Impact of the State of Emergency Declaration for Severe Acute Respiratory Syndrome Coronavirus-2 Pandemic Suppression on Individuals with Type 1 Diabetes Mellitus.

Objective To examine the impact of lifestyle changes caused by the first emergency declaration issued in 2020 on glycemic control and body weight changes in Japanese individuals with type 1 diabetes mellitus. Methods This study included Japanese individuals with type 1 diabetes mellitus who visited Tokyo Women's Medical University Hospital between January 2019 and September 2020 (n=278). Seasonal changes in glycated hemoglobin (HbA1c) levels and the body mass index (BMI) were compared. A self-administered questionnaire regarding changes in treatment, diet, exercise, sleep, and telecommuting was used to assess lifestyle changes. Results Although HbA1c levels decreased from winter to summer in 2019 and 2020, the annual change was slightly but significantly greater in 2020 than in 2019. Seasonal changes in the BMI between 2019 and 2020 were also significantly different. An increase in the daily insulin dose, overall blood glucose level, diurnal change in blood glucose level, and food intake were significantly associated with increased HbA1c levels. Furthermore, HbA1c levels decreased with increasing moderate physical activity and sleep duration. The change in the BMI increased with increasing insulin dose, overall high blood glucose levels, and food intake. However, an increase in moderate physical activity was associated with a decrease in the BMI. HbA1c levels were significantly lower after the first emergency declaration in individuals with type 1 diabetes mellitus than that before the emergency declaration, even after accounting for seasonal variations. Conclusion Decreased HbA1c levels were associated with a decreased food intake, increased moderate exercise, and increased sleep duration during the state of emergency. The BMI remained relatively unchanged.

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.

Recovery of hypoglycemic confidence using intermittently scanned continuous glucose monitoring among adults with type 1 diabetes with level 3 hypoglycemia: A prospective, single-center, single-arm study.

AIM: To investigate whether the FreeStyle Libre, an intermittent scanning continuous glucose monitoring (isCGM) system, influences confidence in managing hypoglycemia in adults with type 1 diabetes. MATERIALS AND METHODS: This longitudinal, observational study conducted at one facility included 121 adults with type 1 diabetes. Participants used the conventional finger-prick method for self-testing glucose before using isCGM. At baseline and 12 months after initiating isCGM, the Hypoglycemic Confidence Scale (HCS), Diabetes Treatment Satisfaction Questionnaire (DTSQ), and HbA1c were performed. At 12 months, the percentage of individuals utilizing isCGM trend arrows for glucose management was observed. The primary endpoint was hypoglycemic confidence change attributed to using isCGM. RESULTS: After using isCGM, HCS scores improved significantly from 2.89 (2.56, 3.22) to 3.00 (2.20, 3.33) (p < 0.001); median (25%, 75%). Among participants with level 3 hypoglycemia at baseline, hypoglycemic confidence during sleep (p < 0.05), in social situations (p < 0.05), and in avoiding serious hypoglycemia-related problems (p < 0.05) were improved. Despite hypoglycemia risk, participants could continue daily activities by using isCGM (p < 0.05), and sixty-nine percent utilized trend arrows effectively. CONCLUSION: Using isCGM improved hypoglycemic confidence among adults with type 1 diabetes. Data analysis indicated that people with type 1 diabetes could live more freely and better manage hypoglycemia using isCGM.

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.

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.

Factors associated with hypoglycemia unawareness and severe hypoglycemia in type 1 diabetes mellitus patients.

AIMS/INTRODUCTION: Several factors are associated with hypoglycemia unawareness and severe hypoglycemia, but few large studies have analyzed Japanese patients with type 1 diabetes. The aim of this study was to analyze the risk factors for hypoglycemia unawareness and severe hypoglycemia in Japanese type 1 diabetes patients. MATERIALS AND METHODS: A self-administered questionnaire investigated events, complications and treatments associated with hypoglycemia in patients with type 1 diabetes. Multiple logistic regression analysis of factors associated with hypoglycemia unawareness and severe hypoglycemia requiring medical treatment was carried out. The coefficient of variation (CV) of blood glucose levels was determined using blood samples collected at six outpatient visits. RESULTS: Of the 1,619 participants, 44.2% and 10.4% experienced hypoglycemia unawareness and severe hypoglycemia, respectively. Mean HbA1c levels in patients with hypoglycemia unawareness were lower than those in patients without hypoglycemia unawareness. The type 1 diabetes subtype, glycated hemoglobin (HbA1c) level, CV of blood glucose levels and history of severe hypoglycemia requiring medical treatment were significant independent variables predicting the presence of hypoglycemia unawareness. The glucose CV and a history of hypoglycemia unawareness were significant independent variables predicting severe hypoglycemia requiring medical treatment. In stratified analyses of patients divided into four groups according to glucose CV and HbA1c levels, the high-glucose-CV/low-HbA1c group had the highest odds ratios for hypoglycemia unawareness (2.60) and severe hypoglycemia requiring medical treatment (2.55). CONCLUSIONS: The ambulant glucose CV correlated with both hypoglycemia unawareness and severe hypoglycemia. Patients with high glucose CV and low HbA1c are at high risk of such adverse events, and their treatment strategies should be reviewed.

High prevalence of depressive symptoms among people with pediatric-onset and adolescent-onset type 1 diabetes: A cross-sectional analysis of the Diabetes Study from the Center of Tokyo Women's Medical University.

AIMS/INTRODUCTION: To investigate the prevalence of depressive symptoms by the age of onset of type 1 diabetes, and its association with the condition of individuals with pediatric- and adolescent-onset type 1 diabetes. MATERIALS AND METHODS: This single-center cross-sectional study enrolled Japanese participants with type 1 diabetes. All participants completed a questionnaire about their diabetes-related condition and the Patient Health Questionnaire-9, which was used to evaluate depression. Individuals with a Patient Health Questionnaire-9 score of ≥10 points were defined as having moderate depressive symptoms. RESULTS: A total of 1,267 participants (mean age 40 years; mean duration of type 1 diabetes 21 years; 68% female; mean glycated hemoglobin 7.8%) were included and classified according to the age of onset of type 1 diabetes to identify the proportion of moderate depressive symptoms in each group: 21% (0-12 years), 18% (13-19 years) and 13% (20-40 years). The prevalence of moderate depressive symptoms was significantly higher among participants with pediatric-onset type 1 diabetes (P < 0.05). Moderate depressive symptoms were associated with increased glycated hemoglobin, neuropathy and hypoglycemia unawareness. CONCLUSIONS: Regular screening for depressive symptoms and hypoglycemia awareness is important. Healthcare professionals should provide appropriate psychosocial care for people with pediatric-onset and adolescent-onset type 1 diabetes from childhood through to adulthood.

A sensor augmented pump may improve awareness of hypoglycemia and quality of life in Japanese patients with type 1 diabetes mellitus.

OBJECTIVE: Sensor-augmented pump (SAP) therapy reportedly improves glycemic control and quality of life. However, there is limited information on changes in awareness of hypoglycemia and quality of life (QOL) after starting SAP therapy in Japanese patients with type 1 diabetes. The aim of this study was to evaluate glycemic control, awareness of hypoglycemia, and QOL after initiation of SAP therapy in these patients. METHODS: The study included 20 patients with type 1 diabetes who started SAP therapy. HbA1c levels, values derived from continuous glucose monitoring [including percentages of time in target range (70-180 mg/dL), time below range (< 70 mg/dL), and time above range (> 180 mg/dL)], the Diabetes Treatment Satisfaction Questionnaire score, and the Clarke score were compared between baseline and after 3 and 6 months of SAP therapy. RESULTS: There was a significant decrease in HbA1c at 3 and 6 months after starting on the SAP (p < 0.0001). There was also a significant decrease in time above range (> 180 mg/dL) at the two time points (p = 0.0069 and p = 0.0042, respectively). There was no significant change in time below range (< 70 mg/dL). There was a significant reduction in the Clarke score (p = 0.0347 and p = 0.0003, respectively) and a significant increase in the treatment satisfaction score (both p < 0.0001). There was no significant change in any of the three MOS 36-Item Short-Form Health Survey v2 component summary scores. CONCLUSION: SAP therapy was associated with improvement of glycemic control, mainly by reducing hyperglycemia, and patients' satisfaction with treatment.

The incidences of and risk factors for severe retinopathy requiring photocoagulation and albuminuria in Japanese patients with childhood-onset type 1 diabetes.

The aim of this study was to clarify the incidences of and the risk factors for severe retinopathy requiring photocoagulation therapy and albuminuria in Japanese patients with childhood-onset type 1 diabetes mellitus. A total of 756 patients from a cohort study by the Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes were included in the study. Patients were registered in 1995 or 2000, and HbA1cwas measured every 4 months and analyzed in central hospital for an average of 6 years. The presence of severe retinopathy requiring laser photocoagulation and the presence of albuminuria was checked for during the period 2010-2011. During a median of 18 (range: 15-21) years, 34 out of 756 patients underwent laser photocoagulation and 57 out of 605 patients developed albuminuria. A Cox proportional hazards model showed that the risk of severe retinopathy requiring laser photocoagulation increased by 1.15 (95% confidence interval [CI] 1.03-1.29, p = 0.012) with each increase of a year in the age at onset, by 4.03 (95% CI 1.20-13.5, p = 0.024) in females, and by 2.05 (95% CI 1.69-2.49, p < 0.0001) with each increase of 1% in HbA1c. The risk of albuminuria increased significantly, by 1.09 (95% CI 1.01-1.18 p = 0.037), with each increase of a year in the age at onset and by 2.38 (95% CI 1.93-2.97 p < 0.0001) with each increase of 1% in HbA1c. In Japanese patients with childhood-onset type 1 diabetes, older age at the onset of diabetes, female rather than male gender, and higher HbA1c were found to increase the risk of requiring photocoagulation. No patients with HbA1c < 7.5% developed severe retinopathy requiring photocoagulation therapy. The risk of developing albuminuria increased with age at onset of diabetes and HbA1c. Female gender was a strong risk factor for severe retinopathy requiring photocoagulation, but not for albuminuria.

Four cases of type 1 diabetes mellitus showing sharp serum transaminase increases and hepatomegaly due to glycogenic hepatopathy.

Poorly controlled diabetes mellitus (DM) patients sometimes show serum transaminase elevations due to steatohepatitis. However, we experienced four cases with type 1 DM with sharp elevations in serum transaminases that could not be explained by steatohepatitis alone and showed bright liver. They were diagnosed with glycogenic hepatopathy (GH) clinicopathologically. The four patients had a median age of 22.5 years (range, 19-29 years) and 12.5 (4-15)-year histories of type 1 DM and showed marked increases in serum transaminases (aspartate aminotransferase, 698 U/L [469-2763 U/L]; alanine transaminase, 255 U/L [216-956 U/L]). Diabetes mellitus control was poor and hemoglobin A1c was 12.7% (11-16.5%). Three cases had a past history of diabetic ketoacidosis. Hepatomegaly and hyperdense liver were seen on computed tomography scans. Magnetic resonance imaging showed low intensity in T2-weighted images. The pathological findings revealed pale and swollen hepatocytes and glycogenated nuclei. The architecture of the liver was preserved, and steatosis and fibrosis were mild. The cytoplasm of hepatocytes stained densely positive with periodic acid-Schiff, and the positive staining disappeared after diastase digestion, suggesting glycogen deposition. No other cause of hepatitis was evident, and the diagnosis was GH. Elevated transaminases improved within 1 month with good glycemic control. Transaminase elevations were observed several times in three cases with poor glycemic control. Glycogenic hepatopathy is rare, but extremely high serum elevations of transaminases are important to identify clinically. Despite showing a good clinical course in general, GH sometimes recurs and requires strict glycemic control. Clinicians should be aware of and recognize GH when dealing with uncontrolled DM patients.

Follow-up survey of all participants at the first and second juvenile diabetes summer camp in Japan in 1963 and 1964.

This report documents the status of all 10 participants in the first (1963) and second (1964) summer camp in Japan as of 31 December 2008. The eight living participants continue to function as adults in society without hemodialysis.

Incidence and development of diabetic microangiopathy of fulminant type 1 diabetes--comparison with non-fulminant type 1 diabetes.

OBJECTIVE: The data from the Fulminant Type 1 Diabetes Committee suggested that patients with fulminant type 1 diabetes are a subgroup at high risk for diabetic microangiopathy in the first 5 years after diagnosis associated with the lack of endogenous insulin secretion from the onset of diabetes. The aim of this study was to assess the development of microangiopathy in patients with fulminant type 1 diabetes followed in our diabetes center. METHODS: Sixteen patients with fulminant type 1 diabetes and 60 age-matched patients with non-fulminant type 1 diabetes were recruited as subjects. The existence or lack of diabetic retinopathy and nephropathy, average HbA(1C) level, serum C-peptide level, average blood pressure, insulin level, whether or not they were taking antihypertensive agents, and smoking history were investigated retrospectively based on medical records. RESULTS: The 5-year incidence of microangiopathy was lower in fulminant than in non-fulminant type 1 diabetes patients; retinopathy cases occurred in 0% vs. 8.3% of patients, and nephropathy occurred in 0% vs. 1.7% of patients. The 10-year incidence of retinopathy was 0% vs. 24.1%, and that of nephropathy was 11.1% vs. 3.4%. The cumulative incidence of microangiopathy did not differ between the fulminant and non-fulminant type 1 diabetes patients. Mean HbA(1C) levels and systolic blood pressure were significantly lower in fulminant type 1 diabetes patients. CONCLUSION: No difference between the patients visiting the center with fulminant type 1 diabetes and those with non-fulminant type 1 diabetes was observed in the development of microangiopathy complications.

Time-course changes in clinical features of early-onset Japanese type 1 and type 2 diabetes: TWMU hospital-based study.

Using a database of patients with type 1 (n=1675) and type 2 (n=2259) diabetes diagnosed before the age of 30 years at the Diabetes Center, Tokyo Women's Medical University (TWMU), in which such Japanese patients have been registered at the time of first visit since the 1960s, we performed a hospital-based study over the last 40 years to clarify time-course changes in clinical features of type 1 and type 2 diabetes diagnosed before the age of 30 years. Type 2 diabetes had a male dominancy, while there has been a female dominancy in patients with type 1 diabetes as in previous reports of Japanese childhood-onset type 1 diabetes. Such dominances had been continued over the last 40 years. The number of patients with type 2 diabetes and with a past history of obesity increased with time. The age at which type 2 diabetes was diagnosed was suggested to have been getting lower with time, whereas that of type 1 diabetes has been higher with time. There was no marked difference in family history of diabetes in the first-degree relatives of patients with type 2 diabetes, regardless of the presence or absence of a past history of obesity. More female patients with type 2 diabetes diagnosed before the age of 15 years had mothers with type 2 diabetes compared to corresponding male patients.

Nationwide survey to compare the prevalence of transient elevation of liver transaminase during treatment of diabetic ketosis or ketoacidosis in new-onset acute and fulminant type 1 diabetes mellitus.

BACKGROUND AIMS: A mild increase in liver enzyme levels is sometimes observed in patients with diabetic ketosis or ketoacidosis. The aim of the present study was to assess the cause and prevalence of the elevation of liver transaminase levels in fulminant and acute-onset type 1 diabetic patients experiencing diabetic ketosis or ketoacidosis. METHODS: We analyzed data on the liver transaminase levels of 108 patients over 18 years of age with newly diagnosed type 1 diabetes complicated by ketosis or ketoacidosis. The data were collated from a nationwide survey on fulminant type 1 diabetes and retrospective medical records. RESULTS: Thirty-two (60.4%) out of the 53 patients suffering from fulminant type 1 diabetes were detected with transient elevation of liver transaminase (TELT) levels during the first month after initiation of insulin therapy; in the case of acute-onset type 1 diabetes, such an observation was noted in 16 (29.1%) out of 55 patients. Fatty liver was diagnosed in 20% of the patients, and 65% of these patients exhibited TELT. The dosage of insulin injected in these patients was significantly high. CONCLUSIONS: High blood glucose and fatty liver may influence the elevation of liver transaminase levels during the treatment of new-onset type 1 diabetes.

Characteristics and learning effects of the predictability of the self-monitored blood glucose level in children with type 1 diabetes.

To know how the blood glucose level obtained by SMBG are recognized by type 1 diabetic children with relatively stable HbA(1c), they were requested to record the levels estimated before SMBG, and the estimated and SMBG levels of blood glucose were compared. In error grid analysis, the children overestimated the blood glucose level when it was lower than around 140 mg/dl, and underestimated it when it was higher than 140 mg/dl in daily life. Seventy-nine percents of the results were included in areas A and B in the error grid analysis. It is likely that the predictability of blood glucose levels in daily life was not difficult for the children with relatively stable HbA(1c) (6.9 +/- 0.5%). Error grid analysis also showed that the results were changed to higher ranks in the second half of this study period. This tendency was observed irrespective of the SMBG level, indicating the learning effects.

Impact on mortality and incidence of end-stage renal disease of education and treatment at a diabetes center among patients with type 1 diabetes: comparison of two subgroups in the Japanese DERI cohort.

The aim of this study was to compare mortality and incidence of end-stage renal disease (ESRD) in patients with type 1 (insulin-dependent) diabetes who had attended a diabetes center with those who had not. The cohort consisted of a total of 1430 patients diagnosed with Type 1 diabetes at 18 years or younger, and between 1965 and 1979. This population-based cohort in Japan was subdivided into two groups: patients who had visited a large diabetes center in Tokyo (n=162) and those who had not (n=1212). Mortality and incidence of ESRD were compared between the two subgroups as of January 1, 1990. Crude mortality was 1.95 per 1000 person-years (95% CI: 0.49-5.06) for those who had visited the center and 6.05 (4.86-7.41) for those who had not. A multivariate Cox proportional hazard model showed that the patients who had visited the center were three times less likely to die (hazard ratio: 0.31, 95% CI: 0.10-0.98) than those who had not. Crude incidence of ESRD was 1.32 (0.22-4.09) and 5.86 (4.65-7.26) for those who had visited the center and for those who had not, respectively. After adjusting for covariates, the patients who had visited the center were five times less likely to develop ESRD (hazard ratio: 0.19, 0.05-0.78) than those who had not. Education and treatment of type 1 diabetes with an integrated management system under specialists and a multidisciplinary team appears to be associated with a better prognosis.

Transient elevation of liver transaminase after starting insulin therapy for diabetic ketosis or ketoacidosis in newly diagnosed type 1 diabetes mellitus.

A mild increase of AST and/or ALT is sometimes observed among patients with diabetic ketosis or diabetic ketoacidosis (DKA) after initial insulin treatment, and the exact mechanism is still undefined. Therefore, we compared the clinical background between patients with and without transient elevation of liver transaminase (TELT) at the onset of type 1 diabetes mellitus with diabetic ketosis or DKA. Among 50 patients, 13 patients showed TELT. The TELT group was characterized by higher plasma glucose (P<0.05), higher HbA1c (P<0.05), and higher triglyceride (P<0.01) before insulin therapy than those without TELT. The TELT group needed significantly more insulin (P<0.05) for the treatment. In echo-histogram analysis of three patients with TELT, the increase of liver-kidney contrast after insulin treatment suggested fat deposition to the liver. The fat deposition to the liver might be one of the causes of the mild increase of AST and/or ALT after initial treatment of insulin in diabetic ketosis or DKA.