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

The effect of acarbose, an alpha-glucosidase inhibitor, on postprandial glucose and lipid metabolism was investigated in patients with type 2 diabetes mellitus. Twenty patients (10 men and 10 women) with type 2 diabetes mellitus were studied. A test meal was taken with or without 100 mg of acarbose. The levels of plasma glucose, and serum immunoreactive insulin, lipids, apolipoproteins, and remnant-like particle cholesterol were investigated. Acarbose inhibited the postprandial increase of both plasma glucose and serum immunoreactive insulin. Acarbose also significantly suppressed the increase of serum triglycerides at 60, 90, and 120 min (P < 0.05 to P < 0.01), and the increase of serum remnant-like particle cholesterol at 60 and 120 min (P < 0.05). Acarbose inhibited the postprandial decline of apolipoprotein C-II, and decreased the postprandial serum apolipoprotein C-III level. These results suggest that acarbose may improve postprandial hyperlipidemia as well as postprandial hyperglycemia in patients with type 2 diabetes mellitus.
Diabetes Res Clin Pract 1998 Jul
PMID:Effect of acarbose on postprandial lipid metabolism in type 2 diabetes mellitus. 976 72

Acarbose, an alpha-glucosidase inhibitor, is a new antihyperglycaemic agent which has been proposed as add-on therapy in Type 2 diabetic patients not well-controlled with diet alone, sulphonylurea, metformin or insulin, and in Type 1 diabetic patients with large meal-related plasma glucose excursions. Numerous controlled studies investigating the clinical effects of acarbose in Type 2 diabetes versus either placebo or, more rarely, versus a reference drug (sulphonylurea or metformin) have been published during the last 10 years. All placebo-controlled studies have demonstrated the superiority of acarbose, at a dose of 150-600 mg/day, in decreasing fasting and postprandial glucose levels as well as HbA1c concentrations (mean decrease of 0.7%), whether acarbose was given as first-line therapy in diet-treated diabetic patients or in combination in individuals already receiving a sulphonylurea, metformin or insulin. Only a few controlled studies have compared the effects of acarbose with those of either sulphonylurea or metformin, yielding controversial results. In Type 1 diabetic patients, a small reduction of HbA1c levels was also reported after addition of acarbose to insulin therapy, which in some cases allowed a slight reduction of daily insulin needs. All these favourable biological effects occurred without exposing the patient to hypoglycaemia or weight gain. A few studies have also reported favourable effects on postprandial lipid profile and some other vascular risk factors. However, it is not clear whether the extra cost of acarbose, when compared to that of older oral antidiabetic agents, is justified since no study has yet demonstrated its potential benefit on the complications and long-term prognosis of diabetic patients.
Diabetes Metab 1998 Sep
PMID:Clinical efficacy of acarbose in diabetes mellitus: a critical review of controlled trials. 980 41

Our objective was to determine the efficacy of adding acarbose to the combination of metformin and a sulfonylurea in the treatment of type II diabetes mellitus. Acarbose was added to the treatment regimen of 11 type II diabetic patients who were not adequately controlled on the combination of a sulfonylurea and metformin. Glycosylated hemoglobin before and after the addition of acarbose was compared to assess the efficacy of this additional therapy. One patient did not tolerate acarbose therapy. Of the remaining ten patients, the mean improvement in glycosylated hemoglobin with the addition of acarbose was 1.4 percentage points, p = 0.01. Eight patients had improvements in glycosylated hemoglobin; mean improvement, 2.0 percentage points. Two patients' glycohemoglobin values worsened. Thus, the addition of acarbose to the treatment regimen of type II diabetic patients presently on a combination of a sulfonylurea and metformin improves glycemic control.
J Diabetes Complications
PMID:Triple oral antidiabetic therapy. 987 64

Acarbose, an alpha-glucosidase inhibitor, delays the absorption of complex carbohydrates and sucrose, thereby lowering post-prandial blood glucose. In this study, we evaluated the effects of Acarbose on glycaemic control in Type 2 diabetic patients in secondary oral hypoglycaemic agent failure. Due to its mode of action, we also used indirect calorimetry to examine its effects on energy expenditure (EE), diet induced thermogenesis (DIT) and respiratory quotient (RQ) after a standard breakfast (440 calories with 60 g carbohydrates). A total of 12 patients (male/female, 8/4; age, 56+/-9 years; duration of diabetes 10.1+/-4.6 years; body mass index (BMI) 29.6 + 2.7 kg/m2) with poor glycaemic control (HbA1c, 8.8+/-0.9%) completed 8 weeks treatment with Acarbose (100 mg). After treatment, HbAlc was lower compared to the baseline (8.8+/-0.9% vs. 8.0+/-0.9%; t = 2.7; P = 0.02). Acarbose acutely lowered post-prandial blood glucose and insulin area under the curve by a mean of 16.9% and 9.2%, respectively. Long term changes in HbA1c correlated strongly with acute changes in blood glucose area due to Acarbose administration (r = 0.87; P < 0.01). There was a significant effect of Acarbose on EE and DIT for the first 120 min post meal (F3,92 = 3.4; P = 0.03, F2,69 = 6.3; P = 0.008, respectively). After Acarbose treatment, RQ was lower at 30 min compared to the baseline (0.86+/-0.04 before, and 0.83+/-0.05 after; t = 2.8; P = 0.02). In conclusion, Acarbose improves glycaemic control and changes post-prandial energy expenditure of Type 2 diabetic patients in secondary failure. The magnitude of long term reduction in hyperglycaemia differs amongst individuals. This is largely due to intrinsic variations in patients' response to Acarbose rather than differences in medication compliance or dietary composition.
Diabetes Res Clin Pract 1998 Dec
PMID:The use of Acarbose in Type 2 diabetic patients in secondary failure: effects on glycaemic control and diet induced thermogenesis. 992 48

Glycaemic control in Type 1 diabetes has been proven efficient in preventing microvascular and neurological complications. The assumption that good control of hyperglycaemia may also have significant impact on alleviation of complications in Type 2 diabetes has gained growing support in recent years. Measures such as body weight reduction and exercise improve the metabolic defects, but pharmacological therapy is most frequently used. The sulphonylureas stimulate insulin secretion. Metformin and troglitazone increase glucose disposal and decrease hepatic glucose output without causing hypoglycaemia. Acarbose helps to spread the dietary carbohydrate challenge to endogenous insulin over time. These pharmacological treatments can improve blood glucose regulation in Type 2 diabetes patients. However, the key to strict glycaemic control with use of exogenous insulin lies in the creation of delivery methods that emulate physiologic insulin secretion. Insulin lispro, a recombinant insulin analogue, is identical to human insulin except for the transposition of proline and lysine at positions 28 and 29 in the C-terminus of the B chain. Evidence suggests that patients perceive their quality of life to be improved with insulin lispro when compared with regular human insulin, and that satisfaction with treatment is greater with the insulin analogue. Numerous new pharmacological approaches are under active investigation, with the aim of promoting insulin secretion, improving the action of insulin, or slowing carbohydrate absorption. With respect to continuous subcutaneous insulin infusion therapy and implantable pumps, despite that this approach is not widely utilised, it appears to bring us as close to achieving glycaemic control as is feasible with current treatment approaches. However, general application of such technology requires significant improvements in several areas, such as improvement of patency of catheter, pump failures due to early battery depletion incidents, and pump miniaturisation. Future perspective resides on insulin analogues with longer half-lives that would provide better basal insulin coverage in association with fast-acting analogues.
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PMID:Pharmacological management of diabetes: recent progress and future perspective in daily drug treatment. 1005 Nov 77

The recently developed Otsuka Long-Evans Tokushima Fatty (OLETF) rat is known to develop insulinopenic diabetes after a prolonged period in a condition resembling non-insulin-dependent diabetes mellitus (NIDDM). We examined the effect of pharmacological intervention with a potent intestinal alpha-glucosidase inhibitor, acarbose, on the metabolic and histopathologic changes in this rat model. The first two groups of rats received an acarbose-rich diet (150 mg/100 g normal chow) from 12 weeks of age (ie, before the onset of diabetes) or from 28 weeks of age (ie, after the onset of diabetes), while a third group received the acarbose-rich diet for the initial 16 weeks only (from 12 to 28 weeks of age). A control group received standard rat chow. Acarbose-fed rats gained less weight or lost weight despite increased food intake when switched to the acarbose-rich diet. Acarbose also reduced visceral adipose depots and fasting triglyceride (TG), glucose, and insulin levels. At the end of the study at 72 weeks, the pancreatic wet weight and insulin content were significantly higher in the treated groups versus control rats. The morphological changes observed in control rats, such as atrophy of the pancreas and reduced number and size of islets, were not present in acarbose-treated rats. Rats fed acarbose from 12 to 28 weeks of age gradually gained weight after switching to standard chow, and hyperinsulinemia, hyperglycemia, and hyperlipidemia appeared (in that order). The pancreatic insulin content in these rats was significantly higher and the visceral adipose depot was significantly smaller than in control rats. Our study demonstrates that acarbose prevented and reversed the metabolic derangement and histopathological changes in genetically diabetic rats. Moreover, treatment with acarbose even for a short period produced a marked delay in the development of insulin insensitivity and frank diabetes.
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PMID:Metabolic abnormalities in the genetically obese and diabetic Otsuka Long-Evans Tokushima Fatty rat can be prevented and reversed by alpha-glucosidase inhibitor. 1009 12

The pseudooligosaccharide acarbose is a potent inhibitor of amylases, glucosidases, and cyclodextrin glycosyltransferase and is clinically used for the treatment of so-called type II or insulin-independent diabetes. The compound consists of an unsaturated aminocyclitol, a deoxyhexose, and a maltose. The unsaturated aminocyclitol moiety (also called valienamine) is primarily responsible for the inhibition of glucosidases. Due to its structural similarity to maltotetraose, we have investigated whether acarbose is recognized as a substrate by the maltose/maltodextrin system of Escherichia coli. Acarbose at millimolar concentrations specifically affected the growth of E. coli K-12 on maltose as the sole source of carbon and energy. Uptake of radiolabeled maltose was competitively inhibited by acarbose, with a Ki of 1.1 microM. Maltose-grown cells transported radiolabeled acarbose, indicating that the compound is recognized as a substrate. Studying the interaction of acarbose with purified maltoporin in black lipid membranes revealed that the kinetics of acarbose binding to LamB is asymmetric. The on-rate of acarbose is approximately 30 times lower when the molecule enters the pore from the extracellular side than when it enters from the periplasmic side. Acarbose could not be utilized as a carbon source since the compound alone was not a substrate of amylomaltase (MalQ) and was only poorly attacked by maltodextrin glucosidase (MalZ).
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PMID:Acarbose, a pseudooligosaccharide, is transported but not metabolized by the maltose-maltodextrin system of Escherichia coli. 1019 28

Acarbose is a naturally occurring pseudo-tetrasaccharide. It has been used in conjunction with other drugs in the treatment of diabetes where it acts as an inhibitor of intestinal glucosidases. To probe the interactions of acarbose with other carbohydrate recognition enzymes, the crystal structure of E. coli maltodextrin phosphorylase (MalP) complexed with acarbose has been determined at 2.95 A resolution and refined to crystallographic R-values of R (Rfree) = 0.241 (0.293), respectively. Acarbose adopts a conformation that is close to its major minimum free energy conformation in the MalP-acarbose structure. The acarviosine moiety of acarbose occupies sub-sites +1 and +2 and the disaccharide sub-sites +3 and +4. (The site of phosphorolysis is between sub-sites -1 and +1.) This is the first identification of sub-sites +3 and +4 of MalP. Interactions of the glucosyl residues in sub-sites +2 and +4 are dominated by carbohydrate stacking interactions with tyrosine residues. These tyrosines (Tyr280 and Tyr613, respectively, in the rabbit muscle phosphorylase numbering scheme) are conserved in all species of phosphorylase. A glycerol molecule from the cryoprotectant occupies sub-site -1. The identification of four oligosaccharide sub-sites, that extend from the interior of the phosphorylase close to the catalytic site to the exterior surface of MalP, provides a structural rationalization of the substrate selectivity of MalP for a pentasaccharide substrate. Crystallographic binding studies of acarbose with amylases, glucoamylases, and glycosyltranferases and NMR studies of acarbose in solution have shown that acarbose can adopt two different conformations. This flexibility allows acarbose to target a number of different enzymes. The two alternative conformations of acarbose when bound to different carbohydrate enzymes are discussed.
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PMID:The crystal structure of the Escherichia coli maltodextrin phosphorylase-acarbose complex. 1022 Mar 20

Short-term studies with acarbose have demonstrated its efficacy in reducing postprandial blood glucose levels and glycated haemoglobin (HbA(1c)) levels. These effects would be expected to translate into improvements in long-term complications of diabetes, but such data are not yet available due to the long follow-up times required. Animal models of diabetes have, however, demonstrated the efficacy of acarbose in combating the long-term complications of the disease. The 18 animal studies reviewed here showed that acarbose treatment reduced postprandial blood glucose concentrations and decreased protein glycation. Through these actions, acarbose delayed or prevented the onset of renal, retinal, lens and neurological changes and the development of ischaemic myocardial lesions. Acarbose treatment can therefore be expected to benefit patients with Type 2 and, in combination with insulin, Type 1 diabetes. This is being investigated in ongoing clinical studies in patients with Type 2 diabetes and impaired glucose tolerance (IGT).
Diabetes Metab Res Rev
PMID:Effects of the alpha-glucosidase inhibitor acarbose on the development of long-term complications in diabetic animals: pathophysiological and therapeutic implications. 1049 78

Acarbose (Glucobay, Bayer) is a competitive inhibitor of intestinal alpha-glucosidases, which use causes inhibition of carbohydrate digestion. The aim of the study was to prospectively observe scheme of acarbose use as well as efficacy and safety of the drug in diabetic patients in general health care. The study was performed in general health care centres all around Poland. 200 physicians were involved, each one was asked to supervise use of acarbose in 3 patients. The whole patients population consisted of 600 persons. The physicians were asked to make records in provided formularies, prior to acarbose use and then after 4 and 8 weeks of the treatment: data from the interview (among others on diabetes type, disease duration, used diet, treatment incl. sulphonylurea or biguanide derivatives); personal data (age, height, weight, etc.); blood glucose level prior to and 2 hours postprandial; glycosuria; basic additional tests; basic lipid tests (total cholesterol, triglycerides); overall score of acarbose use (side effects, withdrawal, physicians and patients opinion on the drug). Fasting glycaemia was the criterion of inclusion into the analysis. Full data on this parameter were obtained in 480 patients (267 female and 213 male, aged 31-88 years). Acarbose was used as the only antidiabetic drug in 34% of the patients, combined with sulphonylurea in 44%, combined with sulphonylurea and biguanide (metformine) in 19% and combined with metformine only in several cases (3%). During the observation, significant weight and BMI loss, 3% reduction average (for both parameters), was observed in the whole studied group. Fasting and 2 hours postprandial glycaemia was markedly improved in the whole studied population (26.8% and 28.1% glucose level reduction, respectively), and particularly in those who was initially qualified into the group of bad diabetes control (29.4% and 32.4% glucose level decrease, respectively). The most favourable effect on glycaemia was observed for acarbose monotherapy (p < 0.005) when compared to combined treatment). No difference was found in glycaemic response referred to the initial body mass index (BMI). Tested lipid parameters improved during 8-week observation: serum cholesterol level decreased by 4.6% in the whole studied population, and by 8.9% in the group of bad diabetes control, respectively. Value differences did not reach, however, presumed statistical significance (p < 0.005). Significant improvement was noted in triglyceride levels: reductions by 17.5% in the whole group and by as much as 26.8% in the sub-group of bad diabetes control (initial level 200 mg/dl). Acarbose observational study performed in the routine treatment conditions confirmed efficacy of the drug in diabetes mellitus, for both--carbohydrate and lipid metabolism. The study showed low significance of side effects and high acceptation of the treatment by the patients and the physicians.
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PMID:[Evaluation of acarbose efficacy and safety for treatment of diabetes mellitus. Testing of observations under general health care conditions]. 1055 69


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