Association between future events of brain infarction and soluble levels of intercellular adhesion molecule-1 and C-reactive protein in patients with type 2 diabetes mellitus

https://doi.org/10.1016/j.diabres.2008.07.006Get rights and content

Abstract

We investigated the influence of the reciprocal association between serum levels of high-sensitivity C-reactive protein (hs-CRP) and intercellular adhesion molecule-1 (sICAM-1) on the risk of brain infarction in type 2 diabetic patients. One hundred seventy nine middle-aged and elderly diabetic patients without histories of cardiovascular events were followed up for an average of 8 years. Fourteen patients developed symptomatic brain infarction (BI) during follow-up. These patients had significantly higher blood pressure, longer duration of diabetes, silent brain infarction, microvascular complications such as macroalbuminuria, and higher creatinine, sICAM-1 and hs-CRP levels at baseline as compared with those without BI. A high risk of stroke was observed in patients with high levels of sICAM-1 (>260 μg/L) and hs-CRP (>0.83 mg/L) at baseline, respectively, and patients with high levels of both were more likely to develop BI. In addition, sICAM-1 levels were significantly correlated with systolic blood pressure and glycemic control index, whereas hs-CRP levels were correlated with fasting insulin levels, HDL-cholesterol, triglycerides, and uric acid. Consequently, sICAM-1 and hs-CRP levels were, respectively, reflected in different cardiovascular risk factors. This study suggests that both measurements of hs-CRP and sICAM-1 levels are useful as a predictor of future stroke in diabetic subjects.

Introduction

It is widely recognized that diabetic patients have a higher incidence of stroke [1], [2], [3]. In Japan, the incidence of cerebral infarctions in middle-aged and elderly people is higher than in Western countries and that of cardiovascular complications is increasing [3], [4]. A serious problem is that the complication of cerebrovascular disease is associated with a less favorable functional prognosis and not only increases mortality but also greatly reduces quality of life [5], [6]. As the elderly population gradually increases, it is predicted that the number of elderly diabetic patients will also increase. Strategies to prevent complications in diabetic patients will therefore become more important than they are now, since aging itself is a risk factor for vascular breakdown.

It has been reported that atherosclerosis is the result of inflammatory changes [7] and increased levels of inflammatory markers such as C-reactive protein (CRP) may reflect vascular complications and predict future events [8], [9], [10]. It is well known that adhesion molecules are expressed at the initial stage of atherosclerosis and play an important role in its progression [11]. Also, an association between increased levels of adhesion molecules and atherosclerotic disease has been reported, although their pathophysiological role and metabolism remain unclear [12], [13]. Furthermore, recent studies have found high rates of cardiovascular [14], [15] and cerebrovascular disease [16] in subjects who had increased levels of soluble adhesion molecules beforehand. Therefore, it is likely that hs-CRP and sICAM-1 are predictive markers of future events and they may possibly be used to assess the effectiveness of treatment.

In a previous study, we noted that levels of soluble adhesion molecules were higher in elderly diabetic patients with silent brain infarction (SBI) than those without SBI [17]. In addition, it was found that SBI had progressed in diabetic patients with high levels of sICAM-1, but not in those with high hs-CRP levels after 3 years follow-up. We also found that patients who developed symptomatic stroke had higher levels of sICAM-1 and hs-CRP at baseline [18]. Therefore, in this study we investigated the influence of the reciprocal association between hs-CRP and sICAM-1 on the risk of symptomatic brain infarction and monitored the changes in their levels during an average 8 years of follow-up.

Section snippets

Patients

For this study, which were from 1995 to 2003, we recruited 179 consecutive patients with type 2 diabetes mellitus who were older than 45 years of age and had no history or clinical symptoms of cerebrovascular diseases (mean, 62.7 ± 8.2 years; range 46–81 years at baseline; 83 males, 61.4 ± 7.6 years; 96 females, 63.9 ± 8.6 years), from a group of outpatients at Chubu Rosai Hospital's Diabetic Center. The exclusion criteria at the time of registration were as follows: malignancy, chronic inflammatory

Comparisons of clinical and biochemical characteristics at baseline between type 2 diabetic patients with and without onset of brain infarction during follow-up (Table 1)

Significant differences were observed in duration of diabetes, systolic blood pressure, presence of SBI, treatment modality, microvascular complications and their severity, serum creatinine concentrations and levels of sICAM-1 and hs-CRP at baseline between diabetic patients with and without onset of brain infarction during follow-up. Also, a trend toward development of brain infarction was found for sex (male), diastolic blood pressure, and HbA1c levels at baseline. SBI was observed in 51 of

Discussion

It is well established that hypertension and aging are powerful risk factors for the development of stroke and this is irrespective of diabetes [20], [21]. Hypertension and diabetes mellitus often occur concomitantly and it is clear that when they are both present the risk of stroke increases dramatically [22]. In this study, hypertensive patients were the most likely to have a brain infarction and no patients with an average systolic pressure of less than 130 mmHg had one.

Diabetes mellitus has

Conflicts of interest

There are no conflicts of interest.

Acknowledgments

This research was supported by research funds to promote the hospital function of Japan Labor Health and Welfare Organization. We are grateful to N. Kajita for her excellent technical assistance.

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