Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Proteoheparan sulfate can be adsorbed onto a methylated silica surface in a monomolecular layer via its transmembrane hydrophobic protein core domain. Due to electrostatic repulsion, its anionic glycosaminoglycan side chains are stretched out into the blood substitute solution, thereby representing a receptor site for specific lipoprotein binding through basic amino acid-rich residues within their apolipoproteins. The binding process was studied by ellipsometric techniques suggesting that HDL has a high binding affinity and a protective effect on interfacial heparan sulfate proteoglycan layers with respect to LDL and Ca(2+) complexation. LDL was found to be deposited strongly at the proteoheparan sulfate-coated surface, particularly in the presence of Ca(2+), apparently through complex formation 'proteoglycan-low density lipoprotein-calcium'. This ternary complex build-up may be interpreted as arteriosclerotic nanoplaque formation on the molecular level responsible for the arteriosclerotic primary lesion. In a receptor-based biosensor application, this system was tested on its reliability to unveil possible acute pleiotropic effects of the lipid lowering drug fluvastatin. The VLDL/IDL/LDL and VLDL/IDL/LDL/HDL plasma fractions from a high risk patient with dyslipoproteinaemia and type 2 diabetes mellitus showed the start of arteriosclerotic nanoplaque formation at a normal blood Ca(2+) concentration, with a strong increase at higher Ca(2+) concentrations. Nanoplaque formation and size of the HDL-containing lipid fraction remained well below that of the LDL-containing lipid fraction. Fluvastatin, whether applied acutely to the patient (one single 80 mg slow release matrix tablet) or in a 2-month medication regimen, markedly slowed down this process of ternary aggregational nanoplaque build-up and substantially inhibited nanoplaque size development at all Ca(2+) concentrations used. The acute action gave no significant change in lipid concentrations of the patient. Furthermore, after nanoplaque generation, fluvastatin, similar to HDL, was able to reduce nanoplaque formation and size. These immediate effects of fluvastatin have to be taken into consideration when interpreting the clinical outcome of long-term studies.
Cardiovasc Res 2003 Jun 01
PMID:Reduction of arteriosclerotic nanoplaque formation and size by fluvastatin in a receptor-based biosensor model. 1279 44

The metabolic syndrome is a highly prevalent clinical entity. The recent Adult Treatment Panel (ATP III) guidelines have called specific attention to the importance of targeting the cardiovascular risk factors of the metabolic syndrome as a method of risk reduction therapy. The main factors characteristic of this syndrome are abdominal obesity, atherogenic dyslipidemia, elevated blood pressure, insulin resistance (with or without glucose intolerance), prothrombotic and proinflammatory states. An insulin resistance following nuclear peroxisome proliferator activated receptors (PPAR) deactivation (mainly obesity-related) is the key phase of metabolic syndrome initiation. Afterwards, there are 2 principal pathways of metabolic syndrome development: 1) with preserved pancreatic beta cells function and insulin hypersecretion which can compensate for insulin resistance. This pathway leads mainly to the macrovascular complications of metabolic syndrome; 2) with massive damage of pancreatic beta cells leading to progressively decrease of insulin secretion and to hyperglycemia (e.g. overt type 2 diabetes). This pathway leads to both microvascular and macrovascular complications. We suggest that a PPAR-based appraisal of metabolic syndrome and type 2 diabetes may improve our understanding of these diseases and set a basis for a comprehensive approach in their treatment.
Cardiovasc Diabetol 2003 Mar 23
PMID:Metabolic syndrome and type 2 diabetes mellitus: focus on peroxisome proliferator activated receptors (PPAR). 1283 41

The prevalence of diabetes is increasing, particularly in developing regions of the world. The social and economic consequences of this disease and its complications are enormous. We discuss the scope and implications of the increasing burden of diabetes and describe the rationale and design of a new international study examining blood pressure lowering and glucose control interventions aimed at reducing the risk of vascular complications in people with type 2 diabetes. This study is the first large-scale randomized trial in diabetes to include participants from both lower- and higher-income regions of the world.
Asian Cardiovasc Thorac Ann 2003 Jun
PMID:Diabetes and vascular disease: a new international trial. 1287 75

There are many metabolic consequences of insulin resistance and multiple conditions associated with insulin resistant states. The most obvious pathology associated with insulin resistance is type 2 diabetes mellitus, but other manifestations include hypertension, central obesity, a hypercoagulable state, and dyslipidemia. The atherogenic dyslipidemia associated with insulin resistant states is characterized by hypertriglyceridemia; an increase in very-low-density lipoprotein secretion from the liver; an increase in atherogenic small, dense low-density lipoprotein; and a decrease in high-density lipoprotein cholesterol. Each of these lipid abnormalities is an independent risk factor for coronary artery disease, and in concert, the cardiovascular risk is magnified. Therefore, insulin resistant states should be identified as early as possible in patients, and these lipid abnormalities should be assessed and treated.
Rev Cardiovasc Med 2003
PMID:Lipid abnormalities in insulin resistant states. 1466 90

Type 2 diabetes has become the most frequently encountered metabolic disorder in the world, currently affecting 5% to 10% of most populations, and the incidence continues to grow among developing nations. Two fundamental abnormalities are involved in the pathogenesis of type 2 diabetes: Resistance to the biologic activities of insulin in glucose and lipid metabolism and inadequate insulin secretion from the pancreatic B cells. In genetically predisposed individuals, type 2 diabetes is pathogenically linked with progressive obesity, especially adiposity that is visceral or ectopic in distribution. While microvascular complications (retinopathy, nephropathy, neuropathy) continue to plague patients with longstanding type 2 diabetes, cardiovascular disease has assumed particular importance, accounting for more than 80% of adverse outcomes among patients. Since the aggressive management of diabetes and its complications poses a considerable challenge, large trials to prevent the progression to overt diabetes in persons at high risk have recently demonstrated that lifestyle modification and pharmaceutical therapy can be successful approaches. A better understanding of the complex relationship between obesity and both the development of type 2 diabetes and its cardiovascular complications may provide additional treatment targets in the future to prevent the devastating chronic morbidity of this disorder.
Rev Cardiovasc Med 2003
PMID:Insulin resistance: from benign to type 2 diabetes mellitus. 1466 98

Diabetes mellitus is one of the most common problems challenging physicians in the 21st century. Type 2 diabetes mellitus accounts for at least 90% of all cases, which can be attributed in part to an aging population and the prevalence of obesity and sedentary lifestyles. In addition to the major impact on quality of life, diabetes accounts for a significant proportion of global healthcare expenditure, with the majority of costs attributable to treatment of its long-term complications. The principal cause of diabetes mortality is cardiovascular disease (CVD). There is a long period, prior to clinical detection of the disease, in which insulin resistance and hyperglycemia gradually worsen, and vascular complications develop. This article reviews the relationship between diabetes and the risk of CVD.
Rev Cardiovasc Med 2003
PMID:The relation of insulin resistance syndromes to risk of cardiovascular disease. 1466 99

Diabetes, a leading cause of morbidity and mortality in the United States, is associated with a 2- to 4-fold increase in the risk of coronary artery disease. As the population in the United States has aged, the incidence of obesity, hypertension, glucose intolerance, and dyslipidemia has increased significantly, culminating in the current epidemic of type 2 diabetes mellitus. Strict glycemic control must, therefore, be accompanied with proven therapies (such as antihypertensives and lipid-lowering agents) to reduce cardiovascular events. Patients with type 2 diabetes have average low-density lipoprotein (LDL) levels but have an increased number of small, dense LDL particles, which are associated with a 3-fold increase in cardiovascular disease. Type 2 diabetes mellitus is also associated with increased triglyceride rich atherogenic particles, which trigger inflammation. In addition to glycemic control and drug therapy, lifestyle modifications (eg, diet, weight loss, and exercise) also play an important role in managing diabetes. Therefore, strict glycemic control, pharmacologic therapy, and lifestyle modifications are parts of a comprehensive strategy to prevent both microvascular and macrovascular events in patients with type 2 diabetes.
Rev Cardiovasc Med 2003
PMID:Treating the diabetic patient: appropriate care for glycemic control and cardiovascular disease risk factors. 1466

The American Diabetes Association's objective for treating patients with type 2 diabetes mellitus is to normalize glycemia and glycosylated hemoglobin concentrations while controlling blood pressure, cholesterol, and other cardiovascular risk factors. This article focuses on the role of thiazolidinediones (TZDs) in the management of patients with type 2 diabetes with comorbid cardiovascular disease. Insulin resistance is one of the earliest and main defects in type 2 diabetes and is strongly linked to comorbid cardiovascular conditions. The TZDs rosiglitazone and pioglitazone work mainly by reducing insulin resistance and may have the potential to alter the natural history of type 2 diabetes and reduce the cardiovascular mortality and morbidity associated with this condition.
Rev Cardiovasc Med 2003
PMID:The role of the thiazolidinediones in the practical management of patients with type 2 diabetes and cardiovascular risk factors. 1466 1

5-hydroxytryptamine (5-HT) is closely related to pathogenesis of angiopathy in type 2 diabetes. Acute and chronic effects of sarpogrelate hydrochloride (sarpogrelate), a 5-HT2 blocker, on glucose tolerance and insulin resistance were examined. Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of type 2 diabetes, were randomly assigned to 2 groups; those with 30 mg/kg BW/d sarpogrelate treatment of 4 weeks (HTB group) and without (control group). The glucose infusion rate was significantly increased in the HTB group compared with the control group. The blood glucose levels after oral glucose tolerance test and levels of plasma insulin and lipids were significantly lower in the HTB group than in the control group. To investigate mechanism of the improvement by sarpogrelate, acute effect of 5-HT and its blocking effect by sarpogrelate on blood levels of glucose were examined in 25-week-old Sprague-Dawley rats. Blood glucose levels were significantly increased by administration of 5-HT. This increase was reversed by pretreatment of sarpogrelate. A plasma adrenaline level also rose significantly by injection of the 5-HT and was prevented by pretreatment of sarpogrelate. These results indicate that sarpogrelate improves insulin resistance in type 2 diabetic rats.
J Cardiovasc Pharmacol 2004 Feb
PMID:Effect of sarpogrelate hydrochloride, a 5-HT2 blocker, on insulin resistance in Otsuka Long-Evans Tokushima fatty rats (OLETF rats), a type 2 diabetic rat model. 1471 15

It has been clearly shown that lowering low density lipoprotein-cholesterol (LDL-C) [most often with an HMG-CoA reductase inhibitor] decreases the risk of a cardiovascular event. However, this risk reduction was, at most, 35% in clinical trials, meaning that many events could not be prevented. Moreover, reaching target lipid values as recommended by the current guidelines is often difficult, mainly in high-risk situations such as secondary prevention or type 2 diabetes mellitus. As the two main classes of lipid-lowering drugs (HMG-CoA reductase inhibitors and fibric acid derivatives) have complementary effects on lipid parameters, it seems logical to combine both treatments particularly in patients with combined hyperlipidemia. In fact, combination therapy with an HMG-CoA reductase inhibitor and a fibric acid derivative induces a further decrease in LDL-C levels compared with monotherapy and improves other lipid values such as high density lipoprotein-cholesterol (HDL-C) and triglyceride (TG) levels. Unfortunately, there are currently no available randomized, prospective clinical data on the reduction of the incidence of cardiovascular events with such a combination. This is mainly because the use of HMG-CoA reductase inhibitor and fibric acid derivative combinations was initially described as dangerous. It is true that such a combination increases the risk of muscle toxicity that already exists with monotherapy. Muscle toxicity can eventually lead to life-threatening rhabdomyolysis and some precautions of use are required; however, the risk seems actually lower than what has been initially reported. The use of combined therapy with an HMG-CoA reductase inhibitor and a fibric acid derivative requires the respect of some rules such as avoiding the prescription in patients with concomitant conditions like renal failure and avoiding the use of gemfibrozil as a fibric acid derivative in such a combination. It is now imperative to design clinical trials to determine the clinical efficacy and precise safety of this combined treatment especially in patients with abnormalities in every parameter of the lipid triad (LDL, HDL and TG) and a high vascular risk such as patients with type 2 diabetes mellitus.
Am J Cardiovasc Drugs 2003
PMID:Combination therapy with an HMG-CoA reductase inhibitor and a fibric acid derivative: a critical review of potential benefits and drawbacks. 1472 29


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