ao-128 and Insulin-Resistance

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

Topics: Carbohydrate Metabolism; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Enzyme Inhibitors; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemic Agents; Inositol; Insulin; Insulin Resistance; Insulin Secretion; Sulfonylurea Compounds

Topics: Acarbose; Animals; Biguanides; Chromans; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Enzyme Inhibitors; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemic Agents; Inositol; Insulin Resistance; Pioglitazone; Sulfonylurea Compounds; Thiazoles; Thiazolidinediones; Troglitazone

Topics: Acarbose; Administration, Oral; Biguanides; Chromans; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemic Agents; Inositol; Insulin Resistance; Sulfonylurea Compounds; Thiazoles; Thiazolidinediones; Trisaccharides; Troglitazone

Topics: Acarbose; Administration, Oral; Animals; Biguanides; Cardiovascular System; Chromans; Drug Interactions; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemia; Hypoglycemic Agents; Inositol; Insulin Resistance; Sulfonylurea Compounds; Thiazoles; Thiazolidinediones; Trisaccharides; Troglitazone

Topics: Acarbose; Animals; Chromans; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemic Agents; Inositol; Insulin Resistance; Pioglitazone; Thiazoles; Thiazolidinediones; Trisaccharides; Troglitazone

Topics: Acarbose; Diabetes Mellitus, Type 2; Diet, Diabetic; Exercise Therapy; Humans; Hyperglycemia; Hypoglycemic Agents; Inositol; Insulin; Insulin Resistance; Postprandial Period; Sulfonylurea Compounds; Trisaccharides

Dipeptidyl peptidase 4 (DPP4) inhibitors improve glycemic control by promoting GLP1-mediated glucose-dependent insulin secretion and suppression of glucagon. Sitagliptin and vildagliptin have been shown to improve insulin sensitivity in patients with type 2 diabetes mellitus (T2DM). However, these patients had uncontrolled blood glucose at inclusion; therefore, the improvement in insulin sensitivity observed in these studies could be attributed to the drug per se and/or reduction in glucotoxicity. This study examines the effect of linagliptin on insulin sensitivity and β-cell function in patients with well-controlled T2DM.. Thirty patients with T2DM of duration ≤5 years, and having HbA1c < 7.5% were randomized to receive linagliptin, voglibose or placebo (n = 10 each), and were followed up for 6 months. Insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamp, and insulin secretory response was measured by basal (M. The median HbA1c of the study subjects at inclusion was 6.9% and there was no significant difference among the groups in terms of age, duration of diabetes, body mass index (BMI), HbA1c, insulin sensitivity, AUC of C-peptide and M. Linagliptin modestly improves glycemic profile in patients with well controlled T2DM; however, it may not have an effect on insulin sensitivity in these patients.. Retrospectively Registered in Clinicaltrials.gov (ID number, NCT02097342 ). Registered: March 27, 2014.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Inositol; Insulin Resistance; Insulin-Secreting Cells; Linagliptin; Male; Middle Aged; Postprandial Period

Type 2 diabetes mellitus (T2DM) associated with metabolic syndrome (MetS) represents a high risk of cardiovascular disease. We compared the effect of early intervention with pioglitazone versus voglibose on physical and metabolic profiles and serum adiponectin level in patients with T2DM associated with MetS. Sixty patients who were diagnosed for the first time as T2DM associated with MetS were analyzed for insulin sensitivity, lipid profile, serum adiponectin and systemic inflammation. Those patients were randomly assigned to oral pioglitazone group (n = 30) or voglibose group (n = 30) in addition to conventional diet and exercise training. Body mass index and waist circumference did not change in the pioglitazone group, whereas these physical parameters significantly decreased in the voglibose group during a 6-month follow-up period. However, glycosylated hemoglobin, fasting plasma glucose, and HOMA-IR more significantly decreased in the pioglitazone group. The level of serum adiponectin especially high-molecular weight adiponectin markedly increased in the pioglitazone group. Moreover, high sensitive CRP significantly decreased only in the pioglitazone group. These results suggest that voglibose is superior in improving obesity, while pioglitazone is superior in ameliorating insulin sensitivity and increasing serum adiponectin in patients with an early stage of T2DM associated with MetS.

Topics: Adiponectin; Diabetes Mellitus, Type 2; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemic Agents; Inositol; Insulin Resistance; Metabolic Syndrome; Metabolome; Obesity; Pioglitazone; Thiazolidinediones

To investigate short-term effects of pioglitazone and voglibose on serum concentrations of both total and high-molecular-weight (HMW) adiponectin measured with a novel sandwich enzyme-linked immunosorbent assay (ELISA) ,and on plasma fibrinolysis indicators, in Type 2 diabetic patients with inadequate glycaemic control on sulphonylureas.. Thirty-four diabetic patients were randomized to receive pioglitazone or voglibose treatment for 12 weeks, after which serum HMW adiponectin was measured. Plasma plasminogen activator inhibitor (PAI) 1 and thrombin-activatable fibrinolysis inhibitor (TAFI), a recently identified inhibitor of fibrinolysis, were measured as fibrinolysis inhibitors.. At baseline, serum HMW adiponectin correlated negatively with plasma TAFI in all patients with Type 2 diabetes (r = -0.367, P = 0.0423). Both groups showed similar improvements in glycaemic control. Serum total and HMW adiponectin increased in patients treated with pioglitazone, but did not change in patients treated with voglibose. The HMW : total adiponectin ratio increased significantly after treatment with pioglitazone (P = 0.0004). The change in HbA(1c) correlated negatively with changes in serum HMW adiponectin in patients treated with pioglitazone (r = -0.694, P = 0.0034). Plasma PAI-1 and TAFI did not change with pioglitazone treatment.. Increased serum HMW adiponectin may contribute to the improvement in glycaemic control after pioglitazone treatment. Plasma PAI-1 and TAFI were unchanged by either drug.

Topics: Adiponectin; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Enzyme-Linked Immunosorbent Assay; Female; Humans; Hypoglycemic Agents; Inositol; Insulin Resistance; Male; Molecular Weight; Pioglitazone; Plasminogen Activator Inhibitor 1; Thiazolidinediones; Treatment Outcome

Unfortunately, clinicians are diagnosing a growing number of patients on hemodialysis (HD) with insulin-resistant, Type 2 diabetes in Japan. While alpha-glucosidase inhibitors (alpha-GI) such as oral antidiabetic agents are indicated for Japanese diabetics on HD, pioglitazone and other PPARgamma agonists are now contraindicated. No prospective study has evaluated the use of thiazolidinediones in diabetics with end-stage renal disease (ESRD) in combination with alpha-GI. In this study we evaluated the efficacy and safety of pioglitazone in Japanese diabetics on HD.. An open-label randomized study was performed on 31 Type 2 diabetics on HD with unstable glycemic control receiving constant doses of voglibose. The patients were randomly assigned to two groups: a combination therapy group (pioglitazone group) administered pioglitazone (fixed dose 30 mg) plus voglibose, and a monotherapy group (control group) administered voglibose alone. The efficacy of the treatments was determined by monitoring glycemic control (plasma glucose and HbA1c) and insulin resistance. Insulin resistance was assessed using the homeostasis model assessment for insulin resistance (HOMA-R). Safety and tolerance were determined by monitoring clinical and laboratory parameters.. The pioglitazone was effective in reducing plasma glucose and HbA1c from the baseline levels from Week 4 onward. It was also effective in reducing triglycerides. HOMA-R decreased significantly at 4 weeks in the pioglitazone group, and the decrease continued up to the last measurement at Week 12. Systolic and diastolic blood pressures at 4 weeks were statistically lower in the pioglitazone group than in the control group. No serious adverse effects such as hypoglycemia, liver impairment or rhabdomyolysis were observed in any of the patients.. Pioglitazone was safe and effective as a treatment for diabetics on dialysis therapy. The 30 mg daily dose of pioglitazone was sufficient for Japanese HD patients, obese and nonobese alike. The combination therapy of pioglitazone with voglibose will add to the list of first-line drug treatments for glycemic control in uremic Type 2 diabetes.

Topics: Aged; Asian People; Blood Glucose; Case-Control Studies; Demography; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Inositol; Insulin Resistance; Japan; Lipids; Male; Pioglitazone; Renal Dialysis; Thiazolidinediones

To investigate the effects of voglibose, an alpha-glucosidase inhibitor, on daily glycemic excursions, insulin secretion, and insulin sensitivity in non-insulin-treated NIDDM patients.. An open prospective study was conducted in 27 NIDDM patients receiving diet therapy alone or treatment with a sulfonylurea drug. Of the study subjects, 14 patients were treated with voglibose; the remaining 13 patients served as the control group. The metabolic parameters were evaluated before treatment and at week 4 of treatment as follows: glycemic excursions by M-value and 1,5-anhydro-D-glucitol (1,5-AG), insulin secretion by area under the curve of daily serum insulin (AUCinsulin), and insulin sensitivity by the K index of the insulin tolerance test (KITT).. After the study treatment, HbA1c and plasma glucose in the patients who had received voglibose were comparable to those of patients in the control group. M-value was lower in the patients treated with voglibose than in the control subjects (5.7 +/- 0.9 vs. 9.8 +/- 1.2, P < 0.05). 1,5-AG was higher in the patients treated with voglibose than in the control subjects (12.2 +/- 1.0 vs. 8.2 +/- 0.7 micrograms/ml, P < 0.01). A statistically significant increase in AUCinsulin occurred after treatment with voglibose (2,223.5 +/- 390.6 to 1,546.7 +/- 303.4 pmol.l-1.h, P < 0.05), but no change occurred in the control group (2,364.5 +/- 315.4 to 2,464.2 +/- 269.3 pmol.l-1.h, P = 0.60). Insulin sensitivity (KITT) was improved to a statistically significant level in both the patients treated with voglibose and the patients in the control group. KITT in the patients after voglibose treatment was comparable to that of the control group (3.18 +/- 0.30 vs. 3.21 +/- 0.23%/min, P = 0.94).. The results suggest that voglibose lowers the daily glycemic excursions and inhibits overwork of the pancreatic beta-cells but has little effect on insulin sensitivity in NIDDM patients.

Topics: Blood Glucose; Cholesterol; Cholesterol, HDL; Data Interpretation, Statistical; Diabetes Mellitus, Type 2; Enzyme Inhibitors; Fatty Acids, Nonesterified; Female; Glycated Hemoglobin; Glycoside Hydrolase Inhibitors; Humans; Inositol; Insulin; Insulin Resistance; Insulin Secretion; Male; Middle Aged; Triglycerides

We tested whether long-term administration of voglibose (VO) prevents diet induced obesity in addition to hypoglycemic effects in high fat fed mice and further investigated the underlying mechanisms by which voglibose exerts its weight lowering effect. Male C57BL/6 mice were fed ad libitum for 12 weeks with the control diet (CTL), high-fat diet (HFD) or the HFD with VO supplementations. Blood lipid profile, plasma leptin levels and hepatic triglyceride content, as well as expressions of genes involved in appetite and mitochondrial function were examined. The results showed that VO significantly reduced body weight, fat mass and energy intakes in high fat fed mice. VO showed improved metabolic profiles including blood glucose, triglyceride and free fatty acid. Elevated levels of plasma leptin in HFD were significantly reduced with the VO, furthermore, VO modulated the hypothalamic expressions of leptin receptors and appetite related genes. VO showed the upregulated expressions of PGC-1 in the liver and epididymal adipose tissue. In conclusion, VO may exert antiobesity properties through reductions in energy intake and improvement in mitochondrial function, indicating that VO has potential therapeutic use in patients with obesity, type 2 diabetes, and related complications.

Topics: Adiposity; Agouti-Related Protein; Animals; Appetite; Body Weight; Diet, High-Fat; Energy Intake; Gene Expression Regulation; Glucose Transporter Type 4; Hypothalamus; Inositol; Insulin; Insulin Resistance; Insulin-Secreting Cells; Leptin; Liver; Male; Mice; Mice, Obese; Nerve Tissue Proteins; Neuropeptide Y; Organ Specificity; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Pro-Opiomelanocortin; Receptors, Leptin; Transcription Factors; Triglycerides

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

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Enzyme Inhibitors; Glycoside Hydrolase Inhibitors; Humans; Inositol; Insulin; Insulin Resistance; Insulin Secretion; Treatment Outcome

To know whether the insulin resistance is improved by delaying carbohydrate absorption from the small intestine, we studied the effect of a disaccharidase inhibitor, AO-128, on insulin resistance of Wistar fatty rats. Rats were kept on standard laboratory chow with and without 10 ppm of AO-128 for 4 weeks, and then subjected to the glucose clamp. At the end of the 4-week treatment, plasma glucose level at 14:00 to 16:00 of AO-128 treated rats was 121 +/- 14 mg/100 ml (mean +/- S.D.), significantly lower than 226 +/- 72 mg/100 ml of the rats without AO-128. During clamp steady state under 20 mU.kg (-1).min (-1) continuous insulin infusion, glucose uptake of AO-128 treated rats was only 7.62 +/- 0.70 mg.kg (-1). min (-1), not different from 6.64 +/- 0.91 mg.kg (-1).min (-1) of rats without AO-128, but much lower than the lean littermates (20.81 +/- 3.11 mg.kg (-1).min (-1)). However, the percent suppression of hepatic glucose output was 55.2 +/- 23.8%, which, though incomplete, was significantly higher than 17.4 +/- 11.2% of rats without AO-128. The present study suggested that there were at least two, components of insulin resistance, a genetically determined and a poor-glycemic control-related, and that the latter insulin resistance was ameliorated by AO-128.

Topics: Animals; Blood Glucose; Body Weight; Cyclohexanols; Disaccharidases; Eating; Fasting; Glucose; Glucose Clamp Technique; Glycosuria; Infusions, Intravenous; Insulin; Insulin Resistance; Liver; Rats; Rats, Wistar; Urine