Low-density lipoprotein cholesterol levels in adults with type 2 diabetes: An alternative equation for accurate estimation and improved cardiovascular risk classification

Abstract

Low-density lipoprotein cholesterol (LDL-C) is a major risk factor for atherosclerotic disease. Despite its limitations, Friedewald-calculated LDL-C (F-LDL-C) remains widely used for LDL-C determination. In this observational study of 1999 adults with type 2 diabetes mellitus (T2DM), we compare the accuracy of F-LDL-C to directly measured LDL-C (M-LDL-C) and derived and validated a new [SMART2D (Singapore Study of MAcro-angiopathy and Micro-Vascular Reactivity in Type 2 Diabetes)] formula to estimate LDL-C. From 1000 randomly selected patients, M-LDL-C was compared to F-LDL-C. Using multiple linear regression to identify independent predictors for M-LDL-C, the SMART2D equation was derived and subsequently validated in the next 981 patients. F-LDL-C was 0.367 (0.216) mmol/L lower than M-LDL-C. This difference was −0.009 (0.189) for SMART2D-LDL-C. Using F-LDL-C, 27% with M-LDL-C ≥2.6 mmol/L were classified as LDL-C <2.6 mmol/L, reduced to 2.1% when using SMART2D-LDL-C. With F-LDL-C, misclassification was greater when triglycerides were ≥2.2 mmol/L, especially for the lower LDL-C cut-offs (1.8 and 2.6 mmol/L), and this was markedly improved with SMART2D-LDL-C. In conclusion, in T2DM, F-LDL-C underestimates M-LDL-C, with misclassifications that may potentially have an impact on therapeutic decisions in T2DM. The SMART2D equation improves accuracy of estimate, reducing misclassifications. Trials will be needed to ascertain the clinical significance of these findings.

LDL-cholesterol measurement in diabetic type 2 patients: a comparison between direct assay and popular equations

“…According to American Diabetes Association (ADA) guideline in diabetic patient without overt CVD, the goal of serum LDL-level is < 100 mg/dL [ 25 ]. By using 100 mg/dL as the threshold level, more than 10% of patients will be misclassified, if Friedwald formula compared to direct measurement of LDL-C is used, this is the same as results reported by Chai Kheng et al [ 24 ].…”

“…Some studies on general population and diabetic patients have shown that Friredwald formula give significantly higher results compared to direct method [ 14 ]. In a study on diabetic patients same result was obtained [ 22 ] but in two separate studies on diabetic patient, Friedewald equation showed negative bias which this issue can be very important in values near the cutoff points [ 23 , 24 ]. According to American Diabetes Association (ADA) guideline in diabetic patient without overt CVD, the goal of serum LDL-level is < 100 mg/dL [ 25 ].…”

Impact of Adoption of Directly Measured Low-Density Lipoprotein-Cholesterol (LDL-C) on Targets of Lipid Control and Its Comparison With Friedewald Formula-Calculated LDL Cholesterol in People With Type-2 Diabetes Mellitus

“…The tendency for FF values of c-LDL-C to misclassify people with various LDL levels, especially at higher levels of TG is seen in the literature. 13,17,[19][20][21] In a study of 1999 adults with type-2 diabetes, more than 10% of patients were misclassified by the c-LDL-C by the FC method for LDL target of 100 mg/dL compared to a modified equation. 16 This was more pronounced in people with TG >203 mg/dL.…”

Impact of glucose and lipid markers on the correlation of calculated and enzymatic measured low‐density lipoprotein cholesterol in diabetic patients with coronary artery disease

“…FE as the most widely applied method in clinical practice is recommended in several guidelines related to the therapy of dyslipidemia. 11,12,15,16 It assumes the ration of the mass of TG to very low-density lipoprotein cholesterol (VLDL-C) to be relatively constant. 8 However, in the real world, the ratios are variable in different individuals leading to less accuracy of FE, especially in the population with TG > 4.5 mmol/L and non-fasting state.…”

“…FE as the most widely applied method in clinical practice is recommended in several guidelines related to the therapy of dyslipidemia . It assumes the ration of the mass of TG to very low‐density lipoprotein cholesterol (VLDL‐C) to be relatively constant .…”