To cite this article: Sauls DL, Banini AE, Boyd LC, Hoffman M. Elevated prothrombin level and shortened clotting times in subjects with type 2 diabetes. J Thromb Haemost 2007; 5: 638-9.The partial thromboplastin time [1] and its successor, the activated partial thromboplastin time (aPTT) [2], have long been used to detect coagulation factor deficiencies and monitor replacement therapy in patients at risk of bleeding. More recently, a correlation has been reported between short aPTT values and the risk of thrombosis [3,4], as well as the risk of recurrence in patients who have already suffered a thromboembolic event [5]. High factor (F)VIII or IX levels can contribute, but are not the only determinants of a short aPTT [6]. An elevated level of prothrombin has also been associated with thrombosis [7], and elevated levels of prothrombin lead to increased thrombin generation in an in vitro model of hemostasis [8]. Thus, it seems likely that elevated prothrombin levels could contribute both to thrombotic risk and to a shortening of the aPTT.Insulin resistance and type 2 diabetes mellitus (DM) are associated with an increased risk of atherothrombotic events [9], as well. In order to determine whether the levels of prothrombin or other plasma clotting factors might play a role in the thrombotic tendency in diabetes, we assayed clotting times, and prothrombin, antithrombin, fibrinogen and plasminogen activator inhibitor-1 (PAI-1) levels in subjects with or without type 2 DM. The prothrombin time (PT) and aPTT assays were performed in the Durham Veterans Affairs Medical Center Clinical Hematology Laboratory on an STA analyzer (Diagnostica Stago, Asnie`res, France) using Neoplastin (ISI 1.3) and PTT Automate reagents, respectively. The reference range for the PT International Normalized Ratio (INR) is 0.89-1.20 and for the aPTT it is 23.5-35.1 s. Levels of prothrombin, fibrinogen and PAI-1 were determined by ELISA. The subjects were the first 40 of 81 subjects recruited into a trial on the effects of muscadine grape juice on parameters related to glycemic control and cardiovascular risk [10]. This study was conducted under a protocol approved by the Institutional Review Board of North Carolina State University. The details of this study, including subject characterization have been published previously [10]. Blood samples were collected before and after a period during which some of the subjects consumed wine or grape juice. Blood samples collected before the dietary intervention were used to assess coagulation parameters. Subjects were provisionally classified as DM based on their report of having been so diagnosed by a physician. They were subsequently reclassified based on fasting glucose, insulin and glycated hemoglobin (HbA1C) levels. Selfclassification into DM or control groups was verified for all except three subjects, who were excluded from the analysis because the fasting glucose, insulin and HbA1C levels did not allow them to be unambiguously classified. Data from a total of 10 male and 9 female controls, and 8...
Red wines and grape juices contain phenolic compounds with antioxidant properties believed to be protective against oxidative stress conditions that are associated with cardiovascular events including hypertension, insulin resistance, and Type 2 Diabetes. This study was designed to evaluate the effects of muscadine grape juice, muscadine grape wine and dealcoholized muscadine grape wine on blood constituents, antioxidant capacity, and erythrocyte membrane lipids of Type 2 diabetics and control, non-diabetic subjects. Control subjects were randomized into two groups: control group without supplementation (n = 15) and control group on muscadine juice (n = 8). Type 2 Diabetics were in the following categories: muscadine juice (n = 10), dealcoholized wine (n = 9), and muscadine wine (n = 10) groups. In addition to their regular diet, each group consumed 150 mL of the grape product. A 3-day diet record, anthropometric indices, and blood pressure were recorded. Blood samples were obtained for the analyses of erythrocyte membrane lipid, plasma total polyphenols, oxygen radical absorbance capacity (ORAC), total reduced glutathione, glycated hemoglobin, and insulin. A comprehensive metabolic panel, blood coagulating indices, and liver, renal, and cardiac function tests were determined. All tests were carried out at baseline and 28 days post-treatment. Glucose and glycated hemoglobin decreased post-supplementation in all T2D groups, with the greatest decrease observed among the T2D-wine group. Dietary chromium and biotin levels were below 50% of recommended daily value for all subjects. Serum sodium and chloride levels significantly decreased in the T2D-wine group compared to their counterparts. Blood folate and vitamin B 12 increased significantly in the T2D who were consuming dealcoholized wine compared to T2D who consumed wine. Trends of lowered triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL) were observed among T2D taking dealcoholized wine and T2D taking wine compared to T2D taking juice. Alanine aminotransferase (ALT) and aspartate transaminase (AST) were significantly lower in T2D taking wine compared to T2D who consumed dealcoholized wine. Increased ORAC values post-supplementation compared to baseline were not significant. Decreased levels of blood glucose and glycated hemoglobin post-supplementation indicated better glycemic control, especially in the T2D-wine group. Low dietary chromium and biotin indicates insulin inefficiency in stimulating glucose uptake. Reduced serum sodium and chloride levels among T2D-wine group after supplementation suggest reduced risk for hypertension. High folate and vitamin B 12 levels in T2D on dealcoholized wine indicate a favorable environment for homocysteine clearance and increased insulin sensitivity. Lowered TG, TC, and LDL among T2D taking wine and DzW suggest improved lipid metabolism. Decreased ALT and AST in T2D-wine group indicates better insulin sensitivity and reduced risk of impaired liver function. Finally, T2D-wine and DzW gro...
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