Sex inequalities in cardiovascular risk factors and their management in primary prevention in adults living with type 1 diabetes in Germany and France: findings from DPV and SFDT1.

Introduction & Objectives: To evaluate whether cardiovascular risk factors and their management differ in primary prevention between adult males and females with type 1 diabetes (T1D) in two European countries in 2020-2022 and sex inequalities in achievement of standards of care in diabetes.

Methods: We used 2020-2022 data of patients without a cardiovascular history in the Prospective Diabetes Follow-up registry (DPV) centres, in Germany, and the Société Francophone du Diabète- Cohorte Diabète de Type 1 cohort (SFDT1), in France.

Results: We included 2,657 participants from the DPV registry and 1,172 from the SFDT1 study.

Q-Score Complements the Time in Range in the Evaluation of Short-Term Glycemic Control.

Background And Aims: The Q-Score is a single-number composite metric that is constructed based on the following components: central glycemic tendency, hyperglycemia, hypoglycemia, and intra- and interday variability. Herein, we refined the Q-Score for the screening and analysis of short-term glycemic control using continuous glucose monitoring (CGM) profiles.

Methods: Continuous glucose monitoring profiles were obtained from noninterventional, retrospective cross-sectional studies.

Patient-Tailored Decision Support System Improves Short- and Long-Term Glycemic Control in Type 2 Diabetes.

Background: The increasing prevalence of type 2 diabetes mellitus (T2D) and specialist shortage has caused a healthcare gap that can be bridged by a decision support system (DSS). We investigated whether a diabetes DSS can improve long- and/or short-term glycemic control.

Methods: This is a retrospective observational cohort study of the Diabetiva program, which offered a patient-tailored DSS using Karlsburger Diabetes-Management System (KADIS) once a year.

Applications of Variability Analysis Techniques for Continuous Glucose Monitoring Derived Time Series in Diabetic Patients.

Methods from non-linear dynamics have enhanced understanding of functional dysregulation in various diseases but received less attention in diabetes. This retrospective cross-sectional study evaluates and compares relationships between indices of non-linear dynamics and traditional glycemic variability, and their potential application in diabetes control. Continuous glucose monitoring provided data for 177 subjects with type 1 ( = 22), type 2 diabetes ( = 143), and 12 non-diabetic subjects.

Characterization of the Human Pancreas Side Population as a Potential Reservoir of Adult Stem Cells.

Objectives: The side population (SP) contains cells with stem cell/progenitor properties. Previously, we observed that the mouse pancreas SP expanded after pancreatic injury. We aimed to characterize the SP in human pancreas as a potential source of stem cells.

Localization of dipeptidyl peptidase-4 (CD26) to human pancreatic ducts and islet alpha cells.

Aim: DPP-4/CD26 degrades the incretins GLP-1 and GIP. The localization of DPP-4 within the human pancreas is not well documented but is likely to be relevant for understanding incretin function. We aimed to define the cellular localization of DPP-4 in the human pancreas from cadaveric organ donors with and without diabetes.

Q-Score: development of a new metric for continuous glucose monitoring that enables stratification of antihyperglycaemic therapies.

Background: Continuous glucose monitoring (CGM) has revolutionised diabetes management. CGM enables complete visualisation of the glucose profile, and the uncovering of metabolic 'weak points'. A standardised procedure to evaluate the complex data acquired by CGM, and to create patient-tailored recommendations has not yet been developed.

Declining ß-cell function is associated with the lack of long-range negative correlation in glucose dynamics and increased glycemic variability: A retrospective analysis in patients with type 2 diabetes.

Objective: To determine whether characteristics of glucose dynamics are reflections of β-cell function or rather of inadequate diabetes control.

Materials/methods: We analyzed historical liquid meal tolerance test (LMTT) and continuous glucose monitoring (CGM) data, which had been obtained from 56 non-insulin treated type 2 diabetic outpatients during withdrawal of antidiabetic drugs. Computed CGM parameters included detrended fluctuation analysis (DFA)-based indices, autocorrelation function exponent, mean amplitude of glycemic excursions (MAGE), glucose SD, and measures of glycemic exposure.

Antigen-based vaccination and prevention of type 1 diabetes.

Insulin-dependent or type 1 diabetes (T1D) is a paradigm for prevention of autoimmune disease: Pancreatic β-cell autoantigens are defined, at-risk individuals can be identified before the onset of symptoms, and autoimmune diabetes is preventable in rodent models. Intervention in asymptomatic individuals before or after the onset of subclinical islet autoimmunity places a premium on safety, a requirement met only by lifestyle-dietary approaches or autoantigen-based vaccination to induce protective immune tolerance. Insulin is the key driver of autoimmune β-cell destruction in the nonobese diabetic (NOD) mouse model of T1D and is an early autoimmune target in children at risk for T1D.

Evaluation of the mean absolute glucose change as a measure of glycemic variability using continuous glucose monitoring data.

Background: The mean absolute glucose (MAG) change, originally developed to assess associations between glycemic variability (GV) and intensive care unit mortality, has not yet been validated. We used continuous glucose monitoring (CGM) datasets from patients with diabetes to assess the validity of MAG and to quantify associations with established measures of GV.

Subjects And Methods: Validation was based on retrospective analysis of 72-h CGM data collected during clinical studies involving 815 outpatients (48 with type 1 diabetes and 767 with type 2 diabetes).

The Karlsburg Diabetes Management System: translation from research to eHealth application.

Background: Several telemedicine-based eHealth programs exist, but patient-focused personalized decision support (PDS) is usually lacking. We evaluated the acceptance, efficiency, and cost-effectiveness of telemedicine-assisted PDS in routine outpatient diabetes care.

Methods: Data are derived from the Diabetiva® program of the German health insurance company BKK TAUNUS.

Translation of personalized decision support into routine diabetes care.

Objective: The aim of this study was to evaluate the impact of personalized decision support (PDS) on metabolic control in people with diabetes and cardiovascular disease.

Research Design And Methods: The German health insurance fund BKK TAUNUS offers to its insured people with diabetes and cardiovascular disease the possibility to participate in the Diabetiva® program, which includes PDS. Personalized decision support is generated by the expert system KADIS® using self-control data and continuous glucose monitoring (CGM) as its data source.

Morphology of pancreatic islets: a time course of pre-diabetes in Zucker fatty rats.

The Zucker fatty rat (fa/fa; ZR) is considered as a model for pre-diabetes, as characterised by a genetic defect in the leptin receptor, which results in hyperphagia, insulin resistance, hyperinsulinaemia, hyperlipoproteinaemia, and obesity. These animals become glucose intolerant but do not develop type 2 diabetes. As a consequence of increased adiposity and insulin resistance, the endocrine pancreas of ZR undergoes adaptive and compensatory changes.

Glycemic variability correlates strongly with postprandial beta-cell dysfunction in a segment of type 2 diabetic patients using oral hypoglycemic agents.

Objective: Glucose fluctuations trigger activation of oxidative stress, a main mechanism leading to secondary diabetes complications. We evaluated the relationship between glycemic variability and beta-cell dysfunction.

Research Design And Methods: We conducted a cross-sectional study in 59 patients with type 2 diabetes (aged 64.

Dominance of cytokine- over FasL-induced impairment of the mitochondrial transmembrane potential (Deltapsim) in the pancreatic beta-cell line NIT-1.

Mitochondria of pancreatic beta-cells are potential targets of intrinsic and extrinsic apoptotic pathways in the autoimmune pathogenesis of type 1 diabetes. We aimed to investigate whether cytokine- and FasLigand (FasL)-induced apoptosis is associated with impaired mitochondrial transmembrane potential (Deltapsim) in the pancreatic beta-cell line NIT-1. NIT-1 cells were exposed to the interleukin-1beta/interferon-gamma (IL-1beta/IFN-gamma) cytokine combination to induce apoptosis in vitro.

Telemedicine-based KADIS combined with CGMS has high potential for improving outpatient diabetes care.

Background: The Karlsburg Diabetes Management System (KADIS) was developed over almost two decades by modeling physiological glucose-insulin interactions. When combined with the telemedicine-based communication system TeleDIAB and a continuous glucose monitoring system (CGMS), KADIS has the potential to provide effective, evidence-based support to doctors in their daily efforts to optimize glycemic control.

Methods: To demonstrate the feasibility of improving diabetes control with the KADIS system, an experimental version of a telemedicine-based diabetes care network was established, and an international, multicenter, pilot study of 44 insulin-treated patients with type 1 and 2 diabetes was performed.

Outpatient assessment of Karlsburg Diabetes Management System-based decision support.

Objective: We sought to assess the benefit of the Karlsburg Diabetes Management System (KADIS) in conjunction with the continuous glucose monitoring system (CGMS) in an outpatient setting.

Research Design And Methods: A multicentric trial was performed in insulin-treated outpatients (n = 49), aged 21-70 years, with a mean diabetes duration of 14.2 years.

Chronic hyperglycemia but not glucose variability determines HbA1c levels in well-controlled patients with type 2 diabetes.

To determine the relationships between HbA1c, characteristics of hyperglycemia and glycemic variability in well-controlled type 2 diabetes (HbA1c<7.0%), we studied 63 primary-care patients (36 men and 27 women), aged 34-75 years, with type 2 diabetes for 2-32 years using a continuous glucose monitoring system (CGMS) and standardized meal test (MMT). Duration of hyperglycemia (>8.

Cytokines activate caspase-3 in insulinoma cells of diabetes-prone NOD mice directly and via upregulation of Fas.

In type 1 diabetes, autoimmune inflammation of pancreatic islets of Langerhans ('insulitis') results in destruction of insulin-producing beta cells. Cytokines released from islet-infiltrating mononuclear cells are known to be cytotoxic both directly and by upregulating Fas for FasL-induced apoptosis. To investigate the role of caspase-3, a major effector of apoptosis in beta-cell death, we asked whether cytokine- and/or FasL-induced apoptosis was associated with increased activity of caspase-3 in NIT-1 insulinoma cells and islets of autoimmune diabetes-prone NOD mice.

IL-1beta, IFN-gamma and TNF-alpha increase vulnerability of pancreatic beta cells to autoimmune destruction.

In the pathogenesis of type-1 diabetes insulin-producing beta-cells are destroyed by cellular autoimmune processes. The locality of beta-cell destruction is the inflamed pancreatic islet. During insulitis cytokines released from islet-infiltrating mononuclear cells affect beta-cells at several levels.

Disabling an integral CTL epitope allows suppression of autoimmune diabetes by intranasal proinsulin peptide.

Insulin is a major target of the autoimmune response associated with destruction of pancreatic beta cells in type 1 diabetes. A peptide that spans the junction of the insulin B chain and the connecting (C) peptide in proinsulin has been reported to stimulate T cells from humans at risk for type 1 diabetes and autoimmune diabetes-prone NOD mice. Here we show that proinsulin B24-C36 peptide binds to I-A(g7), the MHC class II molecule of the NOD mouse, and, after intranasal administration, induces regulatory CD4(+) T cells that, in the absence of CD8(+) T cells, block the adoptive transfer of diabetes.

Prevention of autoimmune diabetes in NOD mice by troglitazone is associated with modulation of ICAM-1 expression on pancreatic islet cells and IFN-gamma expression in splenic T cells.

Thiazolidinediones acting as PPAR-gamma agonists are a new generation of oral antidiabetics addressing insulin resistance as a main feature of type-2 diabetes. In accordance to our results, pre-clinical studies have demonstrated that the thiazolinedione troglitazone prevents the development of insulin-dependent autoimmune type-1 diabetes. To investigate whether TGZ acts by affecting the ICAM-1/LFA-1 pathway and/or the Th1/Th2 cytokine balance in NOD mice, we analysed the IL-1beta-induced ICAM-1 expression on islet-cells and the LFA-1, CD25, IL-2, IFN-gamma, IL-4, and IL-10 expression on splenocytes.