ABSTRACT
We aimed to determine if increased non-enzymatic glycosylation of the LDL was sufficient to increase the susceptibility to in vivo oxidation of the LDL particles. Twenty-two type 2 diabetic patients (11 males and 11 females) were included in this study. They were enrolled on the basis of good [glycated hemoglobin (HbA1c) < 7%] and poor glycemic control [(HbA1c) > 8%]. LDL were isolated by sequential ultracentrifugation and analyzed by capillary electrophoresis (CE) for diene conjugate content and for electronegativity. The glyc-LDL levels were increased in all diabetic type 2 patients, peaking in the diabetic subjects in poor diabetic control (17.3 +/- 8.07%). The LDL content of diene conjugates was similar between the two groups (6.65 +/- 0.77% for the patients with good glycemic control versus 6.88 +/- 0.74% for those with poor glycemic control; P = 0.49) as was the electrophoretic mobility ((-1.14544 +/- 0.089) x 10(-4) cm2/(V s) for the patients with good glycemic control and (-1.13666 +/- 0.073) x 10(-4) cm2/(V s) for those with poor glycemic control; P = 0.80). The susceptibility to in vivo oxidation of LDL from type 2 diabetic patients in poor glycemic control did not differ from that of well-controlled diabetic patients. LDL glycosylation was not able to increase the oxidizability of LDL in the diabetic patients with poor glycemic control.
Subject(s)
Cholesterol, LDL/metabolism , Diabetes Mellitus, Type 2/diagnosis , Glycated Hemoglobin/analysis , Oxidation-Reduction , Aged , Blood Glucose/analysis , Cholesterol, LDL/analysis , Chromatography, Gel , Chromatography, High Pressure Liquid , Cohort Studies , Diabetes Mellitus, Type 2/blood , Female , Humans , Lipid Peroxidation/physiology , Male , Middle Aged , Particle Size , Probability , Reference Values , Risk Assessment , Sensitivity and SpecificityABSTRACT
We investigated the possibility that the DNA HindIII polymorphism of human lipoprotein lipase (LPL) is associated with the severity of coronary artery disease (CAD) determined by angiography in young patients who survived a myocardial infarction (MI). Conflicting studies have explored the relationship linking CAD severity to the HindIII restriction site polymorphism at the LPL gene locus, and to our knowledge, no data are available from Italy. The patients were aged less than 45 years (mean age, 40.1 +/- 3.9 years); 83 were male and four were female. The 87 case-patients had a Q-wave or non-Q-wave infarction (67.3% and 32.7%, respectively); the MI was anterior (50.5%), lateral (41.7%), or inferior (7.8%). Analysis of coronary angiograms showed the absence of critical stenosis in 13.8% and the presence of monovessel disease in 50.6% and multivessel disease in 35.6% of the case-patients. The allelic frequency of the HindIII H(-) and H(+) allele was 0.37 and 0.63, respectively. There was a striking association between the HindIII polymorphism and the number of diseased vessels. The patients with HindIII(+/+) genotypes were significantly more likely to have double- or triple-vessel disease and less likely to have no significantly diseased vessels. In this study, we demonstrated that the homozygous form of the LPL HindIII(+) allele increases the risk of multivessel disease by a factor of 4 in an Italian group of young MI survivors. This association was independent from the smoking status and a positive family history for CAD and hypertension, which are known to predict CAD severity. The discrepancies in the results of these studies are difficult to explain. The lack of homogeneity in the study populations (age at which CAD occurred, number of enrolled patients, and geographical origin) and differences in the assessment of CAD severity may account for these conflicting results.
Subject(s)
Lipoprotein Lipase/genetics , Myocardial Infarction/genetics , Polymorphism, Genetic , Adult , Alleles , Coronary Angiography , Coronary Disease/etiology , Deoxyribonuclease HindIII , Electrocardiography , Female , Gene Frequency , Genotype , Humans , Italy , Lipids/blood , Lipoproteins/blood , Male , Myocardial Infarction/enzymology , Polymorphism, Restriction Fragment Length , Regression Analysis , Risk FactorsABSTRACT
Apo E phenotype and plasma Tg, Chol, LDL-Chol, HDL-Chol and Apo B levels were determined in a sample of 228 healthy Italian subjects (124 men and 104 women) aged 18-93. The allele frequencies were: epsilon 2 = 0.070; epsilon 3 = 0.829; epsilon 4 = 0.101 (among the lowest values in the literature). Division of the sample into four age groups indicated that epsilon 4 frequency decreased with age to 0 in persons aged over 75. Covariance analysis of the influence of each allele on plasma lipids showed that epsilon 4 was significantly associated with the highest Chol, LDL-Chol and Apo B levels. These data are evidence of the influence of epsilon 4 on Chol metabolism in an Italian population. They also show that its frequency decreases with age.
Subject(s)
Aging/physiology , Alleles , Apolipoproteins E/genetics , Gene Frequency , Lipids/blood , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Italy , Male , Middle Aged , Polymorphism, GeneticABSTRACT
Non-insulin-dependent diabetes mellitus (NIDDM) is often characterized by an increase in VLDL-triglyceride, VLDL-cholesterol, LDL-cholesterol and a reduction in HDL-cholesterol. HMG-CoA reductase inhibitors significantly lower cholesterol rates and have an indirect effect on the LDL receptor. We measured the effect of simvastatin in 28 hypercholesterolemic subjects, including 14 with NIDDM in good metabolic control (HbAIc 7.8% +/- 1.3%). A 24-week treatment with 10 mg/day (weeks 1-4), 20 mg/day (weeks 5-8) and 40 mg/day (weeks 9-24) simvastatin revealed different responses in diabetic and non-diabetic patients. Total cholesterol, LDL-cholesterol and apo B decreased significantly in both groups (less in the diabetics), whereas only NIDDM patients displayed a significant reduction in VLDL-cholesterol and VLDL-apo B. In the non-diabetics, the reduction in plasma cholesterol was mainly confined to the LDL fraction (276 +/- 65 vs. 132 +/- 28 mg/dl), whereas a significant fall in VLDL-cholesterol (45 +/- 19 vs. 21 +/- 10 mg/dl) was more evident in the NIDDM patients. Simvastatin also influenced plasma apo B levels (221 +/- 33 vs 134 +/- 23 mg/dl in non-diabetics and 182 +/- 44 vs. 134 +/- 30 mg/dl in diabetics). Significant reduction of apo B, LDL-apo B (205 +/- 39 vs. 128 +/- 23 mg/dl) in the non-diabetics and VLDL-apo B (16 +/- 5 vs. 9 +/- 2 mg/dl) in the diabetics, indicates that the VLDL are primarily concerned when statins are administered in NIDDM.(ABSTRACT TRUNCATED AT 250 WORDS)
Subject(s)
Anticholesteremic Agents/therapeutic use , Cholesterol, LDL/blood , Cholesterol, VLDL/blood , Diabetes Mellitus, Type 2/complications , Hypercholesterolemia/drug therapy , Lovastatin/analogs & derivatives , Apolipoproteins/blood , Female , Humans , Hypercholesterolemia/blood , Hypercholesterolemia/complications , Lipids/blood , Lovastatin/therapeutic use , Male , Middle Aged , SimvastatinABSTRACT
Renal transplantation modifies the dyslipidemia characteristic of chronic renal failure (CRF). The change in lipoprotein and lipid values of 51 transplant recipients, on cyclosporine and corticosteroid treatment, was studied during 2 years after transplantation to examine the short- and medium-term variations of lipid metabolism. Compared with control values of (all in mg/dL) triglycerides (Tg) 111 +/- 44, very-low-density lipoprotein (VLDL) Tg 69 +/- 18, total cholesterol (Chol) 201 +/- 32, VLDL-Chol 32 +/- 9, low-density lipoprotein (LDL) Chol 118 +/- 28, and high-density lipoprotein (HDL) Chol 50 +/- 10, uremic patients pretransplantation exhibited values of Tg 200 +/- 82 (P less than .001), VLDL-Tg 133 +/- 70 (P less than .001), Chol 193 +/- 51 (NS), VLDL-Chol 52 +/- 16 (P less than .001), LDL-Chol 100 +/- 37 (P less than .007), HDL-Chol 40 +/- 16 (P less than .001), which changed to Tg 118 +/- 18 (P less than .001), VLDL-Tg 64 +/- 45 (P less than .001), Chol 223 +/- 48 (P less than .006), VLDL-Chol 26 +/- 33 (P less than .001), LDL-Chol 134 +/- 43 (P less than .001), at HDL-Chol 63 +/- 21 (P less than .001) at 3 months and Tg 135 +/- 76, VLDL-Tg 81 +/- 62, Chol 218 +/- 55, VLDL-Chol 22 +/- 20, LDL-Chol 139 +/- 46, and HDL-Chol 58 +/- 18 at 24 months without evidence of a significative variations in the 3- to 24-month posttransplant period.(ABSTRACT TRUNCATED AT 250 WORDS)