[The effect of apolipoprotein e polymorphism on plasma cholesteryl ester transfer protein activity in type 2 diabetic patients].

We studied the relationship between apo E polymorphism and cholesteryl ester transfer protein (CETP) activity in 127 type 2 diabetic patients who did not take lipid lowering drugs. Furthermore, we studied the relationship between apo E and CETP in modulating plasma triglyceride and HDL cholesterol. Apo E genotypes were determined by PCR-RFLP and CETP activity was measured using an exogenous way. Our results showed that the CETP activity increased significantly in E2 carrier group compared to E4 carriers and E3E3 homozygous (84.7 +/- 43.9 vs 62.5 +/- 35.9 vs 52.6 +/- 23.6 nmol CE/ml 2h respectively; p = 0.015). However, there was no association between apoE polymorphism and lipid parameter variations. Even after adjustment for CETP activity the results remained unchanged showing that CETP did not step in the relationship between apo E and lipid parameter variations. In conclusion there is an association between apo E polymorphism and CETP activity and this association did not affect the relationship between apo E polymorphism and triglyceride and HDL cholesterol concentrations.

Hyperhomocysteinemia and elevated ox-LDL in Tunisian type 2 diabetic patients: role of genetic and dietary factors.

INTRODUCTION: Total plasma homocysteine (tHcy) is an emerging risk factor for the development of atherosclerosis. However, its relationship with diabetes is still unclear. OBJECTIVES: We evaluated the association between tHcy levels and methylenetetrahydrofolate reductase (MTHFR) 677C-->T genotype in a type 2 diabetes mellitus (DM) population and their relationship with oxidized LDL (ox-LDL) according to dietary habits and vascular complications. DESIGN AND METHODS: Eighty-six DM patients were compared to 120 healthy volunteers. RESULTS: Associated higher tHcy levels and significantly higher ox-LDL levels (p<0.001) were found in DM patients compared to healthy subjects. Homozygosity for the T allele of MTHFR was more frequent in diabetics than in healthy subjects (12.8% vs. 7.2%) and it was associated with higher tHcy levels. Moreover, this elevated level was associated with significantly higher ox-LDL levels in DM patients with hypertension (p<0.05). Improving folate and vitamin C intakes could have beneficial effects on lowering the tHcy and ox-LDL levels. CONCLUSIONS: The interplay of genetic and dietary factors modulates the effect of homocysteine on cardiovascular risk factors.

Association between dietary fat and antioxidant status of Tunisian type 2 diabetic patients.

BACKGROUND: The antioxidant enzymes: superoxide dismutase (Cu/Zn SOD) and glutathione peroxidase (GSH-Px) provide a defense against the damage of cells by reactive oxygen species, which increased in diabetic state. It was demonstrated that dietary treatment could improve the antioxidant status in patients with type 2 diabetes mellitus. This study was undertaken to determine if erythrocyte Cu/Zn SOD and GSH-Px activities correlate with dietary nutrients in 35 selected type 2 diabetic patients (21 women and 14 men) without diabetic complications. RESULTS: We found that erythrocyte Cu/Zn SOD was diminished in patients with poor controlled diabetes and GSH-Px activity was significantly decreased in obese compared with non-obese type 2 diabetic patients (1.07+/-0.87 and 2.36+/-1.99 U/ml, respectively; P=0.024). Both erythrocyte Cu/Zn SOD and GSH-Px activities were positively correlated to erythrocyte omega3-polyunsaturated fatty acids (PUFA). In non-obese diabetic patients, only GSH-Px activity was correlated negatively to the fraction of linoleic acid (18:2omega6) and arachidonic acid (20:4omega6) in erythrocytes phospholipids. CONCLUSIONS: The data of this study reveal that activities of erythrocyte antioxidant enzymes were altered in type 2 diabetic patients. Further studies are needed to determine if diet supplemented with omega3-PUFA is required to improve antioxidant defense system in diabetic state.

Modulation of plasma cholesteryl ester transfer protein activity by unsaturated fatty acids in Tunisian type 2 diabetic women.

BACKGROUND AND AIM: Type 2 diabetes mellitus is associated with atherosclerosis, which has been, in part, ascribed to abnormalities in the reverse cholesterol transport system. Among the key actors involved in this pathway is cholesteryl ester transfer protein (CETP) which mediates the transfer of cholesteryl esters (CE) from HDL to apoB-containing lipoproteins. METHODS AND RESULTS: The purpose of this study was to examine CETP activity in 220 patients with type 2 diabetes mellitus (type 2 DM) treated with diet alone or diet and sulphonylurea drugs and to identify the factors that may regulate it in the diabetic state. We also examined the effect of diet on the activity of plasma CETP in a subgroup of type 2 DM women. CETP activity was assessed by measuring plasma-mediated cholesteryl ester transfer (CET) between pooled exogenous HDL and apoB-containing lipoproteins. In 220 patients with type 2 DM, CET was significantly higher in conjunction with higher plasma triglycerides and lower HDL-cholesterol compared to 100 matched healthy controls. Correlation analysis showed that CETP activity was significantly correlated with the HDL-C to apoA1 ratio (r = -0.205, P = 0.003) and to LDL-C to HDL-C ratio in diabetic women (P = 0.010). Furthermore, CETP activity was correlated marginally with total energy intake (P = 0.052) but to a statistically significant extent with the amount of fat consumed daily (P = 0.008). A significant negative correlation was found between plasma CETP activity and MUFA of plasma phospholipids or free PUFA (P = 0.032), especially with omega3-fatty acids (P = 0.001). CONCLUSION: Our findings indicate that CET is accelerated in patients with type 2 DM and that this may be regulated by dietary fatty acids in the diabetic state.

Association of plasma cholesteryl ester transfer protein activity and polymorphism with coronary artery disease extent in Tunisian type II diabetic patients.

INTRODUCTION: Cholesteryl ester transfer protein (CETP), a key protein in reverse cholesterol transport, has a controversial role in atherosclerosis. OBJECTIVES: : We investigated CETP activity and polymorphism in Tunisian type II diabetes and its relationship with coronary artery disease (CAD). DESIGN AND METHODS: 173 type II diabetic patients with or without CAD were compared to 67 controls. RESULTS: The HDL cholesterol concentration was low in a Tunisian population. The B1 allele of the CETP gene was associated with a low concentration of HDL cholesterol and was more frequent in Tunisians than in other populations. In type II diabetic patients, the B1 allele was associated with increased prevalence of CAD only in men (OR=0.357, CI=0.161-0.791, P=0.01). The CETP activity increased in type II diabetic patients compared to controls (P=0.05). Furthermore, the CETP activity was increased in patients with double or triple vessel disease compared to those with single vessel disease (P=0.025). CONCLUSIONS: Our data are in favour of an association between CETP and developing CAD, as well as the extent of CAD.

Lipids and lipoprotein(a) concentrations in Tunisian type 2 diabetic patients; Relationship to glycemic control and coronary heart disease.

The aim of this study was to evaluate plasma lipoprotein(a) [Lp(a)] concentrations in Tunisian patients with type 2 diabetes mellitus (DM), to correlate the values with other lipid parameters, and to examine the relationship to glycemic control and coronary heart disease (CHD). Diabetic patients with and without CHD (n=200) had significantly higher levels of Lp(a) (327.94+/-239.93 mg/l) and a greater proportion of elevated (>300 mg/l) Lp(a) concentrations (46%) compared with 100 healthy nondiabetic controls (269.83+/-225.6 mg/l, P<.01, and 26%, P<.01), while there were no statistically significant difference between diabetics without CHD (n=100) and controls. No significant association of Lp(a) with glycemic control (HbAlc or fasting blood glucose) was noted in diabetic patients. Positive correlations were observed between Lp(a) levels and total cholesterol and LDL-C in all diabetic patients and particularly in diabetic men. Male patients with CHD showed significantly higher plasma Lp(a) levels than those without CHD (P=.023), and 57.3% of patients with CHD showed increase (>300 mg/l) Lp(a) compared with 33.3% of patients without CHD. Elevated levels of Lp (a) and abnormal lipid profile in diabetic men suggest their involvement in atherogenesis and subsequent development of CHD.

[Lipoprotein (a) and ischemic heart diseases in patients with type 2 diabetes]. / Lipoprotéine (a) et cardiopathies ischémiques chez les patients diabétiques de type 2.

Lipoprotein (a) is a new independent coronary risk factor, but the role of lipoprotein (a) in type 2 diabetes remains controversial. The objective of this study was to demonstrate the relationship between the level of lipoprotein (a) and the coronary artery diseases (CAD) in type 2 diabetes. Recruitment was carried out in 3 groups of patients: Group 1: 110 control subjects, Group 2: 115 diabetics (D), Group 3: 105 diabetics with CAD (DC). The mean age was, 51 + 7; 52 + 6; 56 + 6 respectively. Total cholesterol, triglyceride, HDL-C, LDL-C, Apo A-I, Apo B and lipoprotein (a) were measured for the patients. The Lp (a) level was significantly higher in the diabetic groups as compared to the controls (p < 0.05), but this level was different between D and DC: 312 + 232 vs 347.8 + (NS). However, when the Lp (a) level is higher than 300 mg/ml, there is a significant difference between DC and D (53% vs 42% p = 0.05). There is no correlation between Lp level and total cholesterol; however, there is a significant variation of Lp (a) level with LDL-C (r = -0.14, P = 0.01). There is a negative correlation between Lp (a) and HDL-C (r = -0.13, p = 0.03), Lp (a) and ApoA-I (r = - 0.11, p = 0.05); but there is a positive correlation between Lp (a) and ApoB (r = 0.14, p = 0.02). Lp(a) level higher than 300 mg/L constitutes a coronary risk factor in type 2 diabetes. This contributes, with the other lipid disorders, to the increase of the coronary risk factors in diabetes.