Acute-Phase Markers of Inflammation and Glomerular Structure in Patients with Type 2 Diabetes

Abstract

Type 2 diabetes is frequently associated with an inflammatory status; the relationships between low-grade inflammation and diabetic nephropathy are still unclear. The aim of this study was to evaluate the relationships between acute-phase markers of inflammation, glomerular structure, and albumin excretion rate (AER) in type 2 diabetes. In 74 patients with type 2 diabetes (23 normoalbuminuric, 30 microalbuminuric, and 21 proteinuric) fibrinogen, serum amyloid A protein (SAA), C-reactive protein (CRP), and IL-6 were determined. AER was measured on three 24-h urine collections; GFR was measured by 51 Cr EDTA plasma clearance. A kidney biopsy was performed, and mesangial fractional volume [Vv(mes/glom)] and glomerular basement membrane (GBM) width were estimated by electron microscopic morphometric analysis. CRP, fibrinogen, SAA, and IL-6 differed among groups, with proteinuric patients having the highest levels. SAA and fibrinogen correlated with AER (P < 0.03 and P < 0.001, respectively). GBM width and Vv(mes/glom) increased from normoalbuminuric to proteinuric patients [P < 0.005 normoalbuminuric and microalbuminuric versus proteinuric for GBM, P < 0.01 normoalbuminuric versus proteinuric for Vv(mes/glom)]. In patients with increased GBM width (>396 nm), CRP, SAA, and IL-6 were higher than in patients with normal GBM width (P < 0.003, P < 0.004, and P < 0.0004, respectively). GBM width was directly correlated with fibrinogen (r ‫؍‬ 0.33, P < 0.002) and IL-6 (r ‫؍‬ 0.25 P < 0.05). In conclusion, this study demonstrates that acute-phase markers of inflammation are associated with nephropathy status and GBM thickening, suggesting a role for inflammation in the pathogenesis of diabetic glomerulopathy. T ype 2 diabetes is frequently associated with an acutephase reaction, suggestive of a low-grade inflammatory status (1,2). In fact, markers of acute-phase response, including serum amyloid A (SAA), C-reactive protein (CRP), and IL-6, the main mediators of the response, have been shown to be elevated in patients with type 2 diabetes and with the metabolic syndrome (2). It is well known that in the general population, as well as in diabetes, these acute-phase markers are associated with increased cardiovascular risk, because chronic inflammation is one of the pathogenetic mechanisms of atherosclerosis (3). In contrast, the relationships between lowgrade inflammation and diabetic microangiopathy are still unclear. As far as nephropathy is concerned, several studies have examined the relationships with inflammation, leading to conflicting results (4 -11). Overall, however, most studies have reported an increase in acute-phase markers in patients with nephropathy and also in patients with microalbuminuria (5,7-9). The coexistence of an inflammatory condition with diabetic nephropathy could explain in part the tremendously increased cardiovascular risk among these patients.Also fibrinogen has been reported to be associated with both cardiovascular risk and nephropathy in type 1 and type 2 diabetes (10,11). The Diabetes Cont...

Association of Race/Ethnicity, Inflammation, and Albuminuria in Patients With Diabetes and Early Chronic Kidney Disease

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High Ambient Glucose Augments Angiotensin II-Induced Proinflammatory Gene mRNA Expression in Human Mesangial Cells: Effects of Valsartan and Simvastatin

“…Several studies reported AII-induced LIF and IL-6 gene expression in different cell types [49,52,53,54]. Importantly, it has been shown that increased systemic [18] and renal [55] expression of IL-6 is associated with diabetic nephropathy. Thus, the involvement of the IL-6 family of cytokines in mediating adverse cardiovascular [49] and renal [18, 55] outcomes appears well documented.…”

“…Importantly, it has been shown that increased systemic [18] and renal [55] expression of IL-6 is associated with diabetic nephropathy. Thus, the involvement of the IL-6 family of cytokines in mediating adverse cardiovascular [49] and renal [18, 55] outcomes appears well documented. HG by itself increased LIF mRNA levels 2.71 ± 0.35-fold over NG (p < 0.001; fig.…”

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