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.

Role of patatin-like phospholipase domain-containing 3 gene for decreasing kidney function in recently diagnosed diabetes mellitus.

Aims: We examined the association of the G allele in the single-nucleotide polymorphism (SNP) rs738409 in the third exon of patatin-like phospholipase domain-containing 3 gene (PNPLA3) gene, with chronic kidney disease in diabetes endotypes.

Methods: Participants with recent-onset diabetes (n = 707) from the prospective German Diabetes Study (GDS) underwent cluster assignment, detailed phenotyping, genotyping and magnetic resonance spectroscopy to quantify hepatocellular lipid content (HCL).

Results: Severe insulin-resistant diabetes (SIRD) had the lowest glomerular filtration rates (eGFR) and highest HCL compared to severe insulin-deficient, moderate obesity-related, moderate age-related and severe autoimmune diabetes endotypes (all p < 0.

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.

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.

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.

Intramyocellular Triglyceride Content During the Early Course of Type 1 and Type 2 Diabetes.

Unlabelled: Intramyocellular lipid content (IMCL) is elevated in insulin-resistant humans, but it changes over time, and relationships with comorbidities remain unclear. We examined IMCL during the initial course of diabetes and its associations with complications. Participants of the German Diabetes Study (GDS) with recent-onset type 1 (n = 132) or type 2 diabetes (n = 139) and glucose-tolerant control subjects (n = 128) underwent 1H-MRS to measure IMCL and muscle volume, whole-body insulin sensitivity (hyperinsulinemic-euglycemic clamps; M-value), and cycling spiroergometry (VO2max).

Comparison of diabetes distress and depression screening results of emerging adults with type 1 diabetes onset at different ages: findings from the German early-onset T1D study and the German Diabetes Study (GDS).

Background: Diabetes distress is increasingly considered one of the most important psychosocial issues in the care of people with type 1 diabetes (T1D). We analyse whether diabetes distress and depression screening results of emerging adults are associated with the age at T1D onset.

Methods: Data were taken from two cohort studies conducted at the German Diabetes Center, Düsseldorf, Germany.

Relative validity of a glycemic index extended food-frequency questionnaire.

Background And Aims: The dietary glycemic index (GI) and glycemic load (GL) are increasingly recognized as important for the prevention and management of diabetes mellitus. To extend the portfolio of assessment methods for large-scale epidemiological studies, we propose a GI-specific addition to an already established FFQ.

Methods And Results: The German version of the EPIC-FFQ was extended by GI-specific questions for major carbohydrate sources varying notably in GI (breakfast cereals, bread, pasta, rice, potato etc.

Metabolic Factors Predict Changes in Endothelial Function During the Early Course of Type 1 and Type 2 Diabetes.

Context: Endothelial dysfunction may occur early in the development of cardiovascular and metabolic diseases; however, it remains often underestimated and studies rarely discriminate between diabetes types. We have examined endothelial function and its determinants during the early course of type 1 and type 2 diabetes.

Methods: Caucasian participants of the prospective German Diabetes Study (GDS) with known diabetes duration <1 year (n = 398) or without diabetes, but of similar age, body mass index (BMI) and sex distribution (n = 109), underwent measurements of flow-mediated dilation (FMD) and nitroglycerin-mediated dilatation (NMD).

Socio-economic inequalities in glycaemic control in recently diagnosed adults with type 1 and type 2 diabetes.

Background And Aims: It is unclear whether socio-economic status (SES) is associated with glycaemic control in people with recently diagnosed diabetes. The aim was to investigate whether SES is related to haemoglobin A1c (HbA1c) during the first year after diagnosis in people with type 1 and type 2 diabetes and if metabolic, quality of care or mental factors may explain the association.

Methods: In the German Diabetes Study, people with type 1 (n = 274, median age 36 [25th; 75th percentile: 28; 48] years) and type 2 diabetes (n = 424, 54 [47; 60] years) underwent detailed metabolic characterisation within the first year after diagnosis.

Hepatic energy metabolism in a family with a glucokinase gene mutation and dysglycemia.

Carriers heterozygous for the D124N (c.370, GAC > AAC in exon 4) variant of GCK not only exhibit reduced insulin-secretion, but also impaired adipose insulin sensitivity, which may shift fatty acids towards the liver. This could contribute to increased hepatic lipid-accumulation and alterations of liver energy metabolism resulting in dysglycemia.

Polymorphism Is Associated With Physical Activity-Mediated Metabolic Changes in Type 2 Diabetes.

Unlabelled: The rs540467 SNP in the gene, encoding a mitochondrial complex I subunit, has been shown to modulate adaptations to exercise training. Interaction effects with diabetes mellitus remain unclear. We assessed associations of habitual physical activity (PA) levels with metabolic variables and examined a possible modifying effect of the rs540467 SNP.

Branched-Chain Amino Acids Associate Negatively With Postprandial Insulin Secretion in Recent-Onset Diabetes.

Context: In addition to unfavorable effects on insulin sensitivity, elevated plasma branched-chain amino acids (BCAA) stimulate insulin secretion, which, over the long-term, could impair pancreatic β-cell function.

Objective: To investigate cross-sectional and prospective associations between circulating BCAA and postprandial β-cell function in recently diagnosed type 1 and type 2 diabetes.

Methods: The study included individuals with well-controlled type 1 and type 2 diabetes (known diabetes duration <12 months) and glucose-tolerant participants (controls) of similar age, sex, and body mass index (n = 10/group) who underwent mixed meal tolerance tests.

Impact of mixed meal tolerance test composition on measures of beta-cell function in type 2 diabetes.

Background: Application of mixed meal tolerance tests (MMTT) to measure beta-cell function in long-term studies is limited by modification of the commercial products occurring over time. This study assessed the intra-individual reliability of MMTTs and compared the effects of liquid meals differing in macronutrient composition on the estimation of beta-cell function in type 2 diabetes (T2DM).

Methods: To test the reliability of MMTTs, 10 people with T2DM (age 58 ± 11 years, body mass index 30.

Improving insulin sensitivity, liver steatosis and fibrosis in type 2 diabetes by a food-based digital education-assisted lifestyle intervention program: a feasibility study.

Purpose: Recent trials demonstrated remission of type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) following formula diet-induced weight loss. To improve the outreach for populations in need, many mobile health apps targeting weight loss have been developed with limited scientific evaluation of these apps. The present feasibility study investigated the effects of a novel approach incorporating a regular 'whole food-based' low-calorie diet combined with app-based digital education and behavioral change program on glucose metabolism and disease management.

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.

Reduced Muscle Strength Is Associated With Insulin Resistance in Type 2 Diabetes Patients With Osteoarthritis.

Context: Type 2 diabetes is associated with a greater risk for musculoskeletal disorders, yet its impact on joint function remains unclear.

Objective: We hypothesized that patients with type 2 diabetes and osteoarthritis would exhibit musculoskeletal impairment, which would associate with insulin resistance and distinct microRNA profiles.

Methods: Participants of the German Diabetes Study with type 2 diabetes (T2D, n = 39) or normal glucose tolerance (CON, n = 27), both with (+OA) or without osteoarthritis (-OA) underwent intravenous glucose tolerance and hyperinsulinemic-euglycemic clamp tests.

Role of Patatin-Like Phospholipase Domain-Containing 3 Gene for Hepatic Lipid Content and Insulin Resistance in Diabetes.

Objective: The rs738409(G) single nucleotide polymorphism (SNP) in the patatin-like phospholipase domain-containing 3 () gene associates with increased risk and progression of nonalcoholic fatty liver disease (NAFLD). As the recently described severe insulin-resistant diabetes (SIRD) cluster specifically relates to NAFLD, this study examined whether this SNP differently associates with hepatic lipid content (hepatocellular lipids [HCL]) and insulin sensitivity in recent-onset diabetes.

Research Design And Methods: A total of 917 participants in the German Diabetes Study (GDS) underwent genotyping, hyperinsulinemic-euglycemic clamps with stable isotopic tracer dilution, and MRS.

Expansion and Impaired Mitochondrial Efficiency of Deep Subcutaneous Adipose Tissue in Recent-Onset Type 2 Diabetes.

Context/objective: Impaired adipose tissue (AT) function might induce recent-onset type 2 diabetes (T2D). Understanding AT energy metabolism could yield novel targets for the treatment of T2D.

Design/patients: Male patients with recently-diagnosed T2D and healthy male controls (CON) of similar abdominal subcutaneous AT (SAT)-thickness, fat mass, and age (n = 14 each), underwent hyperinsulinemic-euglycemic clamps with [6,6-2H2]glucose and indirect calorimetry.

Short-term dietary reduction of branched-chain amino acids reduces meal-induced insulin secretion and modifies microbiome composition in type 2 diabetes: a randomized controlled crossover trial.

Background: Epidemiological studies have shown that increased circulating branched-chain amino acids (BCAAs) are associated with insulin resistance and type 2 diabetes (T2D). This may result from altered energy metabolism or dietary habits.

Objective: We hypothesized that a lower intake of BCAAs improves tissue-specific insulin sensitivity.

Risk of diabetes-associated diseases in subgroups of patients with recent-onset diabetes: a 5-year follow-up study.

Background: Cluster analyses have proposed different diabetes phenotypes using age, BMI, glycaemia, homoeostasis model estimates, and islet autoantibodies. We tested whether comprehensive phenotyping validates and further characterises these clusters at diagnosis and whether relevant diabetes-related complications differ among these clusters, during 5-years of follow-up.

Methods: Patients with newly diagnosed type 1 or type 2 diabetes in the German Diabetes Study underwent comprehensive phenotyping and assessment of laboratory variables.