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

The high-density lipoprotein (HDL)-Atherosclerosis Treatment Study showed that simvastatin plus niacin (mean daily dose 13 mg and 2.4 g, respectively) halt angiographic atherosclerosis progression and reduce major clinical events by 60% in patients with coronary artery disease (CAD) who have low HDL, in comparison with placebos, over 3 years. How safe and well-tolerated is this combination? One hundred sixty patients with CAD, including 25 with diabetes mellitus, with mean low-density lipoprotein cholesterol of 128 mg/dl, HDL cholesterol of < or =35 mg/dl (mean 31), and mean triglycerides of 217 mg/dl were randomized to 4 factorial combinations of antioxidant vitamins or their placebos and simvastatin plus niacin or their placebos. Patients were examined monthly or bimonthly for 38 months; side effects (gastrointestinal upset, nausea, anorexia, vision, skin, and energy problems, or muscle aches) were directly queried and recorded. Aspartate aminotransferase, creatine phosphokinase (CPK), uric acid, homocysteine, and fasting glucose levels were regularly monitored. A safety monitor reviewed all side effects and adjusted drug dosages accordingly. Patients who received simvastatin plus niacin and those on placebo had similar frequencies of clinical or laboratory side effects: any degree of flushing (30% vs 23%, p = NS), symptoms of fatigue, nausea, and/or muscle aches (9% vs 5%, p = NS), aspartate aminotransferase (SGOT) > or =3 times upper limit of normal (3% vs 1%, p = NS), CPK > or =2 times upper limit of normal (3% vs 4%, p = NS), CPK > or =5 times upper limit of normal, new onset of uric acid > or =7.5 mg/dl (18% vs 15%, p = NS), and homocysteine > or =15 micromol/L (9% vs 4%, p = NS). Glycemic control among diabetics declined mildly in the simvastatin-niacin group but returned to pretreatment levels at 8 months and remained stable for rest of the study. This combination regimen was repeatedly described by 91% of treated patients and 86% of placebo subjects as "very easy" or "fairly easy" to take. Thus, the simvastatin plus niacin regimen is effective, safe, and well tolerated in patients with or without diabetes mellitus.
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PMID:Safety and tolerability of simvastatin plus niacin in patients with coronary artery disease and low high-density lipoprotein cholesterol (The HDL Atherosclerosis Treatment Study). 1475 79

Large-scale intervention trials demonstrate that treatment with statins, the most effective lipid lowering drug class, significantly reduces the risk of coronary heart disease events. Recent evidence suggests that more aggressive LDL cholesterol lowering with newly developed statins may provide greater clinical benefit, even in individuals with moderately elevated serum cholesterol levels. There is increasing evidence that statins exert a myriad of other beneficial pleiotropic effects on the vascular wall, thus altering the course of atherosclerotic disease. In the long-term treatment, non-life-threatening side effects may occur in up to 15% of patients receiving one statin. Significant elevations in the activity of serum aminotransferase and creatine kinase alone or in combination with muscle pain in statin-treated patients should be taken seriously. The combination of the statins with gemfibrozil results in higher rates of drug toxicity. Reports show possible adverse effects of statins on nervous system function including mood alterations, however, statins have also been associated with improvement in central nervous system disorders. Special attention must be paid to the tolerability of the statins in children, elderly and transplant patients. Future clinical studies and surveillance information will warrant long term safety of each member of this class of lipid-lowering agents. New classes of patients with diabetes, metabolic syndrome and renal diseases may have clinical benefits from statins. New upcoming clinical trials will address the fundamental question of whether statin treatment can protect from the natural history of atherosclerotic-related diseases. This will require a more prolonged follow-up (i.e., 10 to 15 years). Finally, the basic understanding of newer pathogenic mechanisms involving the effects of statins on angiogenesis and the nitric oxide pathway should be explored in the clinical setting as well as the study of pathogenic mechanisms by which statins can affect plaque instability.
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PMID:Statin treatment and the natural history of atherosclerotic-related diseases: pathogenic mechanisms and the risk-benefit profile. 1496 3

Erdheim-Chester disease is an idiopathic systemic histiocytosis hystologically different to Langerhans histiocytosis which is characterized by symmetric sclerotic bone lesions, predominantly affecting the diaphyseal and metaphyseal areas of large bones. It is not classified within malignant histiocytosis, but the clinical course tends to be aggressive with a poor response to different schedules of treatment. In rare cases the association of both entities has been reported: Erdheim-Chester disease and Langerhans histiocytosis. We present a new case with histological data of both histiocytosis whose clinical course included bone and muscle pain, insipidus diabetes, exophthalmos, bilateral symmetrical sclerosing bone lesions and a cerebellar syndrome.
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PMID:[Erdheim-Chester disease and Langerhans histiocytosis. A fortuitous association?]. 1562 55

Diabetic muscle infarction (DMI) is a largely unfamiliar disease. It affects mainly patients around 40 years of age with long-standing diabetes and concomitant end-organ complications. The symptoms represent a classic pattern of a musculoskeletal disease with muscle pain without trauma, swelling, and functional impairment. Although its short-term prognosis is good, with improvement of the symptoms over weeks or months under analgesia and rest, a high recurrence rate of up to 60% can be observed. Additionaly, the long-term survival of patients after DMI is reduced mostly due to major vascular complications. Since many diabetic patients are in orthopedic care for musculoskeletal disorders, the orthopedic surgeon should be aware of this disease to avoid unnecessary invasive diagnostic procedures and initiate suitable therapy. Furthermore, a better knowledge of the disease could lead to definite conclusions regarding its real incidence and aid in establishing new therapeutic measures for prophylaxis and better long-term survival.
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PMID:[Diabetic muscle infarction-an orthopedic disease pattern?]. 1565 99

Hyperlipidaemia is a pivotal risk factor for the development of atherosclerotic disease. A large number of studies have demonstrated that the treatment of abnormalities in lipoprotein levels reduces the risk for myocardial infarction, peripheral vascular disease, carotid artery disease, stroke, and cardiovascular mortality. Despite the development of multiple drug classes to treat dyslipidaemias and the promulgation of clearly defined guidelines for the management of lipid disorders, dyslipidaemia tends to be undertreated in the majority of patients at risk for cardiovascular disease. A part of the reluctance to treat different lipoprotein fractions to goal levels is attributable to physician- and patient-related concerns over the increasing toxicity of available therapies, as their dosages are increased. The risks of hepatotoxicity, myalgia, and rhabdomyolysis are fairly well characterised in patients receiving statins, fibrates and niacin. Another issue affecting treatment success rates is the fact that many patients with complex dyslipidaemias are inadequately responsive to single-agent therapy. As the epidemics of obesity, metabolic syndrome and diabetes mellitus continue to worsen, physicians will encounter severe, mixed dyslipidaemias more frequently. Many of these patients will require combinations of drugs to address the various metabolic derangements causing changes in multiple lipoprotein fractions. Although the need for combination therapy is well-established in the management of disorders, such as hypertension and diabetes, it is less often used for the treatment of dyslipidaemias. The development of safe, cost-effective, and efficacious combination dyslipidaemic therapy is an important goal in cardiovascular medicine. Simvastatin plus ezetimibe has recently been combined as a fixed dose therapy, which offers clinicians the opportunity to simultaneously inhibit two key pathways in cholesterol metabolism: hepatic cholesterol biosynthesis and the absorption of cholesterol at the level of the proximal jejunum. This dual mechanism of inhibition substantially increases the capacity to decrease serum levels of atherogenic low-density lipoproteins and increase high-density lipoprotein, compared with that observed when either drug is used alone. This combination increases the likelihood of therapeutic success in patients with dyslipidaemia.
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PMID:Simvastatin plus ezetimibe: combination therapy for the management of dyslipidaemia. 1570 90

Insulin-like growth factor-1 (IGF-1) and its receptors share considerable homology with insulin and insulin receptors, and their respective signaling pathways interact at the post receptor level. While the growth hormone (GH)-IGF-1 axis principally regulates tissue growth and differentiation, insulin exerts it primary effects on fuel metabolism. However, these two endocrine systems interact at multiple levels and in diabetes mellitus the GH-IGF-1 axis is grossly disturbed, with increased secretion of GH, reduced plasma levels of IGF-1, and complex tissue-specific changes in IGF binding proteins (IGFBPs). These observations have given rise to the view that GH-IGF-1 axis dysfunction, particularly low plasma levels of circulating IGF-1, probably play a significant role in several aspects of the pathophysiology of diabetes mellitus, including insulin resistance and poor glycemic control, and may also influence the development of microvascular complications. The availability of recombinant human IGF-1 (rhIGF-1; mecasermin), used either alone or in combination with insulin, has led to experimental studies and clinical trials in humans testing these hypotheses. These studies have examined the impact of subcutaneous rhIGF-1 injections on sensitivity and metabolic parameters. In patients with type 1 and 2 diabetes mellitus, insulin sensitivity is significantly improved, insulin requirements are reduced, and glycemic control of dyslipidemia is generally improved in short-term studies. rhIGF-1 is a particularly attractive possibility in patients with type 2 diabetes mellitus, where insulin resistance is the fundamental problem. Some patients with genetic syndromes of severe insulin resistance also benefit from treatment with rhIGF-1, which can bypass blocks in the insulin signaling pathway. The common adverse effects reported for rhIGF-1 are dose-related and include edema, jaw pain, arthralgia, myalgia, hypotension, injection site pain, and less commonly, Bell's palsy and raised intracranial pressure. Although disturbance of the GH-IGF-1 axis participates in the development of diabetic complications, the functional consequences of the complex changes in IGFBP expression at the tissue level are uncertain, and it is not known whether systemic IGF-1 therapy or other manipulations of the GH-IGF-1 axis would be helpful or harmful. Experimentally, IGF-1 has a protective effect on neuropathy, and could find an application in the healing of neuropathic ulcers. The potential benefits of IGF-1 therapy in diabetes mellitus have yet to be realised.
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PMID:Therapeutic potential of insulin-like growth factor-1 in patients with diabetes mellitus. 1583 92

Treating Hepatitis C among HIV patients under antiretroviral drug therapy requires a high degree of vigilance and continuous monitoring because of frequent problems with intolerance and/or drug interactions. Recent studies, including three therapeutic trials, on Ribavic, APRICOT, and ACTG A5671, have given some insights on following these patients up. The adverse effects are relatively similar in HCV-HIV-co-infected patients and patients infected by HCV only. Their frequency is, on the other hand, higher among HCV-HIV-Co-infected patients. The adverse-effects are consistent, in a non-exhaustive way, with pseudo influenza-like symptoms, fever, myalgia, cephalgia, with psychiatric disorders (irritability, depression, etc.); endocrine disorders (thyroid dysfunction, diabetes...); and with hematological anomalies especially anemia and leucopenia. But the percentage of lymphocyte T CD4 is not modified, therefore there is no risk of opportunistic infection. Pharmacokinetic interactions between antiretroviral drugs and treatment for HCV infection including ribavirin plus interferon alpha (IFN-alpha) or pegylated IFN are described. They are almost exclusively due to the combination of ribavirin and of nucleoside analogue reverse transcriptase inhibitors. One of the principal consequences is the emergence of mitochondrial toxicity defined by the occurrence of hyperlactatemia, or acute pancreatitis). Thus, some combinations should be avoided such as ddI+ribavirin and ddI+d4T+ribavirin. The d4T+ribavirin combination must also be used with caution.
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PMID:[Intolerance to and/or drug interactions of anti-HIV and anti-HVC therapy]. 1591 Nov 83

Intravenous immunoglobulin (IVIg) is administered for various indications and generally considered a safe therapy. Most of the adverse effects (AEs) associated with IVIg administration are mild and transient. The immediate AEs include headache, flushing, malaise, chest tightness, fever, chills, myalgia, fatigue, dyspnea, back pain, nausea, vomiting, diarrhea, blood pressure changes, tachycardia, and anaphylactic reactions, especially in IgA-deficient patients. Late AEs are rare and include acute renal failure, thromboembolic events, aseptic meningitis, neutropenia, and autoimmune hemolytic anemia, skin reactions, and rare events of arthritis. Pseudohyponatremia following IVIg is important to be recognized. Renal failure, usually oliguric and transient, occurs mostly on using sucrose-containing products owing to osmotic injury. Among high-risk patients who have a previous renal disease, dehydration, diabetes mellitus, advanced age, hypertension, hyperviscosity, or are treated by other nephrotoxic medications, administration of a non-sucrose-containing IVIg product after accomplishing hydration, in a low concentration and a slow infusion rate while supervising urine output and kidney function, is recommended. Thromboembolic complications occur because of hyperviscosity especially in patients having risk factors including advanced age, previous thromboembolic diseases, being bedridden, diabetes mellitus, hypertension, dyslipidemia, or those receiving high-dose IVIg in a rapid infusion rate. Immediate AEs can be treated by the slowing or temporary discontinuation of the infusion and symptomatic therapy with analgesics, nonsteroidal anti-inflammatory drugs, antihistamines, and glucocorticoids in more severe reactions. Slow infusion rate of low concentration of IVIg products and hydration, especially in high-risk patients, may prevent renal failure, thromboembolic events, and aseptic meningitis.
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PMID:Intravenous immunoglobulin: adverse effects and safe administration. 1639 92

A 76-year-old man with a history of myocardial infarction, Type 2 diabetes, hypertension, hypercholesterolemia, and heart failure presents with muscle pain and spasm. A number of medication-related problems are identified by the pharmacist. Prioritization of medication-related problems and therapeutic recommendations are provided. The medication-related problems described in this case reinforce the need for establishing individualized action plans and avoiding making too many changes in medication regimens at one time. In addition, the issue of nonpharmacological causes of symptoms can be overlooked when focusing on medication-induced illness.
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PMID:Multiple cardiovascular considerations in a 76-year-old man. 1654 50

Atherosclerosis is a progressive, lifelong condition that is the leading cause of death among middle-aged and elderly individuals aged > or =65 years. Up to 80% of elderly patients are found to have evidence of obstructive coronary heart disease at autopsy. Demographic trends, including the advancing median age and life expectancy of Western societies, suggest that a large share of the burden of atherosclerotic plaque is likely to be borne by elderly individuals. These trends are in part due to increases in a number of chronic diseases associated with adverse cardiovascular outcomes, including metabolic syndrome, diabetes mellitus and chronic kidney disease. Because the elderly have a higher attributable risk of coronary heart disease as a result of hypercholesterolaemia, more coronary deaths and overall events can be prevented via treatment in this age group compared with younger persons with hypercholesterolaemia. The efficacy, safety and tolerability of HMG-CoA reductase inhibitors (statins) have been confirmed in randomised, controlled, multicentre trials involving large numbers of patients aged > or =65 years. Although muscle symptoms such as myalgia are relatively common adverse events, more severe signs of myolysis such as myopathy and rhabdomyolysis are rare, but their risk is elevated by conditions (e.g. concomitant medications) that increase the systemic exposure of these agents. Statins differ in their susceptibility to increases in systemic exposure, but most statins have been demonstrated to be well tolerated and safe when administered to elderly patients. These favourable clinical findings should help clinicians counter highly prevalent 'ageism' bias in statin prescribing, whereby elderly patients, particularly those at highest cardiovascular risk, are often denied the benefits of statins without any meaningful foundation.
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PMID:Overcoming 'ageism' bias in the treatment of hypercholesterolaemia : a review of safety issues with statins in the elderly. 1668 57


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