ao-128 and Hyperinsulinism

Topics: Acarbose; Animals; Diabetes Mellitus, Type 2; Enzyme Inhibitors; Glycoside Hydrolase Inhibitors; Humans; Hyperglycemia; Hyperinsulinism; Hyperlipidemias; Hypoglycemic Agents; Inositol; Obesity; Postprandial Period

To compare the therapeutic effects between sitagliptin and voglibose both with sensor-augmented insulin pump (SAP) in newly diagnosed type 2 diabetes mellitus (T2DM).. Fifty-six newly diagnosed hospitalized T2DM patients in Department of Endocrinology of the First Affiliated Hospital of Dalian Medical University, with hemoglobin A1c (HbA1c) value of 9%-11%, were randomized into the sitagliptin (S) group (n=28) and the voglibose (V) group (n=28) by block randomisation. Participants in S group received sitagliptin 100 mg per day, and V group received voglibose 0.2 mg for 3 times per day. All patients were treated with SAP for 9 days. Real-time continuous glucose monitoring (RT-CGM) was used. Glucose variability parameters were observed. The research has been approved by the ethics committee of the First Affiliated Hospital of Dalian Medical University(KY2014-08).. No significant differences were observed in baseline characteristics between the two groups (all P>0.05). In V group and S group, fasting blood glucose (FPG) [(6.4±1.1) vs (11.4±3.0) mmol/L, P=0.008; (5.5±0.8) vs (11.0±2.1) mmol/L, P<0.001], mean blood glucose(MBG) [(7.5±0.8) vs (12.0±1.1) mmol/L, P=0.045; (6.7±0.7) vs (12.5±1.3) mmol/L, P=0.002], standard deviation of blood glucose (SDBG) (P=0.023, 0.036) decreased and homeostasis model assessment (HOMA)-β (P=0.002, 0.001) increased significantly after 9 days therapy. The mean of daily differences (MODD)(P=0.027), coefficient of variation-FPG (CV-FPG) (P=0.033) and HOMA-IR (P=0.039) in S group significantly decreased, while postprandial glycemic excursion (PPGE)(P=0.003, 0.026, 0.011, 3 meals respectively)and the low glycemic index(LBGI)(P=0.025) in V group decreased, the peak postprandial level of glucose(Δt)was longer compared with before (P=0.028, 0.026, 0.030, 3 meals respectively). After therapy, PPGE in V group significantly became lower than those in S group (P=0.041, 0.032, 0.036, 3 meals respectively), while FPG and MBG in S group were significantly lower than those in V group (P=0.041, 0.039).. Sitagliptin or voglibose combined with SAP can improve glucose control and protect islet function for patients with newly diagnosed T2DM. Sitagliptin has advantages in controlling MBG and FPG compared with voglibose. Voglibose has more striking advantages in reducing the postprandial blood glucose fluctuation.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Glucose; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Hyperinsulinism; Inositol; Insulin Infusion Systems; Insulins; Postprandial Period; Sitagliptin Phosphate

This study was undertaken to investigate the effect of voglibose, a new alpha-glucosidase inhibitor, on glucose and lipid metabolism in nondiabetic hyperinsulinemic subjects. Sixteen nondiabetic subjects with hyperinsulinemia participated in the study. They were divided into two groups of eight subjects with normal (NGT) and impaired (IGT) glucose tolerance. A meal tolerance test and a 75-g oral glucose tolerance test (OGTT) were performed at the beginning (baseline phase) and end (treatment phase) of the 12-week treatment. Serum lipid levels were measured every 4 weeks throughout the treatment phase and follow-up phase (8 weeks). All patients received 1 0.2-mg tablet of voglibose before each test meal (3 tablets per day). We also measured insulin sensitivity using a steady-state plasma glucose (SSPG) method in eight normotensive hyperinsulinemic subjects and in eight age- and body mass index (BMI)-matched control subjects before and after the drug treatment. Voglibose significantly decreased the responses of plasma glucose and insulin on the meal tolerance test. The area under the curve for 2-hour insulin during the 75-g OGTT decreased after treatment, whereas that for 2-hour glucose did not change before and after treatment. SSPG was reduced after treatment, indicating improvement of insulin sensitivity. Moreover, treatment with voglibose resulted in a significant decline of triglyceride level and an elevation of high-density lipoprotein (HDL) cholesterol and apolipoprotein A-1. These values returned to near-baseline levels after the drug was discontinued. Consequently, we conclude that this agent not only has a direct hypoglycemic effect through decreased absorption of carbohydrate, but also a hypoinsulinemic and hypolipidemic effect via improved insulin sensitivity.

Topics: Blood Glucose; Cyclohexanols; Enzyme Inhibitors; Female; Glycoside Hydrolase Inhibitors; Humans; Hyperinsulinism; Hyperlipidemias; Insulin; Male; Middle Aged

The present study was designed to determine the possible significance of a therapeutic dose (0.2 mg) of AO-128 on carbohydrate absorption by measuring the breath hydrogen concentration, which is an index of the amount of unabsorbed carbohydrate in the large intestine. Post-prandial hyperglycemia is common among diabetic patients. AO-128, a potent alpha-glucosidase inhibitor, suppressed post-prandial hyperglycemia and hyperinsulinemia in healthy volunteers at a dose of 0.2 mg with each meal. These volunteers increased the breath hydrogen concentration in response to ingestion of non-absorbable lactulose, but decreased only slightly its concentration from the basal level after sucrose ingestion, indicating complete absorption. When AO-128 (0.2 mg) was given with sucrose, hydrogen production increased only slightly compared with placebo, suggesting that the inhibitory effect of AO-128 on sucrose absorption was minimal. Only 5 g of the 100 g of sucrose was not absorbed and this 5% reduction is too small to explain the observed inhibitory effect on the post-prandial rise in plasma glucose. Sucrose loading in rats (about 443 mg) sharply increased blood glucose and was accompanied by the rapid disappearance of sucrose from the upper small intestine. AO-128 (0.03 or 0.1 mg/kg) lessened the elevation of blood glucose after sucrose ingestion. The lower dose (0.03 mg/kg) retarded small intestinal absorption, but did not induce an influx of sucrose into the cecum and large intestine, while the higher dose (0.1 mg/kg) caused an increased influx of sucrose into the large bowel. These results indicated that AO-128 retards the absorption of carbohydrate and reduces post-prandial hyperglycemia.

Topics: Adolescent; Adult; Animals; Blood Glucose; Cross-Over Studies; Cyclohexanols; Dietary Carbohydrates; Eating; Enzyme Inhibitors; Glycoside Hydrolase Inhibitors; Humans; Hydrogen; Hyperglycemia; Hyperinsulinism; Intestinal Absorption; Male; Rats; Rats, Sprague-Dawley; Respiration; Single-Blind Method; Sucrose