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Background: We investigated the association between glucose excursions and the dawn phenomenon, and the effects of oral-glucose lowering drugs on the dawn phenomenon in patients with type 2 diabetes (T2D). Methods: We conducted a post hoc analysis using data from a previous randomized trial. Patients with T2D on metformin monotherapy were randomized to receive add-on acarbose or glibenclamide for 16 weeks. Ambulatory continuous glucose monitoring (CGM) was conducted before randomization and at the end of the study. Using the CGM data, we assessed glucose excursions as indicated by mean amplitude of glycemic excursions (MAGE). The magnitude of the dawn phenomenon was calculated as the difference between the nocturnal nadir (0:00 to 6:00 a.m.) and prebreakfast glucose level. Results: A total of 50 patients with T2D [mean age 53.5 ± 8.2 years, mean glycated hemoglobin (HbA1c) 8.4 ± 1.2%] were analyzed. There was an independent association between MAGE and the dawn phenomenon [β coefficient 0.199, 95% confidence interval (CI) 0.074–0.325, p = 0.003]. HbA1c improved significantly after treatment with acarbose or glibenclamide. However, only treatment with acarbose significantly improved glucose excursions. The dawn phenomenon decreased significantly only in patients treated with acarbose (from 35.9 ± 15.7–28.3 ± 16.5 mg/dl, p = 0.037), but not in those treated with glibenclamide (from 35.9 ± 20.6–34.6 ± 17.0 mg/dl, p = 0.776). Conclusion: Glucose excursions were independently associated with the dawn phenomenon in patients with T2D on metformin monotherapy. Both glucose excursions and the dawn phenomenon improved after treatment with acarbose, but not after treatment with glibenclamide.

BACKGROUND Cyclophilin A plays a pathogenic role in the development and progression of atherosclerosis, which can be assessed by measuring carotid intima-media thickness. The primary aim of this study was to examine the interaction between plasma Cyclophilin A level and carotid intima-media thickness in patients with acute ischemic stroke. METHOD Plasma concentration of Cyclophilin A was measured on admission in 66 consecutive patients who had been hospitalized for acute cerebral stroke and in 52 case-control subjects without a history of acute stroke. Subjects in both groups also underwent ultrasound B-mode imaging to measure the mean and maximum intima-media thickness of the carotid artery. Inflammatory biomarkers including high-sensitivity C-reactive protein and fibrinogen were also assessed. RESULTS We found that the plasma concentration of Cyclophilin A was significantly higher in patients with acute ischemic stroke (p = 0.042). Increased Cyclophilin A was also correlated with carotid intima-media thickness in the patient group (p < 0.001). Among the risk factors for cerebral stroke examined in this study, only hypertension was significantly associated with plasma Cyclophilin A level. CONCLUSION Increased plasma Cyclophilin A levels might be involved in the pathophysiology of acute ischemic stroke and Cyclophilin A might serve as a biomarker in risk assessment of acute stroke patients.

Andrographolide is a potent anti-inflammatory agent found in Andrographis paniculata. Endothelin 1 (ET-1) is an endothelium-derived vasoconstrictor with pro-inflammatory properties secreted in response to hypoxia. Mitogen-activated protein kinase phosphatase 5 (MKP-5) is a dual-specificity phosphatase that dephosphorylates threonine and tyrosine residues of MAPKs. We showed previously that hypoxia-induced HIF-1α expression and ET-1 secretion are dependent on p38 MAPK in EA.hy926 cells. Here, we investigate what role MKP-5 plays in andrographolide's inhibition of hypoxia-induced expression of HIF-1α and ET-1. Hypoxic conditions were created using the hypoxia-mimetic agent CoCl2 . Andrographolide enhanced HO-1 and MKP-5 expression and cellular cGMP content in addition to inhibiting hypoxia-induced ROS generation. Concomitantly, the HO-1 byproduct CO and the cGMP analogue 8-bromoguanosine 3',5'-cyclic monophosphate (8-Br-cGMP) increased MKP-5 expression, and pretreatment with CO and 8-Br-cGMP inhibited hypoxia-induced HIF-1α and ET-1 expression. Transfection of HO-1 siRNA or pretreatment with the HO-1 inhibitor ZnPP-9 or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, a specific inhibitor of soluble guanylate cyclase, reduced andrographolide-induced MKP-5 expression. Moreover, silencing MKP-5 or treatment with the phosphatase inhibitor vanadate abrogated andrographolide's suppressing hypoxia-induced p38 MAPK activation and HIF-1α expression. The inhibition of hypoxia-induced HIF-1α and ET-1 expression by andrographolide is likely associated with HO-1/CO/cGMP/MKP-5 pathways, which is involved in inhibiting hypoxia-induced p38 MAPK activation.

Background/Purpose: Comprehensive and continuous care is crucial for patients with diabetes. The diabetes pay-for-performance (P4P) program launched by the National Health Insurance (NHI) administration in Taiwan provides a financial incentive to facilitate this goal. In this study, we explored the characteristics of patients in the P4P program between 2005 and 2014. Methods: Data of patients with diabetes enrolled in the NHI program between 2005 and 2014 were extracted from the NHI research database. Patients were classed as having diabetes if they had three or more outpatient visits within 365 calendar days with an International Classification of Diseases, 9th Revision, Clinical Modification diagnostic code of 250 or hospitalization one or more times with such a diagnosis. The trends of participating in the P4P program were analyzed. Results: Participation rate of the P4P program increased from 12.1% to 19% between 2005 and 2014. Participants were younger and more likely to be female than those not participating in the program. Lower risks of cancer-related mortality, annual mortality and heart failure were seen in patients participating in the P4P program than in those not participating. Conclusion: Older, male patients with a high disease severity may be less likely to enroll in the P4P program. Although participation rate is increasing, a broad enrollment is expected. Keywords: Diabetes, National health insurance, Pay-for-performance

Andrographolide, the main bioactive component of the medicinal plant Andrographis paniculata, has been shown to possess potent anti-inflammatory activity. Endothelin 1 (ET-1), a potent vasoconstrictor peptide produced by vascular endothelial cells, displays proinflammatory property. Hypoxia-inducible factor 1α (HIF-1α), the regulatory member of the transcription factor heterodimer HIF-1α/β, is one of the most important molecules that responds to hypoxia. Changes in cellular HIF-1α protein level are the result of altered gene transcription and protein stability, with the latter being dependent on prolyl hydroxylases (PHDs). In this study, inhibition of pro-inflammatory ET-1 expression and changes of HIF-1α gene transcription and protein stability under hypoxia by andrographolide in EA.hy926 endothelial-like cells were investigated. Hypoxic conditions were created using the hypoxia-mimetic agent CoCl2. We found that hypoxia stimulated the production of reactive oxygen species (ROS), the expression of HIF-1α mRNA and protein, and the expression and secretion of ET-1. These effects, however, were attenuated by co-exposure to andrographolide, bilirubin, and RuCO. Silencing Nrf2 and heme oxygenase 1 (HO-1) reversed the inhibitory effects of andrographolide on hypxoia-induced HIF-1α mRNA and protein expression. Moreover, andrographolide increased the expression of prolyl hydroxylases (PHD) 2/3, which hydroxylate HIF-1α and promotes HIF-1α proteasome degradation, with an increase in HIF-1α hydroxylation was noted under hypoxia. Inhibition of p38 MAPK abrogated the hypoxia-induced increases in HIF-1α mRNA and protein expression as well as ET-1 mRNA expression and secretion. Taken together, these results suggest that andrographolide suppresses hypoxia-induced pro-inflammatory ET-1 expression by activating Nrf2/HO-1, inhibiting p38 MAPK signaling, and promoting PHD2/3 expression. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 918-930, 2017.

Background The aim of the present study was to examine the association between glycemic excursions before treatment and HbA1c reduction after treatment intensification with acarbose or glibenclamide in patients with type 2 diabetes (T2D). Methods Patients receiving single or dual oral antidiabetic drug treatment with an HbA1c of 7.0–11.0 % (53–97 mmol/mol) were switched to metformin monotherapy (500 mg, t.i.d.) for 8 weeks, followed by randomization to either acarbose (100 mg, t.i.d.) or glibenclamide (5 mg, t.i.d.) as add-on treatment for 16 weeks. Glycemic excursions were assessed as mean amplitude of glycemic excursions (MAGE) with 72-h ambulatory continuous glucose monitoring. Treatment efficacy was evaluated as relative HbA1c reduction (%), calculated as (baseline HbA1c – post-treatment HbA1c)/baseline HbA1c × 100. Results Fifty patients (mean [±SD] age 53.5 ± 8.2 years, 48 % men, mean baseline HbA1c 8.4 ± 1.2 %) were analyzed. Baseline MAGE was positively correlated with relative HbA1c reduction from baseline in patients treated with acarbose (r = 0.421, P = 0.029) but not glibenclamide (r = 0.052, P = 0.813). Linear regression analysis revealed that the association between baseline MAGE and relative HbA1c reduction from baseline (β = 0.125, P = 0.029) in patients treated with acarbose remained significant after adjustment for several confounders (P

Aims Our aims were to investigate the prevalence of diabetes mellitus (DM) among patients with newly-diagnosed tuberculosis (TB) and to determine its associated factors in an Asian population. Methods The data were obtained from the National Health Insurance Research Database and included 9831 newly-diagnosed TB individuals in the period of 2000–2010. The data were divided into a DM group and a non-DM group. We measured the prevalence and the associated comorbidities of DM. Results During 2000–2010, the prevalence of DM progressively increased, with an average prevalence rate of 27.9%. The patients with ages of 55–64 years had the highest association of DM (OR = 3.53) compared with those under 45 years. TB patients with heart failure, ischemic heart disease, cerebral vascular disease, hypertension, dyslipidemia, chronic kidney disease, and liver disease were more likely to associate with DM (ORs = 1.27, 1.23, 1.30, 2.32, 3.26, 1.6, and 1.68, respectively) compared to those without the variables. Conclusions The prevalence of DM among TB patients in Taiwan was high and tended to increase in the past decade. Clinically, inquiring about DM history and screening routinely for those without DM history among TB patients should be carried out in Taiwan.

Probiotics have been reported to ameliorate symptoms of type 2 diabetes mellitus (T2DM) in animal models and human studies. We previously demonstrated that oral administration of Lactobacillus reuteri ADR-3 reduced insulin resistance in high-fructose-fed (HFD) rats. In the present study, we first identified another L. reuteri strain, ADR-1, which displayed anti-diabetes activity that reduced the levels of serum HbA1c and cholesterol and that increased antioxidant proteins in HFD rats. We further performed a randomized, double-blinded, placebo-controlled trial with a total of 68 T2DM patients to examine the beneficial effects of oral consumption of L. reuteri strains ADR-1 and ADR-3 and to investigate the associated changes in intestinal flora using a quantitative PCR method to analyze 16 S rRNA in fecal specimens. Significant reductions in HbA1c and serum cholesterol were observed in participants in the live ADR-1 consumption group (n = 22) after 3 months of intake when compared with those in the placebo group (n = 22). Although there was no significant difference in the HbA1c serum level among participants who consumed heat-killed ADR-3 (n = 24), the systolic blood pressure and mean blood pressure were significantly decreased after 6 months of intake. There was no obvious change in serum inflammatory cytokines or antioxidant proteins in participants after intaking ADR-1 or ADR-3, except for a reduction in IL-1β in the ADR-3 consumption group after 6 months of intake. With the analysis of fecal microflora, we found that L. reuteri or Bifidobacterium spp. were significantly increased in the ADR-1 and ADR-3 consumption groups, respectively, after 6 months of intake. Interestingly, a significant reduction in HbA1c was observed in the ADR-1 and ADR-3 consumption participants who displayed at least an 8-fold increase in fecal L. reuteri. We also observed that there was a significantly positive correlation between Bifidobacterium spp. and Lactobacillus spp. in participants with increased levels of fecal L. reuteri. In the ADR-1 intake group, the fecal Lactobacillus spp. level displayed a positive correlation with Bifidobacterium spp. but was negatively correlated with Bacteroidetes. The total level of fecal L. reuteri in participants in the ADR-3 consumption group was positively correlated with Firmicutes. In conclusion, L. reuteri strains ADR-1 and ADR-3 have beneficial effects on T2DM patients, and the consumption of different strains of L. reuteri may influence changes in intestinal flora, which may lead to different outcomes after probiotic intake.

To find the associations of circulating cyclophilin A (CyP A) and CD147/EMMPRIN with renal outcomes in type 2 diabetes patients and possible pathogenesis involved. Total 131 patients were recruited since 2004. Glycated hemoglobin, blood glucose and urine albumin-creatinine ratio levels at baseline and every 3 months were measured. Plasma CyP A and CD147 were also measured at baseline. Patients were divided into two groups based upon the median level of the baseline plasma CyP A value:93.64 ng/mL (group A, n = 65), ≥ 93.64 ng/mL (group B, n = 66). The estimated glomerular filtration rate was calculated at each follow-up visit. Besides, mitochondrial function assay by cellular mitochondrial energy utility was studied when cells were exposed to glucose or exogenous CyP A or both. Multivariate analysis, using median level (93.64) ng/mL as the cut-off value, revealed that circulating CyP A and CD147 levels at baseline were associated with the baseline estimated glomerular filtration rate (eGFR) (p = .042 and p = .001 separately) in cross-sectional analysis. Longitudinally, higher baseline plasma CyP A level was also correlated to a rapid decline in eGFR (p = .016). The results were also significant when using the continuous plasma CyP A level (p = .003). In cells exposed to glucose, results of oxygen consumption rate (OCR) showed a significant reduction in basal respiration, maximal respiration and ATP production. Depressed OCR further occurred when incubated with both of CyP A and glucose. Plasma CyP A and CD147 can serve as indicators of renal disease progression in type 2 diabetes patients.

Probiotics have been reported to ameliorate symptoms of type 2 diabetes mellitus (T2DM) in animal models and human studies. We previously demonstrated that oral administration of Lactobacillus reuteri ADR-3 reduced insulin resistance in high-fructose-fed (HFD) rats. In the present study, we first identified another L. reuteri strain, ADR-1, which displayed anti-diabetes activity that reduced the levels of serum HbA1c and cholesterol and that increased antioxidant proteins in HFD rats. We further performed a randomized, double-blinded, placebo-controlled trial with a total of 68 T2DM patients to examine the beneficial effects of oral consumption of L. reuteri strains ADR-1 and ADR-3 and to investigate the associated changes in intestinal flora using a quantitative PCR method to analyze 16 S rRNA in fecal specimens. Significant reductions in HbA1c and serum cholesterol were observed in participants in the live ADR-1 consumption group (n = 22) after 3 months of intake when compared with those in the placebo group (n = 22). Although there was no significant difference in the HbA1c serum level among participants who consumed heat-killed ADR-3 (n = 24), the systolic blood pressure and mean blood pressure were significantly decreased after 6 months of intake. There was no obvious change in serum inflammatory cytokines or antioxidant proteins in participants after intaking ADR-1 or ADR-3, except for a reduction in IL-1β in the ADR-3 consumption group after 6 months of intake. With the analysis of fecal microflora, we found that L. reuteri or Bifidobacterium spp. were significantly increased in the ADR-1 and ADR-3 consumption groups, respectively, after 6 months of intake. Interestingly, a significant reduction in HbA1c was observed in the ADR-1 and ADR-3 consumption participants who displayed at least an 8-fold increase in fecal L. reuteri. We also observed that there was a significantly positive correlation between Bifidobacterium spp. and Lactobacillus spp. in participants with increased levels of fecal L. reuteri. In the ADR-1 intake group, the fecal Lactobacillus spp. level displayed a positive correlation with Bifidobacterium spp. but was negatively correlated with Bacteroidetes. The total level of fecal L. reuteri in participants in the ADR-3 consumption group was positively correlated with Firmicutes. In conclusion, L. reuteri strains ADR-1 and ADR-3 have beneficial effects on T2DM patients, and the consumption of different strains of L. reuteri may influence changes in intestinal flora, which may lead to different outcomes after probiotic intake.

Aim The aim of this study was to examine the association between glycemic excursions and duration of hypoglycemia after treatment intensification in patients with type 2 diabetes (T2D). Methods Patients with T2D on oral anti-diabetes drug (OAD) with glycated hemoglobin (HbA1c) of 7.0–11.0% were switched to metformin monotherapy (500mg thrice daily) for 8 weeks, followed by randomization to either glibenclamide or acarbose as add-on treatment for 16 weeks. Glycemic excursions were assessed as mean amplitude of glycemic excursions (MAGE) with 72-h ambulatory continuous glucose monitoring (CGM) before randomization and at the end of study. Hypoglycemia was defined as sensor glucose level of less than 60mg/dl in two or more consecutive readings from CGM. Results A total of 50 patients (mean age 53.5±8.2 years, male 48%, mean baseline HbA1c 8.4±1.2%) were analyzed. Duration of hypoglycemia significantly increased after treatment with glibenclamide (from 5.5±13.8 to 18.8±35.8min/day, p =0.041), but not with acarbose (from 2.9±10.9 to 14.7±41.9min/day, p =0.114). Post treatment MAGE was positively associated with change from baseline in duration of hypoglycemia after treatment with either glibenclamide ( β coefficient 0.345, p =0.036) or acarbose ( β coefficient 0.674, p =0.046). The association remained significant after multivariate adjustment ( p Conclusions Post treatment glycemic excursions are associated with changes in duration of hypoglycemia after treatment intensification with OAD in patients with T2D. Glycemic excursions should be an important treatment target for T2D to reduce the risk of hypoglycemia.

Vascular cytokines, total nitrite, and cyclophilin-A (CyP-A) may be related to the pathogenesis of untreated hypertension. Forty males with normotensive and untreated essential hypertension were recruited in this cytokines survey. Body mass index (BMI), hyperlipidemia, and plasma CyP-A were increased in the hypertensive group (p

Increased intercellular reactive oxygen species (ROS) levels are the major cause of podocyte injury with proteinuria. Caveolin‑1 (CAV‑1) is an essential protein component of caveolae. CAV‑1 participates in signal transduction and endocytic trafficking. Recent research has indicated that CAV‑1 regulates oxidative stress‑induced pathways. The present study used hydrogen peroxide (H2O2) at nontoxic concentrations to elevate the level of ROS in E11 podocytes. Treatment with 500 and 1,000 µM H2O2 for 1 h significantly reduced CAV‑1 expression levels. Simultaneously, the treatment significantly reduced the expression of the antioxidant enzymes glutamine‑cysteine ligase catalytic subunit, superoxide dismutase 2 and catalase. To determine the role of CAV‑1 in mediating oxidative stress, E11 podocytes were administered antenapedia‑CAV‑1 (AP‑CAV‑1) peptide for 48 h. The AP‑CAV‑1 treatment enhanced CAV‑1 expression and inhibited cyclophilin A expression, thus reducing ROS‑induced inflammation. Moreover, CAV‑1 protected against H2O2‑induced oxidative stress responses by enhancing the expression of antioxidant enzymes. Furthermore, CAV‑1 attenuated H2O2‑induced changes oxidative phosphorylation, and the expression of optic atrophy 1 and translocase of the inner membrane 23, as well as preserving mitochondrial function. CAV‑1 treatment significantly suppressed apoptosis, as indicated by a higher B‑cell lymphoma 2/BCL2‑associated X protein ratio. Therefore, enhancing the expression of CAV‑1 may be an important therapeutic consideration in treating podocyte injury.

Far infrared radiation (FIR) is currently investigated as a potential therapeutic strategy in various diseases though the mechanism is unknown. Presently, we tested if FIR mediates beneficial effects in a cell model of the neurodegenerative disease spinocerebellar ataxia type 3 (SCA3). SCA3 is caused by a mutation leading to an abnormal polyglutamine expansion (PolyQ) in ataxin-3 protein. The consequent aggregation of mutant ataxin-3 results in disruption of vital cell functions. In this study, neuroblastoma cells (SK-N-SH) was transduced to express either non-pathogenic ataxin-3-26Q or pathogenic ataxin-3-78Q proteins. The cells expressing ataxin-3-78Q demonstrated decreased viability and increased sensitivity to metabolic stress in the presence rotenone, an inhibitor of mitochondrial respiration. FIR exposure was found to protect against these effects. Moreover, FIR improved mitochondrial respiratory function, which was significantly compromised in ataxin-3-78Q and ataxin-3-26Q expressing cells. This was accompanied by decreased levels of mitochondrial fragmentation in FIR treated cells, as observed by fluorescence microscopy and protein expression analysis. Finally, the expression profile LC3-II, Beclin-1 and p62 suggested that FIR prevent the autophagy inhibiting effects observed in ataxin-3-78Q expressing cells. In summary, our results suggest that FIR have rescuing effects in cells expressing mutated pathogenic ataxin-3, through recovery of mitochondrial function and autophagy.

Andrographolide, the main bioactive component of the medicinal plant Andrographis paniculata, has been shown to possess potent anti-inflammatory activity. Endothelin 1 (ET-1), a potent vasoconstrictor peptide produced by vascular endothelial cells, displays proinflammatory property. Hypoxia-inducible factor 1α (HIF-1α), the regulatory member of the transcription factor heterodimer HIF-1α/β, is one of the most important molecules that responds to hypoxia. Changes in cellular HIF-1α protein level are the result of altered gene transcription and protein stability, with the latter being dependent on prolyl hydroxylases (PHDs). In this study, inhibition of pro-inflammatory ET-1 expression and changes of HIF-1α gene transcription and protein stability under hypoxia by andrographolide in EA.hy926 endothelial-like cells were investigated. Hypoxic conditions were created using the hypoxia-mimetic agent CoCl

Granulocyte colony-stimulating factor (G-CSF) may protect ischemic brain injury either in animal or human. No studies have reported that endogenous G-CSF (enG-CSF) level is related to the severity of ischemic stroke. This study was designed to assess the severity of ischemic patients correlated with the alteration of enG-CSF on the 1st day after an ischemic event. Patient's plasma enG-CSF and scoring of National Institute of Health Stroke Scale were measured on the 1st day after ischemic stroke. The acute ischemic stroke could significantly induce enG-GCF secretion as compared with healthy control group (16.77 vs. 22.86 μg/L, p = 0.001). Elevated enG-CSF concentration was positively correlated with the severity of stroke patients on day 1 after the event (p = 0.006; Spearman correlation coefficient = 0.268). The enG-CSF is a good biomarker for prediction of severity of acute ischemic stroke.

Flavonoids exhibit chemopreventive and chemotherapeutic effects. Butein, a bioactive flavonoid isolated from numerous native plants, has been shown to induce apoptosis in human cancer cells. In the current study, the molecular mechanisms of butein action on cell proliferation and apoptosis of neuroblastoma cells were evaluated. Treatment with butein decreased the viability of Neuro-2A neuroblastoma cells in a dose- and time-dependent manner. The dose-dependent nature of butein-induced apoptosis was characterized by an increase in the sub-G1 phase population. Treatment with butein significantly increased intracellular reactive oxygen species (ROS)levels and reduced the Bcl-2/Bax ratio, triggering the cleavage of pro-caspase 3 and poly-(ADP-ribose) polymerase (PARP). Pre-treatment with the antioxidant agent, N-acetyl cysteine (NAC), blocks butein-induced ROS generation and cell death. NAC also recovers butein-induced apoptosis-related protein alteration. In conclusion, butein-triggered neuroblastoma cells undergo apoptosis via generation of ROS, alteration of the Bcl-2/Bax ratio, and cleavage of pro-caspase 3 and PARP. Our results suggest that butein may serve as a potential therapeutic agent for the treatment of neuroblastoma.

Although sulfonylurea added to metformin is the first oral drug combination regimen for patients with type 2 diabetes recommended by the American Diabetes Association/European Association for the Study of Diabetes consensus statement, it does not allow for individualizing and optimizing therapy with respect to sustaining glycemic control and the reduction of glucose variability. We therefore sought to investigate acarbose as an alternative to glibenclamide in combination with metformin and compare the effects on metabolic control and glucose variability.Type 2 diabetic patients 30-70 years of age with glycosylated hemoglobin 7.0%-11.0% while treated with one or two oral antidiabetic drugs were successively enrolled. After 8 weeks of run-in with metformin 500 mg thrice daily, either acarbose 50 mg or glibenclamide 2.5 mg three times daily was randomly added on and force titrated to acarbose 100 mg or glibenclamide 5.0 mg three times daily for the subsequent 16 weeks. Demographic data, biochemical data and continuous glucose monitoring system data were recorded upon randomization and at the end of the study. Various parameters that measure glucose variability were derived from the continuous glucose monitoring system data.Of the 51 type 2 diabetes patients enrolled, data from 40 subjects, 20 in each group, were analyzed after excluding those unqualified information. Both drug combinations improved glycemic control. Glucose variability, expressed as mean amplitude of glycemic excursion or continuous overall net glycemic action and mean of daily differences, decreased significantly (all P.05) after the addition of acarbose but not glibenclamide. The acarbose-metformin combination has the additional benefits of weight reduction and shorter durations of hyperglycemia compared with metformin monotherapy.This study suggests that both intraday and interday glucose variability are more effectively reduced by the acarbose-metformin combination than by the glibenclamide-metformin combination, while both combinations reduce the overall glucose level equally.

Statins are among the most widely used drugs in the management of hypercholesterolemia. In addition to inhibiting endogenous cholesterol synthesis, however, statins decrease coenzyme Q10 (CoQ10) synthesis. CoQ10 has been reported to have antioxidant properties, and administration of drugs that decrease CoQ10 synthesis might lead to increased oxidative stress in vivo. Our present study examined the hypothesis that atorvastatin increased oxidative stress in hypercholesterolemic patients due to its inhibition of CoQ10 synthesis. We investigated the effects of atorvastatin (10 mg/ d) administration for 5 months on lowering hypercholesterolemia and blood antioxidant status. The study population included 19 hypercholesterolemic outpatients. Blood levels of lipid and antioxidant markers, consisting of vitamin C, vitamin E, CoQ10, and glutathione (GSH), and urinary levels of 8hydroxy-2′-deoxyguanosine (8-OHdG) were examined pre- and postadministration of atorvastatin. Atorvastatin administration resulted in a significant decrease in blood levels of total cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol, vitamin E, and CoQ10 (P b .05); however, a significant increase in the ratios of vitamin E/LDL cholesterol and CoQ10/LDL cholesterol was noted (P b .05). Atorvastatin had no significant effect on red blood cell (RBC) level of GSH and urinary 8-OHdG. The present study provides evidence that atorvastatin exerts a hypocholesterolemic effect, but on the basis of the urinary level of 8-OHdG and the blood ratios of vitamin E/LDL cholesterol and CoQ10/LDL cholesterol, has no oxidative stress-inducing effect. © 2010 Published by Elsevier Inc.

Supplemental Digital Content is available in the text, No study has evaluated whether subnormal estimated glomerular filtration rate (eGFR) (between 61 and 90 mL/min) and high normal albumin–creatinine ratio (ACR) (

The aim of the present study was to examine the association between glycemic excursions before treatment and HbA1c reduction after treatment intensification with acarbose or glibenclamide in patients with type 2 diabetes (T2D).Patients receiving single or dual oral antidiabetic drug treatment with an HbA1c of 7.0-11.0 % (53-97 mmol/mol) were switched to metformin monotherapy (500 mg, t.i.d.) for 8 weeks, followed by randomization to either acarbose (100 mg, t.i.d.) or glibenclamide (5 mg, t.i.d.) as add-on treatment for 16 weeks. Glycemic excursions were assessed as mean amplitude of glycemic excursions (MAGE) with 72-h ambulatory continuous glucose monitoring. Treatment efficacy was evaluated as relative HbA1c reduction (%), calculated as (baseline HbA1c - post-treatment HbA1c)/baseline HbA1c × 100.Fifty patients (mean [±SD] age 53.5 ± 8.2 years, 48 % men, mean baseline HbA1c 8.4 ± 1.2 %) were analyzed. Baseline MAGE was positively correlated with relative HbA1c reduction from baseline in patients treated with acarbose (r = 0.421, P = 0.029) but not glibenclamide (r = 0.052, P = 0.813). Linear regression analysis revealed that the association between baseline MAGE and relative HbA1c reduction from baseline (β = 0.125, P = 0.029) in patients treated with acarbose remained significant after adjustment for several confounders (P 0.05 for all models).In patients with T2D on metformin monotherapy, baseline MAGE was positively correlated with relative HbA1c reduction from baseline after treatment with acarbose, but not glibenclamide. These findings highlight the importance of glycemic excursions in individualized treatment for patients with T2D.

Background This study aimed to explore parameters which will predict good control of HbA1c after adding a second anti-diabetic drug in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin monotherapy. Methods Fifty-one patients (M/F: 25/26, mean age: 53.7 ± 8.2 years, mean glycated hemoglobin [HbA1c] 8.4 ± 1.2%) with T2DM inadequately controlled with metformin were randomized to add-on glibenclamide or acarbose for 16 weeks. Before and after combination therapy, the subjects underwent a 2-hour liquid mixed meal tolerance test to determine insulin secretion (HOMA-β, insulinogenic index, and disposition index [DI]) and insulin sensitivity (HOMA-IR and Matsuda insulin sensitivity index). Results At baseline, there was a significant inverse relationship between DI120 and HbA1c (p = 0.001) in all subjects. The addition of glibenclamide and acarbose improved HbA1c significantly from 8.6 ± 1.6% to 7.4 ± 1.2% (p

Glycemic excursion is significantly associated with oxidative stress, which plays a role in the development of chronic complications in type 2 diabetes mellitus (T2DM). Acarbose has been reported to reduce cardiovascular risk in patients with impaired glucose tolerance and T2DM. We hypothesize that treatment with acarbose could attenuate glycemic excursions and reduce oxidative stress in patients with T2DM.This study aimed to evaluate the effects of acarbose versus glibenclamide on mean amplitude of glycemic excursions (MAGE) and oxidative stress in patients with T2DM who are insufficiently controlled by metformin.T2DM outpatients aged 30 to 70 years who were taking single or dual oral antidiabetic drugs for ≥3 months and had a glycosylated hemoglobin (HbA(1c)) value between 7.0% and 11.0% were eligible. Patients were treated with metformin monotherapy (1500 mg daily) for 8 weeks, followed by randomization to either acarbose or glibenclamide add-on for 16 weeks. The dosage of acarbose and glibenclamide was 50 mg TID and 2.5 mg TID, respectively, for the first 4 weeks. In the following 12 weeks, the dosage was doubled in both groups. Continuous glucose monitoring (CGM) for 72 hours and a meal tolerance test (MTT) after a 10-hour overnight fast were conducted before randomization and at the end of study. MAGE was calculated from CGM data. β-cell response to postprandial glucose increments was assessed by the ratio between incremental AUC of insulin and glucose during MTT. Oxidative stress was estimated by plasma oxidized LDL (ox-LDL) and urinary excretion rates of 8-iso prostaglandin F(2α) (8-iso PGF(2α)). The primary outcomes included changes in MAGE, plasma ox-LDL, and urinary excretion of 8-iso PGF(2α). Adverse events, including hypoglycemia, were recorded.A total of 55 patients were randomized (mean age, 54 years; males, 47%; mean body mass index, 25.9 kg/m(2); mean duration of diabetes, 6.9 years; mean HbA(1c), 8.3%) and 51 patients completed this study (acarbose, n = 28; glibenclamide, n = 23). HbA(1c) decreased significantly in both treatment groups (acarbose: 8.2 [0.8]% to 7.5 [0.8]% [P0.001]; glibenclamide: 8.6 [1.6]% to 7.4 [1.2]% [P0.001]). MAGE did not change significantly in glibenclamide-treated patients (6.2 [2.8] mmol/L to 6.3 [2.3] mmol/L; P = 0.82), whereas ox-LDL (242.4 [180.9] ng/mL to 470.7 [247.3] ng/mL; P = 0.004) and urinary excretion of 8-iso PGF(2α) (121.6 [39.6] pmol/mmol creatinine to 152.5 [41.8] pmol/mmol creatinine; P = 0.03) increased significantly. Acarbose decreased MAGE (5.6 [1.5] mmol/L to 4.0 [1.4] mmol/L; P0.001) without significant change in ox-LDL levels (254.4 [269.1] ng/mL to 298.5 [249.8) ng/mL; P = 0.62) or 8-iso PGF(2α) excretion rates (117.9 [58.1] pmol/mmol creatinine to 137.8 [64.4] pmol/mmol creatinine; P = 0.12). Body weight and serum triglycerides (fasting and 2-hour postprandial) decreased (all, P0.01) and serum adiponectin increased (P0.05) after treatment with acarbose, whereas HDL-C decreased (P0.01) after treatment with glibenclamide. β-cell response to postprandial glucose increments was negatively correlated with MAGE (r = 0.570, P0.001) and improved significantly with acarbose (35.6 [32.2] pmol/mmol to 56.4 [43.7] pmol/mmol; P = 0.001) but not with glibenclamide (27.9 [17.6] pmol/mmol to 36.5 [24.2] pmol/mmol; P = 0.12).In this select population of adult Taiwanese patients with T2DM who were inadequately controlled by metformin, add-on acarbose or glibenclamide significantly reduced HbA(1c). However, treatment with acarbose decreased MAGE, body weight, and serum triglyceride and increased serum adiponectin without significant effect on oxidative stress. Treatment with glibenclamide had no statistically significant effect on MAGE but increased oxidative stress and decreased HDL-C. ClinicalTrials.gov identifier: NCT00417729.

Aims: Metabolic syndrome (MetS) is characterized by a group of defects of metabolic origin which are possibly involved in mitochondrial DNA (mtDNA) alteration of mtDNA content [Lee et al. Exp Biol Med, 2007; 232(5):592-606]. The present study was undertaken to ascertain whether alteration of leukocyte mtDNA copy number is related to MetS.Methods: Eighty non-MetS subjects and 50 subjects with MetS were recruited. The mtDNA copy number of leukocytes from each group of subjects was measured using quantitative polymerase chain reaction.Results: The mtDNA copy number of leukocytes in subjects with MetS was significantly lower than that of non-MetS subjects. Depleted mtDNA copy number is correlated with lower plasma HDL, higher triglyceride, higher HOMA-IR and hypertension, and is even more sensitive to MetS criteria.Conclusions: Depleted leukocyte mtDNA copy number is related to the severity of MetS. Alteration of mtDNA copy number in leukocytes is proposed as a MetS biomarker involved in the bioenergetic change of mitochondria.

Usually to finish a complicated task often requires different fields of professionals to contribute his knowledge because no one has the complete knowledge of the task. And if the knowledge is sharing by web pages in internet, users need to visit these pages one by one to grab piece of knowledge we needed on the pages and then integrate it manually. This approach takes lots of effort in searching, retrieving and integrating knowledge. To overcome this issue, we propose an approach to do this task. We first represent knowledge by some ontologies in internet and each of them represents a subdomain knowledge respectively, and then we integrate it through a web service platform. Sharing ontology in internet based on web service provides a simple and flexible manner for knowledge sharing, retrieval and integration. To demonstrate the feasibility of our approach, we use diabetes care as an example to use this system because it needs different professionals to make up a care plan. The result of our research shows, our system can retrieve and integrate diabetes care suggestion from related ontology in internet according to patient's condition. Thus It can reduce the consumption of medical resources while provide consistent care quality at the same time.

Because of changing in lifestyle and diet, and lacking of moderate exercise, diabetes prevalence increases rapidly. Diabetes is an incurable chronic disease, but through proper care, patients can control the disease and prevent complications. According to patient's personal need, a proper diabetes care plan requires different fields of professionals together to make up the plan. So if it is done manually, it would restrict to the experience and knowledge of these professionals, and consume lots of expensive medical resources as well. The main purpose of this research is to use artificial intelligence techniques to generate personalized diabetes care plan. To do that, we first use case-based reasoning to search matched diabetes care plan in our case database according to personal condition and similarity function. The matched plan can be used directly or further modify it to better fit current problem. The modified case is saved in our case database for next time usage. The expansion of case database makes the system can propose care plan more in line with user requirement later. When there is no matched case, embedded in our system is a diabetes care ontology which can be consulted. The ontology generated a basic care plan to care professionals for adjustment. Again, this adjusted plan becomes the new case and the system deposits it in case database. The result of our research shows our system can provide personalized diabetes care plan efficiently. In the future, this system can be expanded to other diseases care and eventually becomes a total diseases care decision support system.

BACKGROUND previous studies examining the contributions of fasting glucose (FG) and postprandial glucose (PPG) to glycated haemoglobin (HbA(1c)) have yielded conflicting results. We aimed to clarify the contributions of PPG to hyperglycaemia in Asian type 2 diabetic patients using continuous glucose monitoring. METHODS continuous glucose monitoring was conducted in 121 non-insulin-using type 2 diabetic outpatients, who were divided into five groups according to quintiles of HbA(1c) (ranging from 5.7 to 12.7%). Glucose area under the curve (AUC) above a glucose value of 5.5 mmol/L 24 or 4 h after meals was defined as AUC(total). Glucose AUC above FG or preprandial glucose levels was defined as AUC(PPG). The contribution of PPG to hyperglycaemia was calculated as (AUC(PPG)/AUC(total) × 100%. The contribution of FG or preprandial glucose was calculated as [(AUC(total) - AUC(PPG))/AUC(total)] × 100%. RESULTS the contribution of PPG to either 24-h hyperglycaemia or 4-h hyperglycaemia after meals was significantly higher than FG and preprandial glucose in the lowest quintile of HbA(1c) (both p < 0.001). However, no difference was observed in the other four quintiles. Peak PPG and glucose excursions were higher after breakfast than those after lunch and dinner (p < 0.01 for all comparisons). CONCLUSIONS in Asian patients with type 2 diabetes, PPG 24 and 4 h after meals was a predominant contributor to excess hyperglycaemia in well-controlled patients and was equally important as FG or preprandial glucose in moderately to poorly controlled patients with mean HbA(1c) up to 10%.

Background: The benefits of insulin pump therapy on the metabolic control of both type 1 and type 2 diabetes have been reported. Such reports have prompted our interest to investigate the long-term metabolic effects of insulin pump therapy at our institution. Methods: We retrospectively analyzed the management of type 1 and type 2 diabetic patients who began extended insulin pump therapy at Changhua Christian Hospital between November 2004 and October 2007. One-way ANOVA and post hoc analysis were used to compare baseline glycosylated hemoglobin (HbA1C) values with subsequent values. Results: We studied 12 patients who were on continuous subcutaneous insulin infusion (CSII) therapy at the time of data collection. Mean duration of CSII therapy was 2.3 years. A reduction in HbA1C was found after administering CSII, which was sustained after 1, 2 and 3 years of therapy (7.0%, 6.7% and 6.6%, respectively), with statistical significance (p < 0.05). No incidence of severe hypoglycemia or diabetic ketoacidosis occurred during the treatment period. Conclusion: Our preliminary experience demonstrated the effectiveness of insulin pump therapy for both type 1 and type 2 diabetic patients. The reduction in their HbA1C values was both statistically and clinically significant. This treatment should be considered for patients poorly controlled by subcutaneous insulin injection therapy. [J Chin Med Assoc 2008; 71(7):353–356]

We report the case of a young woman with Sheehan's syndrome who presented with ventricular arrhythmia and congestive heart failure. The patient was admitted because of postpartum hemorrhage and hypovolemic shock; a massive blood transfusion was required to restore blood volume. After initial stabilization, the patient developed acute respiratory distress and congestive heart failure accompanied by hemodynamic instability 2 weeks after delivery. Episodes of ventricular tachycardia of the torsade de pointes type and a prolonged QT interval were noted on baseline electrocardiogram. A low cortisol level was found incidentally, which led to the suspicion of hypopituitarism. The diagnosis was later supported by laboratory findings of multiple pituitary hormone deficiencies. After administration of corticosteroids and thyroxine, the patient's clinical condition improved dramatically. A pituitary magnetic resonance imaging scan 32 days after delivery revealed a diminished and flattened pituitary gland with prominent intrasellar cerebrospinal fluid loculation, which was compatible with the clinical diagnosis of empty sella with panhypopituitarism. The syndrome of acute anterior pituitary necrosis secondary to postpartum hemorrhage and shock was first described by Sheehan in 1939. Although the occurrence of Sheehan's syndrome is now rare, it should still be considered in any woman with a history of peripartum hemorrhage who develops manifestations of pituitary hormone deficiency. Appropriate hormone replacement therapy is essential and always results in dramatic clinical improvement.