ao-128 and Diabetes-Mellitus

Despite considerable literature supporting the potential health benefits of reducing postprandial glucose (PPG), and insulin (PPI) exposures, the size of a clinically relevant reduction is currently unknown. We performed a systematic review and meta-analysis to quantify effects of alpha-glucosidase-inhibiting (AGI) drugs on acute PPG and PPI responses.. We searched EMBASE and MEDLINE until March 13, 2018 for controlled studies using AGI drugs together with a standardized carbohydrate load or mixed meal. The mean incremental PPG and PPI levels were calculated as outcomes. Meta-analyses, stratified by diabetes state, were performed by using random effects models.. The 66 included publications comprised 127 drug-control comparisons for PPG, and 106 for PPI, mostly testing acarbose or miglitol. The absolute effects on PPG were larger among individuals with diabetes (-1.5 mmol/l mean PPG [95% CI -1.9, -1.1] by acarbose, and -1.6 [-1.9, -1.4] by miglitol) as compared to individuals without diabetes (-0.4 [95% CI -0.5, -0.3] by acarbose, and -0.6 [-0.8, -0.4] by miglitol). Relative reductions in PPG by both drugs were similar for diabetic and non-diabetic individuals (43-54%). Acarbose and miglitol also significantly reduced mean PPI, with absolute and relative reductions being largest among individuals without diabetes.. The present meta-analyses provide quantitative estimates of reductions of PPG and PPI responses by AGI drugs in diabetes and non-diabetic individuals. These data can serve as benchmarks for clinically relevant reductions in PPG and PPI via drug or diet and lifestyle interventions.

Topics: 1-Deoxynojirimycin; Acarbose; Diabetes Mellitus; Glucose; Glycoside Hydrolase Inhibitors; Humans; Inositol; Insulin; Postprandial Period

The alpha (α)-amylase is a calcium metalloenzyme that aids digestion by breaking down polysaccharide molecules into smaller ones such as glucose and maltose. In addition, the enzyme causes postprandial hyperglycaemia and blood glucose levels to rise. α-Amylase is a well-known therapeutic target for the treatment and maintenance of postprandial blood glucose elevations. Various enzymatic inhibitors, such as acarbose, miglitol and voglibose, have been found to be effective in targeting this enzyme, prompting researchers to express an interest in developing potent alpha-amylase inhibitor molecules. The review mainly focused on designing different derivatives of drug molecules such as benzofuran hydrazone, indole hydrazone, spiroindolone, benzotriazoles, 1,3-diaryl-3-(arylamino) propan-1-one, oxadiazole and flavonoids along with their target-receptor interactions, IC

Topics: 1-Deoxynojirimycin; Acarbose; alpha-Amylases; Benzofurans; Blood Glucose; Diabetes Mellitus; Drug Discovery; Flavonoids; Glycoside Hydrolase Inhibitors; Humans; Hydrazones; Hypoglycemic Agents; Indoles; Inositol; Oxadiazoles; Structure-Activity Relationship

A 69-year-old man was diagnosed as having myasthenia gravis (MG) in September 2004, and treated with thymectomy and prednisolone. He was then diagnosed as having steroid-induced diabetes mellitus, and received sulfonylurea (SU) therapy in May 2005. An alpha-glucosidase inhibitor (alphaGI) was added in March 2006, resulting in good glycemic control. He experienced symptoms of abdominal distention, increased flatus, and constipation in October 2007, and was admitted into our hospital in late November with hematochezia. Plain abdominal radiography revealed small linear radiolucent clusters in the wall of the colon. Computed tomography (CT) showed intramural air in the sigmoid colon. Colonoscopy revealed multiple smooth surfaced hemispherical protrusions in the sigmoid colon. The diagnosis of pneumatosis cystoides intestinalis (PCI) was made on the basis of these findings. As the alphaGI voglibose was suspected as the cause of this patient's PCI, treatment was conservative, ceasing voglibose, with fasting and fluid supplementation. The patient progressed well, and was discharged 2 wk later. Recently, several reports of PCI associated with alphaGI therapy have been published, predominantly in Japan where alphaGIs are commonly used. If the use of alphaGIs becomes more widespread, we can expect more reports of this condition on a global scale. The possibility of PCI should be considered in diabetic patients complaining of gastrointestinal symptoms, and the gastrointestinal tract should be thoroughly investigated in these patients.

Topics: Aged; Diabetes Mellitus; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemic Agents; Inositol; Male; Pneumatosis Cystoides Intestinalis

Several epidemiological studies have shown an association between postprandial hyperglycemia and mortality from cardiovascular disease. Postprandial hyperglycemia is frequently associated with visceral obesity which plays a key role in metabolic abnormalities such as dyslipidemia and hypertension. Inhibitors of alpha-glucosidase and nateglinide have beneficial effects on the metabolic syndrome associated with visceral obesity. Voglibose in combination with diet therapy reduces visceral fat deposition and ameliorates insulin resistance. Acarbose slightly reduces blood pressure of hypertensive diabetic patients. Nateglinide, a rapidly acting insulin secretagogue, lowers postprandial glucose levels without significant body weight gain. These drugs may protect pancreatic beta-cells from postprandial glucose toxicity and prevent the progression of diabetes.

Topics: Acarbose; Cyclohexanes; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Type 2; Enzyme Inhibitors; Glycoside Hydrolase Inhibitors; Humans; Hyperglycemia; Hypertension; Hypoglycemic Agents; Inositol; Insulin Resistance; Nateglinide; Obesity; Phenylalanine; Postprandial Period

It is widely accepted that the most challenging goal in the management of patients with diabetes mellitus is to achieve blood glucose levels as close to normal as possible. In general, normalising postprandial blood glucose levels is more difficult than normalising fasting hyperglycaemia. In addition, some epidemiological studies suggest that postprandial hyperglycaemia (PPHG) or hyperinsulinaemia are independent risk factors for the development of macrovascular complications of diabetes mellitus. Recently, several drugs with differing pharmacodynamic profiles have been developed which target PPHG. These include insulin lispro, amylin analogues, alpha-glucosidase inhibitors and meglitinide analogues. Insulin lispro has a more rapid onset of action and shorter duration of efficacy compared with regular human insulin. In clinical trials, the use of insulin lispro was associated with improved control of PPHG and a reduced incidence of hypoglycaemic episodes. Repaglinide, a meglitinide analogue, is a short-acting insulinotropic agent which. when given before meals, stimulates endogenous insulin secretions and lowers postprandial hyperglycaemic excursions. Both insulin lispro and repaglinide are associated with postprandial hyperinsulinaemia. In contrast, amylin analogues reduce PPHG by slowing gastric emptying and delivery of nutrients to the absorbing surface of the gut. Alpha-Glucosidase inhibitors such as acarbose, miglitol and voglibose also reduce PPHG primarily by interfering with the carbohydrate-digesting enzymes and delaying glucose absorption. With the availability of agents which preferentially reduce postprandial blood glucose excursions, it is now possible to achieve glycaemic goals in a larger proportion of individuals with diabetes mellitus.

Topics: 1-Deoxynojirimycin; Acarbose; Amyloid; Carbamates; Diabetes Mellitus; Enzyme Inhibitors; Glucosamine; Glyburide; Humans; Hyperglycemia; Hypoglycemic Agents; Imino Pyranoses; Inositol; Insulin; Insulin Lispro; Islet Amyloid Polypeptide; Piperidines; Postprandial Period; Trisaccharides

Topics: Administration, Oral; Blood Glucose; Diabetes Mellitus; Diet, Diabetic; Dietary Carbohydrates; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemic Agents; Inositol; Patient Selection

Postprandial hyperglycemia and hyperinsulinemia have been considered as important determinants for the development of atherosclerosis. However, it remains to be elucidated whether correction of the postprandial glycemic status prevents atherosclerotic changes.. The DIANA (DIAbetes and diffuse coronary NArrowing) study is a prospective randomized open-label multicenter trial. The 302 patients with coronary artery disease (CAD), impaired glucose tolerance/diabetes mellitus (DM) pattern according to 75-g oral glucose tolerance test and HbA(1c) <6.9% were randomly assigned to life-style intervention (n=101), voglibose (0.9 mg/day, n=100) or nateglinide treatment (180 mg/day, n=101). We compared 1-year coronary atherosclerotic changes evaluated by quantitative coronary arteriography. Although voglibose significantly increased the number of patients with normal glucose tolerance at 1 year, there were no significant differences in coronary atherosclerotic changes at 1 year. However, overall, less atheroma progression was observed in patients in whom glycemic status was improved at 1 year (%change in total lesion length: 3.5% vs. 26.2%, P<0.01, %change in averaged lesion length: 0.7% vs. 18.6%, P=0.02).. Although coronary atherosclerotic changes were similar for voglibose and nateglinide, an improvement in glycemic status at 1 year was associated with less atheroma progression regardless of the treatment. Our findings underscore the management of glycemic abnormality to prevent coronary atherosclerotic changes in Japanese early-stage DM patients with CAD.

Topics: Aged; Coronary Artery Disease; Cyclohexanes; Diabetes Complications; Diabetes Mellitus; Female; Glycemic Index; Humans; Hypoglycemic Agents; Inositol; Male; Middle Aged; Nateglinide; Phenylalanine

The authors examined blood pressure, glucose, insulin, and neurotensin before and after intake of 75 g glucose with or without voglibose in 28 neurologic patients and 20 healthy controls. Voglibose significantly prevented hypotension and neurotensin increment after glucose intake and had no influence on glucose or insulin increment. These results suggest that voglibose benefits postprandial hypotension.

Topics: Adult; Aged; Aged, 80 and over; Autonomic Nervous System Diseases; Blood Glucose; Diabetes Mellitus; Female; Glycoside Hydrolase Inhibitors; Humans; Hypotension; Inositol; Insulin; Male; Middle Aged; Multiple System Atrophy; Neurotensin; Postprandial Period

Bullous pemphigoid (BP) is a common autoimmune blistering disorder with unknown etiology. Recently, increasing numbers of BP cases which developed under the medication with dipeptidyl peptidase-4 inhibitors (DPP4i), widely used antihyperglycemic drugs, have been reported in published works. Here, we report a case of DPP4i (teneligliptin)-associated BP that developed in a 70-year-old Japanese man. Interestingly, the patient had acquired reactive perforating collagenosis (ARPC), which is also known to be associated with the onset of BP. In the present case, clinical, histopathological and immunological findings suggested that DPP4i rather than ARPC was associated with the onset of BP.

Topics: Aged; Autoantigens; Biopsy; Collagen Diseases; Collagen Type XVII; Diabetes Mellitus; Dipeptidyl-Peptidase IV Inhibitors; Drug Substitution; Enzyme-Linked Immunosorbent Assay; Glycoside Hydrolase Inhibitors; Humans; Inositol; Male; Non-Fibrillar Collagens; Pemphigoid, Bullous; Pyrazoles; Skin; Thiazolidines

In the DIANA(DIAbetes and diffuse coronary NArrowing) study, which evaluated the impact of glucose-lowering therapy in early-stage diabetics with coronary artery disease(CAD), optimal glycemic control resulted in reduced disease progression on angiography. However, despite having a favorable glycemic status, some patients continued to exhibit disease progression. Factors associated with disease progression despite optimal glucose control remain to be elucidated. We sought to investigate clinical characteristics associated with substantial atheroma progression in early-stage diabetic patients with CAD who achieve favorable glycemic control.. The DIANA study is a prospective randomized trial comparing the effects of lifestyle intervention and treatment with voglibose or nateglinide on disease progression on angiography in 302 CAD patients with impaired glucose tolerance/newly diagnosed diabetes. Of these patients, 137 CAD subjects who achieved optimal glycemic control were stratified according to the presence of disease progression on angiography: progressors(n=64) and non-progressors(n=73). Serial coronary angiography studies and quantitative coronary angiography analyses were conducted to evaluate disease progression. A multivariate analysis was performed to elucidate factors associated with disease progression.. Despite the achievement of optimal glycemic control, atheroma progression was observed in 46% of the study subjects. The progressors exhibited lower decreases in systolic blood pressure(SBP: p=0.007) and reduced baseline total lesion lengths(TLL: p=0.01). The multivariate analysis demonstrated that a greater increase in SBP(p=0.006), treatment without statins(p=0.03) and the baseline TLL(p=0.007) were independently associated with disease progression.. Residual risk factors contribute to the progression of coronary atherosclerosis in early-stage diabetics who exhibit improvements in their glycemic status. The present findings underscore the need to intensively modify multiple risk factors during the early diabetic phase in order to prevent atheroma progression.

Topics: Blood Glucose; Coronary Angiography; Coronary Artery Disease; Cyclohexanes; Diabetes Mellitus; Disease Progression; Double-Blind Method; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Inositol; Life Style; Male; Middle Aged; Nateglinide; Phenylalanine; Plaque, Atherosclerotic; Prospective Studies; Risk Factors; Ultrasonography, Interventional

Topics: Coronary Artery Disease; Cyclohexanes; Diabetes Mellitus; Female; Glycemic Index; Humans; Inositol; Male; Nateglinide; Phenylalanine

The aim of this study was to clarify the influence of hyperglycemia on the deposition of aggregated protein in the glomeruli of diabetic mice. KK-A(y) mice injected with aggregated bovine serum albumin accumulated more of it in the glomeruli than did ICR mice. There were no histological alterations in the glomeruli of KK-A(y) mice. KK-A(y) mice given voglibose in mouse-chow for 2 weeks had significantly reduced blood glucose, glycated albumin, and hemoglobin A(1C) levels compared with control mice. The voglibose-treated KK-A(y) mice were injected with aggregated bovine serum albumin and accumulated significantly less albumin in the glomeruli than did the control mice. Pioglitazone decreased blood glucose levels compared with the control, and reduced the glomerular deposition of aggregated albumin. Glomerular aggregated bovine serum albumin levels and blood glucose levels were reduced significantly by the injection of insulin. Six times more advanced glycation endproducts were produced from aggregated bovine albumin than from non-aggregated bovine albumin on incubation with glucose and L-lysine in vitro. Glucose-loaded ICR mice generated more advanced glycation endproducts from aggregated albumin, and had more aggregated bovine albumin in the glomeruli. It was suggested that hyperglycemia contributes to an increase in the deposition of aggregated protein in glomeruli even early on in diabetes.

Topics: Animals; Blood Glucose; Diabetes Mellitus; Glucose; Glycated Hemoglobin; Glycated Serum Albumin; Glycation End Products, Advanced; Hyperglycemia; Hypoglycemic Agents; Inositol; Insulin; Kidney Glomerulus; Lysine; Male; Mice; Mice, Inbred ICR; Pioglitazone; Serum Albumin; Serum Albumin, Bovine; Thiazolidinediones

A 56-year-old woman was admitted to our hospital for treatment of non-specific interstitial pneumonitis (NSIP). The patient started prednisone treatment, but one month later treatment with voglibose, an alpha-glucosidase inhibitor (alpha-GI), was started because of prednisone-induced diabetes mellitus. One week later, a massive volume of free air below the diaphragm was detected by a chest X-ray examination. An abdominal CT examination demonstrated pneumatosis coli and the patient was diagnosed with pneumatosis cystoides intestinalis (PCI). Voglibose was discontinued and parenteral nutrition and oxygen inhalation were initiated. Radiographic findings of PCI disappeared within 7 days. We encountered a rare case of PCI, that was associated with alpha-GI treatment.

Topics: Diabetes Mellitus; Enzyme Inhibitors; Female; Glucocorticoids; Glucosidases; Humans; Hypoglycemic Agents; Inositol; Lung Diseases, Interstitial; Middle Aged; Pneumatosis Cystoides Intestinalis; Prednisone

Topics: Administration, Oral; Cardiovascular Diseases; Cyclohexanes; Diabetes Complications; Diabetes Mellitus; Drug Therapy, Combination; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemia; Hypoglycemic Agents; Indoles; Inositol; Insulin; Insulin Resistance; Insulin Secretion; Isoindoles; Nateglinide; Phenylalanine; Risk Factors; Stimulation, Chemical; Sulfonylurea Compounds; Thiazolidinediones

To determine whether diabetic care can be improved by combination of voglibose and gymnemic acid (GA), we compared the combinative and individual effects of voglibose and GA on maltose absorption in small intestine.. The small intestine 30 cm long from 2 cm caudal ward Treitz's ligament of Wistar rat was used as an in situ loop, which was randomly perfused in recircular mode with maltose (10mmol/L) with or without different dosages of voglibose and/or GA for an hour. To compare the time course, perfusion of 10 mmol/L maltose was repeated four times. Each time continued for 1 hour and separated by 30 minutes rinse. In the first time, lower dosages of GA (0.5g/L) and/or voglibose (2 micromol/L) were contained except control.. Absorptive rate of maltose was the lowest in combinative group (P<0.05, ANOVA), for example, the inhibition rate was about 37% during the first hour when 0.5 g/L-GA and 2 micromol/L voglibose with 10 mmol/L maltose were perfused in the loop. The onset time was shortened to 30 minutes and the effective duration was prolonged to 4 hours with the combination; therefore the total amount of maltose absorption during the effective duration was inhibited more significantly than that in the individual administration (P < 0.05, U test of Mann Whitney). The effect of GA on absorptive barriers of the intestine played an important role in the combinative effects.. There are augmented effects of voglibose and GA. The management of diabetes mellitus can be improved by employing the combination.

Topics: Animals; Diabetes Mellitus; Enzyme Inhibitors; Inositol; Intestine, Small; Male; Maltose; Rats; Rats, Wistar; Saponins; Triterpenes

Alpha-glucosidase inhibitor can suppress postprandial hyperglycemia by delaying the absorption of carbohydrates in the intestine, and may be useful in obese patients with non-insulin-dependent diabetes mellitus (NIDDM) and preserved insulin secretion. We encountered an obese elderly patient with NIDDM in whom gait disturbance had developed after cerebral hemorrhage and who suffered from ileus after treatment with voglibose. The patient had received voglibose which is reported to cause fewer abdominal symptoms than acarbose, for 15 days. The patient, a 63-year-old woman, was given a diagnosis of NIDDM in February 1995, and was treated with a sulfonylurea agent. However, her glycemic control remained poor and she was admitted to our hospital in April 1995. Her body mass index was 30.5 kg/m2 and laboratory investigation revealed a fasting plasma glucose level of 211 mg/dl, a postprandial (2 h) plasma glucose level of 288 mg/dl, HbAlc of 9.9%, a fasting insulin level of 9 microU/ml, urinary C-peptide excretion of 95.7 micrograms/ day, and an coefficient of variation of R-R value of 2.1%. Fifteen days after glibenclamide was replaced by to voglibose, abdominal pain, nausea, constipation, and ausculatory sounds of gurgling developed, and niveau were noted on an abdominal roentgenogram which indicated that simple ileus had developed. Voglibose was discontinued and the patient was treated with an enema and hot air. She recovered from simple ileus on the next day. This patient had had two abdominal surgeries and a cerebral hemorrhage, and her daily physical activities were limited, which might have contributed to ileus. In elderly patients with NIDDM, a history of abdominal surgery and the amount of daily exercise must be considered when deciding whether or not to give alpha-glucosidase inhibitors.

Topics: Cerebral Hemorrhage; Cyclohexanols; Diabetes Mellitus; Diabetes Mellitus, Type 2; Enzyme Inhibitors; Female; Gait; Glycoside Hydrolase Inhibitors; Humans; Intestinal Obstruction; Middle Aged; Obesity

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.

Topics: Animals; Body Weight; Cyclohexanols; Diabetes Mellitus; Eating; Enzyme Inhibitors; Glycoside Hydrolase Inhibitors; Male; Obesity; Rats; Rats, Wistar

Topics: Animals; Cyclohexanols; Diabetes Mellitus; Drug Evaluation; Gliclazide; Glyburide; Humans; Hypoglycemic Agents; Imidazoles; Insulin; Insulin Secretion; Molecular Structure; Pyrrolidines; Stimulation, Chemical; Sulfonylurea Compounds