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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acarbose--the most extensively investigated and widely prescribed alpha-glucosidase inhibitor--reduces postprandial plasma glucose excursions by delaying the absorption of carbohydrate from the small intestine. Acarbose is an effective first-line therapy for patients with newly diagnosed type 2 diabetes, and induces a further improvement in glycemic control when used in combination with other antidiabetes agents. By decreasing postprandial hyperglycemia and improving insulin sensitivity, acarbose therapy also reduces fasting and postprandial serum insulin, fasting plasma glucose, and hemoglobin A1c levels. As the burden of type 2 diabetes continues to grow, there is a great need for an oral antidiabetes agent with a proven ability to prevent the development of micro- and macrovascular complications, and maintain long-term glycemic control. More than 15 years of clinical investigation have confirmed the sustained efficacy, tolerability, and excellent safety profile of acarbose in a wide range of patient types. Furthermore, the results of the recent Study to Prevent Non-Insulin-Dependent Diabetes Mellitus (STOP-NIDDM) showed that acarbose therapy significantly decreased the risk of cardiovascular events in high-risk individuals with glucose intolerance. Acarbose is therefore a convenient and effective long-term option for the treatment of type 2 diabetes, with the added benefit of reducing cardiovascular risk.
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PMID:Review of acarbose therapeutic strategies in the long-term treatment and in the prevention of type 2 diabetes. 1470 48

Acarbose (Glucobay; Bayer) is an alpha-glucosidase inhibitor used to treat diabetes and which may have a role in the prevention of type 2 diabetes. The present study investigated the effects of acarbose treatment on the site and extent of starch digestion, large-bowel fermentation and intestinal mucosal cell proliferation. Eighteen young male Wistar rats were fed "Westernised" diets containing 0, 250 and 500 mg acarbose/kg (six rats/diet) for 21 d. For most variables measured, both acarbose doses had similar effects. Acarbose treatment suppressed starch digestion in the small bowel but there was compensatory salvage by bacterial fermentation in the large bowel. This was accompanied by a substantial hypertrophy of small- and large-bowel tissue and a consistent increase in crypt width along the intestine. Caecal total SCFA pool size was increased more than 4-fold, with even bigger increases for butyrate. These changes in butyrate were reflected in increased molar proportions of butyrate in blood from both the portal vein and heart. There was little effect of acarbose administration on crypt-cell proliferation (significant increase for mid-small intestine only). This is strong evidence against the hypothesis that increased fermentation and increased supply of butyrate enhances intestinal mucosal cell proliferation. In conclusion, apart from the increased faecal loss of starch, there was no evidence of adverse effects of acarbose on the aspects of large-bowel function investigated.
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PMID:Starch digestion, large-bowel fermentation and intestinal mucosal cell proliferation in rats treated with the alpha-glucosidase inhibitor acarbose. 1500 21

Burgeoning obesity is increasing the prevalence of type II diabetes mellitus. As a consequence, there will be an even greater burden of cardiovascular disease, end-stage renal disease, blindness, and lower extremity amputations. If diagnosed, impaired glucose tolerance presents an opportunity for intervention that potentially could delay or prevent the development of diabetes. Recent prospective studies document the effectiveness of exercise and weight reduction in preventing diabetes. Metformin is less effective than intense lifestyle interventions. Acarbose, losartan, orlistat, pravastatin, ramipril, and hormone replacement therapy are associated with lower rates of the development of diabetes. The Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication (DREAM) trial and the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial were designed to assess not only the prevention of diabetes but also the impact on cardiovascular morbidity and mortality.
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PMID:Preventing type II diabetes mellitus. 1505 49

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 prevalence of glucose intolerance is increasing dramatically worldwide. Both impaired glucose tolerance (IGT) and type 2 diabetes are associated with excess mortality from cardiovascular disease. It is now generally accepted that these cardiovascular complications are related to prevailing hyperglycemia, particularly postprandial hyperglycemia. Acarbose specifically decreases the postprandial glycemic surge in IGT and diabetic subjects. The Study To Prevent Non-insulin-dependent Diabetes Mellitus (STOP-NIDDM) trial has shown that acarbose treatment in IGT subjects decreased the risk of progression to diabetes by 36%. Furthermore, it was associated with a 49% risk reduction of cardiovascular events. In a subgroup of subjects, acarbose treatment was accompanied by a 50% decrease in the progression of intima-media thickness of the carotids. Finally, a meta-analysis of seven major studies on the use of acarbose in the treatment of diabetes indicated that acarbose treatment was associated with a 35% risk reduction of cardiovascular disease. It is proposed that the mechanism by which acarbose can lower the risk of cardiovascular events is through diminution of oxidative stress induced by postprandial glycemic excursion.
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PMID:Acarbose in the prevention of cardiovascular disease in subjects with impaired glucose tolerance and type 2 diabetes mellitus. 1578 Aug 29

Acarbose, a pseudomaltotetraose, is produced by strains of the genus Actinoplanes and is a potent inhibitor of alpha-glucosidases, including those from the human intestine. Therefore, it is used in the treatment of patients suffering from type 2 diabetes. The benefits of acarbose for the producer are not known; however, besides acting as an inhibitor of alpha-amylases secreted by competitors, a role as a 'carbophor' has been proposed. This would require a transport system mediating its uptake into the cytoplasm of Actinoplanes sp. A putative sugar ATP binding cassette (ABC) transport system, the genes of which are included within the biosynthetic gene cluster for acarbose, was suggested to be a possible candidate. The genes acbHFG encode a possible sugar binding protein (AcbH) and two membrane integral subunits (AcbFG). A gene coding for an ATPase component is missing. Since Actinoplanes sp. cannot yet be genetically manipulated we performed experiments to identify the substrate(s) of the putative transporter by assessing the substrate specificity of AcbH. The protein was overproduced in Escherichia coli as His10-fusion protein, purified under denaturating conditions and renatured. Refolding was verified by circular dichroism spectroscopy. Surface plasmon resonance studies revealed that AcbH binds acarbose and longer derivatives, but not maltodextrins, maltose or sucrose. Immunoblot analysis revealed the association of AcbH with the membrane fraction of Actinoplanes cells that were grown in the presence of maltose, maltodextrins or acarbose. Together, these findings suggest that the AcbHFG complex might be involved in the uptake of acarbose and are consistent with a role for acarbose as a 'carbophor'.
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PMID:The acbH gene of Actinoplanes sp. encodes a solute receptor with binding activities for acarbose and longer homologs. 1580 35

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 results of the Diabetes Control and Complications Trial (DCCT) and UK Prospective Diabetes Study trials in type 1 and type 2 diabetes, respectively, have proved the importance of intensive glucose management in the prevention of microvascular complications (retinopathy, nephropathy, and neuropathy). Both trials showed encouraging trends for a decrease in macrovascular complications, and this is being pursued in new studies. These findings have led to more strict goals for glucose control. As glucose levels are aimed to be closer to the normal range, the risk for hypoglycemia also increases dramatically. The choice of the agent therefore is more influenced currently by the risk for hypoglycemia. There are presently four classes of oral antihyperglycemic agents. These agents differ greatly in terms of mechanisms of action, efficacy, side effect profiles, and cost. Except for Acarbose, all classes decrease the glycosylated hemoglobin by a similar magnitude: 1.0 to 1.5%. In chronic renal failure, the oral agents that can be used therefore include the insulin secretagogues repaglinide and nateglinide and the thiazolidinediones (rosiglitazone and pioglitazone) with caution. Insulin also can be used safely in renal failure.
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PMID:Oral antihyperglycemic agents and renal disease: new agents, new concepts. 1593 25

We assessed the cost-effectiveness of acarbose in the management of patients with impaired glucose tolerance (IGT) in Sweden, based on progression to type 2 diabetes (T2D) and cardiovascular (CV) events reported in the STOP-NIDDM trial population, including high-risk subgroups. The cost per patient free from T2D was SEK28,000 or SEK1260 per diabetes free month prior to progression to T2D. The cost per patient free from CV events was SEK101,000 or SEK5000 per CV event free month. For the high CV risk subgroups, acarbose treatment dominated placebo (i.e. acarbose was more effective, less costly). Acarbose significantly reduces the incidence of diabetes and CV events in IGT patients. We predict this may translate into healthcare cost savings that partially or, in patients at high CV risk, fully offset the cost of acarbose. We conclude that acarbose is likely to be cost-effective in the management of impaired glucose tolerance.
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PMID:Cost-effectiveness of acarbose for the management of impaired glucose tolerance in Sweden. 1617 80

Impaired glucose metabolism is associated with an increased risk of cardiovascular events and cardiovascular-associated mortality. Postprandial hyperglycaemia is one of the earliest identifiable indicators of impaired glucose control. It contributes to the progression from impaired glucose tolerance to overt type 2 diabetes and exacerbates chronic hyperglycaemia in established diabetes. It is also an independent risk factor for cardiovascular disease in patients with impaired glucose tolerance and type 2 diabetes. Thus, an important strategy to reduce cardiovascular risk in patients with impaired glucose metabolism is to reduce postprandial glucose excursions. Acarbose, an alpha (alpha)-glucosidase inhibitor, reduces postprandial hyperglycaemia by delaying carbohydrate absorption from the small intestine. This mechanism of action provides glycaemic control without increasing insulin levels and exacerbating coexisting cardiovascular risk factors. The Study to Prevent Non-Insulin Dependent Diabetes Mellitus (STOP-NIDDM) assessed the ability of acarbose to reduce cardiovascular risk. In this study of 1429 individuals with impaired glucose tolerance, acarbose therapy reduced the risk of any cardiovascular event by 49% (P=0.03), of an acute myocardial infarction by 91% (P=0.02) and of developing hypertension by 34% (P=0.006). Furthermore, a retrospective meta-analysis of randomised studies of acarbose in type 2 diabetes patients showed that acarbose therapy reduced the risk of any cardiovascular event by 35% (P=0.006) and the risk of a myocardial infarction by 64% (P=0.012). These results suggest that acarbose is useful in reducing the risk of cardiovascular events in patients with impaired glucose metabolism.
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PMID:Cardiovascular benefits of acarbose in impaired glucose tolerance and type 2 diabetes. 1633 93


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