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.

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.

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.

Myocardial inflammation is associated with impaired mitochondrial oxidative capacity in ischaemic cardiomyopathy.

Aims: Myocardial inflammation and impaired mitochondrial oxidative capacity are hallmarks of heart failure (HF) pathophysiology. The extent of myocardial inflammation in patients suffering from ischaemic cardiomyopathy (ICM) or dilated cardiomyopathy (DCM) and its association with mitochondrial energy metabolism are unknown. We aimed at establishing a relevant role of cardiac inflammation in the impairment of mitochondrial energy production in advanced ischaemic and non-ischaemic HF.

Adherence to the Dietary Approaches to Stop Hypertension (DASH) diet is associated with lower visceral and hepatic lipid content in recent-onset type 1 diabetes and type 2 diabetes.

Aim: To investigate the associations of the Dietary Approaches to Stop Hypertension (DASH) score with subcutaneous (SAT) and visceral (VAT) adipose tissue volume and hepatic lipid content (HLC) in people with diabetes and to examine whether changes in the DASH diet were associated with changes in these outcomes.

Methods: In total, 335 participants with recent-onset type 1 diabetes (T1D) and type 2 diabetes (T2D) from the German Diabetes Study were included in the cross-sectional analysis, and 111 participants in the analysis of changes during the 5-year follow-up. Associations between the DASH score and VAT, SAT and HLC and their changes were investigated using multivariable linear regression models by diabetes type.

Resource use and costs of transitioning from paediatric to adult care for patients with chronic endocrine disease.

Objective: Structured transition of adolescents and young adults with a chronic endocrine disease from paediatric to adult care is important. Until now, no data on time and resources required for the necessary components of the transition process and the associated costs are available.

Design, Patients And Measurements: In a prospective cohort study of 147 patients with chronic endocrinopathies, for the key elements of a structured transition pathway including (i) assessment of patients' disease-related knowledge and needs, (ii) required education and counselling sessions, (iii) compiling an epicrisis and a transfer appointment of the patient together with the current paediatric and the future adult endocrinologist resource consumption and costs were determined.

Glucose Load Following Prolonged Fasting Increases Oxidative Stress- Linked Response in Individuals With Diabetic Complications.

Objective: Prolonged catabolic states in type 2 diabetes (T2D), exacerbated by excess substrate flux and hyperglycemia, can challenge metabolic flexibility and antioxidative capacity. We investigated cellular responses to glucose load after prolonged fasting in T2D.

Research Design And Methods: Glucose-tolerant individuals (CON, n = 10) and individuals with T2D with (T2D+, n = 10) and without (T2D-, n = 10) diabetes complications underwent oral glucose tolerance test before and after a 5-day fasting-mimicking diet.

Accumulation of Non-Pathological Liver Fat Is Associated with the Loss of Glyoxalase I Activity in Humans.

The underlying molecular mechanisms for the development of non-alcoholic fatty liver (NAFL) and its progression to advanced liver diseases remain elusive. Glyoxalase 1 (Glo1) loss, leading to elevated methylglyoxal (MG) and dicarbonyl stress, has been implicated in various diseases, including obesity-related conditions. This study aimed to investigate changes in the glyoxalase system in individuals with non-pathological liver fat.

Diffusion tensor imaging in anisotropic tissues: application of reduced gradient vector schemes in peripheral nerves.

Background: In contrast to the brain, fibers within peripheral nerves have distinct monodirectional structure questioning the necessity of complex multidirectional gradient vector schemes for DTI. This proof-of-concept study investigated the diagnostic utility of reduced gradient vector schemes in peripheral nerve DTI.

Methods: Three-Tesla magnetic resonance neurography of the tibial nerve using 20-vector DTI (DTI) was performed in 10 healthy volunteers, 12 patients with type 2 diabetes, and 12 age-matched healthy controls.

Utility of bioelectrical phase angle for cardiovascular risk assessment among individuals with and without diabetes mellitus.

Purpose: Low values of bioimpedance-derived phase angle (PA) have been associated with various adverse outcomes. We investigated the association of PA with cardiovascular markers in individuals with and without diabetes mellitus (DM).

Methods: PA was measured in 452 adults (without DM = 153, T1DM = 67, T2DM = 232).

Phase Angle of Bioelectrical Impedance Analysis as an Indicator for Diabetic Polyneuropathy in Type 2 Diabetes Mellitus.

Context: Due to the heterogenous clinical symptoms and deficits, the diagnosis of diabetic polyneuropathy (DPN) is still difficult in clinical routines, leading to increased morbidity and mortality.

Objective: We studied the correlation of phase angle (PhA) of bioelectrical impedance analysis (BIA) with clinical, laboratory, and physical markers of DPN to evaluate PhA as a possible diagnostic method for DPN.

Materials And Methods: In this cross-sectional observational study as part of the Heidelberg Study on Diabetes and Complications, we examined 104 healthy individuals and 205 patients with type 2 diabetes mellitus (T2D), among which 63 had DPN.

Magnetization transfer ratio of the sciatic nerve differs between patients in type 1 and type 2 diabetes.

Background: Previous studies on magnetic resonance neurography (MRN) found different patterns of structural nerve damage in type 1 diabetes (T1D) and type 2 diabetes (T2D). Magnetization transfer ratio (MTR) is a quantitative technique to analyze the macromolecular tissue composition. We compared MTR values of the sciatic nerve in patients with T1D, T2D, and healthy controls (HC).

Non-cross-linking advanced glycation end products affect prohormone processing.

Advanced glycation end products (AGEs) are non-enzymatic post-translational modifications of amino acids and are associated with diabetic complications. One proposed pathomechanism is the impaired processing of AGE-modified proteins or peptides including prohormones. Two approaches were applied to investigate whether substrate modification with AGEs affects the processing of substrates like prohormones to the active hormones.

Impaired Detoxification of Trans, Trans-2,4-Decadienal, an Oxidation Product from Omega-6 Fatty Acids, Alters Insulin Signaling, Gluconeogenesis and Promotes Microvascular Disease.

Omega-6 fatty acids are the primary polyunsaturated fatty acids in most Western diets, while their role in diabetes remains controversial. Exposure of omega-6 fatty acids to an oxidative environment results in the generation of a highly reactive carbonyl species known as trans, trans-2,4-decadienal (tt-DDE). The timely and efficient detoxification of this metabolite, which has actions comparable to other reactive carbonyl species, such as 4-hydroxynonenal, acrolein, acetaldehyde, and methylglyoxal, is essential for disease prevention.

A diminished sciatic nerve structural integrity is associated with distinct peripheral sensory phenotypes in individuals with type 2 diabetes.

Aims/hypothesis: Quantitative sensory testing (QST) allows the identification of individuals with rapid progression of diabetic sensorimotor polyneuropathy (DSPN) based on certain sensory phenotypes. Hence, the aim of this study was to investigate the relationship of these phenotypes with the structural integrity of the sciatic nerve among individuals with type 2 diabetes.

Methods: Seventy-six individuals with type 2 diabetes took part in this cross-sectional study and underwent QST of the right foot and high-resolution magnetic resonance neurography including diffusion tensor imaging of the right distal sciatic nerve to determine the sciatic nerve fractional anisotropy (FA) and cross-sectional area (CSA), both of which serve as markers of structural integrity of peripheral nerves.

Impact of physical fitness and exercise training on subcutaneous adipose tissue beiging markers in humans with and without diabetes and a high-fat diet-fed mouse model.

Aims: Exercise training induces white adipose tissue (WAT) beiging and improves glucose homeostasis and mitochondrial function in rodents. This could be relevant for type 2 diabetes in humans, but the effect of physical fitness on beiging of subcutaneous WAT (scWAT) remains unclear. This translational study investigates if beiging of scWAT associates with physical fitness in healthy humans and recent-onset type 2 diabetes and if a voluntary running wheel intervention is sufficient to induce beiging in mice.

Sensory Phenotypes Provide Insight Into the Natural Course of Diabetic Polyneuropathy.

Unlabelled: We aimed to investigate the characteristics and longitudinal course of sensory phenotypes identified through quantitative sensory testing (QST) in the frame of diabetic sensorimotor polyneuropathy (DSPN). A total of 316 individuals with diabetes were examined (type 2 diabetes 78.8%), 250 of whom were undergoing follow-up visits at 1, 2, and/or 4 (2.

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.

Insulin Resistance Is Associated With Reduced Capillary Permeability of Thigh Muscles in Patients With Type 2 Diabetes.

Context: Insulin-mediated microvascular permeability and blood flow of skeletal muscle appears to be altered in the condition of insulin resistance. Previous studies on this effect used invasive procedures in humans or animals.

Objective: The aim of this study was to demonstrate the feasibility of a noninvasive assessment of human muscle microcirculation via dynamic contrast-enhanced (DCE)-magnetic resonance imaging (MRI) of skeletal muscle in patients with type 2 diabetes (T2D).

Association of Small Fiber Function with Microvascular Perfusion of Peripheral Nerves in Patients with Type 2 Diabetes : Study using Quantitative Sensory Testing and Magnetic Resonance Neurography.

Introduction/aims: Diabetic small fiber neuropathy (SFN) is caused by damage to thinly myelinated A‑fibers (δ) and unmyelinated C‑fibers. This study aimed to assess associations between quantitative sensory testing (QST) and parameters of peripheral nerve perfusion obtained from dynamic contrast enhanced (DCE) magnetic resonance neurography (MRN) in type 2 diabetes patients with and without SFN.

Methods: A total of 18 patients with type 2 diabetes (T2D, 8 with SFN, 10 without SFN) and 10 healthy controls (HC) took part in this cross-sectional single-center study and underwent QST of the right leg and DCE-MRN of the right thigh with subsequent calculation of the sciatic nerve constant of capillary permeability (K), extravascular extracellular volume fraction (V), and plasma volume fraction (V).

Effects of TM6SF2 rs58542926 polymorphism on hepatocellular lipids and insulin resistance in early type 2 diabetes.

Background And Aims: Increased hepatocellular lipid content (HCL) is linked to insulin resistance, risk of type 2 diabetes and related complications. Conversely, a single-nucleotide polymorphism (TM6SF2; rs58542926) in the transmembrane 6 superfamily member 2-gene has been associated with nonalcoholic fatty liver disease (NAFLD), but lower cardiovascular risk. This case-control study tested the role of this polymorphism for tissue-specific insulin sensitivity during early course of diabetes.