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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Type 2 diabetes mellitus and the closely related metabolic syndrome markedly increase the risk of cardiovascular disease a major contributor is the dyslipidemia. Recent studies and new national guidelines suggest these very high risk patients with cardiovascular disease achieve optional low density lipoprotein cholesterol (LDL-C) level of less than 70 mg/dl. In addition there may be no threshold to begin therapeutic lifestyle change and pharmacologic therapy to reduce LDL-C by 30-40%. Although randomized controlled trials with statins indicate that LDL reduction clearly reduces cardiovascular risk in these patients, the typical dyslipidemia of type 2 diabetes mellitus is also characterized by low high density lipoprotein cholesterol (HDL-C) levels, increased triglyceride-rich lipoproteins and small dense LDL, as well as increased postprandial lipemia. The later lipoproteins increase non-HDL-C levels. In order to address these abnormalities it may be necessary to utilize combined approaches with a fibrate or nicotinic acid, or other agents with statins to help reduce risk beyond statins. In addition, supervised, therapeutic life-style change is often underutilized therapy in patients with established coronary artery disease. This review will focus on maximizing the treatment of dyslipidemia in type 2 diabetes and the metabolic syndrome and discuss the evidence based studies and new developments in the management in these very high risk patients.
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PMID:Cardiovascular disease risk of type 2 diabetes mellitus and metabolic syndrome: focus on aggressive management of dyslipidemia. 1822 May 88

Whilst statin monotherapy is often sufficient to reach LDL-C goals, treatment may not reach all lipid goals in individuals with mixed dyslipidaemia typically associated with metabolic syndrome or type 2 diabetes. Double or triple combination therapy, which provides the opportunity to address multiple lipid abnormalities simultaneously, may be required to achieve targets in some patients. Addition of fenofibrate or niacin (nicotinic acid) to statin therapy is likely to be the first option, as recommended by national treatment guidelines; omega-3 fatty acids may also be useful. Careful monitoring is required when adding additional agents given the increased potential for drug interactions and side effects.
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PMID:Combination therapy in the management of mixed dyslipidaemia. 1832 28

The last 20 years have witnessed dramatic reductions in cardiovascular risk using 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors ("statins") to lower levels of low-density lipoprotein cholesterol (LDL-C). Using this approach one can achieve a reduction in the risk of major cardiovascular events of 21% for every 1 mmol/l (39 mg/dl) decrease in LDL-C. However, despite intensive therapy with high dose "statins" to lower LDL-C levels below 2.6 mmol/l (100 mg/dl), the risk of a major cardiovascular event in patients with established coronary artery disease remains significant at a level approaching an annual risk of 9%, paving the way for new strategies for reducing the residual cardiovascular risk in this patient group. Early epidemiological studies have identified low levels of high-density lipoprotein cholesterol (HDL-C) (<1.0 mmol/l or 40 mg/dl), a common feature of type 2 diabetes mellitus and the metabolic syndrome, to be an independent determinant of increased cardiovascular risk. The beneficial effects of HDL-C on the cardiovascular system have been attributed to its ability to remove cellular cholesterol, as well as its anti-inflammatory, antioxidant and antithrombotic properties, which act in concert to improve endothelial function and inhibit atherosclerosis, thereby reducing cardiovascular risk. As such, raising HDL-C in patients with aggressively lowered LDL-C provides an additional strategy for addressing the residual cardiovascular risk present in these patients groups. Studies suggest that for every 0.03 mmol/l (1.0 mg/dl) increase in HDL-C, cardiovascular risk is reduced by 2-3%. Raising HDL-C can be achieved by both lifestyle changes and pharmacological means, the former of which include smoking cessation, aerobic exercise, weight loss and dietary manipulation. Therapeutic strategies have included niacin, fibrates, thiazolidinediones and bile acid sequestrants. Newly developed pharmacological agents include apolipoprotein A-I mimetics and the cholesteryl ester transfer protein (CETP) inhibitors, JTT-705 and torcetrapib, the latter of which has been recently withdrawn from clinical testing because of serious adverse effects. Emerging experimental studies investigating the complex pathways of HDL metabolism have identified several new targets for raising HDL-C with new pharmaceutical agents currently in development. For the time being, the long-acting formulations of nicotinic acid remain the most effective and best tolerated pharmacological strategy for raising HDL-C in patients already on statin therapy to control LDL-C. Therefore, raising HDL-C represents an important strategy for reducing residual cardiovascular risk in patients already optimally treated with statins, and should lead to further improvements in clinical outcomes in these patient groups.
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PMID:Targeting residual cardiovascular risk: raising high-density lipoprotein cholesterol levels. 1848 Mar 46

Metabolic syndrome (MS) is a common condition strongly associated with the development of type 2 diabetes and coronary heart disease (CHD). High triglycerides (TG) and low high density lipoprotein cholesterol (HDL-C) often occur together and represent the fundamental dyslipidemia of patients with MS. This abnormal lipoprotein profile is a major risk factor for premature cardiovascular disease. This review briefly discusses new findings on structure and functions of HDL in the atherogenic dyslipidemic condition known as MS. While the knowledge of the association between HDL-C and CHD began with the observation of an inverse relationship between HDL-C values and CHD risk, information in recent years shows the important role of HDL function in the pathogenesis of atherosclerosis. HDL particles are heterogeneous in structure, intravascular metabolism and antiatherogenic activity. Reductions in HDL-C concentrations, as seen in MS, are frequently associated with an abnormal HDL subclass distribution, altered HDL chemical composition, reduced antiinflamatory and antioxidative properties, and low capacity to promote cholesterol efflux. Deficiency of HDL particle number and attenuated antiaterogenic activity favor accelerated atherosclerosis. These data justify renewed emphasis on low HDL-C as a major risk factor in the prevention and treatment of CHD. Pharmacological interventions that increase HDL-C can also improve the quality and biological activities of HDL particles. Fibrates, nicotinic acid, cholesteryl ester transfer protein inhibitors, and reconstituted HDL are being investigated. Patients with MS constitute a high risk group that would particularly benefit from intervention to rise HDL-C.
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PMID:[Some physiopathologic features of metabolic syndrome]. 1893 96

Current treatment guidelines recommend lowering elevated low-density lipoprotein (LDL) cholesterol levels with a statin as the primary lipid-modifying intervention to reduce cardiovascular risk in patients with type 2 diabetes mellitus or metabolic syndrome. However, even with high-dose statin therapy or the combination of statin plus ezetimibe, many patients remain at substantial risk of a cardiovascular event. Increasingly, there is recognition of the importance of treating all components of the atherogenic dyslipidemic profile associated with both conditions, specifically low high-density lipoprotein cholesterol and elevated triglyceride levels, in addition to lowering LDL cholesterol. Both niacin (nicotinic acid) and fibrates are recommended as options for combination with a statin in this setting. Data from ongoing prospective outcomes studies are needed to evaluate the efficacy and safety of these combinations.
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PMID:A review of the current status of the management of mixed dyslipidemia associated with diabetes mellitus and metabolic syndrome. 1908 86

The last 20 years have witnessed dramatic reductions in cardiovascular risk using 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors ("statins") to lower levels of low-density lipoprotein cholesterol (LDL-C). Using this approach one can achieve a reduction in the risk of major cardiovascular events of 21% for every 1 mmol/l (39 mg/dl) decrease in LDL-C. However, despite intensive therapy with high dose "statins" to lower LDL-C levels below 2.6 mmol/l (100 mg/dl), the risk of a major cardiovascular event in patients with established coronary artery disease remains significant at a level approaching an annual risk of 9%, paving the way for new strategies for reducing the residual cardiovascular risk in this patient group. Early epidemiological studies have identified low levels of high-density lipoprotein cholesterol (HDL-C) (<1.0 mmol/l or 40 mg/dl), a common feature of type 2 diabetes mellitus and the metabolic syndrome, to be an independent determinant of increased cardiovascular risk. The beneficial effects of HDL-C on the cardiovascular system have been attributed to its ability to remove cellular cholesterol, as well as its anti-inflammatory, antioxidant and antithrombotic properties, which act in concert to improve endothelial function and inhibit atherosclerosis, thereby reducing cardiovascular risk. As such, raising HDL-C in patients with aggressively lowered LDL-C provides an additional strategy for addressing the residual cardiovascular risk present in these patients groups. Studies suggest that for every 0.03 mmol/l (1.0 mg/dl) increase in HDL-C, cardiovascular risk is reduced by 2-3%. Raising HDL-C can be achieved by both lifestyle changes and pharmacological means, the former of which include smoking cessation, aerobic exercise, weight loss and dietary manipulation. Therapeutic strategies have included niacin, fibrates, thiazolidinediones and bile acid sequestrants. Newly developed pharmacological agents include apolipoprotein A-I mimetics and the cholesteryl ester transfer protein (CETP) inhibitors, JTT-705 and torcetrapib, the latter of which has been recently withdrawn from clinical testing because of serious adverse effects. Emerging experimental studies investigating the complex pathways of HDL metabolism have identified several new targets for raising HDL-C with new pharmaceutical agents currently in development. For the time being, the long-acting formulations of nicotinic acid remain the most effective and best tolerated pharmacological strategy for raising HDL-C in patients already on statin therapy to control LDL-C. Therefore, raising HDL-C represents an important strategy for reducing residual cardiovascular risk in patients already optimally treated with statins, and should lead to further improvements in clinical outcomes in these patient groups.
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PMID:Targeting residual cardiovascular risk: raising high-density lipoprotein cholesterol levels. 1910 17

Low levels of high-density lipoprotein cholesterol (HDL-C) represent a major cardiovascular risk factor, with a stronger relationship to coronary heart disease than that seen with elevated levels of low-density lipoprotein cholesterol (LDL-C). HDL-C has important antiatherogenic effects, including reverse cholesterol transport, inhibition of LDL-C oxidation, and antiplatelet and anti-inflammatory actions. Patients with low HDL-C are also at an amplified risk of coronary heart disease due to the common coexistence of other risk factors, including excess adiposity, metabolic syndrome, type 2 diabetes mellitus, hypertriglyceridemia, and the atherogenic dyslipidemia characterized by small dense LDL-C. First-line therapy of low HDL-C generally consists of nonpharmacologic measures such as improved fitness and weight loss. Current pharmaceutical options include statins, fibrates, and nicotinic acid. A host of novel approaches involving HDL-C and reverse cholesterol transport hold the promise of fundamentally changing the natural history of atherosclerosis, the most common and important chronic disease in humans.
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PMID:The importance of recognizing and treating low levels of high-density lipoprotein cholesterol: a new era in atherosclerosis management. 1912 82

Diabetes mellitus type 2 is reaching epidemic proportions in western societies. The treatment of diabetic dyslipidemia to prevent cardiovascular disease is of increasing clinical and scientific interest. In the pathogenesis of this disease plasma triglycerides play a central role. Triglyceride rich particles by themselves are not considered atherogenic; however, they are hydrolysed to chylomicron and VLDL remnant particles. Furthermore, mediated by cholesteryl ester transfer protein (CETP), atherogenic small dense LDL particles (sdLDL) emerge, and HDL cholesterol decreases. All these factors yield into a significantly increased atherogenesis and cardiovascular risk. Weight reduction and low fat diets have shown positive effects in general, but a specific therapy to treat diabetic dyslipidemia is still missing. Studies so far have failed to show a reliable benefit for fibrates and for nicotinic acid. Thus, statin therapy to decrease LDL cholesterol to target is the essential treatment for diabetic dyslipidemia to reduce cardiovascular risk. Other lipid lowering drugs can be added optionally.
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PMID:[Diabetic dyslipoproteinemia: beyond LDL]. 1942 32

Trigonelline (TRG) and nicotinic acid (NA), in which the former but not the latter improved the blood glucose level in the oral glucose tolerance test (OGTT) in Goto-Kakizaki (GK) rats were tested for anti-diabetic effects in mellitus models of KK-A(y) obese mice that had type 2 diabetes. Blood glucose level in OGTT carried out on day 22-23 was lowered after feeding in mice fed TRG and NA than that of the control mice not fed these compounds, indicating that both TRG and NA have sufficient activity to improve glucose tolerance in diabetes with obesity. The serum insulin levels at fasting showed significantly lower levels in mice fed TRG, and a lower tendency in mice fed NA, compared with the control mice. The triglyceride (TG) levels in the liver and adipose tissue in mice fed TRG and NA showed lower values or a lower tendency than those of the control mice, indicating that TRG and NA were also effective to improve the changes in lipid levels accompanied with diabetes. Higher values or a higher tendency of the glucokinase (GLK)/glucose-6-phosphatase (G6Pase) ratio in the liver and lower levels of the serum tumor necrosis factor (TNF)-alpha in the TRG- and NA-fed mice, compared to the control mice, suggested that the regulation of GLK and G6Pase, and TNF-alpha production by TRG and NA are closely related in suppressing the progression of diabetes in the KK-A(y) mice.
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PMID:Anti-diabetic effect of trigonelline and nicotinic acid, on KK-A(y) mice. 2042 1

Retinoid X receptor (RXR) agonists are candidate agents for the treatment of metabolic syndrome and type 2 diabetes via activation of peroxisome proliferator-activated receptor (PPAR)/RXR or liver X receptor (LXR)/RXR-heterodimers, which control lipid and glucose metabolism. Reporter gene assays or binding assays with radiolabeled compounds are available for RXR ligand screening, but are unsuitable for high-throughput screening. Therefore, as a first step towards stabilizing a fluorescence polarization (FP) assay system for high-throughput RXR ligand screening, we synthesized fluorescent RXR ligands by modification of the lipophilic domain of RXR ligands with a carbostyril fluorophore, and selected the fluorescent RXR agonist 6-[ethyl(1-isobutyl-2-oxo-4-trifluoromethyl-1,2-dihydroquinolin-7-yl)amino]nicotinic acid 8d for further characterization. Compound 8d showed FP in the presence of RXR and the FP was decreased in the presence of the RXR agonist LGD1069 (2). This compound should be a lead compound for use in high-throughput assay systems for screening RXR ligands.
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PMID:Fluorescent retinoid X receptor ligands for fluorescence polarization assay. 2066 26


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