Decreased cognitive function is associated with preceding severe hypoglycemia and impaired blood glucose control in the elderly individuals with type 1 diabetes.

Aim/Introduction: This investigation aimed to clarify the relationship between cognitive function and blood glucose control in the elderly individuals with type 1 diabetes. Materials and methods: In total, 45 patients with type 1 diabetes, age 74.9 ± 6.7 years, and HbA1c levels of 7.9 ± 0.9% were studied. Severe hypoglycemia occurred in 33% of patients, and the number of severe hypoglycemia episodes was 0.6 ± 1.2 in the past 5 years before the time of the cognitive function tests. We analyzed clinical data and dementia scores on the Revised Hasegawa's Dementia Scale (HDS-R), Mini-Mental State Examination (MMSE), and Dementia Assessment Sheet for Community-based Integrated Care System, and 21 items (DASC-21). Results: There was a significant correlation between HbA1c and HDS-R, MMSE, respectively. There was a significant correlation between the number of severe hypoglycemic episodes and HDS-R, MMSE, and DASC-21, respectively. When the group with experience of severe hypoglycemia was compared to the control group, HDS-R, MMSE, and DASC-21 were meaningfully different after adjusting for age modeling analysis of covariance. Conclusions: In elderly individuals with type 1 diabetes, our results suggest that high HbA1c for the past 5 years from the cognitive function test and a history of severe hypoglycemic episodes from the time of disease diagnosis are related to decreased cognitive function.

Type 1 diabetes related to immune checkpoint inhibitors.

Type 1 diabetes, in part, has been recently reported as a side effect of immune checkpoint inhibitors (ICIs). The frequency of type 1 diabetes related to ICIs is estimated to be ∼3.5%. However, type 1 diabetes related to ICIs often presents with diabetic ketoacidosis or ketosis within approximately 2 weeks after hyperglycemic symptoms, such as dry mouth, polydipsia, and polyuria, necessitating urgent diagnosis and insulin treatment. Endogenous insulin secretion is depleted within 3 weeks of the clinical onset of type 1 diabetes. Moreover, the positive rate for islet-related autoantibodies has been shown to vary from 5% to 50%, and exocrine pancreatic enzyme levels are mildly increased. Thus, the clinical course of type 1 diabetes associated with ICIs is similar to that of fulminant type 1 diabetes. In this review, we describe the clinical features of type 1 diabetes associated with ICIs.

Fulminant type 1 diabetes: recent research progress and future prospects.

To clarify the clinical and etiological characteristics of fulminant type 1 diabetes, we reviewed data from patients who had developed type 1 diabetes following anti-programmed cell death 1/programmed cell death ligand 1 (anti-PD-1/PD-L1) therapy, and research on pancreatic beta cells derived from induced pluripotent stem (iPS) cells from patients with fulminant type 1 diabetes. As determined from the disease classifications and clinical and genetic characteristics, anti-PD-1/PD-L1 therapy-related type 1 diabetes includes both fulminant type 1 diabetes and acute-onset type 1 diabetes. Using insulin-positive cells derived from iPS cells, beta-cell fragility to inflammatory cytokines, but not its regeneration failure, was observed in fulminant type 1 diabetes. Moreover, severe hyperglycemia was reported as a risk factor of sudden death or cardiac arrest at disease onset, diffusion-weighted magnetic resonance imaging was suggested as an additional tool for making a diagnosis, and the CSAD/lnc-ITGB7-1 locus was genetically associated with fulminant type 1 diabetes. To fully understand fulminant type 1 diabetes, it is important to clarify the molecular mechanisms step by step through multifaceted approaches such as through analyses of the genetic factors, clinical features, histological findings, and cell biology. The careful and detailed study of patients is a great means for clarifying the etiology and pathophysiology of the disease.

"Preserved" glucagon secretion in fulminant type 1 diabetes.

Mixed-meal tolerance tests were carried out after an overnight fast. Healthy control participants (■), type 1A diabetespatients (○) and fulminant type 1 diabetic patients (▲). Data are presented as the mean ± standard error of the mean.

Taurine improves glucose tolerance in STZ-induced insulin-deficient diabetic mice.

Blood glucose levels fluctuate considerably in diabetic patients with reduced secretion of endogenous insulin. We previously reported that glucagon is secreted excessively in these patients and that taurine increases glucagon secretion in vitro. Therefore, we hypothesized that glucose tolerance would further deteriorate when taurine was administered to diabetic mice incapable of insulin secretion. We generated four groups of streptozotocin (STZ)-treated C57BL/6J mice (STZ-mice): STZ-mice without taurine treatment (STZ-Con), STZ-mice treated with 0.5% (w/v) taurine (STZ-0.5% Tau), STZ-mice treated with 1% (w/v) taurine (STZ-1% Tau), and STZ-mice treated with 2% (w/v) taurine (STZ-2% Tau). Mice were treated for 4 weeks, and then, we evaluated glucose tolerance, pancreatic ß-cell area and α-cell area, pancreatic insulin and glucagon content, and daily blood glucose variability. As a result, following the administration of taurine, glucose tolerance improved, both pancreatic ß- and α-cell area increased, and both insulin and glucagon content increased. In the 1% taurine administration group, blood glucose variability decreased. These unexpected results suggest that taurine improves glucose tolerance, in spite of its subsequent increased glucagon production, partly by increasing pancreatic ß-cells and insulin production in vivo.