Response: Basal C-peptide Level as a Surrogate Marker of Subclinical Atherosclerosis in Type 2 Diabetic Patients (Diabetes Metab J 2011;35:41-9).

We appreciate the comments on our study "Basal C-peptide level as a surrogate marker of subclinical atherosclerosis in type 2 diabetes patients," which was published in Diabetes & Metabolism Journal 2011;35:41-49 [1].

Many studies have reported that high levels of HbA1c are strongly associated with increased risks of cardiovascular disease and microvascular complications [2]. However, recent studies have reported that while the use of intensive therapy to target glycated hemoglobin levels below 6% reduces 5-year nonfatal myocardial infarctions, it increases 5-year mortality [3]. Other studies have reported that high density lipoprotein cholesterol, but probably not HbA1c, influences cardiovascular outcomes [4]. It is still unknown, however, whether HbA1c levels are associated with macrovascular complications such as stroke, atherosclerosis, cardiovascular disease, and peripheral arterial disease.

In our study [1], the 10-year risk of coronary heart disease (CHD) was calculated according to the United Kingdom Prospective Diabetes Study (UKPDS) risk engine for each patient based on smoking status, total serum cholesterol, age, serum low density lipoprotein cholesterol, and systolic blood pressure. However, the 10-year CHD risk engine does not take levels of glucose or HbA1c into account. Therefore, in the present study, we show that basal C-peptide is not associated with UKPDS risk engine-related factors and does not independently influence 10-year CHD risk. However, intima media thickness (IMT) can be directly assessed based on arterial vessel wall changes and smooth muscle cell (SMC) proliferation. Insulin resistance and C-peptide are associated with SMC proliferation. Therefore, C-peptide is thought to be an independent factor predicting IMT. In the Atherosclerosis Risk in the Communities (ARIC) study [5], higher levels of endogenous insulin were significantly associated with increased thickness of the carotid artery wall. Reducing the levels of C-peptide and insulin resistance in type 2 diabetic patients, who are especially likely to exhibit many components of metabolic syndrome, may be improved in the outcomes of cases with cardiovascular complications.