Serum Interleukin-18 Levels Are Associated With Nephropathy and Atherosclerosis in Japanese Patients With Type 2 Diabetes

Nakamura, Akihiko; Shikata, Kenichi; Hiramatsu, Masayuki; Nakatou, Tatsuaki; Kitamura, Toshio; Wada, Jun; Itoshima, Tatsuya; Makino, Hírofumi

doi:10.2337/diacare.28.12.2890

Cited by 193 publications

(155 citation statements)

References 41 publications

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“…The present findings for IL-18 examined in a long-term follow-up study extend the findings of previous crosssectional association studies in patients with type 1 and type 2 diabetes mellitus [17][18][19]. Nakamura et al reported that serum and urinary IL-18 levels in Japanese patients with type 2 diabetes mellitus correlated positively with urinary AER at baseline and after 6 months, a relatively short period [19].…”

Section: Discussionsupporting

confidence: 78%

“…Nakamura et al reported that serum and urinary IL-18 levels in Japanese patients with type 2 diabetes mellitus correlated positively with urinary AER at baseline and after 6 months, a relatively short period [19]. Our longer observational follow-up study clearly showed a prognostic impact of serum IL-18 levels on the future development of microalbuminuria.…”

Section: Discussionsupporting

confidence: 53%

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Predictive impact of elevated serum level of IL-18 for early renal dysfunction in type 2 diabetes: an observational follow-up study

et al. 2007

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Aims/hypothesis The early identification of type 2 diabetic patients at risk of developing microalbuminuria-an independent risk factor for renal and cardiovascular diseasesis important to improve the patients' outcomes. We investigated whether serum levels of IL-18, a proinflammatory cytokine, were a predictor of early renal dysfunction. Materials and methods A total of 249 Japanese type 2 diabetic patients without overt proteinuria were enrolled in an observational follow-up study (median follow-up 7 years), and their stage of diabetic nephropathy was classified and their estimated glomerular filtration rate (eGFR) was calculated annually. Results At baseline, serum levels of IL-18 were higher in subjects with microalbuminuria (n=76) than in those with normoalbuminuria (n=173). Elevated serum levels of IL-18 were associated with the progression of nephropathy to a higher stage in normoalbuminuric subjects (118 [ ng/l, p=0.50). The adjusted risk for developing microalbuminuria was 3.6 (95% CI 1.2-10.4) in normoalbuminuric subjects with serum IL-18 levels above the median (≥134.6 ng/l), and was significantly enhanced in those urinary AERs at the upper end of the normal range (7.5 μg/min ≤ AER < 20 μg/min). Furthermore, the annual rate of decline in eGFR, when examined in the study population as a whole, was significantly greater in subjects with serum IL-18 levels above the median than in other subjects. Conclusions/interpretationThe results of our observational follow-up study indicate that elevated serum levels of IL-18 may be a predictor of future renal dysfunction in type 2 diabetic patients with normoalbuminuria.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionsupporting

confidence: 53%

Predictive impact of elevated serum level of IL-18 for early renal dysfunction in type 2 diabetes: an observational follow-up study

et al. 2007

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“…Moreover, elevated IL-18 serum levels were reported in patients with type 1 diabetes complicated by nephropathy [26]. Other authors have also demonstrated increased IL-18 serum levels in relation to the presence of persistent complications in the course of type 2 diabetes [12].…”

Section: Discussionmentioning

confidence: 84%

“…In pathological conditions, IL-18 is involved in angiogenesis [10], arteriosclerosis [11], tissue destruction, and seems to play a role in the autoimmune b-cell destruction [12]. Recent studies have shown that circulating IL-18 may be a predictor of progression of diabetic nephropathy as well as cardiovascular diseases [13].…”

Section: Introductionmentioning

confidence: 99%

Microvascular abnormalities in capillaroscopy correlate with higher serum IL-18 and sE-selectin levels in patients with type 1 diabetes complicated by microangiopathy

Kuryliszyn-Moskal¹,

Dubicki²,

Zarzycki³

et al. 2011

Folia Histochem Cytobiol.

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Microvascular abnormalities are one of the most important causes of persistent diabetic complications. The aim of this study was to compare microvascular changes examined by nailfold capillaroscopy with serum concentrations of soluble E-selectin (sE-selectin) and IL-18 in type 1 diabetic patients with and without microangiopathy. Serum levels of sE-selectin and IL-18 were determined by an enzyme-linked immunosorbent assay in 106 patients with type 1 diabetes and in 40 healthy controls. All diabetic patients were evaluated by extensive clinical, laboratory and capillaroscopic studies. Morphological changes were observed by nailfold capillaroscopy in 86 out of 106 (81%) diabetic patients. Severe capillaroscopic changes were seen in 32 out of 54 (59%) patients with microangiopathy, but in only seven out of 52 (13%) patients without microangiopathy. Higher serum levels of sE-selectin (p < 0.001) and IL-18 (p < 0.05) were demonstrated in diabetic patients compared to controls. Significant differences of sE-selectin (p < 0.001) and IL-18 (p < 0.01) serum concentrations were observed between diabetic patients with microangiopathy and controls. Moreover, comparison between patients with and without microangiopathic complications showed a significantly higher capillaroscopic score and sE-selectin serum concentration in the group with microangiopathy (p < 0.001). Furthermore, diabetic patients with severe microvascular changes in capillaroscopy showed significantly higher IL-18 (p < 0.001) and sE-selectin (p < 0.05) serum levels than subgroups without changes or with mild abnormalities. Our findings suggest that abnormalities in nailfold capillaroscopy may reflect the extent of microvascular involvement and are associated with higher sE-selectin and IL-18 serum levels, as well as with microangiopathic complications in diabetic patients.

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“…Likewise, IFN-γ secretion by T-cells can initiate and further accelerates inflammation by the activation of macrophages and vascular cells and exacerbation of oxidative stress within renal tissues [32,16]. Besides, IL-18 levels increase in diabetic patients with the development of urinary albumin excretion [64]. So, elevated urinary excretion levels of IL-18 reported in patients with diabetic nephropathy seems to be closely related to the progression of diabetic nephropathy [63].…”

Section: Cytokines and Chemokinesmentioning

confidence: 99%

Microinflammation as a Candidate for Diabetic Nephropathy

hafez

2014

Interdiscip J Microinflammation

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Diabetic Nephropathy (DN) is a major cause of mortality in patients with Type 1 and 2 diabetes throughout the world. This review draws attention to the important role of microinflammation and the complex pathways implicated in the development and progression of DN. These pathways include the collaboration of metabolic, hemodynamic and hormonal factors with oxidative stress in patients with genetic susceptibility to create an inflammatory milieu. The key role of inflammatory cells in the kidney, particularly infiltrating macrophages and T-lymphocytes is highlighted. The major inflammatory cytokines and chemokines, receptors, adhesion molecules as well as transcription factors and transduction pathways involved in the pathogenesis of DN are also discussed. Understanding of these inflammatory pathways guides important therapeutic appliances and improves the discovery of new therapeutic targets that can be translated into clinical treatments for DN.

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Serum Interleukin-18 Levels Are Associated With Nephropathy and Atherosclerosis in Japanese Patients With Type 2 Diabetes

Cited by 193 publications

References 41 publications

Predictive impact of elevated serum level of IL-18 for early renal dysfunction in type 2 diabetes: an observational follow-up study

Predictive impact of elevated serum level of IL-18 for early renal dysfunction in type 2 diabetes: an observational follow-up study

Microvascular abnormalities in capillaroscopy correlate with higher serum IL-18 and sE-selectin levels in patients with type 1 diabetes complicated by microangiopathy

Microinflammation as a Candidate for Diabetic Nephropathy

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