Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.20 (alpha-glucosidase)
 4,237 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the recent years there has been increasing interest in the effects of oral hypoglycemic drugs on the cardiovascular system. This has arisen because of recognitions that thiazolidine-diones, peroxisome proliferators-activated receptor gamma (PPAR-gamma), may have antiatherogenic actions and that sulphonylureas are capable of closing the ATP-dependent potassium channel. PPAR-gamma agonists exert antiatherogenic action by inhibition the production of monocyte inflammatory cytokines, inhibition of expression of adhesion molecules in endothelial cells, inhibition of the proliferation of vascular smooth muscle cells and have antioxidative effects. The United Kingdom Prospective Diabetes Study (UKPDS), published in 1998, found that the use of sulphonylureas had no increase in cardiovascular mortality and that metformin therapy in obese individuals with type 2 diabetes mellitus was associated with reduced cardiovascular death. Recently, the STOP-NIDDM trial has been shown that patients with impaired glucose tolerance treated with the alpha-glucosidase inhibitor acarbose had a significant reduction in the risk of cardiovascular disease. Currently, the results of the UKPDS trial are the only available clinical data on which to base the choice of treatment for type 2 diabetic patients. When a glucose-lowering oral drug is considered necessary and is not contraindicated, the firstline choice is a sulphonylurea or a glinide (repaglinide or nateglinide) for diabetics who are not overweight and metformin for those who are.
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PMID:[Cardiovascular effects of oral hypoglycemie drugs]. 1534 Jul 37

Protective effects of the alpha-glucosidase inhibitor acarbose have been reported for various diabetic complications. In the STOP-NIDDM study, even patients without overt diabetes, but with impaired glucose tolerance, had a reduction in cardiovascular events when treated with acarbose. Therefore, we investigated the effect of repetitive postprandial hyperglycemia on the cardiac ischemia/reperfusion injury in vivo. Mice were treated daily by single applications of placebo, sucrose (4 g/kg body weight), or sucrose + acarbose (10 mg/kg body weight) by gavage for 7 days. Acarbose treatment significantly reduced the sucrose-induced increase in plasma glucose concentration. Subsequently, animals underwent 30 min of ischemia by coronary artery ligation and 24 h of reperfusion in vivo. In the sucrose group, ischemia/reperfusion damage was significantly increased (infarct/area at risk, placebo vs. sucrose, 38.8+/-7.5% vs. 62.2+/-4.8%, P<0.05). This was prevented by acarbose treatment (infarct/area at risk 30.7+/-7.2%). While myocardial inflammation was similar in all groups, oxidative stress as indicated by a significant increase in lipid peroxides was enhanced in the sucrose, but not in the sucrose + acarbose group. In summary, repetitive postprandial hyperglycemia increases ischemia/reperfusion damage. This effect can be prevented by treatment with the alpha-glucosidase inhibitor acarbose.
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PMID:Repetitive postprandial hyperglycemia increases cardiac ischemia/reperfusion injury: prevention by the alpha-glucosidase inhibitor acarbose. 1567 Nov 53

The metabolic syndrome is strongly associated with insulin resistance and has been recognized as a cluster of risk factors for cardiovascular diseases such as visceral obesity, hypertension, diabetes, and atherogenic dyslipidemia. Recently, insulin resistance in the absence of overt diabetes or the metabolic syndrome itself has been associated with endothelial dysfunction, one of the initial steps in the process of atherosclerosis. Postprandial hyperglycemia, one of the characteristic features of insulin resistance, induces oxidative stress generation and elicits vascular inflammation and platelet activation, thus being involved in the pathogenesis of atherosclerosis. A recent multicenter, placebo-controlled randomized trial, STOP-NIDDM trial, revealed that acarbose (Glucobay R), an alpha-glucosidase inhibitor, improved postprandial hyperglycemia and subsequently reduced the risk of development of type 2 diabetes in patients with impaired glucose tolerance (IGT). In this study, acarbose treatment was also found to slow the progression of intima-media thickness of the carotid arteries, a surrogate marker for atherosclerosis, and to reduce the incidence of cardiovascular diseases and newly diagnosed hypertension in subjects with IGT. Acarbose significantly reduced body mass index and waist circumference in these patients over 3 years. Furthermore, a meta-analysis of seven long-term studies has also shown that intervention with acarbose prevents myocardial infarction and cardiovascular diseases in type 2 diabetic patients. In this analysis, glycemic control, triglyceride levels, body weight and systolic blood pressure was also significantly improved during acarbose treatment. These observations suggest that prevention of postprandial hyperglycemia by acarbose may be a promising therapeutic strategy for reducing the increased risk for diabetes, hypertension, dyslipidemia, obesity, and cardiovascular diseases in patients with the metabolic syndrome. Acarbose improves postprandial hyperglycemia by delaying the release of glucose from complex carbohydrates in the absence of an increase in insulin secretion. Therefore, we would like to hypothesize here that this improvement in glucose metabolism could be associated with amelioration in insulin sensitivity, thus explaining the above-mentioned beneficial cardiometabolic actions of acarbose. Large clinical trials will provide us with more definite information whether acarbose treatment can improve insulin sensitivity and resultantly reduce the risk of diabetes, hypertension and cardiovascular diseases in patients with the metabolic syndrome.
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PMID:Inhibition of postprandial hyperglycemia by acarbose is a promising therapeutic strategy for the treatment of patients with the metabolic syndrome. 1589 33

The metabolic syndrome is strongly associated with insulin resistance and has been recognized as a cluster of risk factors for cardiovascular diseases such as visceral obesity, hypertension, and diabetes. There is a growing body of evidence to show that nonalcoholic steatohepatitis (NASH) is the hepatic manifestation of insulin resistant patients with the metabolic syndrome. Indeed, insulin resistance increases adipocyte lipolysis and subsequently elevates circulating free fatty acids, thus stimulating the accumulation of fatty acids in the liver (hepatic steatosis). Fatty acids elicit reactive oxygen species generation, thereby promoting disease progression to NASH by both lipid peroxidation and inflammatory cytokine production. Postprandial hyperglycemia, one of the characteristic features of insulin resistance, also induces oxidative stress generation, being involved in dysfunction of pancreatic beta cells and vascular wall cells in the metabolic syndrome. Recently, STOP-NIDDM trial revealed that acarbose (Glucobay), an alpha-glucosidase inhibitor, improved postprandial hyperglycemia and subsequently reduced the risk of development of type 2 diabetes and newly diagnosed hypertension in patients with impaired glucose tolerance. In this study, acarbose treatment was also found to reduce body mass index and waist circumference in these patients. Furthermore, a meta-analysis of seven long-term studies has also shown that intervention with acarbose improved triglyceride levels, body weight and systolic blood pressure and subsequently prevented myocardial infarction in type 2 diabetic patients. Since acarbose improves postprandial hyperglycemia by delaying the release of glucose from complex carbohydrates in the absence of an increase in insulin secretion, the beneficial aspects of acarbose could be ascribed to improvement of insulin sensitivity in these patients. Given the pathological link between NASH and insulin resistance, we would like to hypothesize here that acarbose may become a promising therapeutic strategy for the treatment of patients with NASH. Does acarbose treatment improve steatohepatitis histologically? Is the extent of histological improvement by acarbose parallel to that of insulin sensitivity in these patients? Large clinical trials will provide us with more definite information whether acarbose treatment can improve insulin sensitivity and resultantly reduce the risk of progression of liver diseases in patients with NASH.
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PMID:Acarbose is a promising therapeutic strategy for the treatment of patients with nonalcoholic steatohepatitis (NASH). 1592 16

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

The STOP-NIDDM trial was an international, double-blind, placebo-controlled randomised study in people with impaired glucose tolerance (IGT). They were treated with an alpha-glucosidase inhibitor, acarbose, to prevent diabetes; the overall number needed to treat (NNT) was 11. In a secondary analysis, we considered the impact of single traits and overall metabolic syndrome (MetS) respectively on risk of diabetes and NNT respectively. In all, there were 1,368 patients. They were followed up for 3.3 years, and the prevalence of MetS was 61%. Multivariate analysis revealed treatment group 2-hour (post-challenge) plasma glucose, glycosylated haemoglobin (HbA1C), triglycerides and leukocyte count as independent predictors. The annual incidence of diabetes in the placebo group with MetS was 18.7% vs. 11.2% in patients without MetS; the corresponding figures in the acarbose group were 13.5% and 9.4%, respectively. The NNT in patients was 5.8 in patients with MetS and 16.5 in those without MetS. In conclusion, most single traits and overall MetS label a very high-risk group in people with IGT. People with MetS reach a NNT to prevent development of new diabetes with acarbose of 5.8.
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PMID:Metabolic syndrome and its single traits as risk factors for diabetes in people with impaired glucose tolerance: the STOP-NIDDM trial. 1915 26