Barriers and new opportunities in developing effective therapies for diabetic neuropathy: International expert consensus recommendations.

Background: Diabetic neuropathy (DN) affects up to half of individuals with type 1 and type 2 diabetes. Despite evidence that improving metabolic and cardiovascular health can slow its progression, DN remains a significant clinical challenge due to the lack of disease-modifying therapies and effective pain management strategies. This consensus aimed to identify gaps and recommend strategies to address these challenges.

Role of Ciliary Neurotrophic Factor in Angiotensin II-Induced Hypertension.

Background: Ciliary neurotrophic factor (CNTF), mainly known for its neuroprotective properties, belongs to the IL-6 (interleukin-6) cytokine family. In contrast to IL-6, the effects of CNTF on the vasculature have not been explored. Here, we examined the role of CNTF in AngII (angiotensin II)-induced hypertension.

Painful diabetic neuropathy is associated with accelerated epigenetic aging.

About one out of two diabetic patients develop diabetic neuropathy (DN), of these 20% experience neuropathic pain (NP) leading to individual, social, and health-economic burden. Risk factors for NP are largely unknown; however, premature aging was recently associated with several chronic pain disorders. DNA methylation-based biological age (DNAm) is associated with disease risk, morbidity, and mortality in different clinical settings.

Longitudinal association between DNA methylation and type 2 diabetes: findings from the KORA F4/FF4 study.

Background: Type 2 diabetes (T2D) has been linked to changes in DNA methylation levels, which can, in turn, alter transcriptional activity. However, most studies for epigenome-wide associations between T2D and DNA methylation comes from cross-sectional design. Few large-scale investigations have explored these associations longitudinally over multiple time-points.

Type 1 diabetes incidence curves differ by age for girls and boys between 1996 and 2022: Results from the North Rhine-Westphalia Diabetes Registry, Germany.

The type 1 diabetes incidence was analyzed in 0- to 14-year-old children in North Rhine-Westphalia, Germany, from 1996 to 2022. The data revealed an overall increasing trend, with variations by age and sex. The incidence increased in boys across age groups but peaked in girls in the 5-9-year age group.

Associations between biomarkers of inflammation and depressive symptoms-potential differences between diabetes types and symptom clusters of depression.

Inflammation is a probable biological pathway underlying the relationship between diabetes and depression, but data on differences between diabetes types and symptom clusters of depression are scarce. Therefore, this cross-sectional study aimed to compare associations of a multimarker panel of biomarkers of inflammation with depressive symptoms and its symptom clusters between people with type 1 diabetes (T1D) and type 2 diabetes (T2D). This cross-sectional study combined data from five studies including 1260 participants (n = 706 T1D, n = 454 T2D).

Effect of applying a diabetes risk score on lifestyle counselling and shared decision-making in primary care: A pragmatic cluster randomised trial.

Aims: There is a lack of studies on the impact of diabetes risk scores on diabetes prevention. The aim of this study was to investigate the effect of applying a non-invasive diabetes risk score as component of routine health checks on counselling intensity and shared decision-making (SDM) in primary care.

Methods: Cluster randomised trial, in which primary care physicians (n = 30) enrolled participants (n = 315) with statutory health insurance without known diabetes, ≥ 35 years of age with a body mass index (BMI) ≥ 27.

High-resolution whole-genome DNA methylation revealed unique signatures of painful diabetic neuropathy.

The aim of this work was to describe the DNA methylation signature and to identify genes associated with neuropathic pain in type 2 diabetes mellitus. We analyzed two independent diabetic neuropathy cohorts: PROPGER consisting of 72 painful and 67 painless patients recruited at the German Diabetes Center in Düsseldorf (DE), and PROPENG comprising 27 painful and 65 painless diabetic neuropathy patients recruited at the University of Manchester (UK). Genome-wide methylation data was generated using Illumina Infinium Methylation EPIC v1.

Proteomic and Metabolomic Signatures in Prediabetes Progressing to Diabetes or Reversing to Normoglycemia Within 1 Year.

Objective: Progression of prediabetes to type 2 diabetes has been associated with β-cell dysfunction, whereas its remission to normoglycemia has been related to improvement of insulin sensitivity. To understand the mechanisms and identify potential biomarkers related to prediabetes trajectories, we compared the proteomics and metabolomics profile of people with prediabetes progressing to diabetes or reversing to normoglycemia within 1 year.

Research Design And Methods: The fasting plasma concentrations of 1,389 proteins and the fasting, 30-min, and 120-min post-oral glucose tolerance test (OGTT) plasma concentrations of 152 metabolites were measured in up to 134 individuals with new-onset diabetes, prediabetes, or normal glucose tolerance.

Determinants of increased muscle insulin sensitivity of exercise-trained versus sedentary normal weight and overweight individuals.

The athlete's paradox states that intramyocellular triglyceride accumulation associates with insulin resistance in sedentary but not in endurance-trained humans. Underlying mechanisms and the role of muscle lipid distribution and composition on glucose metabolism remain unclear. We compared highly trained athletes (ATHL) with sedentary normal weight (LEAN) and overweight-to-obese (OVWE) male and female individuals.

Novel type 2 diabetes prediction score based on traditional risk factors and circulating metabolites: model derivation and validation in two large cohort studies.

Background: We aimed to evaluate the incremental predictive value of metabolomic biomarkers for assessing the 10-year risk of type 2 diabetes when added to the clinical Cambridge Diabetes Risk Score (CDRS).

Methods: We utilized 86,232 UK Biobank (UKB) participants (recruited between 13 March 2006 and 1 October 2010) for model derivation and internal validation. Additionally, we included 4383 participants from the German ESTHER cohort (recruited between 1 July 2000 and 30 June 2002 for external validation).

The role of exosomes for sustained specific cardiorespiratory and metabolic improvements in males with type 2 diabetes after detraining.

Background: High-intensity interval training (HIIT) has been shown to improve cardiorespiratory fitness (V˙O max) but may ameliorate insulin sensitivity only in insulin-resistant humans. It is yet unclear whether these benefits persist after detraining and to which extent duration and effectiveness of metabolic improvements differ between individuals without and with prediabetes or type 2 diabetes (T2D). Understanding these differences is relevant for developing targeted exercise training modes for individuals with different stages of dysglycemia.

Optimising the treatment of chronic ischemic heart disease by training general practitioners to deliver very brief advice on physical activity (OptiCor): protocol of the systematic development and evaluation of a complex intervention.

Background: Chronic ischemic heart disease (IHD) is one of the leading causes of morbidity and mortality. Physical activity (PA) is an effective secondary preventive strategy in IHD management. The German treatment guideline recommends that general practitioners (GPs) deliver PA advice to patients.

Prehospital telemedicine support for urban stroke care: Analysis of current state of care and conceptualization.

Background: The reduction of processing times in the treatment of acute ischemic stroke is of outstanding importance. Our objective is to analyze the acute stroke care chain from onset to treatment in a city in Germany comprising three stroke units. Additionally, we discuss solutions for detected treatment delays.

Prediction Model for Polyneuropathy in Recent-Onset Diabetes Based on Serum Neurofilament Light Chain, Fibroblast Growth Factor-19 and Standard Anthropometric and Clinical Variables.

Background: Diabetic sensorimotor polyneuropathy (DSPN) is often asymptomatic and remains undiagnosed. The ability of clinical and anthropometric variables to identify individuals likely to have DSPN might be limited. Here, we aimed to integrate protein biomarkers for reliably predicting present DSPN.

Carrageenan and insulin resistance in humans: a randomised double-blind cross-over trial.

Background: The potential impact of specific food additives, common in Western diets, on the risk of developing type 2 diabetes is not well understood. This study focuses on carrageenan, a widely used food additive known to induce insulin resistance and gut inflammation in animal models, and its effects on human health.

Methods: In a randomised, double-blind, placebo-controlled, cross-over trial conducted at a university hospital metabolic study centre, 20 males (age 27.

Cutaneous Carbonyl Stress Is Associated With Nerve Dysfunction in Recent-Onset Type 2 Diabetes.

Objective: Endogenous carbonyl stress leads to the formation of advanced glycation end products (AGEs). AGEs represent a potential target to prevent or treat diabetic sensorimotor polyneuropathy (DSPN). The current study aimed to characterize cutaneous carbonyl stress, oxidative stress, immune cells, and endothelial cell damage in early type 2 diabetes compared with normal glucose tolerance (NGT) using novel cutaneous biomarkers.

Evaluation of spatiotemporal associations between COVID-19 pandemic waves and the incidence of pediatric type 1 diabetes in Germany considering time lags: A register-based ecological study.

To analyze the ecological relationship between COVID-19 incidence in the total population and type 1 diabetes (T1D) incidence in children and adolescents, spatiotemporal models were applied considering time lags from 0 to 12 months. The results do not indicate a positive correlation between COVID-19 incidence and T1D incidence.

Health-Related Quality of Life and Experiences of Minor Children With Parental Cancer-A Family-Based Multilevel Analysis of Determinants.

Objective: Children in families with parental cancer may experience emotional, social or physical problems. The aims are to analyze child, parent and family-based determinants of children's health-related quality of life (HRQoL) and their experiences of parental cancer.

Methods: As part of a mixed-methods, multicenter, prospective, interventional non-randomized study "Family-SCOUT," a family-centered intervention in the form of care and case management was developed.