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)

Although circumstantial evidence supports raising high-density lipoprotein cholesterol (HDLC) in patients with low levels of HDLC, the scarcity of event-based trials has led to uncertainty with regard to the benefit of high-density lipoprotein (HDL)-raising therapy. Based on the National Cholesterol Education Program guidelines, therapy for dyslipidemia is focused initially on targeting low-density lipoprotein cholesterol (LDLC), and in patients with hypertriglyceridemia, secondarily on targeting non-HDLC. When HDLC remains low, the decision to target HDLC depends on the assessment of risk of cardiovascular events. We often consider drug therapy specifically to raise HDLC in high-risk patients, such as those with established atherosclerotic vascular disease, type 2 diabetes, or a Framingham risk score of 20% or above. The majority of high-risk patients require drug therapy, usually a statin, to achieve aggressive LDLC and non-HDLC goals, and thus many patients with low HDLC are candidates for statin therapy. However, a second drug is often required to achieve substantial HDL raising. Although no formal goals for HDLC exist, reasonable goals are HDLC greater than 40 mg/dL in men and greater than 50 mg/dL in women. We often add either niacin or a fibrate to a statin in high-risk patients with low HDLC levels. Targeting HDLC with pharmacologic therapy is a more difficult decision in moderate-risk patients, in whom therapy must be highly individualized.
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PMID:Current Drug Options for Raising HDL Cholesterol. 1591

The metabolic syndrome integrates, in a single diagnosis, the manifestations of insulin resistance that may lead to increased cardiovascular morbidity and precedes type 2 diabetes. Here we discuss the strengths and limitations of the definitions of the metabolic syndrome and the epidemiology of the syndrome including information from non-Caucasian populations. The definitions proposed by the World Health Organization (WHO) and the National Cholesterol Education Program (NCEP) are the most frequently used. The relative risk of having long-term complications is greater for the WHO definition; this is explained by the inclusion of the insulin resistance criteria. The cut-off points used in these definitions should be, but are not, adjusted for ethnicity; as a result, in non-Caucasian subjects, there is lack of agreement among these criteria. In a Mexican population-based survey the prevalence was 13.61% using the WHO definition and 26.6% using the NCEP-III criteria. Cases identified by the WHO criteria had a more severe form of the disease. We propose that the metabolic syndrome should be viewed as a progressive long-term process that leads to major complications. Its definition should reflect the continuous nature of the disease; the categorical approach of the current criteria oversimplifies the complexity of the syndrome. The threshold for defining abnormality should be based on the associated risk of the identified phenotype. Refinement of the definition of both affected and nonaffected subjects is required. The available definitions include, in each of these categories, heterogeneous groups with a broad range of risk of future complications.
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PMID:The metabolic syndrome: a concept hard to define. 1592 12

It has been estimated that 92% of individuals with type 2 diabetes, without cardiovascular disease (CVD), have a dyslipidaemic profile. Several guidelines on cardiovascular risk now recommend that patients with diabetes should be considered at high risk of CVD and should thus receive lipid-lowering therapy to reduce low-density lipoprotein cholesterol (LDL-C) to below 2.5 mmol/L. Since their introduction in 1987, statins have revolutionized the management of CVD. The most recent statin to be introduced, rosuvastatin, has been shown to be the most effective at lowering LDL-C, as well as consistently raising HDL-C across the 10-40 mg dose range. This has been confirmed by many studies, including the Measuring Effective Reductions in Cholesterol Using Rosuvastatin Therapy (MERCURY I) study in which rosuvastatin 10 mg was shown to be more effective than commonly used doses of other statins, both for LDL-C reduction and achieving treatment target goals. The effectiveness of rosuvastatin has also been studied in type 2 diabetes patients in three studies: the URANUS (Use of Rosuvastatin vs. Atorvastatin iN type 2 diabetes mellitUS), ANDROMEDA (A raNdomized, Double-blind study to compare Rosuvastatin [10 & 20 mg] and atOrvastatin [10 & 20 Mg] in patiEnts with type II DiAbetes) and CORALL (COmpare Rosuvastatin [10-40 mg] with Atorvastatin [20-80 mg] on apo B/apo A-1 ratio in patients with type 2 diabetes meLLitus and dyslipidaemia) studies. URANUS and ANDROMEDA showed rosuvastatin to be more effective than atorvastatin at reducing LDL-C and achieving treatment target goals. CORALL demonstrated rosuvastatin 10, 20 and 40 mg to be more effective at lowering LDL-C than 20, 40 and 80 mg of atorvastatin, respectively. Ongoing studies will evaluate whether these properties of rosuvastatin translate into beneficial effects on atherosclerosis and significant reductions in cardiovascular events.
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PMID:A review of the efficacy of rosuvastatin in patients with type 2 diabetes. 1603 94

Both the American Diabetes Association (ADA) and the National Cholesterol Education Program (NCEP) consider type 2 diabetes mellitus to be a coronary artery disease (CAD) risk equivalent and thus suggest that patients with either diabetes or CAD should have their plasma levels of low-density lipoprotein (LDL) cholesterol lowered to <2.59 mmol/L (<100 mg/dL). Recently the NCEP issued a white paper suggesting an even lower plasma LDL cholesterol goal of <1.81 mmol/L (<70 mg/dL) for patients at high cardiovascular risk, including patients with diabetes. This rationale was based partly on the higher risk of future cardiovascular disease seen in patients who have diabetes with or without preexisting cardiovascular disease than in nondiabetic subjects with preexisting cardiovascular disease. Additionally, as reported in the Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE-IT) study, high-dose lipid-lowering therapy has been shown to further reduce CAD event rates compared with conventional therapy.
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PMID:Rationale for new American Diabetes Association Guidelines: are national cholesterol education program goals adequate for the patient with diabetes mellitus? 1609 41

The metabolic syndrome, also known as the dysmetabolic syndrome, syndrome X, or the insulin resistance syndrome, refers to the clustering of cardiovascular disease risk factors that are present in many individuals who are at increased risk for cardiovascular events and/or type 2 diabetes. The criteria for metabolic syndrome include a combination of categorical and borderline risk factors that can be readily measured in clinical practice. Although the Adult Treatment Panel III of the National Cholesterol Education Program set the criteria to identify cardiovascular risk, the syndrome had already been well recognized in the endocrine community as identifying people at risk for diabetes. Recently, the International Diabetes Federation proposed a worldwide definition with ethnic-specific criteria for waist circumference. Therapies targeted to specific components of the metabolic syndrome, such as improving glycemic control, managing dyslipidemia, and reducing the prothrombotic state, should help to minimize cardiovascular risk, particularly if initiated early.
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PMID:Metabolic syndrome: demographic features, etiology, and clinical management. 1610 82

A substantial portion of the population of the United States has the Metabolic Syndrome, a condition that greatly increases risk for cardiovascular disease and diabetes. Insulin resistance, and the resulting compensatory hyperinsulinemia, is the principal pathophysiologic abnormality underlying the majority of these cases. Based on the most recent recommendations of the National Cholesterol Education Panel, such patients can be identified by the presence of three or more of the following traits: impaired fasting glucose, abdominal obesity, hypertension, elevated levels of triglycerides, and low concentrations of HDL-cholesterol. However, a significant number of insulin resistant (and thus high risk) individuals will not be identified using these criteria. This discrepancy occurs because insulin resistance is a continuous variable, without an absolute cut-off between normal and abnormal, and those fitting the definition are the most insulin resistant. Moreover, easily applicable testing to diagnose insulin resistance accurately in the general population is currently not feasible. It is therefore necessary to broaden the criteria that define the metabolic syndrome to include other conditions associated with the presence of insulin resistance. Such conditions include the following: a family history of type 2 diabetes or coronary artery disease in first- or second-degree relatives, signs of an over active sympathetic nervous system, and elevated concentrations of uric acid. By recognizing these "other conditions," appropriate lifestyle changes and medication can be recommended to help prevent cardiovascular disease and diabetes from developing in these high-risk patients.
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PMID:Toward an improved diagnosis of the metabolic syndrome other clues to the presence of insulin resistance. 1610 24

The HIV lipodystrophy syndrome, a condition characterized by subcutaneous fat loss sometimes associated with relative or absolute accumulation of central fat, has a high prevalence in the treatment of HIV infection. Associated metabolic alterations include peripheral and hepatic insulin resistance, impaired glucose tolerance, type 2 diabetes, hypertriglyceridemia, hypercholesterolemia, increased free fatty acids, and decreased HDL. Often, these metabolic abnormalities appear or deteriorate before the manifestation of fat redistribution. Hypertriglyceridemia is the leading lipid abnormality after initiation of HIV therapy frequently observed together with low HDL cholesterol. Raised levels of tissue plasminogen activator and plasminogen activator inhibitor-1 have been found in these patients, and there are reports about hypertension associated with antiretroviral therapy. Thus, the lipodystrophy syndrome in HIV therapy resembles a clinical situation that is known as the "metabolic syndrome" in HIV-negative patients. There is now good evidence that the metabolic abnormalities of HIV-infected patients harbor a significant risk for cardiovascular disease with as yet unknown consequences. In addition, several studies report a reduced quality of life in patients with body habitus changes leading to reduced therapy adherence. Current data indicate a rather multifactorial pathogenesis where HIV infection, its therapy, and patient-related factors are major contributors. Therapeutic and preventive strategies have, so far, been of only limited or no success. For reduction of the cardiovascular risk, recommendations proposed for non-HIV-infected patients like the National Cholesterol Education Program (NECP) have been adapted for HIV-infected patients. These should be regarded as rather preliminary and need to be evaluated in further clinical trials. General recommendations include dietary changes and physical activity, switch of antiretroviral drugs (replacement of protease inhibitors), and, finally, use of metabolically active drugs. Lipid-lowering agents can be considered for the treatment of severe hypertriglyceridemia, elevated LDL, or a combination of both. Some HMG-CoA reductase inhibitors, however, share common hepatic metabolization pathways with protease inhibitors (cytochrome P450 3A4 system), thereby potentially leading to additional liver and muscle toxicity. Although clinicians should assess cardiovascular risk factors and target risk reduction in HIV-infected patients, the primary goal in HIV therapy remains to be the effective suppression of viral replication leading to reduced morbidity and mortality.
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PMID:[Metabolic syndrome and hyperlipidemia in HIV-positive patients]. 1617 Jun 75

Patients with diabetes mellitus are at higher risk for cardiovascular events than those without diabetes. Furthermore, patients with diabetes have a characteristic 'lipid triad' of low high-density lipoprotein-cholesterol (HDL-C) levels, high triglyceride levels, and normal or slightly raised low-density lipoprotein-cholesterol (LDL-C) levels, with a preponderance of small, dense LDL-C particles. Current guidelines on preventing cardiovascular disease recognize the need not only to reduce LDL-C levels, but also to increase HDL-C and decrease triglyceride levels in diabetic patients. Some clinical trials of HMG-CoA reductase inhibitors (statins) have included large populations of diabetic patients. In some of these trials (such as 4S [Scandinavian Simvastatin Survival Study], CARE [Cholesterol and Recurrent Events] trial, and the HPS [Heart Protection Study]), HMG-CoA reductase inhibitor treatment significantly reduced cardiovascular events in diabetic patients, whereas in other trials (ALLHAT-LLT [Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial], ASCOT [Anglo-Scandinavian Cardiac Outcomes Trial]) the reductions were not significant. In CARDS (Collaborative Atorvastatin Diabetes Study), the first large HMG-CoA reductase inhibitor study to enroll only patients with type 2 diabetes, atorvastatin reduced cardiovascular events by 37% (p=0.001) compared with placebo. Fibric acid derivatives (fibrates), which are agonists of peroxisome proliferator-activated alpha receptors, exert their effects by altering the transcription of genes encoding proteins that control lipoprotein metabolism. Fibric acid derivatives are a valuable tool in the treatment of dyslipidemia in patients with diabetes, as they reduce plasma triglyceride levels by 30--50%, increase HDL-C levels by 10--15%, and shift the distribution of LDL subfractions towards larger, less atherogenic particles. The DAIS (Diabetes Atherosclerosis Intervention Study), which was conducted exclusively in patients with type 2 diabetes, found that fenofibrate reduces the progression of angiographic coronary artery disease. The VA-HIT (Veterans Affairs Cooperative Studies Program HDL-C Intervention Trial) showed that gemfibrozil reduced cardiovascular events in subgroups of diabetic patients. A large clinical event study, FIELD (Fenofibrate Intervention and Event Lowering in Diabetes), which is currently being completed, will provide further information on the value of fenofibrate for the reduction of cardiovascular risk in patients with diabetes.
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PMID:A new perspective in the treatment of dyslipidemia : can fenofibrate offer unique benefits in the treatment of type 2 diabetes mellitus? 1618 99

Despite meaningful progress in the identification of risk factors and the development of highly effective clinical tools, deaths from cardiovascular disease continue to increase worldwide. Sparked by an obesity epidemic, the metabolic syndrome and the rising incidence of type 2 diabetes have led to an upsurge of cardiovascular risk. Although pharmacologic treatments with the statin class of drugs have reduced cholesterol levels and lowered mortality rates, several large controlled clinical trials, including the Scandinavian Simvastatin Survival Study, the Cholesterol and Recurrent Events trial, the Air Force/Texas Coronary Atherosclerosis Prevention studies, and Long-term Intervention with Pravastatin in Ischemic Disease study, have indicated that cardiovascular events continue to occur in two thirds of all patients. Follow-up studies, such as the Heart Protection Study and the Pravastatin or Atorvastatin Evaluation and Infection Therapy/Thrombolysis In Myocardial Infarction-22 trials, reinforced these earlier results. Although therapy with gemfibrozil, a fibric acid derivative, showed reduced occurrence of cardiovascular events in the Helsinki Heart Study and the Veterans Affairs HDL Intervention Trial, results of other studies, e.g., the Bezafibrate Intervention Program and the Diabetes Atherosclerosis Intervention study, showed less encouraging results. Although lifestyle modifications, such as improved diet and increased exercise levels, benefit general health and the metabolic syndrome and insulin resistance in particular, most people continue to resist changes in their daily routines. Thus, physicians must continue to educate their patients regarding an optimal balance of drug therapy and personal behavior.
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PMID:The forgotten majority: unfinished business in cardiovascular risk reduction. 1619 35

Interest in insulin resistance as a candidate pathway in the pathogenesis of vascular disease continues to grow, in part fuelled by the rapidly increasing rates of obesity worldwide which drives insulin resistance in susceptible individuals. Insulin resistance is associated with a range of metabolic perturbances and many of these can accelerate the atherogenic process. There is thus considerable clinical interest in assessing the degree of insulin resistance in subjects at risk for vascular disease. Direct measurements of insulin resistance are generally unsuitable for widespread clinical use. Rather metabolic syndrome criteria based on readily measured factors associated insulin resistance have been proposed by the World Health Organisation and the National Cholesterol Education Panel. Although such criteria predict coronary heart disease events and more strongly type 2 diabetes, their clinical applicability requires much more study. One recent benefit, however, is that vascular risk physicians now more frequently document obesity and glucose concentrations in their patients, and more commonly consider lifestyle interventions. Ongoing clinical trials will further determine the value of lifestyle factors and insulin sensitising agents in reducing risk of vascular and metabolic disease in high risk subjects.
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PMID:Insulin resistance and the metabolic syndrome as predictors of cardiovascular risk: where are we now? 1620 4


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