Cardiovascular disease is the leading cause of death in patients with diabetes. The BARI 2D study is designed to determine the potential value of specific treatment regimens for those with diabetes and will test the hypothesis that """"""""with a target HbA1C of less than 7.5%, a strategy of hyperglycemic management directed at insulin sensitization results inn lower 5 year mortality compared to a strategy of insulin provision."""""""" This proposed ancillary study is designed to provide mechanistic insight into potential benefits derived from two different treatment strategies employed by characterizing the thrombotic potential in those patients assigned to the aggressive medical management strategy and long-range goal is to demonstrate that treatment of diabetes with regimens that reduce thrombotic potential decreases cardiovascular risk. The results of this ancillary study should help to define the extent to which specific regimens diminish the pro- thrombotic state. Thrombotic potential will be assessed by determination of both platelet reactivity and thrombin generation and activity. In preliminary studies we have found that patients with diabetes have increased coronary intervention. Further, thrombin generation and activity is increased in diabetic subjects. Our preliminary evidence suggests that treatment with an insulin-sensitizing regimen reduces platelet reactivity, thrombin generation and thrombin activity. The BARI 2D study is ideally suited for determination of the effect of the method of glycemic control on pro-thrombotic potential.
In aim 1 we will determine platelet reactivity before and during the first year of treatment in patients randomized to medical treatment and randomized also to either an insulin-sensitizing regimen or an insulin-providing regimen. We will use a flow cytometry-based assay of platelet function that we have developed and validated.
In aim 2 we will determine the effect of treatment on thrombin generation and activity in the same group of patients. Thrombin generation will bbe determined by measeuring the concentration in blood of a cleavage fraggment (prothrombin fragment 1+2). Thrombin activity will be determined by measuring the concentration in blood of a second cleavage fragment (fibrinopeptide A). The results of the proposed studies will determine the effect of the method of hyperglycemic management on pro- thrombotic potential. Further, these results will define the importance of prothrombotic potential in diabetic subjects while potentially identifying new therapeutic targets in patients with diabetes and other insulin resistant states.
| Schneider, David J; Hardison, Regina M; Lopes, Neuza et al. (2009) Association between increased platelet P-selectin expression and obesity in patients with type 2 diabetes: a BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) substudy. Diabetes Care 32:944-9 |
| Keating, Friederike K; Sobel, Burton E; Schneider, David J (2003) Effects of increased concentrations of glucose on platelet reactivity in healthy subjects and in patients with and without diabetes mellitus. Am J Cardiol 92:1362-5 |
