Use Of Acarbose Research Articles

Liver alpha-amylase gene expression as an early obesity biomarker

Obesity is a major health problem worldwide, for which preventive and therapeutic means are still needed. Alpha-amylase is a digestive enzyme whose inhibition has been targeted as a potential anti-obesity strategy. However, alpha-amylase gene expression has not been particularly attended to, and in contrast with pancreatic and salivary amylases, fewer studies have focused on liver alpha-amylase. The present study aimed at investigating the expression of alpha-amylase gene in obese and normal mice at RNA and protein level as well as acarbose effect on this gene expression in hepatocyte cell culture. Control and case groups were fed by normal mouse pellet and high-fat diet respectively, during 8 weeks. After this period, serum biochemical parameters including glucose, cholesterol, triglycerides, AST, ALT and alpha-amylase were assayed. Liver alpha-amylase gene was analyzed by real time PCR, and liver enzyme was assayed with Bernfeld and ELISA methods Hepatocyte cell culture derived from both group were also treated by acarbose and alpha-amylase activity and gene expression was analyzed by above mentioned methods. All biochemical factors showed an increase in obese mice, but the increase in ALT and AST were not statistically significant. Alpha-amylase levels were also increased in obese mice, both at RNA and protein level, while a decrease was seen in obese mice derived hepatocytes after acarbose treatment. Elevated liver alpha-amylase levels may be indicative of initial stages of obesity and the use of acarbose could be considered as a treatment of obesity which could be potentially effective at multiple levels.

PDB8 - Iatrogenic Hypoglycaemia in the Elderly: An Analysis of Diabetic Medication Usage Patterns According to Age

We performed a retrospective data analysis to examine the use of medications that can cause hypoglycaemia in elderly diabetes mellitus patients in Malaysia. We utilised data from the National Diabetes Registry from 2012 containing data from diabetes patients followed up in Malaysian public sector primary care clinics. Medications analysed were anti-diabetic (metformin, sulphonylurea, acarbose, insulin) and anti-hypertensive drugs classes (ACE-inhibitors, beta-blockers) which were widely used in the study population. Descriptive and univariate analyses were performed to examine the use of these medications across various age groups. A total of 130,246 patients with T2DM were included in the study. The patients were divided into 4 age groups, with 8.4% under 45 years old, 58.3% aged between 45–64 years, 29.8% between 65-79 years old and 3.5% over 80 years of age. The mean HbA1c of patients in the <45 years age group was the highest at 8.68% and lowest in the ≥80 years age group at 7.11%. There were significant reductions in the use of metformin (from 83.97% to 68.69% of patients) and insulin (24.70% to 12.03%) with age (all P<0.001). However, sulphonylurea use was similar cross all age groups (52.55% to 57.44%, P=0.500) while use of acarbose was generally higher in older patients (3.12% to 3.94%, P<0.001). In the subset of diabetics with hypertension, use of ACE inhibitors declined with age (64.43% to 49.95%, P<0.001) while use of beta blockers increased with age (20.11% to 35.56%, P<0.001). Despite limitations of our study especially related to reasons for prescribing different drugs, we note that a large proportion of older patients are still prescribed with medications that potentially cause hypoglycaemia, in particular, sulphonylureas and beta-blockers. This finding is to remind doctors to proceed with caution in treating the elderly when treating the elderly with certain medications.

Important Aspects of Post-Prandial Antidiabetic Drug, Acarbose.

Acarbose, a well known and efficacious α-amylase and α-glucosidase inhibitor, is a postprandial acting antidiabetic drug. DNS-based α-amylase inhibitory assays showed that use of acarbose at concentrations above 125 µg/ml resulted in release of reducing sugar in the reaction, an unexpected observation. Objective of the present study was to design experimental strategies to address this unusual finding. Acarbose was found to be susceptible to thermo-lysis. Further, besides being an inhibitor, it could also be hydrolyzed by porcine pancreatic α-amylase, but had weaker affinity for α - amylase compared to starch. GRIP docking was done for the mechanistic analysis of the active site in the enzyme for substrate, inhibitor and, inhibitor's metabolite (K2). Interaction between acarbose and α-amylase involved significant hydrogen binding compared to that of starch, producing a stronger enzyme-inhibitor complex. Further, docking analysis led us to predict the site on α-amylase where the inhibitor (acarbose) bound more tightly, which possibly affected the binding and hydrolysis of starch exerting its effective anti-diabetic function.

Acarbose Decreases the Rheumatoid Arthritis Risk of Diabetic Patients and Attenuates the Incidence and Severity of Collagen-induced Arthritis in Mice.

Acarbose has been found to decrease some inflammatory parameters in diabetic patients. This study aimed to examine the influence of acarbose on rheumatoid arthritis (RA) risk in diabetes mellitus (DM) patients and on the incidence and severity of collagen-induced arthritis (CIA) in mice. In a nationwide, matched case–control study, we identified 723 incident RA cases and selected 7,230 age-, sex- and RA diagnosis date–matched controls from all newly treated DM patients. We found that use of acarbose at > 16,950 mg per year was associated with a lower RA risk (odds ratio 0.60; 95% CI, 0.41–0.89). In the CIA mouse study, acarbose was orally administered from days -7 to 38 relative to type II collagen (CII) immunization. The results revealed that acarbose at the dose of 500 mg/kg/day attenuated the incidence and severity of arthritis and the expression of proinflammatory cytokines, including TNF-α, IL-6 and IL-17 in the paw tissues. Acarbose further decreased the productions of anti-CII-IgG, IL-17 and IFN-γ by collagen-reactive lymph node cells. This work suggests that the use of acarbose decreased RA risk in DM patients and the incidence of CIA in mice. Acarbose also attenuated the severity of CIA via anti-inflammatory and immunomodulatory effects.

Clinical review: Drugs commonly associated with weight change: a systematic review and meta-analysis.

Various drugs affect body weight as a side effect. We conducted this systematic review and meta-analysis to summarize the evidence about commonly prescribed drugs and their association with weight change. MEDLINE, DARE, and the Cochrane Database of Systematic Reviews were searched to identify published systematic reviews as a source for trials. We included randomized trials that compared an a priori selected list of drugs to placebo and measured weight change. We extracted data in duplicate and assessed the methodological quality using the Cochrane risk of bias tool. We included 257 randomized trials (54 different drugs; 84 696 patients enrolled). Weight gain was associated with the use of amitriptyline (1.8 kg), mirtazapine (1.5 kg), olanzapine (2.4 kg), quetiapine (1.1 kg), risperidone (0.8 kg), gabapentin (2.2 kg), tolbutamide (2.8 kg), pioglitazone (2.6 kg), glimepiride (2.1 kg), gliclazide (1.8 kg), glyburide (2.6 kg), glipizide (2.2 kg), sitagliptin (0.55 kg), and nateglinide (0.3 kg). Weight loss was associated with the use of metformin (1.1 kg), acarbose (0.4 kg), miglitol (0.7 kg), pramlintide (2.3 kg), liraglutide (1.7 kg), exenatide (1.2 kg), zonisamide (7.7 kg), topiramate (3.8 kg), bupropion (1.3 kg), and fluoxetine (1.3 kg). For many other remaining drugs (including antihypertensives and antihistamines), the weight change was either statistically nonsignificant or supported by very low-quality evidence. Several drugs are associated with weight change of varying magnitude. Data are provided to guide the choice of drug when several options exist and institute preemptive weight loss strategies when obesogenic drugs are prescribed.

Cardiovascular risk associated with acarbose versus metformin as the first-line treatment in patients with type 2 diabetes: a nationwide cohort study.

Metformin is the first-line oral therapy for type 2 diabetes with proven benefits against cardiovascular risk. Recent evidence suggested that acarbose might be similar to metformin in glucose-lowering efficacy and cardiovascular risk reduction. Therefore, international guidelines have suggested the use of acarbose as alternative first-line antidiabetic therapy. To compare the cardiovascular outcomes in the first-line users of acarbose vs metformin. DESIGN, SETTING, PATIENTS, AND OUTCOME MEASURES: A nationwide cohort study was conducted by analyzing the Taiwan National Health Insurance (NHI) Database. A total of 17,366 acarbose initiators and 230,023 metformin initiators were identified between January 1, 2009 and December 31, 2010. The primary outcome is hospitalization due to any cardiovascular events, including acute myocardial infarction, congestive heart failure, and ischemic stroke. The propensity score method was used to adjust for baseline differences between the two groups. Patients were followed from drug initiation to the earliest of outcome occurrence, death or disenrollment from NHI, or study termination. In intention-to-treat analyses, acarbose was associated with a higher risk of any cardiovascular event (adjusted hazard ratio [HR]: 1.05; 95% confidence interval [CI], 1.01-1.09), heart failure (HR, 1.08; 95% CI, 1.00-1.16), and ischemic stroke (HR, 1.05, 95% CI, 1.00-1.10) than metformin. No significant difference in risk was found in subgroups of patients with or without underlying hypertension, ischemic heart disease, or cerebrovascular disease. Similar results were found in auxiliary as-treated analyses or analyses stratified by propensity score quintiles. Our data do not support that acarbose has a cardio-protective effect similar to metformin as a first-line antidiabetic agent.

Combined use of basal insulin analog and acarbose reduces postprandial glucose in patients with uncontrolled type 2 diabetes.

Aims/IntroductionEarly initiation of basal insulin therapy is recommended for normalizing fasting blood glucose in type 2 diabetes mellitus. However, basal insulin treatment might not adequately control postprandial glucose levels. The present study evaluated whether the combination of the α-glucosidase inhibitor, acarbose, and basal insulin improved blood glucose control under daily-life treatment conditions in a large sample of Korean patients.Materials and MethodsThe present study was a multicenter, prospective, observational study under daily-life treatment conditions. A total of 539 patients with type 2 diabetes who were treated with basal insulin and additional acarbose were enrolled and followed up for 20 weeks. Changes in hemoglobin A1c, fasting and postprandial blood glucose were evaluated at baseline and at the end of the observation period. The physician and patient satisfaction of the combination treatment and safety were assessed.ResultsHemoglobin A1c decreased by 0.55 ± 1.05% from baseline (P < 0.0001). Fasting and postprandial blood glucose levels were reduced by 0.89 ± 3.79 and 2.59 ± 4.77 mmol/L (both P < 0.0001). The most frequently reported adverse drug reactions were flatulence (0.37%) and abnormal gastrointestinal sounds (0.37%), and all were mild in intensity and transient. In the satisfaction evaluation, 79.0% of physicians and 77.3% of patients were ‘very satisfied’ or ‘satisfied’ with the combined basal insulin and acarbose therapy.ConclusionsCombination therapy of basal insulin and acarbose in patients with type 2 diabetes improved glucose control, and had no drug-specific safety concerns, suggesting that the treatment might benefit individuals who cannot control blood glucose with basal insulin alone.

Safety and efficacy of acarbose in the treatment of diabetes in Chinese patients

Acarbose is an α-glucosidase inhibitor that is commonly used to control postprandial blood glucose. It functions as a competitive and reversible inhibitor of small intestinal brush border glucosidase, blocks the degradation of starch and sucrose, and delays the absorption of glucose and fructose in the alimentary tract. The starch content of a diet might alter the hypoglycemic effects of acarbose because of its mechanism of action. Chinese individuals consume a typical Eastern diet, which is characterized by a high intake of whole grains, legumes, vegetables, fruits, and fish. These dietary habits allow acarbose to be used extensively in the People’s Republic of China. Several Chinese-based studies have demonstrated that the use of acarbose as a monotherapy had similar effects on other anti-diabetes agents in decreasing glycosylated hemoglobin (HbA1c) and blood glucose levels, and acarbose in combination with other anti-diabetic drugs could further reduce blood glucose and decrease the mean amplitude of glycemic excursions. Importantly, acarbose is safe and well tolerated, with a low incidence of adverse effects. This article provides a comprehensive review of the safety and efficacy of acarbose for the treatment of diabetes in Chinese patients.

Acarbose treatment and the risk of cardiovascular disease in type 2 diabetic patients: a nationwide seven-year follow-up study.

Objective. To investigate the potential benefits of acarbose treatment on cardiovascular disease (CVD) in patients with type 2 diabetes by using nationwide insurance claim dataset. Research Design and Methods. Among 644,792 newly diagnosed type 2 diabetic patients without preexisting CVD in a nationwide cohort study, 109,139 (16.9%) who had received acarbose treatment were analyzed for CVD risk. Those with CVD followed by acarbose therapy were also subjected to analysis. Result. During 7 years of follow-up, 5,081 patients (4.7%) developed CVD. The crude hazard ratio (HR) and adjusted HR were 0.66 and 0.99, respectively. The adjusted HR of CVD was 1.19, 0.70, and 0.38 when the duration of acarbose use was <12 months, 12–24 months, and >24 months, respectively. Adjusted HR was 1.14, 0.64, and 0.41 with acarbose cumulative doses <54,750 mg, 54,751 to 109,500 mg, and >109,500 mg, respectively. Conclusion. In patients with type 2 diabetes without preexisting CVD, treatment with acarbose showed a transient increase in incidence of CVD in the initial 12 months followed by significant reductions of CVD in prolonged acarbose users. After the first CVD events, continuous use of acarbose revealed neutral effect within the first 12 months. The underlying mechanisms require further investigations.

Combined Effects of Green Tea Extracts, Green Tea Polyphenols or Epigallocatechin Gallate with Acarbose on Inhibition against α-Amylase and α-Glucosidase in Vitro

Green tea, green tea polyphenols and epigallocatechin gallate (EGCG) are confirmed to have beneficial effects in the treatment of diabetes mellitus, and a possible mechanism can be ascribed to their inhibitory effect against α-amylase and α-glucosidase in the digestive tract. In this paper, we first investigated the combined inhibitory effect of green tea extracts, green tea polyphenols or EGCG with acarbose on α-amylase and α-glucosidase in vitro. Our results indicated that the interaction between green tea extracts (green tea polyphenols or EGCG) and acarbose was complicated. The combination of green tea extracts, green tea polyphenols or EGCG with acarbose had a synergistic effect on α-amylase and α-glucosidase at low concentrations and the combined effect turned out to be antagonistic at high concentrations according to the Combination Index (CI) values. These findings not only provided some significant quantitative values, but also provide some valuable implications for the combined use of acarbose and GTE (GTP or EGCG) in the treatment of diabetes mellitus.

Acarbosa y propofol: ¿una peligrosa combinación?

Hepatotoxicity is a rare complication following the use of propofol and can be potentially serious if an early diagnosis is not made. Propofol is being increasingly used in daily practice, not only in surgery, but also in outpatient sedation procedures, such as endoscopy. Acarbose is a well-known drug used in type 2 diabetes treatment, particularly in the early phase. A case is reported on a patient who suffered an acute hepatitis secondary to the use of propofol in ophthalmology surgery, a hepatitis probably enhanced by prior use of acarbose, a drug that also can cause hepatotoxicity. An early diagnosis and it was resolved without complications. This case could contribute to improve pre-anesthetic evaluation of patients who will be undergoing sedation with propofol in order to avoid the possible appearance of hepatitis.

Improvement in blood glucose fluctuations of insulin-treated type 1 diabetic patients with additional use of acarbose and assessed by continuous blood glucose monitoring program

To investigate the effect of combined use of insulin and acarbose on glucose excursion in type 1 diabetic patients. 120 cases were randomly divided into control group and observation group. The control group received preprandial ultra-short effect insulin and long-acting insulin before bedtime while the observation group received acarbose 50 mg added to the medicine taken by the control group. Continuous Glucose Monitoring System (CGMS) was used to watch the blood glucose fluctuations. Data related to blood glucose level, glucose excursions after meals and hypoglycemia at night were compared between patients in the two groups. The average blood glucose (9.37 ± 1.70) mmol/L, the largest amplitude of glycemic excursions (LAGE) (11.42 ± 2.73) mmol/L, hyperglycemia-area under curve 0.89 ± 0.54, mean amplitude of glycemic excursions (MAGE) (5.13 ± 2.23) mmol/L, M-value (18.93 ± 11.43) mmol/L and insulin dosage (42.11 ± 14.42) U/day of observation group were significantly lower than in the control group (P < 0.05). Glucose excursions after meals and the times (0.33 ± 0.50)/day, the maintenance time (43.75 ± 43.50)/min and low glycemic index (LBGI) (0.005 ± 0.002) mmol/L of hypoglycemia at night were also significantly lower than in the control group, with statistically significant (P < 0.05) differences. The blood glucose fluctuation was significantly improved, with the decrease of insulin dosage while both glucose excursions and hypoglycemia at night reduced in patients with type1 diabetes mellitus after the acarbose treatment.We suggested that this program deserve further observation.

A Review of the Use of Acarbose for the Treatment of Post-prandial Syndrome (Reactive Hypoglycemia)

Introduction: The term “reactive” hypoglycemia, also known as post-prandial hypoglycemia has been loosely defined in the literature. The term refers to the occurrence of autonomic symptoms including weakness, perspiration, hunger, nausea, anxiety and tremors occurring one to two hours after ingestion of a meal. This collection of symptoms has been described in various patient groups including patients with impaired glucose tolerance, dumping syndrome following gastric surgeries (e.g. Nissen fundoplication, Billroth II and Roux en Y gastric bypass) and in patients in whom no specific cause has been identified. These autonomic symptoms have been reported in patients with and without documented hypoglycemia. This suggests that factors other than hypoglycemia may also be involved in the pathogenesis of this disorder. Data extraction: English-language articles that presented data relevant to the treatment of reactive hypoglycemia were identified in a MEDLINE search from 1966 to 2011. References of these articles and other publications were also reviewed. Search terms were reactive hypoglycemia, functional hypoglycemia, post-prandial hypoglycemia, Nissen fundoplication, Billroth procedure, gastric banding, Roux en Y occurring in association with the term hypoglycemia. Studies were included for review if they evaluated the clinical use of acarbose for the treatment of this syndrome and did not meet our exclusion criteria. Evidence synthesis: Five case reports and four small controlled trials met our inclusion criteria which examined the use of acarbose in the treatment of reactive hypoglycemia. Conclusion: We suggest the term Post-Prandial Syndrome (PPS) rather than reactive hypoglycemia since hypoglycemia is often not documented in patients who nevertheless experience postprandial autonomic symptoms. Acarbose is often used for the treatment of postprandial syndrome, but the evidence for its effectiveness is sparse and not definitive. Although acarbose does cause a statistically significant increase in the post-prandial glucose nadir after sucrose ingestion under experimental conditions, the effect is minimal and may not be clinically significant. There are currently no high-quality placebo-controlled clinical trials for the treatment of this syndrome. Further studies are needed to evaluate the potential therapeutic benefit of acarbose in the treatment of PPS.

Successful use of acarbose to manage post-prandial glycaemia in two patients with type 1 diabetes on continuous subcutaneous insulin infusion

Post-prandial hyperglycaemia is a particular problem for some patients with diabetes despite administering continuous subcutaneous insulin infusion (CSII) to deliver insulin flexibly. We describe two cases of patients on CSII with persistent post-prandial hyperglycaemia despite varying insulin doses and timing. Treatment with acarbose improved their glycaemic control.

Berry Polyphenols Inhibit α-Amylase in Vitro: Identifying Active Components in Rowanberry and Raspberry

Polyphenol-rich extracts from a range of berries inhibited α-amylase in vitro, but the most effective were from raspberry and rowanberry (IC50 values of 21.0 and 4.5 μg/mL, respectively). The inhibitory components were examined by different approaches. Extracts from yellow and red raspberries were equally able to inhibit α-amylase. Because the yellow raspberry extracts effectively lacked anthocyanins, this suggested that they were not crucial for amylase inhibition. Notably, however, higher levels of other phenolic components in yellow raspberries (particularly, ellagitannins) did not increase amylase inhibition. Amylase inhibition in rowanberry was recovered in a fraction enriched in proanthocyanidins (PACs). Inhibition was ameliorated by bovine serum albumin, suggesting that PACs acted by binding to amylase. Co-incubation of rowanberry PACs with acarbose reduced the concentration of acarbose required for effective amylase inhibition. Such synergistic interactions could have implications for the current clinical use of acarbose for postprandial glycaemic control in type-2 diabetics.

Postprandial Hyperglycemia and Cardiovascular Disease

In the recent HEART2D (Hyperglycemia and its Effect After Acute Myocardial Infarction on Cardiovascular Outcomes in Patients with Type 2 Diabetes Mellitus) study, published in this issue of Diabetes Care , Raz et al. (1) try to answer a hotly debated question of the last 10 years: is postprandial hyperglycemia an independent risk factor for cardiovascular disease in diabetes? This question, highlighted recently, has arisen because of the identified linear relationship, widely confirmed in many studies, between the risk of cardiovascular disease death and 2-h oral glucose tolerance test values (2). Consistent with these past results, a recent study has confirmed postprandial hyperglycemia as an independent risk factor for cardiovascular disease in type 2 diabetes (3). At the same time, in the STOP-NIDDM Trial it has been shown, as a predefined secondary end point, that treating postprandial hyperglycemia may reduce the incidence of new cardiovascular events in people with impaired glucose tolerance (4)—a finding confirmed in type 2 diabetes by a meta-analysis on the use of acarbose (5). Another important issue is that prandial glucose regulation, an emerging approach to treating type 2 diabetes, emphasizes the need for moderating the acute surges in plasma glucose levels that follow meals (6). Mechanistic and epidemiological studies indicate that postprandial glucose significantly contributes to overall glycemic exposure (6). In particular, postprandial hyperglycemia is the most important contributor to A1C, particularly when it is lower than 7.5% (7). Therefore, targeting postprandial hyperglycemia is important for the achievement of A1C targets. Numerous prandial therapeutics are now available, and an ever-growing literature on their use shows …

Acarbose for Polycystic Ovary Syndrome

To review the evidence for use of acarbose in the management of polycystic ovary syndrome (PCOS). Relevant publications were identified through a systematic search of PubMed English-language literature (1950-February 2008) using the MeSH terms and key words acarbose and polycystic ovary syndrome. The literature search retrieved 6 primary literature citations. Three randomized controlled clinical trials and one open-label study were evaluated. The other 2 citations were not evaluated due to only a peripheral mention of PCOS in relation to diabetes. PCOS is a complex disorder presenting most commonly with oligomenorrhea or amenorrhea, infertility, hirsutism, acne, and obesity. Acarbose is a promising therapy for PCOS because of its effects on postprandial insulin levels. In multiple clinical studies, acarbose improved hirsutism, acne, and menstrual irregularities through reduction in androgen concentrations and through increased androgen binding. When compared with metformin in women with PCOS and clomiphene-resistant infertility, acarbose induced greater weight loss and improved menstrual regularity and signs of fertility to a similar degree. Markers of cardiovascular risk were also significantly improved following 6 months of acarbose therapy in obese women with PCOS. Adverse effects, specifically gastrointestinal, were documented. Despite promising results, the studies were limited by small sample sizes and, in some cases, methods that were not clearly defined. Several trials have evaluated the use of acarbose in the management of PCOS with positive clinical evidence, but the results of these trials have not been corroborated by more rigorous studies.

Response to Acarbose and Postprandial Hypotension

We thank Gentilcore et al1 for their interest in our recent publication. Our work was focused on the potential therapeutic use of acarbose in the prevention of postprandial hypotension in autonomic failure patients rather than an in-depth research into the complex pathophysiology of this process. We did not include, therefore, several important references dealing with the latter, and we are please that, in their letter, they highlighted their significant work in this …

Effects of a Single Administration of Acarbose on Postprandial Glucose Excursion and Endothelial Dysfunction in Type 2 Diabetic Patients: A Randomized Crossover Study

Postprandial hyperglycemia has been reported to elicit endothelial dysfunction and provoke future cardiovascular complications. A reduction of postprandial blood glucose levels by the alpha-glucosidase inhibitor acarbose was associated with a risk reduction of cardiovascular complications, but effects of acarbose on endothelial function have never been elucidated. This study was aimed to assess the efficacy of acarbose on postprandial metabolic parameters and endothelial function in type 2 diabetic patients. Postprandial peakglucose (14.47 +/- 1.27 vs. 8.50 +/- 0.53 mmol/liter), plasma glucose excursion (PPGE), and change in the area under the curve (DeltaAUC)glucose after a single loading of test meal (total 450 kcal; protein 15.3%; fat 33.3%; carbohydrate 51.4%) were significantly higher in diet-treated type 2 diabetic patients (n = 14) than age- and sex-matched controls (n = 12). The peak forearm blood flow response and total reactive hyperemic flow (flow debt repayment) during reactive hyperemia, indices of resistance artery endothelial function on strain-gauge plethysmography, were unchanged before and after meal loading in controls. But those of diabetics were significantly decreased 120 and 240 min after the test meal. A prior administration of acarbose decreased postprandial peakglucose, PPGE, and DeltaAUCglucose. The peak forearm blood flow and flow debt repayment were inversely well correlated with peakglucose, PPGE, and DeltaAUCglucose but not with DeltaAUCinsulin or the other lipid parameters. Even a single loading of test meal was shown to impair endothelial function in type 2 diabetic patients, and the postprandial endothelial dysfunction was improved by a prior use of acarbose. Acarbose might reduce macrovascular complication by avoiding endothelial injury in postprandial hyperglycemic status.

A new diagnostic assay for glycogen storage disease type II in mixed leukocytes

We have established a new method for the enzymatic diagnosis of glycogen storage disease type II (Pompe disease or acid maltase deficiency) using mixed leukocytes. The method employs glycogen and 4-methylumbelliferyl-α- d-glucopyranoside (4MU-αGlc) as substrates for measuring the lysosomal acid α-glucosidase (acid αGlu) activity, and incorporates acarbose to eliminate the interference of unrelated α-glucosidases (predominantly maltase–glucoamylase). It is shown that 3.0 μmol/L acarbose completely inhibits the maltase–glucoamylase activity at pH 4.0, but the lysosomal acid αGlu activity by less than 5%. With this method, we determined the acid αGlu activity in mixed leukocytes from 25 patients with glycogen storage disease type II (2 infantile and 23 late-onset cases), one GAA2/ GAA2 homozygote and 30 healthy subjects. In the assay with glycogen as substrate, the addition of acarbose created a clear separation between the patient and the control ranges. In the assay with 4MU-αGlc as substrate, the two ranges were fully separated but remained very close despite the use of acarbose. The separation of the patient and normal ranges was improved considerably by taking the ratio of acarbose-inhibited over uninhibited activity. A GAA2/ GAA2 homozygote was correctly diagnosed with 4MU-αGlc but misdiagnosed as patient when glycogen was used as substrate. We conclude that the inclusion of 3.0 μmol/L acarbose in the assays with glycogen and 4MU-αGlc substrates at pH 4.0 allows for the specific measurement of lysosomal acid αGlu activity in mixed leukocytes, thus enabling a reliable diagnosis of glycogen storage disease type II in this specimen.