Peter D Reaven

Phoenix VA Health Care System, Phoenix, Arizona, United States

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Publications (98)588.04 Total impact

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    ABSTRACT: Evidence point to vascular dysfunction and hypoperfusion as early abnormalities in Alzheimer's disease (AD); probing their mechanistic bases can lead to new therapeutic approaches. We tested the hypotheses that β-amyloid peptide induces endothelial dysfunction and oxidative stress in human microvasculature and that response will be similar between peripheral adipose and brain leptomeningeal arterioles.
    Journal of neuroscience methods. 07/2014;
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    ABSTRACT: The mechanisms underlying lipotoxic/diabetic cardiomyopathy remain poorly understood. Saturated fatty acid (SFA) levels, elevated in type 2 diabetes, induce apoptosis in many cell types including cardiomyocytes. Signaling pathways, including the p38α mitogen-activated kinase (MAPK)-dependent pathway, have been implicated in apoptosis due to a diverse range of insults.
    Biochemical and Biophysical Research Communications 06/2014; · 2.41 Impact Factor
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    ABSTRACT: OBJECTIVE Plasma adiponectin levels are reduced in type 2 diabetes mellitus (T2DM) and other insulin-resistant states. We examined whether plasma adiponectin levels at baseline and after pioglitazone treatment in impaired glucose tolerance (IGT) subjects were associated with improved insulin sensitivity (SI) and glucose tolerance status.RESEARCH DESIGN AND METHODSA total of 602 high-risk IGT subjects in ACT NOW were randomized to receive pioglitazone or placebo with a median follow-up of 2.4 years.RESULTSPioglitazone reduced IGT conversion to diabetes by 72% in association with improved β-cell function by 64% (insulin secretion/insulin resistance index) and increased tissue sensitivity by 88% (Matsuda index). In pioglitazone-treated subjects, plasma adiponectin concentration increased threefold from 13 ± 0.5 to 38 ± 2.5 μg/mL (P < 0.001) and was strongly correlated with the improvement in SI (r = 0.436, P < 0.001) and modestly correlated with glucose area under the curve during oral glucose tolerance test (r = 0.238, P < 0.005) and insulin secretion/insulin resistance index (r = 0.306, P < 0.005). The increase in adiponectin was a strong predictor of reversion to normal glucose tolerance and prevention of T2DM. In the placebo group, plasma adiponectin did not change and was not correlated with changes in glucose levels. There was an inverse association between baseline plasma adiponectin concentration and progression to diabetes in the placebo group but not in the pioglitazone group.CONCLUSIONS Baseline adiponectin does not predict the response to pioglitazone. The increase in plasma adiponectin concentration after pioglitazone therapy in IGT subjects is strongly related to improved glucose tolerance status and enhanced tissue sensitivity to insulin.
    Diabetes care 04/2014; · 7.74 Impact Factor
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    ABSTRACT: The aim of this study was to test the hypothesis that intensive glycaemic control (INT) and higher plasma C-peptide levels in patients with poorly controlled diabetes would be associated with better eye outcomes. The incidence and progression of diabetic retinopathy (DR) was assessed by grading seven-field stereoscopic fundus photographs at baseline and 5 years later in 858 of 1,791 participants in the Veterans Affairs Diabetes Trial (VADT). After adjustment for all covariates, risk of progression (but not incidence) of DR increased by 30% for each 1% increase in baseline HbA1c (OR 1.3; 95% CI 1.123, 1.503; p = 0.0004). Neither assignment to INT nor age was independently associated with DR in the entire cohort. However, INT showed a biphasic interaction with age. The incidence of DR was decreased in INT participants ≤55 years of age (OR 0.49; 95% CI 0.24, 1.0) but increased in those ≥70 years old (OR 2.88; 95% CI 1.0, 8.24) (p = 0.0043). The incidence of DR was reduced by 67.2% with each 1 pmol/ml increment in baseline C-peptide (OR 0.328; 95% CI 0.155, 0.7; p = 0.0037). Baseline C-peptide was also an independent inverse risk factor for the progression of DR, with a reduction of 47% with each 1 pmol/ml increase in C-peptide (OR 0.53; 95% CI 0.305, 0.921; p = 0.0244). Poor glucose control at baseline was associated with an increased risk of progression of DR. INT was associated with a decreased incidence of DR in younger patients but with an increased risk of DR in older patients. Higher C-peptide at baseline was associated with reduced incidence and progression of DR.
    Diabetologia 03/2014; · 6.49 Impact Factor
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    ABSTRACT: HDL carries a rich protein cargo and examining HDL protein composition promises to improve our understanding of its functions. Conventional mass spectrometry methods can be lengthy and difficult to extend to large populations. In addition, without prior enrichment of the sample, the ability of these methods to detect low abundance proteins is limited. Our objective was to develop a high-throughput approach to examine HDL protein composition applicable to diabetes and cardiovascular disease (CVD). We optimized two multiplexed assays to examine HDL proteins using a quantitative immunoassay (Multi-Analyte Profiling- MAP) and mass spectrometric-based quantitative proteomics (Multiple Reaction Monitoring-MRM). We screened HDL proteins using human xMAP (90 protein panel) and MRM (56 protein panel). We extended the application of these two methods to HDL isolated from a group of participants with diabetes and prior cardiovascular events and a group of non-diabetic controls. We were able to quantitate 69 HDL proteins using MAP and 32 proteins using MRM. For several common proteins, the use of MRM and MAP was highly correlated (p < 0.01). Using MAP, several low abundance proteins implicated in atherosclerosis and inflammation were found on HDL. On the hand, MRM allowed the examination of several HDL proteins not available by MAP. MAP and MRM offer a sensitive and high-throughput approach to examine changes in HDL proteins in diabetes and CVD. This approach can be used to measure the presented HDL proteins in large clinical studies.
    Lipids in Health and Disease 01/2014; 13(1):8. · 2.31 Impact Factor
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    ABSTRACT: Objective Our objective was to examine the role of hypertriglyceridemia on the capacity of HDL to facilitate ABCA-1 mediated cholesterol efflux in type 2 diabetes (T2DM). Methods HDL mediated cholesterol efflux through the ABCA-1 transporter was measured using BHK cell lines in samples of 71 participants with T2DM in presence or absence of high triglyceride levels (TG). Additionally, HDL mediated efflux was measured in 13 diabetic and non-diabetic participants fasting and four hours after a high-fat test challenge. Results HDL mediated cholesterol efflux function was increased in participants with T2DM with hypertriglyceridemia when compared to participants with T2DM without hypertriglyceridemia (efflux ratio mean ± standard deviation (SD), T2DM + TG: 1.17 ± 0.25 vs. T2DM – TG: 1.03 ± 0.19, p = 0.0098). In the fat challenge study, we observed a significant increase in ABCA-1 mediated cholesterol efflux capacity following an ingestion of high-fat test meal by participants in both groups of T2DM (n = 6, efflux ratio, mean ± SD, pre: 0.86 ± 0.4 vs. post: 1.34 ± 0.6, p = 0.01) and non-diabetic participants (n = 7, efflux ratio mean ± SD pre : 1.24 ± 0.31 vs. post: 1.39 ± 0.42, p = 0.04) that was partly explained by the difference in CETP activity (r = 0.6, p = 0.03). Conclusion Our study suggests that high triglyceride levels facilitate ABCA-1 mediated efflux function of HDL in part by activating CETP.
    Metabolism: clinical and experimental 01/2014; · 3.10 Impact Factor
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    ABSTRACT: Insulin resistance is a significant factor in the development of type 2 diabetes mellitus, however the connection between the Western diet and the development of insulin resistance has not been fully explained. Dietary macronutrient composition has been examined in a number of articles, and diets enriched in saturated fatty acids, and possibly in fructose, appear to be most consistently associated with the development of insulin resistance. However, mechanistic insights into the metabolic effects of such diets are lacking, and merit further study.
    Metabolism. 01/2014;
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    ABSTRACT: Insulin-like growth factor 1 (IGF1) is an important biomarker for the management of growth hormone disorders. Recently there has been rising interest in deploying mass spectrometric (MS) methods of detection for measuring IGF1. However, widespread clinical adoption of any MS-based IGF1 assay will require increased throughput and speed to justify the costs of analyses, and robust industrial platforms that are reproducible across laboratories. Presented here is an MS-based quantitative IGF1 assay with performance rating of >1,000 samples/day, and a capability of quantifying IGF1 point mutations and posttranslational modifications. The throughput of the IGF1 mass spectrometric immunoassay (MSIA) benefited from a simplified sample preparation step, IGF1 immunocapture in a tip format, and high-throughput MALDI-TOF MS analysis. The Limit of Detection and Limit of Quantification of the resulting assay were 1.5 μg/L and 5 μg/L, respectively, with intra- and inter-assay precision CVs of less than 10%, and good linearity and recovery characteristics. The IGF1 MSIA was benchmarked against commercially available IGF1 ELISA via Bland-Altman method comparison test, resulting in a slight positive bias of 16%. The IGF1 MSIA was employed in an optimized parallel workflow utilizing two pipetting robots and MALDI-TOF-MS instruments synced into one-hour phases of sample preparation, extraction and MSIA pipette tip elution, MS data collection, and data processing. Using this workflow, high-throughput IGF1 quantification of 1,054 human samples was achieved in approximately 9 hours. This rate of assaying is a significant improvement over existing MS-based IGF1 assays, and is on par with that of the enzyme-based immunoassays. Furthermore, a mutation was detected in ∼1% of the samples (SNP: rs17884626, creating an A→T substitution at position 67 of the IGF1), demonstrating the capability of IGF1 MSIA to detect point mutations and posttranslational modifications.
    PLoS ONE 01/2014; 9(3):e92801. · 3.53 Impact Factor
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    ABSTRACT: Objective To test the hypothesis that high levels of plasminogen activating inhibitor -1(PAI-1) and fibrinogen at baseline were associated with the onset and/or progression of diabetic retinopathy (DR) during the VADT.Research Design and Methods The VADT was an open-label, prospective, randomized controlled trial to test standard glycemic control (STD) compared to intensive control (INT) on cardiovascular events in patients with advanced type 2 diabetes mellitus (T2DM). Retinopathy (DR) outcomes were also collected. Incidence and progression of DR was assessed by grading 7-field stereoscopic fundus photographs at baseline and 5 years later taken in 858 of a total of 1791 participants who completed both eye examinations.ResultsOnset of DR during the study: Assignment to INT was not independently associated with decreased risk of onset of DR. However, after adjusting for multiple covariates (CVs), baseline level of PAI-1 was an independent risk factor for the onset of DR. The risk for incidence of DR increased by 12% for each 10 ng/dl increase in baseline PAI-1 concentration (OR 1.012 CI 1.00-1.024, p = 0.042).Progression of DR during the Study: Assignment to INT was not independently associated with decreased risk of progression of DR. However, there was an interaction between glycemic treatment assignment and fibrinogen level at baseline. INT was associated with decreased progression of retinopathy in those with fibrinogen less than 296 mg/dl (OR=0.55 CI 0.31- 1, p=0.03.Conclusion The results require confirmation but are consistent with greater hypercoagulabilty and inflammation, as measured by higher levels of PAI-1 and fibrinogen, being related to DR and responsiveness to INT.
    Diabetes care 10/2013; · 7.74 Impact Factor
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    ABSTRACT: OBJECTIVE Individuals with impaired glucose tolerance (IGT) are at high risk for developing type 2 diabetes mellitus (T2DM). We examined which characteristics at baseline predicted the development of T2DM versus maintenance of IGT or conversion to normal glucose tolerance.RESEARCH DESIGN AND METHODS We studied 228 subjects at high risk with IGT who received treatment with placebo in ACT NOW and who underwent baseline anthropometric measures and oral glucose tolerance test (OGTT) at baseline and after a mean follow-up of 2.4 years.RESULTSIn a univariate analysis, 45 of 228 (19.7%) IGT individuals developed diabetes. After adjusting for age, sex, and center, increased fasting plasma glucose, 2-h plasma glucose, G0-120 during OGTT, HbA1c, adipocyte insulin resistance index, ln fasting plasma insulin, and ln I0-120, as well as family history of diabetes and presence of metabolic syndrome, were associated with increased risk of diabetes. At baseline, higher insulin secretion (ln [I0-120/G0-120]) during the OGTT was associated with decreased risk of diabetes. Higher β-cell function (insulin secretion/insulin resistance or disposition index; ln [I0-120/G0-120 × Matsuda index of insulin sensitivity]; odds ratio 0.11; P < 0.0001) was the variable most closely associated with reduced risk of diabetes.CONCLUSIONS In a stepwise multiple-variable analysis, only HbA1c and β-cell function (ln insulin secretion/insulin resistance index) predicted the development of diabetes (r = 0.49; P < 0.0001).
    Diabetes care 09/2013; · 7.74 Impact Factor
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    ABSTRACT: Type 2 diabetes (T2DM) is an important risk factor for cardiovascular disease (CVD)-the leading cause of death in the US. Yet not all subjects with T2DM are at equal risk for CVD complications; the challenge lies in identifying those at greatest risk. Therapies directed towards treating conventional risk factors have failed to significantly reduce this residual risk in T2DM patients. Thus newer targets and markers are needed for the development and testing of novel therapies. Herein we review two complementary mass spectrometry-based approaches-Mass Spectrometric Immunoassay (MSIA) and tandem mass spectrometry as multiple reaction monitoring (MRM)-for the analysis of plasma proteins and post translational modifications (PTMs) of relevance to T2DM and CVD. Together, these complementary approaches allow for high-throughput monitoring of many PTMs and the absolute quantification of proteins near the low picomolar range. In this review article, we discuss the clinical relevance of the HDL proteome and Apolipoprotein A-I PTMs to T2DM and CVD as well as provide illustrative MSIA and MRM data on high density lipoprotein (HDL) proteins from T2DM patients to provide examples of how these mass spectrometry approaches can be applied to gain new insight regarding cardiovascular risk factors. Also discussed are the reproducibility, interpretation and limitations of each technique with an emphasis on their capacities to facilitate the translation of new biomarkers into clinical practice. This article is protected by copyright. All rights reserved.
    PROTEOMICS - CLINICAL APPLICATIONS 05/2013; · 1.81 Impact Factor
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    ABSTRACT: AIMS: This study examined effects of pioglitazone on body weight and bone mineral density prospectively in patients with impaired glucose tolerance since pioglitazone (TZD) increases body weight and body fat in diabetic patients and increases the risk of bone fractures. MATERIALS AND METHODS: A total of 71 men and 163 women aged 49.3 (10.7) years [mean (SD)]; BMI, 34.5 (5.9) kg/m(2) were recruited at 5 sites for measurements of body composition by dual energy x-ray absorptiometry at baseline and at conversion to diabetes or study end, if they had not converted. RESULTS: Mean follow-up was 33.6 months in the pioglitazone group and 32.1 months in the placebo group. Body weight increased 4.63±0.60 (m±SE) kg in the pioglitazone group compared to 0.98±0.62 kg in the PIO group (p <0.0001). Body fat rose 4.89±0.42 kg in the pioglitazone group compared to 1.41±0.44 kg, p <0.0001) in placebo-treated subjects. The increase in fat was greater in legs and trunk than in the arms. Bone mineral density (BMD) was higher in all regions in men and significantly so in most. PIO decreased BMD significantly in the pelvis in men and women, decreased BMD in the thoracic spine and ribs of women and the lumbar spine and legs of men. Bone mineral content also decreased significantly in arms, legs, trunk, and in the total body. CONCLUSIONS: Pioglitazone increased peripheral fat more than truncal fat and decreased bone mineral density in several regions of the body.
    Diabetes Obesity and Metabolism 04/2013; · 5.18 Impact Factor
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    ABSTRACT: OBJECTIVE Intensive glucose-lowering therapy (INT) did not reduce macrovascular events in the recent randomized trials, possibly because it did not improve or worsen other traditional or novel cardiovascular risk factors.RESEARCH DESIGN AND METHODS Standard plasma lipids, cholesterol content of lipoprotein subfractions, and plasma inflammatory and prothrombotic markers were determined in a subgroup of the Veterans Affairs Diabetes Trial (VADT) participants (n = 266) at baseline and after 9 months of INT or standard therapy.RESULTSINT lowered glycated hemoglobin (by a median of 2% vs. a median of 0.7% by standard treatment; P < 0.0001); increased BMI (4 vs. 1%; P < 0.001), total HDL (9 vs. 4%; P < 0.05), HDL2 (14 vs. 0%; P = 0.009), LDL2 (36 vs. 1%; P < 0.0001), and plasma adiponectin (130 vs. 80%; P < 0.01); and reduced triglycerides (-13 vs. -4%; P = 0.02) and small, dense LDL4 (-39 vs. -13%; P < 0.001), but had no effect on levels of plasma apolipoproteins B-100 and B-48, C-reactive protein, interleukin-6, lipoprotein-associated phospholipase A2, myeloperoxidase, fibrinogen, and plasminogen activator inhibitor 1. Incident macrovascular events were associated with baseline interleukin-6 (hazard ratio per each quartile increase 1.33 [95% CI 1.06-1.66]), total LDL (1.25 [1.01-1.55]), apolipoprotein B-100 (1.29 [1.01-1.65]), and fibrinogen (1.26 [1.01-1.57]) but not changes in any cardiovascular risk factors at 9 months.CONCLUSIONSINT was associated with improved adiponectin, lipid levels, and a favorable shift in LDL and HDL subfractions after 9 months. These data suggest that the failure of INT to lower cardiovascular outcomes occurred despite generally favorable changes in standard and novel risk factors early in the study.
    Diabetes care 03/2013; · 7.74 Impact Factor
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    ABSTRACT: AIMS/HYPOTHESIS: Chronic sub-acute inflammation contributes to the pathogenesis of type 2 diabetes mellitus and cardiovascular disease. High doses of salicylate reduce inflammation, glucose and triacylglycerols, and may improve insulin sensitivity, suggesting therapeutic potential in impaired fasting glucose and/or impaired glucose tolerance. This trial aimed to evaluate the effect of salsalate vs placebo on insulin resistance and glycaemia in impaired fasting glucose and/or impaired glucose tolerance. METHODS: We conducted a 12 week, two-centre, randomised, placebo-controlled study to evaluate the effect of salsalate (up to 4 g/day) vs placebo on systemic glucose disposal. Secondary objectives included treatment effects on glycaemia, inflammation and cardiovascular risk factors. Seventy-eight participants with impaired fasting glucose and/or impaired glucose tolerance from two VA healthcare systems were enrolled. Randomisation assignment was provided by the coordinating center directly to site pharmacists, and participants and research staff were blinded to treatment assignment. RESULTS: Seventy-one individuals were randomised to placebo (n = 36) or salsalate (n = 35). Glucose disposal did not change in either group (salsalate 1% [95% CI -39%, 56%]; placebo 6% [95% CI -20%, 61%], p = 0.3 for placebo vs salsalate). Fasting glucose was reduced by 6% during the study by salsalate (p = 0.006) but did not change with placebo. Declines in glucose were accompanied by declines in fasting C-peptide with salsalate. Insulin clearance was reduced with salsalate. In the salsalate group, triacylglycerol levels were lower by 25% (p = 0.01) and adiponectin increased by 53% (p = 0.02) at the end of the study. Blood pressure, endothelial function and other inflammation markers did not differ between groups. Adipose tissue nuclear factor κB (NF-κB) activity declined in the salsalate group compared with placebo (-16% vs 42%, p = 0.005), but was not correlated with metabolic improvements. The frequency of tinnitus was low but tended to be higher with salsalate therapy (n = 4 vs n = 2). CONCLUSIONS/INTERPRETATION: In summary, salsalate therapy was well tolerated, lowered fasting glucose, increased adiponectin and reduced adipose tissue NF-κB activity. These changes were not related to changes in peripheral insulin sensitivity, suggesting additional mechanisms for metabolic improvement. TRIAL REGISTRATION: ClinicalTrials.gov NCT00330733 FUNDING: Office of Research and Development, Medical Research Service, Department of Veterans Affairs and NIH K24 DK63214.
    Diabetologia 01/2013; · 6.49 Impact Factor
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    ABSTRACT: OBJECTIVE: To determine whether changes in standard and novel risk factors during the Actos Now for Prevention of Diabetes trial explained the slower rate of carotid intima media thickness (CIMT) progression with pioglitazone treatment in persons with prediabetes. METHODS AND RESULTS: CIMT was measured in 382 participants at the beginning and up to 3 additional times during follow-up of the Actos Now for Prevention of Diabetes trial. During an average follow-up of 2.3 years, the mean unadjusted annual rate of CIMT progression was significantly (P=0.01) lower with pioglitazone treatment (4.76×10(-3) mm/year; 95% CI: 2.39×10(-3)-7.14×10(-3) mm/year) compared with placebo (9.69×10(-3) mm/year; 95% CI: 7.24×10(-3)-12.15×10(-3) mm/year). High-density lipoprotein cholesterol, fasting and 2-hour glucose, HbA(1c), fasting insulin, Matsuda insulin sensitivity index, adiponectin, and plasminogen activator inhibitor-1 levels improved significantly with pioglitazone treatment compared with placebo (P<0.001). However, the effect of pioglitazone on CIMT progression was not attenuated by multiple methods of adjustment for traditional, metabolic, and inflammatory risk factors and concomitant medications, and was independent of changes in risk factors during pioglitazone treatment. CONCLUSIONS: Pioglitazone slowed progression of CIMT, independent of improvement in hyperglycemia, insulin resistance, dyslipidemia, and systemic inflammation in prediabetes. These results suggest a possible direct vascular benefit of pioglitazone.
    Arteriosclerosis Thrombosis and Vascular Biology 11/2012; · 6.34 Impact Factor
  • Aramesh Saremi, Gideon Bahn, Peter D Reaven
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    ABSTRACT: OBJECTIVE To determine the effect of statin use on progression of vascular calcification in type 2 diabetes (T2DM). RESEARCH DESIGN AND METHODS Progression of coronary artery calcification (CAC) and abdominal aortic artery calcification (AAC) was assessed according to the frequency of statin use in 197 participants with T2DM. RESULTS After adjustment for baseline CAC and other confounders, progression of CAC was significantly higher in more frequent statin users than in less frequent users (mean ± SE, 8.2 ± 0.5 mm(3) vs. 4.2 ± 1.1 mm(3); P < 0.01). AAC progression was in general not significantly increased with more frequent statin use; in a subgroup of participants initially not receiving statins, however, progression of both CAC and AAC was significantly increased in frequent statin users. CONCLUSIONS More frequent statin use is associated with accelerated CAC in T2DM patients with advanced atherosclerosis.
    Diabetes care 08/2012; 35(11):2390-2392. · 7.74 Impact Factor
  • Raymond Q Migrino, Peter Reaven
    Cardiovascular & hematological agents in medicinal chemistry 07/2012;
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    ABSTRACT: The incidence of type 2 diabetes (T2DM) is increasing rapidly worldwide and is a strong risk factor for cardiovascular disease (CVD) events. Although hyperglycemia is associated with increased CVD, intensive glycemic control with current diabetes medications has failed in recent large clinical trials to reduce macrovascular disease, demonstrating that intensive glucose control alone is insufficient to reduce major CVD events. A new approach to lowering glucose takes advantage of the incretin system and medications that raise or mimic glucagon-like peptide-1 (GLP-1). These agents not only improve glycemic control by mechanisms that minimize hypoglycemia, but also improve lipoprotein profiles, blood pressure control and weight loss. There is also increasing evidence that at least pharmacologic concentrations of GLP-1 or GLP-1 mimetics may improve endothelial function and have direct vascular-protective effects. Importantly, these benefits transpired even before the improvements in weight and overall glucose control occurred. It remains to be seen whether the chronic effects of GLP-1 activity on glucose, CVD risk factors and vascular function will lead to lasting beneficial effects on CVD risk. If preliminary findings on the vasculoprotective effects of GLP-1 agents are validated and confirmed in longitudinal clinical trials, this class of drugs may represent a paradigm shift in the treatment of vascular disease in both patients with diabetes and in non-diabetic individuals at high risk for CVD. Recent patents regarding GLP-1 agents are discussed in this review article.
    Recent patents on cardiovascular drug discovery. 01/2012; 7(1):2-9.
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    ABSTRACT: Diabetes is increasing rapidly worldwide and frequently results in severe vascular complications. A target glycated hemoglobin of less than 7% has commonly been recommended in hopes of preventing both macrovascular and microvascular complications. Although results from trials of intensive glycemic control have generally supported the notion that lower glycated hemoglobin values reduce microvascular disease, the evidence for similar benefits for macrovascular disease has been less clear. As macrovascular disease is the major cause of morbidity and mortality in type 2 diabetes, this remains one of the more important unresolved clinical questions. Recent results from the ACCORD, ADVANCE, and VADT studies have challenged the conventional believe that lower glycated hemoglobin values should be pursued in all diabetic patients. Factors that may influence whether intensive glucose management is advisable include duration of diabetes, pre-existing macrovascular disease, hypoglycemic unawareness, and significant comorbidities. Glycated hemoglobin goals should account for these factors and be individualized for each patient.
    Current Cardiology Reports 12/2011; 14(1):79-88.
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    ABSTRACT: The goal of the VA Diabetes Trial (VADT) was to determine the effect of intensive glucose control on macrovascular events in subjects with difficult-to-control diabetes. No significant benefit was found. This report examines predictors of the effect of intensive therapy on the primary outcome in this population. This trial included 1791 subjects. Baseline cardiovascular risk factors were collected by interview and the VA record. The analyses were done by intention to treat. Univariate analysis at baseline of predictors of a primary cardiovascular (CV) event included a prior CV event, age, insulin use at baseline, and duration of diagnosed diabetes (all P < .0001). Multivariable modeling revealed a U-shaped relationship between duration of diabetes and treatment. Modeled estimates for the hazard ratios (HRs) for treatment show that subjects with a short duration (3 years or less) of diagnosed diabetes have a nonsignificant increase in risk (HR > 1.0) after which the HR is below 1.0. From 7 to 15 years' duration at entry, subjects have HRs favoring intensive treatment. Thereafter the HR approaches 1.0 and over-21-years' duration approaches 2.0. Duration over 21 years resulted in a HR of 1.977 (CI 1.77-3.320, P < .01). Baseline c-peptide levels progressively declined up to 15 years and were stable subsequently. In difficult-to-control older subjects with type 2 DM, duration of diabetes altered the response to intensive glucose control. Intensive therapy may reduce CV events in subjects with a duration of 15 years or less and may increase risks in those with longer duration.
    Journal of diabetes and its complications 11/2011; 25(6):355-61. · 2.11 Impact Factor

Publication Stats

5k Citations
588.04 Total Impact Points

Institutions

  • 2008–2014
    • Phoenix VA Health Care System
      Phoenix, Arizona, United States
  • 2013
    • Joslin Diabetes Center
      Boston, Massachusetts, United States
  • 2004–2012
    • VHA National Center for Organization Development (NCOD)
      Cincinnati, Ohio, United States
    • Stanford University
      • Department of Medicine
      Stanford, CA, United States
  • 2011
    • University of Texas Health Science Center at San Antonio
      • Division of Diabetes
      San Antonio, Texas, United States
  • 2009
    • Arizona State University
      Phoenix, Arizona, United States
  • 2003–2008
    • Stanford Medicine
      • Department of Medicine
      Stanford, California, United States
  • 2007
    • Medical University of South Carolina
      Charleston, South Carolina, United States
  • 2006
    • United States Department of Veterans Affairs
      Bedford, Massachusetts, United States
  • 2003–2006
    • U.S. Department of Veterans Affairs
      Washington, Washington, D.C., United States
  • 2005
    • University of Southern Mississippi
      • School of Human Performance and Recreation
      Hattiesburg, MS, United States
  • 2002
    • University of Southern California
      • School of Pharmacy
      Los Angeles, California, United States
  • 1990–2002
    • University of California, San Diego
      • • Division of Endocrinology & Metabolism
      • • Department of Medicine
      San Diego, CA, United States
  • 1998
    • Indiana University-Purdue University Indianapolis
      Indianapolis, Indiana, United States