Modulating the Autoimmune Response in Type 1 Diabetes: A Report on the 64th Scientific Sessions of the ADA, June 2004, Orlando, FL, USA

Type 1 diabetes mellitus results from a loss of insulin-producing β-cells in the pancreatic islets caused by an immune-mediated chronic destructive process. It is generally believed that immune tolerance to β-cells is broken by environmental factors in genetically susceptible individuals, leading to β-cell destruction that is mediated by T lymphocytes. A key assumption in the current pathogenic concept of type 1 diabetes is a defective immunoregulation affecting both central and peripheral mechanisms of tolerance induction against β-cell antigens. In animal models of type 1 diabetes, disease-protective modulation of the islet autoimmune response can be effected by various strategies including administration of islet antigens. In human type 1 diabetes, therefore, new strategies are currently being developed with the aim of actively suppressing the autoimmune process and inducing a lasting tolerance against islet antigens. In this context, inducing regulatory T cells in vivo (i.e. CD4(+)CD25(+) T cells or type 1 regulatory T cells) is currently becoming more widespread. The following report highlights some of the recent studies on immunotherapy of type 1 diabetes, presented at the 64(th) Scientific Sessions, held in June 2004, in Orlando, Florida

Elimination of Dietary Gluten and Development of Type 1 Diabetes in High Risk Subjects

Removal of dietary gluten is associated with a lower frequency of type 1 diabetes (T1D) in patients with celiac disease. Therefore, we performed a pilot study in which seven islet-antibody-positive first degree relatives of patients with T1D were placed on a gluten-free diet for 12 months, followed by gluten re-exposure for 12 months, to investigate whether this could reduce levels of circulating autoantibodies. We found that islet autoantibody levels at the end of the gluten-free period were not different to those before the commencement of the diet nor to antibody levels at the end of the gluten re-exposure period. In the present study, we have followed the 7 children formerly placed on a gluten-free diet for the manifestation of T1D for up to 5 years (mean follow-up time after fulfilling inclusion criteria: 4.8 years, SE 0.82 years) and compared them to 30 siblings and offspring of patients with T1D with similar characteristics to the intervention group (mean follow-up time: 5 years, SE 0.62 years). The cumulative 5-year risk of T1D in the intervention group did not differ from that in the prediabetic control group (42.9%, 95 CI (6.3-79.5%) vs. 49.7%, 95 CI (30.9-68.5%), p=0.87, log-rank test). These findings suggest that removing gluten from the diet over a period of one year is effective neither in the short nor in the long term in high-risk prediabetic individuals with a fully activated immune response to different islet antigens close to manifestation of T1D. These and recent data showing that exposure to dietary gluten in offspring of mothers and fathers with T1D very early in life is associated with an increased risk of developing islet antibodies also suggest that removal of dietary gluten should be tested as early as possible in children with an increased risk of islet autoimunity, i.e. before an immune response to islet antigens is established

The Real-World Observational Prospective Study of Health Outcomes with Dulaglutide and Liraglutide in Patients with Type 2 Diabetes (TROPHIES): Patient disposition, clinical characteristics and treatment persistence at 12 months

Aims The primary objective of the TROPHIES observational study is to estimate the duration of treatment on dulaglutide or liraglutide without a significant treatment change by 24 months in patients with type 2 diabetes (T2D) initiating their first injectable treatment with these glucagon-like peptide-1 receptor agonists (GLP-1 RAs). This manuscript presents 12-month interim data. Materials and Methods TROPHIES is a prospective, non-comparative, observational study of patients with T2D in Europe, naive to injectable antihyperglycaemic treatments and initiating dulaglutide or liraglutide. Data on clinical characteristics, GLP-1 RA persistence and treatment patterns of glucose-lowering medication were collected at initiation of first injectable therapy and by 12 months. Results By 12 months, 1014 dulaglutide and 991 liraglutide patients were eligible across France, Germany and Italy. Both cohorts presented a high probability [95% confidence interval (CI)] of GLP-1 RA persistence [dulaglutide, 0.88 (0.86 to 0.90); liraglutide, 0.83 (0.80 to 0.85)] and reduction in mean glycated haemoglobin percentage (95% CI) from baseline [dulaglutide, -1.18 (-1.27 to -1.08); liraglutide, -1.15 (-1.26 to -1.05)] with 48.2% of dulaglutide and 41.2% of liraglutide patients reaching their individualized glycated haemoglobin percentage target set by the physician at baseline. Mean weight (95% CI) change from baseline was -3.2 kg (-3.6 to -2.8) for dulaglutide and -3.4 kg (-3.9 to -3.0) for liraglutide. Slight changes in concomitant medications were observed compared with baseline. Conclusions In the real-world setting, dulaglutide and liraglutide cohorts achieved good persistence with similarly improved glycaemic control that was accompanied by weight loss at 12 months, consistent with previous clinical trial results.Aims The primary objective of the TROPHIES observational study is to estimate the duration of treatment on dulaglutide or liraglutide without a significant treatment change by 24 months in patients with type 2 diabetes (T2D) initiating their first injectable treatment with these glucagon-like peptide-1 receptor agonists (GLP-1 RAs). This manuscript presents 12-month interim data. Materials and Methods TROPHIES is a prospective, non-comparative, observational study of patients with T2D in Europe, naive to injectable antihyperglycaemic treatments and initiating dulaglutide or liraglutide. Data on clinical characteristics, GLP-1 RA persistence and treatment patterns of glucose-lowering medication were collected at initiation of first injectable therapy and by 12 months. Results By 12 months, 1014 dulaglutide and 991 liraglutide patients were eligible across France, Germany and Italy. Both cohorts presented a high probability [95% confidence interval (CI)] of GLP-1 RA persistence [dulaglutide, 0.88 (0.86 to 0.90); liraglutide, 0.83 (0.80 to 0.85)] and reduction in mean glycated haemoglobin percentage (95% CI) from baseline [dulaglutide, -1.18 (-1.27 to -1.08); liraglutide, -1.15 (-1.26 to -1.05)] with 48.2% of dulaglutide and 41.2% of liraglutide patients reaching their individualized glycated haemoglobin percentage target set by the physician at baseline. Mean weight (95% CI) change from baseline was -3.2 kg (-3.6 to -2.8) for dulaglutide and -3.4 kg (-3.9 to -3.0) for liraglutide. Slight changes in concomitant medications were observed compared with baseline. Conclusions In the real-world setting, dulaglutide and liraglutide cohorts achieved good persistence with similarly improved glycaemic control that was accompanied by weight loss at 12 months, consistent with previous clinical trial results

Opening a window to skin biomarkers for diabetes stage with optoacoustic mesoscopy

Abstract Being the largest and most accessible organ of the human body, the skin could offer a window to diabetes-related complications on the microvasculature. However, skin microvasculature is typically assessed by histological analysis, which is not suited for applications to large populations or longitudinal studies. We introduce ultra-wideband raster-scan optoacoustic mesoscopy (RSOM) for precise, non-invasive assessment of diabetes-related changes in the dermal microvasculature and skin micro-anatomy, resolved with unprecedented sensitivity and detail without the need for contrast agents. Providing unique imaging contrast, we explored a possible role for RSOM as an investigational tool in diabetes healthcare and offer the first comprehensive study investigating the relationship between different diabetes complications and microvascular features in vivo. We applied RSOM to scan the pretibial area of 95 participants with diabetes mellitus and 48 age-matched volunteers without diabetes, grouped according to disease complications, and extracted six label-free optoacoustic biomarkers of human skin, including dermal microvasculature density and epidermal parameters, based on a novel image-processing pipeline. We then correlated these biomarkers to disease severity and found statistically significant effects on microvasculature parameters as a function of diabetes complications. We discuss how label-free RSOM biomarkers can lead to a quantitative assessment of the systemic effects of diabetes and its complications, complementing the qualitative assessment allowed by current clinical metrics, possibly leading to a precise scoring system that captures the gradual evolution of the disease

Risk of Herpes Zoster incidence and recurrence in adult patients with underlying conditions - a retrospective cohort study based on German claims data, 2007-2018

Witte J, Batram M, Schwarz M, et al. Risk of Herpes Zoster incidence and recurrence in adult patients with underlying conditions - a retrospective cohort study based on German claims data, 2007-2018. In: Abstracts zum 127. Kongress der Deutschen Gesellschaft für Innere Medizin e.V. Der Internist. Vol 62. Heidelberg: Springer ; 2021: 193

Burden of Herpes Zoster in Adult Patients with Underlying Conditions: Analysis of German Claims Data, 2007–2018

Batram M, Witte J, Schwarz M, et al. Burden of Herpes Zoster in Adult Patients with Underlying Conditions: Analysis of German Claims Data, 2007–2018. Dermatology and Therapy. 2021;11:1009–1026