Prevalence of diabetic peripheral neuropathy and relation to glycemic control therapies at baseline in the BARI 2D cohort

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74968/1/j.1529-8027.2009.00200.x.pd

Detection of silent myocardial ischemia in asymptomatic patients with diabetes: results of a randomized trial and meta-analysis assessing the effectiveness of systematic screening

<p>Abstract</p> <p>Background</p> <p>Most guidelines recommend a systematic screening of asymptomatic high risk patients with diabetes for silent ischemia, but the clinical benefit of this strategy has not been demonstrated compared with the simple control of cardiovascular risk factors. We sought to determine whether referring asymptomatic diabetic patients for screening of silent ischemia decreases the risk of cardiovascular events compared with usual care.</p> <p>Methods</p> <p>DYNAMIT was a prospective, randomized, open, blinded end-point multicenter trial run between 2000 and 2005, with a 3.5 year mean follow-up in ambulatory care in 45 French hospitals. The study included 631 male and female with diabetes aged 63.9 ± 5.1 years, with no evidence of coronary artery disease and at least 2 additional cardiovascular risk factors, receiving appropriate medical treatment. The patients were randomized centrally to either screening for silent ischemia using a bicycle exercise test or Dipyridamole Single Photon Emission Computed Tomography (N = 316), or follow-up without screening (N = 315). The main study end point was time to death from all causes, non-fatal myocardial infarction, non-fatal stroke, or heart failure requiring hospitalization or emergency service intervention. The results of a meta-analysis of DYNAMIT and DIAD, a similar study, are also presented.</p> <p>Results</p> <p>The study was discontinued prematurely because of difficulties in recruitment and a lower-than expected event rate. Follow-up was complete for 98.9% patients regarding mortality and for 97.5% regarding the main study end point. Silent ischemia detection procedure was positive or uncertain in 68 (21.5%) patients of the screening group. There was no significant difference between the screening and the usual care group for the main outcome (hazard ratio = 1.00 95%CI 0.59 to 1.71). The meta-analysis of these and DIAD results gave similar results, with narrower confidence intervals for each endpoint.</p> <p>Conclusions</p> <p>These results suggest that the systematic detection of silent ischemia in high-risk asymptomatic patients with diabetes is unlikely to provide any major benefit on hard outcomes in patients whose cardiovascular risk is controlled by an optimal medical treatment.</p> <p>Trial registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00627783">NCT00627783</a></p

The Anti-Ischemic and Anti-Anginal Properties of Statins

Angina pectoris resulting from myocardial ischemia afflicts half of all patients with coronary heart disease (CHD). Chronic angina remains a major public health burden despite state-of-the-art therapies, and improvement in survival from myocardial infarction and CHD has only increased its prevalence. There is growing experimental and clinical evidence pointing to the anti-ischemic and anti-anginal properties of statins. Some data suggest that the degree of anti-ischemic efficacy of statins may be comparable to the current standard pharmacologic and mechanical strategies. The pleiotropic effects of statins are postulated to be primarily responsible for their anti-ischemic and anti-anginal properties. These include improvement of endothelial function, enhancement of the ischemic vasodilatory response, modulation of inflammation, and protection from ischemia-reperfusion injury. The anti-ischemic effects of statins further strengthen their role as a crucial component of the optimal medical therapy for CHD

Clinical Study Sex, Prescribing Practices and Guideline Recommended, Blood Pressure, and LDL Cholesterol Targets at Baseline in the BARI 2D Trial

Background. Research has shown less aggressive treatment and poorer control of cardiovascular disease (CVD) risk factors in women than men. Methods. We analyzed sex differences in pharmacotherapy strategies and attainment of goals for hemoglobin A1c (HbA1c), blood pressure (BP), and low density lipoprotein cholesterol (LDL-C) in patients with type 2 diabetes and established coronary artery disease enrolled into the BARI 2D trial. Results. Similar numbers of drugs were prescribed in both women and men. Women were less frequent on metformin or sulfonylurea and more likely to take insulin and to be on higher doses of hydroxymethylglutaryl-CoA reductase inhibitors (statins) than men. After adjusting for baseline differences and treatment prescribed, women were less likely to achieve goals for HbA1c (OR = 0.71, 95% CI 0.57, 0.88) and LDL-C (OR = 0.64, 95% CI 0.53, 0.78). More antihypertensives were prescribed to women, and yet BP ≤ 130/80 mmHg did not differ by sex. Conclusions. Women entering the BARI 2D trial were as aggressively treated with drugs as men. Despite equivalent treatment, women less frequently met targets for HbA1c and LDL-C. Our findings suggest that there may be sex differences in response to drug therapies used to treat diabetes, hypertension, and hyperlipidemia. Background Control of blood glucose, blood pressure (BP), and lowdensity lipoprotein cholesterol (LDL-C) in patients with type 2 diabetes (DM) and cardiovascular disease (CVD) is key to achieve optimal outcomes The bypass angioplasty revascularization investigation 2 diabetes (BARI 2D) trial was designed to evaluate outcomes in a cohort of patients with type 2 diabetes and known angiographically documented coronary artery disease (CAD), defined as one or more significant lesions deemed suitable for elective revascularization Methods BARI 2D (ClinicalTrials.gov Identifier: NCT00006305) is a multicenter, randomized NIH-funded trial designed to determine optimal treatment strategies for patients with DM and documented CAD suitable for elective revascularization. A detailed description of the study design and patient population has been previously reported At the time of randomization, demographics, clinical history, physical exam, test results, and medications were collected. HbA1c and lipids were measured in a BARI 2D core laboratory and secondarily at point of care for clinical management decisions. Only those patients with quality baseline information were included in the present analysis. To classify level of control for study-designated treatment targets, measures of HbA1c, fasting LDL-C, and BP were collected. United States guideline recommendations for treatment goals for diabetes, hypertension, and cholesterol were set at &lt;7% for HbA1c, &lt;100 mg/dL for LDL-C, and ≤130/80 mm Hg for BP during the BARI 2D recruitment years Therapeutic agents were categorized into antianginal/antihypertensive, antiplatelet/anticoagulant, antihyperlipidemic, and antidiabetes agents. Antidiabetes drugs were further subdivided into insulin providing (IP), insulin sensitizing (IS), and IP-IS neutral Statistical comparisons of proportions and means were made between sexes for demographic variables, clinical history, lab measures, and use of pharmacotherapeutic agents. For lipid lowering and oral diabetes agents, the proportion of patients whose clinical measures were at target was also compared by sex according to dose stratification. Chi-square tests and -tests were performed as appropriate; values less than 0.05 were considered statistically significant. In order to test sex differences in achieving treatment goals, outcomes of multiple logistic regression models for the defined targets of HbA1c and LDL-C BP were evaluated. Odds ratios of achieving treatment targets for women and men were calculated using logistic models adjusted for age, race ethnicity, education, physical activity, current cigarette smoking status, BMI, duration of diabetes, history of CAD prior to enrollment, hypertension, and number of relevant medications. All analyses were performed using SAS version 9.1.3 (Cary, NC). Results Among the 2368 patients enrolled, 2321 subjects had quality data and were included in the analysis. Among this group, there were 686 women, (mean age 62.9 years, 44.5% nonwhite) and 1635 men (mean age 62.2 years; 30.2% nonwhite). Demographic and clinical history characteristics are shown in The average number of drugs prescribed for each category of risk was determined. Within the category of antidiabetes agents, the number of drugs being taken did not differ between women and men (1.54 ± 0.81 versus 1.58 ± 0.88, = 0.30). However, women were taking more antihypertensive drugs (2.36 ± 1.05 versus 2.17 ± 1.01, &lt; 0.001) and fewer lipid lowering drugs (0.84 ± 0.53 versus 0.91 ± 0.58, = 0.004) than men. The average number of drugs being taken for the 4 risk categories assessed, including antiplatelet/anticoagulants, approached 7 agents and did not differ between women and men (6.64 ± 2.08 versus 6.57 ± 2.17, = 0.43). An analysis by sex of the percent of subjects who met the prespecified clinical targets for HbA1c, BP, LDL-C, and BP is detailed in Discussion Control of CVD risk factors substantially improves outcome among high-risk patients with DM [1]. Based on this information, clinical guidelines specific to individuals with diabetes that were in effect at the time of BARI 2D recruitment specified benchmark targets for control of HbA1c, LDL-C, and BP. The BARI 2D baseline data analysis allows comparison of physician prescribing practices, intensity of drug therapy prescribed, and degree of attainment of standards of care for HbA1c, LDL-C, and BP in women and men with DM 4 International Journal of Endocrinology diabetes, and BMI. In addition, HbA1c was adjusted for a number of diabetes agents; lipids targets were adjusted for a number of lipids agents and CABG or PCI prior to randomization; blood pressure target was adjusted for a number of antihypertensive agents, CABG or PCI prior to randomization, and history of hypertension. The attainment on all 3 targets was controlled for a number of total drugs, CABG or PCI prior to randomization, and history of hypertension. and established CAD across a diversity of physician practice settings. The findings of these baseline data suggest that women enrolled in the BARI 2D trial were as intensively treated with drugs for DM and CVD prevention as men at study entry, with the exception of aspirin which was taken by fewer women than men. Despite equivalence in prescribing practices, women met benchmark targets for HbA1c and LDL-C less often than men. The adjusted odds ratio was in the same direction and of similar magnitude for HbA1c and LDL-C, compared with the unadjusted odds. This demonstrates a robust relationship between sex and achievement of targets. Our findings are consistent with some prior reports that demonstrated that women are less likely than men to achieve control of HbA1c [6, Women have been shown to receive less aggressive therapies to treat or prevent CVD than men It is possible that there are inherent biological differences by sex in the response to the pharmacotherapeutic agents used to treat CVD. For example, studies have shown sex differences in the biologic and clinical response to antiplatelet drugs It is also possible that the differences in the outcomes reported by sex relate to higher pretreatment levels of HbA1c, LDL-C, and BP. Some studies have demonstrated that the ability to adequately lower LDL-C is directly correlated with starting LDL-C values Limitations Baseline data presented in this analysis were obtained by each subject&apos;s self-report. Therefore, information on drugs previously prescribed, their side effects, and information on subject adherence with the prescribed therapy were not available. Each of these variables could potentially impact sex differences in target attainment and limits our ability to determine whether the differential attainment of targets between the sexes is due to adherence factors or actual response to therapy. In addition, the recruitment of subjects from academic medical centers may bias the data, limiting the ability to extrapolate findings to community practices. Conclusions Women enrolling in BARI 2D were being treated as intensively with diabetes, lipid lowering, and blood pressure drugs as men. Despite equivalence of therapies prescribed, including number of agents prescribed and an apparently equivalent degree of drug dose titration, women less frequently met targets for HbA1c and LDL-C than men. These findings suggest that sex differences in attaining clinical targets cannot be explained solely by sex bias in drug prescribing practices. Other variables such as differences in medication adherence or differences in therapeutic responses to agents used for secondary CVD prevention among women compared to men must be considered. As we strive to decrease the percentage of both women and men with type 2 diabetes who die from CVD, further studies are needed to investigate sex-specific factors that may impact targeted management of risk factors for CVD

Triglyceride High-Density Lipoprotein Ratios Predict Glycemia-Lowering in Response to Insulin Sensitizing Drugs in Type 2 Diabetes: A Post Hoc Analysis of the BARI 2D

Glycemic management is central in prevention of small vessel and cardiovascular complications in type 2 diabetes. With the plethora of newer medications and recommendations for a patient centered approach, more information is necessary to match the proper drug to each patient. We showed that BARI 2D, a five-year trial designed to compare two different glycemic treatment strategies, was suitable for assessing different responses according to different phenotypic characteristics. Treatment with insulin sensitizing medications such as thiazolidinediones and metformin was more effective in improving glycemic control, particularly in the more insulin resistant patient, when compared to the insulin provision strategy using insulin and or sulfonylureas. Triglyceride and high density lipoprotein ratio (TG/HDL-cholesterol ratio) was found to be a readily available and practical biomarker that helps to identify the insulin resistant patient. These results support the concept that not all medications for glycemic control work the same in all patients. Thus, tailored therapy can be done using phenotypic characteristics rather than a &quot;one-size-fits-all approach. &quot

Sex, Prescribing Practices and Guideline Recommended, Blood Pressure, and LDL Cholesterol Targets at Baseline in the BARI 2D Trial

Background. Research has shown less aggressive treatment and poorer control of cardiovascular disease (CVD) risk factors in women than men. Methods. We analyzed sex differences in pharmacotherapy strategies and attainment of goals for hemoglobin A1c (HbA1c), blood pressure (BP), and low density lipoprotein cholesterol (LDL-C) in patients with type 2 diabetes and established coronary artery disease enrolled into the BARI 2D trial. Results. Similar numbers of drugs were prescribed in both women and men. Women were less frequent on metformin or sulfonylurea and more likely to take insulin and to be on higher doses of hydroxymethylglutaryl-CoA reductase inhibitors (statins) than men. After adjusting for baseline differences and treatment prescribed, women were less likely to achieve goals for HbA1c (OR = 0.71, 95% CI 0.57, 0.88) and LDL-C (OR = 0.64, 95% CI 0.53, 0.78). More antihypertensives were prescribed to women, and yet BP ≤ 130/80 mmHg did not differ by sex. Conclusions. Women entering the BARI 2D trial were as aggressively treated with drugs as men. Despite equivalent treatment, women less frequently met targets for HbA1c and LDL-C. Our findings suggest that there may be sex differences in response to drug therapies used to treat diabetes, hypertension, and hyperlipidemia