Reduced high-density lipoprotein 2b in non-obese type 2 diabetic patients analysed by a microfluidic chip method in a case-control study.

BACKGROUND: Alterations in high-density lipoprotein (HDL) subfractions, especially in the HDL2b subfraction, have been reported in type 2 diabetes mellitus (T2DM). However, new methods for convenient and reliable quantitation of HDL2b are yet to be developed. METHODS: Thirty-eight patients with T2DM were enrolled and age-, sex- and body mass index (BMI)-matched controls were selected from the same population. A microfluidic chip method was employed to analyse serum HDL subfractions. RESULTS: The microfluidic chip method revealed a significant reduction in HDL2b and its ratio to total HDL in T2DM patients. There was a reverse correlation for total HDL and HDL2b, and its ratio with triglycerides, homeostasis model assessment-insulin sensitivity index (HOMA-IS) and insulin resistance index (HOMA-IR). CONCLUSIONS: We have shown a reduction of HDL2b and its ratio to total HDL by a novel chip method in T2DM patients. The significant correlation between HDL2b and HOMA-IS and HOMA-IR may have further predictive value in clinical utility.

A case-control study on the relationship between HDL2b and non-alcoholic fatty liver disease in Chinese type 2 diabetic patients.

BACKGROUND: It has been shown that low concentrations of high-density lipoprotein cholesterol (HDL-C) are associated with non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM). HDL2b, a major subfraction of high-density lipoprotein (HDL), is more significantly correlated with coronary heart disease (CHD) compared with total HDL. In this study, we analysed HDL2b in a cohort of Chinese T2DM subjects with or without NAFLD. METHODS: A highly sensitive and reliable microfluidic chip method was adopted to measure HDL2b. In total, 48 T2DM patients with NAFLD diagnosed by a B-ultrasound were enrolled from our Beijing Community Pre-Diabetes (BCPD) study cohort. A total of 48 age and gender matched diabetic controls without NAFLD were selected from the same population. RESULTS: Clinical characteristics and serum biochemical analyses demonstrated a significantly increased body mass index (BMI), waist circumference, homeostasis model assessment-insulin resistant index (HOMA-IR), total cholesterol (TC), and triglyceride (TG) concentrations in the NAFLD group. However, the concentrations of HDL2b and its ratio to total HDL in NAFLD patients was decreased, compared with controls (p<0.01). Significantly increased concentrations of high sensitive C-reactive protein (hs-CRP) (p<0.01) were also found. Multifactor logistic regression analysis showed that BMI and TG were the predominant risk factors for fatty liver, while HDL2b was a protective factor. CONCLUSIONS: T2DM patients with NAFLD have characteristics including obesity, marked insulin resistance, high TG, high hs-CRP, low HDL2b and a low HDL2b ratio to total HDL. These factors may increase the incidence of atherosclerosis as well as the risk of CHD.

PROCAM Study: risk prediction for myocardial infarction using microfluidic high-density lipoprotein (HDL) subfractionation is independent of HDL cholesterol.

BACKGROUND: High-density lipoprotein (HDL) subfractions are among the new emerging risk factors for atherosclerosis. In particular, HDL 2b has been shown to be linked to cardiovascular risk. This study uses a novel microfluidics-based method to establish HDL 2b clinical utility using samples from the Prospective Cardiovascular Muenster (PROCAM) Study. METHODS: Method performance was established by measuring accuracy, precision, linearity and inter-site precision. Serum samples from 503 individuals collected in the context of the PROCAM study were analyzed by electrophoresis on a microfluidics system. Of these, 251 were male survivors of myocardial infarction (cases), while 252 individuals were matched healthy controls. HDL cholesterol, HDL 2b concentration and HDL 2b percentage were analyzed. RESULTS: This novel method showed satisfactory assay performance with an inter-site coefficient of variance of <10% for HDL 2b percentage. Parallel patient testing on 52 samples between two sites resulted in a correlation coefficient of r=0.95. Significant differences were observed in the HDL 2b subfraction between cases and controls independent of other risk factors. Including HDL 2b percentage in logistic regression reduced the number of false positives from 64 to 39 and the number of false negative cases from 48 to 45, in the context of this study. CONCLUSIONS: The novel method showed satisfactory assay performance in addition to drastically reduced analysis times and improved ease of use as compared to other methods. Clinical utility of HDL 2b was demonstrated supporting the findings of previous studies.