Hyperlipidemias: Vergès B

Vergès B. · Service d'Endocrinologie, Diabétologie et Maladies Métaboliques, Hôpital du Bocage, C.H.U. Dijon, France. · Fundam Clin Pharmacol. · Pubmed #18001314 No free full text.

Abstract: Both pioglitazone and rosiglitazone are effective hypoglycaemic agents in monotherapy as in combined therapy. Interestingly, their reducing effect on fasting glycaemia and HbA1c is maintained over time, suggesting a potential protective effect of glitazones on the pancreatic beta-cells. The effects on lipids of pioglitazone are more favourable than those of rosiglitazone. Indeed, pioglitazone appears to be well suited for diabetic dyslipidaemia, increasing high-density lipoprotein (HDL)-cholesterol, decreasing triglycerides and small, dense low-density (LDL) particles with usually no effect on plasma LDL-cholesterol. Rosiglitazone also increases HDL-cholesterol, but has no effect on triglycerides and increases plasma LDL-cholesterol.

Vergès B. · Service Endocrinologie-Diabétologie et Maladies Métaboliques, Hôpital du Bocage, Dijon, France. · Curr Med Res Opin. · Pubmed #15811197 No free full text.

Abstract: BACKGROUND: Lipid abnormalities in people with diabetes are likely to play an important role in the development of atherogenesis. These lipid disorders include potentially atherogenic quantitative (increased triglyceride levels and decreased high-density lipoprotein-cholesterol [HDL-C] levels) and qualitative abnormalities of lipoproteins (changes in lipoprotein size, increase in triglyceride content of low-density lipoprotein (LDL) and HDL, glycation of apoproteins and increased susceptibility of LDL to oxidation). Guidelines from the two main diabetes organizations, the International Diabetes Federation and the American Diabetes Association, recommend the aggressive management of diabetic dyslipidaemia to reduce the risk of cardiovascular disease (CVD). Statins are the first choice pharmacological therapy to address diabetic dyslipidaemia due to their effectiveness at lowering LDL-C levels in patients with diabetes. Fibrates (peroxisome proliferator-activated receptor [PPAR]alpha ligands) target another aspect of dyslipidaemia by lower ing triglycerides (to a greater extent than statins) and raising HDL-C levels, especially when baseline levels are low. The PPARgamma agonist, pioglitazone appears to affect lipid metabolism by decreasing plasma triglycerides, increasing HDL-C and decreasing the number of small, dense atherogenic LDL particles. SCOPE: This paper provides a review of the current literature (based on searches of MEDLINE and EMBASE from 1985 to 2005, inclusive) supporting the recommendations for the management of dyslipidaemia among patients with type 2 diabetes, including new strategies involving drug combinations that achieve good glycaemic and lipidaemic control that could potentially reduce the morbidity and mortality associated with type 2 diabetes.

Vergès B. · Service endocrinologie, diabétologie et maladies métaboliques, CHU Dijon, hôpital du Bocage, Dijon, France. · Arch Mal Coeur Vaiss. · Pubmed #15669365 No free full text.

Abstract: The effectiveness of statins in the treatment of hypercholesterolaemia and the reduction in cardiovascular risk have now been clearly demonstrated. While their beneficial effects on the reduction of atherosclerosis and its clinical manifestations occur mainly due to the reduction in LDL-cholesterol, some pleiotropic actions which are independent of LDL-cholesterol have frequently been put forward in recent years. In effect, an improvement in endothelial function (increased vasodilatation in particular), an in vitro reduction in smooth muscle cell proliferation, a reduction in thrombosis, promotion of fibrinolysis and positive effects on atheromatous plaque stabilisation have been observed. Elsewhere, some anti-oxidant and anti-inflammatory properties have been attributed to statins. However, many of the described 'pleiotropic' effects are not due to the direct action of statins, but occur with the reduction in LDL-cholesterol. Furthermore, certain in vitro effects only occur at much higher than therapeutic doses. These considerations have therefore caused doubt about the clinical significance of the statins' pleiotropic effects. Finally, analysis of the results of human clinical trials on statins have proved that their effectiveness relies on the reduction in LDL-cholesterol and that the pleiotropic effects do not actually have a clinical implication.

Vergès B. · Service d'Endocrinologie, Diabétologie et Maladies Métaboliques, CHU de Dijon, 21000 Dijon. · Journ Annu Diabetol Hotel Dieu. · Pubmed #11565462 No free full text.

This publication has no abstract.

Vergès B, Petit JM. · Service Endocrinologie, Diabétologie et Maladies métaboliques, Hôpital du Bocage, F 21034 Dijon. bruno.verges@chu-dijon · Presse Med. · Pubmed #11413853 No free full text.

Abstract: HYPERLIPIDEMIA: HIV-1 protease-inhibitors therapy is associated with increased levels of triglycerides, LDL-cholesterol and Lp(a). But the understanding of hyperlipidaemia occurring in patients treated with HIV-1 protease-inhibitors is not easy since HIV infection itself is associated with lipid abnormalities and since HIV-1 protease-inhibitors therapy is also responsible for the development of a lipodystrophy syndrome (insulin resistance) which may influence lipid metabolism. However, many data indicate that HIV-1 protease-inhibitors therapy itself modifies significantly lipid metabolism. UNDERLYING MECHANISMS: The mechanisms involved in HIV-1 protease-inhibitors induced hyperlipidaemia are still unclear. HIV-1 protease-inhibitors could bind to LRP (Low density lipoprotein receptor Related Protein), impairing hepatic chylomicron-remnants and VLDL uptake. They could interact with the retinoid X receptor (RXR), which functions as a heterodimer with PPAR (Peroxisome Proliferator Activator Receptor). HIV-1 protease-inhibitors could also modify lipoprotein metabolism through cytokines.

Vergès B. · Service Endocrinologie, Diabétologie et Maladies métaboliques CHU de Dijon, Hôpital du Bocage, F-21000 Dijon. · Ann Endocrinol (Paris). · Pubmed #11240415 No free full text.

Abstract: Type 2 diabetic patients show frequent lipid abnormalities characterized by increased triglyceride and decreased HDL-cholesterol levels, but also by qualitative and metabolic abnormalities of all lipoproteins (VLDL, IDL, LDL et HDL). Treatment of diabetic hyperlipidemia is important in order to reduce the incidence of cardiovascular events, which is high in type 2 diabetes. Treatment with statins is recommended when hypercholesterolemia is associated with diabetes. But the efficacy of statins in the treatment of the typical diabetic hyperlipidemia (hypertriglycerideùmia, decreased HDL-cholesterol) remains to be demonstrated, since their effects on triglycerides and HDL-cholesterol is moderate. However, the new statins (cerivastatine, atorvastatine), which are more powerful to reduce hypertriglyceridemia could be useful for the treatment of diabetic hyperlipidemia. But, only on going clinical trials with statins in diabetic patients will be able to precise their possible efficacy on the prevention of cardiovascular disease.

Rigaud D, Tallonneau I, Vergès B. · CESG-CNRS UMR 5170, 21000 Dijon, France. · Diabetes Metab. · Pubmed #19101189 No free full text.

Abstract: High total cholesterol (TC) is common in patients with anorexia nervosa (AN), but its mechanisms remain unclear. PATIENTS AND METHODS: We prospectively studied plasma lipoprotein (LP), haptoglobin, free (f) T3, fT4, TSH, transthyretin and albumin in 120 malnourished adult AN patients (BMI: 13.5+/-1.5 kg/m(2)), 116 non-AN malnourished patients and 119 healthy subjects, matched for age and gender. RESULTS: In 18% of our AN patients, TC was higher than 270 mg/100mL (in non-AN: 5%; P<0.01). TC, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and HDL2 levels were higher in AN patients than in non-AN patients (P<0.001). Low TC (<150 mg/100mL) and LP levels were observed in 8% of AN patients, but only when BMI was less than 13 kg/m(2). Cholesterol ester transfer protein (CETP) activity was higher in AN patients than in healthy subjects. LP was positively correlated with BMI, albumin, fT3 and haptoglobin levels. In AN patients, there was a biphasic LP profile (low values when BMI was very low, normal values in an intermediate state, and high values when BMI was highest and where bulimia was also present). CONCLUSION: In AN, both high and low cholesterol-rich LP levels were observed. Low T3 and low catabolism allow LP to be maintained, while CETP activity increases cholesterol turnover as an adaptation to its low intake. In severely malnourished AN patients, this fails and LP drops. On the other hand, LP values were higher in the bingeing-purging type of AN than in the restrictive type. Recovery from AN results in the normalization of the LP profile.

Duvillard L, Caslake MJ, Petit JM, Vergès B, Gambert P, Packard CJ. · INSERM Research Center 866, Dijon F-21000, France. · Atherosclerosis. · Pubmed #18177876 No free full text.

Abstract: Very low density lipoprotein (VLDL) 1 and 2 were fractionated by heparin affinity chromatography into a bound and an unbound fraction and the different subfractions were quantified in 17 normolipidaemic (NL), 13 hypercholesterolaemic (HC), 10 hypertriglyceridaemic (HTG) and 11 combined hyperlipidaemic subjects (CHL). Unbound VLDL1 and VLDL2 were, respectively, 1.9- and 2.2-fold richer in triglycerides than bound VLDL1 and VLDL2. In HTG and CHL the concentration of all the VLDL subfractions was increased and plasma triglyceride level was correlated to unbound VLDL1 and to bound VLDL1 (respectively, r=0.86 (p<0.001) and r=0.77 (p<0.01) in HTG and r=0.73 (p<0.001) and r=0.62 (p<0.05) in CHL). In HC unbound VLDL2 and bound VLDL2 concentration were increased compared to NL and in CHL, the concentration of bound VLDL2 was particularly increased (3.2-fold compared to NL (p<0.001)). In both HC and CHL bound VLDL2 concentration was correlated to low density lipoprotein cholesterol (LDL-C) concentration (respectively, r=0.67 (p<0.01) and r=0.62 (p<0.05)). In hypertriglyceridaemic states the intravascular accumulation of both unbound and bound VLDL1 appears as the determinant of plasma triglyceride concentration, whereas in moderately hypercholesterolaemic states the concentration of bound VLDL2 is strikingly correlated to LDL-C concentration, suggesting that these two species are linked metabolically, e.g. bound VLDL2 contain the precursor pool of LDL.

Guerci B, Paul JL, Hadjadj S, Durlach V, Vergès B, Attia N, Girard-Globa A, Drouin P. · Service de Diabétologie, Maladies Métaboliques & Maladies de la Nutrition, Centre d'Investigation Clinique/INSERM, CHU de Nancy, Hôpital Jeanne d'Arc, 54201 Toul Cedex, France. · Diabetes Metab. · Pubmed #11547218 links to  free full text

Abstract: OBJECTIVES: The oral fat load tests used to study postprandial lipemia are complex and costly and time consuming. A simplified fat load test could be more convenient and more appropriate in routine clinical practice because of the number of lipid determinations required. RESEARCH DESIGN AND METHODS: We evaluated the capacity of a postprandial test model that reduced the number of blood samples taken in thirty three normal weight controls and 17 normotriglyceridemic obese patients (study 1), 10 normolipidemic type 2 diabetic patients and 7 healthy controls (study 2), and 10 hyperlipidemic type 2 diabetic patients studied before and after hypolipidemic therapy (study 3). Blood samples were taken before and up to 8 hours after giving the oral fat load containing retinol. Triglyceride (TG) and retinyl palmitate (RP) concentrations in the plasma, chylomicrons (CM) and non-chylomicron (nCM) fractions were measured. Postprandial lipid responses using conventional area under the curves (AUCc using 5 to 7 lipid determinations) were compared to a 3-point test that uses only three sample points to predict the area under the curve (AUCp: triglycerides at T0, triglycerides at average peak-time (T4), and triglycerides at T8). RESULTS: The AUCc and AUCp for triglycerides and retinyl palmitate were highly correlated in each of the groups and whatever the lipid subfraction (r=0.664 - 0.995, p<0.0001). When incremental AUC (iAUC) were used, the coefficients of correlation for triglycerides remained highly significant between iAUCc and iAUCp (r=0.718 - 0.979, p<0.01 - 0.0001). The same trend of differences was found between cases and controls when AUCp was used instead of AUCc. The means of differences between AUCc and AUCp for triglyceride values were small (0.34 - 0.74 mmol/L.h), and the confidence intervals were acceptable considering the range of the AUCs values (5.60 to 79.8 mmol/L.h for plasma triglycerides). CONCLUSIONS: We found that data obtained with a simplified model of AUC using only 3 points to analyse postprandial lipemia are well correlated with those obtained by conventional AUC, and that the AUCp allows to the same conclusions as AUCc when healthy subjects were compared to patients with altered postprandial metabolism. Thus AUCp may be a good evaluation of the AUCc, and the simplified 3-point protocol may well be used and suitable for studies on large groups of subjects who are eligible for an oral fat load test.

Desrumaux C, Athias A, Bessède G, Vergès B, Farnier M, Perségol L, Gambert P, Lagrost L. · Laboratoire de Biochimie des Lipoprotéines, INSERM U498, Université de Bourgogne Point, Dijon, France. · Arterioscler Thromb Vasc Biol. · Pubmed #9974406 links to  free full text

Abstract: Mean plasma phospholipid transfer protein (PLTP) concentrations were measured for the first time by using a competitive enzyme-linked immunosorbent assay. PLTP mass levels and phospholipid transfer activity values, which were significantly correlated among normolipidemic plasma samples (r=0.787, P<0.0001), did not differ between normolipidemic subjects (3.95+/-1.04 mg/L and 575+/-81 nmol. mL-1. h-1, respectively; n=30), type IIa hyperlipidemic patients (4. 06+/-0.84 mg/L and 571+/-43 nmol. mL-1. h-1, respectively; n=36), and type IIb hyperlipidemic patients (3.90+/-0.79 mg/L and 575+/-48 nmol. mL-1. h-1, respectively; n=33). No significant correlations with plasma lipid parameters were observed among the various study groups. In contrast, plasma concentrations of the related cholesteryl ester transfer protein (CETP) were higher in type IIa and type IIb patients than in normolipidemic controls, and significant, positive correlations with total and low density lipoprotein cholesterol levels were noted. Interestingly, plasma PLTP mass concentration and plasma phospholipid transfer activity were significantly higher in patients with non-insulin-dependent diabetes mellitus (n=50) than in normolipidemic controls (6.76+/-1. 93 versus 3.95+/-1.04 mg/L, P<0.0001; and 685+/-75 versus 575+/-81 nmol. mL-1. h-1, P<0.0001, respectively). In contrast, CETP levels did not differ significantly between the 2 groups. Among non-insulin-dependent diabetes mellitus patients, PLTP levels were positively correlated with fasting glycemia and glycohemoglobin levels (r=0.341, P=0.0220; and r=0.382, P=0.0097, respectively) but not with plasma lipid parameters. It is proposed that plasma PLTP mass levels are related to glucose metabolism rather than to lipid metabolism.