Plasma concentration of C-reactive protein is increased in Type I diabetic patients without clinical macroangiopathy and correlates with markers of endothelial dysfunction: evidence for chronic inflammation

Abstract

Moderately increased plasma concentrations of C-reactive protein are associated with an increased risk of cardiovascular disease. C-reactive protein, its relation to a low degree of inflammatory activation and its association with activation of the endothelium have not been systematically investigated in Type I (insulin-dependent) diabetes mellitus. C-reactive protein concentrations were measured in 40 non-smoking patients with Type I diabetes without symptoms of macrovascular disease and in healthy control subjects, and in a second group of Type I diabetic patients (n = 60) with normo- (n = 20), micro- (n = 20) or macroalbuminuria (n = 20). Differences in glycosylation of alpha1-acid glycoprotein were assayed by crossed affinity immunoelectrophoresis. Activation of the endothelium was measured with plasma concentrations of endothelial cell markers. The median plasma concentration of C-reactive protein was higher in Type I diabetic patients compared with healthy control subjects [1.20 (0.06-21.64) vs. 0.51 (0.04-9.44) mg/l; p<0.02]. The Type I diabetic subjects had a significantly increased relative amount of fucosylated alpha1-acid glycoprotein (79+/-12% vs. 69+/-14% in the healthy control subjects; p<0.005), indicating a chronic hepatic inflammatory response. In the Type I diabetic group, log(C-reactive protein) correlated significantly with von Willebrand factor (r = 0.439, p<0.005) and vascular cell adhesion molecule-1 (r = 0.384, p<0.02), but not with sE-selectin (r = 0.008, p = 0.96). In the second group of Type I diabetic patients, increased urinary albumin excretion was associated with a significant increase of von Willebrand factor (p<0.0005) and C-reactive protein (p = 0.003), which were strongly correlated (r = 0.53, p<0.0005). Plasma concentrations of C-reactive protein were higher in Type I diabetic patients without (clinical) macroangiopathy than in control subjects, probably due to a chronic hepatic inflammatory response. The correlation of C-reactive protein with markers of endothelial dysfunction suggests a relation between activation of the endothelium and chronic inflammation.

Diabetic nephropathy is associated with low-grade inflammation in Type 1 diabetic patients

“…Within the diabetic group, patients with micro-and macroalbuminuria had higher concentrations of CRP than normoalbuminuric pa- A finding of our study is that in Type 1 diabetic patients low-grade inflammation is present already at the stage of microalbuminuria. We confirm the previous finding that Type 1 diabetic patients with proteinuria have increased CRP concentrations [14], but extend the finding to increased concentrations of IL-6. This is important since IL-6 is considered to be the main stimulus for the hepatic production of CRP.…”

“…In this respect the finding that serumfree pentosidine, the first AGE to be shown in tissue and plasma in diabetes, and the monocyte activation marker neopterin has been shown to correlate with the rate of progression of diabetic nephropathy [23], supports the hypothesis that AGEs might activate monocytes to produce IL-6. Furthermore, given the fact that low-grade inflammation has been linked to markers of endothelial dysfunction (von Willebrand factor and soluble form of vascular cell adhesion molecule-1) in Type 1 diabetic patients with macroalbuminuria [14], the source of IL-6 could also reside in the smooth muscle cells of the vasculature and be the result of chronic exposure to AGEs.…”

“…The second study, in contrast, depicted an association between CRP and DN, but the authors did not find a difference between normo-and microalbuminuric patients. Furthermore, IL-6 was not measured nor was low-grade inflammation related to features such as smoking, waist-to-hip ratio (WHR), lipids, blood pressure or a history of parental Type 2 diabetes [14].…”

Orosomucoid in urine is a powerful predictor of cardiovascular mortality in normoalbuminuric patients with type 2 diabetes at five years of follow-up

“…In a study of 40 patients with type 1 diabetes the plasma concentrations of orosomucoid were normal and comparable to healthy control persons. However, signs of chronic inflammation were found in diabetic patients where an increased amount of fucosylated orosomucoid was found by crossed immunoelectrophoresis [17]. The differences observed for orosomucoid in serum in our study occur within the reference interval.…”

Increased serum adiponectin levels in type 1 diabetic patients with microvascular complications

“…However, the finding can also be interpreted in the opposite way, as elevated ADPN levels could represent a beneficial compensatory mechanism. Several markers of inflammation are increased in type 1 diabetes, suggesting that it is a state of chronic lowgrade inflammation [42,43]. Having the anti-inflammatory and anti-atherosclerotic properties of ADPN in mind, one could hypothesise that increased ADPN levels serve to protect patients at high risk of CVD against the harmful actions of proinflammatory and atherosclerotic agents.…”