Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.2.1.20 (alpha-glucosidase)
4,237 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetes Mellitus is thought as the presymptomatic stage to cause various vascular diseases. From the point of view that diabetes is already a disease, this paper discusses the prevention of the manifestation of diabetes in the elderly. STOP-NIDDM study demonstrated that acarbose, an alpha-glucosidase inhibitor, reduced the onset of diabetes in impaired glucose tolerance (IGT) subjects by 24%. On the other hand, the Diabetes Prevention Program (DPP) study for IGT subjects revealed that intensive life style intervention prevented diabetes most powerfully by 58% and metformin treatment also reduced by 31%. Furthermore, HOPE, LIFE, and SCOPE studies against hypertension showed that ACI or ARB reduced diabetes by 20-32%, and the WOSCOT study that pravastatin, a HMG-CoA reductase inhibitor, reduced diabetes by 30%. These accumulated results suggest that the most suitable strategy to prevent diabetes in the elderly is intensive life style intervention, and in cases incapable of exercise and diet therapy, acarbose or metformin are recommended for IGT. When associated with hypertension and/or hyperlipidemia, the subjects have to receive ACI or ARB and statins to prevent diabetes.
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PMID:[Prevention of the manifestation of diabetes in the elderly in the presymptomatic stage]. 1652 11

Oral administration of alpha-glucosidase inhibitor reduces postprandial serum glucose and insulin concentrations; thus, alpha-glucosidase inhibitor is used for the treatment of diabetes mellitus worldwide. In our study, we have evaluated the effect of alpha-glucosidase inhibitor, acarbose, on age-related glucose intolerance and pancreatic atrophy in the Long-Evans Tokushima Otsuka (LETO) rat. The first group of rats received a standard rat diet (control). The second group received a diet containing acarbose (150 mg/100 g food) from 12 to 28 weeks and then switched to a standard rat diet until 72 weeks of age (A12-28W). The third group was administered the same diet containing acarbose from 12 to 72 weeks of age (A12-72W). Fasting serum glucose and insulin concentrations gradually increased with increasing age in the control group, but these increases were completely prevented (A12-72W) or delayed (A12-28W) by acarbose treatment. In addition, acarbose treatment prevented the deterioration in insulin resistance with increasing age. At 72 weeks of age, pancreatic wet weight and DNA content in the A12-72W group were significantly higher than those in the control group. Although most islets were enlarged, and some portions of pancreatic tissue contained fatty and connective tissue in the control group, these alterations were mild in the A12-28W group and remained minimal in the A12-72W group. Our study suggests that acarbose is useful in the prevention of age-related glucose intolerance and pancreatic atrophy.
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PMID:Effect of inhibition of alpha-glucosidase on age-related glucose intolerance and pancreatic atrophy in rats. 1654 85

Diabetogenic effect of glucocorticoids is determined by dose volume, duration of administration and structure and type of particular preparation. The effect is influenced also by the state of glucocorticoid receptors (increased sensitivity of some gene mutations, resistance syndromes) and times of year and day when glucocorticoids are administered. Development of impaired glucose tolerance or diabetes mellitus depends on the ability of islets of Langerhans to control insulin resistance induced by glucocorticoids. The compensatory function of islets of Langerhans decreases with age and that is why steroid diabetes mellitus affects mostly seniors. Besides treatment regimes and application of sulfonylurea and insulin, there are some new therapeutic methods available: thiazolidindiones, metformin, short-acting secretagogue, alpha-glucosidase, and theoretically also antiglucocorticoids. Application of insulin in type 2 diabetics is justified by the effort to prevent nonketotic hyperosmolar coma. In type 1 diabetes, it is usually necessary to increase the overall insulin dose and change its dosage during the day.
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PMID:[Glucocorticoids and diabetes mellitus]. 1677 Oct 98

Acarbose, an alpha-glucosidase inhibitor, is administered to control blood glucose levels. The drug also reduces the risk of cardiovascular disease, but the underlying mechanism is still to be elucidated. We therefore hypothesized that treatment with acarbose ameliorates the atherogenecity of low-density lipoprotein (LDL), a key molecule in atherogenesis. Patients with impaired glucose tolerance were or were not treated with acarbose (acarbose-treated group [n = 20] and control group [n = 20], respectively) for 3 months under dietary therapy. The oxidative susceptibility of LDL was determined by measuring lag time for the formation of dienes in the presence of CuSO(4). The lag time was significantly longer in the acarbose-treated group than in the control group before treatment. Moreover, the density gradient lipoprotein separation and disk polyacrylamide gel electrophoresis analyses showed that acarbose reduced the amount of small dense LDL, a more atherogenic and oxidatively susceptible form of LDL. We also found that the fatty acid composition of LDL changed after the treatment: polyunsaturated (omega-3) fatty acid, a beneficial substance for preventing cardiovascular disease, was significantly increased, whereas saturated fatty acids and triglyceride were decreased in the LDL of the acarbose-treated group. The present findings suggest that acarbose treatment reduces the risk of cardiovascular diseases by ameliorating the atherogenecity of LDL.
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PMID:Acarbose ameliorates atherogenecity of low-density lipoprotein in patients with impaired glucose tolerance. 1678 69

The highly prevalent, prediabetic condition of impaired glucose tolerance (IGT) confers a high risk for type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). There is an emerging body of cost-effectiveness literature in the management of IGT. For acarbose, an alpha-glucosidase inhibitor, economic analyses have been conducted for Spain, Germany, Sweden and Canada. In Spain, acarbose was more effective and less costly (dominant) compared with placebo. In Germany, the cost per patient free of diabetes was under Pounds 800; acarbose was dominant for those at high risk for T2DM, CVD or both, and a similar outcome in the Swedish study. In Canada, acarbose was dominant compared with no intervention and very cost-effective compared with metformin [C Dollars 1798/life years gained (LYG)]. The particularly cost-effective outcomes or cost savings delivered by acarbose for IGT subjects at high risk for T2DM and/or CVD render an IGT-intervention program prioritised to such high-risk individuals an economically attractive strategy.
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PMID:A review of the economic evidence for acarbose in the prevention of diabetes and cardiovascular events in individuals with impaired glucose tolerance. 1685 56

We recently encountered a 96-year-old Japanese woman who suffered from frequent hypoglycemia. Endocrinological and imaging data eliminated the possibility of insulinoma, whereas oral glucose tolerance testing revealed impaired glucose tolerance and subsequent reactive hypoglycemia. The patterns between insulin or C-peptide secretions and glucose excursions demonstrated that the discrepancy occurred in the late postprandial stage. Administration of small doses of alpha-glucosidase inhibitor (alpha-GI) dramatically inhibited the rapid rise and subsequent precipitous fall of plasma glucose. Reactive hypoglycemia may be one of the important cause of hypoglycemia in the elderly, and alpha-GI could effectively and safely prevent such hypoglycemic attacks in those patients.
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PMID:Postprandial reactive hypoglycemia in an oldest-old patient effectively treated with low-dose acarbose. 1696 25

Insulin resistance is one of the determinants of post-prandial hyperglycaemia. Recently, acarbose, an alpha-glucosidase inhibitor that delays the absorption of carbohydrates from the small intestine, has been found to reduce the incidence of cardiovascular disease in patients with impaired glucose tolerance or diabetes. However, the molecular mechanism by which acarbose inhibits cardiovascular events remains unknown. In this study, we examined whether oral administration of acarbose could suppress expression of monocyte chemoattractant protein-1 (MCP-1) in fructose-fed rats, a widely used animal model of insulin resistance. Serum MCP-1 levels were elevated in fructose-fed rats after 4 weeks. Acarbose treatment for 4 weeks reduced the fructose-induced elevation of serum MCP-1 levels. Acarbose treatment for 8 weeks decreased MCP-1 mRNA levels in the aortae of fructose-fed rats. These results suggest that the cardioprotective effects of acarbose could be due, at least in part, to the suppression of MCP-1 expression.
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PMID:Acarbose, an alpha-glucosidase inhibitor, decreases aortic gene expression and serum levels of monocyte chemoattractant protein-1 in fructose-fed rats. 1713 82

Since 1) dilated cardiomyopathy (DCM) causes chronic heart failure (CHF), and 2) augmentation of neurohumoral factors such as angiotensin II impairs glucose metabolism, we examined the rate of abnormal glucose metabolism in patients having both DCM and CHF and whether correction of the impairment of glucose metabolism would improve the pathophysiology of CHF in DCM patients. A 75-g oral glucose tolerance test (OGTT) was performed in 56 patients with DCM-induced CHF and 168 age- and sex-matched control subjects. Among the CHF patients, 26.8% and 50.0% suffered from diabetes mellitus (DM) and impaired glucose tolerance (IGT), respectively, showing that abnormal glucose tolerance was more prevalent in DCM patients than in the control subjects (7.7% and 14.3%, respectively). In the patients with DCM-induced CHF, a correlation was observed between the brain natriuretic peptide (BNP) levels and the difference between the plasma glucose levels at the time of fasting and at 2 h of OGTT. Since neither DM nor IGT are thought to cause DCM, the abnormalities of glucose metabolism may be attributed to the progression of CHF. Furthermore, we tested whether correction of the abnormal glucose tolerance using voglibose (an alpha-glucosidase inhibitor) would improve the severity of CHF in another group of 30 patients with DCM-induced CHF and IGT. The patients treated with voglibose for 24 weeks showed decreases in left ventricular dimension, NYHA functional classification values, and plasma BNP levels, and an improvement in cardiac function. In conclusion, abnormal glucose tolerance was more prevalent among patients with DCM-induced CHF than controls, and the correction of IGT improved the pathophysiology of CHF.
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PMID:Abnormal glucose tolerance contributes to the progression of chronic heart failure in patients with dilated cardiomyopathy. 1728 58

Dysglycaemic disease is one of the most important health issues facing the world in the 21st century. Patients with type 2 diabetes and individuals with prediabetes are at risk of developing macrovascular and microvascular complications. Long-term management strategies are therefore required that are effective at controlling dysglycaemia, well tolerated and, ideally, offer additional cardiovascular disease (CVD) risk-reduction benefits. The efficacy, safety and tolerability of the alpha-glucosidase inhibitor acarbose have been well-established in a wide range of patient populations in both clinical and community trials. In addition, acarbose has been shown to reduce cardiovascular complications in type 2 diabetes and prevent hypertension and CVD in individuals with impaired glucose tolerance (IGT). Acarbose has a very good safety profile and, owing to its straightforward, non-systemic mode of action, avoids most adverse events. The most common side-effects of acarbose are mild-to-moderate gastrointestinal complaints that subside as treatment continues. They can be minimised through the use of an appropriate stepwise dosing regimen and careful choice of diet. Acarbose is therefore a valuable option for the management of type 2 diabetes and, as the only oral antidiabetes agent approved for the treatment of prediabetes, can help to improve clinical management across the dysglycaemic disease continuum.
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PMID:Cardiovascular benefits and safety profile of acarbose therapy in prediabetes and established type 2 diabetes. 1769 84

Acarbose is an alpha-glucosidase inhibitor acting specifically at the level of postprandial glucose excursion. This compound lowers HbA(1c) by 0.5-1% in patients with Type 2 diabetes, either drug naive or in combination with other antidiabetic drugs. In those with impaired glucose tolerance (IGT), it reduces the incidence of newly diagnosed diabetes by 36.4%. Furthermore, it has beneficial effects on overweight, reduces blood pressure and triglycerides, and downregulates biomarkers of low-grade inflammation. In the Study To Prevent Non-Insulin-Dependent-Diabetes-Mellitus (STOP-NIDDM) trial, acarbose significantly reduced the progression of intima media thickness, incidence of cardiovascular events and of newly diagnosed hypertension. In a meta-analysis of patients with Type 2 diabetes (MERIA), acarbose intake was associated with a reduction of cardiovascular events by 35%. Acarbose is a very safe drug but in approximately 30% of patients, it can cause gastrointestinal complaints due to its mode of action, which in the majority disappear after 1-2 months. Acarbose is approved for treatment of IGT in 25 countries. It can be given alone or in combination with other oral antidiabetics and insulin. Acarbose is particularly effective in those with IGT and early diabetes and patients with comorbidities of the metabolic syndrome.
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PMID:Acarbose: oral anti-diabetes drug with additional cardiovascular benefits. 1824 70


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