35), TNFRII (1.27),
IL1ra (1.24) and CRP (1.64) were associated with incident
T2D. In multivariate models, IL13 (0.77), EN-RAGE
(1.23) and CRP (1.26) remained associated with pre-diabetes.
IL13 (0.67), IL17 (0.76) and CRP (1.32) remained
associated with T2D. IL13 (0.55) was the only marker
associated with initiation of insulin therapy in diabetics.
Various inflammatory markers are associated with progression
from normoglycemia to pre-diabetes (IL13, ENRAGE,
CRP), T2D (IL13, IL17, CRP) or insulin therapy
start (IL13). Among them, EN-RAGE is a novel inflammatory
marker for pre-diabetes, IL17 for incident T2D and
IL13 for pre-diabetes, incident T2D and insulin therapy
start.