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Recent studies have shown that plasma concentrations of vitamin A (retinol) and its carrier proteins, retinol-binding protein (RBP), and transthyretin (TTR), are decreased in human subjects with insulin-dependent (IDDM) but not with noninsulin dependent diabetes mellitus (NIDDM). Rats made diabetic with streptozotocin (STZ) have also been shown to have reduced levels of plasma vitamin A while its hepatic concentrations elevate. The circulatory vitamin A levels remained low while its hepatic concentrations were further elevated following supplementation of the vitamin. The reduced circulatory status of vitamin A in diabetic animals was not caused by its impaired intestinal absorption. Further experimental studies have pointed to the fact that IDDM is associated with a deficiency of vitamin A, which is secondary to an impaired transport mechanism of this vitamin from its hepatic storage to the target site, such as retina of the eyes. The diabetes-associated changes in vitamin A metabolism were reserved to normal by insulin treatment. The underlying cause for decreased metabolic availability in uncontrolled diabetes, is not clearly understood. It appears that the increased hepatic store of vitamin A is attributed to a decreased availability of its carrier proteins. Subnormal vitamin A status in poorly controlled diabetic subjects may not respond to vitamin A supplementation, rather it may increase its load in the liver leading to hepatoxicity. These results clearly suggest that there is need for further research identifying the importance of vitamin A in diabetes mellitus.
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PMID:Vitamin A homeostasis and diabetes mellitus. 999 May 81

Cardiovascular primary prevention may consist of strategies concerning the entire population (population strategy) or individuals at high risk for a cardiovascular event (high risk strategy). Clinicians are mainly involved in the identification and treatment of high risk individuals. Even more so, preventive measures should be focused on patients who are already affected by coronary artery disease (CAD) or other manifestations of atherosclerosis (secondary prevention). According to the beneficial effect anticipated by cardiovascular prevention, there should be a priority list guiding the therapeutic measures: first priority therapy should be reserved for patients with existing CAD, then persons without CAD symptoms at high risk for disease manifestation due to an accumulation of coronary risk factors (hypercholesterolemia, hypertension, smoking, diabetes mellitus, lack of physical activity, adipositas) should be treated. Third priority for preventive therapy for cardiovascular diseases is reserved for asymptomatic 1st degree relatives of CAD patients with an early onset CAD. Fourth priority have persons who are close relatives of high risk individuals, and fifth priority prevention is cardiovascular risk factor assessment in the general population. Estimation of the risk for future cardiovascular events is very important because it provides a rational basis for the necessity and relevance of a treatment strategy. In this review, several therapeutic options for cardiovascular prevention are described and discussed.
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PMID:[Cardiovascular risk patient--how much prevention is necessary and rational?]. 952 31

Do we need impotence testing? Yes, it is the clinician's obligation to establish the etiology of impotence: end organ vascular failure vs neurologic dysfunction vs psychosexual dysfunction, classify the severity of that dysfunction, and select a therapy that is not only acceptable to the patient but also addresses his pathology. The most commonly utilized diagnostic tests for erectile dysfunction are outlined in this monograph. Nocturnal erections are evaluated by tests commonly known as nocturnal penile tumescence (NPT) studies. NPT has been measured by each of the following methods: stamp test, Snap Gauges, strain gauges, NPTR (Rigiscan, Osbon Medical Systems), and sleep lab NPTR. Normal Nocturnal Penile Tumescence and Rigidity (NPTR) depends on both the integrity of the corticospinal efferents to the penis and vascular responsiveness of the penile tissues to those nerve signals. When nocturnal erections are of appropriate duration and strength the central and peripheral neuroeffectors and intra-corporal regulators of penile hemodynamics are intact. Unfortunately, abnormal NPTR is of little value in determining the etiology or classifying the severity of vascular impotence; the most prevalent kind of end organ failure. The sacral reflex arc of erection consists of somatosensory afferents via the dorsal and pudendal nerves and autonomic efferents via the pelvic and cavernous nerves. These afferents have been measured indirectly by somatosensory evoked potentials (SSEP) and bulbocavernosus reflex latency (BCR). Penile EMG's have recently been recorded, corporal cavernosal smooth muscle electrical activity: CC-EMG. This technology is far from standardized; computer-assisted interpretations of penile electrical potentials may eventually differentiate afferent nerve pathologies so long inferred in: diabetes, spinal cord injury and following radical pelvic surgery. Numerous diagnostic tests have been employed to evaluate penile hemodynamics: penile plethysmography, penile blood pressures, penile brachial index, selective internal pudendal pharmacoangiography, Doppler sonography, dynamic infusion cavernosometry/cavernosography, nuclear washout radiography, and color duplex Doppler ultrasound. Insufficient corporal veno-occlusion is implicated in up to 50% of patients. The diagnosis and demonstration of venous leakage requires complete smooth muscle relaxation. Veno-occlusive dysfunction is associated with poorly sustained erections; this pathology has traditionally been evaluated with Dynamic Infusion Cavernosometry and Cavernosography. DICC is an invasive test, and is now primarily reserved for patients considering the option of vascular reconstructive procedure. Pharmacotesting consists of intracavernous injection and visual rating of the subsequent erection; the test is the most commonly used office procedure for diagnosing erectile dysfunction. It is simple, minimally invasive, and performed without monitoring equipment. Hemodynamic investigations suggest that a positive injection test is associated with normal veno-occlusion, but not necessarily with normal arterial function. When the penile response to pharmacotesting is suboptimal or equivocal, diagnostic testing with duplex Doppler assessment should be performed. The penile blood flow study (PBFS) provides an objective, minimally invasive evaluation of a suboptimal/equivocal erectile response.
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PMID:Evidence based assessment of erectile dysfunction. 964 64

The importance of glycemic control in reducing the microvascular complications of type 1 diabetes has been clearly demonstrated with a long-term prospective, randomized interventional trial. The data are not as strong with regards to type 2 diabetes. The results of several prospective studies and one interventional study, however, all report benefits of improved glycemic indices on reducing microvascular complications. The available literature evaluating the relationship between glycemic control and macrovascular disease in type 1 and type 2 diabetes demonstrates the importance of glucose control. One could make rational scientific arguments or criticize the design and interpretations of any one individual study. Yet collectively the evidence is powerful. Additionally, there have been no negative studies reported. Lowering the glycosylated hemoglobin to less than 2 percentage points above the upper limit of normal should be the first glycemic goal for most patients with diabetes. Obviously, some patients cannot obtain this degree of control for a variety of reasons. Moreover, the intensity of therapy needs to be individualized and tailored to each patient. In addition, intensive glycemic control does not necessarily mean multiple injections or insulin pumps or home glucose monitoring 10 times a day. Intensive glycemic control means that the glycohemoglobin (hemoglobin and A1C and blood glucose values are in a normal or near-normal range, no matter how simple or how complex the treatment regimen. The most controversial issue is with regards to the relationship between hyperinsulinemia and accelerated atherosclerosis. This association is not consistently found in many of the large prospective studies, and certainly there has never been a direct cause-and-effect relationship proven. Most experts in the field recommend that insulin be reserved for patients with type II diabetes when oral therapy cannot achieve near-normal glycemic control. Weight gain and hypoglycemia are adverse effects of sulfonylurea and insulin therapy. These adverse effects are dwarfed, however, by the acute and chronic complications of poorly controlled diabetes. Lastly, estimates on the economic benefits of reducing long-term microvascular and macrovascular complications in populations are staggering. Based on the available literature, all patients with diabetes should be educated and have access to an appropriate individualized treatment regimen with the goal to normalize or near-normalize glycemic control. This should be the standard of care until proven otherwise.
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PMID:Importance of glucose control. 970 16

We retrospectively analysed the long-term treatment results (median 8 years) of 31 patients with macroprolactinoma. 17 patients were treated by pituitary surgery (group 1) followed by long-term dopamine agonist therapy whereas 14 patients received long-term dopamine agonist therapy alone (group 2). 2 patients of group 1 and 1 patient of group 2 had external pituitary irradiation because of progressive disease. The two groups were comparable with respect to age, gender and initial prolactin (PRL) levels. At the end of the observation period dopamine agonist dosage could be reduced by 50% in group 1 and by 39.3% in group 2. Pituitary function did not change substantially during therapy. Complete remissions (no visible tumour in CT or MRI, normal PRL levels under current dopamine agonist medication) were achieved in 23.5% of group 1 vs. 21.4% of group 2, partial remissions (reduction of PRL and tumour size) in 35.3% vs. 64.3%, stable disease in 23.5% vs. 7.1% and progressive disease in 17.7% vs. 7.1% (differences not significant). Visual field defects showed 28.4% remissions (complete and partial) in group 1 versus 50% in group 2. Dopamine agonist therapy could be stopped definitively in only 1 patient of group 2 with an invasive macroprolactinoma. Initial surgical reduction of tumour load followed by medical therapy does not seem to guarantee a better long-term outcome than dopamine agonist therapy alone if the patient responds to and tolerates dopamine agonist therapy. Surgery should be reserved for non-responders, drug-intolerant or non-compliant patients, and for those with acute severe neurological compromise.
Exp Clin Endocrinol Diabetes 1998
PMID:Surgery combined with dopamine agonists versus dopamine agonists alone in long-term treatment of macroprolactinoma: a retrospective study. 971 Mar 62

Obesity management includes primary weight loss, prevention of weight regain, and the management of associated risk factors, such as smoking, hyperlipidaemia and hypertension. All these require lifestyle modification. The success or failure of management will depend on the characteristics of both the patient and the physician (or therapeutic team). Thus, direct statistical comparisons between methods of management may be misleading. Weight loss of 5-10% (usually 5-10 kg and equivalent to 5-10 cm waist reduction for most patients) is generally achievable within 3-4 months. Attempts to achieve weight loss over longer periods of time are usually unsuccessful. Improved clinical, symptomatic and biochemical benefits are very significant with this degree of weight loss. It is therefore unreasonable to pursue an 'ideal' bodyweight. In reported studies, the weight decrease over the first 3-4 months represents the total weight loss. Data collected after this time reflect both the initial weight loss and the ability of the patient and the programme to maintain weight loss. Many reports and study designs do not make this distinction. The principal goal of weight management, whether in primary prevention or in treatment of the obese, is weight maintenance. This goal has to be viewed in the context of a normal tendency to gain weight through adult life. In good hands, dietary and behavioural techniques can maintain significant weight loss for 1 year or longer in about 40% of patients. This increases to about 70% for patients receiving appetite modifying drugs; professional resource requirements are also lower. Surgical approaches are reserved for those with more serious clinical risks. Weight loss in individuals with non-insulin dependent diabetes mellitus (NIDDM) can be achieved in newly diagnosed patients and non-diabetics with comparable success. The goal of interventions in established NIDDM patients should be improved weight maintenance evaluated over 1-2 years, not acute loss achieved in 3 months.
Exp Clin Endocrinol Diabetes 1998
PMID:Obesity--what are the current treatment options? 979 77

Approximately 150 million people worldwide have diabetes mellitus, of whom 90% are type II diabetics. It is therefore of no surprise that diabetic nephropathy has become the leading cause of end-stage renal disease. Opposite to what has been known previously, kidney disease is at least as common in type II as in type I diabetes. However, because the majority of type II diabetics has hypertension for many years before diabetes mellitus becomes clinically relevant, renal lesions are often heterogeneous with frequent exclusive presence of ischemic changes. For the treatment of hypertension in diabetics without nephropathy (no microalbuminuria), drugs that exert beneficial effects or are at least neutral with respect to lipid and glucose metabolism, such as ACE inhibitors, angiotensin II-receptor antagonists, non-dihydropyridine-calcium channel blockers and the thiazide-like indapamide, are to be preferred. Although metabolically neutral, dihydropyridine calcium channel blockers should be used with caution, since an increase in cardiovascular morbidity and mortality in type II diabetics treated with these compounds has most recently been described. Once that diabetic nephropathy is established, blood pressure should be lowered to 120/80 mmHg (measured in seated position). Antihypertensive treatment should primarily be based on ACE inhibitors; angiotensin II-receptor antagonists are a valuable alternative if ACE inhibitors are not tolerated. Both ACE inhibitors and angiotensin II-receptor antagonists should be used with high caution in elderly patients with severe atherosclerosis in whom acute renal failure could occur due to the presence of bilateral renal artery stenosis. Newer studies indicate that non-dihydropyridine calcium channel blockers such as verapamil and diltiazem may be as effective as ACE inhibitors in preserving renal function in diabetic nephropathy. A fix-dose combination of the ACE inhibitor trandolapril with verapamil is now available; it should be reserved for patients whose blood pressure and/or proteinuria can not be adequately controlled with ACE inhibitors. Finally, indapamide is the only antihypertensive diuretic with nephroprotective properties.
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PMID:[Antihypertensive therapy in diabetes mellitus]. 1006 31

The incidence of major cardiac events (death, infarction) is over 5% after programmed aortic vascular surgery. The aim of this study was to evaluate a management strategy of this risk based on the clinical status and targeted indication of myocardial scintigraphy, coronary angiography and myocardial revascularisation. A first phase (1991-1993, 451 patients) confirmed the prognostic value of clinical (age, previous cardiac history, diabetes, hypertension, electrocardiogrammes) and scintigraphic features: the cardiac mortality was 1.25% in patients with a low clinical risk (70.3% of cases) and 4.5% in patients with a high clinical risk (2 factors, 29.3% of cases) (p < 0.01). In the latter group, the mortality was zero after normal myocardial scintigraphy and 7.2% after abnormal myocardial scintigraphy (p < 0.01) and 12.5% in cases with reversible defects (p < 0.01). During the second phase of the study (1994-1997, 531 patients) coronary angiography was performed in patients with a high clinical risk and abnormal scintigraphy (10.9% of cases). This led to a myocardial revascularisation in 3.6% of patients. The cardiac mortality was then the same in the low and high a priori clinical risk: 2.3 and 2.8% (NS). The use of simple clinical criteria enables surgery in the majority of candidates for aortic vascular surgery, scintigraphy being reserved for about one patient in ten with myocardial revascularisation in less than 4% of cases. The operative cardiac mortality then decreases to under 2.5%.
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PMID:[Evaluation of a clinical and scintigraphic management strategy for cardiac risk before abdominal aorta surgery. Apropos of 982 surgical patients]. 1007 40

The purpose of this article is to review the data from pharmacotherapeutic and surgical intervention studies for the management of obesity. Clinical outcomes assessed include weight changes over time and the effects of weight loss on blood pressure, serum lipid profiles and blood glucose control. Quality of life and economic data have been incorporated where available. Double-blind, randomised controlled trials were used preferentially over shorter term open studies. The literature evaluation was based on a Medline search of published data between January 1990 and January 1998. Obesity affects 65 million adults in the US. Estimates based on 1990 data suggest that obesity and comorbid illness contributed to $US46 billion in direct costs and $US23 billion in indirect costs in the US. Obesity is a chronic condition which requires long term management. The risk of developing cardiovascular disease, hypertension, type 2 (non-insulin-dependent) diabetes mellitus, osteoarthritis, Pickwickian syndrome and cancer is increased in the obese population, resulting in excess morbidity and mortality. There are no long term prospective studies that have demonstrated that weight reduction in obese patients improves survival. However, on the basis of epidemiological data using the prevalence of disease and associated body mass index, it is generally accepted that weight reduction of 5 to 10% in obese patients is associated with significant health benefits. Current treatment modalities include diet and behaviour modification, exercise and, where indicated, pharmacological intervention. Surgical intervention is reserved for the clinically severe obese patient [body mass index (BMI) > 40 kg/m2]. Many studies have demonstrated weight loss and improved metabolic fitness over 6 to 12 months. Few studies have been conducted over a longer period. Limited data are available regarding reduced morbidity and mortality, improved quality of life and functional or employment status and even fewer have incorporated any economic assessments of the impact of medical or surgical intervention. Although prospective data have demonstrated reduced morbidity following surgical intervention, only retrospective data have demonstrated reduced mortality. Studies of new drugs and interventions under development should demonstrate long term safety and efficacy in terms of sustained weight loss and subsequent weight maintenance. Future studies should incorporate assessment of patient perceived satisfaction with weight loss, health status and quality-of-life evaluations and pharmacoeconomic data to aid clinicians in the decision-making process in terms of weight management of their obese patients.
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PMID:Outcomes of pharmacological and surgical treatment for obesity. 1018 66

Although qualitative reports in the surgical literature suggest that people with diabetes mellitus (DM) and transmetatarsal amputation (TMA) walk well with regular shoes and a toe-filler, recent data indicates that this population has multiple complications and difficulty with functional mobility. A thorough description of their gait characteristics may provide insights to the cause of these difficulties. The purpose of this study was to compare selected gait characteristics of people with DM and TMA to age-matched controls. We studied 15 subjects with DM and a TMA, and 15 age-matched controls with an overall mean age of 62.3+/-9.2 years. Data were collected with computer assisted video as subjects walked across a force platform. Range-of-motion (ROM), moments, and power were estimated at the ankle, knee, and hip in the sagittal plane using standard link-segment methods. People with DM and TMA had decreased ROM excursion, peak moments, and peak power at the ankle. At the hip, people with DM and a TMA had decreased ROM excursion, an earlier onset of the hip flexor moment, but no differences in peak moments or peak power. Since people with DM and TMA have reduced ability to generate plantar flexor power at the ankle, they appear to rely more heavily on 'pulling' their leg forward from the hip using their hip flexor muscles. This compensation is not complete, however, as people with DM and a TMA take shorter steps and walk slower than controls. Additional research is needed to determine methods to improve or better compensate for these gait deviations during late stance phase. Copyright 1998 Elsevier Science B.V. All rights reserved
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PMID:Differences in the gait characteristics of people with diabetes and transmetatarsal amputation compared with age-matched controls. 1020 Mar 85

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