RESUMEN
Lipid profile is often performed on heparinized-plasma because nothing in particular is explained in the technical data sheet about anticoagulant and because few data (mainly with EDTA anticoagulant) are available in literature. In order to evaluate heparinized-plasma vs serum differences, 50 normo- or hyperlipidemic samples were collected and assayed in 3 clinical laboratories in Lyon on Hitachi analysers with Roche Diagnostic reagents. Lipid values are lower in plasma than in serum; the average negative bias for cholesterol levels is 2 to 4,5% and for triglycerides about 3%, depending on the laboratory; the effect on HDL-cholesterol values is not significant. These results were confirmed by manual procedure on 28 samples with Roche Diagnostic reagent and two similar other reagents (Biomerieux and Randox). A negative bias of 4% on total cholesterol and triglycerides levels is not very important for clinical diagnosis but it is more serious for LDL-cholesterol estimated with Friedewald equation; LDL-cholesterol value needs accuracy because it is a therapeutic goal with statin therapy and an high negative bias (until 0,70 g/L in our results) is unacceptable; moreover, there is a real risk of providing false total cholesterol results. Therefore it is essential to collect blood for lipid profile without any anticoagulant.
Asunto(s)
Anticoagulantes/sangre , Colesterol/sangre , Heparina/sangre , Triglicéridos/sangre , Anticoagulantes/farmacología , Heparina/farmacología , HumanosRESUMEN
AIMS/HYPOTHESIS: Non-alcoholic steatohepatitis is frequent in Type II (non-insulin-dependent) diabetes mellitus and can lead to fibrosis and cirrhosis. The interindividual variability in the occurrence of nonalcoholic steatohepatitis suggests, however, a genetic modulation. Microsomal triglyceride transfer protein (MTP) is necessary for the assembly and secretion of VLDL and when the protein is not functional, such as in abetalipoproteinaemia, a steatohepatitis occurs. We therefore assessed the association between a functional polymorphism in the promoter region of MTP gene (-493 G/T) and the biological features of steatohepatitis in Type II diabetic patients. METHODS: We studied 271 patients with Type II diabetes. Determination of -493 G/T polymorphism was made by PCR-RFLP. Increased liver enzymes were used as surrogates of liver steatosis and alanine aminotransferase concentration was the outcome variable for the multivariate analysis. Liver ultrasonography was available for a subgroup of patients with newly diagnosed diabetes. RESULTS: The proportion of patients with increased alanine aminotransferase was higher in GG than in GT and TT subgroups (23%, 11% and 6%, respectively, p = 0.01). Additionally, patients with high alanine aminotransferase concentrations were more likely to be young (p = 0.01), male (p = 0.001), obese (p = 0.04) and have low HDL-cholesterol (p = 0.01). In multivariate analysis, the MTP genotype was independently associated with alanine aminotransferase concentration (p = 0.0023) as well as sex and body mass index but not HDL-cholesterol. CONCLUSION/INTERPRETATION: The -493 G/T MTP gene polymorphism is associated with biological surrogates of steatohepatitis in patients with Type II diabetes. The G allele which is responsible for a decrease in MTP gene transcription is prone to increase the intrahepatic triglycerides content, conferring by this a genetic susceptibility for steatohepatitis.
Asunto(s)
Proteínas Portadoras/genética , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/genética , Glicoproteínas , Hepatitis Crónica/etiología , Polimorfismo Genético , Regiones Promotoras Genéticas , Adulto , Anciano , Apolipoproteínas/genética , Proteínas de Transferencia de Ésteres de Colesterol , Diabetes Mellitus Tipo 2/fisiopatología , Femenino , Francia , Genotipo , Hepatitis Crónica/genética , Hepatitis Crónica/fisiopatología , Humanos , Hígado/diagnóstico por imagen , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Ultrasonografía , Población BlancaRESUMEN
Only a few cases of type I hyperlipidemia occurring in patients with autoimmune disease have been reported. We describe the case of a 35-yr-old woman suffering from severe type I hyperchylomicronemia. A combination of various hypolipidemic treatments, including strict hypolipidemic dietary therapy and administration of fibrates or n-3 fatty acids, was inefficient. Because of a history of familial autoimmunity, we introduced an immunosuppressive therapy that resulted in consistent long term and stable remission. Two attempts to reduce the immunosuppressor dose resulted in major relapses. To explain the defect of chylomicron hydrolysis, we investigated the postheparin plasma lipase activities. Hepatic triglyceride lipase activity was normal, whereas that of lipoprotein lipase (LPL) was reduced to about 30% of normal. Immunosuppressive therapy resulted in a complete and durable normalization of LPL activity. Using Western blot analysis, we found in the plasma of the patient a circulating IgG specifically directed against LPL, which became undetectable during immunosuppressive therapy. Western blot analysis revealed that the whole circulating anti-LPL autoantibody was bound to chylomicrons. Proteins extracted from patient's chylomicrons were able to induce a dose-related inhibition of LPL activity in vitro, whereas that of hepatic triglyceride lipase remained unchanged. These data constitute the first description of autoimmune hyperchylomicronemia due to an exclusive defect of LPL activity, and they show that a complete remission has been obtained after immunosuppressive therapy. Finally, our finding that the anti-LPL autoantibody is bound to chylomicrons emphasizes their previously unrecognized ability to transport LPL, already described for other lipoprotein fractions.