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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Orally taken alpha-glucosidase inhibitors are used for the management of diabetes mellitus. These drugs can prevent the postprandial rise of the blood glucose level by inhibiting the enzymatic digestion of carbohydrates in the intestinal lumen. Non-absorbable inhibitors such as acarbose are expected to function exclusively in the intestine, but absorbable inhibitors such as miglitol may exert an inhibitory effect on non-intestinal alpha-glucosidases present in the various cell types of the body. The potential side-effects of absorbable inhibitors are evaluated in this literature review. It is concluded that there is little risk of inducing unwanted side-effects when miglitol is taken in an oral dose of approximately 1 mg kg-1 body weight. The use of absorbable inhibitors is, however, not advised in case of kidney dysfunction.
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PMID:An evaluation of the potential side-effects of alpha-glucosidase inhibitors used for the management of diabetes mellitus. 800 22

In Diabetes Mellitus, type IV collagen biosynthesis is increased: the alpha 1(IV) procollagen specific mRNA concentration is elevated, particularly in the kidney, and the type IV collagen protein is accumulating is the thickened basement membranes. Aldose reductase inhibitors like sorbinil do prevent basement membrane thickening and type IV collagen overproduction. The latter seems related to intracellular sorbitol accumulation and also to protein kinase C activation. Autocrine or paracrine TGF beta may be involved in the type IV collagen oversecretion. The secreted type IV collagen is subject to posttranslational alterations, especially glycation which leads to advanced glycation end-products and covalent crosslinks. This decreases collagen extractability and susceptibility to collagenases and favours basement membrane thickening. Disaccharide unit-specific alpha-glucosidase activity is inhibited by glucose (Kp = 7.5 mM). Type IV collagenase activity secreted by endothelial cells cultured at high glucose concentrations appears to be diminished. Therefore type IV collagen catabolism may be decreased in Diabetes Mellitus.
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PMID:[Changes in collagen type IV metabolism in diabetes]. 801 6

Eight non-insulin-dependent diabetes mellitus patients, in whom oral hypoglycaemic agents were not effective, were treated with an alpha-glucosidase inhibitor, AO-128 (0.9 mg/day) for 6 months. After 6 months of treatment there was a statistically significant decrease in the blood glucose level 1 and 2 h postprandially. The 2 h blood glucose level was also significantly reduced after 2 months' treatment. The insulin and HbA1c levels after 2 and 6 months' treatment were lower than those before administration. Faecal weight, the frequency of bowel movements, the ratio of hydroxy fatty acids to total fatty acids, and faecal short-chain carboxylic acid content were all increased significantly during treatment. The initially hard stools became normal or soft, although no actual diarrhoea developed. Both faecal bile-acid excretion and the ratio of primary bile acids to total bile acids were increased significantly after 2 months, but they showed some recovery towards the pretreatment levels after 6 months' treatment. There was no distinct change in neutral sterol and fatty acid excretion. Breath hydrogen excretion showed a slight increase after treatment. These results suggest that intestinal fermentation was promoted and the intestinal transit time was shortened by AO-128 administration.
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PMID:Effect of an alpha-glucosidase inhibitor on intestinal fermentation and faecal lipids in diabetic patients. 811 83

Diabetes is characterized by hyperphagia, polydipsia, polyuria, elevations in blood and urinary glucose, and alterations in the adrenergic nervous system. Insulin treatment is effective in reversing most of the adverse conditions of diabetes in the streptozotocin-treated rat. Acarbose (BAY G 5421), an intestinal alpha-glucosidase inhibitor, decreases postprandial glycemia by delaying carbohydrate absorption and also affords some beneficial effects in the diabetic animal. The purpose of this study was to evaluate the effects of chronic insulin (< or = 2 U/day) with and without acarbose treatment (20 mg/100 g of diet) on the metabolic and adrenergic parameters altered in streptozotocin (50 mg/kg, intravenously)-induced diabetes in female rats. Insulin dosage was changed weekly after the first 2 weeks of treatment in both insulin-treated groups in an attempt to maintain a level of blood glucose that was comparable to that achieved with acarbose treatment alone. Insulin dosage was reduced to a greater extent in the dual-treated group than in the group treated with insulin alone. Diabetic rats were hyperphagic, polydipsic, and polyuric within 1 week of streptozotocin treatment. Each treatment alone was effective in reducing these alterations. However, these reductions were more apparent in the combined therapy group. Only in this combined therapy group was glycated hemoglobin returned to normal. All treatments also prevented the significant weight loss observed in untreated diabetic animals. Adrenergic responses were assessed by monitoring the rise in tail skin temperature associated with administration of isoproterenol. Diabetic rats were less responsive than controls, and each of the treatments restored this response.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of insulin and acarbose alone and in combination in the female streptozotocin-induced diabetic rat. 830 97

The effect of the alpha-glucosidase inhibitor acarbose on retinal capillary basement membrane thickening was examined in the spontaneously diabetic BB/W-rat. Four months of diabetes resulted in significant thickening of the basement membranes of both the superficial and deep capillary nets of the retina. This characteristic change of the retinal microvasculature in diabetes was completely prevented by acarbose treatment that substantially reduced postprandial hyperglycemia. A similar but less pronounced effect was seen on the age-related increase in basement membrane thickening in acarbose-treated non-diabetic control rats who demonstrated decreased glycated hemoglobin levels compared to non-treated control rats. Significant positive correlations between basement membrane thickness and glycated hemoglobin area suggest that diabetic retinal microangiopathy may be prevented by lowering the cumulative glucose exposure to the microvasculature, and that age-related basement membrane thickening is mediated by long-term exposure to normal glucose levels.
Diabetes Res Clin Pract 1993 May
PMID:The effect of acarbose on diabetes- and age-related basement membrane thickening in retinal capillaries of the BB/W-rat. 837 64

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

Acarbose is an inhibitor of intestinal alpha-glucosidase and has been reported to decrease blood glucose concentrations and glycosuria in diabetic patients and animals. In this study we investigated whether this drug could prevent the abnormalities detected in retinal circulation of diabetic rats. Longitudinal paired studies were performed and the changes in retinal circulation were analyzed using video based fluorescein angiography (VFA) methodology in the same animal. Baseline VFA recordings were obtained from 41 rats. These rats were separated into 4 different groups: In group A (n = 12), diabetes was induced by streptozotocin (STZ) injection and the rats were fed with acarbose (40 mg/100 g powdered chow) mixed into regular rat chow; In group B (n = 10), diabetes was induced by STZ injection and the rats were fed with normal chow; In group C (n = 9), the non-diabetic rats were fed with acarbose; In group D (n = 10), the non-diabetic rats were fed with normal chow. At the end of 2 weeks, all rats again underwent VFA recordings. Blood glucose levels and body weights of rats were monitored during the experiment. The mean blood glucose concentration of Group B was raised from 98.5 +/- 8.7 to 342 +/- 30 mg/dl after STZ injection while in Group A, this change in glucose level was partially ameliorated by acarbose (from 102 +/- 15 to 247 +/- 48 mg/dl). In Group C and D, the blood glucose levels were not significantly changed during the experiment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reversal of abnormal retinal hemodynamics in diabetic rats by acarbose, an alpha-glucosidase inhibitor. 852 12

The treatment of Type II diabetes (NIDDM) includes an appropriate diet and prudent exercise program. If these measures are insufficient to control the blood sugar, oral agents (sulphonylureas or biguanides) or insulin are added to the therapeutic regimen. Although the diet prescription has undergone some changes and refinements, this approach has been the traditional treatment for NIDDM for nearly 40 years. Recently a new class of oral agents, the alpha-glucosidase inhibitors, has become available. These drugs are competitive inhibitors of the alpha-glucosidase enzymes in the brush border of the bowel wall. They act to slow and delay the rate of carbohydrate absorption, thereby decreasing postprandial hyperglycemia. A recent study was designed to evaluate the long-term efficacy of acarbose, an alpha-glucosidase inhibitor, in improving the glycemic control of patients with NIDDM who were sub-optimally controlled on either diet alone, or diet plus sulphonylurea, metformin or insulin. A total of 354 patients with NIDDM were studied, 77 on diet alone, 83 on metformin, 103 and sulphonylurea and 91 on insulin. Subjects in each treatment stratum were randomized, double-blind to either acarbose or placebo, for 1 year. At baseline and every 3 months thereafter, fasting and postprandial glucose and C-peptide, HbA1c and fasting lipids were measured. Compared to placebo, acarbose treatment resulted in a decrease in mean postprandial glucose in all four strata (19 +/- 0.8 to 15.3 +/- 0.7 mmol/l: P < 0.001). This effect was even more pronounced and highly statistically significantly different when comparing the postprandial plasma glucose incremental area under the curve between placebo and acarbose treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes Res Clin Pract 1995 Aug
PMID:Acarbose for the treatment of type II diabetes: the results of a Canadian multi-centre trial. 852 10

The development of the alpha-glucosidase inhibitor acarbose provides a new approach in the management of diabetes. By competitive and reversible inhibition of intestinal alpha-glucosidases, acarbose delays carbohydrate digestion, prolongs the overall carbohydrate digestion time, and thus reduces the rate of glucose absorption. After oral administration of acarbose, the postprandial rise in blood glucose is dose-dependently decreased, and glucose-induced insulin secretion is attenuated. Because of diminished postprandial hyperglycemia and hyper-insulinemia by acarbose, the triglyceride uptake into adipose tissue, hepatic lipogenesis, and triglyceride content are reduced. Therefore, acarbose treatment not only flattens postprandial glycemia, due to the primary and secondary pharmacodynamic effects, but also ameliorates the metabolic state in general. In diabetic animals, acarbose reduced urinary glucose loss, the blood glucose area under the curve, and prevented the decrease in skeletal muscle GLUT4 glucose transporters. As a consequence of the reduced mean blood glucose area under the curve, the amount of protein nonenzymatically glycated was diminished, as was the formation of advanced glycation end-products (AGEs). The prevention of basement membrane glycation and thickening in various tissues indicated that acarbose treatment of diabetic animals produced beneficial effects against the development of nephropathy, neuropathy, and retinopathy. Thus, the alpha-glucosidase inhibitor acarbose may have the potential to delay or possibly prevent the development of diabetic complications.
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PMID:The mechanism of alpha-glucosidase inhibition in the management of diabetes. 854 17

The treatment of non-insulin-dependent diabetes mellitus (NIDDM) is based on dietary and oral hypoglycemic therapy. Present therapy includes diet and exercise, sulfonylureas, biguanides, and, if these measures fail, incremental doses of insulin. Current therapeutic strategies include the combination of different agents in an attempt to optimize glycemic control. Acarbose, an alpha-glucosidase inhibitor which delays carbohydrate digestion and the subsequent absorption of glucose, has been used with other agents to improve glycemic control. Also, in several clinical trials, acarbose monotherapy has been shown to result in significant reductions in postprandial plasma glucose levels as well as glycosylated hemoglobin. This agent is a useful addition to the current armamentarium for the treatment of NIDDM. Recently, the usefulness of acarbose as a first-line drug for the treatment of NIDDM has been evaluated and is reviewed here.
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PMID:Clinical experience with acarbose as first line therapy in NIDDM. 854 18


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