International Journal of Medical Laboratory

Introduction
Diabetes mellitus is a common metabolic disorder impinging on people worldwide. It is well known that people with diabetes bear elevated cardiovascular risk, and the relative risk of death from cardiovascular disease (CVD) is about twice as high [1]. Dyslipidemia, which is common in diabetes, is associated with increased risk of CVD in diabetic patients [2]. Elevated triglycerides (TG), low levels of high-density lipoprotein cholesterol (HDL-C), an increased presence of small dense atherogenic low density lipoprotein cholesterol (LDL-C) particles are the most common patterns of dyslipidemia in diabetic patients [3]. In the presence of hypertriglyceridemia, the exchange of TG and cholesteryl ester between LDL and VLDL and then lipolysis of triglyceride-rich LDL results in the formation of small and dense LDL particles. These LDL particles can be easily oxidized and thus penetrate the artery wall and increase the risk of CVD. Although small dense LDL particles are far more than normal-sized LDL, LDL-C value may be normal because small dense LDL particles are poor in lipid. Therefore, even though LDL-C levels are typically normal in patients with diabetes, they can produce highly atherogenic apoprotein-B containing particles such as very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL) as well as small, dense atherogenic LDL particles [4]. Therefore, relying on LDL-C targets alone to identify patients at risk of CVD can be misleading in such patients. In this regard, finding other measurements can help identify diabetic people who are at increased risk of atherosclerosis. Recently, it has been found that non-high density lipoprotein cholesterol (non-HDL-C), which is obtained by subtracting the level of HDL-C from total cholesterol, has a distinct advantage over LDL-C in predicting CVD [5]. Indeed, non-HDL-C measurement provides a single index of all the atherogenic apolipoprotein-B containing particles such as LDL, VLDL, IDL and chylomicron remnants [5]. From a practical point of view, direct measurement of apo-B is not widely available in clinical laboratories while assessment of non HDL-C is practical, convenient, reliable, and cost-effective [6].
There are several reports from different populations that non-HDL-C has more predictive power than LDL-C in detecting CVD [7, 8]; however, no such trials can be found in the Iranian population as to the high prevalence of CVD. Hence, the aim of this study was to compare the novel risk factor non-HDL-C versus LDL-C parameter as the primary therapeutic target in the treatment of dyslipidemia, in diabetic and non-diabetic Iranian subjects.
Materials and Methods
Included in the study was a data set of 2142 individuals (consists of 1505 non-diabetics and 637 diabetics) from Tehran city. This research was approved by the Ethics Committee of Tehran University of Medical Sciences (IR.TUMS.VCR.REC.1398.374). Blood samples were obtained at the Reference Laboratory of Social Security Organization in Tehran city (Iran). The blood was collected in plain tubes after a 12-hour fast and then centrifuged at 3000 rpm for 15 min. All samples were analyzed in terms of lipid profiles comprising total cholesterol (TC), TG, HDL-C, and LDL-C. Lipid profiles were determined by the standard homogenous enzymatic method using an automatic chemistry analyzer (Hitachi 902, Roche®) and the calibrating and internal controls were provided by the Pars Azmon Company. Non-HDL-C values were calculated by subtracting the level of HDL-C from TC.
Statistical analysis
Statistical analysis was performed using SPSS Statistics 16.0. Continuous data were expressed as a mean and standard deviation. Statistical independent T-test was used to evaluate the significance of differences between diabetic and non-diabetic groups. The level of significance was considered as p<0.05.
Results and discussion
There is an association between abnormal lipid levels and cardiovascular risk in patients with diabetes [1]. Although LDL-C is the main therapeutic target (<2.5 mmol/L) in the treatment of dyslipidemia, several studies have shown that non-HDL-C is a better predictor of atherosclerosis [7, 8]. In this regard, the adult treatment panel III of the National Cholesterol Education Program (NCEP) has recommended such use for non-HDL-C as a secondary treatment target (<3.3 mmol/L) in patients with elevated triglycerides [9]. The results of this study indicated non-HDL-C concentrations being approximately 0.7 mmol/L higher than LDL-C ones (mean non-HDL-C=3.3±0.93 mmol/L and mean LDL-C=2.5±0.64 mmol/L), as the NCEP guidelines have described (Table 1) [9]. Both LDL-C ≤2.5 mmol/L and non-HDL-C ≤3.3 mmol/L targets were achieved in 1095 (51%) subjects.
Several studies have examined the LDL-C and non-HDL-C goals in different patients. Malic et al found patients with diabetes not achieving LDL-C <2.5 mmol/L and non-HDL-C <3.3 mmol/L, 64.6% and 71.5%  respectively [10]. In another study, 74% of coronary heart disease patients attained LDL-C goal while only 51% achieved both non-HDL-C and LDL-C targets [11]. In the present study, 48% of patients with diabetes were identified as achieving combined LDL-C ≤2.5 mmol/L and non-HDL-C ≤3.3 mmol/L targets. Whereas 50.2% of diabetic patients attained non-HDL-C goal (≤3.3 mmol/L), 58.2% achieved LDL-C one (Fig. 1). In other words, despite LDL-C level of ≤2.5 mmol/L, about 10% of diabetic patients had non-HDL-C above the target range. In addition, our study revealed non-HDL-C being significantly higher in diabetic subjects than non-diabetic subjects (P=0.0001) while no statistically significant difference was identified regarding LDL-C between the groups (P=0.179) (Table 1). These findings are in accordance with the findings of previous studies. Therefore, non-HDL-C might be a better predictor of vascular events than LDL-C.
 

Table 1. Characteristics of study subjects and comparison between diabetic and non diabetic subjects

 
 

Non–HDL-C has crucial preferences in comparison with other lipid parameters.
Non–HDL-C has a specific pathophysiologic link to the atherosclerosis and predicts both subclinical atherosclerosis and adverse clinical outcomes. Moreover, non-HDL-C is a valid surrogate marker of Apo B in patients with diabetes which can be calculated from non-fasting serum samples [12]. Accordingly, it is a more practical, reliable and cost-effective value such that it reduces the risk of hypoglycemia in a diabetic patient [6]. Measuring and reporting non–HDL-C routinely can improve clinical outcomes through CVD risk identification, therapy decisions, and evaluation of response to treatment. All in all, this study indicated that non-HDL can be beneficial in assessing the risk of CVD in diabetic populations, therefore it can be included in the lipid profile for assessing the risk and thus guiding the treatment.
Conflict of Interest
The authors declare that they have no conflict of interest.
Acknowledgment
We thank the University of Tehran and Reference Laboratory of Social Security Organization for supporting this manuscript.
 
 
References