It has been postulated that type 2 diabetes is a manifestation of the inflammatory host response (1). Increased inflammatory activity is believed to play a critical role in development of atherogenesis and to predispose established atherosclerotic plaques to rupture (2). Interleukin (IL)-8 is a potent chemoattractant (chemokine) and induces recruitment of neutrophils and T-cells into the subendothelial space, as well as adhesion of monocytes to endothelium (3). IL-18 is a potent proinflammatory cytokine reported to play a role in plaque destabilization and to predict cardiovascular death in patients with coronary artery disease (4). Adiponectin is an adipocyte-derived plasma protein (adipokine) that accumulates in the injured artery and has potential antiatherogenic properties; male patients with hypoadiponectinemia present a twofold increase in coronary artery disease prevalence (5).

We studied 30 patients (age 42 ± 4 years, BMI 26.9 ± 1.2 kg/m2, and HbA1c 7.2 ± 0.6% [mean ± SD]) with newly diagnosed type 2 diabetes (within 6 months of diagnosis) without hypertension or evidence of vascular complications treated only by diet. Thirty healthy subjects, matched for age, sex, and body weight, served as the control group. None of the subjects (diabetic and nondiabetic) were taking any drugs. Serum samples for IL-8, IL-18, and adiponectin were stored at −80°C and measured in duplicate using enzyme-linked immunosorbent kits. All samples for a given patient were analyzed in the same series.

Circulating levels of IL-8 and -18 concentrations were higher in diabetic patients (13.7 ± 2.8 and 205 ± 39 pg/ml, respectively) than in control subjects (8.7 ± 1.9 and 120 ± 25 pg/ml, P < 0.05–0.001), while circulating adiponectin levels were lower (4.9 ± 1.2 vs. 7.1 ± 1.9 μg/ml, P < 0.01). There was a significant correlation between fasting glucose and IL-8 levels in diabetic patients (r = 0.31, P < 0.05); adiponectin concentrations were negatively correlated with fasting insulin levels (r = −0.43, P < 0.01).

Our study shows that circulating IL-8 concentrations are significantly higher and adiponectin levels are significantly lower in type 2 diabetic patients than matched control subjects. Previous studies reported similar findings (6,7). To our knowledge, this is the first demonstration that circulating IL-18 concentrations are increased in type 2 diabetic patients, as compared with age-, sex-, and body weight-matched nondiabetic subjects. In a prospective study of 1,229 subjects, including one-sixth of diabetic patients, with documented coronary artery disease, serum IL-18 concentration was identified as a strong independent predictor of future cardiovascular events (5). The correlation we found between IL-18 and glucose levels in diabetic patients and the evidence that acute hyperglycemia may increase circulating IL-18 levels in healthy subjects and IGT patients (8) suggest a role for this cytokine in plaque destabilization associated with stress hyperglycemia (9).

1.
Pickup JC, Mattock MB, Chusney GD, Burt D: NIDDM as a disease of the innate immune system: association of acute-phase reactants and interleukin-6 with metabolic syndrome.
Diabetologia
40
:
1286
–1292,
1997
2.
Libby P, Ridker PM, Maseri A: Inflammation and atherosclerosis.
Circulation
105
:
1135
–1143,
2002
3.
Gerzten RE, Garcia-Zepeda EA, Limm YC, Yoshida M, Ding HA, Gimbrone Jr MA, Luster AD, Luscinskas FW, Rosenzweig A: MCP-1 and IL-8 trigger firm adhesion of monocytes to vascular endothelium under flow conditions.
Nature
398
:
718
–723,
1999
4.
Blankenberg S, Tiret L, Bickel C, Peetz D, Cambien F, Meyer J, Rupprecth HJ: Interleukin-18 is a strong predictor of cardiovascular death in stable and unstable angina.
Circulation
106
:
24
–30,
2002
5.
Kumada M, Kihara S, Sumitsuji S, Kawamoto T, Matsumoto S, Ouchi N, Arita Y, Okamoto Y, Shimomura I, Hiraoka H, Nakamura T, Funahashi T, Matsuzawa Y, the Osaka CAD Study Group: Association of hypoadiponectinemia with coronary artery disease in man.
Arterioscler Thromb Vasc Biol
23
:
85
–89,
2003
6.
Zozuliñska D, Majchrzak A, Sobieska M, Wiktorowicz K, Wierusz-Wysocka B: Serum interleukin-8 levels is increased in diabetic patients.
Diabetologia
42
:
117
–123,
1999
7.
Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, Tataranni PA: Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia.
J Clin Endocrinol Metab
86
:
1930
–1935,
2001
8.
Esposito K, Nappo F, Marfella R, Giugliano G, Giugliano F, Ciotola M, Quagliaro L, Ceriello A, Giugliano D: Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: role of oxidative stress.
Circulation
106
:
2067
–2072,
2002
9.
Capes SE, Hunt D, Malberg K, Gerstein HC: Stress hyperglycemia and increased risk of death after myocardial infarction in patients with and without diabetes: a systemic overview.
Lancet
355
:
773
–778,
2000

Address correspondence to Katherine Esposito, MD, Dipartimento di Geriatria e Malattie del Metabolismo, Policlinico Universitario, Piazza L. Miraglia, 80138 Napoli, Italy. E-mail: katherine.esposito@unina2.it.