Modulation of circulating vasoactive peptides and extracellular matrix proteins are two novel mechanisms in the cardioprotective action of acarbose.

BACKGROUND: Acarbose, an alpha-glucosidase inhibitor, unexpectedly reduced the incidence of hypertension and cardiovascular endpoints in the STOP-NIDDM study. Based on the growing evidence of a link between vasoregulatory peptides and metabolic traits, we hypothesized that changes of the Glycemic Index by acarbose may modulate vasoregulatory peptide levels via regulation of postprandial metabolism. METHODS: Subjects with type 2 diabetes and with metabolic syndrome were treated with acarbose (12 weeks, 300mg/d) in a double-blind, placebo-controlled, cross-over intervention. Changes in fasting and postprandial levels of midregional pro-atrial natriuretic peptide (MR-proANP), C-terminal pro-endothelin-1 (CT-proET-1) and midregional pro-adrenomedullin (MR-proADM), WNT1 Inducible Signaling Pathway Protein 1 (WISP1) as well as fasting and postprandial glucose/insulin levels in the liquid meal test were assessed. RESULTS: Acarbose strongly decreased postprandial insulin concentrations in subjects with metabolic syndrome (P=0.004), and postprandial glucose excursions in both groups. Postprandial MR-proANP and CT-proET-1 levels increased after acarbose treatment (P<0.01 and P<0.05, respectively) in subjects with metabolic syndrome only. No effect of acarbose treatment on MR-prADM was observed in both groups. All three peptides were correlated with each over, but neither with insulin sensitivity in euglycemic clamps, nor with adiponectin levels. WISP1 decreased after acarbose treatment in subjects with metabolic syndrome. CONCLUSIONS: Plasma MR- proANP and CT-proET-1 concentrations, but not MR-prADM concentrations, were affected by treatment with acarbose over 12 weeks. Our findings provide new possible mechanisms of acarbose action in diabetes and metabolic syndrome.

Critical evaluation of the role of acarbose in the treatment of diabetes: patient considerations.

The alpha-glucosidase inhibitor acarbose has been used for more than 20 years in the management of hyperglycemia. Owing to its unique mode of action in the gastrointestinal tract, its properties are very different from other antidiabetic medications. Patients on long-term treatment to control a chronic disease are not only interested in good treatment efficacy, but are also even more interested in the safety and side effects of their medications. Significant aspects of acarbose predominantly regarding safety and tolerability in the management of type 2 diabetes and prediabetes are reviewed. It is concluded that acarbose is a convenient long-term treatment option, with benefits for both type 2 diabetics and patients in a prediabetic state.

Effects of acarbose on proinsulin and insulin secretion and their potential significance for the intermediary metabolism and cardiovascular system.

The alpha-glucosidase inhibitor acarbose is administered to control blood glucose levels in type 2 diabetic patients and, in several countries, in those with impaired glucose tolerance. The efficacy and safety of the drug has been well established in these patient populations. Acarbose shows no weakening of efficacy in long-term diabetes treatment, reduces the development of type 2 diabetes in those with impaired glucose tolerance, and also appears to reduce the risk of cardiovascular disease. The underlying mechanisms of its effect on the risk of developing macrovascular complications have still to be elucidated. The mode of action of acarbose, which precedes all other metabolic processes involved in blood glucose regulation, inhibits high increases in postprandial blood glucose. Due to this early mode of action, acarbose also modifies insulin and proinsulin secretion which are both involved in ss-cell dysfunction and insulin resistance and may be independent risk factors for cardiovascular mortality. Based on the literature available the present state of knowledge on insulin and proinsulin as risk factors for cardiovascular mortality is reviewed as well as the effect of acarbose on the regulation of the ss-cells as monotherapy and in combination regimens. Possible associated interactions with the cardiovascular system are identified.

Meal-related structured self-monitoring of blood glucose: effect on diabetes control in non-insulin-treated type 2 diabetic patients.

OBJECTIVE: To investigate the effect of meal-related self-monitoring of blood glucose on glycemic control and well-being in non-insulin-treated type 2 diabetic patients. RESEARCH DESIGN AND METHODS: This 6-month study, which included 6 months of follow-up, adopted a prospective, multicenter, randomized controlled design. Subjects were randomized to two groups: one group used a blood glucose-monitoring device, kept a blood glucose/eating diary, and received standardized counseling; the control group received nonstandardized counseling on diet and lifestyle. The primary efficacy parameter was the change in HbA(1c). Secondary efficacy variables included changes in body weight, lipids, and microalbumin and changes in treatment satisfaction and well-being. RESULTS: In the per-protocol analysis, the use of a self-monitoring blood glucose device significantly reduced HbA(1c) levels by 1.0 +/- 1.08% compared with 0.54 +/- 1.41% for the control group (P = 0.0086); subgroup analysis showed three types of responders. Body weight, total cholesterol, and microalbumin improved when using a glucometer, but there was no statistically significant difference between the two groups. Treatment satisfaction increased in both groups to a similar extent (P = 0.9). Self-monitoring resulted in a marked improvement of general well-being with significant improvements in the subitems depression (P = 0.032) and lack of well-being (P = 0.02). CONCLUSIONS: Meal-related self-monitoring of blood glucose within a structured counseling program improved glycemic control in the majority of non-insulin-treated type 2 diabetic patients in this study. The finding of three types of responders will be important for future planning of counseling and educational interventions.