Prospective randomized comparative study of the effect of pemafibrate add-on or double statin dose on small dense low-density lipoprotein-cholesterol in patients with type 2 diabetes and hypertriglyceridemia on statin therapy.

AIMS/INTRODUCTION: Small dense low-density lipoprotein (sdLDL) is a more potent atherogenic lipoprotein than LDL. As sdLDL-cholesterol (C) levels are determined by triglyceride and LDL-C levels, pemafibrate and statins can reduce sdLDL-C levels. However, it remains unclear whether adding pemafibrate or increasing statin doses would more effectively reduce sdLDL-C levels in patients receiving statin therapy. MATERIALS AND METHODS: A total of 97 patients with type 2 diabetes and hypertriglyceridemia who were treated with statins were randomly assigned to the pemafibrate 0.2 mg/day addition or statin dose doubled, and followed for 12 weeks. sdLDL-C was measured by our established homogenous assay. RESULTS: The percentage and absolute reductions of sdLDL-C levels were significantly greater in the pemafibrate add-on group than the statin doubling group (-32.8 vs -8.1%; -16 vs -3 mg/dL, respectively). Triglyceride levels were reduced only in the pemafibrate add-on group (-44%), and LDL-C levels were reduced only in the statin doubling group (-8%), whereas levels of non-high-density lipoprotein-C and apolipoprotein B were similarly decreased (7-9%) in both groups. The absolute reductions of sdLDL-C levels were closely associated with decreased triglyceride, LDL-C, non-high-density lipoprotein-C and apolipoprotein B. In the subgroup analysis, the effect of pemafibrate add-on on sdLDL-C reductions was observed irrespective of baseline lipid parameters or statin type. No serious adverse effects were observed in both groups. CONCLUSIONS: In patients with type 2 diabetes and hypertriglyceridemia, the addition of pemafibrate to a statin is superior to doubling a statin in reducing sdLDL-C without increasing adverse effects.

[A case of neurosyphilis presenting as bilateral temporal, cortical and subcortical encephalitis].

A 37-year-old man who had a low grade fever for 5 days admitted to our hospital due to disturbance of consciousness and seizure. Brain MRI showed abnormal hyperintensity in the bilateral temporal lobes, cortical and subcortical lesions on fluid-attenuated inversion recovery image. Treponemal and non-treponemal specific antibodies were positive in serum and cerebrospinal fluid, therefore he was diagnosed as having neurosyphilis. Treatment with intravenous penicillin G and metylpredonisolone improved his clinical symptons, imaging abnormalities and CSF findings. Patients of neurosyphilis with mesiotemporal encephalitis show common features such as young age, HIV-negative, subacute cognitive impairment and seizure, as seen in our case. Early diagnosis of neurosyphilis and appropriate treatment make clinical improvement, however the clinical diagnosis of neurosyphilis is sometime difficult because most patients present with disturbance of consciousness or seizure. The possibility of neurosyphilis should be considered when MRI results indicate temporal abnormalities.

Circadian Rhythm of Subspecies of Low-Density Lipoprotein-Cholesterol and High-Density Lipoprotein-Cholesterol in Healthy Subjects and Patients with Type 2 Diabetes.

AIMS: We established automated assay kits for quantifying small dense low-density lipoprotein (sdLDL)-cholesterol (C), LDL-triglyceride (TG), and high-density lipoprotein (HDL)3-C, and apolipoprotein (apo)E-rich HDL-C, and these have been recognized as sensitive biomarkers for predicting coronary artery disease. We investigated the circadian rhythms of these novel lipids to determine if fasting is required to determine basal levels. METHODS: Forty-eight inpatients with type 2 diabetes and 19 healthy volunteers were studied. Blood samples were collected at seven time points, which were obtained after an overnight fast, before and 2 h after each meal, and before the next breakfast. sdLDL-C, LDL-TG, remnant-like particle (RLP)-C, TG-rich lipoprotein (TRL-C), HDL3-C, and apoE-rich HDL-C were measured by the homogeneous methods. NonHDL-C, large buoyant (lb)LDL-C and HDL2-C were calculated by subtracting sdLDL-C from LDL-C or HDL3-C from HDL-C, respectively. RESULTS: Serum TG levels were significantly increased after meals in both healthy participants and patients with diabetes. RLP-C and TRL-C were also increased postprandially. LDL-TG, LDL-C, nonHDL-C, HDL2,3-C, and apoE-rich HDL-C did not exhibit significant fluctuation during the day in healthy participants and patients with diabetes. sdLDL-C was slightly increased postprandially in subjects with diabetes (1-2 mg/dl, 3%-9%), though its increase was not significant compared to the baseline (fasting) level. Significant postprandial reduction was observed with LDL-C and lbLDL-C. There was no influence of statin therapy or oral anti-diabetes drugs on the circadian rhythm of LDL-C subspecies. CONCLUSIONS: Subtle postprandial increase in sdLDL-C is considered a negligible level in general clinical practice. Fasting is not mandatory to measure basal concentrations of LDL and HDL subspecies.

Clinical characteristics and management of headache in patients with myeloproliferative neoplasms.

Background: Headache is frequently reported as a neurological manifestation of myeloproliferative neoplasms (MPNs), including polycythemia vera and essential thrombocythaemia. This study sought to clarify the clinical characteristics and response to treatment of headaches in patients with MPNs. Methods: We prospectively studied 137 patients with MPNs. The following information was gathered to assess the features of headache at baseline and at follow-up (>6 months): (1) average duration of headache attacks, (2) number of headache days per month, (3) numerical rating scale (NRS), (4) Headache Impact Test-6 (HIT-6), and (5) Migraine Disability Assessment (MIDAS). We compared those parameters for headaches between the baseline and follow-up interviews according to the management. Results: Thirty-seven (27.0%) patients had headache. The prevalence of headaches gradually decreased with increasing age (Age ≤ 49 years: 61.0%, 50-59 years: 38.5%, 60-69 years: 17.2%, 70-79 years: 5.1%, and ≥80 years: 0.0%, P < 0.001). Multiple logistic regression analysis showed that younger age, but not platelet counts or the JAK2 V617F mutation, was independently associated with headaches (Odds Ratios 2.004, 95% confidence intervals 1.293-3.108, P = 0.002). Scintillating scotomas were present in 22 (59.5%) of 37 patients with headaches, while four patients developed sudden headaches that lasted for only 0-10 min. Follow-up interviews were available for 31 (83.8%) of 37 patients with headaches. Twenty-one (67.7%) patients were treated with low-dose aspirin (100 mg once daily) [low-dose aspirin alone: n = 9; combined cytoreductive therapy: n = 12] for headache management. All parameters for headache [average duration of headache attacks, number of headache days per month, NRS score, HIT-6 score, and MIDAS score (all P < 0.001)] were significantly improved at follow-up in patients taking low-dose aspirin. However, there were no significant differences in these parameters of headaches in patients who did not receive low-dose aspirin. Conclusion: Headaches is common in patients with MPNs, particularly in younger patients. MPN-related headaches may be managed by using low-dose aspirin and controlling MPNs.

Effectiveness of treatment for 31 patients with seropositive autoimmune autonomic ganglionopathy in Japan.

Background: Autoimmune autonomic ganglionopathy (AAG) is characterized by serum autoantibodies against the ganglionic acetylcholine receptor (gAChR). Immunomodulatory treatments may alleviate AAG symptoms, but the most appropriate treatment strategy is unclear. Objective: This study aimed to confirm the effectiveness of treatments, particularly immunotherapy, in patients with seropositive AAG in Japan, as well as to determine the most effective treatment and the best assessment method for clinical response to treatment. Methods: We collected data from a previous cohort study of patients with seropositive AAG. The clinical autonomic and extra-autonomic symptoms were objectively counted and subjectively assessed using the modified Composite Autonomic Symptom Score. Post-treatment changes in the gAChR antibody level were evaluated. Results: Thirty-one patients received immunotherapy. Among them, 19 patients received intravenous methylprednisolone; 27, intravenous immunoglobulin; 3, plasma exchange; 18, oral steroids; 2, tacrolimus; 1, cyclosporine; and 1, mycophenolate mofetil. Patients who received immunotherapy showed improvements in the total number of symptoms (from 6.2 ± 2.0 to 5.1 ± 2.0) and modified Composite Autonomic Symptom Score (from 37.4 ± 15.3 to 26.6 ± 12.8). Orthostatic intolerance, sicca, and gastrointestinal symptoms were ameliorated by immunotherapy. Immunotherapy decreased the antibody levels (gAChRα3 antibodies, from 2.2 ± 0.4 to 1.9 ± 0.4, p = 0.08; gAChRß4 antibodies, from 1.6 ± 0.1 to 1.0 ± 0.2, p = 0.002), but antibody levels increased in 10 patients despite immunotherapy. The rate of improvement in the total number of symptoms was higher in patients with combined therapy than in patients with non-combined therapy (70.7% vs 28.6%). Conclusions: The scores in many items on the rating scale decreased after immunotherapy in patients with seropositive AAG, particularly in the combined immunotherapy group. However, more accurate assessment scales for clinical symptoms and multicenter randomized, placebo-controlled prospective studies are warranted to establish future treatment strategies.

Efficacy of a new enzyme-linked immunosorbent assay system for three islet cell autoantibodies in Japanese patients with acute-onset type 1 diabetes.

To evaluate the clinical efficacy of a new enzyme-linked immunosorbent assay (ELISA) system for simultaneously detecting three islet cell autoantibodies against glutamic acid decarboxylase (GADA), insulinoma-associated antigen-2 (IA-2A), and zinc transporter 8 (ZnT8A) (3 Screen ICA ELISA) in Japanese patients with acute-onset type 1 diabetes (T1D). In addition, clinical factors affecting the 3 Screen ICA ELISA index were investigated. We compared the positivity values of 3 Screen ICA ELISA with that of each autoantibody alone in 97 patients with acute-onset T1D (mean age 48.7 years, 49% male) and 100 non-diabetic subjects (mean age 47.0 years, 50% male). Serum thyroid stimulating hormone receptor antibody, thyroid peroxidase antibody (TPOAb) and thyroglobulin autoantibody levels were also evaluated. The cut-off value of the 3 Screen ICA ELISA was determined based on the 97th percentile of 100 non-diabetic controls (threshold for positivity, ≥14 index). The mean age of disease onset and duration of diabetes were 34.2 years and 14.5 years, respectively. Among all T1D patients, the positivity of 3 Screen ICA ELISA was 71.1%, while that of GADA, IA-2A, and ZnT8A were 59.8%, 25.8%, and 25.8%, respectively. The median 3 Screen ICA index was 121.9 (8.7-468.2) and was associated with titers of each autoantibody, most so with GADA, and was significantly higher in TPOAb-positive patients than in TPOAb-negative patients. Our findings suggests that the 3 Screen ICA ELISA may be a time-saving diagnostic tool for evaluating islet autoantibodies in acute-onset T1D patients.

FLAMES with Elevated Myelin Basic Protein Followed by Myelitis.

The pathophysiology of unilateral cortical fluid-attenuated inversion recovery (FLAIR)-hyperintense lesions in anti-myelin oligodendrocyte glycoprotein (MOG)-associated encephalitis with seizures (FLAMES) is unclear. A 26-year-old man was referred because of a seizure. FLAIR showed an increased signal intensity and swelling of the right frontal cortex. His symptoms and imaging abnormalities were improved after intravenous methylprednisolone therapy. MOG antibody was detected both in serum and cerebrospinal fluid (CSF). Therefore, the patient was diagnosed with FLAMES. Myelin basic protein (MBP) was elevated in CSF. The high MBP value in the CSF in the present case suggested that demyelination as well as inflammation can occur in some FLAMES patients.

Estimation and Sharpening of Blur in Degraded Images Captured by a Camera on a Moving Object.

In this research, we aim to propose an image sharpening method to make it easy to identify concrete cracks from blurred images captured by a moving camera. This study is expected to help realize social infrastructure maintenance using a wide range of robotic technologies, and to solve the future labor shortage and shortage of engineers. In this paper, a method to estimate parameters of motion blur for Point Spread Function (PSF) is mainly discussed, where we assume that there are two main degradation factors caused by the camera, out-of-focus blur and motion blur. A major contribution of this paper is that the parameters can properly be estimated from a sub-image of the object under inspection if the sub-image contains uniform speckled texture. Here, the cepstrum of the sub-image is fully utilized. Then, a filter convoluted PSF which consists of convolution with PSF (motion blur) and PSF (out-of focus blur) can be utilized for deconvolution of the blurred image for sharpening with significant effect. PSF (out-of-focus blur) is a constant function unique to each camera and lens, and can be confirmed before or after shooting. PSF (motion blur), on the other hand, needs to be estimated on a case-by-case basis since the amount and direction of camera movement varies depending on the time of shooting. Previous research papers have sometimes encountered difficulties in estimating the parameters of motion blur because of the emphasis on generality. In this paper, the main object is made of concrete, and on the surface of it there are speckled textures. We hypothesized that we can narrow down the candidates of parameters of motion blur by using these speckled patterns. To verify this hypothesis, we conducted experiments to confirm and examine the following two points using a general-purpose camera used in actual bridge inspections: 1. Influence on the cepstrum when the isolated point-like texture unique to concrete structures is used as a feature point. 2. Selection method of multiple images to narrow down the candidate minima of the cepstrum. It is novel that the parameters of motion blur can be well estimated by using the unique speckled pattern on the surface of the object.

Sustained atrial fibrillation is related to a higher severity of stroke in patients taking direct oral anticoagulants.

BACKGROUND: Atrial fibrillation (AF) includes paroxysmal and sustained (persistent or permanent) AF, and both forms are considered risk factors for ischemic stroke. This study aimed to investigate the differences in stroke severity at admission between patients with paroxysmal AF and sustained AF when treated with direct oral anticoagulants (DOACs). METHODS: Using data from DOAC-treated 300 nonvalvular patients with AF and acute anterior circulation stroke who were registered in the Multicenter Prospective Analysis of Stroke Patients Taking Oral Anticoagulants study, patients were divided into two groups, namely, paroxysmal AF and sustained AF. We compared the clinical characteristics between the two groups and determined the effect of these two types of AF on stroke severity on admission. RESULTS: Of 300 patients, 246 (males, n = 149; median age, 80 years) and 54 (males, n = 32; median age, 78 years) were assigned to the sustained AF and paroxysmal AF groups, respectively. The sustained AF group had a higher proportion of severe stroke (National Institutes of Health Stroke Scale score, >20) on admission (22.0% vs. 5.7%, p = 0.006) and internal carotid artery occlusion (11.4% vs. 1.9%, p = 0.03) compared to the paroxysmal AF group. Multivariate analysis showed that sustained AF was independently associated with severe stroke on admission (odds ratio 4.31, 95% confidence interval 1.24-15.0, p = 0.02). CONCLUSIONS: Sustained AF was associated with a higher severity of stroke accompanied with major vessel occlusion than paroxysmal AF, even prior to DOACs treatment. Registration https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034958.

Metabolic Properties of Lowdensity Lipoprotein (LDL) Triglycerides in Patients with Type 2 Diabetes, Comparison with Small Dense LDL-Cholesterol.

AIMS: Abnormal compositional changes in low-density lipoprotein (LDL) particles, such as triglyceride (TG) enrichment and size reduction, are common in patients with diabetes. Several cohort studies have demonstrated that LDL-TG and sdLDL-cholesterol (C) are sensitive biomarkers for predicting atherosclerotic cardiovascular diseases beyond LDL-C. Although sdLDL has been extensively studied, little is known about the properties of LDL-TG. We investigated similarities or differences between LDL-TG and sdLDL-C. METHODS: Fasting plasma was obtained from 1,085 patients with type 2 diabetes who were enrolled in the diabetes regional cohort study (ViNA Cohort). LDL-TG and sdLDL-C concentrations were measured using a homogeneous assay established by us. In a subset of subjects, LDL-TG and sdLDL-C levels were measured postprandially or after treatment with lipid-lowering drugs. RESULTS: In a quartile analysis, higher LDL-TG quartiles were associated with higher frequency of female and fibrate users, whereas sdLDL-C quartiles were associated with frequency of men, drinking, and metabolic syndrome-related measurements. Higher quartiles of LDL-TG/LDL-C were associated with smoking, drinking, fibrate users, and statin users. LDL-TG was significantly correlated with TG, LDL-C, sdLDL-C, and apolipoprotein (apo) B, with apoB being the primary determinant. LDL-TG correlated to high sensitive C-reactive protein (CRP) independently of other lipids. Mean LDL-TG did not change with fasting/non-fasting. Statin treatment reduced LDL-TG, whereas fibrates increased it, but these drugs reduced sdLDL-C equally. CONCLUSIONS: LDL-TG levels were more tightly regulated by the number of LDL particles than plasma TG levels were. SdLDL-C was closely associated with metabolic syndrome-related factors, whereas LDL-TG was associated with low-grade systemic inflammation.

Dyslipidemia in diabetic kidney disease classified by proteinuria and renal dysfunction: A cross-sectional study from a regional diabetes cohort.

AIMS/INTRODUCTION: Diabetic kidney disease (DKD) exacerbates dyslipidemia and increases the incidence of atherosclerotic cardiovascular disease. DKD is a concept that includes typical diabetic nephropathy and an atypical phenotype without proteinuria. We investigated dyslipidemia in different DKD phenotypes that have not been fully studied. MATERIALS AND METHODS: Fasting plasma was obtained from 1,073 diabetes patients enrolled in the regional diabetes cohort (ViNA cohort). Non-proteinuric and proteinuric DKD were defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2 in the absence or presence of urinary albumin-to-creatinine ratio >300 mg/g. Novel lipid risk factors, low-density lipoprotein (LDL) triglyceride (TG) and small dense LDL cholesterol were measured using our established homologous assay. RESULTS: The proportion of atherosclerotic cardiovascular disease patients was higher in non-proteinuric DKD and even higher in proteinuric DKD than in non-DKD. Increased estimated glomerular filtration rate grade and albuminuric stage were independently correlated with higher TG, TG-rich lipoprotein cholesterol and apolipoprotein CIII. Therefore, proteinuric DKD had the highest of these levels. Small dense LDL cholesterol and LDL-TG were higher in the proteinuria without renal dysfunction group in the lipid-lowering drug-free subset. Lipoprotein(a) was higher in DKD regardless of proteinuria. CONCLUSIONS: Proteinuria was associated with an atherogenic subspecies of LDL, whereas renal dysfunction was associated with increased lipoprotein(a). Proteinuria and renal dysfunction independently exacerbated TG-rich lipoprotein-related dyslipidemia. This is in good agreement with the results of large-scale clinical studies in which proteinuria and renal dysfunction synergistically increased the risk of atherosclerotic cardiovascular disease in populations with diabetes.

Unilateral Isolated Trochlear Nerve Palsy due to Ipsilateral Midbrain Infarction.

Ischemic stroke is a very rare etiology in cases of isolated trochlear nerve palsy, and no reports of ipsilateral trochlear nerve palsy caused by unilateral stroke have so far been published. However, we now report a case of isolated trochlear nerve palsy due to ipsilateral dorsal small midbrain infarction in a 70-year-old woman who presented with acute onset of diplopia. There were no other clinical manifestations, but brain magnetic resonance imaging revealed a small ischemic lesion in the right dorsal midbrain, showing that isolated trochlear nerve palsy can be caused by stroke.

Dapagliflozin Influences Ventricular Hemodynamics and Exercise-Induced Pulmonary Hypertension in Type 2 Diabetes Patients　- A Randomized Controlled Trial.

BACKGROUND: This prospective randomized multicenter open-label trial evaluated whether sodium-glucose cotransporter-2 inhibitor (SGLT2-i) improves left ventricular (LV) pump function and suppresses elevation of LV filling pressure (LVFP) and right ventricular systolic pressure (RVSP) during exercise in type 2 diabetes mellitus (T2DM) patients.Methods and Results:Based on HbA1c and LV ejection fraction, 78 patients with poorly controlled T2DM were randomly assigned to D-group (dapagliflozin 5 mg/day add-on) or C-group (conventional therapy add-on). Physical examination, home and office blood pressure examination, blood tests, and echocardiography at rest and during ergometer exercise were performed at baseline and at 1.5 and 6 months after treatment. The primary endpoint was defined as the change in RVSP (mmHg) between baseline and 6-month follow up. The secondary endpoints were changes in LVFP (ratio), stroke volume index (SVi; mL/m2), and cardiac index (CI; L/min/m2). Both RVSP and LVFP during exercise significantly decreased from baseline to 6 months after starting treatment in the D-group (P<0.001). No changes to either parameter was observed in the C-group. The SVi and CI did not improve in either group. Both home and office blood pressure significantly decreased in the D-group. Decreases in HbA1c were somewhat greater in the C-group. CONCLUSIONS: Dapagliflozin significantly improved RVSP and LVFP during exercise in patients with T2DM and cardiovascular risk, which may contribute to favorable effects on heart failure.

Pancreatic fat accumulation evaluated by multidetector computed tomography in patients with type 2 diabetes.

AIMS: To clarify the clinical impact of pancreatic fat volume on beta cell function in type 2 diabetes patients. MATERIALS AND METHODS: One hundred thirty two consecutive type 2 diabetic patients (mean age, 63.7 years) were enrolled in this cross-sectional study. Total pancreatic volume (TPV), pancreatic fat volume (PFV), and pancreatic parenchymal volume (PPV), and visceral fat volume were examined quantitatively with multidetector computed tomography using SYNAPSE VINCENT image analysis system (Fujifilm Inc., Tokyo, Japan). Pancreatic fat was identified using Hounsfield Units of less than zero. The capacity of insulin secretion was assessed by C-peptide immunoreactivity (CPR) index (100 × fasting CPR/fasting plasma glucose). Insulin sensitivity was evaluated using CPR-insulin resistance (20/fasting CPR × fasting plasma glucose). RESULTS: TPV, PFV, PPV, and visceral fat volume were significantly correlated with body weight (BW). PPV/BW, but not PFV/BW, significantly decreased with increasing duration of diabetes and aging. PFV/BW was positively associated with body mass index and visceral fat volume/BW. PFV/BW was significantly correlated with CPR index, while inversely associated with insulin sensitivity. CPR index, but not CPRinsulin resistance was progressively decreased in patients with a longer duration of diabetes. When patients were divided into two groups according to a median PFV/BW value, CPR index in high PFV/BW group with diabetes duration >5 years was significantly lower than those ≤5 years. However, duration-dependent decrease in CPR index was not observed in low PFV/BW group. CONCLUSIONS: Our present study suggests that PFV might predict the progression of beta cell dysfunction in patients with type 2 diabetes.

Relationship between glucose variability evaluated by continuous glucose monitoring and clinical factors, including glucagon-stimulated insulin secretion in patients with type 2 diabetes.

AIMS: To evaluate the clinical factors affecting daily and day-to-day glucose variability by using continuous glucose monitoring. METHODS: We performed a cross-sectional analysis of patients with type 2 diabetes mellitus (T2DM) who underwent a glucagon stimulation test (GST) with 72 h of continuous glucose monitoring. Daily glucose variability was evaluated by mean amplitude of glycemic excursions [MAGE], percentage coefficient of variation for glucose (%CV), and day-to-day glucose variability (mean of daily differences [MODD]) by using continuous glucose monitoring. Correlations of clinical factors, including insulin secretion ability by the GST with MAGE, %CV, and MODD, were analyzed. RESULTS: In 83 T2DM with insulin therapy, age and hemoglobin A1c (HbA1c) correlated with MAGE and %CV, fasting plasma glucose with MAGE and MODD, and increment of C-peptide immunoreactivity (ΔCPR) by GST correlated inversely with MAGE, %CV, and MODD. In 126 T2DM without insulin therapy, age, diastolic blood pressure, and triglycerides correlated with MODD, HbA1c with MAGE and MODD, and ΔCPR inversely correlated with %CV. Use of α-glucosidase inhibitors inversely correlated with %CV, whereas that of sulfonylurea was associated with MAGE and %CV. CONCLUSIONS: These results suggest that ΔCPR correlated with stability of glycemic control, whereas poorly controlled diabetes is associated with increase in glucose variability. α-glucosidase inhibitors may be superior to sulfonylureas in reducing the glucose variability in T2DM.

Association of glucose and blood pressure variability on oxidative stress in patients with type 2 diabetes mellitus and hypertension: a cross-sectional study.

BACKGROUND: The present study evaluated the effects of glucose and blood pressure (BP) variability on oxidative stress in patients with type 2 diabetes mellitus (T2DM) and hypertension. METHODS: A total of 60 inpatients with T2DM underwent continuous glucose monitoring (CGM) and ambulatory BP monitoring (ABPM). Oxidative stress was estimated using the diacron-reactive oxygen metabolites (d-ROMs) test. Glucose variability, mean glucose level, percentage coefficient of variation for glucose, mean amplitude of glycemic excursions (MAGE), and area under the postprandial plasma glucose curve were determined through CGM. BP variability was assessed by measuring average BP, standard deviation (SD) of systolic and diastolic BP, and coefficient of variation (CV) of systolic and diastolic BP during daytime and nighttime ABPM. RESULTS: Participants had a mean age of 64.5 ± 13.3 years with the duration of the disease 13.9 ± 12.4 years and HbA1c of 8.5 ± 1.2%. Univariate analysis showed that MAGE, nighttime SDs of systolic and diastolic BP, and nighttime CV of systolic BP were significantly correlated with d-ROMs. Further, stepwise multiple regression analysis identified MAGE, nighttime SD and CV of diastolic BP, estimated glomerular filtration rate, and smoking as independent contributors to d-ROMs. CONCLUSIONS: Oxidative stress was associated with daily glucose and nighttime diastolic BP variability in patients with T2DM and hypertension.Trial registration UMIN Clinical Trial Registry UMIN000035615, Registered January 22, 2019-retrospectively registered.

Effect of brain atrophy in quantitative analysis of 123I-ioflupane SPECT.

OBJECTIVE: Dopamine transporter (DAT) imaging such as 123I-ioflupane (123I-FP-CIT) SPECT is a useful tool for the diagnosis of parkinsonism and dementia. The Southampton method is the quantitative method for evaluating 123I-FP-CIT SPECT and is less affected by the partial volume effect of the striatum. The method may be vulnerable to contamination by low-uptake areas of cerebrospinal fluid in whole brain, and the threshold of voxel value (threshold method, TM) was developed to correct the contamination. The purpose of this study is to evaluate the TM in the patients with neurological disease. METHODS: We studied 99 subjects, including 39 patients with Alzheimer's disease (AD), 15 patients with Parkinson's disease (PD) and 10 patients with dementia with Lewy bodies (DLB). Each subject had undergone 123I-FP-CIT SPECT. We calculated the SBR with and without the TM. The SBR laterality was assessed using the asymmetry index (AI). We investigated the relationship between the SBR change with TM and brain atrophy, which were assessed using Evans index (EI), sylvian index (SI) and cerebral atrophy index (CAI). Cutoff value for EI was 0.3, and cutoff values for SI and CAI were the first quartile, respectively. RESULTS: The SBR with TM was 0.53 percentage points lower than the SBR without TM overall (p < 0.01). Positive and negative reversal of AI increased with age. The rate of the SBR change with TM was tended to be lower in groups with brain atrophy. The number of voxels excluded by TM in striatal volumes of interest (VOIs) was larger with high groups for EI, SI and CAI than in low groups. The number of voxels excluded using TM in reference VOIs was related to SI. CONCLUSIONS: The SBR was decreased using TM. The effect of TM on the SBR tended to be small in the subjects with severe brain atrophy. The effect of brain atrophy in the TM is larger in the striatal VOIs than in the reference VOIs. Even if quantitative analyses are available, visual assessment of 123I-FP-CIT SPECT is essential for diagnosis.

Circulating anti-glutamic acid decarboxylase-65 antibody titers are positively associated with the capacity of insulin secretion in acute-onset type 1 diabetes with short duration in a Japanese population.

AIMS/INTRODUCTION: To elucidate the relationship between titers of islet autoantibodies, the C-X-C motif chemokine 10 - a circulating chemokine that activates T-helper 1 cells leading to ß-cell destruction - and ß-cell function in type 1 diabetes. MATERIALS AND METHODS: In total, 58 type 1 diabetes patients positive for glutamic decarboxylase-65 autoantibodies (GADA)-radioimmunoassay (mean age 54.1 years; 27 acute-onset cases and 31 slowly progressive cases) were enrolled; serum C-X-C motif chemokine 10 (n = 50), zinc transporter 8 autoantibodies (n = 50) and GADA (n = 58) by an enzyme-linked immunosorbent assay, and insulinoma-associated antigen-2 autoantibodies by radioimmunoassay (n = 50) were measured. The ratio of 100 × random C-peptide (ng/mL)-to-plasma glucose levels (mg/dL; C-peptide index [CPI]) was measured. RESULTS: The CPI significantly decreased in both groups with the progression of disease duration. GADA titers by radioimmunoassay and enzyme-linked immunosorbent assay were strongly correlated with the CPI in acute-onset type 1 diabetes patients with a shorter disease duration (≤10 years), but not in those with a longer duration or slowly progressive type 1 diabetes. Neither insulinoma-associated antigen-2 nor zinc transporter 8 autoantibodies titers were correlated with the CPI. Serum C-X-C motif chemokine 10 levels in both groups were significantly higher than in non-diabetic controls, and persisted at high levels even in those with chronic duration. CONCLUSIONS: Among islet autoantibodies, the intensity of the humoral immune response, as defined by GADA titers, reflected the degree of residual ß-cell function in acute-onset type 1 diabetes patients with short duration. Prolonged disease activity might accelerate ß-cell impairment in both subtypes of type 1 diabetes.

Effect of Dulaglutide Versus Liraglutide on Glucose Variability, Oxidative Stress, and Endothelial Function in Type 2 Diabetes: A Prospective Study.

INTRODUCTION: To compare the effect of dulaglutide and liraglutide on oxidative stress and endothelial function in patients with type 2 diabetes mellitus (T2DM). METHODS: Twenty-two patients with T2DM who received treatment with liraglutide for at least 12 weeks were randomized to either continue liraglutide or receive dulaglutide for 24 weeks. The primary end points were changes in the diacron-reactive oxygen metabolite (d-ROMs) test, as a marker of oxidative stress, and endothelial function, as determined by the reactive hyperemia index (RHI). The secondary end points were changes in body weight (BW), glucose variability, diabetes treatment satisfaction questionnaire (DTSQ) score, and eating behavior. RESULTS: There were no significant differences in changes in d-ROMs and logarithmic-scaled RHI (L-RHI) between the two groups after 24 weeks of treatment. Notably, the treatment with dulaglutide was superior to that with liraglutide in terms of mean glucose levels and mean amplitude of glycemic excursions following the 24-week treatment. However, in this regard, the outcome following the treatment with dulaglutide was maintained, whereas that with the treatment with liraglutide was aggravating. The DTSQ score for "convenience" improved in the dulaglutide group. No statistically significant changes in fasting plasma glucose, hemoglobin A1c, and BW were observed between the two groups. CONCLUSION: We showed that once-weekly dulaglutide was comparable to once-daily liraglutide in terms of oxidative stress and endothelial function. Switching from liraglutide to dulaglutide improved convenience by decreasing the number of injections without deteriorating glucose metabolism. TRIAL REGISTRATION: This trial was registered with the University Hospital Medical Information Network (UMIN no. 000034353) on 10 October 2018.