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)

The postprandial blood glucose rise after a standard meal in six non-insulin dependent diabetics was significantly lower when acarbose 200 mg was taken together with the meal than without acarbose. Eight weeks acarbose treatment (300 mg), however, did not change fasting blood glucose. The effect of four weeks administration of the alpha-glucosidase inhibitor acarbose (300 mg) on diabetes regulation in another ten non-insulin dependent diabetics was compared with metformin (500 mg) in a double-blind cross-over study. Acarbose lowered postprandial blood glucose level from 11.5 +/- 4.2 to 8.9 +/- 1.8 mmol/l (p less than 0.02) and haemoglobin Alc from 8.1 +/- 1.8 to 7.7 +/- 1.7% (p less than 0.05). Urinary glucose was also decreased. Metformin did not significantly change postprandial blood glucose, haemoglobin A1c and urinary glucose excretion with the prescribed dose. The postprandial blood glucose and haemoglobin A1c after 4 weeks of treatment with acarbose and of metformin did not differ significantly. Side-effects of both drugs were mild and mainly gastrointestinal, but the frequency of side-effects was not different.
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PMID:Acarbose treatment of sulfonylurea-treated non-insulin dependent diabetics. A double-blind cross-over comparison of an alpha-glucosidase inhibitor with metformin. 639 73

The biguanide metformin (dimethylbiguanide) is an oral antihyperglycaemic agent widely used in the management of non-insulin-dependent diabetes mellitus (NIDDM). Considerable renewal of interest in this drug has been observed in recent years. Metformin can be determined in biological fluids by various methods, mainly using high performance liquid chromatography, which allows pharmacokinetic studies in healthy volunteers and diabetic patients. Metformin disposition is apparently unaffected by the presence of diabetes and only slightly affected by the use of different oral formulations. Metformin has an absolute oral bioavailability of 40 to 60%, and gastrointestinal absorption is apparently complete within 6 hours of ingestion. An inverse relationship was observed between the dose ingested and the relative absorption with therapeutic doses ranging from 0.5 to 1.5 g, suggesting the involvement of an active, saturable absorption process. Metformin is rapidly distributed following absorption and does not bind to plasma proteins. No metabolites or conjugates of metformin have been identified. The absence of liver metabolism clearly differentiates the pharmacokinetics of metformin from that of other biguanides, such as phenformin. Metformin undergoes renal excretion and has a mean plasma elimination half-life after oral administration of between 4.0 and 8.7 hours. This elimination is prolonged in patients with renal impairment and correlates with creatinine clearance. There are only scarce data on the relationship between plasma metformin concentrations and metabolic effects. Therapeutic levels may be 0.5 to 1.0 mg/L in the fasting state and 1 to 2 mg/L after a meal, but monitoring has little clinical value except when lactic acidosis is suspected or present. Indeed, when lactic acidosis occurs in metformin-treated patients, early determination of the metformin plasma concentration appears to be the best criterion for assessing the involvement of the drug in this acute condition. After confirmation of the diagnosis, treatment should rapidly involve forced diuresis or haemodialysis, both of which favour rapid elimination of the drug. Although serious, lactic acidosis due to metformin is rare and may be minimised by strict adherence to prescribing guidelines and contraindications, particularly the presence of renal failure. Finally, only very few drug interactions have been described with metformin in healthy volunteers. Plasma levels may be reduced by guar gum and alpha-glucosidase inhibitors and increased by cimetidine, but no data are yet available in the diabetic population.
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PMID:Clinical pharmacokinetics of metformin. 874 35

This paper reviews the effects of renal insufficiency on the pharmacokinetics of oral antidiabetic drugs. Of the 3 groups of drugs currently available for the treatment of non-insulin-dependent diabetes mellitus (NIDDM), the sulphonylureas and metformin are, in general, well-tolerated and generally safe. In patients with chronic renal insufficiency, however, care must be exercised in the use of many of these drugs, as accumulation, either of the active drug or of active metabolites, can lead to serious adverse effects such as hypoglycaemia or, with metformin, lactic acidosis. The sulphonylurea drugs, to a greater or lesser degree, are metabolised in the liver to a variety of active or inactive compounds which, in general, are excreted by the kidneys. In addition, varying amounts of parent compound may depend on renal elimination. As a result, sulphonylurea drugs such as tolazamide, acetohexamide, chlorpropamide and glibenclamide (glyburide) are more likely to cause significant hypoglycaemia, as the metabolism of these drugs, compared with other commonly prescribed sulphonylureas, can lead to the accumulation of either the parent drug or the active metabolite in the presence of renal insufficiency. Tolbutamide, glipizide, gliclazide and gliquidone are much less likely to cause hypoglycaemia as their metabolites are either inactive or have minimal hypoglycaemic potency. Metformin is dependent on renal excretion and is not significantly metabolised. As a result, caution is required when treating patients with renal insufficiency where metformin accumulation can occur, with the danger of lactic acidosis. Although the correlation between creatinine clearance (CLCR) and total oral clearance of drug is weaker than the correlation between CLCR and renal clearance (CLR) of metformin, it is clear that renal insufficiency is associated with most cases of metformin-induced lactic acidosis. For this reason, clinicians in general would regard a raised plasma creatinine as a contraindication to metformin treatment. Acarbose, an alpha-glucosidase inhibitor, and a relatively new agent for treating NIDDM, is likely to be safe in patients with impaired renal function, as the drug is not significantly absorbed from the gut, but data on this subject are lacking.
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PMID:Pharmacokinetics of oral antihyperglycaemic agents in patients with renal insufficiency. 885 33

Since impaired glucose tolerance (IGT) is a major risk factor for non-insulin-dependent diabetes mellitus (NIDDM), some kinds of intervention aiming to prevent or to delay the onset of NIDDM in subjects with IGT might be considered. Besides life style modification, drug therapy which could correct insulin deficiency and insulin resistance, might prevent progression to NIDDM. One agent is an alpha-glucosidase inhibitor, which delays the absorption of glucose from the intestine. The resulting decrease in postprandial hyperglycemia and hyperinsulinemia could theoretically decrease insulin resistance in IGT subjects and, it is hoped, prevent or delay progression to NIDDM. Metformin, an antihyperglycemic drug of the biguanide class, may be effective in subjects with IGT by reducing hepatic glucose output, enhancing insulin sensitivity, or through other mechanisms such as weight loss. New insulin sensitizers, such as troglitazone and pioglitazone, improve insulin-mediated glucose disposal by enhancing tissue sensitivity to the actions of insulin and reversing the insulin resistance, characteristic of NIDDM. Sulfonylureas might be another candidates of drug intervention to IGT whose insulin secretory abilities are markedly reduced. As far as the question, "Can NIDDM be prevented or delayed?" is concerned, a prospective study using life style modification or above-mentioned drugs, should be performed on long-term basis.
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PMID:[Drug therapy in subjects with impaired glucose tolerance]. 891 39

Over the past few years, several oral agents for the treatment of type 2 diabetes have become available in the United States. Metformin, a biguanide that has been used for decades in other countries throughout the world, improves glycemic control without exacerbating hyperinsulinemia or promoting weight gain. This agent has recently been reintroduced in the United States. Acarbose is an alpha-glucosidase inhibitor that improves glycemic control by decreasing the intestinal absorption of glucose, thereby decreasing postprandial glucose elevations. The use of metformin and acarbose may be limited by their side effects and potential risks, especially the risk of lactic acidosis with metformin. The third newly available agent, troglitazone, has been shown to improve insulin sensitivity. Combinations of metformin, acarbose and troglitazone may facilitate improved glycemic control without the use of insulin, or they may allow sulfonylurea or insulin dosages to be reduced, in this way minimizing the adverse effects of hyperinsulinemia. Unfortunately, current oral therapies do not prevent the inevitable decline in glycemic control that occurs during the natural history of type 2 diabetes.
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PMID:New oral therapies for type 2 diabetes. 937 Oct 13

Obesity is common in NIDDM; in a cohort of 314 diabetics in Singapore, 44.3% are overweight. Management of obesity in diabetics differs from that in non-diabetics in that it is more urgent; weight maintenance is more difficult and hypoglycaemic medication may cause weight changes. Like in the non-diabetic, management of obesity in diabetic requires a pragmatic and realistic approach. A team approach is required: the help of the nurse educator, the dietitian, behaviour modification therapist, exercise therapist etc are required. A detailed history, careful physical examination and relevant investigations are required to assess the severity of the diabetic state and to exclude an occasional underlying cause of the obesity in the obese NIDDM. Weight loss is urgent in the obese NIDDM, especially those with android obesity. There must be a reduction in caloric intake. Weight loss leads to improvement in the glucose tolerance, insulin sensitivity, reduction in lipid levels and fall in blood pressure in the hypertensive. Exercise is of limited value except in the younger obese NIDDM. Metformin is the hypoglycaemic drug of choice as it leads to consistent weight reduction. The sulphonylureas may cause weight gain. Insulin should be avoided where possible as it causes further weight gain. Other hypoglycaemic agents include Glucobay (alpha-glucosidase inhibitor) and Troglitazone (insulin sensitizer) which do not alter the weight. Orlistat (lipase inhibitor) is promising as it causes reduction of weight, blood-glucose and lipid levels. Anti-obesity drugs (noradrenergic and serotonergic agents) have modest effects on weight reduction in the obese NIDDM; a widely use preparation, Dexfenfluramine (Adifax) has been withdrawn because of side effects. Surgery such as gastric plication is the last resort in treating the morbidly obese NIDDM. The discovery of leptin in 1994 has led to intense research into energy homeostasis in obesity; hopefully this will lead to better treatment of obesity in diabetics and non-diabetics.
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PMID:Management of obesity in NIDDM (non-insulin-dependent diabetes mellitus). 984 3

The UK Prospective Diabetes Study (UKPDS) provides the first conclusive proof for the importance of intensifying diabetes control in individuals with type 2 diabetes mellitus. However, reduction in cardiovascular disease risk with intensive therapy was modest and did not reach statistical significance. Metformin therapy in obese individuals with type 2 diabetes mellitus was associated with reduced cardiovascular death. These observations should be re-evaluated to determine whether various therapeutic agents available for treatment of type 2 diabetes mellitus have different effects on cardiovascular complications of diabetes. The addition of alpha-glucosidase inhibitor, acarbose, improved glycaemic control irrespective of concomitant therapy for diabetes, although compliance with this agent was poor. The tight blood pressure control study embedded in UKPDS reaffirms the importance of lowering the blood pressure below 150/85 to reduce microvascular and macrovascular complications of diabetes.
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PMID:Implications of the UK prospective diabetes study: questions answered and issues remaining. 1080 56

Although diet and exercise remain the cornerstones of type 2 diabetes therapy, attempts at lifestyle changes seldom result in the achievement of glycaemic control. As a result, the addition of pharmacological agents is usually necessary. Currently available treatment options improve glycaemic control in the short term; however, maintaining long-term glycaemic control, halting disease progression, and preventing the complications of type 2 diabetes have all proven to be elusive therapeutic goals. For more than 30 years, sulphonylureas (SUs) have been first-line therapy for the management of type 2 diabetes. These compounds control hyperglycaemia by stimulating insulin release from pancreatic beta cells, and thus their benefits are limited to patients with preserved beta-cell function. Despite historic reliance on these agents to treat type 2 diabetes, long-term use of SUs may desensitize beta cells. The meglitinides (e.g. repaglinide) are a new class of non-sulphonylurea secretagogues that bind to a different receptor on the beta cell. Repaglinide has a short duration of action and may be useful for the treatment of postprandial hyperglycaemia. The biguanides (e.g. metformin) represent another class of antidiabetic agents and improve glycaemic control primarily by decreasing hepatic glucose output. Metformin and SUs provide similar glucose-lowering effects, and, in combination, may provide additional benefits in some patients. Reducing the rate of glucose absorption with alpha-glucosidase inhibitors (e.g. acarbose) has been explored as an alternative approach to the management of postprandial hyperglycaemia, but these agents do not address the primary defect in type 2 diabetes. Eventually, prolonged overproduction of insulin to compensate for hyperglycaemia leads to dramatically reduced beta-cell function, and exogenous insulin therapy is required.
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PMID:Effects of current therapeutic interventions on insulin resistance. 1122 Feb 86

Type 2 diabetes mellitus is characterized by insulin deficiency but in particular by insulin resistance. Patients where it is not possible to achieve positive results within 4-12 weeks by optimalization of the lifestyle are candidates for treatment with oral antidiabetics. At present the following main groups of oral antidiabetics are discussed: insulin secretagogues (SU derivatives and methiglinide derivatives), biguanides (Metformin), alpha-glucosidase inhibitors (acarbose, miglitol) and insulin sensitizers (thiazolindiones). Traditional SU therapy improves the insulin plasma levels by releasing insulin from the pancreas. This implies further stress on the b-cells and the function of these cells declines reversibly. Biguanides, such as metformin, are effective substances reducing the blood sugar level, they are however associated with the problem of tolerability and are contraindicated in some diabetics. A new approach to the treatment of type 2 diabetes are thiasolinediones, insulin-sensitizing substances, the molecular basis of their action being via activation of PPAR gamma-nuclear receptors with subsequent change in expression of genes participating in carbohydrate and lipid metabolism.
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PMID:[Current and future aspects of oral antidiabetic agents in type 2 diabetes]. 1139 69

In this review we present the agents that are in use in the treatment of type 2 diabetes. Sulfonylureas of the 1st and 2nd generation increase insulin secretion but can induce hyperinsulinemia and sometimes prolonged hypoglycemia. Glimepiride is a new 3rd generation sulfonylurea with some advantages over the other members of this group, such as a lower risk of hypoglycemia, no interaction with cardiovascular KATP-channels and a possibility that it may increase insulin sensitivity. There are also newer insulin secretagogues (such as neteglinide and repaglinide) with a rapid onset of action on the beta-cell, therefore inducing a more physiological profile of insulin secretion during meals. The category of insulin sensitizers includes metformin and thiazolidinediones. Metformin effectively reduces hyperglycemia, hyperlipidemia and macroangiopathy in patients with type 2 diabetes. This agent increases the sensitivity of the liver and peripheral tissues to insulin and, therefore, it could be considered as a drug of choice for the prevention of type 2 diabetes. Thiazolidinediones (rosiglitazone and pioglitazone) increase the sensitivity of the tissues to insulin. This mechanism of action makes them powerful therapeutic tools for the treatment of type 2 diabetes (and possibly other insulin resistant states) either alone or in combination with other oral agents. The category of agents that interfere with the absorption of glucose and lipids includes alpha-glucosidase inhibitors (acarbose and miglitol) and lipase inhibitors (or-listat). alpha-Glucocidase inhibitors improve the time relationship between plasma insulin and glucose increases after a meal. Therefore, these agents may be used in the treatment of patients with type 2 diabetes, either alone at a very early stage of this disease (when insulin secretion is still adequate), or in combination with insulin secretagogues. alpha-Glucosidase inhibition may also prove useful as a supplement to insulin therapy in patients with type 1 diabetes mellitus. The inhibitor of gastrointestinal lipase orlistat may prove a useful adjunct to hypocaloric diets in patients with type 2 diabetes and obesity.
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PMID:Oral hypoglycemic agents: insulin secretagogues, alpha-glucosidase inhibitors and insulin sensitizers. 1146 May 77


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