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 alpha-glucosidase inhibitors acarbose and miglitol have been successfully used to control postprandial hyperglycaemia in diabetics. They probably work by slowing carbohydrate digestion and absorption, but their effect on mouth to caecum transit time has not been studied. The effect acarbose (100 mg), miglitol (100 mg), and placebo on mouth to caecum transit time (380 kcal breakfast with 20 g of lactulose) was investigated in 18 normal volunteers using breath hydrogen analysis. Both miglitol and acarbose significantly increased breath hydrogen excretion (F2,34 = 6.31, p = 0.005) and shortened the mouth to caecum transit time (F2,34 = 3.49, p = 0.04) after breakfast compared with placebo. There was a significant negative correlation between breath hydrogen excretion and mouth to caecum transit time suggesting that with shorter transit times significantly more carbohydrates were spilled into the colon. These results indicate that alpha-glucosidase inhibitors accelerate mouth to caecum transit time by inducing carbohydrate malabsorption.
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PMID:Effects of alpha-glucosidase inhibitors on mouth to caecum transit time in humans. 142 79

In two randomized, placebo-controlled, double-blind studies, the efficacy, duration of action and tolerability of a single morning dose of 25, 50, and 100 mg miglitol (BAY m 1099), an absorbable inhibitor of intestinal alpha-glucosidases, were assessed after repetitive sucrose or maize-starch loads (50 g of carbohydrates in 400 ml of water each at 08.00, 12.00, and 17.00 h). With sucrose, miglitol reduced the postprandial rise in blood glucose, serum insulin and serum gastric inhibitory polypeptide concentrations at any dosage. This effect was dose-dependent and confined to the first carbohydrate load in the morning, thus indicating the duration of alpha-glucosidase inhibition of less than 4 h. Sucrose malabsorption, indicated by breath hydrogen responses, occurred dose-dependently with 50 and 100 mg, but not with 25 mg of miglitol. Similarly, symptoms of carbohydrate malabsorption were absent with 25 mg of the inhibitor and mild to moderate after 50 and 100 mg of miglitol. With starch as the substrate, BAY m 1099 led to a significant amelioration of glycemic and hormonal rises after the first meal, but not thereafter. A numerical dose dependency was recognized, but this was not significant at the 5% level. Symptoms of carbohydrate malabsorption were absent with 25 mg and negligible with 50 mg BAY m 1099, but occurred almost regularly with the 100-mg dose. Breath hydrogen concentrations increased gradually with the dose of miglitol administered. A single morning dose of 25-100 mg of miglitol thus may be useful for the control of postprandial hyperglycemia after breakfast. Due to the duration of action of less than 4 h, this substance should be given with the three main meals.
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PMID:Inhibition of glycemic and hormonal responses after repetitive sucrose and starch loads by different doses of the alpha-glucosidase inhibitor miglitol (BAY m 1099) in man. 178 28

The absorbable deoxynojirimycin derivative emiglitate (BAY o 1248) is a potent competitive inhibitor of small intestinal alpha-glucosidases in man. In two similar randomized, placebo-controlled, double blind investigations, the efficacy, duration of action and tolerability of single doses of 10, 20 and 40 mg emiglitate have been assessed in healthy male volunteers after repeated sucrose or maize-starch loads at 08.00, 12.00 and 17.00 h. Even at the lowest dose used, emiglitate almost abolished the glycaemic (-88%) and hormonal responses after the first sucrose meal, simultaneously evoking significant hydrogen evolution (mean peak H2-concentration greater than 100 ppm), which was not related to the dose, and which induced unacceptable symptoms of carbohydrate malabsorption, i.e. at the dosages tested, the inhibition of glycaemic and hormonal responses was at the expense of intolerable gastrointestinal adverse effects. Flattening of postprandial responses of blood glucose, serum insulin and gastric inhibitory polypeptide was still apparent after a second sucrose load 4 h later, demonstrating long-lasting inhibition of alpha-glucosidase activity. After starch, the dose dependency of inhibition emerged more clearly than after sucrose, i.e. the reduction was less pronounced. However, emiglitate led to significant reduction of the glycaemic and hormonal rises after both the first and second starch meals. Symptoms of carbohydrate malabsorption were absent after 10 mg and were negligible with 20 mg or 40 mg emiglitate. Breath hydrogen concentration increased gradually, indicating slight but significant carbohydrate malabsorption after the highest dose of the alpha-glucosidase inhibitor. The results show that a single morning dose of 20-40 mg emiglitate might be useful in the control of postprandial hyperglycaemia after breakfast and lunch.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of sucrose- and starch-induced glycaemic and hormonal responses by the alpha-glucosidase inhibitor emiglitate (BAY o 1248) in healthy volunteers. 181 67

Epidemiological and experimental studies indicate a strong association between an elevated colon cancer risk and increased fecal excretion of secondary bile acids, neutral sterols, and prolonged gastrointestinal transit time. Starch malabsorption, on the other hand, has been reported to be a possible protective factor in colon carcinogenesis. To study the impact of starch malabsorption on these parameters, 12 healthy volunteers consumed a diet rich in starch for two 4-week periods. During a double-blind crossover trial they received the alpha-glucosidase inhibitor acarbose (BAY g 5421) in one of the study periods and placebo in the other. During acarbose treatment stool wet weight increased by 68%, stool dry weight by 57%, and gastrointestinal mean transit time by 30%. Fecal concentrations (mg/g dry weight) of the neutral sterols coprostanol, coprostanone, campesterol, 4-cholesten-3-one, and beta-sitosterol decreased by 36.8, 48.7, 42.1, 34.6, and 39.4%, respectively, under acarbose. Concentrations of the major secondary bile acids, deoxycholic and lithocholic acid, decreased by 59.9 and 52.2%, respectively. In spite of an increased stool weight, also daily excretion (mg/day) of these two bile acids was lower under acarbose (47.9 and 36.6%, respectively) compared to placebo, whereas excretion of the main primary bile acid, cholic acid, rose from 22.58 mg/day to 379.80 mg/day during the acarbose period. The changes in fecal bile acid and neutral sterol excretion found during acarbose treatment may explain a protective effect of starch malabsorption on colon cancer development.
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PMID:Effect of starch malabsorption on fecal bile acids and neutral sterols in humans: possible implications for colonic carcinogenesis. 186 44

This double-blind study was performed to evaluate the relation of the glycemic and hormonal (insulin, gastric inhibitory polypeptide) responses to standardized starch and sucrose meals to signs (H2 exhalation) and subjective symptoms of carbohydrate malabsorption during administration of 100 mg BAYm 1099 (miglitol) t.i.d. over a period of 8 weeks. Two groups of 8 male healthy volunteers received either placebo or verum. Oral sucrose loading tests (50 g) with and without miglitol were performed at day -5, 1, 25 and 53 of the study, starch loading tests (50 g) with and without the inhibitor were carried out at day -2, 4, 28 and 56. Miglitol significantly flattened the glycemic responses to sucrose and starch without evidence of diminished efficacy over the 8-week period. Also the blunting effect of miglitol on serum insulin and gastric inhibitory polypeptide responses and the stimulation of breath hydrogen exhalation proving carbohydrate malabsorption with starch and sucrose remained unchanged over time. Comparing breath hydrogen exhalation, responses were more pronounced after sucrose than after the starch loading tests. Symptoms (bloating, flatulence, diarrhea, cramps) were merely noticeable with starch as the substrate, but clearly present after sucrose. These symptoms were substantially curtailed during continuous drug intake. It is concluded that - irrespective of the substrate (starch/sucrose) - there is no escape of the desired effects of alpha-glucosidase inhibition by miglitol over 8 weeks, but symptoms of gaseousness due to carbohydrate malabsorption may undergo habituation.
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PMID:Postprandial glycemic control, hormonal effects and carbohydrate malabsorption during long-term administration of the alpha-glucosidase inhibitor miglitol. 229 49

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

Jejunal biopsies from six patients having the small bowel enteropathy associated with common variable immunodeficiency have been subjected to analytical subcellular fractionation and enzymic and regulatory peptide microassay to define the organelle pathology of this syndrome. Compared with normal subjects, the immunodeficient patients had decreased activities of the three brush border enzymes: alkaline phosphatase, gamma-glutamyl transferase and alpha-glucosidase. The other organelle marker enzyme activities and all the regulatory peptide concentrations did not differ from the controls. Density gradient experiments showed a complete loss of particulate beta-glucosidase (lactase) with activity entirely located in the cytosol. The integrity of other organelles was normal. These data indicate that the enteropathy of common variable immunodeficiency is associated with abnormalities in the jejunal brush border analogous to those present in tropical malabsorption syndrome.
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PMID:Jejunal mucosal enzyme activities, regulatory peptides and organelle pathology of the enteropathy of common variable immunodeficiency. 369 46

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


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