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Query: UMLS:C0011860 (type 2 diabetes)
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Patients with insulin resistance or type 2 diabetes have a particularly high risk for heart failure and a poor prognosis once they develop heart failure. The choice of drugs for the management of heart failure in these patients should be directed at changing the natural history of the disease. The various drugs available for the treatment of heart failure, including ACE inhibitors and beta-adrenergic blockers, are known to be beneficial and should be given as first-line agents. Aggressive risk-factor modification and tight blood pressure and glycemic control are crucial. Much work is needed to establish the safety and efficacy of various oral antidiabetic agents, especially the TZDs, for which the theoretic benefits are substantial and overall morbidity and mortality impact remain ill-defined.
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PMID:Cardiomyopathy and heart failure in diabetes. 1172 99

Atherosclerosis kills more patients with diabetes than all other causes combined. Treatment must be focused on several targets: glycemic control, bulk reductions of LDL cholesterol, and shifting LDL particle size. Aggressive treatment and reversal of dyslipidemias is a proven prevention for coronary events in patients with type 2 diabetes. Glycemic control with diet, oral hypoglycemic agents, and insulin, when necessary, is often only partially effective in normalizing lipid values in type 2 diabetes. Intensive treatment with lipid-regulating agents, particularly statins, is often necessary to normalize diabetes-associated dyslipidemias. Statins are also the only agents thus far shown in prospective, controlled trials to reduce the risk of coronary events in diabetic patients definitively.
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PMID:Treatment of dyslipidemia in diabetes. 1172 8

Preliminary evidence from trials with the HMG-CoA reductase inhibitors (statins), simvastatin and pravastatin, suggests that aggressive treatment of diabetic dyslipidaemia will reduce coronary events. Questions regarding the prevention of cardiovascular events in diabetic patients are now being addressed in prospectively designed trials. The first question is, can aggressive treatment of dyslipidaemia lead to primary prevention of cardiovascular events in patients with type 2 diabetes? This is being addressed in the ongoing Atorvastatin Study for the Prevention of coronary heart disease Endpoints in NIDDM (ASPEN) and the Collaborative AtoRvastatin Diabetes Study (CARDS). These trials will randomize over 4000 patients with type 2 diabetes and no previous myocardial infarction to either atorvastatin or placebo for 4 years. The second question is, are there benefits for aggressive lipid lowering to levels below those recommended in current treatment guidelines, i.e. is lower better? Results from the recent Atorvastatin VErsus Revascularization Treatment (AVERT) trial suggest this to be the case. AVERT showed that, in stable coronary heart disease patients who had been referred for revascularization, aggressive lowering of low density lipoprotein (LDL) cholesterol with atorvastatin 80 mg/day (to a mean level of 2.0 mmol/L [77 mg/dL]) reduced the incidence of ischaemic events by 36% compared with angioplasty and usual care (which reduced LDL cholesterol to 3.1 mmol/L [119 mg/dL]). The 36% reduction in events with atorvastatin versus angioplasty and usual care trended towards significance (p=0.048). The benefits of aggressive lipid-lowering therapy are also being investigated in the ongoing Treating to New Targets (TNT) and Incremental Decrease in Endpoints through Aggressive Lipid lowering (IDEAL) trials. These studies will more closely examine the benefits of treating diabetic dyslipidaemia, and will determine how aggressively this abnormal lipid profile should be treated.
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PMID:What does the future hold for diabetic dyslipidaemia? 1182 50

Women suffer more often from depression than males, indicating that hormones might be involved in the etiology of this disease. Low as well as high testosterone (T) levels are related to depression and well-being in women, T plasma levels correlate to depression in a parabolic curve: at about 0.4-0.6 ng/ml plasma free T a minimum of depression is detected. Lower levels are related to depression, osteoporosis, declining libido, dyspareunia and an increase in total body fat mass. Androgen levels in women decrease continuously to about 50% before menopause compared to a 20-year-old women. Androgen levels even decline 70% within 24 h when women undergo surgical removal of the ovaries. Conventional oral contraception or HRT cause a decline in androgens because of higher levels of SHBG. Hyperandrogenic states exist, like hirsutism, acne and polycystic ovary syndrome. Social research suggests high androgen levels cause aggressive behavior in men and women and as a consequence may cause depression. Higher androgen values are more pronounced at young ages and before and after delivery of a baby and might be responsible for the "baby blues". It was found that depression in pubertal girls correlated best with an increase in T levels in contrast to the common belief that "environmental factors" during the time of growing up might be responsible for emotional "up and downs". T replacement therapy might be useful in perimenopausal women suffering from hip obesity, also named gynoid obesity. Abdominal obesity in men and women is linked to type 2 diabetes and coronary heart diseases. Testosterone replacement therapy in hypoandrogenic postmenopausal women might not only protect against obesity but also reduce the risk of developing these diseases. Antiandrogenic progestins might be useful for women suffering from hyperandrogenic state in peri- and postmenopause. Individual dosing schemes balancing side effects and beneficial effects are absolutely necessary. Substantial interindividual variability in T plasma values exists, making it difficult to utilize them for diagnostic purposes. Therefore a "four-level-hormone classification scheme" was developed identifying when estradiol (E) and T levels are out of balance. (1) Low E-low T levels are correlated with osteoporosis, depression, and obesity; (2) high E-low T with obesity, decreased libido; (3) high T-low E levels with aggression, depression, increased libido, and substance abuse; (4) high E-high T with type II diabetes risk, breast cancer and cardiovascular risk. Testosterone delivery systems are needed where beneficial and negative effects can be balanced. Any woman diagnosed for osteoporosis should be questioned for symptoms of depression.
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PMID:The impact of testosterone imbalance on depression and women's health. 1195 93

Coronary heart disease (CHD) is the leading cause of death in patients with type 2 diabetes. The hyperglycaemia that characterises this disease is often accompanied by a cluster of other risk factors, such as dyslipidaemia and hypertension, and effective management of the patient with diabetes requires treatment directed at correcting all of the abnormalities that increase cardiovascular risk. Approximately 90% of patients with diabetes have type 2 disease, and dyslipidaemia in these patients is characterised by elevated plasma triglycerides and very-low-density lipoproteins (VLDL), by reduced high-density lipoprotein cholesterol (HDL-C), and by a shift in LDL distribution towards small, dense particles. All of these lipid abnormalities are important risk factors for CHD. Retrospective subgroup analysis and prospective studies have shown that lipid-lowering therapy can slow the progression of atherosclerosis and reduce the risk for cardiovascular events in patients with diabetes, and both the National Cholesterol Education Program Adult Treatment Panel III and American Diabetes Association have established aggressive treatment goals for lipid-lowering therapy in these patients. All of the major medications used to treat hyperlipidaemia in other populations (niacin, fibrates, bile acid sequestrants and statins) have been used effectively to improve the plasma lipid profile in patients with diabetes. Statins are generally accepted as first-line treatment for these patients, although fibrates also have an important role in patients with pronounced hypertriglyceridaemia. Statins significantly reduce low-density lipoprotein cholesterol (LDL-C) in a broad range of patients. These agents also have substantial effects on plasma triglycerides and, in patients with hypertriglyceridaemia, lower very-low-density lipoprotein cholesterol (VLDL-C) to approximately the same extent as LDL-C. In this regard, the new agent rosuvastatin has been shown, in recent trials, to produce greater decreases in these lipoproteins than currently marketed compounds. Aggressive use of agents that attack the lipid abnormalities characteristic of patients with type 2 diabetes has the potential to significantly reduce CHD risk in these individuals.
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PMID:Management of hypercholesterolaemia in the patient with diabetes. 1229 6

Aggressive treatment of hypertension is effective in reducing both microvascular and macrovascular complications in type 2 diabetes, and target BP less than 130/85 or 130/80 mmHg are now recommended. Inhibition of renin angiotensin aldosterone system (RAAS) plays an essential role in the treatment of hypertension and diabetes-related complications. Studies focusing on renal end-points suggest that angiotensin-converting enzyme inhibitors (ACE-I) are more effective than other traditional agents in reducing the onset of clinical proteinuria in both type 1 and type 2 diabetic patients with incipient nephropathy, mainly in normotensive ones (secondary prevention). However, several small trials in type 2 diabetic patients with overt nephropathy (tertiary prevention) failed to demonstrate a specific renoprotective role for ACE-I, at variance with type 1 diabetes. Three recent large trials address the question of whether angiotensin II receptor blockers (ARB) prevent the development of clinical proteinuria or delay the progression of nephropathy in type 2 diabetes. The IRMA study showed that irbesartan is more effective than conventional therapy in preventing the development of clinical proteinuria and in favoring the regression to normoalbuminuria for comparable BP control in patients with incipient nephropathy. The IDNT and RENAAL trials showed that ARB are more effective than traditional antihypertensive therapies in reducing progression toward end-stage renal failure (ESRF) in type 2 diabetic patients with overt nephropathy independently of changes in BP. Moreover, a reduction in hospitalizations for heart failure was demonstrated for ARB-treated patients compared with placebo. Furthermore, the LIFE study showed that losartan is more effective than conventional therapy in reducing cardiovascular morbidity and mortality in a cohort of diabetic patients with hypertension and left ventricular hypertrophy. In conclusion, ARB seem to be effective in both preventing renal damage and reducing progression toward ESRF in type 2 diabetic patients. Thus, the guidelines for the prevention and treatment of diabetic nephropathy are now changed. In type 1 diabetes ACE-I are the first-choice drug; in type 2 diabetes, ARB are considered first-choice drugs in secondary prevention as well as ACE-I and have been now elected the unique first-choice drug in tertiary prevention of ESRF. Finally, ARB should be considered as the first-choice drug in cardiovascular prevention too, as well as ACE-I.
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PMID:Renal and cardiovascular protection in type 2 diabetes mellitus: angiotensin II receptor blockers. 1246 18

Aggressive therapy for patients with type 2 diabetes mellitus and renal disease is warranted given the natural history of this disease. Although antagonizing the renin-angiotensin system is clearly important, how this is accomplished is of considerable controversy. On the one hand, recent clinical trials of patients with type 2 diabetes mellitus with renal disease demonstrate unequivocally the renal protective effect of angiotensin receptor blockers (ARBs). Although the results of the recently published LIFE trial are encouraging, inconsistencies have been observed with ARBs in reducing cardiovascular end points. On the other hand, angiotensin-converting enzyme inhibitors have a dramatic effect in reducing cardiovascular events but have not been shown convincingly to reduce progression of renal disease in patients with type 2 diabetes mellitus. These studies leave us in a quandary as to the optimal initial treatment regimen for patients with type 2 diabetes mellitus and renal disease despite the recent recommendations from the American Diabetes Association (Alexandria, Va). Given the fact that many of these individuals will require administration of multiple antihypertensive agents, perhaps the initial treatment with a combination of an ARB and angiotensin-converting enzyme inhibitor affords optimal cardiovascular and renal protection for patients with type 2 diabetes mellitus and renal disease. Future clinical trials should be designed to address this issue.
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PMID:Combination therapy with angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists in the treatment of patients with type 2 diabetes mellitus. 1274 99

The endothelium regulates vascular tone through the release of vasodilating and vasoconstricting substances. The most important of these vasodilating substances is nitric oxide (NO), which is also vascular protective and inhibits inflammation, oxidation, vascular smooth muscle cell proliferation, and migration. Damage to the endothelium causes endothelial dysfunction with impaired release of NO and loss of its antiatherogenic protection. Traditional risk factors for coronary artery disease, including diabetes, hypercholesterolemia, hypertension, and low levels of high-density lipoprotein cholesterol, are associated with endothelial dysfunction and thus promote the atherogenic process. More recently, insulin resistance in the absence of overt diabetes or the metabolic syndrome has been associated with endothelial dysfunction. This association provides evidence that the atherosclerotic process may actually begin earlier in the spectrum of insulin resistance, ultimately resulting in a progression of the metabolic syndrome to prediabetes and then to type 2 diabetes. Aggressive treatment of dyslipidemia and hypertension, even before the onset of type 2 diabetes, would appear prudent in decreasing the progression of the atherosclerotic process. The thiazolidinediones are peroxisome proliferator-activated receptor-gamma agonists that improve glucose and lipid metabolism. These agents have recently been shown to improve endothelial function in the early stages of insulin resistance. Results from ongoing trials with thiazolidinediones will reveal whether they will also reduce cardiovascular end points.
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PMID:Role of endothelial dysfunction in insulin resistance. 1295 22

The direct correlation between glucose levels and cardiovascular disease in individuals with type 2 diabetes can now be applied to individuals that share an abnormal metabolic milieu similar to that found in central obesity, the metabolic syndrome, and type 2 diabetes. Premature macrovascular complications with a very high morbidity and mortality rate can be found in these nondiabetic populations. The typical phenotype has visceral or central obesity, excess of free fatty acids, insulin resistance, increased insulin secretion, and hypertension. A more complex metabolic-cardiovascular syndrome develops that includes dyslipidemia, abnormal production of cytokines, chronic inflammatory state, and abnormal coagulation. The interplay of all these cardiovascular risk factors is responsible for the accelerated atherosclerotic process. The different terminologies used for populations sharing this common ground for premature cardiovascular disease now generally accepted as the metabolic syndrome, are also discussed. Aggressive insulin treatment during acute illness in individuals with the abnormal metabolic milieu is beneficial. Insulin treatment is changing from using insulin as a hormone to treat only severe hyperglycemia, to a new paradigm using insulin in high doses as a drug. Aggressive insulin regimens should be used to treat only minimal elevations of blood glucose or to prevent hyperglycemia. The newly observed properties of insulin are reviewed which include suppression of inflammatory cytokines and adhesion molecules, improved hemostasis, and other cardiac beneficial effects. The concomitant administration of intravenous glucose and insulin permits the administration of higher insulin doses that can result in improved outcome due to its nonglycemic-related benefits. The use of aggressive insulin therapy requires both better and more cost-effective algorithms to successfully treat this high-risk population during acute illness.
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PMID:Using insulin as a drug rather than as a replacement hormone during acute illness: a new paradigm. 1450 30

Diabetes complications are common and almost triple the annual cost of managing diabetes. Microvascular complications are the major risk in type 1 diabetes, while macrovascular complications are the major cause of morbidity and mortality in type 2 diabetes. Control of hyperglycaemia (target HbA(1c) level < or = 7%) and hypertension (target blood pressure < or = 130/80 mmHg) prevents microvascular complications in both types of diabetes; a multifactorial approach, comprising behaviour modification and pharmacological therapy for all risk factors, reduces the development of micro- and macrovascular complications in type 2 diabetes. The benefit of treating dyslipidaemia is at least as great in the diabetic population as in the non-diabetic population. Angiotensin-converting enzyme inhibitors and low-dose aspirin are indicated in people with diabetes and other cardiovascular risk factors. Regular annual screening for diabetes complications allows treatable disease to be identified. Aggressive management of hyperglycaemia and other risk factors can prevent many complications
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PMID:3: Preventing complications of diabetes. 1458 83


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