Predictors and Impact of Sulcal SAH after Mechanical Thrombectomy in Patients with Isolated M2 Occlusion.

BACKGROUND AND PURPOSE: Data on SAH after M2 mechanical thrombectomy are limited. We aimed to determine the prevalence of sulcal SAH after mechanical thrombectomy for M2 occlusion, its associated predictors, and the resulting clinical outcome. MATERIALS AND METHODS: The study retrospectively reviewed the data of patients with acute ischemic stroke who underwent mechanical thrombectomy for isolated M2 occlusion. The patients were divided into 2 groups according to the presence of sulcal SAH after M2 mechanical thrombectomy. Angiographic and clinical outcomes were compared. Multivariable analysis was performed to identify independent predictors of sulcal SAH and unfavorable outcome (90-day mRS, 3-6). RESULTS: Of the 209 enrolled patients, sulcal SAH was observed in 33 (15.8%) patients. The sulcal SAH group showed a higher rate of distal M2 occlusion (69.7% versus 22.7%), a higher of rate of superior division occlusion (63.6% versus 43.8%), and a higher M2 angulation (median, 128° versus 106°) than the non-sulcal SAH group. Of the 33 sulcal SAH cases, 23 (66.7%) were covert without visible intraprocedural contrast extravasation. Distal M2 occlusion (OR, 12.04; 95% CI, 4.56-35.67; P < .001), superior division (OR, 3.83; 95% CI, 1.43-11.26; P = .010), M2 angulation (OR, 1.02; 95% CI, 1.01-1.04; P < .001), and the number of passes (OR, 1.58; 95% CI, 1.22-2.09; P < .001) were independent predictors of sulcal SAH. However, covert sulcal SAH was not associated with an unfavorable outcome (P = .830). CONCLUSIONS: After mechanical thrombectomy for M2 occlusion, sulcal SAH was not uncommon and occurred more frequently with distal M2 occlusion, superior division, acute M2 angulation, and multiple thrombectomy passes (≥3). The impact of covert sulcal SAH was mostly benign and was not associated with an unfavorable outcome.

Local Intra-arterial Thrombolysis during Mechanical Thrombectomy for Refractory Large-Vessel Occlusion: Adjunctive Chemical Enhancer of Thrombectomy.

BACKGROUND AND PURPOSE: Data on adjunctive intra-arterial thrombolysis during mechanical thrombectomy for refractory thrombus are sparse. The aim of this study was to evaluate the efficacy and safety of local intra-arterial urokinase as an adjunct to mechanical thrombectomy for refractory large-vessel occlusion. MATERIALS AND METHODS: We retrospectively evaluated patients with acute ischemic stroke who underwent mechanical thrombectomy for anterior circulation large-vessel occlusion between January 2016 and December 2019. Patients were divided into 2 groups based on the use of intra-arterial urokinase as an adjunctive therapy during mechanical thrombectomy for refractory thrombus: the urokinase and nonurokinase groups. Herein, refractory thrombus was defined as the target occlusion with minimal reperfusion (TICI 0 or 1) despite >3 attempts with conventional mechanical thrombectomy. The baseline characteristics, procedural outcomes, and clinical outcome were compared between the 2 groups. RESULTS: One hundred fourteen cases of refractory thrombus were identified. A total of 45 and 69 patients were in the urokinase and the nonurokinase groups, respectively. The urokinase group compared with the nonurokinase group showed a higher rate of successful reperfusion (82.2% versus 63.8%, P = .034), with lower procedural times (54 versus 69 minutes, P = .137). The rates of good clinical outcome, distal embolism, and symptomatic intracranial hemorrhage were similar between the 2 groups. The use of intra-arterial urokinase (OR = 3.682; 95% CI, 1.156-11.730; P = .027) was an independent predictor of successful reperfusion. CONCLUSIONS: The use of local intra-arterial urokinase as an adjunct to mechanical thrombectomy may be an effective and safe method that provides better recanalization than the conventional mechanical thrombectomy for refractory thrombus in patients with embolic large-vessel occlusion.

Clot Meniscus Sign: An Angiographic Clue for Choosing between Stent Retriever and Contact Aspiration in Acute Basilar Artery Occlusion.

BACKGROUND AND PURPOSE: The efficacy of mechanical thrombectomy methods may differ depending on the characteristics of the occlusion. The purpose of this study was to compare the recanalization efficacy and treatment outcome of a stent retriever versus contact aspiration in patients with acute basilar artery occlusion according to the angiographic characteristics of the occlusion. MATERIALS AND METHODS: One hundred sixty-one patients with acute basilar artery occlusion who underwent mechanical thrombectomy were retrospectively analyzed. A stent retriever was compared with contact aspiration thrombectomy according to the clot meniscus sign, defined as a meniscoid/tram-track-like sidewall contrast opacification of the thrombus. A propensity score matching analysis was performed. Clinical/angiographic characteristics and treatment and clinical outcomes were compared. RESULTS: Overall, a stent retriever (n = 118) and contact aspiration (n = 43) did not show significant differences in the successful recanalization (82.2% versus 86.0%) and good clinical outcome rates (32.2% versus 39.5%). In patients with the positive meniscus sign, contact aspiration was associated with shorter procedural time (44 versus 26 minutes, P = .018), a lower number of passes (2 versus 1, P = .041), a higher complete recanalization rate (58.8% versus 85.7%, P = .021), and a higher rate of first-pass effect (27.9% versus 53.6%, P = .031) compared with a stent retriever. After propensity score matching, contact aspiration was associated with higher complete recanalization rates (59.3% versus 85.7%, P = .033). No significant differences in the outcomes were noted between a stent retriever and contact aspiration in patients negative for the meniscus sign. CONCLUSIONS: The efficacy of the mechanical thrombectomy techniques may differ according to the angiographic characteristics of occlusion in patients with basilar artery occlusion. Contact aspiration may be more effective in terms of recanalization compared with a stent retriever in patients with the clot meniscus sign.

Fasting plasma glucose variability in midlife and risk of Parkinson's disease: A nationwide population-based study.

AIM: Despite the recognized association between type 2 diabetes (T2D) and Parkinson's disease (PD), the implications of glycaemic variability for patients with PD are as yet unknown. For this reason, our study assessed the future risk of incident PD according to visit-to-visit fasting plasma glucose (FPG) variability, as calculated by standard deviation (FPG-SD), coefficient variance (FPG-CV) and variability independent of the mean (FPG-VIM). METHODS: Using the Korean National Health Insurance Service Health Screening Cohort, 131,625 Korean adults without diabetes were followed. They were divided into a midlife group (age<65 years) and an elderly group (age≥65 years) throughout a median follow-up of 8.4 years. RESULTS: Adjusted hazard ratios (HRs) were calculated using multivariable Cox proportional-hazards analysis. In the midlife group, HRs for incident PD in the highest quartile of FPG variability (as measured by SD, CV and VIM) were 1.37 [95% confidence interval (CI): 1.09-1.73], 1.33 (95% CI: 1.06-1.68) and 1.35 (95% CI: 1.07-1.70), respectively, vs the lowest variability quartile group. However, while incident PD did not differ according to FPG variability in the elderly group, Kaplan-Meier curves of PD probability in the midlife group showed a progressively increasing risk of PD the higher the FPG variability. According to a multivariable adjusted model, every 1-SD unit increment in glycaemic variability was associated with a 9% higher risk of incident PD in the midlife group. CONCLUSION: Increased long-term glycaemic variability may be a precipitating risk factor for developing PD in the midlife population without diabetes.

MRI-Based Assessment of the Pharyngeal Constrictor Muscle as a Predictor of Surgical Margin after Transoral Robotic Surgery in HPV-Positive Tonsillar Cancer.

BACKGROUND AND PURPOSE: Transoral robotic surgery is an emerging strategy for treating human papillomavirus-positive cancers, but the role of MR imaging in predicting the surgical outcome has not been established. We aimed to identify preoperative MR imaging characteristics that predispose the outcome of transoral robotic surgery toward an insecure (positive or close) surgical margin in human papillomavirus-positive tonsillar squamous cell carcinoma. MATERIALS AND METHODS: Between December 2012 and May 2019, sixty-nine patients underwent transoral robotic surgery at our institution. Among these, 29 who were diagnosed with human papillomavirus-positive tonsillar squamous cell carcinoma, did not receive neoadjuvant treatment, underwent preoperative 3T MR imaging, and had postoperative pathologic reports and were included in this retrospective study. Two neuroradiologists evaluated the preoperative MR imaging scans to determine the tumor spread through the pharyngeal constrictor muscle using a 5-point scale: 1, normal constrictor; 2, bulging constrictor; 3, thinning constrictor; 4, obscured constrictor; and 5, tumor protrusion into the parapharyngeal fat. The risk of an insecure surgical margin (involved or <1 mm) according to the MR imaging scores was predicted using logistic regression with the Firth correction. RESULTS: The interobserver agreement for the MR imaging scores was excellent (κ = 0.955, P < .001). A score of ≥4 could predict an insecure margin with 87.5% sensitivity and 92.3% specificity (area under the curve = 0.899) and was the only significant factor associated with an insecure margin in the multivariable analysis (OR, 6.59; 95% CI, 3.11-22.28; P < .001). CONCLUSIONS: The pre-transoral robotic surgery MR imaging scoring system for the pharyngeal constrictor muscle is a promising predictor of the surgical margin in human papillomavirus-positive tonsillar squamous cell carcinoma.

Dipeptidyl peptidase-4 inhibitor use and risk of diabetic retinopathy: A population-based study.

AIMS: This study examined whether dipeptidyl peptidase (DPP)-4 inhibitor use is beneficial or harmful to diabetic retinopathy (DR) compared with other glucose-lowering agents in patients with type 2 diabetes (T2D). METHODS: From a population-based cohort provided by the National Health Insurance Service in Korea, 67,743 adults with T2D were identified as having been treated with oral glucose-lowering agents between 2008 and 2013. Matching (1:1) was performed for two groups comparing ever-use (cases) and never-use (controls) of DPP-4 inhibitors (n=14,522 in each group). Cox regression analyses were used to assess risk of the following DR events: vitreous haemorrhage; vitrectomy or photocoagulation; intravitreal agent use; and blindness. RESULTS: During a median follow-up of 28.4 (14.0-45.2) months, there were 305 (in controls) and 342 (in cases) composite DR events. DPP-4 inhibitor ever-use was not associated with overall risk of composite DR events [adjusted hazard ratio (HR): 1.08, 95% CI: 0.93-1.26] compared with never-use, nor was the risk of each DR outcome increased with DPP-4 inhibitor therapy either. However, DPP-4 inhibitor administration for<12 months was associated with a greater risk of composite DR events (adjusted HR: 1.31, 95% CI: 1.09-1.57) compared with other glucose-lowering agents over the same treatment period. CONCLUSION: In comparison to other oral glucose-lowering agents, DPP-4 inhibitor treatment did not increase overall risk of DR. However, DPP-4 inhibitors may be associated with an increased risk of retinopathy events early in the treatment phase.

Associations of Low Muscle Mass and the Metabolic Syndrome in Caucasian and Asian Middle-aged and Older Adults.

OBJECTIVE: Age-related declines in skeletal muscle mass may confer significant metabolic consequences for older adults. Associations of low muscle mass and metabolic syndrome (MetS) in Caucasians, and comparisons with associations observed in Asian populations, have not been reported. We examined associations of low muscle mass and metabolic syndrome (MetS) in Asian and Caucasian middle-aged and older men and women using criteria for low muscle mass. DESIGN, SETTING AND PARTICIPANTS: Two population-based studies of Australian (Tasmanian Older Adult Cohort Study; TASOAC; N=1005) and Korean (Korean Sarcopenic Obesity Study; KSOS; N=376) community-dwelling adults, mean age 62 and 58 years, respectively. MEASUREMENTS: Appendicular lean mass (aLM) determined by dual-energy X-ray absorptiometry and normalised to height squared (aLM/Ht2), weight (aLM/Wt) or body mass index (aLM/BMI). Participants in the lowest sex-specific 20% for aLM measures were defined as having low muscle mass. MetS was defined according to National Cholesterol Education Program Adult Treatment Panel III criteria. RESULTS: Although Australians demonstrated generally unfavourable anthropometric and metabolic characteristics compared to Koreans, prevalence of MetS was similar (29.5% in Australians and 31.4% in Koreans, respectively). Low aLM/Ht2 was associated with significantly reduced likelihood of MetS in both Australians (OR: 0.30, 95% CI 0.19 - 0.46) and Koreans (OR: 0.31, 95% CI 0.16 - 0.62). Conversely, low aLM/BMI was associated with increased odds for MetS in Australians (OR: 1.78, 95% CI 1.12 - 2.84), but not Koreans (OR: 1.33, 95% CI = 0.67 - 2.64). CONCLUSION: Low aLM/BMI is associated with significantly increased likelihood of MetS in Australian adults, but not Koreans, suggesting potential differences in effects of low muscle mass relative to body mass on cardiometabolic health in Caucasian and Asian middle-aged and older adults. Low muscle mass relative to height is associated with reduced likelihood of MetS in both populations.

Allogeneic adipose-derived stem cells for the treatment of perianal fistula in Crohn's disease: a pilot clinical trial.

AIM: Many perianal fistulae in Crohn's disease do not respond to conventional surgical and medical management and recurrence rates are high. The study evaluated the safety and feasibility of allogeneic adipose-derived stem cells for the treatment of perianal fistula in Crohn's disease. METHOD: A multicentre, open-label, dose escalation pilot study was performed. The first three patients (group 1) were administered 1 × 10(7) cells/ml based on the size of the fistula tract. Four weeks later, after which time this dose had been confirmed to be safe, the next three patients (group 2) were administered 3 × 10(7) cells/ml. The end-point was complete closure at 8 weeks after the injection. Patients who attended for the 8 week assessment were followed for an additional 6 months. RESULTS: There were no adverse events of Grade 3 or 4 severity and no adverse events related to the treatment with allogeneic adipose-derived stem cells. Two patients in group 1 achieved complete closure of the fistula at month 4 and month 6, and one patient in group 2 achieved complete closure at 8 weeks. The closure was sustained up to month 8 in all three of those patients. CONCLUSION: These data suggest that allogeneic adipose-derived stem cells may be a feasible treatment option for perianal fistula in Crohn's disease.

Lobeglitazone and pioglitazone as add-ons to metformin for patients with type 2 diabetes: a 24-week, multicentre, randomized, double-blind, parallel-group, active-controlled, phase III clinical trial with a 28-week extension.

We aimed to compare the efficacy and safety of lobeglitazone and pioglitazone as add-ons to metformin in patients with type 2 diabetes. Patients who were inadequately controlled by metformin were randomized and treated once daily with either lobeglitazone (0.5 mg, n = 128) or pioglitazone (15 mg, n = 125) for 24 weeks, with a 28-week extension trial of lobeglitazone treatment in patients who consented. The primary endpoint was the change in glycated haemoglobin (HbA1c) concentration from baseline to week 24. At week 24, the mean change from baseline in HbA1c was -0.74% for the lobeglitazone group and -0.74% for the pioglitazone group, with a mean difference of 0.01% [95% confidence interval (CI) of difference, -0.16 to 0.18]. The effects of lobeglitazone on lipid variables and the adverse events associated with lobeglitazone were similar to those observed with pioglitazone. Lobeglitazone was not inferior to pioglitazone as an add-on to metformin in terms of their efficacy and safety.

Anagliptin and sitagliptin as add-ons to metformin for patients with type 2 diabetes: a 24-week, multicentre, randomized, double-blind, active-controlled, phase III clinical trial with a 28-week extension.

We conducted a 24-week, multicentre, double-blind, randomized study with a 28-week extension to compare the efficacy and safety of anagliptin and sitagliptin as an add-on to metformin in patients with type 2 diabetes. Patients inadequately controlled on metformin were randomized to either anagliptin (100 mg twice daily, n = 92) or sitagliptin (100 mg once daily, n = 88). The primary endpoint was the change in glycated haemoglobin (HbA1c) from baseline to week 24. The mean changes in HbA1c were -0.85 ± 0.70% (p < 0.0001) for anagliptin and -0.83 ± 0.61% (p < 0.0001) for sitagliptin, with a mean difference of -0.02% (95% confidence interval of difference, -0.22 to 0.18%). In both groups, the fasting proinsulin : insulin ratio significantly decreased from baseline, with improved insulin secretion. Safety profiles were similar in each group. In conclusion, the non-inferiority of the efficacy of anagliptin to sitagliptin as an add-on therapy was established with regard to efficacy and safety.

Crucial role of calbindin-D28k in the pathogenesis of Alzheimer's disease mouse model.

Calbindin-D28k (CB), one of the major calcium-binding and buffering proteins, has a critical role in preventing a neuronal death as well as maintaining calcium homeostasis. Although marked reductions of CB expression have been observed in the brains of mice and humans with Alzheimer disease (AD), it is unknown whether these changes contribute to AD-related dysfunction. To determine the pathogenic importance of CB depletions in AD models, we crossed 5 familial AD mutations (5XFAD; Tg) mice with CB knock-out (CBKO) mice and generated a novel line CBKO·5XFAD (CBKOTg) mice. We first identified the change of signaling pathways and differentially expressed proteins globally by removing CB in Tg mice using mass spectrometry and antibody microarray. Immunohistochemistry showed that CBKOTg mice had significant neuronal loss in the subiculum area without changing the magnitude (number) of amyloid ß-peptide (Aß) plaques deposition and elicited significant apoptotic features and mitochondrial dysfunction compared with Tg mice. Moreover, CBKOTg mice reduced levels of phosphorylated mitogen-activated protein kinase (extracellular signal-regulated kinase) 1/2 and cAMP response element-binding protein at Ser-133 and synaptic molecules such as N-methyl-D-aspartate receptor 1 (NMDA receptor 1), NMDA receptor 2A, PSD-95 and synaptophysin in the subiculum compared with Tg mice. Importantly, this is the first experimental evidence that removal of CB from amyloid precursor protein/presenilin transgenic mice aggravates AD pathogenesis, suggesting that CB has a critical role in AD pathogenesis.

High-dose of vitamin C supplementation reduces amyloid plaque burden and ameliorates pathological changes in the brain of 5XFAD mice.

Blood-brain barrier (BBB) breakdown and mitochondrial dysfunction have been implicated in the pathogenesis of Alzheimer's disease (AD), a neurodegenerative disease characterized by cognitive deficits and neuronal loss. Besides vitamin C being as one of the important antioxidants, recently, it has also been reported as a modulator of BBB integrity and mitochondria morphology. Plasma levels of vitamin C are decreased in AD patients, which can affect disease progression. However, investigation using animal models on the role of vitamin C in the AD pathogenesis has been hampered because rodents produce with no dependence on external supply. Therefore, to identify the pathogenic importance of vitamin C in an AD mouse model, we cross-bred 5 familial Alzheimer's disease mutation (5XFAD) mice (AD mouse model) with ι-gulono-γ-lactone oxidase (Gulo) knockout (KO) mice, which are unable to synthesize their own vitamin C, and produced Gulo KO mice with 5XFAD mice background (KO-Tg). These mice were maintained on either low (0.66 g/l) or high (3.3 g/l) supplementation of vitamin C. We found that the higher supplementation of vitamin C had reduced amyloid plaque burden in the cortex and hippocampus in KO-Tg mice, resulting in amelioration of BBB disruption and mitochondrial alteration. These results suggest that intake of a larger amount of vitamin C could be protective against AD-like pathologies.

Robotic rectal surgery: what are the benefits?

Robotic rectal surgery is not a rare event for colorectal surgeons any more. Even patients with colorectal diseases obtain information through the mass media and are asking surgeons about robotic surgery. Since laparoscopic rectal surgery has proved to have some benefits compared to open rectal surgery, many surgeons became interested in robotic rectal surgery. Some of them have reported the advantages and disadvantages of robotic rectal surgery over the last decade. This review will report on the outcomes of robotic rectal surgery. Robotic rectal surgery requires a longer operation time than laparoscopic or open surgery, but many authors reduced the gap as they were accustomed to the robotic system and used various additional techniques. The high cost for purchasing and maintaining the robotic system is still a problem, though. However, except for this reason, robotic rectal surgery shows comparable and even superior results in some parameters than laparoscopic or open surgery. They include pathologic and functional outcomes as well as short-term outcomes such as complication rates, length of hospital stay, time to recover normal bowel function or first flatus, time to start diet, and postoperative pain. Moreover, studies on oncologic outcomes show acceptable results. Robotic rectal surgery is safe and feasible and has a number of benefits. Therefore, it can be an alternative option to conventional laparoscopic and open surgery with strict indications.

Association of glypican-4 with body fat distribution, insulin resistance, and nonalcoholic fatty liver disease.

CONTEXT AND OBJECTIVE: Glypican-4 was identified as a novel adipokine capable of enhancing insulin signaling and modulating adipocyte differentiation. We investigated associations between glypican-4 and body composition, insulin resistance, arterial stiffness, and nonalcoholic fatty liver disease (NAFLD) in nondiabetic Asian subjects. DESIGN AND PARTICIPANTS: We analyzed baseline cross-sectional data from the Korean Sarcopenic Obesity Study, an ongoing prospective cohort study. NAFLD was diagnosed by unenhanced computed tomography using the liver attenuation index. We also examined the effects of a 3-month combined aerobic and resistance exercise program on glypican-4 levels and cardiometabolic risk factors. RESULTS: Circulating glypican-4 levels were higher in men than in women (1.83 [1.19, 2.78] ng/mL vs 1.17 [0.66, 2.00] ng/mL, P < .001) and had a significant positive relationship with the waist-to-hip ratio (WHR) (r = 0.20, P = .014) and the ratio of visceral to sc fat area (r = 0.30, P < .001). Furthermore, glypican-4 levels in women were correlated with cardiometabolic risk factors, including insulin resistance and arterial stiffness, and were independently associated with NAFLD by multiple logistic regression analysis (P = .017, R² = 0.33). The 3-month combined exercise training program significantly improved several cardiometabolic parameters and reduced retinol binding protein-4 levels. Changes in glypican-4 levels after the exercise program were significantly different between subjects with an increased WHR compared with those with a decreased WHR (P = .034). CONCLUSION: A gender-based difference in circulating glypican-4 levels was apparent as these were increased in women with NAFLD and related to body fat distribution, insulin resistance, and arterial stiffness.

Gestational diabetes is associated with high energy and saturated fat intakes and with low plasma visfatin and adiponectin levels independent of prepregnancy BMI.

BACKGROUND/OBJECTIVES: Gestational diabetes mellitus (GDM) risk factors are well established for Caucasians, but not for Asians. We hypothesized that nutrient intakes, plasma adipokines and/or gestational hormones might be linked to GDM development among pregnant Korean women. This study sought to identify new risk factors for GDM and adverse pregnancy outcomes according to body weight at prepregnancy. SUBJECTS/METHODS: All subjects were pregnant women visiting the Cheil General Hospital and Women's Healthcare Center between June 2006 and March 2009. Non-GDM (n=531) and GDM (n=215) participants were divided into normal-weight and overweight groups according to prepregnancy body mass index (BMI) above or below 23 kg/m(2) at 24-28th week of gestation. At that time, glucose tolerance, insulin resistance as homeostatic model assessment for insulin resistance, insulin secretory capacity as homeostatic model assessment for ß-cell function, anthropometric measurement, nutrient intakes, and plasma levels of adipokines and gestational hormones were determined. RESULTS: GDM women gained more weight in early pregnancy than non-GDM among normal-weight women. GDM was mainly associated with increased insulin resistance in overweight women and decreased insulin secretory capacity in normal-weight women. Plasma visfatin and adiponectin were lower and progesterone levels higher in GDM than non-GDM independent of BMI while plasma resistin levels were higher in non-GDM, but not GDM, overweight women. Energy and saturated fat intakes were higher in GDM independent of body weight, whereas taurine intakes were lower in GDM than non-GDM only in normal-weight women. CONCLUSIONS: Low visfatin and adiponectin and high progesterone levels in the circulation and high energy and saturated fat intakes were common risk factors for GDM and pregnancy outcome such as large for gestational age. Daily reference intakes for energy and fat during pregnancy need to be re-evaluated according to prepregnancy BMI.

Efficacy and safety of glimepiride/metformin sustained release once daily vs. glimepiride/metformin twice daily in patients with type 2 diabetes.

AIMS: The study investigated the clinical equivalence in reducing haemoglobin A1c (A1C) between glimepiride/metformin sustained release (GM-SR) 2/500 mg, a fixed-dose combination, once daily and glimepiride/metformin (GM) 1/250 mg, a fixed-dose combination, twice daily in patients with type 2 diabetes (T2D). METHODS: A multicentre, randomised, double-blind, double-dummy study was conducted in 14 hospitals in Korea. Inclusion criteria were age 30-75 years, T2D diagnosis no longer than 10 years previously, A1C between 7% and 10%, and body mass index <40 kg/m(2) . A total of 207 subjects were randomised into the GM-SR group (n=101) or the GM group (n=106). Participants were assessed at baseline, 8 weeks and 16 weeks after treatment. RESULTS: After 16 weeks treatment, no difference in baseline-adjusted changes of A1C (primary efficacy variable) was observed between the two groups (-0.59% for GM-SR group vs. -0.61% for GM group, 95% CI: -0.17 to 0.21; p=0.84). In addition, there were no significant differences in secondary efficacy parameters between the two groups, including changes in A1C up to week 8, changes in fasting plasma glucose (FPG) and 2-h-postprandial plasma glucose up to week 8 and week 16, response rate, drug compliance and hypoglycaemic events. However, there was a difference in baseline-adjusted changes of FPG between the two groups (-1.01 mmol/l for GM-SR group vs. -1.52 mmol/l for GM group, p=0.01 in the intention to treat set). CONCLUSIONS: GM-SR 2/500 mg once daily was as effective as GM 1/250 mg twice daily in lowering A1C. In addition, no difference was noted in hypoglycaemic events between the two groups.

A multicentre, multinational, randomized, placebo-controlled, double-blind, phase 3 trial to evaluate the efficacy and safety of gemigliptin (LC15-0444) in patients with type 2 diabetes.

AIM: This study was designed to assess the efficacy and safety of the dipeptidyl peptidase IV inhibitor gemigliptin (LC15-0444) 50 mg versus placebo in patients with type 2 diabetes. METHODS: We conducted a 24-week, randomized, double-blind, placebo-controlled phase III trial in 182 patients (74 from Korea and 108 from India) with type 2 diabetes. After an initial 2 weeks of a diet and exercise programme followed by 2 weeks of a single-blind placebo run-in period, eligible patients were randomized to gemigliptin 50 mg or placebo, receiving the assigned treatment for 24 weeks. HbA1c and fasting plasma glucose (FPG) were measured periodically, and oral glucose tolerance test was performed at baseline and weeks 12 and 24. RESULTS: At week 24, gemigliptin treatment led to significant reductions in HbA1c measurements compared to placebo (adjust mean after subtracting the placebo effect size: -0.71%, 95% confidence interval: -1.04 to -0.37%). A significantly greater proportion of patients achieved an HbA1c <7% with gemigliptin than with placebo. The placebo-subtracted FPG change from baseline at week 24 was -19.80 mg/dl. The overall incidence rates for adverse events were similar in the gemigliptin and placebo groups. CONCLUSIONS: This study showed the efficacy and safety of gemigliptin 50 mg administered once daily as a monotherapy for type 2 diabetes patients.

Patients' education, and its impact on care outcomes, resource consumption and working conditions: data from the International Diabetes Management Practices Study (IDMPS).

AIM: To evaluate the impact of diabetes education provided to patients with type 2 diabetes mellitus (T2DM) in non-controlled studies ("real-world conditions") on quality of care, resource consumption and conditions of employment. METHODS: This cross-sectional study and longitudinal follow-up describe the data (demographic and socioeconomic profiles, clinical characteristics, treatment of hyperglycaemia and associated cardiovascular risk factors, resource consumption) collected during the second phase (2006) of the International Diabetes Management Practices Study (IDMPS). Patients received diabetes education directly from the practice nurse, dietitian or educator, or were referred to ad hoc group-education programmes; all programmes emphasized healthy lifestyle changes, self-care and active participation in disease control and treatment. Educated vs non-educated T2DM patients (n=5692 in each group), paired by age, gender and diabetes duration, were randomly recruited for the IDMPS by participating primary-care physicians from 27 countries in Eastern Europe, Asia, Latin America and Africa. Outcome measures included clinical (body weight, height, waist circumference, blood pressure, foot evaluation), metabolic (HbA(1c) levels, blood lipid profile) and biochemical control measures. Treatment goals were defined according to American Diabetes Association guidelines. RESULTS: T2DM patients' education significantly improved the percentage of patients achieving target values set by international guidelines. Educated patients increased their insulin use and self-care performance, had a lower rate of chronic complications and a modest increase in cost of care, and probably higher salaries and slightly better productivity. CONCLUSION: Diabetes education is an efficient tool for improving care outcomes without having a major impact on healthcare costs.

Serum selenoprotein P levels in patients with type 2 diabetes and prediabetes: implications for insulin resistance, inflammation, and atherosclerosis.

CONTEXT AND OBJECTIVE: The dysregulation of hepatokines may be associated with the pathogenesis of insulin resistance and type 2 diabetes. A recent study has suggested that selenoprotein P (SeP), a novel hepatokine, may play a role in the regulation of glucose metabolism and insulin sensitivity. We examined the relationship between circulating SeP levels and clinical parameters associated with insulin resistance in humans. PARTICIPANTS AND METHODS: We compared serum SeP concentrations in 100 subjects with diverse glucose tolerance statuses. Furthermore, we evaluated the relationship between SeP and cardiometabolic risk factors including insulin resistance, high-sensitivity C-reactive protein, and carotid intima-media thickness. RESULTS: Serum SeP concentrations were significantly higher in patients with type 2 diabetes or prediabetes than those with normal glucose tolerance (all P < 0.01) and decreased in a stepwise manner [1032.4 (495.9-2149.4) vs. 867.3 (516.3-1582.7) vs. 362.0 (252.5-694.5), P = 0.004]. In addition, overweight and obese subjects had significantly increased SeP levels compared with lean subjects (P = 0.002). Spearman's partial correlation analysis adjusted for age and gender showed a significant relationship between SeP and cardiometabolic factors including body mass index, waist circumference, systolic blood pressure, triglycerides, glucose, hemoglobin A1c, aspartate aminotransferase, and insulin resistance. Furthermore, in multiple regression analyses, SeP showed an independent association with carotid intima-media thickness as well as high-sensitivity C-reactive protein, even after adjustment for other confounding factors. CONCLUSIONS: Circulating SeP concentrations were elevated in patients with glucose metabolism dysregulation and were related to various cardiometabolic parameters including insulin resistance, inflammation, and atherosclerosis.

A multicenter, randomized, placebo-controlled, double-blind phase II trial evaluating the optimal dose, efficacy and safety of LC 15-0444 in patients with type 2 diabetes.

AIM: The objective of this study was to evaluate the optimal dose, efficacy and safety of a novel dipeptidyl peptidase-4 (DPP-IV) inhibitor, LC15-0444, in Korean subjects with type 2 diabetes mellitus treated by diet and exercise. METHODS: This study was a double-blind, randomized, multicenter and parallel-group, dose-range finding study. We enrolled 145 patients (91 men and 54 women) with a median age of 53 years and a median body mass index of 25.1 kg/m(2) . The median baseline fasting plasma glucose (FPG) was 8.1 mmol/l, the median HbA1c was 7.9% and the median time since the diagnosis of diabetes was 3 years. After 2 weeks of an exercise/diet programme followed by 2 weeks of a placebo period, the subjects were randomized to one of the four following groups for a 12-week active treatment period: placebo and 50, 100 or 200 mg of LC15-0444. RESULTS: All three doses of LC15-0444 significantly reduced the HbA1c from baseline compared to the placebo group (-0.06 vs. -0.98, -0.74 and -0.78% in the placebo and 50, 100 and 200 mg groups, respectively), without a significant difference between the doses. Subjects with a higher baseline HbA1c (≥8.5%) had a greater reduction in HbA1c. Insulin secretory function, as assessed using homeostasis model assessment-beta cell, C-peptide and the insulinogenic index, improved significantly with LC15-0444 treatment. Insulin sensitivity, as assessed using homeostasis model assessment-insulin resistance, also improved significantly after 12 weeks of treatment. The 50 and 200 mg groups had significantly reduced total cholesterol and low-density lipoprotein cholesterol levels at 12 weeks compared to the placebo group. No dosage of LC15-0444 affected weight or waist circumference. The incidences of adverse events were similar in all study subjects. CONCLUSIONS: LC15-0444 monotherapy (50 mg for 12 weeks) improved the HbA1c, FPG level, oral glucose tolerance test results, ß-cell function and insulin sensitivity measures, and was well tolerated in Korean subjects with type 2 diabetes.