Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aspirin (acetylsalicylic acid, ASA), which is recommended for primary and secondary prevention in diabetes mellitus (DM), has been shown to have a lower antiplatelet activity in diabetic patients. We conducted a crossover designed observational study to evaluate whether there is an association between the parameters relevant to metabolic control of diabetes and platelet sensitivity to aspirin in type 2 diabetic patients. Platelets' ability to adhere and aggregate was monitored with the use of platelet function analyser (PFA-100 collagen/epinephrine closure time, CT(CEPI) or collagen/ADP closure time, CT(CADP)), classical turbidimetric aggregometry and whole blood electrical aggregometry (WBEA), using collagen (WBEA(coll)), ADP (WBEA(ADP)) and arachidonic acid (WBEA(AA)) as platelet agonists, in 48 control healthy volunteers (mean age+/-S.D., 49+/-9 years) and 31 type 2 DM patients (50+/-9 years; HbA(1c) 9.4+/-1.6%). In majority of control subjects (69%) and minority of diabetic patients (29%, p=0.0006), the use of 150 mg aspirin daily for 1 week significantly reduced platelet adhesiveness and reactivity (by 14.1% in diabetes vs. 78.6% in control, p(np)=0.0035, as expressed by the relative changes in CT(CEPI)). Aspirin reduced WBEA(coll) and WBEA(AA) to a lesser extent in diabetic patients (by 2.1% vs. 8.3% in controls, p(np)=0.0397, and by 97.3+/-12.8% vs. 100% in controls, p(np)=0.0383, respectively), which corresponded to ASA-mediated decreased aggregation in platelet-rich plasma (PRP, r(S)=0.45 and r(S)=0.78 for collagen- or arachidonate-agonized platelets, p<0.01 or lower). The maximal inhibition of platelet aggregation was lower and IC(50) higher in diabetic compared to control subjects, both in the presence of arachidonic acid (71% vs. 39%, p(np)0.0001; 0.5 microg/ml vs. 1.3 microg/ml, p<0.0001) and collagen (52% vs. 35%, p<0.0004; 1.6 microg/ml vs. 2.1 microg/ml, p<0.01). The reduced response of platelets from diabetic subjects to aspirin was associated with a higher level of HbA(1c), lower concentration of HDL-cholesterol and a higher total cholesterol concentration. Overall, there is evidence that reduced platelets response to aspirin may occur more often in diabetic patients. Poor metabolic control may play a role in the reduced platelet sensitivity to aspirin in DM patients. Thus, our findings strongly support the requirements for an excellent near-normal metabolic control and may suggest a need for alternative ASA dosing schedules in DM patients.
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PMID:Reduced sensitivity of platelets from type 2 diabetic patients to acetylsalicylic acid (aspirin)-its relation to metabolic control. 1511 64

Previous studies have demonstrated that the gastric mucosa of diabetic rats is highly vulnerable to acute injury but the influence of nonsteroidal anti-inflammatory drugs (NSAID) and their new nitric oxide (NO) releasing derivatives of aspirin (NO-ASA) on the ulcer healing under diabetic conditions has been little studied. In this study streptozocin (STZ, 70 mg/kg injected intraperitoneally) was used to induce diabetes mellitus in rats. Four weeks after STZ injection, gastric ulcers were induced using the acetic acid method and rats with gastric ulcers received the treatment with 1) aspirin (ASA, 30 mg/kg-d i.g.), 2) NO-ASA applied in equimolar dose of 50 mg/kg-d i.g., 3) rofecoxib (5 mg/kg-d i.g.), the selective cyclooxygenase-(COX)-2 inhibitor and 4) SNAP (5 mg/kg-d i.g.), a donor of NO, combined with ASA (30 mg/kg-d i.g.). Ten days after the induction of the ulcers, the healing rate and the gastric blood flow (GBF) were measured by planimetry and hydrogen (H(2))-gas clearance method, respectively and the plasma cytokine such as IL-1beta, TNF-alpha and IL-10 were determined. In addition, the effect of insulin (4 IU/day/rat i.p.) with or without the blockade of NO-synthase by L-NNA (20 mg/kg-d i.p.) on the ulcer healing and the GBF in non-diabetic and diabetic rats was determined. In the diabetic rats, a significant delay in ulcer healing (approximately by 300%) was observed with an accompanied decrease in the GBF at ulcer margin. The prolongation of the healing in diabetic animals was associated with an increase in the plasma cytokine (IL-1beta, TNF-alpha and IL-10) levels. ASA and rofecoxib, that significantly suppressed the mucosal prostaglandin (PG) E(2) generation in ulcer area, delayed significantly the rate of ulcer healing and decreased the GBF at ulcer margin, while elevating plasma IL-1beta, TNF-alpha and IL-10 concentrations in non-diabetic rats and these alterations were significantly augmented in diabetic animals. In contrast to ASA, the treatment with NO-ASA failed to influence both, the ulcer healing and GBF at ulcer margin and significantly attenuated the plasma levels of IL-1beta, TNF-alpha and IL-10 as compared to those recorded in ASA- or rofecoxib-treated animals. Co-treatment of SNAP with native ASA abolished the deleterious effect of ASA on ulcer healing, GBF at ulcer margin and luminal NO release in diabetic rats. Administration of insulin in rats with diabetes, opposed the delay in ulcer healing, and the fall in the GBF at ulcer margin and these effects were counteracted by the concurrent treatment with L-NNA. We conclude that: 1) ulcer healing is dramatically impaired in experimental diabetes and this effect involves the fall in the gastric microcirculation at the ulcer margin and increased release of proinflammatory cytokines; 2) classic NSAID such as ASA and selective COX-2 inhibitors such as rofecoxib, prolong ulcer healing under diabetic conditions probably due to suppression of endogenous PG and the fall in the GBF at the ulcer margin suggesting that both COX isoforms, namely, COX-1 and COX-2, are important sources of PG during ulcer healing in diabetes; and 3) NO-ASA counteracts the impairment of ulcer healing in diabetic rats induced by ASA, mainly due to the release of NO that compensates for PG deficiency resulting in enhancement in the GBF at ulcer margin and suppression of cytokine release in the ulcer area.
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PMID:Healing of chronic gastric ulcers in diabetic rats treated with native aspirin, nitric oxide (NO)-derivative of aspirin and cyclooxygenase (COX)-2 inhibitor. 1561 43

Reduced effectiveness of the most common antiplatelet drug, acetylsalicylic acid (ASA, aspirin), in diabetes mellitus has been associated with a lowered platelet sensitivity to ASA and related to glycemic control in diabetic patients. Our objectives were (a) to monitor the chemical background of how chronic hyperglycemia affects platelet response to ASA in diabetes and (b) to study a chemical competition between the amount of bound acetyl residues and the extent of protein glycation in blood platelets. Using whole-blood impedance aggregometry and platelet function analyzer (PFA-100) we observed a reduced platelet response to ASA in diabetic patients (14% vs. 79% for PFA-100 collagen-epinephrine occlusion time) and an association between the index of glycemic control and platelet refractoriness to ASA (r(S) = -0.378). Impaired platelet response to ASA was related to enhanced platelet protein glycation (3.6+/-0.4 in diabetes vs. 2.3+/-0.4 micromol fructosamine/microg protein in control) and reduced incorporation of acetyl residue into proteins of platelets from diabetic patients (47.4+/-2.0 in control vs. 33.1+/-0.7 micromol acetyl/microg protein in diabetic subjects). Incubation of blood platelets with increasing concentrations of glucose and ASA under in vitro conditions led to excessive modification in protein amino groups: glucose and ASA competed with each other in the course of nonenzymatic modifications, glycosylation, or acetylation, and their contributions to the occupancy of protein amino groups (R2 = 0.22 for glucose, R2 = 0.43 for ASA) were dependent upon the concentrations of glucose and ASA. Overall the effects of high glucose and high ASA on the overall occupancy of protein free amino groups are not additive. While at higher concentrations ASA overcomes the effects of hyperglycemia and retards glycation, high glucose makes acetylation less efficient, and therefore the resultant chemical modification becomes greatly reduced. In conclusion, diminished susceptibility of various platelet proteins and receptors on blood platelet membranes to acetylation and high ambient glucose might underlie the apparently differentiated sensitivity of blood platelets to ASA and determine platelet "insensitivity to aspirin" in diabetic patients.
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PMID:Increased protein glycation in diabetes mellitus is associated with decreased aspirin-mediated protein acetylation and reduced sensitivity of blood platelets to aspirin. 1572 65

Inguinal hernia repair is performed in more than 600,000 cases every year in the United States. However, the true prevalence may be even higher. Many groin hernias are not diagnosed, e.g., Sportmans' hernia, or are asymptomatic. The etiology of classic inguinal hernia, Sportsman's hernia or traumatic hernia may be different. The hernia repair is performed in agreement with a classification of the hernia, e.g., Nyhus classification. According to recent randomized controlled trials and meta-analyses open-mesh repair demonstrates several advantages in comparison to laparoscopic procedures. Laparoscopic procedures require more time and cost more, show a potential for serious complications and may be followed by an increased rate of recurrence. There may be a faster reconvalescence after laparoscopic procedures. However, there may be also a selection bias. Laparoscopic procedures are associated with specific complications, e.g., pneumomediastinum, pneumothorax, gas extravasation, trocar injuries, intraabdominal adhesions, bowel obstruction, which are rarely or never seen in open-mesh repair. In the United States we could observe an uncoupling of hernia repair from classification. In more than 90% of cases the treatment was open-mesh. In many hernia studies the hernias were classified as direct or indirect, primary or recurrent. The existing classifications are based on anatomical findings in relation to the development of the hernia: posterior floor integrity, enlarged interior ring and size of the hernia. However, the size of the hernia may not always be associated with the severity of the hernia and it may be difficult to estimate. The outcome of hernia repair may be influenced by other factors. There may be differences in the presentation of the hernia to the surgeon based on the damage done to the surrounding tissue in the inguinal canal, e.g., external ring, aponeurosis of the external oblique, inguinal ligament, which is most often accompanied by severe adhesions. Further factors influencing outcome of hernia repair may be patient-related factors, e.g., constipation, ASA classification, diabetes, smoking. A classification should be simple to use and easy to remember: (A) indirect hernia, (B) direct hernia, (C) scrotal or giant hernia, (D) femoral hernia. A and B can be classified as (0) uncomplicated, (1) posterior floor defect, (2) posterior floor defect plus defect in the anterior part of the inguinal canal. All four types (A-D) may be either primary or recurrent. In this classification combined femoral, indirect and/or direct hernias can be categorized by using the types A, B, C, or D as in a modular construction system. The category "other" is reserved for rare types of hernia, e.g., obturator hernia, Spieghelian hernia. Aggravating factors are included: Diabetes, obesity, age above 65, constipation, ASA III or more and cigarette smoking. This classification may be helpful to evaluate outcome of hernia repair with regard to patient related factors and the increased demands for the surgeon and the staff. In some health care systems the general belief is that all hernias are equal and be managed equally. However, groin hernias may be complex and need individual treatment.
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PMID:Inguinal Hernia: classification, diagnosis and treatment--classic, traumatic and Sportsman's hernia. 1585 79

Since there are few published reports regarding the impact of urologic surgery on perioperative infections, an epidemiologic analysis was performed on data from 1,156 open or laparoscopic operations in urology collected by the 21 hospitals participating in this study between September 2002 and August 2003. Prophylactic antibiotics were administered intravenously according to our protocol designed on the basis of the invasiveness and contamination levels. The surgical site infection (SSI) rates following clean, clean-contaminated and contaminated surgery were 1.2%. 5.8% and 23.4%, respectively, while the remote infection (RI) rates were 3.5%. 7.1% and 35.9%, respectively. Methicillin-resistant Staphylococcus aureus (MRSA) was most frequently isolated from SSIs as well as RIs, whereas Enterococcus faecalis and Pseudomonas aeruginosa were more frequently discovered in RIs than in SSIs. Several risk factors for SSI and/or RI, such as older age, high ASA score, obesity, diabetes, preoperative chemotherapy, long operation time and much blood loss, were identified by univariate analysis.
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PMID:Perioperative antimicrobial prophylaxis in urology: a multi-center prospective study. 1592 Sep 5

Type 2 diabetes is increasingly common worldwide and is beginning to strike younger age groups. Almost 90% of all patients with diabetes show insulin resistance, which also precedes the first symptoms of diabetes. The mechanisms underlying the development of insulin resistance are not well understood. In recent years, several studies have been published that implicate subclinical chronic inflammation as an important pathogenetic factor in the development of insulin resistance and type 2 diabetes. This opens new perspectives for diagnosis and treatment of early insulin resistance and incipient glucose intolerance. Surrogate markers for this low-grade chronic inflammation include CRP, IL-6 and TNF-alpha. Some antidiabetic agents, for example, glitazones that reduce insulin resistance, and insulin itself, reduce inflammation. Conversely, antiinflammatory drugs (ASA/NSAID) may improve glucose tolerance. Vasoactive drugs that are often prescribed to people with diabetes, for example, statins and ACE inhibitors/angiotensin receptor antagonists, also counteract inflammation and reduce the risk of type 2 diabetes. More specific and sensitive biomarkers should be identified, which may predict early disturbances in insulin sensitivity and cardiovascular risk. Also, inflammatory signalling pathways need to be explored in greater detail, and may form the basis of drugable targets against the epidemic of insulin resistance and atherosclerosis.
Diabetes Metab Res Rev
PMID:Inflammation and the etiology of type 2 diabetes. 1599 Dec 54

Increased platelet inhibition is achieved when clopidogrel is added to aspirin (acetylsalicylic acid [ASA]). A broad variability in platelet inhibition profiles during the early phases of treatment has been demonstrated and may be attributed to ASA resistance. However, the influence of ASA sensitivity on platelet function profiles of patients on long-term dual antiplatelet therapy has yet to be explored. A total of 135 patients who had previously undergone percutaneous coronary intervention on long-term (>1 month) ASA and clopidogrel therapy was included. The PFA-100 system was used to define ASA resistance. Platelet aggregation, after adenosine diphosphate (6 and 20 micromol/L) and collagen (6 microg/ml) stimuli, and platelet activation (glycoprotein IIb/IIIa activation and P-selectin expression), after adenosine diphosphate (2 micromol/L) and thrombin receptor-activating peptide (50 micromol/L) stimuli, were assessed by light transmittance aggregometry and flow cytometry, respectively. Patient variability in response to treatment was defined by the coefficient of variability. ASA resistance was found in 60 of 135 patients (44%). Patients with diabetes were more frequently ASA resistant. Collagen/epinephrine- and collagen/adenosine diphosphate-coated cartridges on the PFA-100 had shorter closure times in the ASA-resistant population compared with ASA-sensitive patients. Platelet aggregation and activation were significantly higher in ASA-resistant patients. A broad variability (coefficient of variation >0.25) in patient response to treatment was observed in ASA-resistant and -sensitive patients. In conclusion, ASA resistance is associated with increased platelet reactivity in patients on long-term dual antiplatelet treatment.
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PMID:Influence of aspirin resistance on platelet function profiles in patients on long-term aspirin and clopidogrel after percutaneous coronary intervention. 1637 81

This study sought to determine the frequency of aspirin resistance in an ambulatory population of patients with type 1 diabetes mellitus (T1D) or type 2 diabetes mellitus (T2D). Platelet aggregation was assessed during the routine clinical evaluation of 203 ambulatory patients with diabetes (T1D, n = 92; T2D, n = 111) who were recommended aspirin for primary or secondary cardiovascular protection. Consecutively received laboratory samples were evaluated using the Ultegra Rapid Platelet Function Assay-ASA. Resistance to aspirin was detected in 18.7% of diabetic aspirin users, with similar rates in T1D (21.7%, p = 0.5) and T2D (16.2%, p = 0.6). Aspirin resistance was not related to age, glycohemoglobin, total cholesterol, or a history of cardiovascular disease. Female gender was a strong independent predictor of aspirin resistance in patients with T1D (p = 0.001). Platelet aggregation was correlated with high-density lipoprotein (HDL) cholesterol in the entire cohort (r = 0.21, p = 0.005) and in patients with T1D (r = 0.32, p = 0.04) or T2D (r = 0.21, p = 0.04), such that patients with low HDL cholesterol levels were more likely to be aspirin sensitive. The results suggest that aspirin can inhibit platelet aggregation in most patients with diabetes and is a reasonable first-line antiplatelet agent in patients with diabetes.
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PMID:Comparison of aspirin resistance in type 1 versus type 2 diabetes mellitus. 1646 Oct 58

The effect of chronic hyperglycaemia on blood platelet response to acetylsalicylic acid was studied in rats with experimental diabetes. Platelet aggregation was determined in non-diabetic and streptozotocin-diabetic rats treated orally with 4 or 40 mg aspirin (ASA)/kg per day (for 8 weeks from the eighth day of diabetes) using whole blood impedance aggregometry with arachidonic acid or ADP as platelet agonists. The dose-dependent effect of ASA 'therapy' on ADP-agonized platelets was significant only in non-diabetic animals, while in diabetic rats both doses were ineffective in reducing ADP-stimulated platelet aggregation. ASA-mediated increased acetylation of platelet proteins favoured reduced platelet aggregation and slower platelet disaggregation (Pr < 0.025 or less). Interestingly, however, the occupation of platelet protein-free amino groups was significantly higher in control rats compared with diabetic rats (P < 0.001), pointing out that proteins of platelets in non-diabetic animals were more vulnerable for the ASA-induced acetylation. We conclude that chronic hyperglycaemia interferes with preventive effects of ASA on platelet reactivity. Our data validate the suggestion that the relationship between aspirin ineffectiveness and poor metabolic control, first revealed in humans, concerns also other animals' platelets and holds regardless of the model or type of diabetes.
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PMID:High glucose contributes to aspirin insensitivity in streptozotocin-diabetic rats: a multiparametric aggregation study. 1647 93

Cardiovascular disease is the leading cause of morbidity and mortality in Western countries, and hypertension-related cardiovascular events affect about 37 million people per year worldwide. In this perspective, treatment of hypertension is a reference illustrating strategies of cardiovascular prevention. Hypertensive patients are at increased risk of undergoing a cardiovascular event throughout their lives, and treatment of high blood pressure is one of the most effective strategies to reduce global cardiovascular risk. However, due to its multifactorial pathophysiology and frequent association with other important risk factors and clinical conditions such as dyslipidemia, diabetes, left ventricular dysfunction, and renal impairment, treatment of hypertension requires an integrated approach, including life-style measures, antihypertensive drugs and other therapies (statins, ASA, etc.). Nonetheless, worldwide, general practitioners continue to focus on managing a single risk factor, e.g. blood pressure, rather than on overall cardiovascular risk profiles. Another debated issue is whether it matters how blood pressure is lowered in hypertensive patients at high risk. In other words, are the latest antihypertensive drugs more effective than older blood pressure strategies in terms of reduction of cardiovascular events? The recent results of the ASCOT Study address these controversial issues and throw new light on the management of cardiovascular risk in hypertension.
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PMID:Integrated cardiovascular risk management for the future: lessons learned from the ASCOT trial. 1664 Jan 73


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