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Query: UMLS:C0011849 (diabetes)
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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

Current therapeutic options for the treatment of non-insulin-dependent diabetes mellitus (NIDDM) focus on regimens that primarily lower fasting blood glucose concentrations. In several short-term studies, the alpha-glucosidase inhibitor, acarbose, has been reported to significantly lower post-prandial plasma glucose levels as well as HbA1c. The primary objective of this present study was to assess the long-term efficacy of adjunctive acarbose therapy to improve metabolic control. Over a 1-y period, acarbose or placebo was administered to 4 groups of patients: those managed by diet only, diet and sulfonylurea, diet and biguanide, and diet and insulin. In all treatment groups, the addition of acarbose resulted in significant reductions in postprandial blood glucose levels. Additionally, HbA1C was significantly lower after 12 months of acarbose therapy, compared with placebo, in all groups except the diet and insulin group. The addition of acarbose consequently expands the armamentarium available to clinicians for the optimization of glycemic control in patients with NIDDM.
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PMID:Clinical experience with acarbose: results of a Canadian multicentre study. 854 19

The onset and progression of long-term complications in diabetes mellitus appear to be related to the degree of hyperglycemia and the overall metabolic control. Therefore, an important goal in the therapy of subjects with diabetes is to avoid wide fluctuations in blood glucose concentrations and increases in lipid levels. The first therapeutic maneuver to achieve glycemic control is to establish a correct diet containing complex carbohydrates and an adequate amount of dietary fibers. Dietary fibers are capable of reducing the intestinal uptake of carbohydrates. An additional strategy to reduce the uptake of carbohydrates across the intestine has recently been proposed by Puls et al. This strategy involves the use of inhibitors of alpha-glucosidase, an intestinal enzyme that participates in the breakdown of polysaccharides into disaccharides and monosaccharides. The inhibition of alpha-glucosidase by these agents is competitive and reversible and results in delayed and reduced uptake of carbohydrates across the intestine. This effect attenuates the post-prandial hyperglycemia and subsequent insulin secretory response particularly in subjects with hyperinsulinemia. The compound acarbose is a member of first generation alpha-glucosidase inhibitors. The administration of high doses of acarbose can be associated with side effects such as flatulence, meteorism, abdominal pain, and diarrhea due to the fermentation of non-absorbed carbohydrates in the intestinal lumen. Usually, these effects subside following a few days of therapy and/or reduction of the initial dose. Acarbose has been effectively used to treat type 2 diabetic patients either as a first choice drug or in association with sulfonylurea agents and in type 1 diabetics in association with insulin therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[alpha-Glucosidase inhibitors in the therapy of diabetes mellitus]. 856 69

The effects of alpha-glucosidase inhibitor (acarbose) were studied in 36 patients with non-insulin-dependent diabetes mellitus (NIDDM), aged 34-67 years with a mean duration of diabetes of 8.8 +/- 0.9 years. They were poorly controlled with diet plus sulfonylurea alone or plus sulfonylurea combined with metformin drugs. Acarbose, 100 mg three times daily, was additionally given to these patients for six months. Results showed small but significant decreases (P < 0.001) in postprandial blood glucose level. Glycosylated hemoglobin level was lowered significantly (P < 0.001) and was normalised (level of < 8%) in 17 per cent of the patients. Fasting serum triglycerides level decreased significantly (P < 0.01), whereas, no significant changes in serum total cholesterol and HDL cholesterol levels were seen. Body weight also decreased significantly (P < 0.001) at the end of acarbose trial. Flatulence was the major side effect of acarbose found in 42 per cent of the patients but it was well-tolerated and may be transient and self-limited. We concluded that the addition of acarbose to the therapeutic regimens of diet therapy plus sulfonylurea or plus sulfonylurea combined with metformin drugs led to significant improvement of glycemic control. Acarbose may be a safe and valuable adjunct to diet and sulfonylurea and metformin treatments in obese, poorly-controlled patients with NIDDM.
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PMID:Effects of alpha-glucosidase inhibitor (acarbose) combined with sulfonylurea or sulfonylurea and metformin in treatment of non-insulin-dependent diabetes mellitus. 857 67

Non-insulin-dependent diabetes mellitus (NIDDM) is a major health concern for clinicians who are responsible for the care of an aging population. The relationship between hyperglycemia and the chronic complications of retinopathy, nephropathy, and neuropathy has been established in patients with insulin-dependent diabetes mellitus, and it is extremely likely that such a relationship exists in patients with NIDDM as well. Diet and exercise are the cornerstone for the management of NIDDM. The assessment of glycemic control should determine which patients with NIDDM need more aggressive intervention to control hyperglycemia. Pharmacologic treatment options include oral administration of the sulfonylureas, a biguanide, and an alpha-glucosidase inhibitor and subcutaneous administration of insulin. Extensive education about diabetes and self-monitoring of blood glucose levels are important components in maximizing glycemic control. Additional pharmacologic treatment options are necessary when adequate individualized treatment goals are not attained. The goal of therapy is to prevent the onset or progression of long-term microvascular and macrovascular complications. In this review, we present the therapeutic options and outline our approach to the pharmacologic treatment of NIDDM. Relevant medical literature on each treatment modality is reviewed, and the cost of therapy with use of each medication is provided.
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PMID:Pharmacologic treatment options for non-insulin-dependent diabetes mellitus. 900 95

Antiobesity and antidiabetic actions of the alpha-glucosidase inhibitor AO-128 were examined using genetically obese-diabetic rats, Wistar fatty. Ten-week-old, male fatty rats were kept on CE-2 diet containing 10 or 25 ppm of AO-128 for 4 weeks. The average drug intake was calculated to be 0.74 or 1.78 mg/kg/day from the average food intake, respectively. The intestinal maltase and sucrase activities were decreased by AO-128 in a dose-related fashion. Food intake of fatty rats treated with AO-128 was decreased throughout the experiment. This decrease in food intake could hardly be explained only by diarrhea which occurred for the first 5 days of the administration of AO-128. AO-128 normalized hyperglycemia and markedly reduced hypertriglyceridemia and hyperinsulinemia in fatty rats. In addition, AO-128 decreased body weight gain, food efficiency, epididymal adipose tissue weight, carcass weight, and body fat deposition. These findings indicate that AO-128 may be useful for treating human obesity and diabetes.
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PMID:AO-128, alpha-glucosidase inhibitor: antiobesity and antidiabetic actions in genetically obese-diabetic rats, Wistar fatty. 869 66


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