Presentation on theme: "High-density lipoprotein subclasses in subjects with impaired fasting glucose Filippatos TD 1, Barkas F 1, Klouras E 1, Liontos A 1, Rizos EC 1, Gazi I."— Presentation transcript:
High-density lipoprotein subclasses in subjects with impaired fasting glucose Filippatos TD 1, Barkas F 1, Klouras E 1, Liontos A 1, Rizos EC 1, Gazi I 1, Tselepis A 2, Elisaf M 1. 1Department of Internal Medicine, University of Ioannina, Ioannina, Greece 2 Laboratory of Biochemistry, Department of Chemistry, University of Ioannina, Ioannina, Greece
Introduction The term “prediabetes” describes the intermediate condition in which fasting plasma glucose level is found above the highest normal value and below the cut-off level used to determine the diagnosis of T2DM. Impaired fasting glucose (IFG) is defined as fasting plasma glucose concentration of 100–125 mg/dL according to the definition of American Diabetes Association (ADA). Prediabetic subjects are at high risk for the development of T2DM and may exhibit increased cardiovascular disease (CVD) risk. Diabetes Care 2008;31:596-615 Diabetes Care 2012;35 Suppl 1:S11-63 Moutzouri et al. Eur J Pharmacol 2011;672:9-19.
Introduction (II) High-density lipoprotein (HDL) includes discrete subfractions that differ with respect to size, density, composition, and other physicochemical properties. HDL particles carry enzymes, such as the HDL-associated lipoprotein-associated phospholipase A2 (HDL-LpPLA2) and paraoxonase-1 (PON1), which may play an essential role in their anti-atherogenic functions. The anti-atherogenic properties of HDL are compromised in T2DM patients, an effect that may play a role in their increased CVD risk. Kontush et al. Nat Clin Pract Cardiovasc Med 2006;3:144-153 Mueller et al. Clin Chem Lab Med 2008;46:490-498 Tselepis et al. Atheroscler Suppl 2002;3:57-68 James R. Clin Chem Lab Med 2006;44:1052-1059
Aims of the study The aim of the present study was to assess any differences in HDL subclass distribution and in activities of HDL-associated enzymes between subjects with IFG and non-prediabetic subjects.
Methods Greek subjects (n = 185) with IFG attending the Outpatient Lipid and Obesity Clinic of the University Hospital of Ioannina (Greece) participated in the present study. Exclusion criteria Coronary heart disease (CHD) or any other clinically evident vascular disease. Abnormal hepatic function (aminotransferase activity > 3 times ULN, and/or history of chronic liver disease Serum creatinine levels > 1.8 mg/dL (159 μmol/L) T2DM [fasting blood glucose > 126 mg/dL (7.0 mmol/L)] Thyroid-stimulating hormone levels > 5.0 μU/L Administration of any drug during recruitment
Results Variable IFG (glucose ≥100 mg/dL) Glucose <100 mg/dLp-value N (females/males)80 (40/40)105 (56/49)NS Age, years51 ± 11 NS BMI, kg/m 2 33.4 ± 6.130.4 ± 5.90.01 Waist circumference, cm107 ± 14102 ± 120.008 Glucose, mg/dL109 ± 890 ± 10<0.001 Insulin, μU/mL12.5 (7.4-18.0)9.1 (6.8–12.3)<0.01 HOMA index3.6 (2.0-4.7)2.0 (1.5-2.9)<0.001 Systolic BP, mmHg138 ± 16133 ± 150.026 Diastolic BP, mmHg89 ± 984 ± 100.003 Values are given as mean ± standard deviation or median (interquartile range) for parametric and non-parametric variables, respectively. IFG = impaired fasting glucose; BMI = body mass index; BP = blood pressure; HOMA = homeostasis model assessment; NS = not significant.
Multivariate regression analysis for the prediction of small HDL3 concentration and its proportion over HDL-C levels Small HDL3 concentrationSmall HDL3 proportion Variablebetap p TG0.10NS0.24<0.01 HDL-C0.56<0.01-0.53<0.01 TC0.45<0.010.43<0.01 Waist circumference0.140.010.09NS Prediabetes presence0.05NS0.130.04 R 2 = 0.71R 2 = 0.52
Conclusions The proportion of small HDL3 over HDL-C was significantly increased in prediabetic subjects compared with their controls (p<0.05). The activity of the anti-atherogenic HDL-associated lipoprotein-associated phospholipase A2 (HDL-LpPLA2) was significantly lower in subjects with prediabetes (p<0.05), whereas the activity of PON1 did not significantly differ between subjects with or without prediabetes. In a stepwise linear regression analysis, the proportion of small HDL3 over HDL-C concentration was independently associated with the presence of prediabetes and with total cholesterol and TG concentration (positively), as well as with HDL-C levels (negatively).