We read with interest the article by Aso et al. (1) showing greater plasma concentrations of interleukin-18 (IL-18) in type 2 diabetic patients compared with matched control subjects. While the authors found no significant associations between fasting levels of IL-18 and homeostasis model assessment, a measure of insulin resistance, they found associations between IL-18 and C-reactive protein concentrations. Moreover, carotid intima-media thickness, a validated surrogate measure of atherosclerosis, was greater in diabetic patients with high IL-18 than in those with normal IL-18. As a whole, these data add to the mounting evidence that diabetes may be regarded as a chronic low-grade inflammatory state.
However, we disagree with the authors’ conclusions that “the present study demonstrated for the first time that plasma IL-18 concentrations were significantly higher in type 2 diabetic patients than in age-matched control subjects” because we have reported similar findings in Diabetes Care (2). In that study, we demonstrated that 30 newly diagnosed, slightly overweight (BMI 26.9 ± 1.2 kg/m2, means ± SD) type 2 diabetic patients without clinical or instrumental evidence of micro- and macrovascular complications presented higher circulating concentrations of IL-18 compared with nondiabetic subjects matched for sex, age, and body weight (205 ± 39 vs. 120 ± 25 pg/ml, P < 0.01). It is reassuring to see that the fasting values of IL-18 in the Japanese diabetic patients studied by Aso et al. (1) were quite similar (203 ± 153 pg/ml) to those of our Caucasian diabetic patients and that the relation between fasting plasma glucose and IL-18 concentrations was present in both studies (r = 0.31, P < 0.05; r = 0.24, P < 0.02, respectively). These results suggest that ethnicity does not to play a major role in these associations.
IL-18 is a potent proinflammatory cytokine reported to play a role in plaque destabilization (3) and predict cardiovascular death in patients with coronary artery disease (4). Although IL-18 is produced mainly by monocyte/macrophages, a contribution from adipose tissue has recently been suggested (5). In the light of the evidence that IL-18 circulating levels are higher in type 2 diabetic patients than matched nondiabetic subjects and correlate with fasting glucose levels, it does not seem hazardous to hypothesize that IL-18 may play a role in acute coronary syndromes through plaque destabilization (6). This working hypothesis, which deserves further investigation, also finds support in the observation that acute hyperglycemia may increase circulation levels of IL-18 in both normal subjects and patients with impaired glucose tolerance (7).
