Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Individuals who survive an acute myocardial infarction (MI) have up to a ninefold greater risk of cardiovascular morbidity and mortality compared with the general population. The modification of traditional coronary risk factors, including hypertension, hyperlipidemia, tobacco use, and diabetes mellitus, constitutes one of the cornerstones of management after acute MI. Therapies aimed at reversing the pathophysiologic disorders that lead to endothelial dysfunction, thrombosis, and atherosclerotic plaque instability may improve the prognosis for patients after acute MI. Aggressive risk stratification diagnostic testing can identify patients at the highest risk for adverse events. Prior to hospital discharge, patients should have an evaluation of left ventricular systolic function, an assessment for the risk for residual myocardial ischemia, and a clinical assessment of the risk for serious ventricular arrhythmias. An array of pharmaceutical agents is available for the secondary prevention of MI, including antiplatelet agents, beta-blockers, angiotensin-converting enzyme inhibitors, and statins.
 ...
PMID:Management After Myocardial Infarction. 1179 27

The need for permanent, nonspecific, and potentially harmful immunosuppression remains a major obstacle for islet transplantation. The response of a type 1 diabetic recipient to an islet graft includes a specific allogenic immune response and the recurrence of autoimmunity. Free or encapsulated in an immunoisolation device, islet cells are exposed to immune aggression, initiated by donor antigen-presenting cells or by indirect, host antigen-presenting cell-mediated antigen presentation. CTLA4-Ig is a genetically engineered fusion protein of human CTLA4 and the IgG 1 Fc region. It prevents T-cell activation by binding to human B7, which costimulates T cells through CD28. Interesting data were reported in experimental islet transplantation, suggesting that CTLA4-Ig may be slightly but significantly beneficial to islet allograft survival, although studies in autoimmune diabetes are scarce. The main limitations include transient and low levels of expression when CTLA4-Ig is delivered locally, a predominant effect on the direct recognition pathway, and the lack of effect on memory cells. Clinical trials in islet transplantation could be discussed in nonuremic patients, with steroid-free and anticalcineurin-free regimens, in combination with another costimulation blocker, rapamycin, and an anti-interleukin 2 receptor antibody, and with a strategy directed against the recurrence of autoimmunity.
 ...
PMID:Immunomodulation with CTLA4-Ig in islet transplantation. 1181 61

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.
 ...
PMID:What does the future hold for diabetic dyslipidaemia? 1182 50

We have previously shown a specific significant overexpression in the exocrine pancreatic tissue of two members of the regenerating gene multifamily: reg I and reg II in the non-obese diabetic (NOD) mouse during active diabetogenesis. To strengthen the hypothesis that the overexpression of these genes may represent a defence of the acinar cell against pancreatic endocrine agression, we studied the pancreatic expression and the localization of another member of this family: the pancreatitis-associated protein (PAP) in NOD mice under the same conditions. We found that NOD mice present significantly higher PAP mRNA levels than control IOPS-OF1 mice. There is no difference between female NOD mice which progressively develop type I diabetes between 100 and 200 days and male NOD mice which are protected. The only difference observed was in function of the age of onset of diabetes. Before 180 days, the PAP mRNA levels were similar to those found in NOD males and nondiabetic females, but above 180 days the levels of PAP mRNA increased significantly. More importantly immunohistological studies demonstrate a striking difference in the protein localization between normal or nondiabetic NOD mice and diabetic NOD mice. If the protein is mainly detected in the islet cells in the absence of diabetes, a specific and intense expression of PAP was observed in the acinar cells of diabetic NOD mice. In conclusion, our data demonstrates that the acinar cells may react to a long-lasting pancreatic endocrine aggression by an induction of PAP and underlines the existence of a symbiotic relationship between endocrine and exocrine tissue.
 ...
PMID:Pancreatitis-associated protein (HIP/PAP) gene expression is upregulated in NOD mice pancreas and localized in exocrine tissue during diabetes. 1184 80

The concept of risk assessment and reduction, introduced initially by the Framingham Heart Study and refined in other models, forms the cornerstone of preventive cardiology. Risk factor assessment determines the therapeutic strategy, because the intensity of preventive intervention is tailored to the patient's risk of coronary heart disease. The conventional risk factors for coronary heart disease include elevated serum total cholesterol and LDL cholesterol, low HDL cholesterol, elevated blood pressure, cigarette smoking, diabetes, vascular disease, menopausal status (women only), and age. Aggressive risk factor reduction, formerly used exclusively in secondary prevention, may be pivotal to optimal patient management in high-risk primary prevention. A number of noninvasive imaging modalities have the potential to measure and to monitor atherosclerosis in asymptomatic individuals and include exercise ECG testing, electron beam computed tomography, magnetic resonance coronary angiography, positron emission tomography, ankle-brachial index, and B-mode ultrasound. Novel serum markers, including C-reactive protein and homocysteine, have the ability to gauge risk in the individual patient. Systemic therapy for risk reduction in primary prevention may be preferable to local therapy (eg, angioplasty and bypass) and may more effectively prevent acute coronary events than these more invasive approaches.
 ...
PMID:New tools for coronary risk assessment: what are their advantages and limitations? 1185 32

This study sought to determine the relationship between Youth Self Report (YSR) scores for behavior problems, YSR scores for social competence, and metabolic control in children and adolescents with Type 1 diabetes. Using a cross sectional design, 234 individuals between 11 and 18 years old were given the YSR at regular clinic appointments; glycosylated hemoglobin (GHb) was also measured. More than 50% of subjects showed GHb levels above 9%; the normal GHb level is 4.2% to 5.8%. Individuals reporting a greater number of behavior problems, though not in the pathological range on the aggression, delinquent behaviors, and attention problems subscales of the YSR, were more than twice as likely to have GHb levels above 9%. Using logistic regression the externalizing scale (aggression and delinquent behaviors combined) predicted elevated GHb at 2.41, p =.003. Youth in this study were middle-class and were receiving subspecialty care. Yet, over half of them had GHb levels above the recommended 9%. The psychological health of youth should be monitored at regular intervals. Longitudinal studies are needed to determine whether aggression, delinquent behaviors, and attention problems in children and adolescents with Type 1 diabetes result later in depression and elevated levels of GHb in these same individuals or whether these elevations are transient. Interviews could be supplemented with instruments such as the YSR and care given for those with a higher number of self-reported problems.
 ...
PMID:Psychosocial factors associated with levels of metabolic control in youth with type 1 diabetes. 1189 92

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.
 ...
PMID:The impact of testosterone imbalance on depression and women's health. 1195 93

Primary care physicians typically encounter patients who are not at obvious risk for CAD but who nonetheless need and can benefit from lipid-lowering therapy. Applying algorithms or scoring systems can be helpful in estimating an individual patient's risk, but the basic tools available in everyday clinical practice can be used to alert physicians to elevated CAD risk in their patients. Those patients whose LDL-C level is at or above 220 mg/dL (5.69 mmol/L) should routinely and deservedly get clinical attention, but they account for only 2.5% to 5% of the population. Those with an "average" LDL-C level number in the millions, and from this patient pool come the coronary events that fill clinics and hospitals. Aggressive treatment approaches are required to meet NCEP objectives, and every indication suggests that these goals are just the minimum. The third report of the NCEP Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) has broadened the indications for drug therapy, reclarifying diabetes and peripheral vascular or cardiovascular disease equivalents and using a global evaluation concept, which will identify 30 million Americans in need of drug treatment. The statins safely and effectively lower LDL-C levels, which is the basis for instituting drug therapy, according to NCEP guidelines. Using these drugs also raises HDL-C levels, which is somewhat protective, and decreases triglyceride levels. The efficacy of statin therapy in both primary and secondary prevention of CAD is now well established. If used more often when dietary therapy fails, which happens quite often, and in doses sufficient to work effectively, statins have the power to turn the corner on the prevention and treatment of atherosclerotic coronary disease in the United States.
 ...
PMID:Keeping an eye on cardiovascular risk. A practical, case-study approach to assessment in office practice. 1198 26

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.
 ...
PMID:Management of hypercholesterolaemia in the patient with diabetes. 1229 6

Aggressive treatment of atherosclerotic risk factors can substantially reduce stroke risk in patients with a history of stroke or transient ischemic attack. Data from several recent large clinical trials provide convincing evidence of benefit for a number of specific therapies directed at this population. The authors recommend treatment with ramipril alone or perindopril plus indapamide regardless of blood pressure, provided there is no contraindication. For patients already taking a different angiotensin- converting enzyme (ACE) inhibitor, the authors do not routinely switch agents. The authors recommend use of simvastatin 40 mg per day in patients with a total cholesterol level of 135 mg/dL or greater, provided no contraindication exists. The authors also recommend consideration of gemfibrozil in patients with isolated low high- density lipoprotein levels. In patients with diabetes mellitus, tight glycemic control has not been shown to reduce macrovascular complications such as stroke, but does reduce microvascular complications. However, diabetics should receive especially aggressive treatment of other vascular risk factors. There is no role for post-menopausal hormone replacement therapy in prevention of stroke. Weight loss for overweight patients, regular exercise, and a diet rich in fruits, vegetables, cereals, and fish, as well as low in fat and cholesterol, should be a standard recommendation for this group of patients. Treatment with folic acid, B(6), and B(12) for patients with elevated homocysteine appears rational, though this is unproven. However, there is no benefit to vitamin E, vitamin C, or beta-carotene supplementation. Smokers should stop. For every 43 smokers who quit, one stroke is prevented. Moderate consumption of alcohol (one to two drinks a day) may be beneficial, but heavy alcohol use (more than five drinks a day) increases stroke risk.
 ...
PMID:Atherosclerotic Risk Factors in Patients with Ischemic Cerebrovascular Disease. 1235 71


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>