Practice guideline: Statement regarding treatment for suspected slowly progressive type 1 diabetes (SPIDDM; probable) cases (English version).

Insulin treatment should be introduced in patients with slowly progressive type 1 diabetes (SPIDDM; definite), according to the revised diagnostic criteria of SPIDDM (2023). In contrast, SPIDDM (probable) patients are in a non-insulin-dependent state; therefore, a more flexible treatment can be considered, although sulfonylurea agents should be avoided. Insulin treatment has been shown to maintain endogenous insulin secretion capacity in SPIDDM (probable); however, this does not mean that all SPIDDM (probable) patients should use insulin from the early phase.

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.].

Prediction of future insulin-deficiency in glutamic acid decarboxylase autoantibody enzyme-linked immunosorbent assay-positive patients with slowly-progressive type 1 diabetes.

Aims/introduction: This study aimed to identify risk factors that contribute to the progression of slowly-progressive type 1 diabetes by evaluating the positive predictive value (PPV) of factors associated with the progression to an insulin-dependent state.

Materials And Methods: We selected 60 slowly-progressive type 1 diabetes patients who tested positive for glutamic acid decarboxylase autoantibodies (GADA) at diagnosis from the Japanese Type 1 Diabetes Database Study. GADA levels in these patients were concurrently measured using both radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) techniques.

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.

Glucagon secretion and its association with glycaemic control and ketogenesis during sodium-glucose cotransporter 2 inhibition by ipragliflozin in people with type 1 diabetes: Results from the multicentre, open-label, prospective study.

Aim: Clinical trials showed the efficacy of sodium-glucose cotransporter 2 inhibitors for type 1 diabetes (T1D) by significant reductions in body weight and glycaemic variability, but elevated susceptibility to ketoacidosis via elevated glucagon secretion was a potential concern. The Suglat-AID evaluated glucagon responses and its associations with glycaemic control and ketogenesis before and after T1D treatment with the sodium-glucose cotransporter 2 inhibitor, ipragliflozin.

Methods: Adults with T1D (n = 25) took 50-mg open-labelled ipragliflozin daily as adjunctive to insulin.

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.

Subcutaneous Infusion of DNA-Aptamer Raised against Advanced Glycation End Products Prevents Loss of Skeletal Muscle Mass and Strength in Accelerated-Aging Mice.

We have developed DNA aptamers that can inhibit the toxic effects of advanced glycation end products (AGE-Apts). We herein evaluated the effects of AGE-Apts on muscle mass and strength in senescence-accelerated mouse prone 8 (SAMP8) mice. Eight-month-old male SAMP8 mice received subcutaneous infusion of control DNA aptamers (CTR-Apts) or AGE-Apts.

Comparison of Effects of Injectable Semaglutide and Dulaglutide on Oxidative Stress and Glucose Variability in Patients with Type 2 Diabetes Mellitus: A Prospective Preliminary Study.

Introduction: Recent trials have shown that glucagon-like peptide-1 receptor agonists considerably reduce atherosclerotic cardiovascular disease in patients with type 2 diabetes mellitus (T2DM). Oxidative stress, a surrogate marker of cardiovascular risk, is associated with glucose variability. However, to the best of our knowledge, no studies have compared the effects of injectable semaglutide and dulaglutide therapies on oxidative stress and glucose variability assessed via continuous glucose monitoring (CGM).

Bi-glandular and persistent enterovirus infection and distinct changes of the pancreas in slowly progressive type 1 diabetes mellitus.

In slowly progressive type 1 diabetes mellitus (SPIDDM), the pancreas shows sustained islet inflammation, pancreatitis, pancreatic acinar cell metaplasia/dysplasia (ADM), and intraepithelial neoplasia (PanIN), a precancerous lesion. The mechanisms underlying these changes remain unclear. The presence of enterovirus (EV) encoded-capsid protein 1 (VP1) and -2A protease (2A) and the innate immune responses of the pancreas were studied using immunohistochemistry and in situ hybridization in 12 SPIDDM and 19 non-diabetic control pancreases.

Comparison of positive rates between glutamic acid decarboxylase antibodies and ElisaRSR™ 3 Screen ICA™ in recently obtained sera from patients who had been previously diagnosed with slowly progressive type 1 diabetes.

Aims/introduction: This study aimed to compare the positivity rates of glutamic acid decarboxylase autoantibodies (GADA) and ElisaRSR™ 3 Screen ICA™ (3 Screen ICA), a newly developed assay for the simultaneous measurement of GADA, insulinoma-associated antigen-2 autoantibodies (IA-2A), and zinc transporter 8 autoantibodies (ZnT8A), in recently obtained sera from patients who had been previously diagnosed with slowly progressive type 1 diabetes (SPIDDM).

Materials And Methods: We enrolled 53 patients with SPIDDM who were positive for GADA at the diagnosis and 98 non-diabetic individuals, and investigated the diagnostic accuracy of the 3 Screen ICA (cutoff index ≥30 units) compared with that of GADA. In addition, we compared the clinical characteristics of patients with SPIDDM who were negative or positive on 3 Screen ICA.

SMTP-44D Inhibits Atherosclerotic Plaque Formation in Apolipoprotein-E Null Mice Partly by Suppressing the AGEs-RAGE Axis.

SMTP-44D has been reported to have anti-oxidative and anti-inflammatory reactions, including reduced expression of receptor for advanced glycation end products (RAGE) in experimental diabetic neuropathy. Although activation of RAGE with its ligands, and advanced glycation end products (AGEs), play a crucial role in atherosclerotic cardiovascular disease, a leading cause of death in diabetic patients, it remains unclear whether SMTP-44D could inhibit experimental atherosclerosis by suppressing the AGEs-RAGE axis. In this study, we investigated the effects of SMTP-44D on atherosclerotic plaque formation and expression of AGEs in apolipoprotein-E null () mice.

Bivalent GAD autoantibody ELISA improves clinical utility and risk prediction for adult autoimmune diabetes.

Aim/introduction: To investigate the differences in the clinical significance and glutamic acid decarboxylase autoantibody (GADA) affinity between RIA (RIA-GADA) and ELISA (ELISA-GADA) in patients with type 1 diabetes.

Methods: A total of 415 patients with type 1 diabetes were enrolled, including 199 acute-onset type 1 diabetes, 168 slowly progressive type 1 diabetes (SPIDDM), and 48 fulminant type 1 diabetes. GADA affinity was measured by a competitive binding experiment using unlabeled recombinant human GAD65 protein, and the diagnostic performance of both assays and the relationship between GADA affinity and the decline of fasting C-peptide (F-CPR) were examined.

Comparing the clinical significance and antigen specificity of insulinoma-associated antigen-2 autoantibodies between radioimmunoassay and enzyme-linked immunosorbent assay in Japanese patients with type 1 diabetes.

Aims/introduction: This study aimed to investigate the clinical significance and antigen specificity of autoantibodies to insulinoma-associated antigen-2 (IA-2A) by radioimmunoassay (RIA; IA-2A-RIA) and enzyme-linked immunosorbent assay (ELISA; IA-2A-ELISA) in Japanese patients with type 1 diabetes.

Materials And Methods: A total of 338 type 1 diabetic patients were enrolled, including 38 fulminant type 1 diabetes, 168 acute-onset type 1 diabetes and 137 slowly-progressive type 1 diabetes (SPIDDM). The concordance, correlation of autoantibody titer, and the relationship between IA-2A and progression to the insulin-deficient state were examined.

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

To evaluate the clinical efficacy of a new enzyme-linked immunosorbent assay (ELISA) system for simultaneously detecting three islet cell autoantibodies against glutamic acid decarboxylase (GADA), insulinoma-associated antigen-2 (IA-2A), and zinc transporter 8 (ZnT8A) (3 Screen ICA ELISA) in Japanese patients with acute-onset type 1 diabetes (T1D). In addition, clinical factors affecting the 3 Screen ICA ELISA index were investigated. We compared the positivity values of 3 Screen ICA ELISA with that of each autoantibody alone in 97 patients with acute-onset T1D (mean age 48.

Luseogliflozin inhibits high glucose-induced TGF-2 expression in mouse cardiomyocytes by suppressing NHE-1 activity.

Objective: Sodium-glucose cotransporter-2 (SGLT2) inhibitors exhibit cardioprotective properties in patients with diabetes. However, SGLT2 is not expressed in the heart, and the underlying molecular mechanisms are not fully understood. We investigated whether the SGLT2 inhibitor luseogliflozin exerts beneficial effects on high glucose-exposed cardiomyocytes via the suppression of sodium-hydrogen exchanger-1 (NHE-1) activity.

Japanese Type 1 Diabetes Database Study (TIDE-J): rationale and study design.

Type 1 diabetes (T1D) is classified into three subtypes: acute-onset, slowly progressive, and fulminant T1D, according to the heterogeneity of clinical course in Japan. Although several cross-sectional databases of T1D have been reported, prospective longitudinal databases to investigate clinical outcomes are lacking in our country. Therefore, we herein construct multi-center prospective longitudinal database of the three subtypes of T1D, accompanied with genetic information and biobanking, which is named Japanese Type 1 Diabetes Database Study (TIDE-J).

Glucose-dependent insulinotropic polypeptide inhibits cardiac hypertrophy and fibrosis in diabetic mice via suppression of TGF-β2.

Diabetic cardiomyopathy is associated with an increased risk for heart failure and death in patients with diabetes. We investigated here whether and how GIP attenuated cardiac hypertrophy and fibrosis in diabetic mice with obesity. Diabetic db/db mice at 7 weeks old were infused with vehicle or GIP (50 nmol/kg/day) for 6 weeks, and hearts were collected for histological and RT-PCR analyzes.

Immunohistochemical detection of enteroviruses in pancreatic tissues of patients with type 1 diabetes using a polyclonal antibody against 2A protease of Coxsackievirus.

Aims/introduction: The need for antiserum for immunohistochemical (IHC) detection of enterovirus (EV) in formaldehyde-fixed and paraffin-embedded samples is increasing. The gold standard monoclonal antibody (clone 5D8/1) against EV-envelope protein (VP1) was proven to cross-react with other proteins. Another candidate marker of EV proteins is 2A protease (2A ), which is encoded by the EV gene and translated by the host cells during EV replication, and participates processing proproteins to viral capsid proteins.

Effects of omarigliptin on glucose variability and oxidative stress in type 2 diabetes patients: A prospective study.

Aims: To date, no clinical studies have compared once-weekly dipeptidyl peptidase 4 (DPP-4) inhibitors with once-daily DPP-4 inhibitors in terms of glucose variability (GV) and oxidative stress (OS).

Methods: Thirty-six patients with type 2 diabetes mellitus (T2DM) treated with once-daily DPP-4 inhibitors for at least 12 weeks were randomized to either continue once-daily DPP-4 inhibitors or receive omarigliptin, a once-weekly DPP-4 inhibitor, for 24 weeks. The primary end points were changes in the diacron-reactive oxygen metabolite (d-ROMs) test, a marker of OS, and GV using flash glucose monitoring.

Glucose-Dependent Insulinotropic Polypeptide Suppresses Foam Cell Formation of Macrophages through Inhibition of the Cyclin-Dependent Kinase 5-CD36 Pathway.

Glucose-dependent insulinotropic polypeptide (GIP) has been reported to have an atheroprotective property in animal models. However, the effect of GIP on macrophage foam cell formation, a crucial step of atherosclerosis, remains largely unknown. We investigated the effects of GIP on foam cell formation of, and expression in, macrophages extracted from GIP receptor-deficient () and mice and cultured human U937 macrophages by using an agonist for GIP receptor, [D-Ala]GIP(1-42).

Association between insulin-like growth factor 1 and pancreatic volume in type 1 and type 2 diabetes: cross-sectional study of a Japanese population.

Aims/hypothesis: Although IGF-1 is known to promote organ growth, including exocrine pancreas, the association between plasma IGF-1 levels and pancreatic size remains unclear in diabetic patients.

Methods: This cross-sectional study was designed to investigate the correlations among pancreatic volume (PV) based on computed tomography, IGF-1 levels, age- and sex-adjusted IGF-1 levels (IGF-1 Z-score), and C-peptide levels in patients with type 1 diabetes (T1D) (n = 51) and type 2 diabetes (T2D) (n = 104) in a Japanese population.

Results: PV was significantly correlated with body weight (BW) in both types of diabetes.

Very rare case of Graves' disease with resistance to methimazole: a case report and literature review.

Background: Methimazole (MMI) is used to treat hyperthyroidism in Graves' disease. It is rare to encounter patients in whom hyperthyroidism cannot be controlled using high doses of MMI.Case presentation: A 21-year-old woman was referred to our hospital because of MMI-resistant Graves' disease.

Glucose Variability is Independently Correlated with Serum Level of Pigment Epithelium-Derived Factor in Type 2 Diabetes.

Introduction: Pigment epithelium-derived factor (PEDF) may play a role in cardiometabolic disorders. The aim of this study was to investigate which biochemical and clinical parameters are independently associated with serum PEDF levels in patients with type 2 diabetes mellitus (T2DM).

Methods: We performed a cross-sectional analysis of 124 patients with T2DM who underwent continuous glucose monitoring (CGM) and blood chemistry analysis, including the diacron-reactive oxygen metabolites (d-ROMs) test and serum PEDF measurement (study 1).

AGE-RAGE Axis Stimulates Oxidized LDL Uptake into Macrophages through Cyclin-Dependent Kinase 5-CD36 Pathway via Oxidative Stress Generation.

Advanced glycation end products (AGEs) are localized in macrophage-derived foam cells within atherosclerotic lesions, which could be associated with the increased risk of atherosclerotic cardiovascular disease under diabetic conditions. Although foam cell formation of macrophages has been shown to be enhanced by AGEs, the underlying molecular mechanism remains unclear. Since cyclin-dependent kinase 5 (Cdk5) is reported to modulate inflammatory responses in macrophages, we investigated whether Cdk5 could be involved in AGE-induced gene expression and foam cell formation of macrophages.

Anti-inflammatory and atheroprotective properties of glucagon.

Although glucagon has been shown to exert pleiotropic actions in various types of cells and organs through the interaction with its receptor, its pathophysiological role in atherosclerotic cardiovascular disease remains unclear. Here, we examined whether and how glucagon could attenuate the progression of atherosclerotic plaques in apolipoprotein E-deficient mice (ApoE), an animal model of atherosclerosis. Glucagon (138 or 413 nmol/kg/day) or vehicle was infused to mice at 16 weeks of age.