Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Type 2 diabetes mellitus is a major health problem associated with excess morbidity and mortality. As the prevalence of this metabolic disorder is rapidly increasing and current treatment fails to stabilise the disease in most patients, prevention should be considered as a key objective in the near future. People who develop type 2 diabetes pass through a phase of impaired glucose tolerance (IGT). Defects in the action and/or secretion of insulin are the two major abnormalities leading to development of glucose intolerance. Any intervention in the impaired glucose tolerance phase that reduces resistance to insulin or protects the beta-cells, or both, should prevent or delay progression to diabetes.Acarbose, miglitol and voglibose act by competitively inhibiting the alpha-glucosidases, a group of key intestinal enzymes involved in the digestion of carbohydrates. They decrease both postprandial hyperglycaemia and hyperinsulinaemia, and thereby may improve sensitivity to insulin and release the stress on beta-cells. These compounds do not induce hypoglycaemia and have a good safety profile, although gastrointestinal adverse effects may limit long-term compliance to therapy. The recent placebo-controlled prospective STOP-noninsulin-dependent diabetes mellitus (STOP-NIDDM) trial demonstrated that acarbose 100mg three times daily reduces the risk of developing type 2 diabetes in patients with IGT (relative risk reduction of 25% after a mean follow-up of 3.3 years). The 6-year Early Diabetes Intervention Trial (EDIT), comparing the effect of acarbose 50mg three times daily to that of metformin, showed a trend to a positive effect of acarbose compared with placebo, in a mid-term 3-year analysis, which should be confirmed in the final analysis. To our knowledge, no such prevention intervention trials have been or are currently being performed with miglitol or voglibose. In conclusion, because of its absence of toxicity and its particular mechanism of action on gastrointestinal tract and indirect consequences on both insulin action and beta-cell function, acarbose may be used to prevent type 2 diabetes. If the ongoing EDIT trial confirms the positive results of the recent STOP-NIDDM trial, acarbose could be used, either as an alternative or in addition to changes in lifestyle, to delay development of diabetes in patients with IGT. However, the best dosage of acarbose for this specific indication remains to be specified, especially when all three important parameters, efficacy, tolerance and cost, are taken into consideration.
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PMID:Is there a role for alpha-glucosidase inhibitors in the prevention of type 2 diabetes mellitus? 1269 98

Although a salted diet appears to be a sine qua non for the development of essential hypertension, low-salt diets often have a modest or even negligible impact on the blood pressure of hypertensives; this suggests that salt, perhaps often acting in concert with other aspects of a modern, rich diet, may set in place certain metabolic vicious cycles that sustain blood pressure elevation even when dietary salt is eliminated. Therapeutic fasting is known to lower elevated blood pressure - presumably in large part because it minimizes insulin secretion - and may have the potential to break some of these vicious cycles. Goldhamer has recently reported that a regimen comprised of a water-only fast of moderate duration, followed by a transition to a low-fat, low-salt, whole-food vegan diet, achieves dramatic reductions in the blood pressure of hypertensives, such that the large majority of patients can be restored to normotensive status, in the absence of any drug therapy. Although long-term follow-up of these subjects has been sporadic, the available data suggest that these large reductions is blood pressure can be conserved in patients who remain compliant with the follow-up diet - in other words, a 'cure' for hypertension may be feasible. If a protein-sparing modified fast can be shown to be virtually as effective as a total fast for achieving these benefits, it may be possible to implement this regimen safely on an outpatient basis. The ability of therapeutic fasts to break metabolic vicious cycles may also contribute to the efficacy of fasting in the treatment of type 2 diabetes and autoimmune disorders. As a general principle, if a metabolic disorder is susceptible to prevention - but not reversal - by a specific diet, and therapeutic fasting has a temporary favorable impact on this disorder, then a more definitive therapy may consist of a therapeutic fast, followed up by the protective diet as a maintenance regimen.
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PMID:A preliminary fast may potentiate response to a subsequent low-salt, low-fat vegan diet in the management of hypertension - fasting as a strategy for breaking metabolic vicious cycles. 1271 Aug 93

The precise molecular cause of insulin resistance has not yet been elucidated. Resistance to the normal action of insulin contributes to the pathogenesis of a number of common human disorders, including type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetes mellitus, hypertension, and the Metabolic Syndrome X, thus constituting a major public health problem. A disease program aimed at combating this disorder should focus on the identification of targets for therapeutic intervention which may overcome insulin resistance and hence the associated metabolic consequences characteristic of the Metabolic Syndrome. Although the primary defect in the pathogenesis of type 2 diabetes is unknown, genetic and environmental factors are likely to contribute to the manifestation of this progressive metabolic disorder, which is usually not clinically apparent until mid-life. Defects at the level of glucose uptake/phosphorylation characterize insulin resistance in skeletal muscle of type 2 diabetic patients. Identification of putative components of the insulin receptor-signaling pathway may offer insights into mechanisms involved in insulin resistance. Enhanced flux of free fatty acids due to impaired lipid metabolism may contribute to impaired insulin secretion and peripheral insulin resistance. Genes regulating lipolysis are prime candidates for susceptibility towards the metabolic syndrome. Here we describe pathways constituting complex interactions that control glucose homeostasis. We will be considering (1) regulation of glucose uptake by the insulin receptor signaling pathway, and (2) control of adipogenesis and insulin sensitivity by the sterol response element binding protein (SREBP) pathway.
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PMID:Analysis of insulin signaling pathways through comparative genomics. Mapping mechanisms for insulin resistance in type 2 (non-insulin-dependent) diabetes mellitus. 1284 56

Metformin, a biguanide, has been available in the US for the treatment of type 2 diabetes mellitus for nearly 8 years. Over this period of time, it has become the most widely prescribed antihyperglycaemic agent. Its mechanism of action involves the suppression of endogenous glucose production, primarily by the liver. Whether the drug actually has an insulin sensitising effect in peripheral tissues, such as muscle and fat, remains somewhat controversial. Nonetheless, because insulin levels decline with metformin use, it has been termed an 'insulin sensitiser'. Metformin has also been shown to have several beneficial effects on cardiovascular risk factors and it is the only oral antihyperglycaemic agent thus far associated with decreased macrovascular outcomes in patients with diabetes. Cardiovascular disease, impaired glucose tolerance and the polycystic ovary syndrome are now recognised as complications of the insulin resistance syndrome, and there is growing interest in the management of this extraordinarily common metabolic disorder. While diet and exercise remain the cornerstone of therapy for insulin resistance, pharmacological intervention is becoming an increasingly viable option. We review the role of metformin in the treatment of patients with type 2 diabetes and describe the additional benefits it provides over and above its effect on glucose levels alone. We also discuss its potential role for a variety of insulin resistant and prediabetic states, including impaired glucose tolerance, obesity, polycystic ovary syndrome and the metabolic abnormalities associated with HIV disease.
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PMID:Metformin: new understandings, new uses. 1293 Jan 61

The prevalence of insulin resistance and type 2 diabetes is rapidly increasing, primarily because of rising rates of obesity and physical inactivity. Insulin resistance syndrome is a metabolic disorder that often leads to a cluster of serious clinical conditions, including type 2 diabetes and cardiovascular disease. Optimal management of diabetes requires not only tight glycemic control but also stringent management of cardiovascular risk factors. Because of their ready access to patients, pharmacists are well positioned to help detect and manage the many conditions associated with insulin resistance.
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PMID:Unraveling the mysteries of syndrome X. As the number of Americans with insulin resistance grows, pharmacists can help patients prevent the onset of type 2 diabetes and cardiovascular disease. 1462 24

Type 2 diabetes has become the most frequently encountered metabolic disorder in the world, currently affecting 5% to 10% of most populations, and the incidence continues to grow among developing nations. Two fundamental abnormalities are involved in the pathogenesis of type 2 diabetes: Resistance to the biologic activities of insulin in glucose and lipid metabolism and inadequate insulin secretion from the pancreatic B cells. In genetically predisposed individuals, type 2 diabetes is pathogenically linked with progressive obesity, especially adiposity that is visceral or ectopic in distribution. While microvascular complications (retinopathy, nephropathy, neuropathy) continue to plague patients with longstanding type 2 diabetes, cardiovascular disease has assumed particular importance, accounting for more than 80% of adverse outcomes among patients. Since the aggressive management of diabetes and its complications poses a considerable challenge, large trials to prevent the progression to overt diabetes in persons at high risk have recently demonstrated that lifestyle modification and pharmaceutical therapy can be successful approaches. A better understanding of the complex relationship between obesity and both the development of type 2 diabetes and its cardiovascular complications may provide additional treatment targets in the future to prevent the devastating chronic morbidity of this disorder.
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PMID:Insulin resistance: from benign to type 2 diabetes mellitus. 1466 98

Diabetes mellitus and its complications constitute a major health problem in modern societies. The disease affects approximately 5% of the adult population in western countries. The underlying process of the metabolic disorder is a defect in insulin secretion, insulin action, or both. Weight reduction, calorie restriction and patient education remain the cornerstones of the management of type 2 diabetes. When lifestyle modification fails to maintain adequate glycaemic control, insulin or oral hypoglycemic agents are typically used to manage the disease. The currently available five classes of oral agents differ in mechanism and duration of action, the degree to which they lower blood glucose and their side-effect profile. For most of these antiglycaemic agents, there is a lack of evidence on the effects on long-term complications. Only metformin has clearly proved that it can reduce mortality in obese patients with type 2 diabetes. Human insulin reduces acute and long-term mortality in patients with CVD. Furthermore, intensive treatment either with insulin or sulfonylurea has proved that it can prevent microvascular complications in type 2 diabetes. Additional randomized controlled trails assessing hard clinical endpoints are needed to better inform patients and enable physicians to establish optimal treatment strategies.
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PMID:[Drug treatment of type 2 diabetes]. 1467 86

Type 2 diabetes mellitus is a major health problem associated with excess morbidity and mortality. Defects in the action and/or secretion of insulin are the two major abnormalities leading to development of glucose intolerance. Any intervention in the impaired glucose tolerance phase that reduces resistance to insulin or protects the beta-cells, or both, should prevent or delay progression to diabetes. The natural history of type 2 diabetes includes a preceding period of impaired glucose tolerance (IGT)/impaired fasting glucose (IFG) which provides an opportunity for targeted intervention within large communities. As the prevalence of this metabolic disorder is rapidly increasing and current treatment fails to stabilise the disease in most patients, prevention should be considered as a key objective in the near future. Lifestyle intervention studies have consistently shown that quite modest changes can reduce the progression from IGT to diabetes by 50-60%. The Diabetes Prevention Program (DPP) randomised trial has shown that a combined program of weight loss, improvement of diet and increase of physical exercise lowers the risk for development of type 2 diabetes by 58% compared with placebo. It may, however, not be possible to translate these successful findings to larger cohorts or maintain the lifestyle changes longer term. This has lead to consideration of pharmacotherapy. Benefits have been found for metformin, acarbose and troglitazone. Treatment with metformin was less effective than lifestyle modifications, resulting in an average reduction of risk for development of type 2 diabetes by 31% compared with placebo. Similarly, acarbose in the STOP-NIDDM trial reduced the risk of developing type 2 diabetes in patients with IGT by 25%. Remarkably, cardiovascular event rates, in particular myocardial infarction, were significantly reduced when acarbose was used instead of placebo in subjects with glucose intolerance. The ACE inhibitors captopril (CAPPP) or ramipril (HOPE) and the Angiotensin-II receptor antagonist losartan (LIFE) have been shown to reduce the appearance of diabetes by one third when given to patients with hypertension. Since many hypertensive patients are insulin-resistant and have an increased risk in developing type 2 diabetes, the protective effect of these classes of antihypertensive drugs might be explained by their antiinsulin-resistance effects.
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PMID:[Progress in the prevention of type 2 diabetes]. 1474 78

Diabetes mellitus is the most frequent metabolic disorder. Just under 5 million people suffer from this disease in Germany. Four types of diabetes mellitus are distinguished: type 1 diabetes, type 2 diabetes, other specific diabetes forms, and gestational diabetes. Many characteristics of diabetes mellitus including skin changes are already manifest in the "prediabetic" stage when glucose tolerance is limited so that every elevation of blood sugar levels must be considered pathological. Changes in skin due to diabetes mellitus can be categorized into four disease groups: skin infections, skin diseases found overly frequently in association with diabetes mellitus, skin alterations due to diabetic complications, and reactions to antidiabetic treatment.
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PMID:[Skin changes in diabetes mellitus]. 1508 79

Defects in pancreatic islet beta-cell function play a major role in the development of diabetes mellitus. Type 1 diabetes is caused by a more or less rapid destruction of pancreatic beta cells, and the autoimmune process begins years before the beta-cell destruction becomes complete, thereby providing a window of opportunity for intervention. During the preclinical period and early after diagnosis, much of the insulin deficiency may be the result of functional inhibition of insulin secretion that may be at least partially and transiently reversible. Type 2 diabetes is characterized by a progressive loss of beta-cell function throughout the course of the disease. The pattern of loss is an initial (probably of genetic origin) defect in acute or first-phase insulin secretion, followed by a decreasing maximal capacity of insulin secretion. Last, a defective steady-state and basal insulin secretion develops, leading to almost complete beta-cell failure requiring insulin treatment. Because of the reciprocal relation between insulin secretion and insulin sensitivity, valid representation of beta-cell function requires interpretation of insulin responses in the context of the prevailing degree of insulin sensitivity. This appropriate approach highlights defects in insulin secretion at the various stages of the natural history of type 2 diabetes and already present in individuals at risk to develop the disease. To date none of the available therapies can stop the progressive beta-cell defect and the progression of the metabolic disorder. The better understanding of the pathophysiology of the disease should lead to the development of new strategies to preserve beta-cell function in both type 1 and type 2 diabetes mellitus.
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PMID:Pathophysiology of insulin secretion. 1512 89


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