Elevated plasma factor VIII and von Willebrand factor in women with type 2 diabetes: inflammatory reaction, endothelial perturbation or else?

The association between type 2 diabetes and cardiovascular disease is long recognized. Although perturbations of haemostatic markers have been shown to be associated with macrovascular disease in patients with type 2 diabetes, it is unclear whether these are primarily due to endothelial dysfunction or a result of inflammation. The present study was undertaken to elucidate whether elevated levels of factor VIII (FVIII) and von Willebrand factor (vWF) in women with type 2 diabetes represent endothelial dysfunction, inflammation or an alternate mechanism. Sixty-four women with type 2 diabetes were evaluated using ultrasonography Doppler for carotid intima-media thickness (IMT) and were classified as group A--having no (<1  mm), group B - mild (≥1  mm and no plaque) and group C--moderate (≥1 mm and presence of plaque and stenosis) macrovascular disease. Several haemostatic markers including, FVIII, vWF and fibrinogen were assessed. In addition, thrombomodulin, a marker for endothelial damage, and high-sensitivity C-reactive protein (hsCRP), an inflammatory marker, were also measured. A significant association of elevated FVIII was found in group B and C patients (i.e. patients with IMT ≥1 mm and with plaque). Elevated fibrinogen and vWF levels were also found but confined to group C patients. No significant difference among subgroups was found for any other variable evaluated (hsCRP, thrombomodulin and FVII). In conclusion, plasma FVIII levels are elevated in women with type 2 diabetes and macrovascular disease. It also appears that this is not mediated by inflammation or endothelial injury and is likely to be due to an alternate mechanism.

Velocidade de hemossedimentação: comparação entre o método Microtest X (microssedimentação) e o método de referência Westergren: [carta ao editor] / Erythrocyte sedimentation rate: comparison between the Microtest X technique (micro-sedimentation) and the Westergren reference method: [letter to editor]

The erythrocyte sedimentation rate (ESR) is an easy and common routine laboratory technique. Over the last few decades, new methods have been proposed to reduce biological sample manipulation, to measure rates using an automated system, to optimize the workflow and to reduce blood volume from venipuncture. The aim of this study was to compare the efficacy of the Microtest X technique with the original Westergren method. EDTA blood samples of 25 subjects were submitted to both methodologies. A positive correlation (p<0.0001; R2=0.809) was found as was agreement with Bland-Altman analysis. In conclusion, the Microtest X technique allows precise and accurate measurements of ESR and can be used to replace the Westergren method. The benefits of Microtest X are the use of very small volumes of EDTA samples, it reduces sample manipulation avoiding occupational hazards and markedly reduces the analytical time.

Frequência do polimorfismo da glicoproteína IIIa de plaquetas (PlA2) em mulheres com diabetes mellitus tipo 2 / Platelet glycoprotein IIIa polymorphism (PlA2) frequency in Type 2 diabetic women

O polimorfismo da glicoproteína IIIa de plaquetas está associado a um aumento no risco de doenças arteriais coronarianas. Mulheres com diabetes mellitus tipo 2 apresentam um aumento de cinco vezes no risco para doenças arteriais coronarianas quando comparadas com mulheres não-diabéticas. O objetivo do presente estudo foi verificar a frequência do polimorfismo da glicoproteína IIIa (PlA2) em mulheres com diabetes mellitus tipo 2 e comparar com a frequência descrita na literatura. A análise do polimorfismo PlA2 foi realizada para 62 mulheres com diabetes mellitus tipo 2 através da reação em cadeia da polimerase seguida de análise do polimorfismo de tamanho de fragmento de restrição (PCR-RFLP). As frequências observadas foram 81 por cento para PlA1A1, 18 por cento para PlA1A2 e 1 por cento para PlA2A2. Não houve diferença significativa entre as frequências observadas e as frequências descritas na literatura. Nossos resultados sugerem que a frequência do polimorfismo PlA2 em mulheres com diabetes mellitus tipo 2 é a mesma observada na população em geral.

The platelet glycoprotein IIIa polymorphism is associated to an increased risk of coronary heart disease. Type 2 diabetic women present a fivefold higher risk of coronary heart disease compared to non-diabetic women. The aim of this study was to verify the frequency of the glycoprotein IIIa polymorphism (PlA2) in type 2 diabetic women and compare this result with the frequency reported for the general population. The PlA polymorphisms of 62 type 2 diabetic women were determined by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The resulting frequencies were 81 percent for PlA1A1, 18 percent for PlA1A2 and 1 percent for PlA2A2. There was no significant difference between observed frequencies and the frequencies described in the literature. Our results suggest that the frequency of the glycoprotein IIIa polymorphism, PlA2, in type 2 diabetic women is similar to that observed in general population

Plasma total homocysteine levels and methylenetetrahydrofolate reductase gene polymorphism in patients with type 2 diabetes mellitus.

BACKGROUND: Thrombotic episodes account for approximately 80% of deaths in type 2 diabetic patients. Hyperhomocysteinaemia is a well recognized independent risk factor for atherosclerosis and thromboembolism. Increased homocysteine levels may occur due to a number of factors including inherited gene polymorphism of methylenetetrahydrofolate reductase (MTHFR) C677T. Here, we evaluate plas- ma total homocysteine (tHcy) levels and frequency of the MTHFR C677T gene polymorphism in asymptomatic healthy volunteers and type 2 diabetic patients with hypertension but without nephropathy. We have also investigated the relationship between tHcy levels and the presence of MTHFR C677T gene polymorphism. METHODS: Plasma tHcy levels and MTHFR C677T genotype were investigated in a total of 53 subjects. These included asymptomatic healthy volunteers (n = 16), patients with type 2 diabetes (n = 7), subjects with hypertension (n = 12) and patients with both type 2 diabetes and hypertension (n = 18). Renal function, serum lipids and other metabolites were also assessed. RESULTS: There was no significant difference in tHcy levels between the groups studied. The frequency of MTHFR C677T gene polymorphism observed was similar to that obtained for the general Brazilian population. In patients with type 2 diabetes and hypertension but without impaired renal function, we observed no meaningful correlation between increased tHcy levels and the presence of MTHFR C677T gene polymorphism. CONCLUSIONS: Type 2 diabetics who are homozygous or heterozygous for the MTHFR C677T gene polymorphism showed normal tHcy levels. Our results further suggest that diabetes without an associated adverse risk profile is not an independent correlate of increased tHcy levels.

High-sensitivity C-reactive protein in subjects with type 2 diabetes mellitus and/or high blood pressure.

Type 2 diabetes mellitus (DM2) and high blood pressure (HBP) may contribute to the development of cardiovascular disease, and inflammation may be an important factor in these diseases. In the present study, plasma levels of high-sensitivity C-reactive protein (hs-CRP) were measured in subjects with DM2 and/or HBP and compared to those of normal subjects. Eighty-nine subjects were analyzed for hs-CRP, including 13 normotensive patients with DM2, 17 patients with HBP, 34 hypertensive patients with DM2 (DM2+HBP) and 25 normal subjects. The plasma hs-CRP levels were significantly lower in the controls than in the HBP+DM2 group (p < 0.05). DM2 associated with HBP was also correlated with increased plasma hs-CRP levels (n = 89, r = 0.25, p = 0.0162). Only hypertensive patients with DM2 had higher levels of hs-CRP, a circulating inflammatory marker, than normal subjects. This finding suggests that patients with two associated diseases have a more active inflammatory state.

High-sensitivity C-reactive protein in subjects with type 2 diabetes mellitus and/or high blood pressure

Type 2 diabetes mellitus (DM2) and high blood pressure (HBP) may contribute to the development of cardiovascular disease, and inflammation may be an important factor in these diseases. In the present study, plasma levels of high-sensitivity C-reactive protein (hs-CRP) were measured in subjects with DM2 and/or HBP and compared to those of normal subjects. Eighty-nine subjects were analyzed for hs-CRP, including 13 normotensive patients with DM2, 17 patients with HBP, 34 hypertensive patients with DM2 (DM2+HBP) and 25 normal subjects. The plasma hs-CRP levels were significantly lower in the controls than in the HBP+DM2 group (p < 0.05). DM2 associated with HBP was also correlated with increased plasma hs-CRP levels (n = 89, r = 0.25, p = 0.0162). Only hypertensive patients with DM2 had higher levels of hs-CRP, a circulating inflammatory marker, than normal subjects. This finding suggests that patients with two associated diseases have a more active inflammatory state.

Diabetes mellitus tipo 2 (DM2) e hipertensão arterial sistêmica (HAS) podem contribuir para o desenvolvimento de doenças cardiovasculares, e os processos inflamatórios relacionados a estas doenças podem ser considerados importantes fatores para o prognóstico das mesmas. O objetivo deste estudo foi determinar os níveis plasmáticos de proteína C-reativa ultra-sensível (us-PCR) em pacientes adultos com diabetes mellitus e/ou hipertensão arterial, comparando-os com indivíduos hígidos. Foram avaliadas 89 indivíduos, incluindo 13 pacientes normotensos com diabetes mellitus tipo 2 (DM2), 17 pacientes hipertensos (HAS), 34 pacientes hipertensos com diabetes mellitus tipo 2 (DM2+HAS) e 25 indivíduos hígidos. Os níveis plasmáticos de us-PCR foram significativamente mais altos no grupo DM2+HAS quando comparado com o grupo controle (p < 0,05), entretanto o mesmo não aconteceu com os grupos DM2 ou HAS. O grupo DM2+HAS também foi associado com o aumento dos níveis plasmáticos de us-PCR (r = 0,25; p < 0,05) e apresentou a maior freqüência de us-PCR > 3,0 mg/L (59 por cento). Esses dados indicam que a presença combinada de diabetes mellitus tipo 2 e hipertensão arterial promoveu uma maior expressão do estado inflamatório, refletido pelos níveis plasmáticos de us-PCR nos indivíduos avaliados.

Murine schistosomiasis mansoni: process of blood coagulation at pre-patent, acute and chronic phases, and consequence of chemotherapeutic cure on the reversion of changes.

The present study aims to elucidate in a sequential manner the changes of the blood coagulation process at different phases of experimental schistosomiasis, comprising the pre-patent, acute, intermediate and chronic phases, and the effect of chemotherapeutic cure, at the acute and chronic phases, on reversion of changes related to the coagulation factors. Mice were infected with Schistosoma mansoni cercariae, and were divided into four groups. Blood samples from these groups were collected 32, 70, 100, and 140 days after infection, corresponding to the pre-patent, acute, intermediate and chronic phases, respectively. Simultaneously, other infected groups were given oxamniquine, 70 and 140 days after infection. At the same time as blood collection from infected and/or treated animal groups, other uninfected control animal groups were punctured and maintained under the same conditions as the infected animals. The vitamin-K-dependent clotting factors were found to be more sensitive to infection at different phases, while factors VIII and XI presented hyperactivity. Results obtained 90 days after chemotherapeutic treatment with oxamniquine, administered at the acute and chronic phases, presented noticeable reversion of the main alterations in the coagulation mechanism. The present study provides unquestionable data on the development of hemostatic changes throughout the course of S. mansoni infection.

Avaliação da incidência das mutações G1691A no gene do fator V (fator V Leiden) e G20210A no gene da protrombina em pacientes com diabetes mellitus tipo 2 / Incidence of G1691A factor V gene (factor V Leiden) and G20210A prothrombin gene mutations in type 2 diabetes patients

Em virtude da alta prevalência de Diabetes mellitus tipo 2 (DM2) na população mundial e da alta taxa de mortalidade decorrente de eventos trombóticos, é de extrema importância o conhecimento das alterações no sistema hemostático em pacientes portadores deste distúrbio. A mutação no gene do fator V (G1691A - fator V Leiden) em heterozigose ou homozigose confere aos portadores o fenótipo de resistência à proteína C ativada, situação que aumenta em sete vezes o risco de desenvolver uma trombose. A mutação G20210A no gene da protrombina resulta no quadro de hiperprotrombinemia, aumentando o risco de trombose em três vezes. A pesquisa dessas mutações de interesse em trombofilia é de grande relevância considerando que a presença das mesmas pode exacerbar o estado de hipercoagulabilidade acelerando as complicações no diabetes. O presente estudo teve como objetivo avaliar a incidência dessas mutações em indivíduos hígidos (Controle, n=16), pacientes com DM2 (n=7), com hipertensão (HAS, n=12) e com DM2+HAS (n=18), através da técnica de PCR-RFLP. As freqüências encontradas nos grupos estudados foram baixas e similares àquelas observadas na população brasileira em geral. Não foi possível estabelecer correlação entre a presença da mutação e características específicas de cada grupo. Dessa forma, ainda não está claro se há ou não uma maior prevalência dessas mutações em indivíduos diabéticos e se a presença das mesmas contribui para o aumento do risco de desenvolver trombose nesses indivíduos, sendo necessário estudos mais amplos para a elucidação da questão.

Because of the high prevalence of type 2 diabetes mellitus (DM2) worldwide and the high mortality rate due to thrombotic events, it is extremely important to know about changes in the hemostatic system of such patients. Factor V mutation (G1691A - factor V Leiden) in either heterozygosis or homozygosis confers the activated protein C resistant phenotype, which increases the risk of thrombotic events by a factor of seven. The G20210A mutation of the prothrombin gene results in hyperprothrombinemia, increasing the risk of thrombotic events by a multiple of three. These mutations are of great relevance considering that the presence of one or both can contribute to a hypercoagulability state accelerating complications in diabetes. The aim of this study was to evaluate the incidence of these mutations in controls (n=16), DM2 subjects (n=7), hypertensive subjects (HAS) (n=12) and DM2+HAS subjects (n=18). The frequencies found were low and similar to those observed in the Brazilian population in general. It was not possible to establish any correlation among mutations and specific features of each group. It is still not clear if there is or not a higher prevalence of these mutations in diabetic individuals or if the mutation contributes to an increase in the risk of thrombotic events in these individuals. Further studies involving a larger number of patients are necessary in order to answer these questions.