Incidence trends of type 1 diabetes before and after the reunification in children up to 14 years of age in Saxony, Eastern Germany.

Aims: The aim of this study was to analyze the incidence rates of type 1 diabetes in Saxony before and after the German reunification.

Methods: The study examined two registries: one until 1990 and one since 1999. Only patients under 15 years of age with type 1 diabetes and living in Saxony were included in the study.

Associations of blood glucose dynamics with antihyperglycemic treatment and glycemic variability in type 1 and type 2 diabetes.

Aims: The dynamical structure of glucose fluctuation has largely been disregarded in the contemporary management of diabetes.

Methods: In a retrospective study of patients with diabetes, we evaluated the relationship between glucose dynamics, antihyperglycemic therapy, glucose variability, and glucose exposure, while taking into account potential determinants of the complexity index. We used multiscale entropy (MSE) analysis of continuous glucose monitoring data from 131 subjects with type 1 (n = 18), type 2 diabetes (n = 102), and 11 nondiabetic control subjects.

Trends in Incidence Rates during 1999-2008 and Prevalence in 2008 of Childhood Type 1 Diabetes Mellitus in Germany--Model-Based National Estimates.

Aims: To estimate the national incidence rate and trend of type 1 diabetes (T1DM) in Germany from 1999 to 2008 and the national prevalence in 2008 in the age group 0-14 years.

Methods: Data were taken from a nationwide registry for incident cases of T1DM in the ages 0-4 years and 3 regional registries (North-Rhine-Westphalia, Baden-Wuerttemberg and Saxony) for incident cases of T1DM in the ages 0-14 years covering 41% of the child population in Germany. The degree of ascertainment was ≥ 97% in all registries.

Glycaemic variability and pancreatic β-cell dysfunction.

The importance of glycaemic variability (GV) as a factor in the pathophysiology of cellular dysfunction and late diabetes complications is currently a matter of debate. However, there is mounting evidence from in vivo and in vitro studies that GV has adverse effects on the cascade of physiological processes that result in chronic β-cell dysfunctions. Glucose fluctuations more than sustained chronic hyperglycaemia can induce excessive formation of reactive oxygen (ROS) and reactive nitrogen species (RNS), ultimately leading to apoptosis related to oxidative stress.

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.

DPP-4 inhibition increases GIP and decreases GLP-1 incretin effects during intravenous glucose tolerance test in Wistar rats.

GIP metabolite [GIP (3-42)] and GLP-1 metabolite [GLP-1 (9-36) amide] have been reported to differ with regard to biological actions. Systemic DPP-4 inhibition can therefore reveal different actions of GIP and GLP-1. In catheter wearing Wistar rats, insulinotropic effects of equipotent doses of GIP (2.

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.

Model-based decision support in diabetes care.

The model-based Karlsburg Diabetes Management System (KADIS®) has been developed as a patient-focused decision-support tool to provide evidence-based advice for physicians in their daily efforts to optimize metabolic control in diabetes care of their patients on an individualized basis. For this purpose, KADIS® was established in terms of a personalized, interactive in silico simulation procedure, implemented into a problem-related diabetes health care network and evaluated under different conditions by conducting open-label mono- and polycentric trials, and a case-control study, and last but not least, by application in routine diabetes outpatient care. The trial outcomes clearly show that the recommendations provided to the physicians by KADIS® lead to significant improvement of metabolic control.

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.

Relationships between glucose variability and conventional measures of glycemic control in continuously monitored patients with type 2 diabetes.

Given the importance of glucose variability in the development of diabetic complications, the present study used continuous glucose monitoring (CGM) to determine various indices of glucose variability and to investigate their relationships with conventional measures of chronic sustained hyperglycemia. We examined 53 women and 61 men, aged 36-79 years afflicted with type 2 diabetes for 1-24 years. The following indices of glycemic variability were computed from CGM data sets: mean amplitude of glycemic excursions (MAGE), CGM glucose range, interquartile range (IQR), SD-score, and average daily risk range (ADRR).

Impact of cytokine- and FasL-induced apoptosis in the beta-cell line NIT-1.

Cytokine- and FasL-induced pathways contribute to beta-cell death in type 1 diabetes. It remains unclear, however, whether pro-apoptotic cyto-kines or FasL have more apoptotic impact. Cytokine- and FasL-induced apoptosis were simulated using IL-1beta/IFN-gamma, Super-FasLigand and the beta-cell line NIT-1.

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.

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.

Fas ligand down-regulates cytokine-induced Fas receptor expression on insulinoma (NIT-1), but not islet cells, from autoimmune nonobese diabetic mice.

In the pathogenesis of autoimmune type 1 diabetes, the apoptosis receptor Fas appears de novo on the surface of insulin-producing beta-cells. Fas expression is thought to be induced by proinflammatory cytokines, such as IL-1beta, interferon-gamma (IFNgamma), and TNFalpha, released by islet-infiltrating mononuclear cells. To determine whether beta-cells can modulate their sensitivity to apoptosis at the level of Fas, we investigated the effect of Fas ligand (FasL) on surface expression of Fas in NIT-1 insulinoma cells from nonobese diabetic (NOD) mice prone to autoimmune diabetes and islet cells from NOD and nonautoimmune BALB/c mice.

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.

Surface and intracellular Fas expression associated with cytokine-induced apoptosis in rodent islet and insulinoma cells.

During the process of insulitis in the pathogenesis of type I (insulin-dependent) diabetes mellitus, proinflammatory cytokines induce expression of the death receptor Fas on the surface of pancreatic beta-cells and thereby contribute to the enhanced susceptibility of beta-cells for apoptosis. The aim of this study was to compare cell-surface and intracellular Fas expression associated with cytokine-induced apoptosis in commonly used beta-cell models such as isolated islets and insulinoma lines derived from mouse and rat. The cell line NIT-1 responded to the interleukin (IL)-1beta+interferon (IFN)-gamma stimulus with translocation of Fas to the cell surface.

Immunoadsorption of immunoglobulins alters intracytoplasmic type 1 and type 2 T cell cytokine production in patients with refractory autoimmune diseases.

Intracellular cytokine staining and flow cytometry were used to investigate whether immunoadsorption (IA) of immunoglobulins alters intracytoplasmic cytokine production in CD4+ and CD8+ T cells from the blood of patients with refractory rheumatoid arthritis (n = 7), membrane proliferative glomerulonephritis (n = 1), and Goodpasture's syndrome (n = 1). Four patients (Group 1) showed severely depressed production of TNF-alpha, IL-2, IFN-gamma, and IL-4 by CD4+ and CD8+ T cells and responded to 3 IA sessions with significant increases in CD4+TNF-alpha+, CD4+IL-2+, and CD8+IL-2+ T cells. Also, a tendency toward increased percentage levels of CD4+ T cells producing IFN-gamma or IL-4 and of CD8+ T cells producing either TNF-alpha or IFN-gamma was seen, but due to the small number of patients investigated, these differences did not attain statistic significance.

Functional alterations in the rat kidney induced either by diabetes or high protein diet.

The aim of this study was to compare the effect of long-term diabetes with that of a long-term high protein diet in vivo on the kidney function and in vitro on cellular parameters of isolated glomeruli of BB rats. Four groups of rats were investigated: Group 1 = normoglycaemic (N) rats > 250 days old; group 2 = age-matched diabetic (D) rats with a diabetes duration of more than 150 days; group 3 = BB rats which were fed a protein diet of 8% (low protein = LP) and group 4 = rats which received a high protein (HP) diet (32%) for more than 80 weeks. From 24-h-urine samples albumin, urea, creatinine and electrolyte excretion were estimated.

Murine monoclonal glutamic acid decarboxylase (GAD)65 antibodies recognize autoimmune-associated GAD epitope regions targeted in patients with type 1 diabetes mellitus and stiff-man syndrome.

To study the immune response to glutamic acid decarboxylase (GAD) in insulin-dependent diabetes mellitus, monoclonal GAD antibodies after fusion of splenocytes from a nondiabetes-susceptible BALB/c mouse immunized with human recombinant GAD65 were generated. Of the 44 monoclonals, 35 are specific for the GAD65 isoform, whereas 9 also react with GAD67. Some 37 monoclonals, including all GAD65/67 reactive antibodies, react with GAD by Western blot analysis.

Temporary anti-CD25/CsA therapy induces a CD4+ T-cell-mediated tolerance in BB/OK rats.

Pancreatic islets obtained from the congenic LEW.1BB/OK rat strain (MHC identical, different in genetic background from BB/OK rats) were grated into diabetic BB/OK rats. The recipients were treated for 10 d with 1.

Monoclonal antibodies specific to the glutamic acid decarboxylase 65 kDa isoform derived from a non-obese diabetic (NOD) mouse.

Two monoclonal antibodies specifically recognizing the 65 kDa isoform of the enzyme glutamic acid decarboxylase (GAD) were generated by fusion of spleen cells of a non-obese diabetic (NOD) mouse which had received a single intraperitoneal injection of 0.2 ml complete Freund's adjuvant followed three days later by one administration of a subdiabetogenic dose of streptozotocin (80 mg/kg body weight) three days before the fusion experiment was performed. Both monoclonals belong to the IgG1 isotype and were screened with an enzyme-linked immunosorbent assay using rat brain extract as a natural source of GAD and additionally with a capture assay by means of immunoglobulins of a patient with Stiff-man syndrome.