Successful Localization by Hyperselective Arterial Calcium Injection Test for Surgical Resection of Insulinoma: A Case Report.

Surgery is the main treatment for insulinoma, and precise preoperative localization is important to determine the extent of resection and to rule out multiple lesions. The selective arterial calcium injection (SACI) test is instrumental in the localization of insulinoma. Here we report a patient in whom the exact location of pancreatic insulinoma could not be determined by the conventional SACI test, and thus surgery was replaced with oral diazoxide. The hyperselective SACI test subsequently localized the lesion accurately, allowing surgical resection of the pancreatic body and tail while preserving the pancreatic head. We recommend the use of the hyperselective SACI test when the conventional SACI test fails to accurately determine the location of insulinoma lesions within the pancreas.

Continuous glucose monitoring-derived time in range and CV are associated with altered tissue characteristics of the carotid artery wall in people with type 2 diabetes.

AIMS/HYPOTHESIS: Previous studies have suggested that glucose variability may accelerate atherosclerosis progression in people with type 2 diabetes. Current guidelines recommend assessing glycaemic control using continuous glucose monitoring (CGM), which provides a comprehensive glycaemic profile to supplement HbA1c measurement. However, the association between CGM-derived metrics and atherosclerosis progression is not entirely clear. METHODS: This exploratory study used baseline data and data obtained after 104 weeks from an ongoing prospective, multicentre, observational study. Six hundred study participants with type 2 diabetes and no apparent history of symptomatic cardiovascular disease underwent CGM and ultrasonographic atherosclerosis measurements of the carotid arteries, including the intima-media thickness (IMT) and grey-scale median (GSM), at baseline and 104 weeks. Non-invasive ultrasonic tissue characterisation of the carotid artery wall or plaque using the GSM reflects vascular composition. Multivariate regression models were used to analyse the association between CGM-derived indices, mainly time in range (TIR) and CV, and changes in carotid atherosclerosis index values. RESULTS: Over the 104-week study period, there were modest increases in mean IMT (from 0.759±0.153 to 0.773±0.152 mm, p<0.001) and thickened-lesion GSM (from 43.5±19.5 to 53.9±23.5 units, p<0.001), but no significant changes in common carotid artery maximum-IMT (from 1.109±0.442 to 1.116±0.469 mm, p=0.453) or mean GSM (from 48.7±19.3 to 49.8±20.8 units, p=0.092). In a linear regression model with adjustment for possible atherosclerotic risk factors, including HbA1c, TIR and CV at baseline were significantly associated with the annual change in mean GSM (regression coefficient per 10% increase in TIR 0.52; 95% CI 0.06, 0.98; Hochberg-adjusted p value 0.038; regression coefficient per 1% increase in CV -0.12; 95% CI -0.22, -0.02; Hochberg-adjusted p value 0.038). TIR and CV at baseline were also significantly associated with the annual change in thickened-lesion GSM (regression coefficient per 10% increase in TIR 0.95; 95% CI 0.12, 1.79; Hochberg-adjusted p value 0.038; regression coefficient per 1% increase in CV -0.19; 95% CI -0.36, -0.01; Hochberg-adjusted p value 0.038). Participants who achieved target CGM-derived metrics at baseline, as proposed by an international consensus, showed significant annual changes in mean GSM compared with those who did not (0.94±6.88 vs -0.21±6.19 units/year, p=0.007). CONCLUSIONS/INTERPRETATION: TIR and CV were significantly associated with changes in the tissue characteristics of the carotid artery wall. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry, number UMIN000032325.

Tofogliflozin long-term effects on atherosclerosis progression and major clinical parameters in patients with type 2 diabetes mellitus lacking a history of cardiovascular disease: a 2-year extension study of the UTOPIA trial.

BACKGROUND: This study aimed to assess the long-term effects of tofogliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, on atherosclerosis progression and major clinical parameters in patients with type 2 diabetes lacking an apparent history of cardiovascular disease. METHODS: This was a prospective observational 2-year extension study of the "Using TOfogliflozin for Possible better Intervention against Atherosclerosis for type 2 diabetes patients (UTOPIA)" trial, a 2-year randomized intervention study. The primary endpoints represented changes in the carotid intima-media thickness (IMT). Secondary endpoints included brachial-ankle pulse wave velocity (baPWV) and biomarkers for glucose metabolism, lipid metabolism, renal function, and cardiovascular risks. RESULTS: The mean IMT of the common carotid artery (IMT-CCA) significantly decreased in both the tofogliflozin (- 0.067 mm, standard error 0.009, p < 0.001) and conventional treatment groups (- 0.080 mm, SE 0.009, p < 0.001) throughout the follow-up period; however, no significant intergroup differences in the changes (0.013 mm, 95% confidence interval (CI) - 0.012 to 0.037, p = 0.32) were observed in a mixed-effects model for repeated measures. baPWV significantly increased in the conventional treatment group (82.7 ± 210.3 cm/s, p = 0.008) but not in the tofogliflozin group (- 17.5 ± 221.3 cm/s, p = 0.54), resulting in a significant intergroup difference in changes (- 100.2 cm/s, 95% CI - 182.8 to - 17.5, p = 0.018). Compared to the conventional treatment group, tofogliflozin significantly improved the hemoglobin A1c and high-density lipoprotein cholesterol levels, body mass index, abdominal circumference, and systolic blood pressure. The frequencies of total and serious adverse events did not vary significantly between the groups. CONCLUSIONS: Tofogliflozin was not associated with improved inhibition of carotid wall thickening but exerted long-term positive effects on various cardiovascular risk factors and baPWV while showing a good safety profile.

Possible involvement of CXCR3-CXCR6 + CD4 + T cells in Langerhans cell histiocytosis.

INTRODUCTION: Langerhans cell histiocytosis (LCH) is a condition characterized by proliferation of Langerhans cells and wide-range pathologies, ranging from single granulomatous lesions to multi-organ involvement, associated with tissue destruction. LCH pathogenesis remains obscure although association with interleukin (IL)-17A has been reported. We report here a case that illustrates the potential pathogenic role of helper T17 (Th17) cells in LCH-related bone destruction. MATERIALS AND METHODS: The patient was a 66-year-old woman. The clinical course included craniectomy and bone mass excision in X-9, diagnosis of LCH confirmed by histopathology, followed by 26-month chemotherapy. In August X, the patient was diagnosed with complete central diabetes insipidus. Symptoms improved after treatment with desmopressin. Pituitary magnetic resonance imaging showed swelling extending from the suprasellar region to the pituitary stalk, suggestive of LCH recurrence. This was followed by chemotherapy combined with mercaptopurine hydrate.  RESULTS: Subsequent peripheral blood lymphocyte analysis showed marked increase in activated Th17 cells (CXCR3-CXCR6+ CD4+ T cells). Double staining for CD4 and IL-17 by immunofluorescence of pathological tissue samples obtained during temporal bone mass excision, which confirmed the diagnosis of LCH in X-9, showed areas of combined presence of CD4-positive cells and IL-17-positive cells. Chemotherapy resulted in size reduction of the pituitary lesion and decrease in peripheral blood-activated Th17 cells. CONCLUSIONS: We found abundant peripheral blood-activated Th17 cells and high percentages of IL-17-producing cells in osteolytic bone lesions in LCH. This finding, together with the decrease in peripheral blood-activated Th17 cells following chemotherapy, suggests the potential involvement of activated Th17 cells in LCH-related osteolysis.

Development and validation of novel nomogram to identify the candidates for extended pelvic lymph node dissection for prostate cancer patients in the robotic era.

OBJECTIVES: To determine candidates for extended pelvic lymph node dissection using a novel nomogram to assess the risk of lymph node invasion in Japanese prostate cancer patients in the robotic era. METHODS: A total of 538 patients who underwent robot-assisted radical prostatectomy with extended pelvic lymph node dissection in three hospitals were retrospectively analyzed. Medical records were reviewed uniformly and the following data collected: prostate-specific antigen, age, clinical T stage, primary and secondary Gleason score at prostate biopsy, and percentage of positive core numbers. Finally, data from 434 patients were used for developing the nomogram and data from 104 patients were used for external validation. RESULTS: Lymph node invasion was detected in 47 (11%) and 16 (15%) patients in the development and validation set, respectively. Based on multivariate analysis, prostate-specific antigen, clinical T stage ≥3, primary Gleason score, grade group 5, and percentage of positive cores were selected as variables to incorporate into the nomogram. The area under the curve values were 0.781 for the internal and 0.908 for the external validation, respectively. CONCLUSIONS: The present nomogram can help urologists identify candidates for extended pelvic lymph node dissection concomitant with robot-assisted radical prostatectomy among patients with prostate cancer.

Evaluation of Fast Diffusion Kurtosis Imaging Using New Software Designed for Widespread Clinical Use.

Clinical research using restricted diffusion-weighted imaging, especially diffusion kurtosis (DK) imaging, has been progressing, with reports on its effectiveness in the diagnostic imaging of cerebral infarctions, neurodegenerative diseases, and tumors, among others. However, the application of DK imaging in daily clinical practice has not spread because of the long imaging time required and the use of specific software for image creation. Herein, with the aim of promoting clinical research using DK imaging at any medical facility, we evaluated fast DK imaging using a new software program. We developed a new macro program that produces DK images using general-purpose, inexpensive software (Microsoft Excel and ImageJ), and we evaluated fast DK imaging using bio-phantoms and a healthy volunteer in clinical trials. The DK images created by the new software with diffusion-weighted images captured with short-time imaging sequences were similar to the original DK images captured with long-time imaging sequences. The DK images using three b-values, which can reduce the imaging time by 43%, were equivalent to the DK images using five b-values. The DK imaging technique developed herein might allow any medical facility to increase its daily clinical use of DK imaging and easily conduct clinical research.

Glucose-lowering effects of 7-day treatment with SGLT2 inhibitor confirmed by intermittently scanned continuous glucose monitoring in outpatients with type 1 diabetes. A pilot study.

The present study used intermittently scanned continuous glucose monitoring (isCGM) in 10 patients with type 1 diabetes mellitus (T1DM) to evaluate the efficacy and safety of 7-day outpatient treatment with the combination of intensive insulin therapy and sodium-glucose transporter 2 inhibitor (SGLT2-I). All participants wore isCGM and were treated with either 50 mg/day ipragliflozin or 5 mg/day dapagliflozin. The primary outcome, percent time with glucose at 70-180 mg/dL (TIR: time in range), improved significantly following the addition of SGLT2-I (p = 0.005). TIR increased from 36.0% before addition of SGLT2-I to 70.7% on day 7. Although none of the patients achieved TIR of 70% or higher before the addition of SGLT2-I, 6 patients met that criteria TIR on day 7. The secondary outcome measures, standard deviation (SD) of glucose, average plasma glucose, percent time with glucose at >180 mg/dL (TAR: time above range), maximum plasma glucose, high blood glucose index (HBGI) and average nocturnal plasma glucose (midnight to 05:59 AM) detected by isCGM, also improved significantly by SGLT2-I. There were no significant differences in percent time with glucose at <70 mg/dL (TBR: time below range), minimum plasma glucose and low blood glucose index (LBGI). Our results using isCGM in an actual clinical setting showed that 7-day use of SGLT2-I with intensive insulin therapy improved plasma glucose fluctuations and mean plasma glucose levels without inducing hypoglycemia in patients with T1DM.

Evaluation of the Imaging Process for a Novel Subtraction Method Using Apparent Diffusion Coefficient Values.

Diffusion-weighted imaging may be used to obtain the apparent diffusion coefficient (ADC), which aids the diagnosis of cerebral infarction and tumors. An ADC reflects elements of free diffusion. Diffusion kurtosis imaging (DKI) has attracted attention as a restricted diffusion imaging technique. The ADC subtraction method (ASM) was developed to visualize restricted diffusion with high resolution by using two ADC maps taken with different diffusion times. We conducted the present study to provide a bridge between the reported basic ASM research and clinical research. We developed new imaging software for clinical use and evaluated its performance herein. This software performs the imaging process automatically and continuously at the pixel level, using ImageJ software. The new software uses a macro or a plugin which is compatible with various operating systems via a Java Virtual Machine. We tested the new imaging software's performance by using a Jurkat cell bio-phantom, and the statistical evaluation of the performance clarified that the ASM values of 99.98% of the pixels in the bio-phantom and physiological saline were calculated accurately (p<0.001). The new software may serve as a useful tool for future clinical applications and restricted diffusion imaging research.

[A Case of Thyroid Dysfunction and Isolated Adrenocorticotropin Deficiency after Nivolumab Therapy for Malignant Melanoma].

The patient was a 34-year-old woman. Surgical resection and chemotherapy had been performed on diagnosis of malignant melanoma in year X-9. Chronic thyroiditis was diagnosed in year X-8, but her thyroid function was normal. In November of the year X-1, the patient, who had metastasis to the left lung and the left main bronchus and radically unresectable metastases with distant metastases, was treated with the anti-PD-1 antibody nivolumab. In December X-1, we initiated levothyroxine sodium for hypothyroidism after the patient suffered indolent thyroiditis due to nivolumab. In March X, the nivolumab treatment was stopped because it proved to be ineffective, then in April, anorexia, fever, and general malaise were noted. Cortisol 5.0 and ACTH 17.5 were confirmed by blood test, and the patient was diagnosed with adrenal insufficiency and was admitted to the hospital. Head MRI showed no organic lesions, and a stress test showed abnormalities only in a CRH test (low response to both ACTH and cortisol). The patient was diagnosed with isolated ACTH deficiency due to nivolumab. Side effects of thyroid dysfunction due to nivolumab are frequently observed in Japan at a rate of 14.3%, and overseas at 5.9%. However, secondary adrenocortical dysfunction is observed in overseas clinical trials at a frequency of only about 0.3%. There are few reports of such complications, and we report this as a rare case.

Eplerenone Improves Vascular Endothelial Function in Patients with Primary Aldosteronism: A Pilot Study.

Primary aldosteronism (PA) is associated with a high risk of cardiovascular complications. Large-scale clinical studies have demonstrated that mineralocorticoid receptor antagonists (MRA) exhibit organ-protective effects and improve the prognosis of patients with heart failure and myocardial infarction, and daily clinical practice suggests that MRA seem to improve vascular endothelial dysfunction. In this pilot study, we treated 10 PA patients with eplerenone for 3 months. We used Endo-PAT to evaluate the effects of MRA on vascular endothelial function and analyzed the data for correlative factors. The primary outcome measure, the reactive hyperemia index (RHI), was 1.71 before therapy and increased significantly to 2.21. Univariate analysis showed a significant correlation between the rate of change in RHI and that in plasma renin activity (PRA). Since plasma aldosterone concentration increases during MRA therapy, PRA may be the best marker for selecting the most appropriate dose of MRA. PRA can potentially be used for adjusting the dose of MRA, in addition to adjusting blood pressure and serum potassium level.

Rationale and design of an investigator-initiated, multicenter, prospective open-label, randomized trial to evaluate the effect of ipragliflozin on endothelial dysfunction in type 2 diabetes and chronic kidney disease: the PROCEED trial.

BACKGROUND: Type 2 diabetes (T2D) is associated with renal impairment and vascular endothelial dysfunction. Therefore, this pathological connection is an important therapeutic target. Recent cardiovascular and renal outcome trials demonstrated that sodium glucose cotransporter 2 inhibitors (SGLT2is) consistently reduced the risks of cardiovascular and renal events and mortality in patients with T2D and various other background risks including chronic kidney disease (CKD). However, the precise mechanisms by which SGLT2is accords these therapeutic benefits remain uncertain. It is also unknown whether these SGLT2is-associated benefits are associated with the amelioration of endothelial dysfunction in patients with T2D and CKD. METHODS: The PROCEED trial is an investigator-initiated, prospective, multicenter, open-label, randomized-controlled trial. The target sample size is 110 subjects. After they furnish informed consent and their endothelial dysfunction is confirmed from their decreased reactive hyperemia indices (RHI), eligible participants with T2D (HbA1c, 6.0-9.0%) and established CKD (30 mL/min/1.73 m2 ≤ estimated glomerular filtration ratio [eGFR] < 60 and/or ≥ urine albumin-to-creatinine ratio 30 mg/g Cr) will be randomized (1:1) to receive either 50 mg ipragliflozin daily or continuation of background treatment (non-SGLT2i). The primary endpoint is the change in RHI from baseline after 24 weeks. To compare the treatment effects between groups, the baseline-adjusted means and their 95% confidence intervals will be estimated by analysis of covariance adjusted for HbA1c (< 7.0% or ≥ 7.0%), age (< 70 y or ≥ 70 y), RHI (< 1.67 or ≥ 1.67), eGFR (< 45 mL/min/1.73 m2 or ≥ 45 mL/min/1.73 m2), and smoking status. Prespecified responder analyses will be also conducted to determine the proportions of patients with clinically meaningful changes in RHI at 24 weeks. DISCUSSION: PROCEED is the first trial to examine the effects of ipragliflozin on endothelial dysfunction in patients with T2D and CKD. This ongoing trial will establish whether endothelial dysfunction is a therapeutic target of SGLT2is in this population. It will also provide deep insights into the potential mechanisms by which SGLT2is reduced the risks of cardiovascular and renal events in recent outcome trials. Trial registration Unique Trial Number, jRCTs071190054 (https://jrct.niph.go.jp/en-latest-detail/jRCTs071190054).

[Short-term Glucose Lowering Effects of Sodium-glucose Cotransporter 2 Inhibitors Confirmed by Flash Glucose Monitoring in Two Outpatients with Type 1 Diabetes].

Case 1 was a 41-year-old man with type 1 diabetes. He presented with poor glycemic control [hemoglobin A1c (HbA1c) of 8-9%] despite treatment with more than 20 units/day of insulin and 150 mg of miglitol. Before administration of sodium glucose cotransporter 2 (SGLT2) inhibitor, hyperglycemia was noted mainly at night by Flash Glucose Monitoring (FGM). Administration of ipragliflozin at 50 mg improved the hyperglycemia mainly at night (mean blood glucose, before administration: 205 mg/dl, day 6 of treatment: 119 mg/dl). Two months later, the HbA1c improved to 7.2% without hypoglycemia or ketosis. Case 2 was a 46-year-old woman with type 1 diabetes. She was morbidly obese and presented with poor glycemic control (HbA1c: 9-11%) although she was being treated with more than 50 units/day of insulin and 2,250 mg of metformin. Before administration of SGLT2 inhibitor, hyperglycemia was noted to be mainly nocturnal by FGM. Administration of dapagliflozin at 5 mg improved the hyperglycemia mainly at night on day 2 with improvement in the mean blood glucose level from 188 mg/dl before administration to 128 mg/dl on day 5. Four months later, the HbA1c improved to 8.0% without hypoglycemia and ketosis, and her body weight decreased from 92.1 to 89.8 kg. The hypoglycemic effect of SGLT2 inhibitors is independent of insulin. These agents also have various other effects, including weight loss, improvement of blood pressure and lipid metabolism. Here we report the short-term glucose lowering effects of two SGLT2 inhibitors, as confirmed by FGM, in two outpatients with type 1 diabetes.

Fulminant Type 1 Diabetes with Diversity in Peripheral Blood Lymphocytes: A Case Report.

A 29-year-old woman was admitted to our hospital for treatment of fulminant type 1 diabetes (FT1D) with diabetic ketoacidosis. The phenotype of peripheral blood lymphocytes was analyzed using an 8-color flow cytometer. An analysis of the CD4-positive T cells showed a tendency for higher proportions of effector and central memory T cells and a normal proportion of regulatory T (Treg) cells, compared to healthy control. An analysis of B cell differentiation showed higher proportions of switched memory B cells and plasmablasts. The differences in lymphocyte phenotypes between our case and previously reported cases suggest a diversity of FT1D pathology.

[Retrospective Study of Image Quality in Pediatric Cardiac Cine MRI].

In pediatric cardiac cine magnetic resonance imaging (MRI), it must overcome several challenges including the patient's size and higher heart rate. The aim of this study was to retrospectively evaluate imaging optimization. Cardiac cine MRI data from 24 patients was analyzed (age range: 3 months-10 years, average age: 5 years, male/female: 11/13, R-R interval: 450±4 to 819±7 ms). About 11 cases out of 24 have good image quality. For small variations in the R-R interval and higher temporal resolution improved image quality with significant difference (P<0.05, Mann-Whitney U-test). In this study, values of temporal resolution <30 ms yielded good image quality for heart rates over 100 bpm. On the other hands, the factors dependent on the patient like heart rate and ejection fraction have no significant difference. The segmentation of data acquisition is more significant than recording small fields of view or thin slices for infantile and pediatric cardiac cine MRI. Similar to adult cases, variations in heart rate affect the image quality; however, we demonstrated that using segmentation of data acquisition results in improved image quality.

[Improvement of Brain Contrast Using Spin Echo T1-weighted Image at 3 T MRI].

Brain T1-weighted images using spin echo (SE) sequence has poor contrast at 3.0 Tesla magnetic resonance imaging (3.0 T MRI) systems from the influence of crosstalk and magnetized transfer (MT) effect, and prolongation of the T1 value. Therefore, improving of scan parameters has been reported such as excitation flip angle (FA) and interleave data acquisition. The purpose of this study was to show the effects of alterations of presaturation pulse amplitude and chemical shift selective (CHESS) pulse amplitude. Gray-to-white matter contrast increased with decreasing amplitude of presaturation pulse in whole brain imaging. Presaturation and CHESS pulse consist of radio frequency pulse. Therefore, both pulses have a similar effect on MT pulse. Manual alteration of presaturation pulse amplitude for each scan lacks versatility on clinical use. However, decreasing amplitude of presaturation pulse is equal to decreasing thickness of presaturation pulse. About CHESS pulse, it requires no manual alteration for each scan. For example, switching fat suppression mode from strong to weak increase T1 contrast. Our study demonstrated that using not only low excitation FA and interleave date acquisition but also low amplitude of presaturation and CHESS pulse increase the contrast in T1 SE brain scans at 3.0 T MRI.

Molecular pathogenesis of interstitial cystitis based on microRNA expression signature: miR-320 family-regulated molecular pathways and targets.

Interstitial cystitis (IC), also known as bladder pain syndrome, is a chronic inflammatory disease that affects the bladder. The symptoms of IC vary, including feeling an urgent need for immediate urination and of needing to urinate often, as well as bladder or pelvic pain. Despite its high incidence, no molecular diagnostic methods are available for IC, and the molecular pathogenesis is unknown. microRNAs (miRNA) can regulate expression of RNA transcripts in cells and aberrant expression of miRNAs is associated with several human diseases. Here, we investigated the molecular pathogenesis of IC based on miRNA expression signatures. RNA sequencing of miRNA levels in IC tissues and comparison with levels in normal bladder tissue and bladder cancer revealed dysregulated expression of 366 miRNAs (203 and 163 down- and upregulated miRNAs, respectively). In particular, miR-320 family miRNAs(miR-320a, miR-320b, miR-320c, miR-320d and miR-320e) had downregulated expression in IC tissues. Genome-wide gene expression analyses and in silico database analyses showed that three transcription factors, E2F-1, E2F-2 and TUB, are regulated by miR-320 family miRNAs. Immunostaining of IC tissues confirmed that these transcription factors are overexpressed in IC tissues. Novel approaches that identify aberrantly expressed miRNA regulatory networks in IC could provide new prognostic markers and therapeutic targets for this disease.

Effects of linagliptin monotherapy compared with voglibose on postprandial lipid profiles in Japanese patients with type 2 diabetes: linagliptin study of effects on postprandial blood glucose (L-STEP) sub-study 1.

Recently, we reported that linagliptin had equivalent efficacy to voglibose in reducing postprandial blood glucose levels in drug-naïve patients with type 2 diabetes (L-STEP Study). As a sub-study of the L-STEP Study we examined the effect of linagliptin on postprandial lipids profile. Between October 2012 and April 2014, the study enrolled patients with type 2 diabetes mellitus who had inadequate glycemic control. Patients were randomly assigned to either the linagliptin group (5 mg once daily, n = 85) or the voglibose group (0.2 mg/meal thrice daily, n = 71). Meal tolerance tests were performed at baseline (week 0) and endpoint (week 12). The increments in 4-h postprandial triglyceride, remnant lipoprotein cholesterol (RLP-C), and apolipoprotein B48 (ApoB48) from baseline to endpoint in the linagliptin group were lower (p < 0.001, p = 0.025 and p < 0.001). 4-h postprandial ApoB48 at endpoint was lower in the linagliptin group (p = 0.007), and positive correlation was detected between change of ApoB48 and changes in both triglyceride (r = 0.67, p < 0.001) and RLP-C (r = 0.73, p < 0.001) at 4 h. This study revealed that in drug-naïve Japanese patients with relatively mild type 2 diabetes mellitus, linagliptin improves not only postprandial blood glucose level but also levels of lipids such as TG and RLP-C by reducing the ApoB48 level compared with voglibose.

The Usefulness of Readout-Segmented Echo-Planar Imaging (RESOLVE) for Bio-phantom Imaging Using 3-Tesla Clinical MRI.

Readout-segmented echo-planar imaging (RESOLVE) is a multi-shot echo-planar imaging (EPI) modality with k-space segmented in the readout direction. We investigated whether RESOLVE decreases the distortion and artifact in the phase direction and increases the signal-to-noise ratio (SNR) in phantoms image taken with 3-tesla (3T) MRI versus conventional EPI. We used a physiological saline phantom and subtraction mapping and observed that RESOLVE's SNR was higher than EPI's. Using RESOLVE, the combination of a special-purpose coil and a large-loop coil had a higher SNR compared to using only a head/neck coil. RESOLVE's image distortioas less than EPI's. We used a 120 mM polyethylene glycol phantom to examine the phase direction artifact.vThe range where the artifact appeared in the apparent diffusion coefficient (ADC) image was shorter with RESOLVE compared to EPI. We used RESOLVE to take images of a Jurkat cell bio-phantom: the cell-region ADC was 856×10-6mm2/sec and the surrounding physiological saline-region ADC was 2,951×10-6mm2/sec. The combination of RESOLVE and the 3T clinical MRI device reduced image distortion and improved SNR and the identification of accurate ADC values due to the phase direction artifact reduction. This combination is useful for obtaining accurate ADC values of bio-phantoms.

Comparison of the Effects of Teneligliptin and Sitagliptin, Two Dipeptidyl Peptidase 4 Inhibitors with Different Half-Lives, on Glucose Fluctuation and Glucagon-Like Peptide-1 in Type 2 Diabetes Mellitus.

Our purpose was to determine the effects of teneligliptin and sitagliptin, two dipeptidyl peptidase 4 inhibitors (DPP4-Is) with different half-lives, on glycemic variability and glucagon-like peptide-1 (GLP-1) levels in Japanese patients with type 2 diabetes mellitus (T2DM). The study subjects were 14 drug-naïve patients with T2DM who were allocated to either a 20 mg/day teneligliptin group (n = 7) or a 50 mg/day sitagliptin group (n = 7) for 7 days, then switched to the other treatment for another 7 days. Meal tolerance tests were performed at the time of no treatment, and after treatment with each DPP4-Is at supper. We evaluated the effects of each drug on glucose fluctuation using continuous glucose monitoring (CGM). There was no significant difference between the two groups in the primary endpoint (maximum glucose level after supper), nor in the secondary endpoint: area under the curve (AUC) for plasma glucose (≥140 mg/dl) after supper (18:00 - 24:00). Teneligliptin significantly improved the AUC for plasma glucose (≥140 mg/dl) after supper (20:00-24:00) (P = 0.048), and also significantly increased the GLP-1 level at 30 minutes after the meal load (P = 0.030). No serious adverse effects were noted in either group, apart from a few episodes of asymptomatic hypoglycemia. A daily dose of teneligliptin improved the AUC for plasma glucose at 20:00 to 24:00 (≥140 mg/dl) after the meal tolerance test, and also significantly increased the levels of activated GLP-1 after the test meal.

Glycemic Profiling in Patients with Drug-Naïve Type 2 Diabetes by Continuous Glucose Monitoring.

The purpose of this study was to determine the glycemic profiles of drug-naïve type 2 diabetes patients according to hemoglobin A1c (HbA1c) level using continuous glucose monitoring. We aimed to clarify factors associated with HbA1c and average blood glucose level. Patients were divided into three groups according to their HbA1c level (< 7.0% n=23, 7.0% ≤ HbA1c < 8.0% n=17 and ≥ 8.0% n=31), and the factors associated with HbA1c and average glucose of each group were evaluated. Pre-meal glucose levels were the highest before lunch, and the 2 hour postprandial blood glucose level was the lowest after lunch. The pre-meal and postprandial blood glucose levels increased after each meal with increases in HbA1c. Average glucose level was the most significant determinant of HbA1c, whereas pre-meal glucose level at dinner was the most significant determinant of average glucose level, and the range of increase in glucose from pre-meal at dinner was the most significant determinant of standard deviation (SD) of 24 hour glucose levels. HbA1c subgroup analysis indicated that pre-meal glucose level at lunch significantly correlated with average glucose level in the HbA1c < 8.0% group, while pre-meal glucose level at dinner significantly correlated with average glucose level in the HbA1c ≥ 8.0% group. The range of increase in glucose from pre-meal in the morning significantly correlated with SD of 24 hour glucose levels in the HbA1c < 8.0% group, and the postprandial peak glucose level at lunch significantly correlated with SD of 24 hour glucose levels in the HbA1c ≥ 8.0% group. The results suggest that improvement of the average glucose level is necessary to improve the HbA1c levels. For patients with HbA1c < 7.0%, it is important to improve blood glucose level after breakfast and before lunch to decrease the average glucose level. For patients with 7.0% ≤ HbA1c < 8.0%, it is important to improve blood glucose level before lunch and after dinner to decrease the average glucose level. For patients with HbA1c ≥ 8.0%, it is important to improve blood glucose levels after lunch and before dinner to decrease the average glucose level.