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

With the aim of identifying areas that may deserve some further thinking the present review deliberately points out controversial issues in cardiovascular research and risk assessment. In the first part of the review general aspects are addressed regarding the evaluation of risk factors. A first point of concern is the frequent practice of combining different vascular events and effects in different vascular beds into a single endpoint. Furthermore, verification of vascular events in clinical reality may be surprisingly inaccurate. Problems in risk assessment also arise from overlapping properties (shared pathophysiological pathways) of traditional risk factors like hypertension, obesity and diabetes. In the second part of the review unresolved issues concerning selected established and emerging risk factors are discussed. The difficulty of establishing causality in cardiovascular disease is addressed, using modification of LDL cholesterol and accumulating evidence for pleiotropic effects of the LDL cholesterol-lowering statins as an example. As an alternative or supplement to the notion of LDL-related cardiovascular risk it is proposed to distinguish between statin-sensitive and statin-insensitive cardiovascular risk. Finally the future prospects of selected new and emerging risk factors like CRP, homocysteine, asymmetrical dimethylarginine (ADMA), oxLDL, and isoprostanes are evaluated. In summary, imprecise terminology and varying definitions of "cardiovascular risk" may lead to a considerable blurring of our current risk estimates, which may also explain some presently controversial issues. With several new risk factors and substantial changes in lifestyle and treatment patterns on the horizon major changes in the hierarchy of risk factors may be inevitable.
 ...
PMID:Old and new cardiovascular risk factors: from unresolved issues to new opportunities. 1466 97

The beta(2)-adrenergic receptor (B2AR) is expressed in pancreatic beta-cells and modulates insulin secretion. The purpose of the present study was to evaluate the influence of the Arg16Gly variant allele of B2AR on insulin secretion in patients with type 2 diabetes. We used minimal model analysis of the frequently sampled insulin-modified intravenous glucose tolerance test (FSIGT) and polymerase chain reaction (PCR)-restriction fragment length polymorphism to examine differences of insulin secretion and insulin resistance among three genotypes. There were no significant differences in baseline clinical characteristics, HbA1c, uric acid, CRP or lipid profiles among the three groups. The Gly/Gly group had significantly higher levels of fasting insulin (38.2+/-4.7 pmol/l versus 23.6+/-3.5 pmol/l) and homeostasis model assessment of insulin resistance (HOMA-R) (1.90+/-0.19 versus 1.32+/-0.24), compared with the Arg/Arg group, but there were no significant differences in acute insulin response to glucose (AIRg) bolus, insulin sensitivity (Si), or glucose effectiveness (Sg) among the three genotypes. Several reports have speculated that the Gly16 allele of B2AR exhibits agonist-promoted downregulation, but our findings, elevated fasting insulin concentrations, and previous clinical studies of blood pressure and lypolysis are controversial. The direct mechanism by which the Gly16 allele of B2AR may influence insulin secretion of pancreatic beta-cells is unknown. Further studies of the expression of the allelic receptor in islet cells may help to resolve the role of B2AR in insulin secretion. However, increased sensitivity to catecholamine-induced lipolysis of the Gly allele promotes higher free fatty acids concentrations in the portal system, which could enhance the higher levels of fasting insulin.
Diabetes Res Clin Pract 2004 Jan
PMID:Genotype Gly/Gly of the Arg16Gly polymorphism of the beta2-adrenergic receptor is associated with elevated fasting serum insulin concentrations, but not with acute insulin response to glucose, in type 2 diabetic patients. 1469 8

The presence of Helicobacter pylori (HP) infection may adversely influence outcome in renal transplant candidates because of its strong association with gastrointestinal disorders. We examined the association between HP infection and nutritional parameters in symptom-free hemodialysis patients and assessed prospectively the nutritional changes in patients who received therapy for the disease. The 163 study patients, including 114 men and 69 women of mean age 41.5 +/- 12.9 years on dialysis for 67.2 +/- 47.6 months, were selected from among the group who underwent routine endoscopic evaluation according to our renal transplant protocol. Patients with active peptic ulcer, acute gastritis, chronic inflammatory disease, malignancy, or diabetes mellitus were excluded. Endoscopy results revealed normal findings in 60 (group 1), gastritis in 86 (group 2), or gastritis with HP in 17 patients (group 3). Group 3 patients received a 2-week course of triple therapy (omeprazole, amoxicillin, clarithromycin). The patient groups were compared for nutritional metrics (albumin, phosphorus, interdialytic weight gain [IDWG], body mass index [BMI]), inflammatory indices (CRP, fibrinogen), and iPTH levels. Group 3 patients were observed to be malnourished when compared with groups 1 and 2, namely abnormal values of albumin (P <.0001), phosphorus (P <.009), IDWG (P <.03), and BMI (P <.02). Repeat endoscopy revealed a 94% rate of eradication of HP with increased levels of albumin and phosphorus in group 3. Although symptom-free hemodialysis patients with HP-associated gastritis displayed a state of malnutrition; its eradication improved the nutritional status. Therefore, the presence of HP infection should be sought and its eradication mandatory for this patient population.
 ...
PMID:Association of helicobacter pylori infection with nutritional status in hemodialysis patients. 1501 97

A 54-year-old man complained of pain in the left upper abdomen with fever. His past medical history was significant for non-insulin-dependent diabetes mellitus and hypertension. Leucocytosis and an elevation of CRP levels were detected. Thoracoabdominal aneurysm of 69 mm in diameter was identified by enhanced computed tomography (CT). An infected thoracoabdominal aortic aneurysm was diagnosed and an emergency operation was performed. The aneurysm was treated by debridement of the infected aortic tissue and in situ prosthetic graft replacement followed by antibiotic therapy. The postoperative course was uneventful and there were no adverse neurological symptoms. After surgery, antibiotics were administered for 1 month intravenously and the patient was discharged on oral antibiotics for 2 months after the operation. The patient is doing well 7 months after the operation.
 ...
PMID:[Infected thoracoabdominal aortic aneurysm; report of a case]. 1515 Oct 44

Inflammation occurs in the vasculature as a response to injury, lipid peroxidation, and perhaps infection. Various risk factors, including hypertension, diabetes, and smoking, are amplified by the harmful effects of oxidized low-density-lipoprotein cholesterol, initiating a chronic inflammatory reaction, the result of which is a vulnerable plaque, prone to rupture and thrombosis. Epidemiological and clinical studies have shown strong and consistent relationships between markers of inflammation and risk of future cardiovascular events. Inflammation can potentially be detected locally by imaging techniques as well as emerging techniques, such as identification of temperature or pH heterogeneity. It can be detected systemically by measurement of inflammatory markers. Of these, the most reliable and accessible for clinical use is currently high-sensitivity C-reactive protein. A combination of methods may provide the best identification of persons at risk for cardiovascular events who would benefit from treatment. In randomized, controlled trials, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, in the form of statins, have been shown to provide effective therapy for lowering CRP, in conjunction with their lipid-lowering effects. Although the magnitude of risk reduction associated with statin use appears to be largest for those with the highest serum levels of CRP, whether CRP reduction per se lowers cardiovascular risk is unknown.
 ...
PMID:Inflammation as a cardiovascular risk factor. 1517 56

New studies have introduced atherosclerosis as an inflammatory disease. Different factors affect the development of inflammation that can be linked to free radicals, hypertention, diabetes mellitus, genetic changes, hypercholesterolemia and some of the microorganisms. Using anti-inflammatory drugs can be useful in preventing atherosclerosis. Finding drugs from natural sources and without side-effects can be useful. Amirkabiria odoratissima (umbelliferae) is from Iranian fl ora and is used traditionally as an anti-inflammatory drug. This study was designed to assess the effects of this plant on the development and progression of fatty streaks. Male rabbits were fed: (a) rabbit chow; (b) 1% cholesterol diet; (c) cholesterol diet supplemented with the plant; (d) normal diet supplemented with the plant. After 12 weeks, the animals were sacrificed and the aorta, right and left branches of coronary arteries were dissected and histologically processed. Before and after the end of the study, biochemical factors were measured. The amounts of cholesterol, LDL, HDL, triglyceride and fasting blood sugar (FBS) were determined by enzymatic methods, quantitative CRP was determined by turbidimetric methods, malondialdehyde (MDA) and antioxidant capacity were determined by speceterophotometric methods. The results indicate that there is a significant difference between the groups supplemented with herbal medicine and others (p < 0.05) in the mean grade of fatty streak of right and left coronary artery and aorta. At the end of the 12-week period cholesterol, LDL and CRP were significantly reduced in the groups which received herbal medicine (p < 0.05). The data suggests that Amirkabiria odoratissima Mozaffarian has beneficial effects to prevent development of fatty streak; however, further studies are needed to understand the mechanisms whereby this plant exerts its anti-atherosclerotic effects.
 ...
PMID:Effect of Amirkabiria odorastissima mozaffarian on the development and progression of fatty streaks in hypercholesterolemic rabbits. 1517 95

Acute and chronic hyperglycemia are proinflammatory states, but the status of proinflammatory cytokines and markers of oxidative stress and cardiovascular risks is not known in hyperglycemic crises of diabetic ketoacidosis (DKA) and nonketotic hyperglycemia (NKH). We studied 20 lean and 28 obese patients with DKA, 10 patients with NKH, and 12 lean and 12 obese nondiabetic control subjects. We measured 1) proinflammatory cytokines (tumor necrosis factor-alpha, interleukin [IL]-6, IL1-beta, and IL-8), 2) markers of cardiovascular risk (C-reactive protein [CRP], homocysteine, and plasminogen activator inhibitor-1 [PAI-1]), 3) products of reactive oxygen species (ROS; thiobarbituric acid [TBA]-reacting material, and dichlorofluorescein [DCF]), and 4) cortisol, growth hormone (GH), and free fatty acids (FFAs) on admission (before insulin therapy) and after insulin therapy and resolution of hyperglycemia and/or ketoacidosis. Results were compared with lean and obese control subjects. Circulating levels of cytokines, TBA, DCF, PAI-1, FFAs, cortisol, and GH on admission were significantly increased two- to fourfold in patients with hyperglycemic crises compared with control subjects, and they returned to normal levels after insulin treatment and resolution of hyperglycemic crises. Changes in CRP and homocysteine in response to insulin therapy did not reach control levels after resolution of hyperglycemia. We conclude that DKA and NKH are associated with elevation of proinflammatory cytokines, ROS, and cardiovascular risk factors in the absence of obvious infection or cardiovascular pathology. Return of these values to normal levels with insulin therapy demonstrates a robust anti-inflammatory effect of insulin.
Diabetes 2004 Aug
PMID:Proinflammatory cytokines, markers of cardiovascular risks, oxidative stress, and lipid peroxidation in patients with hyperglycemic crises. 1527 89

The causal relation of total Homocysteine (tHcy) to coronary heart diseases (CHD) is unclear. In vitro studies suggest a proinflammatory effect. Among 32,826 women from the Nurses' Health Study who provided blood samples in 1989-1990, 237 CHD events were documented during 8 years of follow-up. The cases (1:2) were matched to controls on age, smoking, and month of blood draw. Plasma tHcy was inversely associated with blood levels of folate (partial r = -0.3, P < 0.0001) and B1(2) (r = -0.2, P < 0.0001) and with dietary intake of folate (r = -0.1, P < 0.01) and B(2) vitamin (r = -0.1, P = 0.01). tHcy was positively associated with soluble tumor necrosis receptor (sTNF-R) 1 and 2 (partial r = 0.2, P < 0.0001). In a multivariate model adjusted for age, smoking, BMI, parental history, hypertension, diabetes, postmenopausal hormone use, physical activity and alcohol intake, the relative risk of CHD between the extreme quartiles of tHcy was 1.66 (95% CI; 1.05-2.64, P trend = 0.02). The association was not appreciably attenuated after further adjustments for sTNF-R1, sTNF-R2, CRP, or Total Cholesterol:/HDL-c ratio. tHcy is an independent risk predictor of CHD and modestly associated with TNF-receptors. However, the inflammatory biomarkers measured could not explain its role in CHD.
 ...
PMID:Homocysteine as a risk factor for coronary heart diseases and its association with inflammatory biomarkers, lipids and dietary factors. 1553 Sep 13

The focus of current diabetes research is the clarification of the pathogenetic relationships between subclinical inflammation, diabetes and arteriosclerosis. Even minimal disturbances in glucose tolerance are associated with a chronic, generalized inflammatory reaction that links components of the metabolic syndrome and contributes to the development of diabetic complications as well as to the development and progression of arteriosclerosis. The most important mediators and markers of this inflammation cascade are NF-kappaB, TNF-alpha, IL-6, CRP and PAI-1. For the treatment of subclinical inflammation, substances with anti-inflammatory properties such as statins or ACE inhibitors are of increasing importance.
 ...
PMID:[Inflammation and diabetes]. 1554 May 36

Orlistat lowers lipids and improves insulin sensitivity, but its effect on other metabolic syndrome related parameters is not known. To assess its influence on adiponectin, high sensitive C-reactive protein (hs-CRP) and other metabolic syndrome related parameters, this study enrolled 106 participants in a weight-reduction program and categorized them into a group of 51 who had been treated with orlistat 360 mg/day for one year and a group of 55 age and sex and body mass index (BMI) matched controls. The orlistat group had greater changes in BMI, % body fat (% BF), waist circumference, and insulin resistance, hs-CRP, leptin and adiponectin levels after one year on the program than the controls. After adjusting for % BF and waist circumference, change of serum leptin and adiponectin levels remained significantly different. It was found that orlistat could effectively manage obesity related co-morbidities, especially insulin resistance and atherosclerosis risk. It decreases leptin and increases adiponectin independent of % BF and waist circumference. Therefore, orlistat appears to have anti-diabetic and anti-atherogenic properties and may help prevent metabolic syndrome in the overweight people.
Diabetes Res Clin Pract 2005 Jan
PMID:Orlistat for obesity: benefits beyond weight loss. 1562 Apr 37


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>