ao-128 and Diabetic-Angiopathies

Type 2 diabetes mellitus (T2DM) is currently at epidemic proportions and the forecast is for a continued sharp increase in global prevalence. An even larger proportion of the population has prediabetes (impaired glucose tolerance [IGT]) underscoring the urgent need for preventive strategies. Even in the presence of adequate glycosylated hemoglobin (HbA1c) levels, postprandial hyperglycemia can occur and is known to have a stronger association with cardiovascular morbidity than fasting glucose. The α-glucosidase inhibitor voglibose is widely used in Japan to improve postprandial hyperglycemia.. This review examines the literature for the pharmacology, pharmacokinetics, clinical efficacy and safety of voglibose in patients with T2DM. Particular focus is on its efficacy in preventing T2DM in individuals with IGT and its efficacy as add-on therapy or in combination with other oral antidiabetic agents in patients with T2DM.. As the relationship between glucose levels and cardiovascular risk extends below the diabetic threshold, postprandial hyperglycemia is recognized as a key therapeutic target in the treatment of T2DM. Strategies to prevent the progression of IGT to overt T2DM have enormous potential to reduce the individual and societal burden of disease. Voglibose is the first oral antidiabetic agent to gain approval in Japan for this indication.

Topics: Atherosclerosis; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Drug Therapy, Combination; Glucose Intolerance; Humans; Hypoglycemic Agents; Inositol; Insulin; Practice Guidelines as Topic; Treatment Outcome

Insulin injection, especially with insulin analogs, occasionally induces the production of insulin antibodies with high binding capacity and low affinity, similar to the insulin autoantibodies characteristic of insulin autoimmune syndrome (IAS). Production of these "IAS-like" insulin antibodies causes marked glycemic fluctuations with postprandial hyperglycemia and fasting hypoglycemia.. A 66-year-old man with a 27-year history of diabetes was admitted because of marked glycemic fluctuations. Human insulin treatment had been initiated at age 56, followed by multiple daily injections of insulin analogs 5 years later. After the initial year of insulin analog treatment, the patient began to experience frequent morning hypoglycemic attacks and day-time hyperglycemia. Marked hyperinsulinemia (4500 μU/mL) and high titers of insulin antibodies (80.4%) with high binding capacity and low affinity indicated that IAS-like insulin antibodies were causing severe glucose fluctuations. Altering insulin formulations (insulin aspart → regular human insulin→ insulin lispro) proved to be ineffective. After several therapeutic trials, cessation of exogenous insulin and addition of mitiglinide to liraglutide with voglibose finally attenuated glycemic fluctuations with increased postprandial insulin secretion. Continuous glucose monitoring revealed improvement of morning hypoglycemia and postprandial hyperglycemia with smaller mean amplitude of glycemic excursion. Therefore, compared to exogenously injected insulin, endogenously secreted insulin directly and rapidly acts on hepatocytes and suppresses postprandial glucose output.. Proper enhancement of postprandial endogenous insulin aimed at suppressing postprandial glucose output without stimulating excessive glucose uptake in the periphery is potentially useful for treating diabetes with insulin antibody-induced glycemic instability.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Inositol; Insulin; Insulin Antibodies; Insulin Secretion; Isoindoles; Liraglutide; Male; Postprandial Period; Treatment Outcome

We observed 3 diabetic patients with intolerable dizziness followed by nausea and vomiting immediately after an initial administration of the alpha-glucosidase inhibitor, voglibose. These symptoms did not recur after discontinuation of the drug. Adverse effects as observed in these cases have not been reported previously. Since the 3 patients were relatively old (average age, 72 years old) and had various degrees of micro- and macroangiopathies, these side effects may have been associated with increased micro- and macrocirculatory disturbances in their central nervous systems through alpha-glucosidase inhibition of this agent.

Topics: Aged; Aged, 80 and over; Cerebral Infarction; Cerebrovascular Circulation; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Dizziness; Enzyme Inhibitors; Female; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemic Agents; Inositol; Male; Middle Aged; Nausea; Vomiting