Low-Grade Systemic Inflammation and the Development of Type 2 Diabetes

TLDR

The study investigates whether low‑grade systemic inflammation predicts incident type 2 diabetes and whether this association varies across subgroups. A case‑cohort study of 10,275 ARIC participants measured plasma inflammatory markers in 581 incident diabetes cases and 572 controls. Higher quartiles of inflammatory markers were associated with 1.9–2.8 times greater risk of diabetes; after adjusting for BMI, waist‑to‑hip ratio, glucose, and insulin only IL‑6 remained significant (HR 1.6), and an overall inflammation score predicted diabetes in white nonsmokers (HR 3.7) but not in African Americans or smokers.

Abstract

To examine the association of low-grade systemic inflammation with diabetes, as well as its heterogeneity across subgroups, we designed a case-cohort study representing the ∼9-year experience of 10,275 Atherosclerosis Risk in Communities Study participants. Analytes were measured on stored plasma of 581 incident cases of diabetes and 572 noncases. Statistically significant hazard ratios of developing diabetes for those in the fourth (versus first) quartile of inflammation markers, adjusted for age, sex, ethnicity, study center, parental history of diabetes, and hypertension, ranged from 1.9 to 2.8 for sialic acid, orosomucoid, interleukin-6, and C-reactive protein. After additional adjustment for BMI, waist-to-hip ratio, and fasting glucose and insulin, only the interleukin-6 association remained statistically significant (HR = 1.6, 1.01–2.7). Exclusion of GAD antibody-positive individuals changed associations minimally. An overall inflammation score based on these four markers plus white cell count and fibrinogen predicted diabetes in whites but not African Americans (interaction P = 0.005) and in nonsmokers but not smokers (interaction P = 0.13). The fully adjusted hazard ratio comparing white nonsmokers with score extremes was 3.7 (P for linear trend = 0.008). In conclusion, a low-grade inflammation predicts incident type 2 diabetes. The association is absent in smokers and African-Americans.