Associations between inflammatory markers, traditional risk factors, and complications in patients with type 2 diabetes mellitus

Streja, Dan; Cressey, Pamela J.; Rabkin, Simon W.

doi:10.1016/s1056-8727(02)00204-0

Cited by 55 publications

(43 citation statements)

References 50 publications

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“…A possible explanation for this finding is chronic inflammation, which is well described in patients with diabetes (18,19), because chronic inflammation itself is associated with increased polyclonal FLC (20,21).…”

Section: Discussionmentioning

confidence: 87%

Quantitative Assessment of Serum and Urinary Polyclonal Free Light Chains in Patients with Chronic Kidney Disease

Hutchison¹,

Harding²,

Hewins³

et al. 2008

Clinical Journal of the American Society of Nephrology

311

233

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Results: Serum and FLC concentrations increased progressively with CKD stage (both P < 0.001) and strongly correlated with markers of renal function, including cystatin-C (: R ‫؍‬ 0.8, P < 0.01; and : R ‫؍‬ 0.79, P < 0.01). Urinary FLC concentrations varied significantly between disease groups (: P < 0.001; : P < 0.005) and also rose significantly with increasing CKD stage (both FLC P < 0.0001). Urinary FLC concentrations were positively correlated with their corresponding serum concentration (: R ‫؍‬ 0.63; : R ‫؍‬ 0.65; both P < 0.001) and urinary albumin creatinine ratio (: R ‫؍‬ 0.58; : R ‫؍‬ 0.65; both P < 0.001). The proportion of patients with abnormally high urinary FLC concentrations rose with both the CKD stage and the severity of albuminuria.Conclusions: This study demonstrates significant abnormalities of serum and urinary polyclonal FLC in patients with CKD. These data provide the basis for studies that assess the contribution of polyclonal FLC to progressive renal injury and systemic inflammation in patients with kidney disease.

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Section: Discussionmentioning

confidence: 87%

Quantitative Assessment of Serum and Urinary Polyclonal Free Light Chains in Patients with Chronic Kidney Disease

Hutchison¹,

Harding²,

Hewins³

et al. 2008

Clinical Journal of the American Society of Nephrology

311

233

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“…On the other hand, most patients with chronic inflammatory diseases and associated renal impairment have high concentrations of polyclonal FLCs, but with substantially normal k/ ratio. [17][18][19][20] The clinical study of elevated sFLCs in renal impairment are unclear. Reports have suggested that the elevated FLCs lead to reductions in immune function and therefore should be classified as uremic toxins.…”

Section: Discussionmentioning

confidence: 99%

The association of serum-free light-chain levels with markers of renal function

Erdem¹,

Davran²,

Yılmaz

et al. 2015

Renal Failure

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Background: The kidney is often affected in plasma cell dyscrasias, usually due to the effects of nephrotoxic monoclonal-free light chains. Renal failure due to a monoclonal gammopathy may be detected by the highly sensitive serum-free light-chain (sFLC) ratio yet missed by electrophoretic assays. The aim of this study was to assess sFLC levels in relation to markers of renal function. Methods: Five-hundred thirteen patients were included in this study. sFLC levels were measured by Freelite Õ (The Binding Site Group Ltd, Birmingham, UK) assay using the BNII nephelometer (Siemens Diagnostics, Germany). Kappa/lambda (k/) sFLC ratio was calculated. Serum creatinine levels were analyzed by modified Jaffe method in Cobas 8000 analyser. GFR was estimated by the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation. Patients were assigned to two groups depending on their eGFR values: 60 mL/min/1.73 m

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“…The recognition of microbial components by mammalian TLRs plays an important role in activation of the innate immune response and subsequent proinflammatory reactions. In addition to binding lipopolysaccharide (LPS), TLR-4 also interacts with endogenous ligands such as oxLDL, heat shock proteins 60 and 70, fibrinogen, and fibronectin (11,12), which are also elevated in diabetes (13)(14)(15)(16)(17).…”

Section: Diabetes Care 27:179 -183 2004mentioning

confidence: 99%

Asp299Gly and Thr399Ile Genotypes of the TLR4 Gene Are Associated With a Reduced Prevalence of Diabetic Neuropathy in Patients With Type 2 Diabetes

Rudofsky

Reismann²,

Witte³

et al. 2004

Diabetes Care

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OBJECTIVE -To establish whether single nucleotide polymorphisms (Asp299Gly and Thr399Ile) of the toll-like receptor 4 have an association with late diabetic complications. RESEARCH DESIGN AND METHODS -The study was conducted in 246 type 1 and 530 type 2 diabetic patients. The alleles of both polymorphisms were detected using PCR and subsequent cleavage by NcoI and HinfI restriction endonucleases. RESULTS -No difference was found between type 1 and type 2 diabetic patients in the prevalence of alleles of the Asp299Gly and Thr399Ile polymorphisms. In most cases, the alleles Gly299 and Ile399 occurred in a co-segregatory manner. The prevalence of the Gly299/Ile399 haplotype was 10.6 and 12.1% in type 1 and type 2 diabetic patients, respectively (P ϭ 0.63). No association with diabetic nephropathy or diabetic neuropathy was found in type 1 diabetic patients. In type 2 diabetic patients, however, heterozygote carriers of the Asp299Gly and Thr399Ile genotypes had a significantly reduced prevalence of diabetic neuropathy (odds ratio 0.35 [95% CI 0.19 -0.61]; P ϭ 0.0002); no association with diabetic nephropathy was found.CONCLUSIONS -Our data indicate that Asp299Gly and Thr399Ile genotypes of the TLR4 gene are associated with reduced prevalence of diabetic neuropathy in type 2, but not in type 1, diabetes. Thus different mechanisms may be involved in the pathophysiology of diabetic neuropathy in type 1 and type 2 diabetes. Diabetes Care 27:179 -183, 2004R ecently, our understanding of type 2 diabetes has changed considerably. Levels of C-reactive proteins have been shown to predict the occurrence of type 2 diabetes. Studies in animal models as well as humans have suggested that type 2 diabetes might be associated with changes in the innate immune response (1-5). Furthermore, experiments in which the mitogen-activated protein kinase or inhibitor B-kinase pathways are genetically controlled have shown that activator protein-1 and nuclear factor (NF)-B are central regulators not only of inflammatory reactions (6), but also of the insulin response and glucose metabolism (7,8). In addition, one of the receptors important for developing late diabetic complications, the receptor for advanced glycation end products (RAGE), has been shown to participate in the innate immune response and behave as a pattern recognition receptor (9,10). This implies that factors regulating the innate immune response might be also involved in late diabetic complications. One of the central regulators of the innate immune response is the toll-like receptor (TLR)-4 (11). The recognition of microbial components by mammalian TLRs plays an important role in activation of the innate immune response and subsequent proinflammatory reactions. In addition to binding lipopolysaccharide (LPS), TLR-4 also interacts with endogenous ligands such as oxLDL, heat shock proteins 60 and 70, fibrinogen, and fibronectin (11,12), which are also elevated in diabetes (13)(14)(15)(16)(17).Two common single nucleotide polymorphisms have been found in the coding region of th...

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Associations between inflammatory markers, traditional risk factors, and complications in patients with type 2 diabetes mellitus

Cited by 55 publications

References 50 publications

Quantitative Assessment of Serum and Urinary Polyclonal Free Light Chains in Patients with Chronic Kidney Disease

Quantitative Assessment of Serum and Urinary Polyclonal Free Light Chains in Patients with Chronic Kidney Disease

The association of serum-free light-chain levels with markers of renal function

Asp299Gly and Thr399Ile Genotypes of the TLR4 Gene Are Associated With a Reduced Prevalence of Diabetic Neuropathy in Patients With Type 2 Diabetes

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