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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Background In patients with non-ST elevation acute coronary syndrome (NST-ACS) that is treated invasively, glycoprotein (GP) IIb/IIIa inhibitors can be used either as upstream treatment in a coronary care unit or as downstream provisional treatment in selected patients who are undergoing percutaneous coronary intervention (PCI). The relative advantage of either strategy is unknown. The purpose of this study was to assess 30-day outcome of patients enrolled in a prospective NST-ACS registry and treated invasively with either of these two therapeutic strategies. Methods Patients treated invasively (coronary arteriography within 4 days of admission), in the prospective registry ROSAI-2, were divided into two groups according to the upstream use of GPIIb/IIIa inhibitors (n = 241), or not (n = 548). In the latter group, 76 (14%) patients received GPIIb/IIIa in association with a PCI procedure. Clinical and angiographic characteristics as well as in-hospital and 30-day outcome of these two groups of patients were compared. Results The two groups were similar with respect to age, sex, presence of hypertension, diabetes, number of PCI procedures. However, patients treated with upstream GPllb/llla blockers had more frequently ST-segment depression (P = 0.002), a high TIMI risk score (P = 0.01) and were more frequently admitted to centres with Cath Lab facilities (P = 0.001). At 30-day follow-up, the composite of death, acute myocardial infarction and stroke, as well as major bleeding, was not significantly different between the two groups, although it occurred more frequently in patients who received upstream GPIIb/IIIa blockers (9.5% versus 5.7% and 1.7% versus 0.2%, respectively). By multivariate analysis, diabetes [odds ratio (OR) = 2.22, 95% confidence interval (CI) = 1.2-4.09] and a diagnosis on admission of non-Q-wave myocardial infarction (OR = 2.0, 95% Cl = 1.10-3.6) were independently related to outcome. No additional risk or benefit was related to upstream GPIIb/IIIa inhibitor treatment (OR = 1.5, 95% Cl = 0.84-2.68). Conclusions Among invasively-treated patients with NST-ACS, upstream treatment with GPIIb/IIIa inhibitors was used in those with a higher clinical risk profile, whereas downstream treatment was reserved for a limited number of patients undergoing PCI. Thirty-day outcome was similar in the two groups, irrespective of the treatment strategy used.
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PMID:Use of glycoprotein IIb/IIIa inhibitors in invasively-treated patients with non-ST elevation acute coronary syndrome. 1664 80

We evaluated the in-hospital and 1-year outcomes and predictors of admission heart failure in patients with non-ST-elevation acute coronary syndromes (NSTE-ACSs) without previous heart failure. We analyzed 4,825 patients with NSTE-ACS without a history of congestive heart failure who were included in the multicenter Canadian ACS Registries. Patients in Killip's class II/III on admission (n = 559, 11.6%) were compared with patients in Killip's class I. Patients with heart failure on admission were older (72 [64, 79] vs 64 [54, 73] years, p < 0.0001), with higher baseline creatinine levels (96 vs 88 mmol/dl, p <0.0001), more diabetes (32.2% vs 22.8%, p < 0.0001), hypertension (58% vs 52.4%, p = 0.014), previous myocardial infarction (MI; 38.9% vs 30.3%, p < 0.0001), previous stroke (13.5% vs 7.4%, p < 0.0001), and had more ST depression on admission (27.7% vs 17.3%, p < 0.0001). In-hospital treatment was similar except for a lower rate of aspirin therapy and fewer coronary interventions. Crude event rates were significantly higher in patients with heart failure (in-hospital death 3.6% vs 1.1%, p < 0.0001; death or MI 7.9% vs 4.7%, p = 0.0011; stroke 1.1% vs 0.4%, p = 0.03). One-year event rates were also higher in patients with heart failure (death 14.6% vs 4.4%, p < 0.0001; MI 9.3% vs 6.6%, p = 0.03; death or MI 21.5% vs 10.3%, p < 0.0001). Variables independently associated with heart failure were age (odds ratio 1.57, 95% confidence interval 1.43 to 1.73), diabetes mellitus (odds ratio 1.53, 95% confidence interval 1.24 to 1.89), admission ST depression (odds ratio 1.52, 95% confidence interval 1.22 to 1.90), previous MI, and baseline creatinine. Heart failure on admission was an independent predictor of in-hospital death, death or MI, and stroke and of 1-year death and death or MI. In conclusion, in patients with NSTE-ACS, heart failure on admission is associated with increased short- and long-term rates of death and MI.
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PMID:Prognostic significance of admission heart failure in patients with non-ST-elevation acute coronary syndromes (from the Canadian Acute Coronary Syndrome Registries). 1689 99

In the case of non-ST-segment elevation acute coronary syndromes (NSTE-ACSs), the acute use of certain antiplatelet agents is complicated by concerns about perioperative bleeding risks in patients requiring coronary artery bypass grafting (CABG) during the index hospitalization. As a result, clinicians often withhold potentially useful agents, such as clopidogrel, before determining patients' coronary anatomy. An accurate predictive model could allow for a better balance of this safety concern with the demonstrated benefits of agents such as clopidogrel. To create an accurate decision-making tool that would assess, at hospital presentation, the need for CABG in patients with NSTE-ACSs, we studied 61,974 high-risk patients with NSTE-ACS admitted to 311 CABG-capable hospitals participating in Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the American College of Cardiology/American Heart Association Guidelines (CRUSADE) from 2001 to 2003. A total of 8,395 patients (14%) underwent CABG during their initial hospital stay. A multivariate model was developed and identified 13 presenting clinical characteristics significantly associated with the likelihood of CABG (previous CABG, male gender, previous heart failure, diabetes, hyperlipidemia, renal insufficiency, ST depression and transient ST elevation, age > or = 75 years, previous percutaneous coronary intervention, family history of coronary artery disease, hypertension, trends in CABG rates, and previous stroke). This model had only modest predictive accuracy and calibration (c-index = 0.67). In conclusion, although certain presenting clinical features are associated with an increased likelihood of CABG in patients with NSTE-ACSs during the index hospitalization, it remains difficult to reliably identify, before diagnostic angiography, those who will subsequently undergo surgical revascularization.
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PMID:Challenges in predicting the need for coronary artery bypass grafting at presentation in patients with non-ST-segment elevation acute coronary syndromes. 1692 49

This paper provides a comprehensive up-to-date review of the medical and invasive management of patients with non- ST-segment elevation acute coronary syndromes (NSTE-ACS). The authors have summarized findings from key clinical trials published recent years that contribute to clinicians' understanding of how best to optimize therapy. The goals for the management of NSTE-ACS are rapid and accurate risk stratification, appropriate and institution-specific triage to interventional versus medical strategies and optimal pharmacologic therapy--all of which provide for a smooth and seamless transition of care between the emergency department and the cardiology service. High-risk features or absolute treatment trigger criteria that support more aggressive medical therapy (i.e., addition of small-molecule GP IIb/IIIa inhibitor to a core regimen of aspirin, enoxaparin, and in most cases, clopidogrel) and/or that would direct clinicians toward percutaneous, mechanical/interventional strategies as the preferred modality include, but are not limited to, the presence of one or more of the following: (1) elevated cardiac markers (troponin and/or CK-MB); (2) elevated levels of inflammatory markers (particularly CRP > 3 microg/dl); (3) age > 65 years; (4) presence of ST-T wave changes; (5) TIMI Risk Score greater than or equal to 4; (6) diabetes; and/or (7) clinical instability in the setting of suspected NSTE-ACS. Specific clinical, ECG and/or biochemical trigger points modulate the aggressiveness of both the medical therapy and the propensity to perform early angiography with or without subsequent revascularization in patients with NSTE-ACS. Although additional refinements and changes in ACS management are still to come, evidence-based strategies suggest that prompt mechanical revascularization is associated with the best possible clinical outcomes, particularly for patients with high-risk features and in whom benefits of adjunctive, pharmacoinvasive antithrombotic therapies can be consolidated. Patient transfer for cardiac catheterization/percutaneous coronary intervention (PCI) is strongly recommended in patients who manifest high-risk features and/or aggressive treatment trigger criteria, so that this high-risk subgroup may receive definitive, interventional and/or cardiology-directed specialty care at appropriate sites of care. When available, interventional management is preferred in these patients. The importance of safe and effective anticoagulation in the spectrum of management strategies has been confirmed, and the evidence in support of enoxaparin and other antithrombotic agents has been reviewed. Dosing recommendations for enoxaparin use in the setting of PCI have been issued by the CATH Panel and have been summarized in this consensus report. Similar recommendations have been presented for the use of oral antiplatelet agents and GP IIb/IIIa antagonists. The addition of statins, ACE-inhibitors and beta-blockers is also stressed as part of a comprehensive secondary cardioprotective strategy for patients with coronary heart disease.
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PMID:Strategies for optimizing outcomes in the NSTE-ACS patient The CATH (cardiac catheterization and antithrombotic therapy in the hospital) Clinical Consensus Panel Report. 1719 14

Phosphatase and tensin homologue deleted on chromosome 10 (PTEN), a phosphoinositide 3-phosphatase, is an important regulator of insulin-dependent signaling. The loss or impairment of PTEN results in an antidiabetic impact, which led to the suggestion that PTEN could be an important target for drugs against type II diabetes. Here we report the design and validation of a small- molecule inhibitor of PTEN. Compared with other cysteine-based phosphatases, PTEN has a much wider active site cleft enabling it to bind the PtdIns(3,4,5)P3 substrate. We have exploited this feature in the design of vanadate scaffolds complexed to a range of different organic ligands, some of which show potent inhibitory activity. A vanadyl complexed to hydroxypicolinic acid was found to be a highly potent and specific inhibitor of PTEN that increases cellular PtdIns(3,4,5)P3 levels, phosphorylation of Akt, and glucose uptake in adipocytes at nanomolar concentrations. The findings presented here demonstrate the applicability of a novel and specific chemical inhibitor against PTEN in research and drug development.
ACS Chem Biol 2006 Dec 15
PMID:A small molecule inhibitor for phosphatase and tensin homologue deleted on chromosome 10 (PTEN). 1724 Sep 68

We hypothesized that matrix metalloproteinase (MMP)-2, -9, and tissue inhibitor metalloproteinase-1, -2 (TIMP-1, -2) would be abnormal in diabetes and in acute coronary syndromes (ACS). We measured MMP-2, -9, and TIMP-1, -2 plasma levels in healthy subjects (controls), in type 2 diabetic patients, in nondiabetic patients with ACS (ACS) and in diabetic patients with ACS (DACS). We enrolled 165 controls, 181 diabetic patients, 78 ACS, and 46 DACS. We measured also BMI (body mass index), HbA(1c) (glycated hemoglobin) FPG (fasting plasma glucosa), FPI (fasting plasma insulin), HOMA index (homeostasis model assessment index), SBP (systolic blood pressure), DBP (diastolic blood pressure), TC (total cholesterol), LDL-C (low density lipoprotein cholesterol), HDL-C (high-density lipoprotein cholesterol), Tg (triglycerides), Lp(a) (lipoprotein(a)) PAI-1 (plasminogen activator inhibitor-1), Hct (homocysteine), Fg (fibrinogen), and hs-CRP (high-sensitivity C-reactive protein). A significant increase of BMI was observed in the diabetic group, in ACS and DACS patients compared to controls. A significant increase of SBP and DBP resulted in the diabetic and DACS groups, while only SBP improvement was present in ACS patients with respect to controls. A decrease in SBP and DBP was observed in the ACS group, while SBP variation was present in DACS patients compared to diabetics, and DBP increase was obtained in the DACS group with respect to ACS patients. TC, LDL-C, Tg, and Lp(a) increase was present in diabetics, while TC, Tg, and Lp(a) improvement was present in ACS and DACS patients with a significant decrease of HDL-C levels in diabetic, ACS, and DACS groups compared to controls. A decrease in LDL-C was obtained in ACS and DACS groups, while HDL-C increase was observed in these patients with respect to diabetics. Tg levels were higher in the DACS group compared to diabetics and ACS patients, respectively. Increases in PAI-1, Hct, Fg, and hs-CRP were present in diabetic and DACS groups, while PAI-1, Hct, and hs-CRP improvement was obtained in ACS patients with respect to controls. Higher PAI-1 levels came about in ACS and DACS groups, while HCT and Fg levels were lower in ACS patients compared to diabetics. An increase in Fg was present in the DACS group with respect to ACS patients. A decrease in Hs-CRP was observed in DACS patients compared to diabetics and the ACS group, respectively. Higher MMP-2, MMP-9, TIMP-1, and TIMP-2 levels were present in diabetic, ACS, and DACS patients compared to controls. Significant MMP-2, TIMP-1, and TIMP-2 increases were observed in ACS and DACS groups, while MMP-9 decreased in these patients compared to diabetics. In conclusion, MMP-2, MMP-9, TIMP-1, and TIMP-2 plasma levels were higher in diabetic, ACS, and DACS patients, which may reflect abnormal extracellular matrix metabolism in diabetes and in acute coronary syndrome.
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PMID:Comparison between metalloproteinases-2 and -9 in healthy subjects, diabetics, and subjects with acute coronary syndrome. 1804 92

During 2000 to 2002, 700 men (59 +/- 10 years) and 148 women (65 +/- 9 years) patients with first event of an ACS were randomly selected from cardiology clinics of Greek regions. Afterwards, 1078 population-based, age-matched and sex-matched controls were randomly selected from the same hospitals. The frequency ratio between men and women in the case series of patients was about 4:1, in both south and north Greek areas. Hierarchical classification analysis showed that for north Greek areas family history of coronary heart disease, hypercholesterolemia, hypertension, diabetes (explained variability 35%), and less significantly, dietary habits, smoking, body mass index, and physical activity status (explained variability 4%) were associated with the development of ACS, whereas for south Greek areas hypercholesterolemia, family history of coronary heart disease, diabetes, smoking, hypertension, dietary habits, physical activity (explained variability 34%), and less significantly body mass index (explained variability <1%), were associated with the development of the disease.
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PMID:Hierarchical analysis of cardiovascular risk factors in relation to the development of acute coronary syndromes, in different parts of Greece: the CARDIO2000 study. 1838 34

To determine the prevalence of concomitant microvascular and macrovascular complications of diabetic nephropathy we retrospectively reviewed the medical records of all 1,952 type 2 diabetic patients followed-up at Security Forces Hospital, Riyadh, Saudi Arabia from January 1989 to December 2004. There were 626 (32.1%) patients (294 (47%) were males) who developed diabetic nephropathy. Their mean age was 66.9 +/- 11.4 years, mean duration of diabetes was 15.4 +/- 7.5 years, mean age at the onset of nephropathy was 61.5 +/- 12.4 years, and mean duration of nephropathy was 3.9 +/- 3.8 years. Concomitant diabetic complications included cataract (38.2%), acute coronary syndrome (36.1%), peripheral neuropathy (24.9%), myocardial infarction (24.1%), background retinopathy (22.4%), stroke (17.6%), proliferative retinopathy (11.7%), foot infection (7.3%), limb amputation (3.7%) and blindness (3%). Hypertension was documented in 577 (92.2%) patients, dyslipidemia in 266 (42.5%) and mortality from all causes in 86 (13.7%). There were 148 (23.6%) patients with one complication, 81 (12.9%) with two, 83 (13.3%) with three, and 61 (9.7%) with four or more. Deterioration of glomerular filtration rate was observed in 464 (74%) patients and doubling of serum creatinine in 250 (39.9%), while 95 (15.2%) developed end-stage renal disease (ESRD) at the end of study and 79 (12.6%) required dialysis. Complications were significantly more prevalent among males with greater number reaching ESRD level than females (P< 0.05). Relative risks of developing complications were significant after the onset of nephropathy; ACS (1.41), MI (1.49), stroke (1.48), diabetic foot (1.6), amputation (1.58) and death (1.93). We conclude that complications of diabetes are aggressive and progressive including high prevalence of diabetic nephropathy. Careful monitoring and proper institution of management protocols should be implemented to identify diabetic patients at high risk for complications and mitigate progression into ESRD.
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PMID:Concomitant macro and microvascular complications in diabetic nephropathy. 1941 42

Reactive oxygen species are heavily involved in the pathogenesis of diabetes mellitus (DM) because the insulin-producing beta cells are particularly vulnerable to free-radical-mediated cytotoxicity. Catalytic anti-oxidants have been successfully applied for attenuation of DM and its consequences, but most recent research revealed that preventing the nitration of vital proteins/enzymes might be an even more powerful strategy. We now report an unprecedented efficiency of manganese(III) corroles regarding the protection of rat pancreatic beta cells against intracellular nitration by peroxynitrite and subsequent cell death. A comparison between analogous corroles and porphyrin metal complexes reveals significant superiority of the former in all examined aspects. This is particularly true for the positively-charged manganese(III) corrole, which decomposes peroxynitrite fast enough and through a unique catalytic mechanism that is devoid of potentially nitrating reaction intermediates.
ACS Chem Biol 2009 Nov 20
PMID:Manganese corroles prevent intracellular nitration and subsequent death of insulin-producing cells. 1971 43

Pancreatic beta-cell apoptosis is a critical event during the development of type-1 diabetes. The identification of small molecules capable of preventing cytokine-induced apoptosis could lead to avenues for therapeutic intervention. We developed a set of phenotypic cell-based assays designed to identify such small-molecule suppressors. Rat INS-1E cells were simultaneously treated with a cocktail of inflammatory cytokines and a collection of 2,240 diverse small molecules and screened using an assay for cellular ATP levels. Forty-nine top-scoring compounds included glucocorticoids, several pyrazole derivatives, and known inhibitors of glycogen synthase kinase-3beta. Two compounds were able to increase cellular ATP levels, reduce caspase-3 activity and nitrite production, and increase glucose-stimulated insulin secretion in the presence of cytokines. These results indicate that small molecules identified by this screening approach may protect beta cells from autoimmune attack and may be good candidates for therapeutic intervention in early stages of type-1 diabetes.
ACS Chem Biol 2010 Aug 20
PMID:Small-Molecule Suppressors of Cytokine-Induced beta-Cell Apoptosis. 2055 Jan 76


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