Association between Small Dense Low-Density Lipoproteins and High-Density Phospolipid Content in Patients with Coronary Artery Disease with or without Diabetes.

OBJECTIVE: To evaluate the phospholipid profile in total plasma, non-high-density lipoprotein (HDL), and HDL fractions. We tried to correlate the phospholipid profile to low-density lipoprotein (LDL) size, as reflected by cholesterol content in each LDL subclass. METHODS: We measured small dense LDL-C levels after heparin-magnesium precipitation and measured high-density lipoprotein phospholipid (HDL-P) levels using a colorimetric enzymatic method. RESULTS: The correlation of the phospholipid profile to small dense LDL-C (sdLDL-C) in patients with coronary problems showed a negative association between small dense low-density lipoprotein (sdLDL) and HDL-P (r = -0.73; P = .02). Moreover, a strong positive correlation was detected between TG and the ratio HDL-P/HDL-C (r = 0.83; P <.001). CONCLUSIONS: HDL phospholipid has an antiatherogenic effect in coronary artery disease with or without diabetes. Further, large LDL modulation seems to be associated with diabetes rather than coronaropathy.

Clinical and body composition predictors of bone turnover and mineral content in obese postmenopausal women.

The purpose of this study was to determine the predictors of bone mineral density (BMD), bone mineral content (BMC), and bone turnover markers in obese postmenopausal women. In this cross-sectional study, 81 postmenopausal women aged 58.40 ± 6.08 years were analyzed. Anthropometric parameters were recorded. Serum glucose parameters, serum lipid profiles, adipokines, renal, hepatic parameters, and bone markers concentrations were determined by well-validated laboratory routine methods. BMD, BMC, and body composition were measured by Dual X-ray Absorptiometry. We found a significant correlation of BMD with age, years since menopause, anthropometric parameters, glycemia, alkaline phosphatase, fat mass, and lean mass. Multiple regression analysis demonstrated that years since menopause, waist circumference, alkaline phosphatase, trunk fat, and lean mass were independently associated to BMD. Also, age, years since menopause, anthropometric parameters, total cholesterol, alkaline phosphatase, fat mass, and lean mass were correlated to BMC. However, only waist circumference and trunk fat were independently related to BMC. Bone turnover markers were significantly correlated to the age, glycemia, HbA1c, adipokines, hepatic parameters, and lean mass. Nevertheless, only adipokines, gamma glutamyl transferase (GGT), and alkaline phosphatase were independently associated to bone turnover markers. These observations suggest that number of years since menopause, waist circumference, alkaline phosphatase, trunk fat, and lean mass were the only significant predictors of BMD. However, waist circumference seems to be a stronger predictor than trunk fat for BMC. Moreover, adiponectin, resistin, GGT, and alkaline phosphatase were significant predictors of the bone resorption (CTX-I) and the bone formation (P1NP) markers.

Positive Association of Obesity and Insulin Resistance With Bone Mineral Density in Tunisian Postmenopausal Women.

The association of bone mineral density (BMD) with obesity and insulin resistance remains unclear. This study aimed to explore these associations in Tunisian menopausal women. Eighty-one postmenopausal women were recruited. Data were analyzed for obese (N = 57) and non-obese women (N = 24) and for insulin-resistant (N = 43) and non insulin-resistant women (N = 36). Anthropometric and biochemical parameters were recorded. BMD in different sites and body composition were measured using dual-energy X-ray absorptiometry. Higher BMD was observed in obese women than those non-obese in the left femur (p = 0.0067), right femur (p = 0.0108), total hip (p = 0.0077), and the whole body (p = 0.0276). Also BMD was significantly greater in insulin-resistant women than in non-insulin-resistant women when measured in the left femur and total hip. Positive correlations were recorded between BMD and anthropometric parameters, body composition parameters, and glycemia (r = 0.249, p < 0.05). Multiple linear regression analysis shows that only trunk fat (p < 0.05) and lean mass (p < 0.05) were independently and positively related to BMD, and the waist circumference was the only anthropometric parameter independently and negatively associated to BMD. BMD is improved in obese and insulin-resistant women. Also, trunk fat and lean mass are likely to be key positive independent factors for BMD.

Dual-energy X-ray absorptiometry underestimates in vivo lumbar spine bone mineral density in overweight rats.

Dual-energy X-ray absorptiometry (DXA) is currently the most widely used technique for measuring areal bone mineral density (BMD). However, several studies have shown inaccuracy, with either overestimation or underestimation of DXA BMD measurements in the case of overweight or obese individuals. We have designed an overweight rat model based on junk food to compare the effect of obesity on in vivo and ex vivo BMD and bone mineral content measurements. Thirty-eight 6-month old male rats were given a chow diet (n = 13) or a high fat and sucrose diet (n = 25), with the calorie amount being kept the same in the two groups, for 19 weeks. L1 BMD, L1 bone mineral content, amount of abdominal fat, and amount of abdominal lean were obtained from in vivo DXA scan. Ex vivo L1 BMD was also measured. A difference between in vivo and ex vivo DXA BMD measurements (P < 0.0001) is evidenced with an underestimation of in vivo BMD by (8.47 ± 10.54)%. This difference was found for the chow and high fat, high sucrose diets (P = 0.008), and a significant interaction between in vivo measurements, ex vivo measurements, and diet was observed (P = 0.030). Also, the data show a positive significant correlation of ex vivo BMD with body weight, perirenal fat, abdominal fat, and abdominal lean. Multiple linear regression analysis shows that body weight, abdominal fat, and abdominal lean were independently related to ex vivo BMD. DXA underestimated lumbar in vivo BMD in overweight rats, and this measurement error is related to body weight and abdominal fat. Therefore, caution must be used when one is interpreting BMD among overweight and obese individuals.

Isorhamnetin derivatives and piscidic acid for hypercholesterolemia: cholesterol permeability, HMG-CoA reductase inhibition, and docking studies.

Bioactive compounds, such as isorhamnetin and piscidic acid, were obtained from decoctions of cladodes (stem pads from Opuntia ficus-indica). The effect of these phenolic compounds, in a fiber-free extract, were evaluated as inhibitors of cholesterol permeation through a Caco-2 cell monolayer and as 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. A reduction of 38% in cholesterol permeation through the Caco-2 cell monolayer was obtained, and the phenolic compounds all permeated between 6 and 9%. A mixture of these compounds showed an IC50 of 20.3 µg/mL as an enzyme inhibitor, whereas piscidic acid alone showed an IC50 of 149.6 µg/mL; this was slightly outperformed by the isorhamnetin derivatives. Docking studies confirmed that both piscidic acid and isorhamnetin derivatives, present in the decoction, could adequately bind to the enzyme active site. These results reveal that O. ficus-indica, and cladodes derived there from, is a promising plant for use in the development of new functional foods and pharmaceutical products.

Extra virgin olive oil modulates brain docosahexaenoic acid level and oxidative damage caused by 2,4-Dichlorophenoxyacetic acid in rats.

Oxidative stress is an important pathomechanism of neurological disorders such as Alzheimer disease and Parkinson disease, cardiovascular disorders and many others. This study sought to verify whether extra-virgin olive oil (EVOO), lipophilic fraction (OOLF) and hydrophilic fraction (OOHF) exerted a brain protective effect against the oxidative stress caused by 2,4-dichlorophenoxyacetic acid (2,4-D) pesticide at a dose of 5 mg/kg body weight. 2,4-D, EVOO and its fractions were administered to rats by gavages for four consecutive weeks. Oxidative stress was assessed by measuring brain lipid peroxide level, acetylcholinesterase (AChE), antioxidant enzyme activities and fatty acid composition. 2,4-D induced a decrease in both plasma and brain acetylcholinesterase activity and a rise in Brain TBARS (Thiobarbituric acid reactive substances) level and antioxidant enzyme activities compared with the control group. These changes were partly reversed by either EVOO or its fractions oral administration to 2,4-D treated rats. EVOO enhanced a neuroprotective effect evaluated by the restoration of brain fatty acid composition especially the level of docosahexaenoic acid (DHA). Our results indicate that EVOO exerts a neuroprotective activity against oxidative damage in brain induced by 2,4-D, which could be attributed to its antioxidative property.

Plasma proprotein convertase subtilisin/kexin type 9 is associated with Lp(a) in type 2 diabetic patients.

AIM: Recent in vitro researches have shown that plasma Lp(a) can be reduced using a proprotein convertase subtilisin/kexin type 9 (PCSK9)-inhibitory monoclonal antibody. In our clinical study we tried to investigate the association between plasma Lp(a) and PCSK9 in Type 2 diabetic patients with elevated plasma Lp(a), and to check whether such an association would be related to LDL-receptor (LDL-R) levels. METHODS: Plasma PCSK9 and LDL-R concentrations were measured by sandwich ELISA methods using recombinant human PCSK9 protein and LDL-R protein as standards in a cohort with type 2 diabetic patients (n=50) compared to an age- and sex-matched control group (n=50). Both clinical and biochemical parameters were determined in all patients. RESULTS: Plasma PCSK9 level was significantly elevated in T2DM patients compared to controls (44.61±14.44 and 33.22±11.79ng/mL, respectively, P<0.0001). However LDL-R levels did not differ between the two groups. Remarkably, plasma PCSK9 levels were positively correlated with Lp(a) levels in whole population (r=+0.227, P=0.03) as well as in T2DM group (r=+0.398, P=0.0061) but not in control group. Multiple linear regression analysis showed that plasma Lp(a) levels were independently associated to those of PCSK9. CONCLUSION: Lp(a) has been proposed as a contributing factor to the accelerated development of macrovascular complications in T2DM. Its synergic effect with PCSK9 may explain the enhanced atherogenicity in T2DM patients.

High density lipoprotein-anionic peptide factor effect on reverse cholesterol transport in type 2 diabetic patients with and without coronary artery disease.

OBJECTIVES: To verify if HDL3 Anionic Peptide Factor (HDL3-APF) is as an apolipoprotein that promotes the reverse cholesterol transport. DESIGN AND METHODS: We investigated a possible association between plasma HDL3-APF concentration, cholesterol efflux from Fu5AH cells and cholesteryl ester transfer protein (CETP) activity in type 2 diabetic patients with coronary artery disease (CAD) (n=36), those without CAD (n=20), and 37 healthy subjects. RESULTS: Plasma APF concentrations were decreased in diabetics with CAD compared to controls (p<0.01). Cellular cholesterol efflux was decreased in diabetics without and with CAD, (p<0.01 and p<0.001 respectively). CETP activity was significantly elevated in all patient groups. Multiple linear regression analysis shows that cholesterol efflux was independently and positively related only to APF concentrations in controls. CONCLUSIONS: APF is likely to be a key independent factor for promoting cellular cholesterol efflux in healthy subjects. However this association is altered in type 2 diabetes.

Reverse modulation of the HDL anionic peptide factor and phospholipid transfer protein activity in coronary artery disease and type 2 diabetes mellitus.

OBJECTIVES: The high density lipoprotein Anionic Peptide Factor (HDL(3)-APF) was previously described as an apolipoprotein that promotes the reverse cholesterol transport. Since phospholipid transfer protein (PLTP) is involved in such mechanism we attempted to focus on the two APF and PLTP proteins. DESIGN AND METHODS: We recruited 56 type 2 diabetic patients with (n=36) or without (n=20) coronary artery disease (CAD) and 19 CAD patients. The three groups were compared to 39 healthy control subjects. In all groups, lipid profile was determined and plasma APF concentrations and PLTP activity were measured. RESULTS: In all patients, the PLTP activity was significantly increased in comparison with controls (p<0.01), in concomitance with a plasma APF level decrease in groups with CAD (with and without type 2 diabetes) (p<0.01). Multiple linear regression analysis demonstrated that, when apoA-I, HDL-C, HDL-phospholipids and PLTP activity were taken into account as independent variables (after univariate regression analysis), HDL-PL was positively and independently related to APF (p<0.0001 in whole population; p=0.0090 in controls) and PLTP activity was negatively and independently related to APF in whole population and all patients' groups (all p<0.05), but positively and independently associated to APF in controls (p=0.0005). CONCLUSIONS: APF could be considered as a specific marker against CAD and type 2 diabetes mellitus and our results confirm the atherogenic behavior of PLTP in CAD. Thus, these two proteins are likely to be regulated in a reverse manner.

Association between apolipoprotein E polymorphism, lipids, and coronary artery disease in Tunisian type 2 diabetes.

BACKGROUND: The relationship between apolipoprotein E (ApoE) polymorphism, fasting lipid parameters, and coronary artery disease (CAD) is controversial. METHODS: We studied this relationship, for the first time, in Tunisian type 2 diabetic patients. The studied population comprised 157 type 2 diabetic patients (145 of them were not on any lipid-lowering drugs). Fasting lipids were measured by enzymatic methods and ApoE genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Our results showed that the alleles E2, E3, and E4 were found in 4%, 88%, and 8% of patients, respectively. In the total type 2 diabetic population, no association was found between ApoE polymorphism, lipid parameters, and CAD. However, the E4 allele was associated with elevated low-density lipoprotein cholesterol concentration and with CAD in type 2 diabetic men. CONCLUSION: The effect of ApoE polymorphism on CAD is gender-dependent in the Tunisian type 2 diabetic population. ApoE 4 allele may enhance atherogenesis indirectly by a strong effect on low-density lipoprotein cholesterol.

Increased phospholipid transfer protein activity associated with the impaired cellular cholesterol efflux in type 2 diabetic subjects with coronary artery disease.

Reverse cholesterol transport (RCT) is the pathway, by which the excess of cholesterol is removed from peripheral cells to the liver. An early step of RCT is the efflux of free cholesterol from cell membranes that is mediated by high-density lipoproteins (HDL). Phospholipid transfer protein (PLTP) transfers phospholipids between apolipoprotein-B-containing lipoproteins (i.e., chylomicrons and very low-density lipoproteins) and HDL. PLTP contributes to the HDL maturation and increases the ability of HDL to extract the cellular cholesterol. It is known that RCT is impaired in type 2 diabetic patients, especially when cardiovascular complication is associated with. In this study, we measured the serum capacity that promotes cellular cholesterol efflux and the plasma PLTP activity in type 2 diabetic patients with coronary artery disease (CAD) (n = 35), those without CAD (n = 24), and 35 healthy subjects as a sex- and age-matched control. In patients with CAD, plasma triglyceride level was higher compared to controls (p < 0.01) and HDL-cholesterol was lower (p < 0.01 vs control and the patients without CAD). In diabetic patients with or without CAD, PLTP activity was consistently increased, compared to controls, while cellular cholesterol efflux activity was decreased by 20% (p < 0.001) or 13.5% (p < 0.01), respectively. In conclusion, plasma PLTP activity was increased in type 2 diabetic patients with or without CAD, which could impair cellular cholesterol removal and might accelerate atherosclerosis in diabetic patients.

Association of SNP3 polymorphism in the apolipoprotein A-V gene with plasma triglyceride level in Tunisian type 2 diabetes.

BACKGROUND: Apolipoprotein A-V (Apo A-V) gene has recently been identified as a new apolipoprotein involved in triglyceride metabolism. A single nucleotide polymorphism (SNP3) located in the gene promoter (-1131) was associated with triglyceride variation in healthy subjects. In type 2 diabetes the triglyceride level increased compared to healthy subjects. Hypertriglyceridemia is a risk factor for coronary artery disease. We aimed to examine the interaction between SNP3 and lipid profile and coronary artery disease (CAD) in Tunisian type 2 diabetic patients. RESULTS: The genotype frequencies of T/T, T/C and C/C were 0.74, 0.23 and 0.03 respectively in non diabetic subjects, 0.71, 0.25 and 0.04 respectively in type 2 diabetic patients. Triglyceride level was higher in heterozygous genotype (-1131 T/C) of apo A-V (p = 0.024). Heterozygous genotype is more frequent in high triglyceride group (40.9%) than in low triglyceride group (18.8%); p = 0.011. Despite the relation between CAD and hypertriglyceridemia the SNP 3 was not associated with CAD. CONCLUSION: In type 2 diabetic patients SNP3 is associated with triglyceride level, however there was no association between SNP3 and coronary artery disease.

[Role of cholesteryl ester transfer protein activity and genetic polymorphism in ischemic heart disease in type 2 diabetic patients]. / Rôle de l'activité et du polymorphisme génétique de la protéine de transfert des esters de cholestérol (CETP) dans les cardiopathies ischémiques chez les diabétiques type 2.

Cholesteryl Ester Transfer Protein (CETP) facilates the exchange of triglycerides (TG) and cholesteryl ester between lipoproteins particles. Diabetic subjects have been reported to have higher TG levels and lower high density lipoprotein-cholesterol (HDL-C) levels which contribute to the increased cardiovascular risk observed in some of these patients. The CETP activity was shown to be more important in a group of 93 non insulino-dependant diabetics with coronary artery disease than in a group of 92 healthy subjects (p = 0.033). Several polymorphisms have been reported in the CETP gene. The common Taq IB polymorphism is associated with decreased CETP activity and increased HDL-C. We have observed a frequency of 0.31 for B2 allele in deference to those reported in subjects from Caucasian population. An association between the presence of the B2B2 genotype, decreased CETP activity and increased of plasma HDL-C was observed in healthy subjects but not in diabetics with coronary artery disease.