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.

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.

Immunoprotection Strategies in β-Cell Replacement Therapy: A Closer Look at Porcine Islet Xenotransplantation.

Type 1 diabetes mellitus (T1DM) is characterized by absolute insulin deficiency primarily due to autoimmune destruction of pancreatic β-cells. The prevailing treatment for T1DM involves daily subcutaneous insulin injections, but a substantial proportion of patients face challenges such as severe hypoglycemic episodes and poorly controlled hyperglycemia. For T1DM patients, a more effective therapeutic option involves the replacement of β-cells through allogeneic transplantation of either the entire pancreas or isolated pancreatic islets.

Plasma proteome association with coronary heart disease and carotid intima media thickness: results from the KORA F4 study.

Background And Aims: Atherosclerosis is the main cause of stroke and coronary heart disease (CHD), both leading mortality causes worldwide. Proteomics, as a high-throughput method, could provide helpful insights into the pathological mechanisms underlying atherosclerosis. In this study, we characterized the associations of plasma protein levels with CHD and with carotid intima-media thickness (CIMT), as a surrogate measure of atherosclerosis.

Associations of gestational diabetes and proton density fat fraction of vertebral bone marrow and paraspinal musculature in premenopausal women.

Background And Objective: Fat content in bones and muscles, quantified by magnetic resonance imaging (MRI) as a proton density fat fraction (PDFF) value, is an emerging non-invasive biomarker. PDFF has been proposed to indicate bone and metabolic health among postmenopausal women. Premenopausal women with a history of gestational diabetes (GDM) carry an increased risk of developing type 2 diabetes and an increased risk of fractures.

Association of GLP-1 secretion with parameters of glycemic control in women after gestational diabetes mellitus.

Introduction: Women with a history of gestational diabetes mellitus (GDM) are at high risk of developing type 2 diabetes, while the exact mechanisms underlying its pathophysiology are still unclear. We investigated the association of glucagon-like peptide-1 (GLP-1) response to oral glucose with parameters of glycemic control in women with previous GDM in the prospective PPSDiab (Prediction, Prevention, and Subclassification of Type 2 Diabetes) study.

Research Design And Methods: Glucose metabolism parameters and GLP-1 secretion were analyzed during oral glucose tolerance test (OGTT) in women with previous GDM (n=129) and women with a history of normal glucose tolerance (n=67) during pregnancy (controls).

Mechanisms of weight loss-induced remission in people with prediabetes: a post-hoc analysis of the randomised, controlled, multicentre Prediabetes Lifestyle Intervention Study (PLIS).

Background: Remission of type 2 diabetes can occur as a result of weight loss and is characterised by liver fat and pancreas fat reduction and recovered insulin secretion. In this analysis, we aimed to investigate the mechanisms of weight loss- induced remission in people with prediabetes.

Methods: In this prespecified post-hoc analysis, weight loss-induced resolution of prediabetes in the randomised, controlled, multicentre Prediabetes Lifestyle Intervention Study (PLIS) was assessed, and the results were validated against participants from the Diabetes Prevention Program (DPP) study.

Neonatal islets from human PD-L1 transgenic pigs reduce immune cell activation and cellular rejection in humanized nonobese diabetic-scid IL2rγ mice.

Strong xenorejection limits the clinical application of porcine islet transplantation in type 1 diabetes. Targeting T cell-mediated rejection is one of the main approaches to improve long-term graft survival. Here we study engraftment and survival of porcine islet cells expressing human programmed cell death ligand-1 (hPD-L1) in a humanized mouse model.

Non-invasive in vivo imaging of porcine islet xenografts in a preclinical model with [Ga]Ga-exendin-4.

Introduction: Islet xenotransplantation may be a therapeutic option in type 1 diabetes. Recent advances in generating genetically modified source pigs offer advantages as immune suppressants can potentially be eliminated after the transplantation. Therapy monitoring would greatly benefit from noninvasive methods for assessing the viability of transplanted islets.

Association of Aldosterone with Mortality in the General Population.

Introduction: Aldosterone excess is linked to cardiovascular events and mortality as well as to low-grade inflammation in the context of metabolic diseases. Whether mildly elevated aldosterone levels in the general population promote cardiovascular risk is still under debate. We analyzed the association of plasma aldosterone concentrations with incident cardiovascular events, cardiovascular and all-cause mortality as well as with biomarkers of subclinical inflammation in the population-based KORA F4 study.

Formation of Re-Aggregated Neonatal Porcine Islet Clusters Improves Function and Transplantation Outcome.

Neonatal porcine islet-like cell clusters (NPICCs) are a promising source for islet cell transplantation. Excellent islet quality is important to achieve a cure for type 1 diabetes. We investigated formation of cell clusters from dispersed NPICCs on microwell cell culture plates, evaluated the composition of re-aggregated porcine islets (REPIs) and compared function by transplantation into diabetic NOD-SCID IL2rγ (NSG) mice with native NPICCs.

Lower Hepatic Fat Is Associated With Improved Insulin Secretion in a High-Risk Prediabetes Subphenotype During Lifestyle Intervention.

The objective of this work was to investigate whether impaired insulin secretion can be restored by lifestyle intervention in specific subphenotypes of prediabetes. We assigned 1,045 participants from the Prediabetes Lifestyle Intervention Study (PLIS) to six recently established prediabetes clusters. Insulin secretion was assessed by a C-peptide-based index derived from oral glucose tolerance tests and modeled from three time points during a 1-year intervention.

Subclinical Cardiovascular Disease Markers in Relation to Serum and Dietary Magnesium in Individuals from the General Population: The KORA-MRI Study.

Several studies have implied a role of magnesium in the development of cardiovascular disease (CVD). Thus, magnesium might serve as a potential risk marker for early CVD. Therefore, we investigated the association of serum magnesium and dietary magnesium intake with markers of subclinical CVD in a population-based study.

Associations of the vasoactive peptides CT-proET-1 and MR-proADM with incident type 2 diabetes: results from the BiomarCaRE Consortium.

Background: Endothelin-1 (ET-1) and adrenomedullin (ADM) are commonly known as vasoactive peptides that regulate vascular homeostasis. Less recognised is the fact that both peptides could affect glucose metabolism. Here, we investigated whether ET-1 and ADM, measured as C-terminal-proET-1 (CT-proET-1) and mid-regional-proADM (MR-proADM), respectively, were associated with incident type 2 diabetes.

Altered Circulating Leptin, hGH, and IGF-I in Prediabetes and Screening-Diagnosed T2DM Unrelated to Metabolic Syndrome in Women Post Gestational Diabetes.

Recently, we proposed two pathophysiologic subtypes of type 2 diabetes mellitus (T2DM), one related and one unrelated to metabolic syndrome. To begin to understand the pathophysiology of the subtype unrelated to metabolic syndrome, we now measured selected hormones and signaling molecules in affected individuals. In this cross-sectional analysis, we examined 138 women out of the monocenter, post gestational diabetes study PPSDiab.

Health impact of seven herpesviruses on (pre)diabetes incidence and HbA: results from the KORA cohort.

Aims/hypothesis: The prevalence of type 2 diabetes is increasing worldwide, and previous studies have suggested that it is higher in individuals who are seropositive for herpesviruses. This study examines the prospective association of herpesviruses with (pre)diabetes to evaluate their potential role in diabetes aetiology.

Methods: Two follow-up examinations of the German population-based KORA cohort (F4 and FF4) were used to identify participants with normal glucose tolerance at baseline, thus being at risk for (pre)diabetes (n = 1257).

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.

A Normalized Real-Life Glucose Profile After Diet-Induced Remission of Type 2 Diabetes: A Pilot Trial.

Background/objective Type 2 diabetes related to metabolic syndrome is often partially reversible after weight loss. We conducted a pilot trial on whether complete remission to the point of a normalized real-life glucose profile, measured by continuous subcutaneous monitoring, can be achieved. Methods We conducted a mono-center, single-arm intervention trial between January 20, 2020, and January 12, 2021, in Munich, Germany.

Benefit Assessment and Reimbursement of Digital Health Applications: Concepts for Setting Up a New System for Public Coverage.

In Germany, some digital health applications (DiHA) became reimbursable through the statutory health insurance system with the adoption of the Digital Healthcare Act in 2019. Approaches and concepts for the German care context were developed in an iterative process, based on existing concepts from international experience. A DiHA categorization was developed that could be used as a basis to enable the creation of a reimbursed DiHA repository, and to derive evidence requirements for coverage and reimbursement for each DiHA.

A novel smartphone app to change risk behaviors of women after gestational diabetes: A randomized controlled trial.

Aims: Women after gestational diabetes mellitus (GDM) are a risk group for cardiometabolic diseases but are hard to reach by conventional lifestyle programs. Therefore, we tested whether a novel, smartphone-delivered intervention, TRIANGLE, is accepted by women after GDM and alters cardiometabolic risk behaviors and outcomes. TRIANGLE targets gradual habit change of mind and emotion, physical activity, nutrition, and sleep.

Function outperforms morphology in the assessment of muscular contribution to insulin sensitivity in premenopausal women.

Introduction: Skeletal muscle contributes significantly to insulin sensitivity in humans. However, which non-invasive measurement best reflects this contribution remains unknown. Consequently, this paper compares morphologic and functional measurements.