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.

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.

Depression symptoms, wellbeing, health-related quality of life, and diabetes-related distress in novel subtypes of recent-onset diabetes in Germany: a 5-year observational follow-up study.

Background: The subjective experiences of individuals living with diabetes is commonly assessed with patient-reported outcomes (PROs; eg, depression symptoms, wellbeing, health-related quality of life [HRQOL], and diabetes-related distress). Cluster analyses have identified novel diabetes subtypes differing in phenotypic and metabolic characteristics. We aimed to investigate associations between these subtypes and PROs and whether subtype predicted PROs 5 years later.

Associations between multiple neurological biomarkers and distal sensorimotor polyneuropathy: KORA F4/FF4 study.

Aims: The aim of this study was to assess associations between neurological biomarkers and distal sensorimotor polyneuropathy (DSPN).

Materials And Methods: Cross-sectional analyses were based on 1032 participants aged 61-82 years from the population-based KORA F4 survey, 177 of whom had DSPN at baseline. The prevalence of type 2 diabetes was 20%.

Association of dietary patterns with diabetes-related comorbidities varies among diabetes endotypes.

Background And Aims: Differences of dietary pattern adherence across the novel diabetes endotypes are unknown. This study assessed adherence to pre-specified dietary patterns and their associations with cardiovascular risk factors, kidney function, and neuropathy among diabetes endotypes.

Methods And Results: The cross-sectional analysis included 765 individuals with recent-onset (67 %) and prevalent diabetes (33 %) from the German Diabetes Study (GDS) allocated into severe autoimmune diabetes (SAID, 35 %), severe insulin-deficient diabetes (SIDD, 3 %), severe insulin-resistant diabetes (SIRD, 5 %), mild obesity-related diabetes (MOD, 28 %), and mild age-related diabetes (MARD, 29 %).

Correlates of Skeletal Muscle Mass and Differences Between Novel Subtypes in Recent-Onset Diabetes.

Context: Low skeletal muscle mass (SMM) is associated with long-standing diabetes but little is known about SMM in newly diagnosed diabetes.

Objective: We aimed to identify correlates of SMM in recent-onset diabetes and to compare SMM between novel diabetes subtypes.

Methods: SMM was normalized to body mass index (SMM/BMI) in 842 participants with known diabetes duration of less than 1 year from the German Diabetes Study (GDS).

Serum neurofilament light chain: a novel biomarker for early diabetic sensorimotor polyneuropathy.

Aims/hypothesis: No established blood-based biomarker exists to monitor diabetic sensorimotor polyneuropathy (DSPN) and evaluate treatment response. The neurofilament light chain (NFL), a blood biomarker of neuroaxonal damage in several neurodegenerative diseases, represents a potential biomarker for DSPN. We hypothesised that higher serum NFL levels are associated with prevalent DSPN and nerve dysfunction in individuals recently diagnosed with diabetes.

Environmental risk factors of incident distal sensorimotor polyneuropathy: Results from the prospective population-based KORA F4/FF4 study.

Distal sensorimotor polyneuropathy (DSPN) is a common condition in older populations with high prevalence of obesity and type 2 diabetes. We hypothesised that the risk of DSPN is increased by multiple ubiquitous environmental risk factors, particularly in people with obesity. This study was based on 423 individuals aged 62-81 years without DSPN who participated in the population-based Cooperative Health Research in the Region of Augsburg (KORA) F4 survey (2006-2008) in Southern Germany.

Association of C-Terminal Pro-Endothelin-1 with Mortality in the Population-Based KORA F4 Study.

Introduction: Endothelin-1 and its prohormone C-terminal pro-endothelin-1 (CT-proET-1) have been linked to metabolic alterations, inflammatory responses and cardiovascular events in selected study populations. We analyzed the association of CT-proET-1 with cardiovascular events and mortality, carotid intima-media-thickness as surrogate for early atherosclerotic lesions, biomarkers of subclinical inflammation and adipokines in a population-based study.

Methods: The cross-sectional and prospective analyses used data from the KORA F4 study with a median follow-up time of 9.

Effect of obesity on the associations of 25-hydroxyvitamin D with prevalent and incident distal sensorimotor polyneuropathy: population-based KORA F4/FF4 study.

Background/objectives: The association between vitamin D and DSPN has been investigated in cross-sectional studies in individuals with diabetes. However, evidence from prospective and population-based studies is still lacking. Also, the potential modifying effect of obesity and glucose tolerance has not been investigated.

Association of renin and aldosterone with glucose metabolism in a Western European population: the KORA F4/FF4 study.

Introduction: Primary aldosteronism is associated with impaired glucose tolerance. Whether plasma aldosterone and/or renin concentrations are associated with type 2 diabetes and continuous measures of glucose metabolism in the general population is still under debate.

Research Design And Methods: The analyses included 2931 participants of the KORA F4 study at baseline and 2010 participants of the KORA FF4 study after a median follow-up of 6.

Association of circulating MR-proADM with all-cause and cardiovascular mortality in the general population: Results from the KORA F4 cohort study.

Background And Aim: Despite its vasodilatory effect, adrenomedullin and its surrogate mid-regional pro-adrenomedullin (MR-proADM) have been found to be positively associated with all-cause and cardiovascular mortality. However, the underlying mechanisms thereof remain unclear and the associations were mostly shown in geriatric cohorts or in patients with chronic diseases. Therefore, we aimed to investigate the possible involvement of abdominal obesity, selected adipokines, and biomarkers of subclinical inflammation in the association of MR-proADM with mortality in a population based study cohort.

Association of serum uromodulin with adipokines in dependence of type 2 diabetes.

Background: The renal tubular glycoprotein uromodulin is associated with obesity and type 2 diabetes, but the underlying mechanisms are elusive. We investigated the association of serum uromodulin with adipokines and tested the effect modification by diabetes status.

Methods: The associations of serum uromodulin with eight adipokines were assessed in 795-1080 participants of the KORA F4 study aged 62-81 years using linear regression models adjusted for sex, age, BMI, estimated glomerular filtration rate and diabetes.

Differences in the prevalence of erectile dysfunction between novel subgroups of recent-onset diabetes.

Aims/hypothesis: In men with diabetes, the prevalence of erectile dysfunction increases with advanced age and longer diabetes duration and is substantially higher in men with type 2 diabetes than those with type 1 diabetes. This study aimed to evaluate the prevalence of erectile dysfunction among the five novel subgroups of recent-onset diabetes and determine the strength of associations between diabetes subgroups and erectile dysfunction.

Methods: A total of 351 men with recent-onset diabetes (<1 year) from the German Diabetes Study baseline cohort and 124 men without diabetes were included in this cross-sectional study.

Prediabetes and risk of mortality, diabetes-related complications and comorbidities: umbrella review of meta-analyses of prospective studies.

Aims/hypothesis: The term prediabetes is used for individuals who have impaired glucose metabolism whose glucose or HbA levels are not yet high enough to be diagnosed as diabetes. Prediabetes may already be associated with an increased risk of chronic 'diabetes-related' complications. This umbrella review aimed to provide a systematic overview of the available evidence from meta-analyses of prospective observational studies on the associations between prediabetes and incident diabetes-related complications in adults and to evaluate their strength and certainty.

Novel biomarkers of inflammation, kidney function and chronic kidney disease in the general population.

Background: Inflammatory processes have been implicated in the development of chronic kidney disease (CKD). We investigated the association of a large panel of inflammatory biomarkers reflecting aspects of immunity with kidney function and CKD incidence.

Methods: We used data from two independent population-based studies, KORA F4 (discovery, n = 1110, mean age 70.

Leukocyte Counts and T-Cell Frequencies Differ Between Novel Subgroups of Diabetes and Are Associated With Metabolic Parameters and Biomarkers of Inflammation.

Frequencies of circulating immune cells are altered in those with type 1 and type 2 diabetes compared with healthy individuals and are associated with insulin sensitivity, glycemic control, and lipid levels. This study aimed to determine whether specific immune cell types are associated with novel diabetes subgroups. We analyzed automated white blood cell counts ( = 669) and flow cytometric data ( = 201) of participants in the German Diabetes Study with recent-onset (<1 year) diabetes, who were allocated to five subgroups based on data-driven analysis of clinical variables.

Serum uromodulin is inversely associated with biomarkers of subclinical inflammation in the population-based KORA F4 study.

Background: Uromodulin is a kidney-specific glycoprotein synthesized in tubular cells of Henle's loop exerting nephroprotective and immunomodulatory functions in the urinary tract. A small amount of uromodulin is also released into the systemic circulation, where its physiological role is unknown. Serum uromodulin (sUmod) has been associated with metabolic risk factors and with cardiovascular events and mortality, where these associations were partly stronger in men than in women.

Plasma Proteomics of Renal Function: A Transethnic Meta-Analysis and Mendelian Randomization Study.

Background: Studies on the relationship between renal function and the human plasma proteome have identified several potential biomarkers. However, investigations have been conducted largely in European populations, and causality of the associations between plasma proteins and kidney function has never been addressed.

Methods: A cross-sectional study of 993 plasma proteins among 2882 participants in four studies of European and admixed ancestries (KORA, INTERVAL, HUNT, QMDiab) identified transethnic associations between eGFR/CKD and proteomic biomarkers.

Epidemiology of herpes simplex virus type 2 in Latin America and the Caribbean: systematic review, meta-analyses and metaregressions.

Objective: To characterise epidemiology of herpes simplex virus type 2 (HSV-2) in Latin America and the Caribbean.

Methods: HSV-2 reports were systematically reviewed and synthesised, and findings were reported following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Meta-analyses and metaregressions were conducted.

The association of vitamin D with survival in colorectal cancer patients depends on antioxidant capacity.

Background: Vitamin D plays a role in detoxifying free radicals, which might explain the previously reported lower mortality in colorectal cancer (CRC) patients with higher vitamin D concentrations.

Objectives: We aimed to assess whether the associations of 25-hydroxyvitamin D [25(OH)D] with prognosis in CRC patients differ by total thiol concentration (TTC), a biomarker of antioxidant capacity.

Methods: CRC patients who were diagnosed from 2003 to 2010 and recruited into a population-based study in southern Germany (n = 2,592) were followed over a period of 6 y.

Differences in Biomarkers of Inflammation Between Novel Subgroups of Recent-Onset Diabetes.

A novel clustering approach identified five subgroups of diabetes with distinct progression trajectories of complications. We hypothesized that these subgroups differ in multiple biomarkers of inflammation. Serum levels of 74 biomarkers of inflammation were measured in 414 individuals with recent adult-onset diabetes from the German Diabetes Study (GDS) allocated to five subgroups based on data-driven cluster analysis.