The Bypass Angioplasty Revascularization Investigation 2 Diabetes randomized trial of different treatment strategies in type 2 diabetes mellitus with stable ischemic heart disease: impact of treatment strategy on cardiac mortality and myocardial infarction.

BACKGROUND: The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial in 2368 patients with stable ischemic heart disease assigned before randomization to percutaneous coronary intervention or coronary artery bypass grafting strata reported similar 5-year all-cause mortality rates with insulin sensitization versus insulin provision therapy and with a strategy of prompt initial coronary revascularization and intensive medical therapy or intensive medical therapy alone with revascularization reserved for clinical indication(s). In this report, we examine the predefined secondary end points of cardiac death and myocardial infarction (MI). METHODS AND RESULTS: Outcome data were analyzed by intention to treat; the Kaplan-Meier method was used to assess 5-year event rates. Nominal P values are presented. During an average 5.3-year follow-up, there were 316 deaths (43% were attributed to cardiac causes) and 279 first MI events. Five-year cardiac mortality did not differ between revascularization plus intensive medical therapy (5.9%) and intensive medical therapy alone groups (5.7%; P=0.38) or between insulin sensitization (5.7%) and insulin provision therapy (6%; P=0.76). In the coronary artery bypass grafting stratum (n=763), MI events were significantly less frequent in revascularization plus intensive medical therapy versus intensive medical therapy alone groups (10.0% versus 17.6%; P=0.003), and the composite end points of all-cause death or MI (21.1% versus 29.2%; P=0.010) and cardiac death or MI (P=0.03) were also less frequent. Reduction in MI (P=0.001) and cardiac death/MI (P=0.002) was significant only in the insulin sensitization group. CONCLUSIONS: In many patients with type 2 diabetes mellitus and stable ischemic coronary disease in whom angina symptoms are controlled, similar to those enrolled in the percutaneous coronary intervention stratum, intensive medical therapy alone should be the first-line strategy. In patients with more extensive coronary disease, similar to those enrolled in the coronary artery bypass grafting stratum, prompt coronary artery bypass grafting, in the absence of contraindications, intensive medical therapy, and an insulin sensitization strategy appears to be a preferred therapeutic strategy to reduce the incidence of MI.

Real-time glucose sensing using transdermal fluid under continuous vacuum pressure in children with type 1 diabetes.

BACKGROUND: This study was designed to evaluate the accuracy and tolerance in children of an experimental device for continuous glucose monitoring. This real-time glucose sensing (RTGS) system measures transdermal fluid glucose through micropores in the stratum corneum that are kept open by continuous vacuum pressure. DESIGN AND METHODS: A comparison of self-monitored blood glucose values and RTGS values was obtained in 110 children with type 1 diabetes ranging in age from 2 to 18 years. The RTGS system was worn for two periods of 48-56 h each. Children went home and had no restrictions in diet during the data collection period. Physical activity also was not restricted, with the exception of swimming or other water immersion that would interfere with or damage the RTGS. RESULTS: The procedure for obtaining transdermal fluid was well tolerated, and adequate flow was maintained out to 48 h or more in most study participants. Comparison of RTGS glucose and self-measured glucose paired values (3,064 values) indicated 69% within Clarke Error Grid Zone A and 21% within Grid Zone B when device tracking was maintained. Errors in tracking occurred with displacement of the vacuum device, or damage to the glucose sensor. CONCLUSIONS: Transdermal fluid glucose measurements using a prototype device system were well tolerated by children with type 1 diabetes and showed good correlation with concomitant capillary glucose blood measurements. Changes in glucose as tracked by the RTGS system appeared accurate. The durability of the prototype system will need improvement.

Glucose sensing in transdermal body fluid collected under continuous vacuum pressure via micropores in the stratum corneum.

Application of continuous vacuum pressure on skin perforated with tiny micropores created by a focused beam from a low-cost laser system can result in access to a clear, transdermal body fluid (TDF) for the continuous measurement of glucose in vivo. Two clinical studies were performed to assess the feasibility of this approach. In the first study, 56 diabetic subjects were porated on either the arm or abdomen, and glucose was measured in their TDF using a custom assay system contained in a patch that was affixed to the skin above the poration site. The continuous readings of glucose in TDF were compared with fingerstick blood measured every half-hour over a 2-day period, resulting in 1,167 paired data points that yielded a correlation of 0.8745 with 97.75% of the readings in the Clarke Error Grid A and B zones. In a second study, 187 diabetic and 65 nondiabetic subjects had glucose measurements from their TDF made using a commercially available glucose strip and meter. A total of 4,059 data pairs (discrete TDF and capillary blood) were collected over a 2-day period, resulting in a correlation of 0.946 with 99% of the readings in the Clarke Error Grid A and B zones. These studies indicate that TDF drawn through micropores in the stratum corneum of the skin potentially can provide a lesser invasive and continuous method of measuring glucose in diabetic individuals.

Association between albuminuria and duration of diabetes and myocardial dysfunction and peripheral arterial disease among patients with stable coronary artery disease in the BARI 2D study.

OBJECTIVE: To evaluate the effect of prior duration of diabetes, glycated hemoglobin level at study entry, and microalbuminuria or macroalbuminuria on the extent and severity of coronary artery disease (CAD) and peripheral arterial disease. PATIENTS AND METHODS: We studied baseline characteristics of the 2368 participants of the BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) study, a randomized clinical trial that evaluates treatment efficacy for patients with type 2 diabetes and angiographically documented stable CAD. Patients were enrolled from January 1, 2001, through March 31, 2005. Peripheral arterial disease was ascertained by an ankle-brachial index (ABI) of 0.9 or less, and extent of CAD was measured by presence of multivessel disease, a left ventricular ejection fraction (LVEF) of less than 50%, and myocardial jeopardy index. RESULTS: Duration of diabetes of 20 or more years was associated with increased risk of ABI of 0.9 or less (odds ratio [OR], 1.54; 95% confidence interval [CI], 1.04-2.26), intermittent claudication (OR, 1.61; 95% CI, 1.10-2.35), and LVEF of less than 50% (OR, 2.03; 95% CI, 1.37-3.02). Microalbuminuria was associated with intermittent claudication (OR, 1.53; 95% CI, 1.16-2.02) and ABI of 0.9 or less (OR, 1.31; 95% CI, 0.98-1.75), whereas macroalbuminuria was associated with abnormal ABI, claudication, and LVEF of less than 50%. There was a significant association between diabetes duration and extent of CAD as manifested by number of coronary lesions, but no other significant associations were observed between duration of disease, glycated hemoglobin levels, or albumin-to-creatinine ratio and other manifestations of CAD. CONCLUSION: Duration of diabetes and microalbuminuria or macroalbuminuria are important predictors of severity of peripheral arterial disease and left ventricular dysfunction in a cohort of patients selected for the presence of CAD.

The impact of minor adverse event tracking on subject safety: a web-based system.

BASED ON THE ASSUMPTION THAT MINOR symptoms may presage serious events, we report four years' experience with a web-based adverse event (AE) tracking system (eAETS) designed to capture AEs of a minor nature that would not meet criteria for ethical review. The eAETS has supported 175 diverse clinical protocols, is user-friendly and navigationally intuitive, and restricts access based on protocol ownership. The user creates an initial risk profile for comparison to subsequent AEs to identify unanticipated patterns. Out of 2,440 AE reports, 1,053 did not match the risk profile. Corrective modification was recommended in 6 (13%) protocols. The eAETS provides a framework for weighing the impact of AEs on subject safety.