Cytokine Milieu Tends Toward Inflammation in Type 2 Diabetes

doi:10.2337/diacare.26.5.1647

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Letters: Observations
Letter

Cytokine Milieu Tends Toward Inflammation in Type 2 Diabetes

Katherine Esposito, MD, Francesco Nappo, MD, PHD, Francesco Giugliano, Carmen Di Palo, Myriam Ciotola, Michelangela Barbieri, MD, Giuseppe Paolisso, MD and Dario Giugliano, MD, PHD

From the Department of Geriatrics and Metabolic Diseases, Second University of Naples, Naples, Italy

It has been postulated that type 2 diabetes is a manifestationof the inflammatory host response (1). Increased inflammatoryactivity is believed to play a critical role in developmentof atherogenesis and to predispose established atheroscleroticplaques to rupture (2). Interleukin (IL)-8 is a potent chemoattractant(chemokine) and induces recruitment of neutrophils and T-cellsinto the subendothelial space, as well as adhesion of monocytesto endothelium (3). IL-18 is a potent proinflammatory cytokinereported to play a role in plaque destabilization and to predictcardiovascular 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 antiatherogenicproperties; male patients with hypoadiponectinemia present atwofold increase in coronary artery disease prevalence (5).

We studied 30 patients (age 42 ± 4 years, BMI 26.9 ±1.2 kg/m², and HbA_1c 7.2 ± 0.6% [mean ± SD]) withnewly diagnosed type 2 diabetes (within 6 months of diagnosis)without hypertension or evidence of vascular complications treatedonly 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 samplesfor IL-8, IL-18, and adiponectin were stored at -80°C andmeasured 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 higherin diabetic patients (13.7 ± 2.8 and 205 ± 39pg/ml, respectively) than in control subjects (8.7 ±1.9 and 120 ± 25 pg/ml, P < 0.05–0.001), whilecirculating adiponectin levels were lower (4.9 ± 1.2vs. 7.1 ± 1.9 µg/ml, P < 0.01). There was asignificant correlation between fasting glucose and IL-8 levelsin diabetic patients (r = 0.31, P < 0.05); adiponectin concentrationswere negatively correlated with fasting insulin levels (r =-0.43, P < 0.01).

Our study shows that circulating IL-8 concentrations are significantlyhigher and adiponectin levels are significantly lower in type2 diabetic patients than matched control subjects. Previousstudies reported similar findings (6,7). To our knowledge, thisis the first demonstration that circulating IL-18 concentrationsare increased in type 2 diabetic patients, as compared withage-, sex-, and body weight-matched nondiabetic subjects. Ina prospective study of 1,229 subjects, including one-sixth ofdiabetic patients, with documented coronary artery disease,serum IL-18 concentration was identified as a strong independentpredictor of future cardiovascular events (5). The correlationwe found between IL-18 and glucose levels in diabetic patientsand the evidence that acute hyperglycemia may increase circulatingIL-18 levels in healthy subjects and IGT patients (8) suggesta role for this cytokine in plaque destabilization associatedwith stress hyperglycemia (9).

Footnotes

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

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