RESUMO
Platelets from patients with type 2 diabetes are characterised by hyperactivation and high level of oxidative stress. Docosahexaenoic acid (DHA) may have beneficial effects on platelet reactivity and redox status. We investigated whether moderate DHA supplementation, given as a triglyceride form, may correct platelet dysfunction and redox imbalance in patients with type 2 diabetes. We conducted a randomised, double-blind, placebo-controlled, two-period crossover trial (n=11 post-menopausal women with type 2 diabetes) to test the effects of 400 mg/day of DHA intake for two weeks on platelet aggregation, markers of arachidonic acid metabolism, lipid peroxidation status, and lipid composition. Each two week-period was separated from the other by a six-week washout. Daily moderate dose DHA supplementation resulted in reduced platelet aggregation induced by collagen (-46.5 %, p< 0.001), and decreased platelet thromboxane B2 (-35 %, p< 0.001), urinary 11-dehydro-thromboxane B2 (-13.2 %, p< 0.001) and F2-isoprostane levels (-19.6 %, p< 0.001) associated with a significant increase of plasma and platelet vitamin E concentrations (+20 % and +11.8 %, respectively, p< 0.001). The proportions of DHA increased both in plasma lipids and in platelet phospholipids. After placebo treatment, there was no effect on any parameters tested. Our findings support a significant beneficial effect of low intake of DHA on platelet function and a favourable role in reducing oxidative stress associated with diabetes.
Assuntos
Antioxidantes/uso terapêutico , Plaquetas/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/uso terapêutico , Lipídeos/sangue , Estresse Oxidativo/efeitos dos fármacos , Administração Oral , Antioxidantes/farmacologia , Ácido Araquidônico/metabolismo , Plaquetas/química , Colágeno/farmacologia , Estudos Cross-Over , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/urina , Dinoprosta/análogos & derivados , Dinoprosta/sangue , Ácidos Docosa-Hexaenoicos/farmacologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , F2-Isoprostanos/urina , Ácidos Graxos/sangue , Feminino , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Lipídeos de Membrana/sangue , Pessoa de Meia-Idade , Fosfolipídeos/sangue , Agregação Plaquetária/efeitos dos fármacos , Pós-Menopausa , Tromboxano B2/análogos & derivados , Tromboxano B2/sangue , Tromboxano B2/urina , alfa-Tocoferol/sangueRESUMO
OBJECTIVE: To provide phenotypic and functional data in new patients with APOA5 mutations and to identify genetic and metabolic factors influencing their phenotypic expression. METHODS AND RESULTS: By sequencing APOA5 gene in a cohort of 286 hyperchylomicronemic subjects, free of LPL or APOC2 mutations, we identified 4 unrelated carriers of the Q97X mutation (3 heterozygotes and 1 homozygote) and one heterozygote with a new L242P mutation. Postheparin LPL activity level was reduced by about 50% in Q97X heterozygotes and more than 90% in the Q97X homozygote, but was normal in the L242P patient after resolution of hyperchylomicronemia. Plasma apoAV was undetectable in the Q97X homozygote and in the normal range in the L242P and Q97X heterozygous carriers. In Western blot studies, the association of apoAV with plasma lipoproteins was altered in Q97X heterozygous carriers but not in the L242P carrier. Hyperchylomicronemic heterozygotes for both mutations carried an additional APOA5 variant haplotype and/or APOE variant (E2 or E4). Type 2 diabetes or metabolic syndrome were not a major phenotypic determinant. CONCLUSIONS: The L242P mutation was present in a hyperchylomicronemic proband but its causal involvement remains to be established. The Q97X mutation was clearly involved in hyperchylomicronemia with evidence of concomitant altered intravascular lipolysis, and a complete apoAV deficiency in the homozygote. The phenotypic expression variability of APOA5 mutations was mostly influenced by compound heterozygosity with APOA5 variant haplotypes plus additional genetic factors, and in a lesser extent by the metabolic environment.
Assuntos
Apolipoproteínas A/genética , Hiperlipoproteinemia Tipo I/genética , Lipólise/genética , Mutação , Adolescente , Adulto , Idoso , Apolipoproteína A-V , Apolipoproteína C-III/genética , Apolipoproteínas A/sangue , Apolipoproteínas E/genética , Western Blotting , Criança , Análise Mutacional de DNA , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/genética , Feminino , Haplótipos , Heterozigoto , Homozigoto , Humanos , Hiperlipoproteinemia Tipo I/sangue , Hiperlipoproteinemia Tipo I/tratamento farmacológico , Resistência à Insulina/genética , Lipase Lipoproteica/genética , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/genética , Pessoa de Meia-Idade , FenótipoRESUMO
As clinicians, we are faced to difficult situations in young diabetic patients. The prevalence of type 2 diabetes increases in these patients due to a rising incidence of obesity. We present two clinical observations which both illustrate the insufficiencies of the present classifications. Modern tools are now available for diagnosis such as anti-GAD65 and IA-2 antibodies, genetic tools to investigate for specific mutations, but quantitative means of beta cell mass are lacking. Clinical examination is still accurate to identify type 1 or type 2 diabetes, MODY and mitochondrial diabetes. Weight curve, lesions of acanthosis nigricans, criteria of metabolic syndrome, history of diabetes are critical factors. This problematic has important consequences in our daily practice: the right choice for rapid and good metabolic control.
