Acarbose Group Research Articles

Postprandial endothelial dysfunction in subjects with new-onset type 2 diabetes: an acarbose and nateglinide comparative study

BackgroundPostprandial hyperglycemia is believed to affect vascular endothelial function. The aim of our study was to compare the effects of acarbose and nateglinide on postprandial endothelial dysfunction.MethodsWe recruited a total of 30 patients with newly diagnosed type 2 diabetes (19 men and 11 women, age 67.8 ± 7.3 years). Patients were randomly assigned to 3 groups receiving either 300 mg/day acarbose, 270 mg/day nateglinide, or no medication. A cookie test (consisting of 75 g carbohydrate, 25 g butter fat, and 7 g protein for a total of 553 kcal) was performed as dietary tolerance testing. During the cookie test, glucose and insulin levels were determined at 0, 30, 60, and 120 min after load. In addition, endothelial function was assessed by % flow-mediated dilation (FMD) of the brachial artery at 0 and 120 min after cookie load.ResultsPostprandial glucose and insulin levels were similar in the 3 groups. Postprandial endothelial dysfunction was similar in the 3 groups before treatment. After 12 weeks of intervention, postprandial FMD was significantly improved in the acarbose group compared with the control group (6.8 ± 1.3% vs 5.2 ± 1.1%, p = 0.0022). Area under the curve (AUC) for insulin response was significantly increased in the nateglinide and control groups; however, no significant change was observed in the acarbose group.ConclusionsOur results suggest that acarbose improves postprandial endothelial function by improvement of postprandial hyperglycemia, independent of postprandial hyperinsulinemia. Acarbose may thus have more beneficial effects on postprandial endothelial function in patients with type 2 diabetes than nateglinide.

Postprandial hyperglycemia is a determinant of platelet activation in early type 2 diabetes mellitus.

Chronic hyperglycemia is a major contributor to in vivo platelet activation in diabetes mellitus. To evaluate the effects of acarbose, an alpha-glucosidase inhibitor, on platelet activation and its determinants in newly diagnosed type 2 diabetic patients. Forty-eight subjects (26 males, aged 61 +/- 8 years) with early type 2 diabetes (baseline hemoglobin A(1c) < or = 7% and no previous hypoglycemic treatment) were randomly assigned to acarbose up to 100 mg three times a day or placebo, and evaluated every 4 weeks for 20 weeks. The main outcome measures were urinary 11-dehydro-thromboxane (TX)B(2) (marker of in vivo platelet activation) and 8-iso-prostaglandin (PG)F(2alpha) (marker of in vivo lipid peroxidation) excretion rate, 2-h postprandial plasma glucose (PPG) after a test meal, and assessment of glucose fluctuations by mean amplitude of glycemic excursions (MAGE). Baseline measurements revealed biochemical evidence of enhanced lipid peroxidation and platelet activation. As compared with the placebo group, patients treated with acarbose had statistically significant reductions in urinary 11-dehydro-TXB(2) and 8-iso-PGF(2alpha) excretion rate as early as after 8 weeks and at each subsequent time point (between-group P < 0.0001 at 12, 16 and 20 weeks), following earlier decreases in PPG and MAGE. Multiple regression analyses in the acarbose group revealed that PPG was the only significant predictor of 11-dehydro-TXB(2) urinary excretion rate (beta = 0.39, P = 0.002) and MAGE the only predictor of 8-iso-PGF(2alpha) urinary excretion rate (beta = 0.42, P = 0.001). Postprandial hyperglycemia is associated with enhanced lipid peroxidation and platelet activation in early type 2 diabetes. A moderate decrease in PPG achieved with acarbose causes time-dependent downregulation of these phenomena, suggesting a causal link between early metabolic abnormalities and platelet activation in this setting.

Acarbose Reduces Myocardial Infarct Size by Preventing Postprandial Hyperglycemia and Hydroxyl Radical Production and Opening Mitochondrial KATP Channels in Rabbits

Acarbose, an antidiabetic drug, is an alpha-glucosidase inhibitor that can inhibit glucose absorption in the intestine. A recent large-scale clinical trial, STOP-NIDDM, showed that acarbose reduces the risk of myocardial infarction. We examined whether acarbose reduces myocardial infarct size and investigated its mechanisms. Rabbits were fed with 1 of 2 diets in this study: normal chow, 30 mg acarbose per 100 g chow for 7 days. Rabbits were assigned randomly to 1 of 4 groups: control (n = 10), acarbose (n = 10), acarbose + 5HD (n = 10, intravenous 5 mg/kg of 5-hydroxydecanoate), and 5HD (n = 10, intravenous 5 mg/kg of 5HD). Rabbits then underwent 30 minutes of coronary occlusion followed by 48-hour reperfusion. Postprandial blood glucose levels were higher in the control group than in the acarbose group. The infarct size as a percentage of the left ventricular area at risk was reduced significantly in the acarbose (19.4% +/- 2.3%) compared with the control groups (42.8% +/- 5.4%). The infarct size-reducing effect of acarbose was abolished by 5HD (43.4% +/- 4.7%). Myocardial interstitial 2,5-dihydroxybenzoic acid levels, an indicator of hydroxyl radicals, increased during reperfusion after 30 minutes of ischemia, but this increase was inhibited in the acarbose group. This was reversed by 5HD. Acarbose reduces myocardial infarct size by opening mitochondrial KATP channels, which may be related to the prevention of postprandial hyperglycemia and hydroxyl radical production.

The investigation of the efficacy of insulin glargine on glycemic control when combined with either repaglinide or acarbose in obese Type 2 diabetic patients

Combinations of insulin and oral antidiabetic drugs (OAD) are often prescribed instead of insulin alone. In this study, the effects of insulin glargine (IG) in combination with repaglinide or acarbose on glycemic parameters were investigated. Obese Type 2 diabetic patients with fasting blood glucose (FBG) levels >or= 7.7 mmol/l [corrected] and hemoglobin glycated (A1C) >or=9% under maximal OAD combination therapy were enrolled. Previous therapies were discontinued, and patients were randomized into 2 groups. The combinations of IG and repaglinide were administered to group 1, and of IG and acarbose to group 2 for 13 weeks. Twenty patients in group 1 and 18 patients in group 2 completed the study. A1C levels were significantly decreased from 10.9+/-1.4% to 7.7+/-1.1% in group 1 and 11.0+/-1.4% to 8.1+/-1.4% in group 2. FBG levels were significantly decreased from 11.9+/-2.7 to 7.1+/-2.3 mmol/l in group 1 and 11.1+/-2.5 to 6.8+/-1.4 mmol/l in group 2. Post-prandial glucose levels were significantly decreased from 15.3+/-3.8 to 10.3+/-3.0 mmol/l in group 1 and 14.0+/-3.1 to 8.9+/-2.2 mmol/l in group 2. Intergroup comparisons indicated no significant differences. More weight gain was detected in group 1, compared to the baseline. Symptomatic hypoglycemia incidence was similar in both groups. Severe hypoglycemic attacks were seen in two patients in group 1. Flatulence incidence was higher in acarbose group. Conclusively, repaglinide and acarbose were equally effective when combined with IG for obese Type 2 diabetic patients controlled inadequately with OAD alone. Furthermore, acarbose seems to have advantages over repaglinide concerning weight gain and severe hypoglycemic attacks.

Metabolic syndrome and its single traits as risk factors for diabetes in people with impaired glucose tolerance: the STOP-NIDDM trial

The STOP-NIDDM trial was an international, double-blind, placebo-controlled randomised study in people with impaired glucose tolerance (IGT). They were treated with an alpha-glucosidase inhibitor, acarbose, to prevent diabetes; the overall number needed to treat (NNT) was 11. In a secondary analysis, we considered the impact of single traits and overall metabolic syndrome (MetS) respectively on risk of diabetes and NNT respectively. In all, there were 1,368 patients. They were followed up for 3.3 years, and the prevalence of MetS was 61%. Multivariate analysis revealed treatment group 2-hour (post-challenge) plasma glucose, glycosylated haemoglobin (HbA1C), triglycerides and leukocyte count as independent predictors. The annual incidence of diabetes in the placebo group with MetS was 18.7% vs. 11.2% in patients without MetS; the corresponding figures in the acarbose group were 13.5% and 9.4%, respectively. The NNT in patients was 5.8 in patients with MetS and 16.5 in those without MetS. In conclusion, most single traits and overall MetS label a very high-risk group in people with IGT. People with MetS reach a NNT to prevent development of new diabetes with acarbose of 5.8.

1-Deoxynojirimycin을 생산하는 Bacillus subtilis S10 배양액의 혈당강하 효과

본 연구는 α-glucosidase의 강력한 효소저해제인 1-deoxynojirimycin(DNJ)을 고효율로 생산하는 균주의 선발 및 동정, 배양최적화 및 균 배양액의 혈당강하효과 등에 관하여 조사하였다. 먼저 토양으로부터 α-glucosidase에 대해 강력한 저해능을 나타내는 9균주를 대상으로 이 중에서 DNJ 생산성이 가장 우수한 한 개 균주를 최종 선발하였고, 이 균주를 16S rDNA 염기서열분석으로 균주동정을 하여 Bacillus subtilis S10이라 명명하였다. 본 균주의 배양액을 이온교환수지법(Amberlyst 15 H? form, Dowex 1×2-100 OH? form, Amberlite CG-50 NH₃? form)에 의해 DNJ를 정제하고, 정제된 DNJ를 LC-MS로 분석한 결과 표준 DNJ와 동일한 물질임을 확인하였다. DNJ 대량생산을 위한 S10균주의 배양최적탄소원 및 최적질소원과 이들의 최적농도를 조사한 결과 각각 1% galactose, 1.6% polypeptone임이 밝혀졌으며, 확립된 최적화 조건에서의 DNJ 생산량은 0.75 g/L이었다. 고혈당 유도 마우스를 대상으로 각종 혈당강하제의 효과를 알아보기 위해 혈당치를 비교한 결과 무처리구의 혈당치 510±10.9 ㎎/dL에 비해 acarbose 처리구는 139.4±33.1 ㎎/dL, 누에분말 처리구는 209.1±19.6 ㎎/dL, 그리고 S10 균주 배양액 처리구는 208.6±39.8 ㎎/dL로써 무처리구에 비해 각각 72.7%, 59.0%, 그리고 59.1%의 혈당 억제율을 나타냈다. 이상의 연구결과 S10균주 배양액은 누에분말과 같은 수준의 고혈당 억제 및 완화효과가 있음이 확인되었으며 향후 S10균주의 대량생산을 통해 식후혈당조절을 위한 건강기능식품 개발이 기대된다 하겠다.

Abstract 3213: Acarbose, an α -glucosidase Inhibitor, Reduces Myocardial Infarct Size in Rabbits via Stimulation of GLP-1 Receptors, Opening Mitochondrial KATP Channels, and Preventing Hydroxyl Radical Production

Background: Acarbose, an anti-diabetic drug, is an α– glucosidase inhibitor that can inhibit glucose absorption in the intestine. A recent large-scale clinical trial, STOP-NIDDM, showed that acarbose reduces the risk of myocardial infarction. We examined whether acarbose reduces myocardial infarct size and investigated its mechanisms. Methods and Results: Rabbits were fed with one of four diets in this study: normal chow, 30 mg acarbose/100 g chow, 8 g sucrose/100 g chow, or 30 mg acarbose plus 8 g sucrose/100 g chow for 7 days. Rabbits were assigned randomly to one of eight groups: control (n=10), acarbose (n=10), sucrose (n=10), acarbose+sucrose (n=10), acarbose+i.v. 5-hydroxydecanoate (5HD, a mitochondrial KATP channel blocker, 5 mg/kg) (n=10), 5HD (i.v. 5 mg/kg, n=10), acarbose+exendin(9 –39) (n=10, a Glucagon-Like Peptide-1(GLP-1) receptor blocker, 3 nmol/l) (45.4±1.2%) and exendin(9 –39)(n=10). Rabbits then underwent 30 min of coronary occlusion followed by 48 h reperfusion. Postprandial blood glucose levels were highest in the sucrose group and higher in the control groups, but decreased in the acarbose and sucrose+acarbose groups. The infarct size as a percentage of the left ventricular area at risk was reduced significantly in the acarbose (19.4±2.3%) and sucrose+acarbose groups (19.0±5.6%) as compared with the sucrose (47.4±4.2%) and control groups (42.8±5.4%). The infarct size-reducing effect of acarbose was abolished by 5HD (43.4±4.7%) and exendin(9 –39) (45.4±1.2%). The 5HD and exendin(9 –39) by itself did not affect the infarct size. Myocardial interstitial 2,5-DHBA levels, an indicator of hydroxyl radicals, increased during reperfusion after 30 min of ischemia but this increase was inhibited in the acarbose group. Conclusions: Acarbose reduces myocardial infarct size via stimulation of GLP-1 receptors, opening mitochondrial KATP channels, and preventing hydroxyl radical production.

Effect of Acarbose, an Alpha-Glucosidase Inhibitor, on Serum Lipoprotein Lipase Mass Levels and Common Carotid Artery Intima-Media Thickness in Type 2 Diabetes Mellitus Treated by Sulfonylurea

Previous reports indicate that serum lipoprotein lipase mass levels (LPL mass) and common carotid artery intima-media thickness (CCA-IMT) are independent predictors of atherosclerotic diseases. The aim of this study was to examine the effects of combination therapy of sulfonylurea and acarbose on LPL mass and CCA-IMT. Eighty-four patients with type 2 diabetes mellitus, who were treated with only sulfonylureas and showed CCA-IMT of more than 0.9 mm at baseline, were selected and randomly divided into two groups. One group was administered acarbose 300 mg/day for 12 months (acarbose group, n=41), and the other group was not administered acarbose (non-acarbose group, n=43). After 12 months, a significant increase in LPL mass and a significant decrease in CCA-IMT were observed in the acarbose group (1.024 to 0.964 mm), but no significant changes were observed in the non-acarbose group. In a subgroup analysis of patients with HbA1c improved by 0.5% or more, the increase of LPL mass and decrease of CCA-IMT was significantly greater in the acarbose group than in the non-acarbose group although the changes in HbA1c were similar in two groups. We concluded that reducing postprandial hyperglycemia might increase LPL mass levels and might be useful to prevent macroangiopathy in type 2 diabetic patients treated by sulfonylurea.

Acarbose Attenuates Basal and Postprandial Insulin Concentrations but Fails to Lower Blood Pressure in the Spontaneously Hypertensive Rat

Patients with essential hypertension and the spontaneously hypertensive rat (SHR) are insulin-resistant and hyperinsulinemic. These findings suggest the possibility that insulin resistance and hyperinsulinemia may play a pivotal role in blood pressure regulation. Acarbose, an oral antihyperglycemic drug, decreases hyperinsulinemia and hyperglycemia. The purpose of this study was to assess the influence of acarbose on basal and postprandial insulin and glucose levels and whether changes in beta-cell function result in a change in blood pressure measurements. SHRs were fed custom diets ad libitum, six with and six without acarbose (40mg/100g of chow). Fasting and postprandial glucose and insulin levels were analyzed following glucose administration (1.75 g/kg body weight). Blood pressure was determined by the tail cuff method. Fasting glucose values were similar, but fasting insulin levels declined 23% in the acarbose treated group (P < .05). Postprandial glucose and insulin levels decreased 18% and 20%, respectively (P < .01), in the acarbose group vs the control animals. Despite the decrease in fasting and postprandial insulin concentrations, systolic, mean, and calculated diastolic blood pressures were insignificantly different in the acarbose group after six weeks of treatment compared to control animals. Acarbose decreases fasting insulin levels and postprandial glucose and insulin levels without effectively lowering blood pressure in the SHR. The ability of acarbose to attenuate the hyperinsulinemic state in the SHR without effectively lowering blood pressure suggests that factors other than serum insulin concentration are important in the modulation of blood pressure.

Comparison of insulin monotherapy and combination therapy with insulin and metformin or insulin and rosiglitazone or insulin and acarbose in type 2 diabetes

The aim of this study was to compare the efficacy of treatment with insulin alone, insulin plus acarbose, insulin plus metformin, or insulin plus rosiglitazone in type 2 diabetic subjects who were previously on insulin monotherapy, and to evaluate the effects of these treatments on cardiovascular risk factors including lipid profile, C-reactive protein (CRP) and fibrinogen. Sixty-six poorly controlled type 2 diabetic patients on insulin monotherapy were involved. They were randomized to insulin alone, insulin plus acarbose, insulin plus metformin, or insulin plus rosiglitazone groups for 6 months period. Mean fasting and postprandial glucose values as well as HbA1c levels significantly decreased in all groups. The greatest improvement in HbA1c was observed in insulin plus rosiglitazone (2.4%) and in insulin plus metformin (2%) groups. Daily total insulin dose was increased to 12.7 units/day in insulin alone group, decreased to 4.7 units/day in insulin plus rosiglitazone group, to 4.2 units/day in insulin plus metformin group, and to 2.7 units/day in insulin plus acarbose group. Least weight gain occurred in insulin plus metformin group (1.4 kg) and greatest weight gain occurred in insulin plus rosiglitazone group (4.6 kg). No significant change in lipid levels--except serum triglycerides--was observed in any groups. CRP and fibrinogen levels decreased in all groups, but the decrease in fibrinogen level was significantly greater in insulin plus rosiglitazone group. All groups were comparable in hypoglycemic episodes. No serious adverse event was noted in any group.

Single Nucleotide Polymorphisms of the Peroxisome Proliferator–Activated Receptor-α Gene (PPARA) Influence the Conversion From Impaired Glucose Tolerance to Type 2 Diabetes

Peroxisome proliferator-activated receptor (PPAR) alpha, a transcription factor of the nuclear receptor superfamily, regulates fatty acid oxidation. We evaluated the association of single nucleotide polymorphisms (SNPs) of the PPAR-alpha gene (PPARA) with the conversion from impaired glucose tolerance to type 2 diabetes in 767 subjects of the STOP-NIDDM trial in order to investigate the effect of acarbose in comparison with placebo on the prevention of diabetes. In the placebo group, the G (162V) allele of rs1800206 increased the risk for diabetes by 1.9-fold (95% CI 1.05-3.58) and was associated with elevated levels of plasma glucose and insulin. The effect of this allele on the risk of diabetes in the placebo group was enhanced by the simultaneous presence of the risk alleles of the PPAR-gamma2, PPAR-gamma coactivator 1alpha, and hepatic nuclear factor 4alpha genes (odds ratios 2.2, 2.5, and 3.4, respectively). In the acarbose group, subjects carrying the minor G allele of rs4253776 and the CC genotype of rs4253778 of PPARA had a 1.7- and 2.7-fold increased risk for diabetes. Our data indicate that SNPs of PPARA increase the risk of type 2 diabetes alone and in combination with the SNPs of other genes acting closely with PPAR-alpha.

Short-term Therapeutic Efficacy of Different Oral Hypoglycemic Agents Combined with Once Daily Insulin Glargine in Type 2 Diabetic Subjects with Failure of Sulfonylurea and Metformin Combination

Backgroud: Although the extended duration of action of insulin glargine supports a convenient once daily injection, the combination with other short acting insulins or oral hypoglycemic agents is required to control postprandial hyperglycemia in type 2 diabetes. The present study was designed to compare the short-term therapeutic efficacy of oral hypoglycemic agents with once daily insulin glargine, switching from a multiple daily injection regimen. Methods: After control with the intensive regimen (daily lispro insulin and glargine) during 5~7 days, 80 in-patients with type 2 diabetes were randomized and treated with four oral hypoglycemic agents (glimepiride 4 mg qd, metformin 500 mg bid, nateglinide 90 mg tid, or acarbose 100 mg tid) plus once daily insulin glargine during 5 days. Blood glucose concentration was recorded by seven daily estimations (before each meal, 2 hours after each meal, and bedtime). Blood glucose concentrations and area under the curves (AUCs) of blood glucose were compared among four groups. Results: The area under the curve of blood glucose of metformin, glimepiride, nateglinide, and acarbose groups were 165.5 ± 46.0, 178.5 ± 36.5, 209.9 ± 55.1, and 224.9 ± 55.8 mmol/L/hr respectively. Blood glucose concentrations and area under the curves of blood glucose of glimepiride and metformin groups were significantly lower than those of acarbose group. Also, those of metformin group were significantly lower than those of nateglinide group. Conclusions: Metformin or glimepiride are more effective oral hypoglycemic agent than nateglinide or acarbose in the combination with insulin glargine in type 2 diabetic subjects with failure of sulfonylurea and metformin combination. (J Kor Diabetes Assoc 31:336~342, 2007)

Acarbose improves fibrinolytic activity in patients with impaired glucose tolerance

Acarbose has been shown to ameliorate insulinemia, suggesting that it may exert favorable effects on the impaired fibrinolytic state in prediabetic patients. We therefore conducted a randomized controlled study to examine the effects of acarbose on fibrinolysis in patients with impaired glucose tolerance (IGT). The participants were randomized to receive (n = 20) or not (control, n = 20) 100 mg of acarbose before each meal (300 mg/d) for 3 months. A marked decrease in the plasma levels of plasminogen activator inhibitor 1 (by 42%) and fibrinogen (by 27%) was observed in the acarbose group at the end of the study, whereas no significant changes in the levels of these parameters were observed in the control group. We also conducted postprandial evaluation of insulin-related clinical markers and found ameliorated hyperinsulinemia in the subjects treated with acarbose. These results indicate that acarbose could improve fibrinolysis in patients with IGT, mainly by ameliorating insulinemia. Other favorable effects of acarbose, such as reduction in the plasma levels of oxidized low-density lipoprotein, glucose toxicity, and hyperglycemia, might also contribute, at least in part, to the beneficial effects of the drug on the fibrinolytic state in patients with IGT.

Acarbose in obese patients with polycystic ovarian syndrome: a double-blind, randomized, placebo-controlled study

The present study assessed the effects of low-dose acarbose on obese patients with polycystic ovarian syndrome (PCOS). A double-blind placebo-controlled study was conducted on 30 obese hyperinsulinaemic women with PCOS treated with 150 mg/day acarbose or placebo for 6 months. The women were evaluated for hirsutism, menstrual regularity, body mass index (BMI), insulin resistance and glucose tolerance, sex hormone-binding globulin (SHBG), LH, FSH, testosterone and androstenedione, and side-effects. The patients in the acarbose group showed a reduction in BMI (35.87 +/- 2.60 versus 33.10 +/- 2.94 kg/m(2)) and in the Ferriman-Gallwey index (8.85 +/- 2.31 versus 8 +/- 1.82), and an increased chance of menstrual regularity (rate = 2.67). SHBG concentration increased (21.01 +/- 7.9 versus 23.85 +/- 7.77 nmol/l) and the free androgen index was reduced (14.81 +/- 9.06 versus 11.48 +/- 6.18). None of these parameters were modified in the placebo group. Mild side-effects occurred in 84% of the patients in the acarbose group and disappeared after the first 3 months. A low dose of acarbose administered to obese patients with PCOS promotes a reduction in free androgen index and BMI and an increase in SHBG, with improvement of hirsutism and of the menstrual pattern, and is well tolerated by patients.

The effects of acarbose and Rumex patientia L. on ultrastructural and biochemical changes of pancreatic B cells in streptozotocin-induced diabetic rats

This study was performed to observe the effects of acarbose and Rumex patientia on morphological change of pancreatic B cells in streptozotocin (STZ)-induced diabetic (type 2) rats. Two-day-old Wistar albino rats were intraperitoneally injected with 100mg/kg of STZ or vehicle alone for control. Vehicle and STZ given rats were divided into six groups (1st, 2nd and the 3rd groups are control; the 4th, 5th and 6th groups are STZ groups). The 1st and the 4th groups received water, the 2nd and the 5th groups received 40mg acarbose/100g feed, the 3rd and the 6th groups received 2% decoction of Rumex patientia grain. During experimentation period, blood glucose levels were checked periodically, and HbA1c level was measured from cardiac blood at the end of the experiment. Pancreas tissues were examined by electron microscope. Glucose and HbA1c levels increased by STZ were decreased by acarbose and Rumex patientia. Morphologically, we found a mitochondrial vacuolization and swelling as well as dilatation of the endoplasmic reticulum in the B cells of STZ-induced diabetic rats. Also, a decrease in the secretory granules of B cells was observed in the STZ-induced diabetic group. No pathological changes were observed in the STZ+acarbose group. In the STZ+Rumex patientia group, a weak swelling in the B cells was observed in the some of the mitochondria.

Repetitive postprandial hyperglycemia increases cardiac ischemia/reperfusion injury: prevention by the α‐glucosidase inhibitor acarbose

Protective effects of the alpha-glucosidase inhibitor acarbose have been reported for various diabetic complications. In the STOP-NIDDM study, even patients without overt diabetes, but with impaired glucose tolerance, had a reduction in cardiovascular events when treated with acarbose. Therefore, we investigated the effect of repetitive postprandial hyperglycemia on the cardiac ischemia/reperfusion injury in vivo. Mice were treated daily by single applications of placebo, sucrose (4 g/kg body weight), or sucrose + acarbose (10 mg/kg body weight) by gavage for 7 days. Acarbose treatment significantly reduced the sucrose-induced increase in plasma glucose concentration. Subsequently, animals underwent 30 min of ischemia by coronary artery ligation and 24 h of reperfusion in vivo. In the sucrose group, ischemia/reperfusion damage was significantly increased (infarct/area at risk, placebo vs. sucrose, 38.8+/-7.5% vs. 62.2+/-4.8%, P<0.05). This was prevented by acarbose treatment (infarct/area at risk 30.7+/-7.2%). While myocardial inflammation was similar in all groups, oxidative stress as indicated by a significant increase in lipid peroxides was enhanced in the sucrose, but not in the sucrose + acarbose group. In summary, repetitive postprandial hyperglycemia increases ischemia/reperfusion damage. This effect can be prevented by treatment with the alpha-glucosidase inhibitor acarbose.

Long-Term Efficacy and Tolerability of Acarbose Treatment in Patients with Type 2 Diabetes Mellitus

The aim of the study was to investigate the efficacy and tolerability of long-term acarbose therapy in type 2 diabetic patients. In this double-blind, single-centre group comparison, patients were randomised to receive either acarbose or matching placebo, in addition to their regular antidiabetic therapy, over a period of 78 weeks. Eligibility for inclusion in the efficacy evaluation included a study duration of >/=510 days. The primary efficacy parameter was the change in glycosylated haemoglobin (HbA(1)) from baseline to end of study. Secondary variables included changes in blood glucose and lipid parameters, as well as signs of retinopathy and nephropathy. A total of 139 patients were assessed for safety and 88 patients (44 in each treatment group) were included in the efficacy analysis. Patients were generally overweight and the majority had previously been treated with sulphonylureas. Acarbose significantly improved fasting and 1-hour postprandial blood glucose levels compared with placebo (p = 0.039 and 0.009), and improvements in HbA(1) with acarbose versus placebo fell just short of significance (p = 0.057). There were no differences between treatments in changes in microvascular complications, but blood pressure improved with acarbose treatment. Two patients in the acarbose group experienced elevated liver enzyme levels. Generally, acarbose had a good safety profile and was well tolerated. Long-term treatment with acarbose was safe and efficacious in patients with type 2 diabetes mellitus that was insufficiently controlled by other oral antidiabetics.

Common polymorphisms of the PPAR-?2 (Pro12Ala) and PGC-1? (Gly482Ser) genes are associated with the conversion from impaired glucose tolerance to type 2 diabetes in the STOP-NIDDM trial

We investigated the effects of the common polymorphisms in the peroxisome proliferator-activated receptor gamma2 (PPAR-gamma2; Pro12Ala) and in PPAR-gamma coactivator 1alpha (PGC-1alpha; Gly482Ser) genes on the conversion from impaired glucose tolerance to type 2 diabetes in participants in the STOP-NIDDM trial. This trial aimed to study the effect of acarbose in the prevention of type 2 diabetes. Genotyping was performed in 770 study subjects whose DNA was available. The Gly482Ser variant in the PGC-1alpha gene was determined with the polymerase chain reaction amplification, Hpa II enzyme digestion, and gel electrophoresis. The Pro12Ala polymorphism of the PPAR-gamma2 gene was determined by the polymerase chain reaction-single-strand conformation polymorphism analysis. The Pro12Pro genotype of the PPAR-gamma2 gene predicted the conversion to diabetes in women in the acarbose group (odds ratio 2.89, 95% CI 1.20 to 6.96; p=0.018). The 482Ser allele of the PGC-1alpha gene had a significant interaction with the mode of treatment (p=0.012), and in the placebo group the 482Ser allele was associated with a 1.6-fold higher risk for type 2 diabetes compared to the Gly482Gly genotype (95% CI 1.06 to 2.33; p=0.023). Acarbose prevented the development of diabetes independently of the genotype of the PPAR-gamma2 gene, but only the carriers of the 482Ser allele of the PGC-1alpha gene were responsive to acarbose treatment. We conclude that the Pro12Pro genotype of the PPAR-gamma2 gene and the 482Ser allele of the PGC-1alpha gene are associated with the conversion from impaired glucose tolerance to type 2 diabetes in the STOP-NIDDM trial.

Is acarbose equivalent to tolbutamide as first treatment for newly diagnosed type 2 diabetes in general practice?A randomised controlled trial

We performed a double blind randomised controlled trial in general practice to assess equivalence between tolbutamide and acarbose with respect to the effect on mean HbA1c in newly diagnosed patients with type 2 diabetes. Secondary objectives were to compare the effects of both treatments on fasting and post-load blood glucose and insulin levels, lipids, and adverse events. Patients were randomised to receive acarbose, titrated step-wise to a maximum of 100 mg three times daily (n=48) or tolbutamide, similarly titrated to a maximum of 2000 mg in three doses (n=48). The two treatments were considered equivalent if the two-sided 90% confidence interval (CI) for the difference in mean HbA1c levels was within the range −0.4 to 0.4%. Results were analysed on an intention-to-treat, per-protocol and on worst-case basis. Both agents reduced the HbA1c percentage and fasting blood glucose levels. The difference in mean decrease of HbA1c was 0.6% in favour of tolbutamide (90% CI 0.3, 0.9; 95% CI 0.2, 1.0). A worst-case analysis, assuming no change in HbA1c for dropouts, yielded a difference in mean decrease of 0.9% (90% CI 0.6, 1.2) in favour of tolbutamide. The difference in mean decrease of fasting blood glucose was 1.0 mmol/l in favour of tolbutamide (95% CI 0.3, 1.7). There were no significant differences in post-load blood glucose, fasting and post-load insulin levels, or lipids. In the acarbose group significantly more patients (15 versus 3) discontinued therapy because of adverse effects, mostly of gastrointestinal origin. We conclude that the results of this study favour tolbutamide over acarbose as first treatment for patients with newly diagnosed type 2 diabetes.

Is acarbose equivalent to tolbutamide as first treatment for newly diagnosed type 2 diabetes in general practice?: A randomised controlled trial

We performed a double blind randomised controlled trial in general practice to assess equivalence between tolbutamide and acarbose with respect to the effect on mean HbA 1c in newly diagnosed patients with type 2 diabetes. Secondary objectives were to compare the effects of both treatments on fasting and post-load blood glucose and insulin levels, lipids, and adverse events. Patients were randomised to receive acarbose, titrated step-wise to a maximum of 100 mg three times daily ( n=48) or tolbutamide, similarly titrated to a maximum of 2000 mg in three doses ( n=48). The two treatments were considered equivalent if the two-sided 90% confidence interval (CI) for the difference in mean HbA 1c levels was within the range −0.4 to 0.4%. Results were analysed on an intention-to-treat, per-protocol and on worst-case basis. Both agents reduced the HbA 1c percentage and fasting blood glucose levels. The difference in mean decrease of HbA 1c was 0.6% in favour of tolbutamide (90% CI 0.3, 0.9; 95% CI 0.2, 1.0). A worst-case analysis, assuming no change in HbA 1c for dropouts, yielded a difference in mean decrease of 0.9% (90% CI 0.6, 1.2) in favour of tolbutamide. The difference in mean decrease of fasting blood glucose was 1.0 mmol/l in favour of tolbutamide (95% CI 0.3, 1.7). There were no significant differences in post-load blood glucose, fasting and post-load insulin levels, or lipids. In the acarbose group significantly more patients (15 versus 3) discontinued therapy because of adverse effects, mostly of gastrointestinal origin. We conclude that the results of this study favour tolbutamide over acarbose as first treatment for patients with newly diagnosed type 2 diabetes.