Ultra rapid lispro improves postprandial glucose control compared with lispro in patients with type 1 diabetes: Results from the 26-week PRONTO-T1D study.

AIMS: To evaluate the efficacy and safety of ultra rapid lispro (URLi) versus lispro in adults with type 1 diabetes in a 26-week, treat-to-target, phase 3 trial. MATERIALS AND METHODS: After an 8-week lead-in to optimize basal insulin glargine or degludec, patients were randomized to double-blind mealtime URLi (n = 451) or lispro (n = 442), or open-label post-meal URLi (n = 329). The primary endpoint was change from baseline glycated haemoglobin (HbA1c) to 26 weeks (non-inferiority margin 0.4%), with multiplicity-adjusted objectives for postprandial glucose (PPG) excursions after a meal test. RESULTS: Both mealtime and post-meal URLi demonstrated non-inferiority to lispro for HbA1c: estimated treatment difference (ETD) for mealtime URLi -0.08% [95% confidence interval (CI) -0.16, 0.00] and for post-meal URLi +0.13% (95% CI 0.04, 0.22), with a significantly higher endpoint HbA1c for post-meal URLi versus lispro (P = 0.003). Mealtime URLi was superior to lispro in reducing 1- and 2-hour PPG excursions during the meal test: ETD -1.55 mmol/L (95% CI -1.96, -1.14) at 1 hour and - 1.73 mmol/L (95% CI -2.28, -1.18) at 2 hours (both P < 0.001). The rate and incidence of severe, documented and postprandial hypoglycaemia (<3.0 mmol/L) was similar between treatments, but mealtime URLi demonstrated a 37% lower rate in the period >4 hours after meals (P = 0.013). Injection site reactions were reported by 2.9% of patients on mealtime URLi, 2.4% on post-meal URLi, and 0.2% on lispro. Overall, the incidence of treatment-emergent adverse events was similar between treatments. CONCLUSIONS: The results showed that URLi provided good glycaemic control, with non-inferiority to lispro confirmed for both mealtime and post-meal URLi, while superior PPG control was demonstrated with mealtime dosing.

Genetic differences between type 1 diabetes with and without other autoimmune diseases.

BACKGROUND: Clusters of autoimmune diseases (ADs) are present in some people with type 1 diabetes. This clustering suggests the existence of common genetic backgrounds for abnormal autoimmunity in these individuals. However, the genetic differences between type 1 diabetes patients with and without other ADs are not well known. METHODS: To investigate the clinical background and genetic differences between type 1 diabetes patients with and without other ADs, single nucleotide polymorphisms (SNPs) in the CTLA4, SUMO4, PTPN22, IRF5, STAT4, and BLK genes were analysed by using either a TaqMan assay or direct sequencing. The frequencies of alleles, genotypes of each gene, and the human leukocyte antigen (HLA) haplotype were analysed to investigate differences among 3 groups: type 1 diabetes with systemic ADs (group A), type 1 diabetes with other organ-specific ADs (group B), and type 1 diabetes without other ADs (group C). RESULTS: The frequency of the C allele in the -1123G > C SNP in the PTPN22 gene promoter was significantly higher in groups A and B than in group C (P = .0258 and .0207, respectively). The allele frequencies of the other SNPs were comparable. The frequency of HLA DRB1*0405-DQB1*0401 was significantly higher in groups A and B than in group C (P = .021 and .0395, respectively). CONCLUSIONS: The -1123G > C SNP in the PTPN22 gene promoter and HLA DRB1*0405-DQB1*0401 might influence the concurrence of systemic and organ-specific ADs in patients with type 1 diabetes.

Clinicophysiological outcomes after total pancreatectomy.

PURPOSE: Total pancreatectomy (TP) for pancreatic neoplasms is associated with high morbidity and mortality rates. However, with recent advances in surgical techniques and improved postoperative management, the number of cases with clinical indications for TP is increasing. Here, we evaluated the clinical outcomes post-TP. MATERIALS AND METHODS: Patients (n = 41) who underwent TP between 2004 and 2011 at Tokyo Women's Medical University were retrospectively examined. Pre- and postoperative clinicophysiological data were collected up to 12 months post-TP and then analyzed. RESULTS: Only glycated hemoglobin (HbA1c), percentage of lymphocytes and hepatic Hounsfield unit level on computed tomography (CT) were significantly different between the preoperative state and at 12 months post-TP, while other clinicophysiological parameters remained unchanged. The quantity of the pancreatic enzyme administered significantly influenced glycemic control at 12 months post-TP (p < 0.05). CONCLUSIONS: All clinicophysiological parameters except for HbA1c were temporarily decreased after TP but normalized by 12 months. Thus, TP is a feasible surgical approach to treating pancreatic neoplasms with the potential to spread across the entire pancreas when adequately supplemented by synthetic insulin and pancreatic enzymes.

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.

Type 1 diabetes mellitus following COVID-19 vaccination: a report of two cases and review of literature.

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection, which led to the coronavirus 2019 (COVID-19) pandemic, has promoted the development of novel therapeutic agents and vaccines to combat the global spread of the virus. While the COVID-19 vaccines approved thus far have proven to be effective in clinical settings, there have been reports of autoimmune diseases occurring following vaccination, including autoimmune/inflammatory syndrome induced by adjuvant syndrome. We herein report two cases of type 1 diabetes mellitus that occurred following COVID-19 vaccination and provide a literature review. Both cases received multiple vaccinations as recommended to ensure optimal antibody titers. Moreover, the HLA associated with susceptibility to type 1 diabetes was prototypic in both cases. This indirect evidence suggests that the COVID-19 vaccines may be implicated in the pathogenesis of type 1 diabetes. Further case reports to establish a clearer understanding of a potential association are warranted. Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-024-00695-9.

Predictors of the effectiveness of isCGM usage in adults with type 1 diabetes mellitus: post-hoc analysis of the ISCHIA study.

Aim: The Effect of Intermittent-Scanning Continuous Glucose Monitoring to Glycemic Control Including Hypoglycemia and Quality of Life of Patients with Type 1 Diabetes Mellitus (ISCHIA) study was a randomized, crossover trial that reported the decrease in time below range (TBR) by the use of intermittent-scanning continuous glucose monitoring (isCGM) combined with structured education in adults with type 1 diabetes (T1D) treated by multiple daily injections. The participants were instructed to perform frequent scanning of the isCGM sensor (10 times a day or more) and ingest sugar when impending hypoglycemia is suspected by tracking the sensor glucose levels and the trend arrow. We conducted post-hoc analysis to identify factors affecting difference in TBR (∆TBR), in time in range (∆TIR), and in time above range (∆TAR). Participants and methods: Data from 93 participants who completed the ISCHIA study were used. Multiple regression analyses were performed to identify factors affecting CGM metrics. Results: Pearson's correlation analysis showed the negative association between log-transformed scan frequency and with ∆TBR (r = - 0.255, P = 0.015), while there was no significant association of log-transformed scan frequency with ∆TIR (r = 0.172, P = 0.102) and ∆TAR (r = 0.032, P = 0.761), respectively. The log-transformed scan frequency was an independent predictor of ∆TBR (Beta = - 7.712, P = 0.022), but not of ∆TIR(Beta = 7.203, P = 0.091) and of ∆TAR (Beta = 0.514, P = 0.925). Conclusions: Our findings suggest that more frequent scanning of isCGM may be beneficial to reduce TBR in T1D adults.

Correction: New diagnostic criteria (2023) for slowly progressive type 1 diabetes (SPIDDM): Report from Committee on Type 1 Diabetes in Japan Diabetes Society (English version).

[This corrects the article DOI: 10.1007/s13340-023-00679-1.].

New diagnostic criteria (2023) for slowly progressive type 1 diabetes (SPIDDM): Report from Committee on Type 1 Diabetes in Japan Diabetes Society (English version).

The diagnostic criteria for slowly progressive type 1 diabetes (slowly progressive insulin-dependent diabetes mellitus; SPIDDM) have been revised by the Committee on Type 1 Diabetes of the Japan Diabetes Society. All of the following three criteria must be met for "a definitive diagnosis of SPIDDM": (1) presence of anti-islet autoantibodies at some point in time during the disease course; (2) absence of ketosis or ketoacidosis at the diagnosis of diabetes with no requirement of insulin treatment to correct hyperglycemia immediately after diagnosis in principle; and (3) gradual decrease of insulin secretion over time, with insulin treatment required at more than 3 months after diagnosis, and presence of severe endogenous insulin deficiency (fasting serum C-peptide immunoreactivity < 0.6 ng/mL) at the last observed point in time. When a patient fulfills the only (1) and (2), but not (3), he/she is diagnosed with "SPIDDM (probable)" because the diabetes is non-insulin-dependent state.

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.

New diagnostic criteria (2023) for slowly progressive type 1 diabetes (SPIDDM): Report from Committee on Type 1 Diabetes of the Japan Diabetes Society (English version).

The diagnostic criteria for slowly progressive type 1 diabetes (slowly progressive insulin-dependent diabetes mellitus; SPIDDM) have been revised by the Committee on Type 1 Diabetes of the Japan Diabetes Society. All of the following three criteria must be met for 'a definitive diagnosis of SPIDDM': (1) presence of anti-islet autoantibodies at some point in time during the disease course; (2) absence of ketosis or ketoacidosis at the diagnosis of diabetes with no requirement for insulin treatment to correct hyperglycemia immediately after diagnosis in principle; and (3) gradual decrease of insulin secretion over time, with insulin treatment required at more than 3 months after diagnosis, and the presence of severe endogenous insulin deficiency (fasting serum C-peptide immunoreactivity <0.6 ng/mL) at the last observed point in time. When a patient fulfills only (1) and (2), but not (3), he/she is diagnosed with 'SPIDDM (probable)' because the diabetes is non-insulin-dependent type.