nateglinide and Hypertension

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

Recent studies have identified postprandial glycemic excursions as risk factors for diabetes complications. This study aimed to compare the effects of nateglinide and acarbose treatments on postprandial glycemic excursions in Chinese subjects with type 2 diabetes.. This was a multicenter, open-label, randomized, active-controlled, parallel-group study. One hundred three antihyperglycemic agent-naive subjects with type 2 diabetes (hemoglobin A1c range, 6.5-9.0%) were prospectively recruited from four hospitals in China. The intervention was nateglinide (120 mg three times a day) or acarbose (50 mg three times a day) therapy for 2 weeks. A continuous glucose monitoring system was used to calculate the incremental area under the curve of postprandial blood glucose (AUCpp), the incremental glucose peak (IGP), mean amplitude of glycemic excursions, SD of blood glucose, the mean of daily differences, and 24-h mean blood glucose (MBG). Subjects' serum glycated albumin and the plasma insulin levels were also analyzed.. Both agents caused significant reductions on AUCpp and IGP. Similarly, both treatment groups showed significant improvements in the intra- and interday glycemic excursions, as well as the 24-h MBG and serum glycated albumin compared with baseline (P<0.001). However, neither of the agents produced a significantly better effect (P>0.05). Moreover, the nateglinide-treated group had significantly increased insulin levels at 30 min and at 120 min after a standard meal compared with baseline, whereas the acarbose-treated group decreased. No serious adverse events occurred in either group. The rates of hypoglycemic episodes were comparable in the two groups, and no severe hypoglycemic episode occurred in either group.. Nateglinide and acarbose were comparably effective in reducing postprandial glycemic excursions in antihyperglycemic agent-naive Chinese patients with type 2 diabetes, possibly through different pathophysiological mechanisms.

Topics: Acarbose; Adolescent; Adult; Antihypertensive Agents; Area Under Curve; Blood Glucose; China; Cyclohexanes; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Glycemic Index; Humans; Hypertension; Hypoglycemic Agents; Male; Middle Aged; Nateglinide; Phenylalanine; Postprandial Period; Prospective Studies; Treatment Outcome

To test the effects of novel oral hypoglycemic agent A-4166 on lipolysis and lipogenesis in adipocytes from normal rats and non-obese, hypertriglyceridemic, insulin resistant and hypertensive rats (HTG) fed basal or high fat diet.. Adult male Wistar rats and hereditary HTG rats (from our own colony) were used. They were fed either basal or high fat diet for three weeks. On the day of observation the active substance A-4166 was administered intragastrically by gavage 30 minutes before decapitation. Blood was collected for the determination of insulin, glycemia, non esterified fatty acids (NEFA) by using commercial kits. The isolated adipocytes were prepared from epididymal fat pads and lipolysis (by measurement of glycerol release) and lipogenesis (by estimation of labeled glucose incorporation into lipids) were determined.. The administration of A-4166 results in increased serum insulin and decreased serum glucose level in all rats irrespective of the diet. A significant diminution of serum NEFA levels was observed in A-4166 administered Wistar and HTG rats fed high fat diet. In both groups of rats fed basal diet the lipolysis was not affected by A-4166. However, a decrease of lipolysis was found after A-4166 in Wistar rats fed high fat diet. The stimulation of lipolysis by norepinephrine was not influenced by A-4166. A lowered basal lipolysis was found in HTG rats fed high fat diet. The stimulation of lipolysis by norepinephrine was diminished in HTG rats as compared to Wistar animals. Administration of A-4166 did not affect the stimulation of lipolysis by norepinephrine in HTG rats. A decrease of stimulatory action of insulin on lipogenesis was found in Wistar rats fed high fat diet and in all groups of HTG rats. The administration of A-4166 did not change the basal lipogenesis and also the effect of insulin on lipogenesis.. Besides the hyperinsulinemic and hypoglycemic effect of A-4166 also an influence on nonesterified fatty acid serum levels was observed in rats fed high fat diet. This can be partially explained by an antilipolytic action of hyperinsulinemia after A-4166. The studies of lipogenesis showed that Wistar rats fed high fat diet and HTG animals are resistant to the stimulatory action of insulin on lipogenesis and that administration of A-4166 did not affect this response to insulin.

Topics: Adipocytes; Animals; Blood Glucose; Cyclohexanes; Fatty Acids, Nonesterified; Hypertension; Hypoglycemic Agents; Insulin; Insulin Resistance; Lipids; Lipolysis; Male; Nateglinide; Norepinephrine; Phenylalanine; Rats; Rats, Wistar