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)

This study evaluated the efficacy of adding pioglitazone 30 mg to the therapy of patients with type 2 diabetes mellitus whose glycaemic control was poor on an alpha-glucosidase inhibitor (alpha-GI) alone or in combination with a sulphonylurea (SU). The patients (n = 20) had a HbA(1c) level between 7.0 and 12.0% and the fasting plasma glucose was 7.8 mmol/l or higher. They were treated with 30 mg pioglitazone once daily for 16 weeks. The decrease in HbA(1c) at week 16 of treatment was 0.8% (7.8% at baseline dropping to 7.1% at week 16; p < or = 0.01). An increase in leptin was observed 4 weeks after starting the post-study period (p < or = 0.05). Tumour necrosis factor-alpha (TNF-alpha) and body fat percentage did not show any significant alterations. Correlations between the decrease in HbA1c at week 16 and characteristic variables of patients were examined. A correlation with leptin (p = -0.5632, p < or = 0.05) levels was found. Five patients experienced adverse drug reactions, such as oedema, hypoglycaemia and increased creatine phosphokinase (CK), all of which were mild in severity. The addition of pioglitazone in diabetics whose glycaemic control was poor on a alpha-GI alone or with a alpha-GI and SU combination resulted in a significant decrease in HbA1c, and the treatment was well-tolerated. Our findings also suggest that leptin levels could be useful for assessing responders to pioglitazone.
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PMID:Clinical effect of combination therapy of pioglitazone and an alpha-glucosidase inhibitor. 1468 36

Numerous individuals complain of malaise attributed to hypoglycaemia. However, the diagnosis of hypoglycaemia is rarely documented and most often overstated. Reactive hypoglycaemia in the postprandial state is rather exceptional. The diagnosis relies upon the measurement of plasma glucose concentration (< 3 mmol/l or 55 mg/dl) at the time of the malaise. Reactive hypoglycaemia is generally associated with adrenergic symptoms and, less often, with cognitive disturbances. Importantly, a plasma glucose concentration below 3 mmol/l during an oral glucose tolerance test is not sufficient to decide that the patient suffers from reactive hypoglycaemia. Treatment is based on dietary advices including frequent small split meals and limitation of carbohydrates with high glycaemic index. Acarbose, a specific inhibitor of gut alpha-glucosidase enzymes, may be helpful in case of diet failure. As compared with true reactive hypoglycaemia, a postprandial hyperadrenergic reaction without real concomitant hypoglycaemia is much more prevalent. Careful anamnesis may suspect such a diagnosis, but other diagnoses such as panic attack or vasovagal reaction should be excluded. Treatment is purely symptomatic and essentially empiric.
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PMID:[Reactive hypoglycaemia, a mysterious, insidious but non dangerous critical phenomenon]. 1518 36

Type 2 diabetes mellitus, a disorder of impaired insulin secretion and insulin resistance, has reached epidemic proportions. The effective management of Type 2 diabetes is of vital concern to clinicians. The identification of high-risk individuals and lifestyle management can help control diabetes; however, most patients require pharmacologic intervention. The goals of pharmacologic therapy are to achieve adequate glycemic control while avoiding hypoglycemia and weight gain and to minimize the risk of future micro- and macrovascular complications. There are a number of available glucose-lowering agents from which to choose. This review focuses on the sulfonylureas, the first oral agents introduced for the management of Type 2 diabetes, which are effective, well-tolerated, and well-established drugs, Second-generation sulfonylureas are now widely used in the management of Type 2 diabetes. The most recent addition, glimepiride, can be used in combination with metformin, the thiazolidinediones, alpha-glucosidase inhibitors, and insulin. The unique properties of glimepiride may provide advantages over other currently available insulin secretagogues.
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PMID:The role of glimepiride in the effective management of Type 2 diabetes. 1553 Nov 88

Two landmark intervention studies, the Diabetes Control and Complications Trial (DCCT) in patients with type 1 diabetes mellitus and the United Kingdom Prospective Diabetes Study (UKPDS) in patients with type 2 diabetes mellitus, have unequivocally demonstrated that intensive diabetes therapy reduces the risk of long-term diabetic complications. As a result, the commonly accepted treatment goal for most patients with diabetes is the achievement and maintenance of glycemic control that is as close to the normal range as safely possible. Important adverse effects of intensive diabetes therapy, particularly when the treatment includes insulin or several of the oral antihyperglycemic agents, are an increased risk of hypoglycemia and undesired weight gain. Improvement of glycemic control with insulin, insulin secretagogues (sulfonylureas, meglitinides), and insulin sensitizers (thiazolidinediones) is often accompanied by weight gain. The etiology of this weight gain is likely multifaceted, including a reduction of glucosuria, increased caloric intake to prevent hypoglycemia, and anabolic effects on adipose tissue. Biguanides and alpha-glucosidase inhibitors have a neutral or even positive effect (decrease) on weight, which may partly be attributable to their non-insulinotropic mechanism of action, a modest effect on satiety, and to their gastrointestinal adverse effect profile. Several antihyperglycemic agents that are currently in clinical development may improve glycemic control in conjunction with weight reduction. These include an analog of the pancreatic beta-cell hormone amylin (pramlintide), as well as glucagon-like peptide-1 (GLP-1) and exendin, and their analogs. Pharmacological agents with antihyperglycemic and positive weight effects have the potential to become important additions to our therapeutic armamentarium, in that they may help to achieve glycemic targets while addressing the long-standing clinical problem of weight gain as an adverse effect of intensive diabetes therapy.
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PMID:Weight effect of current and experimental drugs for diabetes mellitus: from promotion to alleviation of obesity. 1587 53

Because management of type 2 diabetes mellitus usually involves combined pharmacological therapy to obtain adequate glucose control and treatment of concurrent pathologies (especially dyslipidaemia and arterial hypertension), drug-drug interactions must be carefully considered with antihyperglycaemic drugs. Additive glucose-lowering effects have been extensively reported when combining sulphonylureas (or the new insulin secretagogues, meglitinide derivatives, i.e. nateglinide and repaglinide) with metformin, sulphonylureas (or meglitinide derivatives) with thiazolidinediones (also called glitazones) and the biguanide compound metformin with thiazolidinediones. Interest in combining alpha-glucosidase inhibitors with either sulphonylureas (or meglitinide derivatives), metformin or thiazolidinediones has also been demonstrated. These combinations result in lower glycosylated haemoglobin (HbA(1c)), fasting glucose and postprandial glucose levels than with either monotherapy. Even if modest pharmacokinetic interferences have been reported with some combinations, they do not appear to have important clinical consequences. No significant adverse effects, except a higher risk of hypoglycaemic episodes that may be attributed to better glycaemic control, occur with any combination. Challenging the classical dual therapy with sulphonylurea plus metformin, there is a recent trend to use alternative dual combinations (sulphonylurea plus thiazolidinedione or metformin plus thiazolidinedione). In addition, triple therapy with the addition of a thiazolidinedione to the metformin-sulphonylurea combination has been recently evaluated and allows glucose targets to be reached before insulin therapy is considered. This triple therapy appears to be safe, with no deleterious drug-drug interactions being reported so far.Potential interferences may also occur between glucose-lowering agents and other drugs, and such drug-drug interactions may have important clinical implications. Relevant pharmacological agents are those that are widely coadministered in diabetic patients (e.g. lipid-lowering agents, antihypertensive agents); those that have a narrow efficacy/toxicity ratio (e.g. digoxin, warfarin); or those that are known to induce (rifampicin [rifampin]) or inhibit (fluconazole) the cytochrome P450 (CYP) system. Metformin is currently a key compound in the pharmacological management of type 2 diabetes, used either alone or in combination with other antihyperglycaemics. There are no clinically relevant metabolic interactions with metformin, because this compound is not metabolised and does not inhibit the metabolism of other drugs. In contrast, sulphonylureas, meglitinide derivatives and thiazolidinediones are extensively metabolised in the liver via the CYP system and thus, may be subject to drug-drug metabolic interactions. Many HMG-CoA reductase inhibitors (statins) are also metabolised via the CYP system. Even if modest pharmacokinetic interactions may occur, it is not clear whether drug-drug interactions between oral antihyperglycaemic agents and statins may have clinical consequences regarding both efficacy and safety. In contrast, a marked pharmacokinetic interference has been reported between gemfibrozil and repaglinide and, to a lesser extent, between gemfibrozil and rosiglitazone. This leads to a drastic increase in plasma concentrations of each antihyperglycaemic agent when they are coadministered with the fibric acid derivative, and an increased risk of adverse effects. Some antihypertensive agents may favour hypoglycaemic episodes when co-prescribed with sulphonylureas or meglitinide derivatives, especially ACE inhibitors, but this effect seems to result from a pharmacodynamic drug-drug interaction rather than from a pharmacokinetic drug-drug interaction. No, or only modest, interferences have been described with glucose-lowering agents and other pharmacological compounds such as digoxin or warfarin. The effects of inducers or inhibitors of CYP isoenzymes on the metabolism and pharmacokinetics of the glucose-lowering agents of each pharmacological class has been tested. Significantly increased (with CYP inhibitors) or decreased (with CYP inducers) plasma levels of sulphonylureas, meglitinide derivatives and thiazolidinediones have been reported in healthy volunteers, and these pharmacokinetic changes may lead to enhanced or reduced glucose-lowering action, and thus hypoglycaemia or worsening of metabolic control, respectively. In addition, some case reports have evidenced potential drug-drug interactions with various antihyperglycaemic agents that are usually associated with a higher risk of hypoglycaemia.
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PMID:Drug interactions of clinical importance with antihyperglycaemic agents: an update. 1596 7

A 42-year-old woman with hypoglycemic symptoms that occurred several hours after a meal visited our hospital. The hypoglycemic symptoms appeared when she was 37 years old, and her plasma glucose level had been assessed as less than 60 mg/dL when she experienced the symptoms. One year before, she had been diagnosed with reactive hypoglycemia by 75 g-oral glucose tolerance test (OGTT), which showed a normal glucose tolerance (NGT) pattern, and had begun taking an alpha-glucosidase inhibitor and nutritional treatment. A 75 g-OGTT on admission showed hypoglycemia at 240 min after glucose loading, excessive insulin secretion and an impaired glucose tolerance (IGT) pattern. A euglycemic-hyperinsulinemic clamp study demonstrated decreased insulin sensitivity. Therefore, we suspected that she had reactive hypoglycemia associated with insulin resistance and treated her with 15 mg/day pioglitazone. Her hypoglycemic symptoms completely disappeared after treatment with pioglitazone; insulin sensitivity in a euglycemic-hyperinsulinemic clamp study improved. Another 75 g-OGTT revealed that the excessive insulin secretion and hypoglycemia at 240 min after glucose loading had disappeared, and glucose tolerance was normalized from an IGT pattern to an NGT pattern. Thus, we believe that pioglitazone is effective for reactive hypoglycemia and aggravated glycemic metabolism associated with insulin resistance.
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PMID:Pioglitazone prevents reactive hypoglycemia in impaired glucose tolerance. 1609 29

The objective of this review of the literature is to analyze the results of studies including diabetic patients aged 70 years and older. Although the risk of treatment is greater in this population because of co-morbid conditions and altered renal function, information on the pharmacokinetics and pharmacodynamics of antidiabetic drugs remains limited. Long-term experience with sulfonylureas is sufficient to establish certain general rules of use; but for biguanides and alpha-glucosidase inhibitors, problems of tolerance limit use; further data are needed on glinides and glitazones. Use of insulin or insulin analogs is frequent and prescription should be adapted to achieve an acceptable balance between the risk of hypoglycaemia and therapeutic goals.
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PMID:Use of antidiabetic drugs in elderly patients. 1641 72

We recently encountered a 96-year-old Japanese woman who suffered from frequent hypoglycemia. Endocrinological and imaging data eliminated the possibility of insulinoma, whereas oral glucose tolerance testing revealed impaired glucose tolerance and subsequent reactive hypoglycemia. The patterns between insulin or C-peptide secretions and glucose excursions demonstrated that the discrepancy occurred in the late postprandial stage. Administration of small doses of alpha-glucosidase inhibitor (alpha-GI) dramatically inhibited the rapid rise and subsequent precipitous fall of plasma glucose. Reactive hypoglycemia may be one of the important cause of hypoglycemia in the elderly, and alpha-GI could effectively and safely prevent such hypoglycemic attacks in those patients.
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PMID:Postprandial reactive hypoglycemia in an oldest-old patient effectively treated with low-dose acarbose. 1696 25

The secondary and adverse effects when biguanides, alpha-glycosidase inhibitor or thiazolidine derivative was used with sulphonylurea agent (SU) as compared with those with SU alone in Type 2 diabetes patients by using Systematic Review. Two-agent concurrent treatment groups, taken from studies in which subjects were assigned to a group given only a sulfonylurea agent and a group given a sulfonylurea agent with the other glycemic control agent (combination of a sulfonylurea agent and a biguanide agent (I), combination of a sulfonylurea agent and an alpha-glucosidase inhibitor (II), and combination of a sulfonylurea agent and thiazolidinedione (III)), were studied in a randomized controlled trial. The secondary efficacy outcome measures were total cholesterol (TC), triglyceride (TG), HDL-C, LDL-C, and change in body weight. The incidence of hypoglycemia, feeling of fullness, diarrhea, liver dysfunction, and edema was investigated as a safety outcome measure, and the clinical significance of concurrent treatment with a sulfonylurea agent in addition to the other glycemic control agent was investigated. With respect to (II), an antidiabetic effect was showed. As for (III), it had the disadvantage of increased body weight. Furthermore, increase of HDL-C levels, in particular, was observed. The improving effect of (III) on serum lipids may be clinically effective for considering the pathologic condition of diabetes, which is often complicated by hyperlipidemia.
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PMID:Lipids behavior and adverse effects for oral antidiabetic agents in patients with Type 2 diabetes treated with sulfonylureas alone based on systematic review. 1791 33

The increasing proportion of elderly persons in the global population, and the implications of this trend in terms of increasing rates of chronic diseases such as type 2 diabetes mellitus, continue to be a cause for concern for clinicians and healthcare policy makers. The diagnosis and treatment of type 2 diabetes in the elderly is challenging, as age-related changes alter the clinical presentation of diabetic symptoms. Once type 2 diabetes is diagnosed, the principles of its management are similar to those in younger patients, but with special considerations linked to the increased prevalence of co-morbidities and relative inability to tolerate the adverse effects of medication and hypoglycaemia. In addition, there are many underappreciated factors complicating diabetes care in the elderly, including cognitive disorders, physical disability and geriatric syndromes, such as frailty, urinary incontinence and pain. Available oral antihyperglycaemic drugs include insulin secretagogues (meglitinides and sulfonylureas), biguanides (metformin), alpha-glucosidase inhibitors and thiazolidinediones. Unfortunately, as type 2 diabetes progresses in older persons, polypharmacy intensification is required to achieve adequate glycaemic control with the attendant increased risk of adverse effects as a result of age-related changes in drug metabolism. The recent introduction of the incretins, a group of intestinal peptides that enhance insulin secretion after ingestion of food, as novel oral antihyperglycaemic treatments may prove significant in older persons. The two main categories of incretin therapy currently available are: glucagon-like peptide-1 (GLP-1) analogues and inhibitors of GLP-1 degrading enzyme dipeptidyl peptidase-4 (DPP-4). The present review discusses the effect of aging on metabolic control in elderly patients with type 2 diabetes, the current treatments used to treat this population and some of the more recent advances in the field of geriatric type 2 diabetes. In particular, we highlight the efficacy and safety of GLP-1 and DPP-4 inhibitors, administered as monotherapy or in combination with other oral antihyperglycaemic agents, especially when the relevant clinical trials included older persons. There is strong evidence that use of incretin therapy, in particular, the DPP-4 inhibitors, could offer significant advantages in older persons. Clinical evidence suggests that the DPP-4 inhibitors vildagliptin and sitagliptin are particularly suitable for frail and debilitated elderly patients because of their excellent tolerability profiles. Importantly, these agents lack the gastrointestinal effects seen with metformin and alpha-glucosidase inhibitors taken alone, and have a low risk of the hypoglycaemic events commonly seen with agents that directly lower blood glucose levels.
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PMID:New approaches to treating type 2 diabetes mellitus in the elderly: role of incretin therapies. 1894 59


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