Alterations And Significance Of Particle Components Of High Density Lipoprotein Subspecies In Type 2 Dibetic Patients

ObjectiveTo study alterations in particle components of high density lipoprotein subspecies and activities of the key lipid transfer proteins for its metabolism in type 2 diabetic patients, possible clinical significances of the alterations were also explored.MethodsWe recruited 26 new-onset type 2 diabetic patients as T2DM group, and 25 healthy subjects as control group. Plasma was fasting sampled for all subjects, and fasting blood glucose (FBG). glycosylated hemoglobin (HbAlc), fasting insulin (FINS) as well as plasma lipid profile were determined. The homeostasis model calculated from FBG and FINS was applied to assess insulin resistance and expressed as HOMA-IR. High density lipoprotein 3(HDL3) was separated from plasma by an established single precipitation method and the following compositions were measured accordingly:cholesterol (CHOL), cholesterol Ester (CE), free cholesterol (FC), Phospholipid (PL), apolipoprotein A-I (ApoA-I) and apolipoprotein A-Ⅱ(ApoA-Ⅱ). Concentrations of CHOL, apoA-Ⅰand apoA-II of HDL2 were collected by subtracted each concentration in HDL3 from its plasma concentration. All subjects were undertaken the standard oral glucose tolerance test (OGTT), and 2-hour postprandial blood glucose (PBG) was assayed. Activities of cholesterol ester transfer protein (CETP) and phospholipid transfer protein (PLTP) was determined by enzyme fluorescence assay kits.Results1. Comparisons and correlation analyses of lipid profile:Plasma levels of triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C) were significantly increased in T2DM group compared with control group (P< 0.01), while ApoA-Ⅰwas significantly decreased (141.8±23.5 vs.159.9±28.0mg/dl, P< 0.05). There were no differences in HDL-C and ApoA-Ⅱbetween T2DM group and control group (P>0.05). In all subjects, plasma ApoA-Ⅰwas significantly and negatively correlated with postprandial blood glucose (PBG) (r=-0.278, P=0.048), plasma HDL-C was significantly and positively correlated with TC(r=0.291, P=0.039) and ApoA-Ⅰ(r=0.738, P<0.001), but not with TG or VLDL (P>0.05).2. Activities of CETP and PLTP: There were no significant differences in either CETP or PLTP activity between T2DM group and control group (473.11±62.46 vs.473.52±76.17 noml/ml/h, P=0.98 and 0.43±0.16 vs.0.66±0.71 noml/ml/min, P=0.12, respectively).3. Comparisons and correlation analyses of particle components of HDL3: HLD3-C (0.60±0.17 vs.0.75±0.22mmol/L, P=0.008), PL (1.14±0.19 vs.1.29±0.22mmol/L, P=0.019), FC (0.021±0.012 vs.0.033±0.012mmol/L, P=0.001) and CE (0.97±0.28 vs.1.19±0.36mmol/L, P=0.014) decreased significantly in T2DM group than those in control group. There were no significant differences in ApoA-Ⅰor ApoA-Ⅱbetween two groups (P>0.05). In all subjects, CE and FC from HDL3 were significantly and negatively correlated with the following indicators:PBG (r=-0.372, P=0.007), HbA1c (r=-0.298, P=0.033), HOMA-IR (r=-0.325, P=0.020).4. Comparisons and analyses of particle components of HDL2: ApoA-Ⅰwas decreased significantly in T2DM group compared with control group (60.48±23.33 vs.75.54±19.80mg/dl,P<0.05). There were no significant differences in CHOL and ApoA-Ⅱbetween two groups. In all subjects, ApoA-Ⅰof HDL2 negatively correlated with the following indicators: HOMA-IR (r=-0.324, P=0.020), PBG (r=-0.303, P=0.031), plasma TG (r=-0.391, P=0.005). Conclusions1. Compare with control group, T2DM patients are characterized by obvious dyslipidemia including increased TC, TG, LDL-C and decreased ApoA-I, while HDL-C is comparable between two groups.2. There were no significant differences in either CETP or PLTP activity between T2DM group and control group.3. Particle components including CE, FC, CHOL and PL of HDL3 from T2DM group are decreased significantly. We then speculate that the size of HDL3 particle shrinks and might relate to hyperglycemia and insulin resistance.4. Compared with control group, as the major component of HDL2 particle, ApoA-I decreases significantly in T2DM group and relates to hyperglycemia and insulin resistance.