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.

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.

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.

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.

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.

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.

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.

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.

The association between the ratio of visceral fat to thigh muscle area and metabolic syndrome: the Korean Sarcopenic Obesity Study (KSOS).

OBJECTIVE: A relationship between visceral fat accumulation and metabolic syndrome (MetS) has been established. However, the effect of a relative increase in visceral fat and a decrease in muscle mass on metabolic disorders has not been investigated. The aim of the present study was to examine the association between the ratio of visceral fat to thigh muscle area (VMR) and MetS in Korean adults. STUDY SUBJECT/MEASUREMENTS: A total of 264 age-and gender-matched subjects recruited from the Korean Sarcopenic Obesity Study (KSOS), an ongoing prospective observational cohort study, were categorized into four groups based on their body mass index (BMI) and VMR. We measured visceral fat area and thigh muscle area using computed tomography. RESULTS: Subjects with MetS showed a significantly higher VMR than those without MetS. In both obese and nonobese groups, the subjects with a higher VMR had a higher prevalence of MetS than those in the lower VMR groups. VMR was significantly related to components of the metabolic syndrome, especially in women, and was positively correlated with a number of MetS components in both men and women. In multiple logistic regression analysis, the odds ratio for MetS was 6·72 (highest vs lowest quartile, 95% confidence interval, 1·60-28·14) after an adjustment of potential confounders, including BMI and waist-to-hip ratio. CONCLUSION: VMR is significantly increased in subjects with MetS and independently associated with MetS. These results suggest that the VMR may be a potential indicator for MetS risk in Korean adults.

Comparison of the efficacy and safety of tramadol/acetaminophen combination therapy and gabapentin in the treatment of painful diabetic neuropathy.

AIMS: This study compared the efficacy and safety of tramadol/acetaminophen (T/A) and gabapentin in the management of painful diabetic neuropathy. METHODS: An open, randomized, comparative study was conducted. Subjects with painful symmetric neuropathy in the lower limbs and mean pain-intensity score > or = 4 on a numeric rating scale were eligible. Subjects were randomized to receive either tramadol (37.5 mg)/acetaminophen (325 mg) or gabapentin (300 mg) for 6 weeks. After 2 weeks of the titration period (1200 mg/day for gabapentin and three tablets/day for T/A), the doses were maintained if the pain was relieved. The primary efficacy outcome was a reduction in pain intensity. Secondary measures evaluated a pain relief scale, a Brief Pain Inventory, a 36-item Short Form Health Survey, average pain intensity and sleep disturbance. RESULTS: One hundred and sixty-three subjects (T/A 79; gabapentin 84) were included. At the final visit, the mean doses were 1575 mg/day for gabapentin and 4.22 tablets/day for T/A. Both groups were similar in terms of baseline pain intensity (mean intensity: T/A 6.7 +/- 1.6; gabapentin 6.3 +/- 1.6, P = 0.168). At the final visit, the mean reductions in pain intensity were similar in both groups (T/A -3.1 +/- 2.0; gabapentin -2.7 +/- 2.1, P = 0.744). Both groups had similar improvements in every Short Form Health Survey category and Brief Pain Inventory subcategory, and in the mean pain relief scores. CONCLUSION: This study suggests that the T/A combination treatment is as effective as gabapentin in the treatment of painful diabetic neuropathy in patients with Type 2 diabetes.

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.

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.

Prevalence of sarcopenia and sarcopenic obesity in Korean adults: the Korean sarcopenic obesity study.

OBJECTIVES: To examine the prevalence of sarcopenia and sarcopenic obesity (SO) as defined by different indices, including appendicular skeletal muscle mass (ASM)/height(2), skeletal muscle mass index (SMI) and residuals for Korean adults, and to explore the association between SO and metabolic syndrome. METHODS: Our study sample included 526 participants (328 women, 198 men) for whom complete data on body composition were collected using available dual X-ray absorptiometry. Modified National Cholesterol Education Program Adult Treatment Panel III criteria were used to identify the individuals with metabolic syndrome. RESULTS: The prevalence of sarcopenia and SO is higher in older adults. Using two s.d. of ASM/height(2) below reference values from young, healthy adults as a definition of sarcopenia, the prevalence of sarcopenia and SO was 6.3% and 1.3% in older (> or =60 years) men and 4.1% and 0.8% in older women, respectively. The prevalence of sarcopenia using the residuals method was 15.4% in older men and 22.3% in older women. In addition, using two s.d. of SMI, the prevalence of sarcopenia and SO was 5.1% and 5.1%, respectively, in older men and 14.2% and 12.5%, respectively, in older women. Among women, SO subjects defined by the SMI had three times the risk of metabolic syndrome (odds ratios (OR)=3.24, 95% confidence interval (CI)=1.21-8.66) and non-sarcopenic obese subjects had approximately twice the risk of metabolic syndrome (OR=2.17, 95% CI=1.22-3.88) compared with normal subjects. Similar trends were observed in men. CONCLUSION: The prevalence and cutoff values of sarcopenia and SO in the Korean population were evaluated using different methods. Among the different indices of sarcopenia and SO, SO only defined using the SMI was associated with the risk of metabolic syndrome. As the Korean population gets older and more obese, the problematics of SO need to be elucidated.

Effect of exercise training on A-FABP, lipocalin-2 and RBP4 levels in obese women.

OBJECTIVE: Lipocalin family proteins, including adipocyte fatty acid-binding protein (A-FABP), lipocalin-2 and retinol-binding protein 4 (RBP4), have recently been identified as novel adipokines associated with obesity, type 2 diabetes and the metabolic syndrome. We have evaluated the effect of exercise training on lipocalin family proteins and inflammatory markers. STUDY SUBJECTS: Thirty obese Korean women and 15 age-matched nonobese control subjects were studied. DESIGN: Concentrations of the lipocalin family proteins were compared between obese and nonobese women and were evaluated before and 3 months after an exercise programme consisting of aerobic exercise (45 min/session, 300 kcal/day) and muscle strength training (20 min/session, 100 kcal/day) five times a week. RESULTS: Obese women exhibited higher A-FABP levels compared to nonobese women (21.4 +/- 6.4 microg/l vs. 13.6 +/- 4.4 microg/l, P < 0.001). However, neither lipocalin-2 nor RBP4 levels were significantly different between the two groups, although the difference in lipocalin-2 was marginally significant (P = 0.054). Circulating A-FABP levels were significantly associated with body mass index (BMI), waist circumference, triglyceride, alanine aminotransferase (ALT), lipocalin-2 and high-sensitivity C-reactive protein (hsCRP) levels. After 3 months of the exercise training programme, serum A-FABP levels decreased significantly from 21.4 +/- 6.4 microg/l to 19.3 +/- 6.8 microg/l (P = 0.038), along with a reduction in weight, BMI, waist circumference, fasting glucose and total cholesterol levels. There was no significant change in the lipocalin-2 and RBP4 levels, although IL-6 levels increased after the exercise programme. CONCLUSION: Exercise training with weight loss induced a significant reduction in circulating A-FABP levels in obese Korean women.

A Ubiquitous Chronic Disease Care system using cellular phones and the internet.

AIMS: The rapidly increasing prevalence of chronic diseases is an important challenge to healthcare systems worldwide. To improve the quality and efficiency of chronic disease care, we investigated the effectiveness and applicability of the Ubiquitous Chronic Disease Care (UCDC) system using cellular phones and the internet for overweight patients with both Type 2 diabetes and hypertension. METHODS: We conducted a randomized, controlled clinical trial over 3 months that included 123 patients at a university hospital and a community public health centre. RESULTS: After 12 weeks, there were significant improvements in HbA(1c) in the intervention group (7.6 +/- 0.9% to 7.1 +/- 0.8%, P < 0.001) compared with the control group (7.4 +/- 0.9% to 7.6 +/- 1.0%, P = 0.03). Furthermore, we observed a significant reduction in systolic and diastolic blood pressure, as well as improvements in total cholesterol, low-density lipoprotein-cholesterol and triglyceride levels in the intervention group. Furthermore, there was a significant increase in adiponectin levels in the intervention group compared with the control group, although high-sensitivity C-reactive protein and interleukin-6 levels did not change in either group. CONCLUSIONS: The novel UCDC system presented in this paper improved multiple metabolic parameters simultaneously in overweight patients with both Type 2 diabetes and hypertension.

Effects of insulin glulisine as mono- or add-on therapy in patients with type 2 diabetes mellitus.

AIM: To evaluate the safety and efficacy of insulin glulisine (glulisine) with and without oral antidiabetic drugs (OAD; sulphonylurea or sulphonylurea + biguanide) relative to that of OAD alone in Japanese and Korean patients with inadequately controlled type 2 diabetes mellitus (T2DM). METHODS: In an open, randomized, parallel-group, comparative, controlled trial, 387 patients were randomized and treated with glulisine + OAD (n = 130), glulisine monotherapy (n = 127) or OAD only (n = 130) for 16 weeks. Glulisine was self-injected subcutaneously three times daily (0-15 minutes before meals) at a starting dose of >or=0.2 U/kg/day. Patients titrated the glulisine dose to achieve a 2-h postprandial plasma glucose (2h-PPG) level of 7.1-9.5 mmol/l (128-172 mg/dl) by administering at least one additional unit at each appropriate meal time if the 2h-PPG level was > 9.5 and < 11.1 mmol/l (> 172 and < 200 mg/dl) and by administering at least two additional units if the 2h-PPG level was >or= 11.1 mmol/l (>or= 200 mg/dl). Therapy with OAD was continued at the stable baseline regimen. The primary efficacy endpoint was change in haemoglobin A(1c) (HbA(1c)) from baseline to endpoint in the intention-to-treat population. RESULTS: At baseline, therapy with OAD was a sulphonylurea only and a sulphonylurea + a biguanide in approximately 24 and 76% of patients respectively. Both glulisine groups had larger reductions in adjusted mean HbA(1c) than the OAD-only group (glulisine + OAD, -2.07%; glulisine monotherapy, -1.25%; OAD only, -0.61%). Superiority of glulisine + OAD and glulisine monotherapy vs. OAD only was shown by differences in adjusted mean HbA(1c) change from baseline values of -1.46% (p < 0.0001) and -0.64% (p < 0.0001) respectively. Both glulisine groups had better 2h-PPG control than the OAD-only group. Mean daily glulisine doses increased from baseline to endpoint (glulisine + OAD, 13.3-22.5 U; glulisine monotherapy, 14.2-38.0 U). The rate of all symptomatic hypoglycaemia events per patient-year in the entire treatment phase was 11.9 in the glulisine + OAD group, 8.8 in the glulisine monotherapy group and 1.7 in the OAD-only group. There was only one event of severe hypoglycaemia, which occurred in the glulisine + OAD group. Efficacy and safety were similar in Japanese and Korean subpopulations. CONCLUSIONS: Both glulisine + OAD and glulisine monotherapy were well tolerated and effective for Japanese and Korean patients with T2DM mellitus inadequately controlled by OAD therapy alone.

Relationship between sleep duration and the metabolic syndrome: Korean National Health and Nutrition Survey 2001.

OBJECTIVES: Previous studies have revealed that both short and long sleep durations are linked to obesity, hyperglycemia and hypertension. We evaluate the relationship between sleep duration and the metabolic syndrome using representative national survey data from the Korean population. METHODS: We analyzed data from the 2001 Korean National Health and Nutrition Survey. The average amount of sleep per night was categorized as: or=9 h. Those reporting 7 h per night served as a reference group. In this cross-sectional study, the data of 4222 participants were finally analyzed. RESULTS: A majority of the components of the metabolic syndrome demonstrated U-shaped patterns based on sleep duration. Although the prevalences of abdominal obesity and hypertension were highest in subjects who slept or=9 h per night. Prevalence of the metabolic syndrome also exhibited U-shape pattern based on sleep duration. More components of the metabolic syndrome were highly associated with sleep duration in subjects under the age of 60 compared to those over the age of 60. Subjects who slept or=9 h per night exhibited increased risk for the metabolic syndrome even after adjustment of other risk variables (OR 1.69, 95% CI 1.17-2.45, P=0.006). CONCLUSIONS: Both short and long sleep durations are related to increased risk of the metabolic syndrome and its components in the Korean population, although adjustment for risk factors attenuates their relationship. Subjects reporting sleep duration of 7 h demonstrated the lowest prevalence of the metabolic syndrome.

Serum retinol-binding protein 4 levels are elevated in non-alcoholic fatty liver disease.

OBJECTIVE: Retinol-binding protein 4 (RBP4) is a recently identified adipokine that is elevated in the serum in several insulin-resistant states. We investigated the relationship between non-alcoholic fatty liver disease (NAFLD) and serum RBP4 in nondiabetic adults. METHODS: One hundred and fifty-nine nondiabetic, non-alcoholic subjects (95 males and 64 females) participated in this study. Division of subjects into a NAFLD group (n = 73; 45 males and 28 females) or a normal group (n = 86; 50 males and 36 females) was based on the presence of fatty liver disease determined by sonography. RESULTS: Serum RBP4 levels in the NAFLD group were significantly higher than those in the normal group (62.8 +/- 16.0 mg/l vs. 51.7 +/- 14.6 mg/l, P < 0.0001). Multiple logistic regression analysis revealed that the RBP4 level was an independent factor associated with NAFLD (P = 0.0042). In addition, serum RBP4 levels were positively correlated with serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyltranspeptidase (GGT) levels. The significant association between serum RBP4 and GGT levels remained even after adjusting for age, gender, body mass index, the homeostasis model of assessment (HOMA) value and the presence of NAFLD (r = 0.3097, P = 0.0002). CONCLUSION: Serum RBP4 levels are significantly associated with NAFLD and liver enzymes.