This was a multicenter, randomized, placebo-controlled, double-blind clinical trial. Patients (N = 381) with T2DM and inadequate glycemic control (glycated hemoglobin [HbA1c] ≥ 7.0% and ≤10.0%) on acarbose monotherapy (at least 50 mg three times daily) were randomized in a 1:1 ratio to receive the addition of sitagliptin 100 mg or matching placebo once daily for 24 weeks.
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The effect of the alpha-glucosidase inhibitor acarbose on pancreatic exocrine and endocrine function was studied using the isolated perfused pancreata prepared from rats fed a normal (control diet) or an acarbose-containing sucrose- (ACS diet) or glucose-supplemented diet (ACG diet) for 10 days. Pancreatic amylase and insulin contents in rats fed the ACS diet were significantly decreased compared with those in rats with the control diet. Rats fed the ACG diet, however, had normal enzyme and hormone contents. Basal and cerulein-stimulated flow rates of pancreatic juice in rats with the ACS or ACG diet were similar to those in rats fed the control diet, suggesting that the pancreata from rats treated with acarbose have normal sensitivity and responsiveness to cerulein. On the other hand, cerulein-stimulated amylase output was significantly decreased in rats with the ACS diet, but was normal in rats with the ACG diet. Insulin secretion to both glucose and cerulein stimulation in rats fed the ACS diet was reduced by approximately 55% compared with the control rats. On the other hand, rats fed the ACG diet showed normal insulin secretion to glucose stimulation, although the insulin response to cerulein stimulation was reduced by 30%. These results suggest that the addition of acarbose to the sucrose-rich diet decreases the secretory responsiveness of amylase to cerulein stimulation and that of insulin to both glucose and cerulein stimulation. All these alterations, except the sensitivity of B cells to cerulein, can be normalized by replacing sucrose with glucose.
Bioassay-guided fractionation of the CHCl(3) soluble portion of the roots of Panax japonicus C. A. Meyer var. major afforded an active fraction with inhibitory activity against baker's yeast alpha-glucosidase with an IC(50) value 1.02 mg/mL. Furthermore, the active fraction isolated contained three previously unreported polyacetylenes, designated panaxjapynes A-C, together with 11 other compounds, including four polyacetylenes, five phenolic compounds, a sesquiterpenoid, and a sterol glucoside. The structures of the compounds were elucidated by spectroscopic and chemical methods. Compared with the control acarbose (IC(50) 677.97 microM), six compounds were shown to be more potent alpha-glucosidase inhibitors with IC(50) values in the range 22.21-217.68 microM.
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In this three-center double-blind study, 90 Chinese NIDDM patients with persistent poor glycemic control despite maximal doses of sulfonylurea and metformin were randomly assigned to receive additional treatment with acarbose 100 mg thrice daily or placebo for 24 weeks, after 6 weeks of dietary reinforcement. Efficacy was assessed by changes in HbA1c, fasting and 1-h postprandial plasma glucose and insulin levels, and fasting lipid levels.
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Tendencies in the consumption of antidiabetic agents in Andalusia between 1986-1994 were analysed, with special emphasis on the impact of the introduction of acarbose and mechanized systems for the injection of insulin.
Falandi is a common strawberry (Fragaria × ananassa Duch.) cultivar in southern China. Further study of the chemical constituents in Falandi fruit led to the isolation of nine norsesquiterpenoids and three triterpenoids. Falandioside D (1) and falandins A (2) and B (3) were new norsesquiterpenoids, and the others excluding tormentic acid (11) were found in strawberry for the first time. Compounds 1 and 11 exhibited potent α-glucosidase inhibitory activity with the half maximal inhibitory concentration (IC50) values of 565.0 and 27.4 μM in comparison to acarbose (619.9 μM). Compounds 3, 7 (blumenol C glucoside), and 11 showed cytotoxicity against human nasopharyngeal carcinoma cell line CNE1 with the IC50 values of 57.6, 56.4, and 36.0 μM, respectively. Among new compounds, 1 showed 2,2'-azinobis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical cation scavenging capacity (IC50=36.2 μM). These results suggested that non-phenolic constituents were also involved in the antidiabetic, antitumour, and antioxidant effects of strawberry fruit.
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Screening for pre-diabetes followed by diet and exercise, or metformin treatment is cost-effective and should be considered for incorporation into current practice. The number of dietitians and exercise physiologists needed to deliver such lifestyle change interventions will need to be increased to appropriately support the intervention.
Combination therapy with repaglinide and troglitazone leads to better glycemic control than monotherapy with either agent alone. Repaglinide monotherapy was more effective in lowering HbA1c levels than troglitazone monotherapy Repaglinide/troglitazone combination therapy was effective and did not show unexpected adverse events.
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Blueberries have been extensively researched, but there are limited studies on other parts of the plant. Here we report the first phytochemical examination of highbush blueberry (Vaccinium corymbosum) flowers, which yielded 21 phenolics. The compounds were identified from extensive NMR and mass spectral analyses and included five caffeic acid (1-5), three coumaric acid (6-8), and two cinnamyl alcohol (9-10) derivatives, eight flavonol glycosides (11-18), and three phenylpropanoid-substituted catechins (19-21). The isolates were evaluated for antioxidant and α-glucosidase inhibitory activities. Overall, the flavonol glycosides and phenylpropanoid-substituted catechins showed superior antioxidant activities compared to the positive controls, vitamin C (IC(50)=63μM) and butylated hydroxytoluene (IC(50)=1548μM). Similarly, these phenolic sub-classes were more potent α-glucosidase inhibitors than the clinical drug, acarbose (IC(50)=200μM). Thus, non-consumed parts of food plants may be exploited as sources of bioactive compounds beyond their edible parts alone for nutraceutical and functional food applications.
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The alpha-glucosidase inhibitor bromoconduritol inhibits the formation of the N-linked, complex-type oligosaccharides of the glycoproteins from influenza viruses (fowl plague virus, influenza virus PR-8) and from sindbis virus. Viral glycoproteins produced in bromoconduritol-treated chicken-embryo and baby-hamster kidney cells are fully glycosylated, but accumulate N-linked, high-mannose oligosaccharides of the composition Glc1Manx (GlcNAc)2 (x = 7, 8, and 9). Other alpha-glucosidase inhibitors (nojirimycin, deoxynojirimycin, acarbose) were not specific inhibitors of oligosaccharide processing under the conditions used in the present investigation. In bromoconduritol-treated, sindbis virus-infected chicken-embryo and baby-hamster kidney cells, the sindbis glycoproteins are metabolically stable. Specific proteolytic cleavage of the polyprotein precursors to form E2 and E1 occurs in bromoconduritol-treated chicken-embryo cells, but cleavage of PE2 to E2 is prevented in the infected baby-hamster kidney cells. Yet, release of infectious sindbis virus particles is inhibited in both cell types indicating that the formation of complex oligosaccharides is required for a late step in virus formation. The release of virus particles from influenza virus PR-8-infected bromoconduritol-treated chicken-embryo cells is not inhibited, and virus with only high-mannose oligosaccharides is formed. In contrast, when chicken-embryo cells were infected with the influenza virus fowl plague virus, release of infectious particles was inhibited. The fowl plague virus hemagglutinin is cleaved in chicken-embryo cells, in contrast to the hemagglutinin of the PR-8 virus. However, the cleavage products HA1 and HA2 do not reach the cell surface. In addition, or as a consequence, HA1 and HA2 are proteolytically broken down, whereas uncleaved hemagglutinin of PR-8 appeared metabolically stable. These results may explain the decrease in formation of fowl plague virus particles and the lack of effect on PR-8 virus in bromoconduritol-treated cells. This work thus shows different biological roles for oligosaccharide processing.
The last two decades have seen an explosive increase in the number of people with diabetes globally. There is now an urgent need for strategies to prevent the emerging global epidemic. Several recent successful intervention studies, both lifestyle and pharmacological, targeting subjects with impaired glucose tolerance (IGT) have stimulated enthusiasm for prevention of Type 2 diabetes. Lifestyle interventions reduced the incidence of diabetes by over 50% in the Finnish Diabetes Prevention Study and the Diabetes Prevention Program. Can the findings of these two studies be applied globally? Underpinning the enthusiasm, there needs to be a realistic approach to interventions in both developed and developing nations, and in ethnic groups where a better understanding of the socio-economic, cultural and demographic issues and perceptions surrounding chronic diseases such as diabetes is required. Whether the strategies used in these two studies can be translated into a 'real world' scenario is doubtful. In practice, it is more than likely that a number of strategies will be needed to compliment the lifestyle approach. These will include pharmacological approaches with metformin, acarbose and other agents used to treat diabetes and its complications, currently under investigation. Longer-term follow-up studies will also clarify whether both lifestyle and pharmacological interventions actually prevent Type 2 diabetes, or merely delay its onset.