Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024523 (malabsorption)
 7,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acarbose, an alpha-glucosidase inhibitor, delays absorption of carbohydrate in the gut, thereby lowering postprandial glucose levels. Safety data on this drug have been gathered in a series of studies on animals and in extensive clinical trials in humans. Although an initial long term feeding study in rats showed an excess of renal tumours at very high dosages of acarbose (up to 300 mg/kg bodyweight daily), further evaluation with similar studies in rats, hamsters, and dogs indicated that the problem was related to carbohydrate malabsorption. With adequate glucose intake and in gavage studies, no difference in tumour incidence between placebo- and acarbose-treated groups was seen. From 1976 to 1989, safety data on acarbose were obtained in approximately 8800 patients in 2 separate groups of clinical trials, the Bayer International Clinical Data Pool and the American phase III trials. Almost all adverse experiences, as reported by 56 to 76% of patients on acarbose vs 32 to 37% of patients on placebo, were related to the digestive system and included diarrhoea, flatulence, bloating and nausea. Most symptoms were of mild to moderate intensity and tended to improve with time. In the American trials a small but significant increase in liver transaminases was seen, 3.8% in acarbose-treated patients vs 0.9% in controls together with a 1% increase in anaemia in the acarbose group. Overall, acarbose was well tolerated and the adverse experience profile was clinically acceptable.
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PMID:Safety profile of acarbose, an alpha-glucosidase inhibitor. 128 May 77

The effect of acarbose on hydrolysis of a pure starch meal was investigated in normal subjects and ileostomy patients by means of 13CO2 breath tests and blood glucose levels as parameters of absorption, and of H2 breath tests, serum acetate levels, and ileal loss of carbohydrate as parameters of malabsorption. Additional information on the effect of acarbose on alpha-amylase activity was obtained by in vitro experiments. Acarbose (200 and 400 mg) significantly delayed starch absorption. Serum acetate was found to be a less sensitive marker of malabsorption than breath H2 excretion. After intake of 50 g starch plus 400 mg acarbose, 23-71% of the starch load was lost in the ileostomy effluent, for a large part as starch. This suggests that acarbose considerably inhibits alpha-amylase, and not only brush-border enzymes. In vitro experiments confirm that an inhibition of two thirds of alpha-amylase activity can be expected from pharmacologically used doses of acarbose.
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PMID:Effects of acarbose on starch hydrolysis. Study in healthy subjects, ileostomy patients, and in vitro. 161 53

Dependent on the dosages used, digestion and absorption inhibitors or disaccharidase inhibitors, such as Acarbose, might cause malabsorption of nutrients, and hence, among other effects, affect caloric balances. This negative effect on caloric balance has actually been well documented in animal experimentation. However, in nondiabetic subjects with excessive degrees of obesity, no consistent weight reduction could be induced by disaccharidase inhibitors. Subsequently, Acarbose has been advocated for type 2 diabetic patients in dosages that might reduce postprandial hyperglycemia and insulinemia, whereas significant degrees of malabsorption should be excluded. At these dosages of the drug, there is no clinical perspective with regard to weight-reducing (side) effects of disaccharidase inhibitors. Whether a hypothetical diminution of serum insulin daily profiles during Acarbose treatment in obese type 2 diabetic patients might contribute to a normalization of the metabolic syndrome and to a facilitation of weight-reducing efforts remains speculative. At present, there does not seem to be much rationale in trying to exploit digestion and/or absorption inhibitors for weight-reduction therapies in obesity, unless they are used to enforce a negative caloric balance by malabsorption of nutrients.
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PMID:Pharmacological treatment of obesity: digestion and absorption inhibitors-clinical perspective. 172 47

Acarbose delays the production of monosaccharides (notably glucose) by inhibiting the alpha-glucosidases associated with the brush-border membrane of the small intestine which are responsible for the digestion of complex polysaccharides and sucrose. In healthy subjects acarbose 100 to 200 mg significantly inhibits postprandial glucose, insulin and triglyceride responses, with some evidence of carbohydrate malabsorption with the higher dose. Clinical trials in patients with non-insulin-dependent diabetes mellitus showed that acarbose improved diabetic control, especially postprandial blood glucose levels, independent of whether the patients were receiving concomitant oral antidiabetic drugs in addition to dietary management. In comparative studies acarbose was significantly superior to placebo, and comparable to biguanides, when used alone or as an adjuvant to sulphonylurea therapy. Trials in patients requiring insulin to control their diabetes demonstrated that acarbose significantly reduced postprandial blood glucose concentrations, resulting in a smoother diurnal blood glucose-time curve and improved symptoms associated with nocturnal hypoglycaemia. Daily insulin requirements were sometimes reduced. In large multicentre trials acarbose up to 600 mg/day for 3 to 12 months improved glycaemic control in approximately 55% of patients with non-insulin-dependent or insulin-dependent diabetes mellitus. Apart from its use in diabetes, encouraging preliminary results have been obtained with acarbose in other therapeutic areas such as dumping syndrome, reactive hypoglycaemia, and types IIb and IV hyperlipoproteinaemias--however, further clinical experience is needed in these settings before clear conclusions can be drawn. No serious side effects have been reported during treatment with acarbose, although it is associated with a high incidence of troublesome gastrointestinal symptoms such as flatulence, abdominal distension, borborygmus and diarrhoea. The incidence of these reactions usually decreases with time. Thus, acarbose represents the first of a new class of oral antidiabetic drugs--the alpha-glucosidase inhibitors. It has proven useful for improving glycaemic control when used as an adjunct to standard therapy involving dietary restriction, oral antidiabetic drugs and/or subcutaneous insulin. That being the case, acarbose should provide the clinician with an interesting treatment option which can be used in a broad range of patients with diabetes mellitus in whom 'traditional' management approaches produce suboptimal glycaemic control.
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PMID:Acarbose. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential. 328 12

A major barrier to the widespread clinical use of an alpha-glucosidase inhibitor such as Acarbose, is the unpleasant gastrointestinal symptoms of carbohydrate malabsorption associated with its use. Acarbose is usually administered as a tablet and eaten with the first mouthful of the meal, making its uniform distribution through the meal unlikely. In the present study, Acarbose was crushed to a powder and mixed through a test meal before it was consumed. Six healthy young men consumed test meals containing 75 g carbohydrate either as whole brown rice or as ground brown rice. When Acarbose was uniformly mixed through a ground rice meal prior to digestion it produced dose-dependent reductions in the postprandial glucose, insulin and GIP responses which were evident at doses as low as 12.5 mg. The responses to whole brown rice were intermediate between those to 12.5 and 25 mg Acarbose in ground brown rice. In tablet form Acarbose was only one quarter as effective in flattening the post prandial glucose and insulin responses as it was in powder form. These results highlight the importance of uniform distribution of Acarbose through a carbohydrate meal in order to achieve maximum effectiveness in delaying digestion and absorption and yet not promoting carbohydrate malabsorption.
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PMID:Optimum effectiveness of intestinal alpha-glucosidase inhibitors: importance of uniform distribution through a meal. 388 43

Acarbose is an alpha-glucosidase inhibitor which reversibly and competitively inhibits the digestion of oligo- and disaccharides at the brush border of the small intestine. This study evaluates the preventive and therapeutic properties of acarbose in the treatment of obesity. Dose-response experiments were performed during repeated sucrose loads in man in order to investigate the effects of acarbose on plasma insulin and blood glucose levels. After titration of efficient doses, a long-term tolerance test of acarbose was undertaken in a small pilot study. Finally, the relapse preventing effect of acarbose was tested during double-blind cross-over conditions in 24 weight reduced obese women. In growing Sprague-Dawley rats, the effects of acarbose on body weight, lipid depots and adipose tissue cellularity were tested during pair-feeding and ad libitum conditions. Such effects were also studied in adult ad libitum-fed rats. Blood glucose, plasma insulin, body fat, depot lipids as well as fat cell weight and number were determined with established techniques. During a sucrose load, acarbose reduced insulin in a dose-dependent fashion. Glucose was also reduced, but not dose-dependently and only to a moderate extent. During a 200 g sucrose load, 400 mg of acarbose did not necessarily result in a maximal reduction of the insulin response while the glucose response was maximally inhibited after 100 mg. Acarbose reduced the relapse rate after weight reduction. No serious side effects were observed. Flatulence and meteorism occurred frequently. In growing rats, acarbose retarded the development of body weight and of lipid depots not only during pair-feeding conditions but also in ad libitum-fed animals eating considerably more than their controls. The spontaneous food consumption was increased by acarbose also in adult rats but in these animals neither body weight nor lipid depots were significantly reduced by acarbose. It is concluded that acarbose induces a carbohydrate malabsorption. Insulin levels are reduced not only via a decreased glycemic stimulus but also by interference with other insulin releasing mechanism(s). Acarbose is the first drug ever tested with long-term relapse reducing effects after weight reduction. Animal experiments suggest that acarbose may be of value in the prevention of obesity, particularly since the drug retards lipid accumulation also during ad libitum-feeding.
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PMID:alpha-Glucosidase inhibition in obesity. 391 27

Acarbose, an alpha-glucosidase inhibitor, lowers the glycemic excursion following the ingestion of carbohydrates, in particular, sucrose. This was confirmed with increasing doses of acarbose (0, 50, and 100 mg) and the causes investigated. The absorption of the glucose moiety of sucrose was determined from plasma tracer concentrations when overnight-fasted normal subjects received a 100-g oral sucrose load labeled with sucrose [(1-14C]glucose and a simultaneous intravenous infusion of [3-3H]glucose. As the dose of acarbose given with the sucrose load was increased from 0 to 100 mg, the percentage of the load appearing in the peripheral circulation decreased from 90% to 62%. Malabsorption was confirmed by the appearance of breath hydrogen. Simultaneously, absorption time increased from 243 to 411 min. Maximal glycemic excursions were therefore lowered from 64 to 31 mg/dl. The plasma concentrations of gastric inhibitory polypeptide and insulin decreased with the acarbose dose so that the fractional disappearance rate of glucose also decreased. However, the concentrations of glucagon-like immunoreactivity (GLI) rose, confirming the ileal appearance of malabsorbed sucrose.
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PMID:The effects of an alpha-glucoside hydrolase inhibitor on glycemia and the absorption of sucrose in man determined using a tracer method. 636 57

Acarbose (Bay g 5421) is a powerful alpha-glucoside hydrolase inhibitor of potential value in the treatment of diabetes and hypoglycemic dumping syndrome after gastric surgery. The extent of its use may be limited by symptoms produced by carbohydrate malabsorption. To minimize these, the action of low doses of acarbose on 24-h blood glucose profiles and hydrogen evolution have been studied on four ambulant volunteers on control diets, after exclusion of sucrose and also after addition of guar in an attempt to enhance the therapeutic effect. Replacement of dietary sucrose by starch abolished significant hydrogen evolution in the morning after low doses of acarbose but did not reduce its effectiveness in decreasing the mean three-meal blood glucose area by 41% (P less than 0.002). Addition of hydrated guar to this diet reduced the mean three-meal glucose area after acarbose further by 72% (P less than 0.001) but increased hydrogen evolution. The results suggest that acarbose will be both effective and acceptable given at low dose when the dietary carbohydrate is starch.
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PMID:Effect of acarbose on the 24-hour blood glucose profile and pattern of carbohydrate absorption. 692 27

The sulphonylureas and the biguanides are widely used as adjuncts to dietary measures in the treatment of non-insulin-dependent (type 2) diabetes mellitus (NIDDM). Adverse effect profiles differ markedly between the sulphonylureas and biguanides, reflecting differences in chemical structure and mode of action. Sulphonylureas are generally well tolerated, although pharmacokinetic differences between these agents have important clinical implications. The main adverse effect associated with sulphonylureas is hypoglycaemia. This effect is a predictable consequence of the principal pharmacological effect of these drugs, i.e. sensitisation of the islet beta-cell to glucose, resulting in enhanced endogenous insulin secretion. Sulphonylurea-induced suppression of hepatic glucose production may cause profound and protracted hypoglycaemia, especially in elderly patients, in individuals with intercurrent illnesses and reduced caloric intake, or when taken in combination with other compounds with hypoglycaemic potential, e.g. alcohol (ethanol). Sulphonylureas with a longer duration of action, notably chlorpropamide and glibenclamide (glyburide), are more liable to induce serious hypoglycaemia, particularly when drug elimination is reduced by renal impairment. Other drugs such as salicylates may potentiate the actions of sulphonylureas, thereby increasing the risk of hypoglycaemia. Biguanide therapy is associated with alterations in lactate homeostasis which under certain clinical circumstances may result in fatal lactic acidosis. Phenformin is associated with a markedly greater risk of lactic acidosis than metformin. Phenformin has been withdrawn in many countries for this reason. All biguanides must be avoided in patients with renal impairment, hepatic dysfunction and cardiac failure--conditions where drug accumulation or disordered lactate metabolism may predispose to lactic acidosis. Phenformin should not be given to individuals who exhibit a severe, genetically conferred hepatic defect of hydroxylation which impedes metabolism of this drug. Less seriously, the biguanides are associated with a relatively high incidence of gastrointestinal adverse effects which limit compliance. Acarbose, a competitive inhibitor of intestinal alpha-glucosidases, has recently been introduced. In contrast to the sulphonylureas and biguanides, acarbose has not been associated with life-threatening adverse effects. This reflects the low systemic absorption of the drug and, predictably, its principal unwanted effects are gastrointestinal disturbances resulting from iatrogenic carbohydrate malabsorption.
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PMID:Comparative tolerability profiles of oral antidiabetic agents. 784 43

Acarbose is a competitive inhibitor of the intestinal alpha-glycosidases, that can delay absorption of intestinal carbohydrates causing their malabsorption. In the present paper we studied the effects of insulin, acarbose and their association on glomerular basement membrane thickening in alloxan-diabetic rats. Twenty-five male and female Wistar rats, approximately 3 months old at the beginning of the experiment, were assigned randomly to each of five experimental groups: normal control rats, alloxan-diabetic control rats, alloxan-diabetic rats treated with acarbose, alloxan-diabetic rats treated with insulin, and alloxan-diabetic rats treated with insulin plus acarbose. Alloxan was administered in a single i.v. dose of 442 mg/kg body weight. Insulin was given subcutaneously at doses of 18 to 30 IU/kg corrected daily on the basis of glycosuria and ketonuria. Acarbose was given mixed with rat chow in a dose of 50 mg/100 g chow. Body weight, water and food intake and diuresis, as well as blood and urine glucose were determined after 1, 3, 6, 9, and 12 months of treatment. Glomerular basement membrane (GBM) thickening was determined by electron microscopy at the same times. Clear clinical and laboratory signs of severe diabetes, with blood glucose levels above 200 mg/dl and urine glucose above 3000 mg/dl, were observed in all alloxan-diabetic control rats, in all periods of follow-up, whereas administration of insulin or acarbose reduced the blood glucose levels of treated groups. The most satisfactory control of blood and urine glucose was observed in animals treated with both insulin and acarbose. However, diarrhea was observed in diabetic rats treated with acarbose associated or not with insulin. GBM thickening was correlated with age in all groups. Beginning at six months after diabetes induction, the GBM of untreated diabetic rats was significantly thicker (mean +/- SEM, 4.446 +/- 0.45 mm) than that of normal rats (2.977 +/- 0.63mm). Both insulin and acarbose prevented GBM thickening and their combination induced thickening similar to the age dependent thickening observed for normal rats of the same age. We conclude that acarbose when combined with insulin may be a good option in the control of diabetes and its renal complications.
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PMID:Effect of long-term treatment with insulin and/or acarbose on glomerular basement membrane thickening in alloxan-diabetic rats. 918 Nov 5


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