Relationships of Plasma Interleukin-18 Concentrations to Hyperhomocysteinemia and Carotid Intimal-Media Wall Thickness in Patients With Type 2 Diabetes
- Yoshimasa Aso, MD,
- Ki-ichi Okumura, MD,
- Kohzo Takebayashi, MD,
- Sadao Wakabayashi, MD and
- Toshihiko Inukai, MD
- From the Department of Internal Medicine, Koshigaya Hospital, Dokkyo University School of Medicine, Koshigaya, Saitama, Japan
- Address correspondence and reprint requests to Yoshimasa Aso, MD, Department of Internal Medicine, Dokkyo University School of Medicine, Koshigaya Hospital, 2-1-50 Minami-Koshigaya, Koshigaya, Saitama 343-8555, Japan. E-mail: yaso{at}dokkyomed.ac.jp
Abstract
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.
- CAD, coronary artery disease
- CRP, C-reactive protein
- CVD, cardiovascular disease
- FPG, fasting plasma glucose
- HOMA-IR, homeostasis model assessment of insulin resistance
- hs-CRP, high-sensitivity CRP
- IL, interleukin
- IMT, intimal-media wall thickness
- PVD, peripheral vascular disease
- tHcy, total homocysteine
- UAE, urinary albumin excretion
Footnotes
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A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
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- Accepted June 9, 2003.
- Received January 31, 2003.
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