Improved Glycemic Control through Robot-Assisted Remote Interview for Outpatients with Type 2 Diabetes: A Pilot Study.

Background and Objectives: Our research group developed a robot-assisted diabetes self-management monitoring system to support Certified Diabetes Care and Education Specialists (CDCESs) in tracking the health status of patients with type 2 diabetes (T2D). This study aimed to evaluate the impact of this system on glycemic control and to identify suitable candidates for its use. Materials and Methods: After obtaining written informed consent from all participants with T2D, the CDCESs conducted remote interviews with the patients using RoBoHoN. All participants completed a questionnaire immediately after the experiment. HbA1c was assessed at the time of the interview and two months later, and glycemic control status was categorized as either "Adequate" or "Inadequate" based on the target HbA1c levels outlined in the guidelines for adult and elderly patients with type 2 diabetes by the Japan Diabetes Society. Patients who changed their medication regimens within the two months following the interview were excluded from the study. Results: The clinical characteristics of the 28 eligible patients were as follows: 67.9 ± 14.8 years old, 23 men (69%), body mass index (24.7 ± 4.9 kg/m2), and HbA1c levels 7.16 ± 1.11% at interview and two months later. Glycemic control status (GCS) was Adequate (A) to Inadequate (I): 1 case; I to A: 7 cases; A to A good: 14 cases; I to I: 6 cases (p-value = 0.02862 by Chi-square test). Multiple regression analyses showed that Q1 (Did RoBoHoN speak clearly?) and Q7 (Was RoBoHoN's response natural?) significantly contributed to GCS, indicating that the naturalness of the responses did not impair the robot-assisted interviews. The results suggest that to improve the system in the future, it is more beneficial to focus on the content of the conversation rather than pursuing superficial naturalness in the responses. Conclusions: This study demonstrated the efficacy of a robot-assisted diabetes management system that can contribute to improved glycemic control.

Heartache and Heartbreak: An Observational and Mendelian Randomization Study.

Background: Depression has a significant effect on cardiovascular disease (CVD), but uncertainties persist regarding which modifiable risk factors mediate the causal effects. We aim to determine whether depression is causally linked to CVD and which modifiable risk factors play potential mediating roles. Methods: We used a two-sample Mendelian randomization (MR) approach and NHANES 2007-2018 data to estimate the effects of depression on various CVD cases and investigated 28 potential mediators of the association between depression and CVD. Results: The results of our MR analysis indicated that genetically determined depression was associated with increased risk of several CVD, including coronary heart disease (odds ratio (OR) = 1.14; 95% confidence interval (CI): 1.05,1.22), myocardial infarction (OR = 1.19; 95% CI, 1.09,1.31), atrial fibrillation (OR = 1.14; 95% CI, 1.06,1.22), and stroke (OR = 1.13; 95% CI, 1.05,1.22). However, there was no causal association between depression and heart failure. Four out of 28 cardiometabolic risk factors, including hyperlipidemia, hypertension, diabetes, and prescription opioid use, were identified as mediators of the association between depression and various CVDs. Observational association analyses from NHANES data yielded consistent results. Conclusion: Our findings demonstrated that depression has a causal detrimental effect on various CVDs. Four causal mediators (hyperlipidemia, hypertension, diabetes, and prescription opioid use) were screened to explain the causal effect. Implementing targeted management strategies for these risk factors may be warranted to mitigate the public health burden of CVD among individuals with depression.

Life-threatening coronary vasospasm in patients with type 2 diabetes with SGLT2 inhibitor-induced euglycemic ketoacidosis: a report of two consecutive cases.

Euglycemic diabetic ketoacidosis (eDKA) has emerged as an adverse event associated with sodium-glucose transporter-2 inhibitors (SGLT2i). We present two consecutive cases of SGLT2i-induced eDKA, both manifested as life-threatening coronary vasospastic angina (VSA). Case 1: A 64-year-old male overweight patient with type 2 diabetes (BMI 28.2 kg/m2), treated with dapagliflozin 5 mg daily for 6 months and a restricted diet for 2 months, experienced loss of consciousness following severe chest pain while driving, resulting in a traffic accident: plasma glucose, 163 mg/dL; urine ketones, (+++); bicarbonate (HCO3-), 13.2 mmol/L; and total ketone body, 1539 µmol/L. Coronary angiography (CAG) performed on day 5 revealed diffusely spastic coronary arteries with 90% stenosis in the right coronary artery, leading to the diagnosis of VSA in the presence of coronary atherosclerosis. Case 2: A 63-year-old male patient with type 2 diabetes (BMI 22.2 kg/m2) experienced severe chest discomfort and faintness following 2 months of chest pain while on dapagliflozin 10 mg daily for 1 year: plasma glucose, 112 mg/dL; urine ketones, (+++); HCO3-, 15.3 mmol/L; and total ketone body, 10,883 µmol/L. CAG performed on day 10 revealed no organic stenosis but diffusely spastic coronary arteries in response to coronary ergonovine infusion, confirming the diagnosis of VSA. SGLT2i has the potential to inhibit acetylcholine and butyrylcholine esterase activities, leading to reduced scavenging of acetylcholine and possible induction of coronary vasospasm. These cases highlight the association between life-threatening VSA and SGLT2i-induced eDKA.

In vivo relationship between bound and free insulin in patients with diabetes having anti-insulin antibodies.

Objective: The Scatchard plot of anti-insulin antibodies is curvilinear, indicating heterogeneity in binding sites. However, the relationship between bound insulin (B) and free insulin (F) in patients with anti-insulin antibodies has not yet been elucidated. This study aimed to determine this relationship. Methods: We studied two insulin-treated patients with diabetes who had high titers of anti-insulin antibodies. The B and F levels were measured using daily blood samples. Assuming that the law of mass action is applicable to the reactions between insulin and anti-insulin antibody forms, we plotted the bound-to-free ratio (B/F) vs. B using patient data. We also performed an equilibrium binding assay in vitro. Results: Some of the B/F vs. B plots of the daily variation showed an approximately linear relationship, while the Scatchard plots of in vitro data became curvilinear. Conclusion: Our study suggests that the one-site (high-affinity site) of anti-insulin antibodies accounts, for the most part, for insulin pharmacokinetics within physiological insulin concentrations. Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-023-00641-1.

Negative correlation between organ heteroplasmy, particularly hepatic heteroplasmy, and age at death revealed by post-mortem studies of m.3243A > G cases.

Mitochondrial DNA m.3243A > G mutation causes mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) and its associated multi-organ disorders, including diabetes. To clarify associations between m.3243A > G organ heteroplasmy and clinical phenotypes, including the age at death, we combined genetic and pathological examinations from seven unreported and 36 literature cases of autopsied subjects. Clinical characteristics of subjects were as follows: male, 13; female, 28; unknown, 2; the age at death, 36.9 ± 20.2 [4-82] years; BMI, 16.0 ± 2.9 [13.0-22.3]; diabetes, N = 21 (49%), diabetes onset age 38.6 ± 14.2 years; deafness, N = 27 (63%); stroke-like episodes (StLEp), N = 25 (58%); congestive heart failure (CHF), N = 15 (35%); CHF onset age, 51.3 ± 14.5 years. Causes of death (N = 32) were as follows: cardiac, N = 13 (41%); infection, N = 8 (25%); StLEp, N = 4 (13%); gastrointestinal, N = 4 (13%); renal, N = 2 (6%); hepatic, N = 1 (2%). High and low heteroplasmies were confirmed in non-regenerative and regenerative organs, respectively. Heteroplasmy of the liver, spleen, leukocytes, and kidney for all subjects was significantly associated with the age at death. Furthermore, the age at death was related to juvenile-onset (any m.3243A > G-related symptoms appeared before 20) and stroke-like episodes. Multiple linear regression analysis with the age at death as an objective variable showed the significant contribution of liver heteroplasty and juvenile-onset to the age at death. m.3243A > G organ heteroplasmy levels, particularly hepatic heteroplasmy, are significantly associated with the age at death in deceased cases.

Effect of Clutter Filter in High-Frame-Rate Ultrasonic Backscatter Coefficient Analysis.

High-frame-rate imaging with a clutter filter can clearly visualize blood flow signals and provide more efficient discrimination with tissue signals. In vitro studies using clutter-less phantom and high-frequency ultrasound suggested a possibility of evaluating the red blood cell (RBC) aggregation by analyzing the frequency dependence of the backscatter coefficient (BSC). However, in in vivo applications, clutter filtering is required to visualize echoes from the RBC. This study initially evaluated the effect of the clutter filter for ultrasonic BSC analysis for in vitro and preliminary in vivo data to characterize hemorheology. Coherently compounded plane wave imaging at a frame rate of 2 kHz was carried out in high-frame-rate imaging. Two samples of RBCs suspended by saline and autologous plasma for in vitro data were circulated in two types of flow phantoms without or with clutter signals. The singular value decomposition was applied to suppress the clutter signal in the flow phantom. The BSC was calculated using the reference phantom method, and it was parametrized by spectral slope and mid-band fit (MBF) between 4-12 MHz. The velocity distribution was estimated by the block matching method, and the shear rate was estimated by the least squares approximation of the slope near the wall. Consequently, the spectral slope of the saline sample was always around four (Rayleigh scattering), independently of the shear rate, because the RBCs did not aggregate in the solution. Conversely, the spectral slope of the plasma sample was lower than four at low shear rates but approached four by increasing the shear rate, because the aggregations were presumably dissolved by the high shear rate. Moreover, the MBF of the plasma sample decreased from -36 to -49 dB in both flow phantoms with increasing shear rates, from approximately 10 to 100 s-1. The variation in the spectral slope and MBF in the saline sample was comparable to the results of in vivo cases in healthy human jugular veins when the tissue and blood flow signals could be separated.

Contrast analysis in ultrafast ultrasound blood flow imaging of jugular vein.

PURPOSE: The contrasts of flowing blood in in vitro experiments using porcine blood and in vivo measurements of human jugular veins were analyzed to demonstrate that the hemorheological property was dependent on the shear rate. METHODS: Blood samples (45% hematocrit) suspended in saline or plasma were compared with examine the difference in viscoelasticity. Ultrafast plane-wave imaging at an ultrasonic center frequency of 7.5 MHz was performed on different steady flows in a graphite-agar phantom. Also, in vivo measurement was performed in young, healthy subjects and patients with diabetes. A spatiotemporal matrix of beamformed radio-frequency data was used for the singular value decomposition (SVD) clutter filter. The clutter-filtered B-mode image was calculated as the amplitude envelope normalized at the first frame in the diastolic phase to evaluate contrast. The shear rate was estimated as the velocity gradient perpendicular to the lateral axis. RESULTS: Although nonaggregated erythrocytes at a high shear rate exhibited a low echogenicity, the echogenicity in the plasma sample overall increased due to erythrocyte aggregation at a low shear rate. In addition, the frequency of detection of specular components, defined as components beyond twice the standard deviation of a contrast map obtained from a clutter-filtered B-mode image, increased in the porcine blood at a high shear rate and the venous blood in healthy subjects versus patients with diabetes. CONCLUSION: The possibility of characterizing hemorheological properties dependent on the shear rate and diabetes condition was indicated using ultrafast plane-wave imaging with an SVD-based clutter filter.

A New Method for Albuminuria Measurement Using a Specific Reaction between Albumin and the Luciferin of the Firefly Squid Watasenia scintillans.

This study demonstrates that the luciferin of the firefly squid Watasenia scintillans, which generally reacts with Watasenia luciferase, reacted with human albumin to emit light in proportion to the albumin concentration. The luminescence showed a peak wavelength at 540 nm and was eliminated by heat or protease treatment. We used urine samples collected from patients with diabetes to quantify urinary albumin concentration, which is essential for the early diagnosis of diabetic nephropathy. Consequently, we were able to measure urinary albumin concentrations by precipitating urinary proteins with acetone before the reaction with luciferin. A correlation was found with the result of the immunoturbidimetric method; however, the Watasenia luciferin method tended to produce lower albumin concentrations. This may be because the Watasenia luciferin reacts with only intact albumin. Therefore, the quantification method using Watasenia luciferin is a new principle of urinary albumin measurement that differs from already established methods such as immunoturbidimetry and high-performance liquid chromatography.

Perioperative C-peptide index is associated with the status of diabetes management after pancreatectomy.

AIMS/INTRODUCTION: This study aimed to identify the clinical factors affecting postoperative residual pancreatic ß-cell function, as assessed by the C-peptide index (CPI), and to investigate the association between perioperative CPI and the status of diabetes management after pancreatectomy. MATERIALS AND METHODS: The associations between perioperative CPI and clinical background, including surgical procedures of pancreatectomy, were analyzed in 47 patients who underwent pancreatectomy, and were assessed for pre-and postoperative CPI. The association between perioperative CPI and glycemic control after pancreatectomy was investigated. RESULTS: The low postoperative CPI group (CPI <0.7) had longer duration of diabetes (17.5 ± 14.5 vs 5.5 ± 11.0 years, P = 0.004), a higher percentage of sulfonylurea users (41.7 vs 8.7%, P = 0.003) and a greater number of drug categories used for diabetes treatment (1.9 ± 1.1 vs 0.8 ± 0.8, P <0.001) than did the high postoperative CPI group. Postoperative CPI was higher (1.4 ± 1.2 vs 0.7 ± 0.6, P = 0.039) in patients with low glycosylated hemoglobin (<7.0%) at 6 months after pancreatectomy; preoperative (2.0 ± 1.5 vs 0.7 ± 0.5, P = 0.012) and postoperative CPI (2.5 ± 1.4 vs 1.4 ± 1.1, P = 0.020) were higher in non-insulin users than in insulin users at 6 months after surgery. CONCLUSIONS: The duration of diabetes and preoperative diabetes treatment were associated with residual pancreatic ß-cell function after pancreatectomy. Furthermore, perioperative ß-cell function as assessed by CPI was associated with diabetes management status after pancreatectomy.

Fragmented QRS on electrocardiography as a predictor for diastolic cardiac dysfunction in type 2 diabetes.

AIMS/INTRODUCTION: Diastolic cardiac dysfunction in type 2 diabetes (DD2D) is a critical risk of heart failure with preserved ejection fraction. However, there is no established biomarker to detect DD2D. We aimed to investigate the predictive impact of fragmented QRS (fQRS) on electrocardiography on the existence of DD2D. MATERIALS AND METHODS: We included in-hospital patients with type 2 diabetes without heart failure symptoms who were admitted to our institution for glycemic management between November 2017 and April 2021. An fQRS was defined as an additional R' wave or notching/splitting of the S wave in two contiguous electrocardiography leads. DD2D was diagnosed according to the latest guidelines of the American Society of Echocardiography. RESULTS: Of 320 participants, 122 patients (38.1%) had fQRS. DD2D was diagnosed in 82 (25.6%). An fQRS was significantly associated with the existence of DD2D (odds ratio 4.37, 95% confidence interval 2.33-8.20; p < 0.0001) adjusted for seven potential confounders. The correlation between DD2D and diabetic microvascular disease was significant only among those with fQRS. Classification and regression tree analysis showed that fQRS was the most relevant optimum split for DD2D. CONCLUSIONS: An fQRS might be a simple and promising predictor of the existence of DD2D. The findings should be validated in a larger-scale cohort.

Astaxanthin, a Marine Carotenoid, Maintains the Tolerance and Integrity of Adipose Tissue and Contributes to Its Healthy Functions.

Recently, obesity-induced insulin resistance, type 2 diabetes, and cardiovascular disease have become major social problems. We have previously shown that Astaxanthin (AX), which is a natural antioxidant, significantly ameliorates obesity-induced glucose intolerance and insulin resistance. It is well known that AX is a strong lipophilic antioxidant and has been shown to be beneficial for acute inflammation. However, the actual effects of AX on chronic inflammation in adipose tissue (AT) remain unclear. To observe the effects of AX on AT functions in obese mice, we fed six-week-old male C57BL/6J on high-fat-diet (HFD) supplemented with or without 0.02% of AX for 24 weeks. We determined the effect of AX at 10 and 24 weeks of HFD with or without AX on various parameters including insulin sensitivity, glucose tolerance, inflammation, and mitochondrial function in AT. We found that AX significantly reduced oxidative stress and macrophage infiltration into AT, as well as maintaining healthy AT function. Furthermore, AX prevented pathological AT remodeling probably caused by hypoxia in AT. Collectively, AX treatment exerted anti-inflammatory effects via its antioxidant activity in AT, maintained the vascular structure of AT and preserved the stem cells and progenitor's niche, and enhanced anti-inflammatory hypoxia induction factor-2α-dominant hypoxic response. Through these mechanisms of action, it prevented the pathological remodeling of AT and maintained its integrity.

Fulminant type 1 diabetes patients display high frequencies of IGRP-specific type 1 CD8+ T cells.

The role of cellular autoimmunity in the pathogenesis of fulminant type 1 diabetes (FT1D) remains largely unknown. In this study, we performed an integrated assay using peripheral blood mononuclear cells to determine the islet antigen-specific CD8+ T cell responses in FT1D and compare the responses among acute-onset T1D (AT1D) and slowly progressive T1D (SP1D). IGRP- and ZnT8-specific IL-6, G-CSF, and TNF-α responses were significantly upregulated in patients with FT1D, while IGRP- and ZnT8-specific IP-10 responses were significantly upregulated in patients with AT1D than in non-diabetics (ND). Furthermore, the frequencies of IGRP-specific type 1 CD8+ cytotoxic T (Tc1) cells were significantly higher in the FT1D group than in the ND, SP1D, and AT1D groups. Additionally, IGRP-specific Tc1 cells were more abundant in the FT1D with HLA-A2 group than in the FT1D without A2 group. In conclusion, our study suggests that IGRP-specific CD8+ T cells significantly contribute to the pathogenesis of FT1D.

Fate of adipocyte progenitors during adipogenesis in mice fed a high-fat diet.

OBJECTIVE: Expansion of adipose tissue during obesity through the recruitment of newly generated adipocytes (hyperplasia) is metabolically healthy, whereas that through the enlargement of pre-existing adipocytes (hypertrophy) leads to metabolic complications. Accumulating evidence from genetic fate mapping studies suggests that in animal models receiving a high-fat diet (HFD), only adipocyte progenitors (APs) in gonadal white adipose tissue (gWAT) have proliferative potential. However, the proliferative potential and differentiating capacity of APs in the inguinal WAT (iWAT) of male mice remains controversial. The objective of this study was to investigate the proliferative and adipogenic potential of APs in the iWAT of HFD-fed male mice. METHODS: We generated PDGFRα-GFP-Cre-ERT2/tdTomato (KI/td) mice and traced PDGFRα-positive APs in male mice fed HFD for 8 weeks. We performed a comprehensive phenotypic analysis, including the histology, immunohistochemistry, flow cytometry, and gene expression analysis, of KI/td mice fed HFD. RESULTS: Contrary to the findings of others, we found an increased number of newly generated tdTomato+ adipocytes in the iWAT of male mice, which was smaller than that observed in the gWAT. We found that in male mice, the iWAT has more proliferating tdTomato+ APs than the gWAT. We also found that tdTomato+ APs showed a higher expression of Dpp4 and Pi16 than tdTomato- APs, and the expression of these genes was significantly higher in the iWAT than in the gWAT of mice fed HFD for 8 weeks. Collectively, our results reveal that HFD feeding induces the proliferation of tdTomato+ APs in the iWAT of male mice. CONCLUSION: In male mice, compared with gWAT, iWAT undergoes hyperplasia in response to 8 weeks of HFD feeding through the recruitment of newly generated adipocytes due to an abundance of APs with a high potential for proliferation and differentiation.

Type 1 diabetes woman with repeated miscarriages successfully gave birth after introducing an insulin pump with a predictive low glucose suspend feature.

Sensor-augmented insulin pump therapy with a predictive low glucose suspend (SAP-PLGS) feature is a remarkably progressed modality for the glycemic management of patients with type 1 diabetes. This technology avoids nocturnal hypoglycemia and severe hypoglycemia. A Brazilian woman developed type 1 diabetes at age 11 and was treated with multiple daily insulin injections. At age 20, she was admitted to our internal medicine department for her first pregnancy. Her HbA1c was 7.9% in the 6 weeks of gestation. Although the combination of continuous subcutaneous insulin infusion and a sensor-augmented pump was introduced, she had a miscarriage in the next week. After 6 months, she became pregnant again. Despite an HbA1c of 7.2%, she had another miscarriage. Thereafter, she returned to multiple daily insulin injections and began using intermittently scanned continuous glycemic monitoring. At age 22, she had her third pregnancy. Her HbA1c was 7.3%. SAP-PLGS was then introduced, which reduced her frequent hypoglycemic events and blood glucose fluctuations. She gave birth to a 4137 g boy at 39 weeks without significant complications. Successful delivery can be obtained in women with type 1 diabetes following repeated miscarriages after introducing SAP-PLGS. We hypothesize that the modality might contributed to our patient's miscarriage avoidance by reducing her glycemic fluctuations.

Gut microbiota, determined by dietary nutrients, drive modification of the plasma lipid profile and insulin resistance.

The gut microbiota metabolizes the nutrients to produce various metabolites that play crucial roles in host metabolism. However, the links between the microbiota established by different nutrients and the microbiota-influenced changes in the plasma lipids remain unclear. Diets rich in cornstarch, fructose, branched chain amino acids, soybean oil (SO), or lard established a unique microbiota and had influence on glucose metabolism, which was partially reproduced by transferring the microbiota. Comparison of plasma lipidomic analysis between germ-free and colonized mice revealed significant impacts of the microbiota on various lipid classes, and of note, the microbiota established by the SO diet, which was associated with the greatest degree of glucose intolerance, caused the maximum alteration of the plasma lipid profile. Thus, the gut microbiota composed of dietary nutrients was associated with dynamic changes in the lipids potentially having differential effects on glucose metabolism.

Diastolic Cardiac Function Improvement by Liraglutide Is Mainly Body Weight Reduction Dependent but Independently Contributes to B-Type Natriuretic Peptide Reduction in Patients with Type 2 Diabetes with Preserved Ejection Fraction.

OBJECTIVES: A single-arm prospective study was conducted among Japanese patients with type 2 diabetes having preserved ejection fraction. The aim was to investigate (1) whether liraglutide therapy could improve B-type natriuretic peptide (BNP) levels and diastolic cardiac function assessed by the E-wave to E' ratio (E/E') using transthoracic echocardiography (TTE), and (2) whether E/E' contributed to BNP improvement independent of bodyweight reduction (UMIN000005565). METHODS: Patients with type 2 diabetes and left ventricular ejection fraction (LVEF) ≥ 40% without heart failure symptoms were enrolled, and daily injection with liraglutide (0.9 mg) was introduced. Cardiac functions were assessed by TTE before and after 26 weeks of liraglutide treatment. Diastolic cardiac function was defined as septal E/E' ≥ 13.0. RESULTS: Thirty-one patients were analyzed. BNP and E/E' improved, with BNP levels declining from 36.8 ± 30.5 pg/mL to 26.3 ± 25.9 pg/mL (p = 0.0014) and E/E' dropping from 12.7 ± 4.7 to 11.0 ± 3.3 (p = 0.0376). The LVEF showed no significant changes. E/E' improved only in patients with E/E' ≥ 13.0. Favorable changes in E/E' were canceled when adjusted for body mass index (BMI). Multivariate linear regression analysis revealed that the left ventricular diastolic diameter and ∆E/E'/∆BMI contributed to ∆BNP/baseline BNP (p = 0.0075, R 2 = 0.49264). CONCLUSIONS: Liraglutide had favorable effects on BNP and E/E' but not on LVEF. E/E' improvement was only seen in patients with diastolic cardiac function. Body weight reduction affected the change of E/E'. The BMI-adjusted E/E' significantly contributed to the relative change of BNP. GLP-1 analog treatment could be considered a therapeutic option against diabetic diastolic cardiac dysfunction regardless of body weight. This trial is registered with the University Hospital Medical Information Network in Japan, with clinical trial registration number: UMIN000005565.

Generation and characterization of a Meflin-CreERT2 transgenic line for lineage tracing in white adipose tissue.

Meflin (Islr) expression has gained attention as a marker for mesenchymal stem cells, but its function remains largely unexplored. Here, we report the generation of Meflin-CreERT2 mice with CreERT2 inserted under the Meflin gene promoter to label Meflin-expressing cells genetically, thereby enabling their lineages to be traced. We found that in adult mice, Meflin-expressing lineage cells were present in adipose tissue stroma and had differentiated into mature adipocytes. These cells constituted Crown-like structures in the adipose tissue of mice after high-fat diet loading. Cold stimulation led to the differentiation of Meflin-expressing lineage cells into beige adipocytes. Thus, the Meflin-CreERT2 mouse line is a useful new tool for visualizing and tracking the lineage of Meflin-expressing cells.

High prevalence of fragmented QRS on electrocardiography in Japanese patients with diabetes irrespective of metabolic syndrome.

AIMS/INTRODUCTION: Fragmented QRS (fQRS) on electrocardiography is a marker of myocardial fibrosis and myocardial scar formation. This study aimed to clarify the relationship of fQRS with diabetes mellitus and metabolic syndrome (MetS) in Japanese patients. MATERIALS AND METHODS: Approximately 702 individuals who had a routine health checkup at the Hokuriku Health Service Association (Toyama, Japan) in October 2014 were enrolled and categorized into one of the following four groups based on MetS and diabetes mellitus status: with diabetes mellitus (+) MetS+ (164 participants); diabetes mellitus+ without MetS (Mets-; 103 participants); diabetes mellitus- MetS+ (133 participants); and diabetes mellitus- MetS- (302 participants). fQRS was assessed using the results of electrocardiography. RESULTS: The prevalence of fQRS was statistically higher in patients with diabetes mellitus+ MetS+ (37%) and diabetes mellitus+ MetS- (35%), than those with diabetes mellitus- MetS+ (14%) or diabetes mellitus- MetS- (10%; P < 0.0001). Significant differences were observed between the fQRS(+) and fQRS(-) groups for age, sex, waist circumference, heart rate, hypertension, hemoglobin A1c, total cholesterol, MetS and diabetes mellitus. The area under the receiver operating characteristic curve for traditional risk factors and diabetes mellitus was 0.72 (P = 0.0007, 95% confidence interval 0.67-0.76), and for traditional risk factors and MetS it was 0.67 (P = 0.28, 95% confidence interval 0.62-0.72). Patients with diabetes mellitus had more than threefold higher likelihood of showing fQRS (odds ratio 3.41; 95% confidence interval 2.25-5.22; P < 0.0001) compared with the reference group without diabetes mellitus, after adjusting for age, sex, dyslipidemia, hypertension and waist circumference. CONCLUSIONS: fQRS was observed more frequently in diabetes mellitus patients than in MetS and control individuals. Diabetes mellitus was the most significant determinant for fQRS among MetS and other traditional metabolic risk factors.

Distinct Phenotypes of Islet Antigen-Specific CD4+ T Cells Among the 3 Subtypes of Type 1 Diabetes.

CONTEXT: Type 1 diabetes (T1D) is classified into 3 subtypes: acute-onset (AT1D), slowly progressive (SP1D), and fulminant (FT1D). The differences in the type of cellular autoimmunity within each subtype remain largely undetermined. OBJECTIVE: To determine the type and frequency of islet antigen-specific CD4+ T cells in each subtype of T1D. PARTICIPANTS: Twenty patients with AT1D, 17 with SP1D, 18 with FT1D, and 17 persons without diabetes (ND). METHODS: We performed an integrated assay to determine cellular immune responses and T-cell repertoires specific for islet antigens. This assay included an ex vivo assay involving a 48-hour stimulation of peripheral blood mononuclear cells with antigen peptides and an expansion assay involving intracytoplasmic cytokine analysis. RESULTS: The results of the ex vivo assay indicated that glutamic acid decarboxylase 65 (GAD65)-specific interleukin-6 and interferon-inducible protein-10 (IP-10) responses and preproinsulin (PPI)-specific IP-10 responses were significantly upregulated in AT1D compared with those of ND. Furthermore, GAD65- and PPI-specific granulocyte colony-stimulating factor responses were significantly upregulated in FT1D. Expansion assay revealed that GAD65- and PPI-specific CD4+ T cells were skewed toward a type 1 helper T (Th1)- cell phenotype in AT1D, whereas GAD65-specific Th2 cells were prevalent in SP1D. GAD65-specific Th1 cells were more abundant in SP1D with human leukocyte antigen-DR9 than in SP1D without DR9. FT1D displayed significantly less type 1 regulatory T (Tr1) cells specific for all 4 antigens than ND. CONCLUSIONS: The phenotypes of islet antigen-specific CD4+ T cells differed among the three T1D subtypes. These distinct T-cell phenotypes may be associated with the manner of progressive ß-cell destruction.