Influence of the combination of SGLT2 inhibitors and GLP-1 receptor agonists on eGFR decline in type 2 diabetes: post-hoc analysis of RECAP study.

Accumulating evidence has demonstrated that both SGLT2 inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP1Ra) have protective effects in patients with diabetic kidney disease. Combination therapy with SGLT2i and GLP1Ra is commonly used in patients with type 2 diabetes (T2D). We previously reported that in combination therapy of SGLT2i and GLP1Ra, the effect on the renal composite outcome did not differ according to the preceding drug. However, it remains unclear how the initiation of combination therapy is associated with the renal function depending on the preceding drug. In this post hoc analysis, we analyzed a total of 643 T2D patients (GLP1Ra-preceding group, n = 331; SGLT2i-preceding group, n = 312) and investigated the differences in annual eGFR decline. Multiple imputation and propensity score matching were performed to compare the annual eGFR decline. The reduction in annual eGFR decline in the SGLT2i-preceding group (pre: -3.5 ± 9.4 mL/min/1.73 m2/year, post: -0.4 ± 6.3 mL/min/1.73 m2/year, p < 0.001), was significantly smaller after the initiation of GLP1Ra, whereas the GLP1Ra-preceding group tended to slow the eGFR decline but not to a statistically significant extent (pre: -2.0 ± 10.9 mL/min/1.73 m2/year, post: -1.8 ± 5.4 mL/min/1.73 m2/year, p = 0.83) after the initiation of SGLT2i. After the addition of GLP1Ra to SGLT2i-treated patients, slower annual eGFR decline was observed. Our data raise the possibility that the renal benefits-especially annual eGFR decline-of combination therapy with SGLT2i and GLP1Ra may be affected by the preceding drug.

3D fluorescence imaging through scattering medium using transport of intensity equation and iterative phase retrieval.

In this paper, we have proposed a method of three-dimensional (3D) fluorescence imaging through a scattering medium. The proposed method combines the numerical digital phase conjugation propagation after measurement of the complex amplitude distribution of scattered light waves by the transport of intensity equation (TIE) with followed iterative phase retrieval to achieve 3D fluorescence imaging through a scattering medium. In the experiment, we present the quantitative evaluation of the depth position of fluorescent beads. In addition, for time-lapse measurement, cell division of tobacco-cultured cells was observed. Numerical results presented the effective range of the phase amount in the scattering medium. From these results, the proposed method is capable of recovering images degraded by a thin scattering phase object beyond a small phase change approximation.

Live Cell Imaging by Single-Shot Common-Path Wide Field-of-View Reflective Digital Holographic Microscope.

Quantitative phase imaging by digital holographic microscopy (DHM) is a nondestructive and label-free technique that has been playing an indispensable role in the fields of science, technology, and biomedical imaging. The technique is competent in imaging and analyzing label-free living cells and investigating reflective surfaces. Herein, we introduce a new configuration of a wide field-of-view single-shot common-path off-axis reflective DHM for the quantitative phase imaging of biological cells that leverages several advantages, including being less-vibration sensitive to external perturbations due to its common-path configuration, also being compact in size, simple in optical design, highly stable, and cost-effective. A detailed description of the proposed DHM system, including its optical design, working principle, and capability for phase imaging, is presented. The applications of the proposed system are demonstrated through quantitative phase imaging results obtained from the reflective surface (USAF resolution test target) as well as transparent samples (living plant cells). The proposed system could find its applications in the investigation of several biological specimens and the optical metrology of micro-surfaces.

Association of scan frequency with CGM-derived metrics and influential factors in adults with type 1 diabetes mellitus.

Introduction: This study aimed to investigate the association between scan frequency and intermittently scanned continuous glucose monitoring (isCGM) metrics and to clarify the factors affecting scan frequency in adults with type 1 diabetes mellitus (T1D). Methods: We enrolled adults with T1D who used FreeStyle® Libre. Scan and self-monitoring of blood glucose (SMBG) frequency and CGM metrics from the past 90-day glucose data were collected. The receiver operating characteristic curve was plotted to obtain the optimal cutoff values of scan frequency for the target values of time in range (TIR), time above range (TAR), and time below range (TBR). Results: The study was conducted on 211 adults with T1D (mean age, 50.9 ± 15.2 years; male, 40.8%; diabetes duration, 16.4 ± 11.9 years; duration of CGM use, 2.1 ± 1.0 years; and mean HbA1c, 7.6 ± 0.9%). The average scan frequency was 10.5 ± 3.3 scan/day. Scan frequency was positively correlated with TIR and negatively correlated with TAR, although it was not significantly correlated with TBR. Scan frequency was positively correlated with the hypoglycemia fear survey-behavior score, while it was negatively correlated with some glycemic variability metrics. Adult patients with T1D and good exercise habits had a higher scan frequency than those without exercise habits. The AUC for > 70% of the TIR was 0.653, with an optimal cutoff of 11 scan/day. Conclusions: In real-world conditions, frequent scans were linked to improved CGM metrics, including increased TIR, reduced TAR, and some glycemic variability metrics. Exercise habits and hypoglycemia fear-related behavior might affect scan frequency. Our findings could help healthcare professionals use isCGM to support adults with T1D.Clinical Trial Registry No. UMIN000039376.

Safety and glycemic control with insulin degludec use in clinical practice: results from a 3-year Japanese post-marketing surveillance study.

Introduction: Insulin degludec (degludec) is a basal insulin with a long duration of action. This post-marketing surveillance study monitored safety and glycemic control during use of degludec for 3 years in normal clinical practice in Japan. Materials and methods: This multicenter, open-label, observational study included patients with diabetes receiving degludec in Japan between 2013 and 2019. The primary outcome was incidence of adverse events occurring over 3 years of treatment. The pre-specified, secondary outcomes were severe hypoglycemic episodes and changes in HbA1c and fasting plasma glucose levels. Results: Of 4167 patients enrolled, 4022 were included in the safety assessments and 3918 in the assessments of glycemic control. Mean age was 58.9 years; 74.1% of patients had type 2 diabetes, and mean HbA1c at baseline was 8.7%. Adverse events and serious adverse events were observed in 19.1% and 8.9% of patients, respectively. Cardiac disorders and neoplasms were reported in 2.0% and 1.8% of patients, respectively, with the majority of these incidents reported as serious adverse events. Adverse drug reactions were seen in 8.0% of patients, mainly hypoglycemia. Hypoglycemic events were observed in 5.6% of patients, and severe hypoglycemic events in 1.7%. No serious allergic or injection-site reactions were seen. Respective changes (from baseline to 3 years' observation) in HbA1c and fasting plasma glucose levels were - 0.55% and - 36.3 mg/dL, and 19.6% of patients reached HbA1c < 7.0%. Conclusions: Using degludec for 3 years in normal clinical practice had a good safety and tolerability profile. Improvements in glycemic control were also seen. Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-023-00657-7.

An ABCB transporter regulates anisotropic cell expansion via cuticle deposition in the moss Physcomitrium patens.

Anisotropic cell expansion is crucial for the morphogenesis of land plants, as cell migration is restricted by the rigid cell wall. The anisotropy of cell expansion is regulated by mechanisms acting on the deposition or modification of cell wall polysaccharides. Besides the polysaccharide components in the cell wall, a layer of hydrophobic cuticle covers the outer cell wall and is subjected to tensile stress that mechanically restricts cell expansion. However, the molecular machinery that deposits cuticle materials in the appropriate spatiotemporal manner to accommodate cell and tissue expansion remains elusive. Here, we report that PpABCB14, an ATP-binding cassette transporter in the moss Physcomitrium patens, regulates the anisotropy of cell expansion. PpABCB14 localized to expanding regions of leaf cells. Deletion of PpABCB14 resulted in impaired anisotropic cell expansion. Unexpectedly, the cuticle proper was reduced in the mutants, and the cuticular lipid components decreased. Moreover, induced PpABCB14 expression resulted in deformed leaf cells with increased cuticle lipid accumulation on the cell surface. Taken together, PpABCB14 regulates the anisotropy of cell expansion via cuticle deposition, revealing a regulatory mechanism for cell expansion in addition to the mechanisms acting on cell wall polysaccharides.

Renoprotective effects of combination treatment with sodium-glucose cotransporter inhibitors and GLP-1 receptor agonists in patients with type 2 diabetes mellitus according to preceding medication.

AIMS: Combination therapy with sodium-glucose cotransporter inhibitors (SGLT2is) and GLP-1 receptor agonists (GLP1Ras) is now of interest in clinical practice. The present study evaluated the effects of the preceding drug type on the renal outcome in clinical practice. METHODS: We retrospectively extracted type 2 diabetes mellitus patients who had received both SGLT2i and GLP1Ra treatment for at least 1 year. A total of 331 patients in the GLP1Ra-preceding group and 312 patients in the SGLT2i-preceding group were ultimately analyzed. Either progression of the albuminuria status and/or a ≥30% decrease in the eGFR was set as the primary renal composite outcome. The analysis using propensity score with inverse probability weighting was performed for the outcome. RESULTS: The incidences of the renal composite outcome in the SGLT2i- and GLP1Ra-preceding groups were 28% and 25%, respectively, with an odds ratio [95% confidence interval] of 1.14 [0.75, 1.73] (p = .54). A logistic regression analysis showed that the mean arterial pressure (MAP) at baseline, the logarithmic value of the urine albumin-to-creatinine ratio at baseline, and the change in MAP were independent factors influencing the renal composite outcome. CONCLUSION: With combination therapy of SGLT2i and GLP1Ra, the preceding drug did not affect the renal outcome.

Protocol: an improved method for inducing sporophyte generation in the model moss Physcomitrium patens under nitrogen starvation.

BACKGROUND: Land plants exhibit a haplodiplontic life cycle, whereby multicellular bodies develop in both the haploid and diploid generations. The early-diverging land plants, known as bryophytes, have a haploid-dominant life cycle, in which a short-lived multicellular body in the diploid generation, known as the sporophyte, develops on the maternal haploid gametophyte tissues. The moss Physcomitrium (Physcomitrella) patens has become one of the most powerful model systems in evolutionary plant developmental studies. To induce diploid sporophytes of P. patens, several protocols are implemented. One of the conventional approaches is to grow approximately one-month-old gametophores for another month on Jiffy-7 pellets made from the peat moss that is difficult to fully sterilize. A more efficient method to obtain all tissues throughout the life cycle should accelerate studies of P. patens. RESULTS: Here, we investigated the effect of nitrogen conditions on the growth and development of P. patens. We provide an improved protocol for the sporophyte induction of P. patens using a BCD-based solid culture medium without Jiffy-7 pellets, based on the finding that the formation of gametangia and subsequent sporophytes is promoted by nitrogen-free growth conditions. The protocol consists of two steps; first, culture the protonemata and gametophores on nitrogen-rich medium under continuous light at 25 °C, and then transfer the gametophores onto nitrogen-free medium under short-day and at 15 °C for sporophyte induction. The protocol enables to shorten the induction period and reduce the culture space. CONCLUSIONS: Our more efficient and shortened protocol for inducing the formation of sporophytes will contribute to future studies into the fertilization or the diploid sporophyte generation of P. patens.

Possible Relationship between the Deteriorated Accuracy of Intermittent-Scanning Continuous Glucose Monitoring Device and the Contact Dermatitis: Post-hoc analysis of the ISCHIA Study.

OBJECTIVE: We previously reported the mean average relative difference (MARD) of the sensor glucose (SG) of the first-generation FreeStyle Libre with the original algorithm, an intermittent scanning continuous glucose monitoring (isCGM) device, was 15.6% in the Effect of Intermittent-Scanning Continuous Glucose Monitoring to Glycemic Control Including Hypoglycemia and Quality of Life of Patients with Type 1 Diabetes Mellitus Study (ISCHIA Study). In the present study, we aimed to further analyze its accuracy in detail by conducting a post-hoc analysis of the study. METHODS: The ISCHIA Study was a multicenter, randomized, cross-over trial to assess the efficacy of isCGM. The SG levels of isCGM and the measured capillary blood glucose (BG) levels of 91 participants were used for the analysis. RESULTS: Bland-Altman analysis showed bias of -13.0 mg/dl when the SG levels were compared to the BG levels, however no proportional bias was observed (r = 0.085). MARD of the participants without and with contact dermatitis were 15.0 ± 6.0% and 27.4 ± 21.4% (P = 0.001), respectively. CONCLUSION: There was negative bias in the SG levels of isCGM compared to the BG levels. There is a possibility that the complication of the contact dermatitis during isCGM use may be related with deteriorated accuracy of the SG levels.

Association of Impaired Awareness of Hypoglycemia with Driving Safety and Hypoglycemia Problem-solving Abilities among Patients with Type 1 Diabetes in Japan: The PR-IAH Study.

Objective Patients with type 1 diabetes (T1D) and impaired awareness of hypoglycemia (IAH) are at an elevated risk of experiencing automobile accidents. We therefore investigated the association of IAH with driving safety and hypoglycemia problem-solving abilities in adults with T1D. Methods This cross-sectional survey used Gold's method in adult patients with T1D at the National Hospital Organization (NHO) Hospital from February 14, 2020, to October 31, 2021. The participants were divided into control and IAH groups. The data included information on demographics, worries and distress regarding hypoglycemia, hypoglycemia problem-solving abilities, and adverse driving events. Patients We enrolled 233 participants (mean age: 48.5±12.8 years old, mean hemoglobin A1c level: 7.6%±0.9%) from NHO collaborating centers in Japan. Results Among a total of 233 participants (mean age: 48.5±12.8 years old, mean hemoglobin A1c level: 7.6%±0.9%), the prevalence rate of IAH was 11.6% [95% confidence interval (CI): 7.8-16.4%]. IAH was significantly associated with near-miss car accidents (odds ratio: 5.41; 95% CI:1.64-17.80). Diabetic peripheral neuropathy was associated with an increased risk of IAH, while treatment with continuous subcutaneous insulin infusion was not associated with a decreased risk of IAH. The average hypoglycemia problem-solving perception, detection control, and seeking preventive strategies scores in the IAH group were significantly reduced compared with those in the control group. Conclusion IAH was associated with an increased risk of near-miss car accidents among adults with T1D. Furthermore, good hypoglycemia problem-solving abilities were associated with a decreased risk of IAH.

Protective and risk factors of impaired awareness of hypoglycemia in patients with type 1 diabetes: a cross-sectional analysis of baseline data from the PR-IAH study.

BACKGROUND: Hypoglycemia in type 1 diabetes (T1D) is associated with mortality and morbidity, especially when awareness of hypoglycemia is impaired. This study aimed to investigate the protective and risk factors for impaired awareness of hypoglycemia (IAH) in adults with T1D. METHODS: This cross-sectional study enrolled 288 adults with T1D (mean age, 50.4 ± 14.6 years; male, 36.5%; diabetes duration, 17.6 ± 11.2 years; mean HbA1c level, 7.7 ± 0.9%), who were divided into IAH and non-IAH (control) groups. A survey was conducted to assess hypoglycemia awareness using the Clarke questionnaire. Diabetes histories, complications, fear of hypoglycemia, diabetes distress, hypoglycemia problem-solving abilities, and treatment data were collected. RESULTS: The prevalence of IAH was 19.1%. Diabetic peripheral neuropathy was associated with an increased risk of IAH (odds ratio [OR] 2.63; 95% confidence interval [CI] 1.13-5.91; P = 0.014), while treatment with continuous subcutaneous insulin infusion and hypoglycemia problem-solving perception scores were associated with a decreased risk of IAH (OR, 0.48; 95% CI, 0.22-0.96; P = 0.030; and OR, 0.54; 95% CI, 0.37-0.78; P = 0.001, respectively). There was no difference in continuous glucose monitoring use between the groups. CONCLUSION: We identified protective factors in addition to risk factors for IAH in adults with T1D. This information may help manage problematic hypoglycemia. TRIAL REGISTRATION: University hospital Medical Information Network (UMIN) Center: UMIN000039475). Approval date 13 February 2020.

Using Spinning Disk Microscopy to Observe the Mitotic and Cytokinetic Apparatus in Physcomitrium patens.

Protonemata of the moss Physcomitrium patens are ideal structures in which to observe cytoskeletal organization and dynamics. Special care is needed to prepare P. patens cultures for high-resolution microscopy. Here, we describe methods for spinning disk microscopy of dividing P. patens cells expressing sGFP-tubulin and H2B-mCherry, including detailed methods for culturing P. patens.

Factors associated with hemoglobin glycation index in adults with type 1 diabetes mellitus: The FGM-Japan study.

AIMS/INTRODUCTION: The discrepancy between HbA1c and glucose exposure may have significant clinical implications; however, the association between the hemoglobin glycation index (HGI) and clinical parameters in type 1 diabetes remains controversial. This study aimed to find the factors associated with HGI (laboratory HbA1c - predicted HbA1c derived from the continuous glucose monitoring [CGM]). MATERIALS AND METHODS: We conducted a cross-sectional study of adults with type 1 diabetes (n = 211, age 50.9 ± 15.2 years old, female sex = 59.2%, duration of CGM use = 2.1 ± 1.0 years). All subjects wore the CGM for 90 days before HbA1c measurement. Data derived from the FreeStyle Libre sensor were used to calculate the glucose management indicator (GMI) and glycemic variability (GV) parameters. HGI was defined as the difference between the GMI and the laboratory HbA1c levels. The participants were divided into three groups according to the HGI tertile (low, moderate, and high). Multivariate regression analyses were performed. RESULTS: The female sex ratio, HbA1c, and % coefficient of variation (%CV) significantly increased over the HGI tertile, while eGFR and Hb decreased over the HGI tertile. In multivariate analysis, the factors associated with HGI were %CV and eGFR, after adjusting for HbA1c level and sex (R2  = 0.44). CONCLUSIONS: This study demonstrated that HGI is associated with female sex, eGFR, and some glycemic variability indices, independently of HbA1c. Minimizing glycemic fluctuations might reduce HGI. This information provides diabetic health professionals and patients with personalized diabetes management for adults with type 1 diabetes.

Novel inhibitors of microtubule organization and phragmoplast formation in diverse plant species.

Cell division is essential for development and involves spindle assembly, chromosome separation, and cytokinesis. In plants, the genetic tools for controlling the events in cell division at the desired time are limited and ineffective owing to high redundancy and lethality. Therefore, we screened cell division-affecting compounds in Arabidopsis thaliana zygotes, whose cell division is traceable without time-lapse observations. We then determined the target events of the identified compounds using live-cell imaging of tobacco BY-2 cells. Subsequently, we isolated two compounds, PD-180970 and PP2, neither of which caused lethal damage. PD-180970 disrupted microtubule (MT) organization and, thus, nuclear separation, and PP2 blocked phragmoplast formation and impaired cytokinesis. Phosphoproteomic analysis showed that these compounds reduced the phosphorylation of diverse proteins, including MT-associated proteins (MAP70) and class II Kinesin-12. Moreover, these compounds were effective in multiple plant species, such as cucumber (Cucumis sativus) and moss (Physcomitrium patens). These properties make PD-180970 and PP2 useful tools for transiently controlling plant cell division at key manipulation nodes conserved across diverse plant species.

To Use or Not to Use a Self-monitoring of Blood Glucose System? Real-world Flash Glucose Monitoring Patterns Using a Cluster Analysis of the FGM-Japan Study.

Objective This study investigated self-monitoring of blood glucose (SMBG) adherence and flash glucose monitoring patterns using a cluster analysis in Japanese type 1 diabetes (T1D) patients with intermittently scanned continuous glucose monitoring (isCGM). Methods We measured SMBG adherence and performed a data-driven cluster analysis using a hierarchical clustering in T1D patients from Japan using the FreeStyle Libre system. Clusters were based on three variables (testing glucose frequency and referred Libre data for hyperglycemia or hypoglycemia). Patients We enrolled 209 participants. Inclusion criteria were patients with T1D, duration of isCGM use ≥3 months, age ≥20 years old, and regular attendance at the collaborating center. Results The rate of good adherence to SMBG recommended by a doctor was 85.0%. We identified three clusters: cluster 1 (low SMBG test frequency but high reference to Libre data, 17.7%), cluster 2 (high SMBG test frequency but low reference to Libre data, 34.0%), and cluster 3 (high SMBG test frequency and high reference to Libra data, 48.3%). Compared with other clusters, individuals in cluster 1 were younger, those in cluster 2 had a shorter Libre duration, and individuals in cluster 3 had lower time-in-range, higher severe diabetic distress, and high intake of snacks and sweetened beverages. There were no marked differences in the incidence of diabetic complications and rate of wearing the Libre sensor among the clusters. Conclusion We stratified the patients into three subgroups with varied clinical characteristics and CGM metrics. This new substratification might help tailor diabetes management of patients with T1D using isCGM.

GRAS transcription factors regulate cell division planes in moss overriding the default rule.

Plant cells are surrounded by a cell wall and do not migrate, which makes the regulation of cell division orientation crucial for development. Regulatory mechanisms controlling cell division orientation may have contributed to the evolution of body organization in land plants. The GRAS family of transcription factors was transferred horizontally from soil bacteria to an algal common ancestor of land plants. SHORTROOT (SHR) and SCARECROW (SCR) genes in this family regulate formative periclinal cell divisions in the roots of flowering plants, but their roles in nonflowering plants and their evolution have not been studied in relation to body organization. Here, we show that SHR cell autonomously inhibits formative periclinal cell divisions indispensable for leaf vein formation in the moss Physcomitrium patens, and SHR expression is positively and negatively regulated by SCR and the GRAS member LATERAL SUPPRESSOR, respectively. While precursor cells of a leaf vein lacking SHR usually follow the geometry rule of dividing along the division plane with the minimum surface area, SHR overrides this rule and forces cells to divide nonpericlinally. Together, these results imply that these bacterially derived GRAS transcription factors were involved in the establishment of the genetic regulatory networks modulating cell division orientation in the common ancestor of land plants and were later adapted to function in flowering plant and moss lineages for their specific body organizations.

Diabetic ketoacidosis after the second dose of SARS-CoV-2 mRNA vaccination in a patient with pembrolizumab-induced fulminant type 1 diabetes.

We report a case of 77-year-old woman with fulminant type 1 diabetes (T1D) who developed diabetic ketoacidosis (DKA) after the second dose of SARS-CoV-2 vaccine tozinameran. The patient had been diagnosed as having T1D associated with an immune-related adverse event caused by pembrolizumab at the age of 75. After the second dose of tozinameran, she developed DKA and needed intravenous insulin infusion and mechanical ventilation. Although the direct causal relationship between the vaccination and the DKA episode could not be proven in this case, published literatures had suggested the possibility of developing DKA after SARS-CoV-2 vaccination in patients with T1D. As the magnitude of the risk of the combination of the known adverse drug reactions of SARS-CoV-2 mRNA vaccine and T1D patients' vulnerability to sick-day conditions is not yet thoroughly assessed, future studies such as a non-interventional study with adequate sample size would be required to address this issue.

Low-invasive 5D visualization of mitotic progression by two-photon excitation spinning-disk confocal microscopy.

Non-linear microscopy, such as multi-photon excitation microscopy, offers spatial localities of excitations, thereby achieving 3D cross-sectional imaging with low phototoxicity even in thick biological specimens. We had developed a multi-point scanning two-photon excitation microscopy system using a spinning-disk confocal scanning unit. However, its severe color cross-talk has precluded multi-color simultaneous imaging. Therefore, in this study, we introduced a mechanical switching system to select either of two NIR laser light pulses and an image-splitting detection system for 3- or 4-color imaging. As a proof of concept, we performed multi-color fluorescent imaging of actively dividing human HeLa cells and tobacco BY-2 cells. We found that the proposed microscopy system enabled time-lapse multi-color 3D imaging of cell divisions while avoiding photodamage. Moreover, the application of a linear unmixing method to the 5D dataset enabled the precise separation of individual intracellular components in multi-color images. We thus demonstrated the versatility of our new microscopy system in capturing the dynamic processes of cellular components that could have multitudes of application.

Protocol for a Randomized, Crossover Trial to Decrease Time in Hypoglycemia by Combined Intervention of the Usage of Intermittent-Scanning Continuous Glucose Monitoring Device and the Structured Education Regarding its Usage: Effect of Intermittent-Scanning Continuous Glucose Monitoring to Glycemic Control Including Hypoglycemia and Quality of Life of Patients with Type 1 Diabetes Mellitus Study (ISCHIA Study).

OBJECTIVE: Intermittent-scanning continuous glucose monitoring (isCGM) is widely used in type 1 diabetes (T1D) patients; however, the education required to prevent hypoglycemia by using isCGM is not established. This study examines the combined effect of isCGM device usage and the education to reduce the time in hypoglycemia in comparison to conventional self-monitoring of blood glucose (SMBG). METHODS: The Effect of Intermittent-Scanning Continuous Glucose Monitoring to Glycemic Control Including Hypoglycemia and Quality of Life of Patients with Type 1 Diabetes Mellitus Study (ISCHIA Study), a randomized, crossover trial, enrolls 104 T1D patients (age, 20-74 years) with T1D. Participants are randomized to use isCGM combined with structured education (Intervention period) or SMBG (Control period) for 84 days, followed by the other for a further 84 days. During the Intervention period, participants have access to the sensor glucose levels and trend arrow of the device. During the Control period, participants conduct SMBG at least three times a day, and retrospective CGM is used to record the blinded sensor glucose levels. The primary endpoint is the decrease of time in hypoglycemia ( < 70 mg/dL) per day (hour/day) during the Intervention period compared with the Control period. The secondary endpoints include other indices of glycemic control, glycoalbumin, accuracy of isCGM, diabetes-related quality of life (QOL), adherence, and cost-effectiveness. The study protocol has received Certified Review Board (CRB) approval from National Hospital Organization Osaka National Hospital (N2018002, Feb 14, 2019). This study is carried out in accordance with the Declaration of Helsinki and the Clinical Trials Act. The findings will be published in peer-reviewed journals. CONCLUSION: The ISCHIA study will contribute to the standardization of patient education regarding the prevention of hypoglycemia by using isCGM.

Lower bone mineral density and higher bone resorption marker levels in premenopausal women with type 1 diabetes in Japan.

AIMS/INTRODUCTION: Type 1 diabetes is associated with poorer bone quality. Quantitative ultrasound provides an estimate of bone mineral density (BMD) and can also be used to evaluate bone quality, which is associated with an increased fracture risk in people with type 1 diabetes. The aim of this study was to evaluate the association between menopausal status and a bone turnover marker with heel BMD using quantitative ultrasound in women with type 1 diabetes and age- and body mass index-matched controls. MATERIALS AND METHODS: A total of 124 individuals recruited in Kyoto and Osaka, Japan - 62 women with type 1 diabetes (mean age 47.2 ± 17.3 years) and 62 age-, menopausal status-, sex- and body mass index-matched non-diabetic control individuals (mean age 47.3 ± 16.3 years) - were enrolled in this study. Heel BMD in the calcaneus was evaluated using ultrasonography (AOS-100NW, Hitachi-Aloka Medical, Ltd., Tokyo, Japan). A bone turnover marker was also measured. RESULTS: The heel BMD Z-score was significantly lower in premenopausal women with type 1 diabetes than in the premenopausal control group, but not in postmenopausal women with type 1 diabetes. Levels of tartrate-resistant acid phosphatase-5b, a bone resorption marker, were significantly higher in premenopausal women with type 1 diabetes than in the premenopausal control group, but not in postmenopausal women with type 1 diabetes. The whole parathyroid hormone level was significantly lower in both pre- and postmenopausal women with type 1 diabetes. CONCLUSIONS: Lower heel BMD, higher tartrate-resistant acid phosphatase-5b level and lower parathyroid hormone were observed in premenopausal women with type 1 diabetes. Premenopausal women with type 1 diabetes require osteoporosis precautions for postmenopause.