Diabetic retinopathy is associated with subclinical atherosclerosis in newly diagnosed type 2 diabetes mellitus

Abstract

Aims

We aimed to evaluate the association between diabetic microangiopathy and subclinical atherosclerosis as a marker of cardiovascular disease (CVD) risk in patients with newly diagnosed type 2 diabetes.

Methods

A total of 142 newly diagnosed type 2 diabetics who were free from CVD underwent evaluation of diabetic microangiopathy. Subclinical atherosclerosis was assessed by measuring carotid intima-media thickness (IMT), and the 10-year absolute risk of CVD was estimated using the UK Prospective Diabetes Study (UKPDS) Risk Engine.

Results

Subclinical atherosclerosis was found in 27 subjects (19.0%). The rates of hypertension and diabetic retinopathy were significantly higher among patients with subclinical atherosclerosis. The UKPDS 10-year risk for CVD was significantly increased in subjects with subclinical atherosclerosis. Old age, hypertension and the presence of diabetic retinopathy showed a significant association to subclinical atherosclerosis after further adjustments for gender, body mass index, smoking status, HbA1c, HDL cholesterol, LDL cholesterol and the presence of diabetic nephropathy.

Conclusions

This study shows that diabetic retinopathy is an independent risk marker for subclinical atherosclerosis in patients with newly diagnosed type 2 diabetes. We suggest that a diagnosis of diabetic retinopathy may warrant a more careful cardiovascular assessment even in the early stages of diabetes.

Introduction

Early detection of atherosclerotic diseases in asymptomatic patients with type 2 diabetes has been emphasized and can lead to a reduction in mortality and morbidity from future cardiovascular disease (CVD) [1], [2]. It is established that the clock for atherosclerosis starts ticking before the onset of diabetes and that metabolic disturbances during the prediabetic period contribute to an increased risk of CVD in patients with impaired glucose tolerance and established diabetes [3]. Thus, several emerging biomarkers and non-invasive measures of early atherosclerosis have received considerable attention in type 2 diabetes [4], [5].

Growing evidence indicates that diabetic microangiopathy has a predictive value for CVD risk in patients with type 2 diabetes. Such evidence is supported by a “common soil” for the development of micro- and macro-angiopathy in type 2 diabetes [6]. Since the Framingham Heart and Eye Study proposed a link between retinopathy and atherosclerotic disease in type 2 diabetes, the importance of diabetic retinopathy beyond visual impairment has been well recognized [7]. Recently, diabetic retinopathy has been suggested to be a predictive risk marker for diabetic macroangiopathy [8], [9]. In addition, the strong association between diabetic nephropathy and macroangiopathy is becoming increasingly apparent, and the presence of diabetic neuropathy including cardiovascular autonomic neuropathy is closely associated with arterial stiffness or carotid intima-media thickness (IMT) in type 2 diabetes [10], [11].

On the other hand, although diabetic microangiopathy has been associated with an increased risk of CVD in type 2 diabetes, such an association was not unexpected because micro- and macro-angiopathy have several shared cardiovascular risk factors. Several previous studies also showed a limited and unequivocal association between diabetic micro- and macro-angiopathy after adjusting for traditional cardiovascular risk factors [12], [13], [14]. Thus, it is still unclear whether diabetic microangiopathy can be independently associated with macroangiopathy and used as a marker of atherosclerotic process in patients with less confounding cardiovascular risk factors, especially in the early stage of diabetes.

At the time of first diagnosis of diabetes, micro- and macro-angiopathy frequently coexist; up to 30% of patients already have subclinical atherosclerosis [15], [16]. The Insulin Resistance Atherosclerosis (IRAS) study and the risk factors in IGT for Atherosclerosis and Diabetes (RIAD) subgroup study clearly showed that patients with newly diagnosed type 2 diabetes have a higher risk of subclinical atherosclerosis than healthy controls, but the association of diabetic microangiopathy with subclinical atherosclerosis was inconclusive [17], [18]. Advances in our understanding of these features have stimulated interest in the evaluation of the association of diabetic microangiopathy with subclinical atherosclerosis in patients with newly diagnosed type 2 diabetes. The assessment of cardiovascular risk in patients with newly diagnosed type 2 diabetes could be an important component of clinical care, allowing the implementation of targeted preventive treatments for patients who are at high risk of CVD.

For macroangiopathy, carotid IMT measurement and carotid plaque (CP) detection are becoming widely accepted ways to evaluate atherosclerosis and predict CVD in patients with type 2 diabetes [19], [20]. We therefore performed a cross-sectional study to evaluate the association of diabetic microangiopathy with increased carotid IMT or the presence of CP as a surrogate marker of subclinical atherosclerosis in patients with newly diagnosed type 2 diabetes.