Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Acarbose is an antidiabetic drug that inhibits alpha-D-glucosidase and alpha-amylase. We have found discrepancies of serum and urine amylase activities (AA) determined with different assay methods using samples collected from diabetes mellitus patients taking acarbose. As a result of our screening test using the urine samples, we found a 22% probability of discrepancy (the differences between the two methods were > or = 10% at AA > or = 100 U/l). We have measured acarbose in five discrepant samples by high-performance liquid chromatography/mass-spectrometry and quantified very low levels (0.36-0.93 micromol/l) of acarbose in three samples of urine. The inhibition of AA was known not only to be caused by acarbose but also its metabolites. We should suppose that the inhibitory effects of its metabolites on amylase measurements are larger than those of acarbose.
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PMID:[Effects of acarbose on amylase tests]. 1567 40

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

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

Acarbose, a pseudomaltotetraose, is produced by strains of the genus Actinoplanes. The compound is an inhibitor of alpha-glucosidases and is used in the treatment of patients suffering from type II diabetes. The benefits of acarbose for the producer are not known; however, a role as carbophor has been proposed. Acarbose synthesis is induced in the presence of maltose and maltotriose. We have investigated the transport activities for these sugars in Actinoplanes sp. strain SN 223/29 grown on different carbon sources, including acarbose. Under the conditions used, Actinoplanes sp. utilized acarbose as sole source of carbon and energy, although growth ceased after 24 h, possibly due to the accumulation of a toxic degradation product in the cytosol. Maltose transport was observed in cells grown on each of the substrates tested except glucose. Maltose transport of acarbose-grown cells was inhibited by sucrose and trehalose and, to a lesser extent, by maltodextrins but not by acarbose. In contrast, in maltose/maltotriose-grown cells maltose uptake was inhibited by acarbose. Maltotriose uptake in these cells was less inhibited by maltose but was more sensitive to acarbose than in acarbose-grown cells. The Km and Vmax values of maltose uptake are in the range of those reported for binding protein-dependent sugar ATP-binding cassette (ABC) transport systems. A maltose-binding protein that does not bind acarbose was isolated from cells grown on either acarbose, glycerol or maltose. These results suggest that an acarbose-insensitive maltose/sucrose/trehalose transporter that also accepts maltodextrins operates in acarbose-grown cells while a maltodextrin transporter that accepts maltose/sucrose/trehalose and is moderately sensitive to acarbose is found in cells grown in maltose/maltotriose-containing media.
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PMID:Characterization of maltose and maltotriose transport in the acarbose-producing bacterium Actinoplanes sp. 1593 74

The alterations in atherogenic index of plasma (AlP) in type 2 diabetic patients and their normoglycemic first-degree relatives (NFDR) were investigated, and the effects of Acarbose or Glimepiride on AIP in 99 type 2 diabetic patients were evaluated. Triglycerride (TG), total cholesterol, high density lipoprotein-cholesterol (HDL-C) levels were analyzed, and Log (TG/HDL-C) was calculated as AIP in 62 type 2 diabetic patients and their 67 NFDR from 29 type 2 diabetic pedigrees and in 45 healthy controls without family histories of diabetes. Also analyzed were the same parameters in 99 type 2 diabetic patients before and after therapy with Acarbose or Glimepiride. The results revealed that diabetic patients and their NFDR had significantly higher AIP than did the controls, whereas no significant differences were seen between diabetic patients and their NFDR. Positive correlation of AIP between type 2 diabetic patients and their offspring were observed (r = 0.241, P < 0.05). After 8 weeks therapy with Acarbose, the AIP of type 2 diabetic patients was decreased significantly, and no differences were observed for AIP levels in Glimepiride group although the AIP was lower when compared with the untreated level. As a significant inverse correlation of small dense low density lipoprotein (sdLDL) with AIP was confirmed, our data suggest that diabetic patients and their NFDR from type 2 diabetic pedigrees had significantly higher AIP than did controls; AIP could be decreased by therapy with Acarbose in type 2 diabetic patients; Glimepiride may bring potential benefit to type 2 diabetic patients by influencing sdLDL.
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PMID:[The change of atherogenic index of plasma (AIP) level in type 2 diabetic pedigrees and the response of AIP to Acarbose or Glimepiride in therapy of type 2 diabetes mellitus]. 1601 60

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

Insulin resistance is one of the determinants of postprandial hyperglycemia. Acarbose is an alpha-glucosidase inhibitor that delays the absorption of carbohydrates from the small intestine, thereby suppressing postprandial hyperglycemia. Recently, acarbose has been found to reduce the incidence of cardiovascular disease (CVD) in patients with diabetes. These observations suggest that intervention of postprandial hyperglycemia with acarbose is a promising strategy for the prevention of CVD in diabetic patients. However, the effects of acarbose on insulin sensitivity are not fully understood. In this study, we examined whether oral administration of acarbose could improve insulin sensitivity in fructose-fed rats, a widely used insulin-resistant animal model. Although plasma glucose levels remained unchanged during the experiments, serum insulin levels were significantly increased in fructose-fed rats, which were suppressed by 4 weeks of treatment with acarbose. Acarbose treatment also increased high-density lipoprotein levels in fructose-fed rats. Furthermore, treatment of acarbose inhibited the elevation of systolic blood pressure levels in fructose-fed rats. These results indicate that oral administration of acarbose improves insulin sensitivity in fructose-fed rats. Our present study suggests that the cardioprotecive effects of acarbose could be ascribed, at least in part, to its insulin-sensitizing property.
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PMID:Acarbose, an alpha-glucosidase inhibitor, improves insulin resistance in fructose-fed rats. 1622 5

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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