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)

It is expected that the number of patients with diabetes mellitus will increase in the near future. The high rate of microvascular and macrovascular complications developing in these patients will place an even higher burden on our healthcare systems. Several pathophysiological factors are involved in the development of complications, among which are hyperglycaemia per se, the consequent formation of advanced glycation end-products (AGEs) and the intracellular accumulation of sorbitol. In addition, hypertension and dyslipidaemia also play an important role, especially in the development of coronary heart disease and stroke. The major therapeutic goals in patients with non-insulin-dependent diabetes mellitus (NIDDM) are to reduce obesity and normalise lipid disturbances and increased blood pressure, in order to improve the well-being of the patient and reduce the risk of the development of late diabetic complications. Often, pharmacological treatment of the hyperglycaemia is necessary, in which case sulphonylureas, metformin, alpha-glucosidase inhibitors such as acarbose, or insulin may be employed. It is believed that medical interventions, by their effect on improving metabolic control, reduce the incidence and severity of diabetic complications, especially when considering the toxic effects of glucose and the accumulation of AGEs as a consequence of raised tissue glucose levels. This concept is also based on extrapolation of the finding of the Diabetes Control and Complications Trial that intensive glycaemic control in IDDM will prevent the progression of at least the microvascular complications like retinopathy and nephropathy. There are, however, no long term studies in NIDDM patients to show that treatment with oral antihyperglycaemic agents helps to postpone or prevent complications. It is expected that the UK Prospective Diabetes Study will show whether better metabolic control, either with oral antihyperglycaemics or with insulin, will indeed improve outcome. Several other studies aiming at specific risk factor intervention (hypertension, hyperlipidaemia, lipid oxidation) in NIDDM patients are currently ongoing.
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PMID:Prevention of complications in non-insulin-dependent diabetes mellitus (NIDDM). 852 59

Bodyweight is an acknowledged independent risk factor for coronary heart disease (CHD). The present model analysis was undertaken to investigate the clinical and economic impact of bodyweight gain in patients with type 2 (non-insulin-dependent) diabetes mellitus and its effects on the development of CHD. Based on a retrospective re-evaluation of data from the Diabetes Intervention Study (DIS), patients with type 2 diabetes mellitus and stable bodyweight (group A) had a significantly lower rate of combined CHD events (30.3%) than patients showing a bodyweight gain (group B; 38.2%) over 10 years. Prevention of bodyweight gain, therefore, appears to be a meaningful strategy in the management of diabetes mellitus. In addition to this clinical advantage, prevention of CHD will also result in economic savings associated with avoided treatment of coronary events. Based on the clinical outcomes from the DIS, the calculated per-patient net savings for a patient with type 2 diabetes mellitus and stable bodyweight amounted to 1085 deutschmarks (DM) when compared with a patient experiencing a bodyweight increase. In a further step, the above situation was projected to current type 2 diabetes mellitus practice. Oral first-line treatment of type 2 diabetes mellitus is usually initiated with glibenclamide (glyburide), which is known to increase bodyweight (reflecting group B). The novel alpha-glucosidase inhibitor acarbose, in contrast, appears to be as effective as glibenclamide, but has the advantage of being bodyweight-neutral (reflecting group A). From the clinical viewpoint, acarbose can thus be considered an alternative to glibenclamide. From the viewpoint of drug costs, monotherapy with acarbose is 4 times as expensive as glibenclamide in Germany, resulting in per-patient incremental costs of DM3527 for acarbose over 10 years. Balanced against the potential 10-year cost saving of DM1085 resulting from the potential of acarbose to prevent CHD, around one-third of the incremental cost of acarbose may be recouped by this single effect. However, further possible benefits of acarbose, including the avoidance of hypoglycaemia and the deferral of costly insulin therapy, may improve the economic value of this novel antidiabetic agent. Given the indirect approach of this evaluation and its many limitations, the above findings need critical appraisal, and comparative trials are urgently required to substantiate our preliminary results.
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PMID:Evaluation of the potential clinical and economic effects of bodyweight stabilisation with acarbose in patients with type 2 diabetes mellitus. A decision-analytical approach. 1017 68

1. We examined whether N-hydroxyethyl-1-deoxynojirimycin (miglitol), a new human anti-diabetic drug with effects to inhibit alpha-1, 6-glucosidase glycogen debranching enzyme and reduce the glycogenolytic rate as well as to inhibit alpha-1,4-glucosidase, could reduce infarct size in the rabbit heart. Rabbits were subjected to 30-min coronary occlusion followed by 48-h reperfusion. 2. The infarct size as a percentage of area at risk was not reduced by pre-ischaemic treatment with 1 mg kg(-1) miglitol (42.7+/-4.0%, n=10) compared with the saline control group (41.7+/-2.3%, n=10). However, it was significantly and dose-dependently reduced by pre-ischaemic treatment with 5 or 10 mg kg(-1) of miglitol (25.7+/-4. 5%, n=10, and 14.6+/-2.4%, n=10, respectively) without altering the blood pressure, heart rate or blood glucose level. However, there was no evidence of an infarct-size reducing effect after pre-reperfusion treatment with 10 mg kg(-1) of miglitol (35.0+/-3.0%, n=10). 3. Another 40 rabbits given 1, 5 and 10 mg kg(-1) of miglitol or saline before ischaemia (n=10 in each) were sacrificed at 30 min of ischaemia for biochemical analysis. Miglitol preserved significantly the glycogen content, and attenuated significantly the lactate accumulation in a dose dependent manner in the ischaemic region at 30 min of ischaemia. 4. Pre-ischaemic treatment, but not pre-reperfusion treatment, with miglitol markedly reduced the myocardial infarct size, independently of blood pressure and heart rate. A dose-dependent effect of miglitol on infarct size, glycogenolysis and lactate formation suggests that the mechanism may be related to the inhibition of glycogenolysis. Thus, miglitol may be beneficial for coronary heart disease as well as diabetes mellitus.
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PMID:A novel anti-diabetic drug, miglitol, markedly reduces myocardial infarct size in rabbits. 1058 21

Renal dysfunction is a common complication of chronic heart failure (CHF). Renal filtration capacity has been evaluated in numerous studies, but there are studies dealing with renal tubular function in patients with coronary heart disease (CHD) concurrent with CHF, which became the subject of the present study. Seventy-nine patients with CHD with different stages of CHF (OCCH, 2002) and 12 healthy individuals were examined. The urinary activity of neutral maltase and L-alanine aminopeptidase was evaluated. The renal tubular dysfunction evaluated by the blood levels on the enzymes was found to increase with the greater severity of CHF.
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PMID:[Diagnosis the state of the proximal renal tubular epithelium in patients with coronary heart disease and chronic heart failure]. 1731 70

In the emerging landscape of cardiovascular (CV) outcome trials evaluating the effects of blood glucose lowering drugs in individuals with type 2 diabetes, it is becoming increasingly apparent that since the promising signals coming from the United Kingdom Prospective Diabetes Study (UKPDS) no unequivocal benefits have been established for any single therapy thus far. There is an unmet need for introducing an effective pharmacological agent which could target both correlates of glycaemic regulation and CV risk factors, to ameliorate the enormous burden of fatal and non-fatal CV events in diabetic patients. Acarbose, like other alpha-glucosidase inhibitors (AGIs), has been proven to be an effective antidiabetic treatment for decades, but the overall significant impact of this class of drugs on modulating CV risk has only recently been appreciated. Accumulating evidence has shown that apart from its multiple effects on primarily postprandial glucose dysmetabolism, a key component of mechanisms linked to increased incidence of CV events, acarbose therapy also associates with a favorable impact on an array of surrogate markers of CV disease. Data stemming from in vitro testing of human cell lines as well as from preliminary trials in diabetic populations, like the Study to Prevent Non-Insulin-Dependent Diabetes Mellitus (STOP-NIDDM) trial, have highlighted - though not undisputed - the potential beneficial effects of the drug on CV morbidity. Large scale trials, like the ongoing Acarbose Cardiovascular Evaluation (ACE) trial, aim at conclusively establishing such a positive effect in patients with coronary heart disease and impaired glucose tolerance. In view of its usually acceptable level of side effects that are, if they occur, mostly limited to transient gastrointestinal symptoms, acarbose could well be a strong future player in CV disease secondary prevention. Current discouraging results from many trials of antidiabetic medications to significantly lower CV event rates in diabetic patients, should only draw further attention on alternative glucose lowering agents, among which acarbose is indeed promising.
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PMID:On the potential of acarbose to reduce cardiovascular disease. 2474 56