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

Several new oral drugs have been approved for the management of type II diabetes. Metformin is an "antihyperglycemic agent" that decreases hepatic glucose production and improves insulin sensitivity. It may be used as monotherapy or in combination with a sulfonylurea. Acarbose slows carbohydrate absorption after a meal, giving endogenous or injected insulin more time to respond to ingested glucose. Glimepiride is an insulin-sparing sulfonylurea with a once-daily dosing schedule. How might these medications fit into the primary care of older diabetics?
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PMID:Type II diabetes: how to use the new oral medications. Interview by David B. Jack. 862 76

It has been previously demonstrated that hyperglycaemia activates haemostasis; diabetes mellitus is considered a thrombosis-prone state. Acarbose, by inhibiting dietary carbohydrate absorption, reduces post-meal hyperglycaemia. In this study we evaluated the effect of post-meal hyperglycaemia on two markers of coagulation activation: prothrombin fragments 1 + 2 and D-dimer. Seventeen non-insulin-dependent diabetic patients maintained on diet therapy alone were randomly assigned to receive- with a cross-over study design-acarbose (100 mg orally) or placebo before a standard meal. Blood samples for measurement of plasma glucose, insulin, prothrombin fragments 1 + 2 and D-dimer were drawn at 0, 60, 120 and 240 min. After both placebo and acarbose, hyperglycaemia and hyperinsulinaemia which followed a standard meal were accompanied by a significant increase of plasma concentration of prothrombin fragments 1 + 2 and D-dimer in comparison to their baseline values. Acarbose administration significantly reduced the rise of glucose, insulin, prothrombin fragments 1 + 2 and D-dimer from 0 to 240 min in comparison to placebo. We conclude that post-meal hyperglycaemia, at the level reached by many diabetic patients on diet therapy alone, induces a coagulation activation. Acarbose, by decreasing post-meal hyperglycaemia, may be useful in reducing meal-induced activation of haemostasis in diabetic patients.
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PMID:Post-meal coagulation activation in diabetes mellitus: the effect of acarbose. 877 97

Acarbose, an alpha-glycosidase inhibitor, treats diabetes mellitus by delaying the digestion and intestinal absorption of dietary carbohydrates. In effective doses, acarbose induces some passage of carbohydrates into the colon. The effect of such chronic carbohydrate transfer on colonic structure and function is unknown. We studied the effects of 1 year of acarbose administration in diabetes mellitus on fecal energy, protein, and fat, including short-chain fatty acids (SCFA) output, fecal pH, and several metabolizing bacterial species. Changes in colonic histology and epithelial cell proliferation were investigated in rectal biopsies. Fecal macronutrient output was unaffected by acarbose, but pH decreased and total SCFA, butyrate, and acetate output were markedly greater. Breath hydrogen output increased after acarbose, but digoxin-metabolizing bacteria and diacylglycerol (DAG) production were unaltered. Compared with the control, acarbose did not induce hyperplasia or change rectal proliferation. However, total fecal SCFA and butyrate output correlated inversely with proliferation in the rectal upper crypt-a biomarker of risk for colonic neoplasia. In conclusion, long-term acarbose administration does not adversely affect colonic function or fecal nutrient output. If increased fecal SCFA and butyrate reduces upper-crypt proliferation, then acarbose may reduce the risk of colonic neoplasia.
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PMID:Effects of acarbose on fecal nutrients, colonic pH, and short-chain fatty acids and rectal proliferative indices. 878 8

This paper reviews the effects of renal insufficiency on the pharmacokinetics of oral antidiabetic drugs. Of the 3 groups of drugs currently available for the treatment of non-insulin-dependent diabetes mellitus (NIDDM), the sulphonylureas and metformin are, in general, well-tolerated and generally safe. In patients with chronic renal insufficiency, however, care must be exercised in the use of many of these drugs, as accumulation, either of the active drug or of active metabolites, can lead to serious adverse effects such as hypoglycaemia or, with metformin, lactic acidosis. The sulphonylurea drugs, to a greater or lesser degree, are metabolised in the liver to a variety of active or inactive compounds which, in general, are excreted by the kidneys. In addition, varying amounts of parent compound may depend on renal elimination. As a result, sulphonylurea drugs such as tolazamide, acetohexamide, chlorpropamide and glibenclamide (glyburide) are more likely to cause significant hypoglycaemia, as the metabolism of these drugs, compared with other commonly prescribed sulphonylureas, can lead to the accumulation of either the parent drug or the active metabolite in the presence of renal insufficiency. Tolbutamide, glipizide, gliclazide and gliquidone are much less likely to cause hypoglycaemia as their metabolites are either inactive or have minimal hypoglycaemic potency. Metformin is dependent on renal excretion and is not significantly metabolised. As a result, caution is required when treating patients with renal insufficiency where metformin accumulation can occur, with the danger of lactic acidosis. Although the correlation between creatinine clearance (CLCR) and total oral clearance of drug is weaker than the correlation between CLCR and renal clearance (CLR) of metformin, it is clear that renal insufficiency is associated with most cases of metformin-induced lactic acidosis. For this reason, clinicians in general would regard a raised plasma creatinine as a contraindication to metformin treatment. Acarbose, an alpha-glucosidase inhibitor, and a relatively new agent for treating NIDDM, is likely to be safe in patients with impaired renal function, as the drug is not significantly absorbed from the gut, but data on this subject are lacking.
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PMID:Pharmacokinetics of oral antihyperglycaemic agents in patients with renal insufficiency. 885 33

Prophylactic insulin treatment prevents the development of hyperglycemia in animal models of insulin-dependent diabetes mellitus. Acarbose is a new antidiabetic drug which improves hyperglycemia by inhibiting alpha-glucosidase. In the present study, we determined the preventive effect of acarbose against multiple low-dose streptozotocin (MLDSTZ)-induced diabetes mellitus. The male ICR mice were fed acarbose (40 mg/100 g) containing powdered chow before the start of STZ administration. The mice were sacrificed at 3 and 10 days after the final STZ injection. MLDSTZ decreased serum immunoreactive insulin (IRI) levels and increased plasma glucose levels. Acarbose administration tended to decrease plasma glucose and serum IRI levels were significantly reduced in vehicle-treated mice. Acarbose administration significantly attenuated the degree of inflammation and destruction in pancreatic islets after MLDSTZ administration. In conclusion, acarbose-induced attenuation of acute hyperglycemia following MLDSTZ partially prevents the severity of pancreatic islet damage.
Diabetes Res Clin Pract 1996 Jun
PMID:Acarbose partially prevents the development of diabetes mellitus by multiple low-dose streptozotocin administration. 887 71

Acarbose is a novel oral anti-hyperglycemic agent approved for the treatment of noninsulin-dependent diabetes mellitus. It inhibits alpha-glucosidases in the small intestine, an action that delays the digestion and absorption of complex carbohydrates. Subsequently, there is a smaller rise in the postprandial plasma glucose levels and an overall decrease in the glycosylated hemoglobin by 0.5-1.0%. Potential advantages of acarbose include a greater effectiveness in controlling postprandial hyperglycemia, a low risk of hypoglycemia, and a possible delay in initiating insulin therapy. Acarbose can potentiate the hypoglycemic effects of sulfonylureas or insulin. It has not been associated with weight gain and hyperinsulinemia, both of which can occur with sulfonylureas or insulin. Gastrointestinal adverse effects are common with acarbose, and may decrease with continued treatment. Although rare, elevated serum transaminase levels have been reported.
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PMID:A review of the safety and efficacy of acarbose in diabetes mellitus. 888 75

The chemistry, pharmacology, pharmacokinetics, and clinical efficacy of acarbose, a new antidiabetic agent, are reviewed. Acarbose reversibly inhibits intestinal alpha-glucosidases, enzymes responsible for the metabolism of complex carbohydrates into absorbable monosaccharide units. This action results in a diminished and delayed rise in blood glucose following a meal, resulting in a reduction in post-prandial hyperglycemia, area under the glucose concentration-time curve, and glycosylated hemoglobin. Other effects include a reduction in postprandial insulin and variable changes in plasma lipid concentrations. In placebo-controlled trials, acarbose caused significant improvements in glycemic control indicators, including glycosylated hemoglobin. Acarbose has demonstrated additional glycemic control when added to other antidiabetic therapies, including sulfonylureas and insulin. Efficacy of acarbose appears to be comparable to or slightly less than that of sulfonylureas or metformin, although it has not been compared with maximal dose of these agents. The most commonly reported adverse drug reactions with acarbose are abdominal pain, diarrhea, and flatulence, which tend to lessen with time. Acarbose may affect the bioavailability of metformin and may be less effective when used in conjunction with intestinal adsorbents and digestive enzyme preparations. Concurrent use with hypoglycemic agents (sulfonylureas and insulin) may cause an increased frequency of hypoglycemia. Acarbose should not be used in individuals with certain intestinal disorders, including inflammatory bowel disease. The dosage should start at 25 mg one to three times daily given with the first bite of each main meal and should be adjusted to a maximum of 50 mg three times daily for patients weighing up to 60 kg or 100 mg three times daily for heavier patients. Acarbose may be considered for first-line antidiabetic therapy in certain patients and may be useful as combination therapy in selected instances. Acarbose is efficacious in improving metabolic control in non-insulin-dependent diabetes mellitus. Further evaluation of its effects on the long-term complications of diabetes is needed.
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PMID:Acarbose: an alpha-glucosidase inhibitor. 889 66

Acarbose represents a new pharmacological approach to achieving the metabolic benefits of a slower carbohydrate absorption in diabetes, by acting as a potent, competitive inhibitor of intestinal alpha-glucosidases. Acarbose molecules attach to the carbohydrate binding sites of alpha-glucosidases, with an affinity constant that is much higher than that of the normal substrate. Because of the reversible nature of the inhibitor-enzyme interaction, the conversion of oligosaccharides to monosaccharides is only delayed rather than completely blocked. Acarbose has the structural features of a tetrasaccharide and does not cross the enterocytes after ingestion. Thus, its pharmacokinetic properties are well suited to the pharmacological action directed exclusively towards the intestinal glucosidases. The most important clinical consequence of the delayed carbohydrate digestion caused by acarbose is the attenuation of postprandial increases in blood glucose levels. Other effects have also been described: a decreased beta-pancreatic response to meals, and influences on gut hormone secretion and plasma lipid levels. Gastrointestinal discomfort is frequently reported as an adverse effect of acarbose administration, but incidence usually decreases with time. The suitability of acarbose for improving glucose homeostasis as an adjunct to dietary control or to administration of sulphonylureas or insulin has been extensively studied in patients both with type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetes mellitus. Acarbose can be used as first-line therapy in patients with type 2 diabetes which is poorly controlled by diet alone. Moreover, the lack of bodyweight gain or hypoglycaemic effects reported during acarbose treatment may be advantageous for obese or elderly patients. Finally, the reduction in fluctuations of glucose levels throughout the day may help to control type 1 diabetes in patients with 'brittle diabetes'. Long term prospective studies are still needed to confirm these indications and the usefulness of acarbose in conditions other than diabetes, notably reactive hypoglycaemia and dumping syndrome.
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PMID:Pharmacokinetic-pharmacodynamic relationships of Acarbose. 890 94

Postprandial hyperglycemia and elevations in glycated hemoglobin A1c (HbA1c) levels have been associated with long-term complications of diabetes. Because not all patients with type II, or non-insulin-dependent diabetes mellitus (NIDDM), respond adequately to diet, exercise, or treatment with oral sulfonylurea drugs, alternate therapies have been investigated. Acarbose, the first alpha-glucosidase inhibitor available in the United States, exerts its activity in the gastrointestinal tract. By reversibly inhibiting the enzymatic cleavage of complex carbohydrates to simple absorbable sugars, treatment with acarbose results in a reduction in postprandial blood glucose and, subsequently, reductions in HbA1c levels. Acarbose may be given as monotherapy with diet or in combination with diet and a sulfonylurea drug. The results of several controlled clinical studies conducted in the United States are reviewed here. Acarbose, in doses of up to 100 mg three times daily for periods of up to 16 weeks, was statistically significantly superior to placebo with respect to the mean reduction in HbA1c levels and mean 1-hour postprandial glucose levels. Adverse events were nonsystemic and primarily gastrointestinal in nature. Acarbose represents a new approach to the management of NIDDM, modulating gastrointestinal carbohydrate metabolism to control postprandial hyperglycemia and to maximize long-term glycemic control.
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PMID:Acarbose: a review of US clinical experience. 908 5

Non-insulin-dependent diabetes mellitus is a metabolic disease that is common and is characterized by insulin insufficiency and resistance. Measures such as body weight reduction and exercise improve the metabolic defects, but pharmacological therapy is the most frequently used and successful therapy. The sulphonylureas stimulate insulin secretion. Metformin and troglitazone increase disposal and decrease hepatic glucose output without causing hypoglycemia. Acarbose is a dietary aid that spreads the dietary carbohydrate challenge to endogenous insulin over time. These pharmacological agents, either alone or in combination, can improve blood glucose regulation in patients with non-insulin-dependent diabetes mellitus.
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PMID:Pharmacological regulation of blood glucose levels in non-insulin-dependent diabetes mellitus. 912 43


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