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

Reduction of low-density lipoprotein cholesterol (LDL-C) is presently the primary focus of lipid-lowering therapy for prevention and treatment of coronary heart disease (CHD). However, the high level of residual risk among statin-treated patients in recent coronary prevention studies indicates the need for modification of other major components of the atherogenic lipid profile. There is overwhelming evidence that a low plasma level of high-density lipoprotein cholesterol (HDL-C) is an important independent risk factor for CHD. Moreover, a substantial proportion of patients with or at risk of developing premature CHD typically exhibit distinct lipid abnormalities, including low HDL-C levels. Thus, therapeutic intervention aimed at raising HDL-C, within the context of reducing global cardiovascular risk, would benefit such patients, a viewpoint increasingly adopted by international treatment guidelines. Therapeutic options for patients with low HDL-C include treatment with statins, fibrates and nicotinic acid, either as monotherapy or in combination. Of these options, nicotinic acid is not only the most potent agent for raising HDL-C but is also effective in reducing key atherogenic lipid components including triglyceride-rich lipoproteins (mainly very low-density lipoproteins [VLDL] and VLDL remnants), LDL-C, and lipoprotein(a). The principal features of the atherogenic lipid profile in type 2 diabetes and the metabolic syndrome make them logical targets for nicotinic acid therapy, either alone or in combination with a statin. The lack of comprehensive European data on the prevalence of low HDL-C levels highlights a critical need for education on the importance of raising HDL-C in CHD prevention and treatment. The development of a reliable and accurate assay for HDL-C, as well as clarification of criteria for low and optimal levels of HDL-C in both men and women, constitute critical factors in the reliable identification and treatment of patients at elevated risk of CHD due to low HDL-C. Based on the available evidence, the European Consensus Panel recommends that the minimum target for HDL-C should be 40 mg/dL (1.03 mmol/L) in patients with CHD or with a high level of risk for CHD, including patients at high global risk with type 2 diabetes or the metabolic syndrome.
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PMID:Raising high-density lipoprotein cholesterol with reduction of cardiovascular risk: the role of nicotinic acid--a position paper developed by the European Consensus Panel on HDL-C. 1532 28

Patients with diabetes mellitus have a higher risk for cardiovascular heart disease (CHD) than does the general population, and once they develop CHD, mortality is higher. Good glycemic control will reduce CHD only modestly in patients with diabetes. Therefore, reduction in all cardiovascular risks such as dyslipidemia, hypertension, and smoking is warranted. The focus of this article is on therapy for dyslipidemia in patients with type 2 diabetes. Patients with the metabolic syndrome (insulin resistance) share similarities with patients with type 2 diabetes and may have a comparable cardiovascular risk profile. Diabetic patients tend to have higher triglyceride, lower high-density lipoprotein cholesterol (HDL), and similar low-density lipoprotein cholesterol (LDL) levels compared with those levels in nondiabetic patients. However, diabetic patients tend to have a higher concentration of small dense LDL particles, which are associated with higher CHD risk. Current recommendations are for an LDL goal of less than 100 mg/dl (an option of < 70 mg/dl in very high-risk patients), an HDL goal greater than 40 mg/dl for men and greater than 50 mg/dl for women, and a triglyceride goal less than 150 mg/dl. Nonpharmacologic interventions (diet and exercise) are first-line therapies and are used with pharmacologic therapy when necessary. Lowering LDL levels is the first priority in treating diabetic dyslipidemia. Statins are the first drug choice, followed by resins or ezetimibe, then fenofibrate or niacin. If a single agent is inadequate to achieve lipid goals, combinations of the preceding Drugs may be used. For elevated triglyceride levels, hyperglycemia must be controlled first. If triglyceride or HDL levels remain uncontrolled, pharmacologic agents should be considered. Fibrates are slightly more effective than niacin in lowering triglyceride levels, but niacin increases HDL levels appreciably more than do fibrates. Unlike gemfibrozil, niacin selectively increases subfraction Lp A-I, a cardioprotective HDL. Niacin is distinct in that it has a broad spectrum of beneficial effects on lipids and atherogenic lipoprotein subfraction levels. Niacin produces additive results when used in combination therapy. Recent data suggest that lower dosages and newer formulations of niacin can be used safely in diabetic patients with good glycemic control. Current evidence and guidelines mandate that diabetic dyslipidemia be treated aggressively, and lipid goals can be achieved in most patients with diabetes when all available products are considered and, if necessary, used in combination.
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PMID:Pharmacologic treatment of type 2 diabetic dyslipidemia. 1558 39

Nicotinic acid has favorable effects on atherogenic dyslipidemia. However, in some patients who have diabetes, crystalline nicotinic acid decreases glycemic control; this effect could be due to a marked rebound of nonesterified fatty acids (NEFAs) observed after nicotinic acid suppression of lipolysis in adipose tissue. Recent reports have indicated that small doses of extended-release nicotinic acid do not cause a substantial decrease in glucose levels. Therefore, in this study, we examined whether 2 g/day of extended-release nicotinic acid abolishes the NEFA rebound that is reported with crystalline nicotinic acid. Seventeen men who had the metabolic syndrome (8 did not have type 2 diabetes and 9 did) were treated for 4 months. At baseline and at 4 months, measurements were made of plasma glucose, insulin, and NEFA during an oral glucose tolerance test. At 3 months, effects of extended-release nicotinic acid on NEFA levels and flux rates were determined on 3 separate days at 3 separate intervals after the final dose of nicotinic acid (4, 9, and 28 hours). Values obtained at 28 hours were taken as baseline (i.e., no nicotinic acid remaining in the circulation). After 4 hours (percent baseline), NEFA levels were -30% without diabetes and -37% with diabetes, and flux rates were -21% without diabetes and -25% with diabetes; after 9 hours, NEFA levels were 43% without diabetes and 50% with diabetes, and flux rates were 38% without diabetes and 70% with diabetes. Extended-release nicotinic acid did not abolish NEFA rebound. Nonetheless, the rebound was much less than previously reported for crystalline nicotinic acid. Moreover, after 4 months of nicotinic acid therapy, levels of NEFA, glucose, and insulin during the oral glucose tolerance test were not significantly different from those before institution of nicotinic acid therapy, suggesting minimal changes in insulin sensitivity.
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PMID:Influence of extended-release nicotinic acid on nonesterified fatty acid flux in the metabolic syndrome with atherogenic dyslipidemia. 1590 34

Individuals with type 2 diabetes and metabolic syndrome are at markedly increased risk of cardiovascular morbidity and mortality. The increasing prevalence of both conditions poses a major challenge for clinicians in the 21st century. Both diabetes and metabolic syndrome are associated with a clustering of cardiovascular risk factors. In particular, dyslipidaemia characterised by low plasma levels of high-density lipoprotein cholesterol (HDL-C), elevated triglycerides and an increase in small, dense low-density lipoprotein (LDL) particles (the lipid triad), has been established as the most important modifiable risk factor for coronary heart disease (CHD). Current treatment guidelines recognise the increased CHD risk associated with diabetes and metabolic syndrome and focus on LDL-C lowering with statin treatment, in addition to dietary and lifestyle modification, as the primary lipid-modifying therapy. However, while there is no doubt that statin therapy significantly reduces CHD risk in these patients, their residual absolute risk remains higher than in individuals without diabetes or metabolic syndrome. Thus, there is a clear need to target other aspects of lipoprotein metabolism, notably low HDL-C and hypertriglyceridaemia, to further reduce CHD risk. Combining statin therapy (targeting LDL-C) with interventions that also modify low HDL-C and elevated triglycerides could be a useful strategy to optimise CHD risk reduction. Cautious combination of a fibrate or nicotinic acid with a statin is useful for the management of combined dyslipidaemia. Nicotinic acid is the more potent agent for raising HDL-C (by up to 29% at clinically recommended doses). It also substantially reduces triglycerides and LDL-C, and promotes a shift from small, dense LDL to larger, more buoyant LDL particles. Preliminary clinical data suggest that combining nicotinic acid with a statin will produce a greater reduction in cardiovascular risk in patients with diabetes and metabolic syndrome than statin monotherapy alone. Nicotinic acid is also safe for use in patients with diabetes, with no evidence of clinically relevant deterioration in glycaemic control at recommended doses (< or = 2 g/day). On review of the available evidence, this European Consensus Panel recommends the combination of nicotinic acid and a statin, together with lifestyle modification, as a useful strategy to lower CHD risk in patients with diabetes and metabolic syndrome. Prolonged-release nicotinic acid with improved tolerability compared with previous formulations may have obvious advantages for use in this setting.
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PMID:Nicotinic acid in the management of dyslipidaemia associated with diabetes and metabolic syndrome: a position paper developed by a European Consensus Panel. 1596 66

The metabolic syndrome is a constellation of interrelated abnormalities that increase the risk for cardiovascular disease and progression to type 2 diabetes. The prevalence of this syndrome is increasing because of the 'obesity epidemic'. The National Cholesterol Education Program Adult Treatment Panel III defined practical criteria for the diagnosis of the metabolic syndrome and established the basic principles for its management. Also, the International Diabetes Federation recently proposed another definition. The metabolic syndrome is a secondary target for cardiovascular risk reduction. Clinicians should identify individuals with this condition, assess their cardiovascular risk and treat them by an aggressive and multifaceted approach. The most effective therapeutic intervention in patients with the metabolic syndrome should focus on modest weight reduction and regular physical activity. Adoption of a healthier diet and smoking cessation are necessary. Drug therapy may be needed to achieve recommended goals if therapeutic lifestyle changes are not sufficient. Low-density lipoprotein cholesterol is the primary target of therapy (new aggressive goals should be achieved). Statins are probably the drugs of choice. Fibrates and nicotinic acid are also useful options. Hypertension should be managed aggressively probably starting with an inhibitor of the renin-angiotensin system or a calcium channel blocker and adding a low dose of a thiazide diuretic if necessary. Aspirin should be administered if the cardiovascular risk is high. In the future acarbose, metformin, meglitinides and thiazolidinediones may be used in patients with the metabolic syndrome to delay the onset of type 2 diabetes and reduce cardiovascular risk. Such an intense and multifactorial approach is likely to reverse the bad prognosis associated with the metabolic syndrome.
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PMID:Diagnosis and management of the metabolic syndrome in obesity. 1624 14

Serum cholesterol is a major risk factor for cardiovascular disease. Total cholesterol, LDL cholesterol and triglycerides are positively related to cardiovascular disease, while HDL cholesterol has an inverse relationship. Measurement of lipids is essential in individuals with established cardiovascular disease or type 2 diabetes, and may also be carried out in healthy individuals as part of cardiovascular risk assessment. Lifestyle measures are important in cardiovascular disease prevention, but the mainstay of lipid lowering therapy is appropriate use of lipid lowering drugs. Total and LDL cholesterol are the primary targets for treatment, but consideration should also be given to raising HDL cholesterol and lowering triglycerides where appropriate. Statins are the most frequently used lipid lowering agents, but there is an important place for other drugs, including ezetimibe, fibrates and nicotinic acid.
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PMID:Lipids for psychiatrists - an overview. 1628 Mar 39

Prolonged-release (PR) nicotinic acid (niacin) [Niaspan] is an oral, once-daily formulation of the lipid-modifying drug designed to produce less vasodilatory flushing than crystalline immediate-release (IR) nicotinic acid and less hepatotoxicity than previous sustained-release formulations of nicotinic acid.PR nicotinic acid appears to retain the same level of efficacy as crystalline IR nicotinic acid and be better tolerated than older nicotinic acid formulations. Nicotinic acid has beneficial effects on all traditional blood lipid and lipoprotein fractions and is the most effective agent for increasing high-density lipoprotein (HDL)-cholesterol (HDL-C) and reducing lipoprotein(a). The effects of PR nicotinic acid are often additive when used in combination with HMG-CoA reductase inhibitors (statins), making it a useful addition when lipid goals are not achieved with the usual statin monotherapy or when additional correction of a specific lipid abnormality is required. PR nicotinic acid also slows atherosclerotic progression and even appears to produce regression of atherosclerosis in patients on stable statin therapy. PR nicotinic acid is a logical drug choice for treating atherogenic dyslipidaemia commonly associated with type 2 diabetes mellitus and the metabolic syndrome, and has been shown to be effective in patients with diabetes without adversely affecting glycaemic control in the majority of patients. The incidence of vasodilatory flushing with PR nicotinic acid is lower than with IR nicotinic acid and it decreases substantially over time as tolerance develops. To date, there has been no clinically significant hepatotoxicity observed with PR nicotinic acid. Therefore, once-daily PR nicotinic acid appears to maximise the potential benefits of nicotinic acid, while minimising any historical tolerability or safety concerns.
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PMID:Prolonged-release nicotinic acid: a review of its use in the treatment of dyslipidaemia. 1639 85

Our understanding of the relationship between the atheroprotective activities of HDL and heterogeneity of HDL particles has advanced greatly. HDL particles are highly heterogeneous in structure, intravascular metabolism and antiatherogenic activity. In this review, we discuss new findings on the antiatherogenic properties of HDL particles. Small, dense HDL possesses potent antioxidative activity but this is compromised under conditions of atherogenic dyslipidemia. HDL functional deficiency frequently coincides with reductions in HDL-cholesterol concentration and alterations in HDL metabolism and structure. Formation of small, dense HDL particles with attenuated antiatherogenic activity can be mechanistically related to HDL enrichment in triglycerides and in serum amyloid A, depletion of cholesteryl esters, covalent modification of HDL apolipoproteins and attenuated antiatherogenic function of apolipoprotein AI. Low circulating levels of HDL cholesterol might, therefore, be associated with the defective functionality of small HDL particles of abnormal structure and composition. In common metabolic diseases, such as type 2 diabetes and metabolic syndrome, deficiency of HDL particle number and function favor accelerated atherosclerosis. Therapeutic normalization of the quantity, quality and biological activities of HDL particles thus represents a novel approach to attenuating atherosclerosis in dyslipidemic individuals with metabolic disease. Cholesteryl ester transfer protein inhibitors, nicotinic acid, reconstituted HDL and other HDL-raising agents are being investigated. Induction of selective increase in the circulating concentrations of small, dense HDL3 particles with increased antiatherogenic activity seems especially promising, particularly for therapy of atherogenic dyslipidemia.
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PMID:Antiatherogenic small, dense HDL--guardian angel of the arterial wall? 1650 60

Impaired effectiveness of glucose to suppress endogenous glucose production (EGP) is an important cause of worsening hyperglycemia in type 2 diabetes. Elevated free fatty acids (FFAs) may impair glucose effectiveness via several mechanisms, including rapid changes in metabolic fluxes and/or more gradual changes in gene expression of key enzymes or other proteins. Thus, we examined the magnitude and time course of effects of FFAs on glucose effectiveness in type 2 diabetes and whether glucose effectiveness can be restored by lowering FFAs. Glucose fluxes ([3-(3)H]-glucose) were measured during 6-h pancreatic clamp studies, at euglycemia (5 mmol/l glucose, t=0-240 min), and hyperglycemia (10 mmol/l, t=240-360 min). We studied 19 poorly controlled subjects with type 2 diabetes (HbA(1c) 10.9 +/- 0.4%, age 50 +/- 3 years, BMI 30 +/- 2 kg/m(2)) on at least two occasions with saline (NA- group) or nicotinic acid (NA group) infusions for 3, 6, or 16 h (NA3h, NA6h, and NA16h groups, respectively) to lower FFAs to nondiabetic levels. As a reference group, glucose effectiveness was also assessed in 15 nondiabetic subjects. There was rapid improvement in hepatic glucose effectiveness following only 3 h of NA infusion (NA3h = 31 +/- 6% suppression of EGP with hyperglycemia vs. NA- = 8 +/- 7%; P<0.01) and complete restoration of glucose effectiveness after 6 h of NA (NA6h = 41 +/- 8% suppression of EGP; P = NS vs. nondiabetic subjects). Importantly, the loss of hepatic glucose effectiveness in type 2 diabetes is completely reversible upon correcting the increased FFA concentrations. A longer duration of FFA lowering may be required to overcome the chronic effects of increased FFAs on hepatic glucose effectiveness.
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PMID:Time-dependent effects of free fatty acids on glucose effectiveness in type 2 diabetes. 1673 40

Type 2 diabetes and atherosclerotic vascular disease develop in parallel. Prospective epidemiologic studies have shown a striking communality of major risk factors for both diseases. This raises the question of a "common soil". The traits of the metabolic syndrome including dyslipidemia, visceral obesity and hypertension are predictors of type 2 diabetes as well as coronary heart disease. The same applies to the environmental factors: overnutrition, physical inertia and smoking. Visceral obesity, insulin resistance and low-grade inflammation are known as major components of the common soil for metabolic syndrome and coronary heart disease. Depending on the quality of metabolic control diabetes will accelerate the progression of atherosclerosis via unstable plaque formation. The "common soil" concept provides a paradigm for an integrated therapeutic approach. This applies to a lifestyle intervention as well as a rational use of drugs in diseases of the metabolic syndrome. The medication should consider coexisting disorders of the metabolic syndrome to use pleiotropic effects. On the other hand, side effect such as the worsening of blood glucose levels caused by beta-blockers and diuretics should be avoided. The following medication should be preferred in context of the metabolic syndrome: oral antidiabetics such as acarbose, metformin and thiazolidinediones, antihypertensives such as ACE inhibitors and ARBs (angiotensin receptor blockers) and lipid-lowering drugs such as atorvastatin, rosuvastatin, and the modern nicotinic acid derivative Niaspan, respectively. The strategy using synergies in drug treatment can reduce polypharmacy and costs and improve the patients' compliance.
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PMID:[Metabolic syndrome: "common soil" for diabetes and atherosclerosis. Novel approaches to an integrated therapy]. 1677 May 62


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