Relationships of plasma interleukin-18 concentrations to hyperhomocysteinemia and carotid intimal-media wall thickness in patients with type 2 diabetes

OBJECTIVE: We compared plasma interleukin (IL)-18 concentrations in patients with type 2 diabetes with those in age-matched control subjects and investigated whether plasma IL-18 was associated with plasma total homocysteine (tHcy) concentration or carotid intimal-media wall thickness (IMT), an early marker of atherosclerosis, in these patients. RESEARCH DESIGN AND METHODS: We measured plasma IL-18 in 103 type 2 diabetic patients and 45 age-matched control subjects. We also measured patients' plasma tHcy and serum high-sensitivity C-reactive protein (hs-CRP). IMT was evaluated for both common carotid arteries. RESULTS: Plasma IL-18 was significantly higher in diabetic patients than in control subjects (203 +/- 153 vs. 118 +/- 37 pg/ml, P < 0.001). High IL-18 was defined as equaling or exceeding the mean + 2 SD of plasma IL-18 in control subjects (192 pg/ml). Patients with high IL-18 showed a greater carotid IMT than those with normal IL-18. Carotid plaques were more numerous in diabetic patients with high IL-18 than in those with normal IL-18. Plasma tHcy concentrations were significantly higher in patients with high IL-18 than in those with normal IL-18. Univariate and multivariate analyses showed a strong independent association between tHcy and IL-18. Plasma IL-18 also correlated positively with serum hs-CRP. CONCLUSIONS: In patients with type 2 diabetes, plasma IL-18 concentrations are greater than in nondiabetic subjects. Plasma IL-18 is an independent determinant of plasma tHcy, which is linked independently with atherosclerotic carotid wall thickening.