TY  - JOUR
AB  - Metabolic diseases affect a consistent part of the human population, leading to rising mortality rates. This raises the need for diagnostic tools to monitor the progress of these diseases. Lately, circulating cell-free DNA (cfDNA) has emerged as a promising biomarker for various metabolic diseases, including obesity, type 2 diabetes, and metabolic-associated fatty liver disease. CfDNA is released from apoptotic and necrotic cells into the bloodstream and other body fluids, and it retains various molecular signatures of its tissue of origin. Thus, cfDNA load and composition can reflect tissue pathologies and systemic metabolic dysfunctions. In addition to its potential as a diagnostic biomarker, interest in cfDNA derives from its recently discovered role in adipose tissue inflammation in obesity. This review discusses detection methods and clinical significance of cfDNA in metabolic diseases.
AU  - Pollastri, A.
AU  - Kovacs, P.*
AU  - Keller, M.
C1  - 73166
C2  - 56942
CY  - 2055 L St Nw, Suite 600, Washington, Dc 20036 Usa
TI  - Circulating cell-free DNA in metabolic diseases.
JO  - J. Endocr. Soc.
VL  - 9
IS  - 2
PB  - Endocrine Soc
PY  - 2025
SN  - 2472-1972
ER  - 

TY  - JOUR
AB  - BackgroundNeck circumference (NC) was proposed as promising marker to assess body fat distribution and cardiometabolic risk.ObjectivesWe
       aimed to assess associations of NC with anthropometric traits, 
      cardiometabolic risk markers and self-reported cardiometabolic diseases.MethodsNC
       was measured in a subsample (5,865 participants) of the German National
       Cohort (NAKO Gesundheitsstudie, NAKO), study region Kiel. Linear and 
      logistic regression models were applied to assess associations of NC 
      with anthropometric and cardiometabolic risk markers and self-reported 
      cardiometabolic diseases, including diabetes, heart failure, gout, and a
       composite endpoint ‘clinical CVD’ (combining history of angina 
      pectoris, stroke, myocardial infarction, and peripheral artery disease).
       Models were adjusted for sex and age, cardiovascular risk factors 
      (systolic blood pressure, diabetes, LDL-cholesterol, use of 
      lipid-lowering and antihypertensive medication, smoking status), and 
      BMI.ResultsMean
       NC values (± SD) were 39.5±3.0 in men and 33.6±2.7 cm in women. NC was 
      positively associated with anthropometric traits, visceral adipose 
      tissue [cm] (β=1.45 [95% confidence interval 0.88; 2.02]), systolic 
      (β=0.37 [0.19; 0.56]) and diastolic (β=0.17 [0.05; 0.29]) blood 
      pressure, HbA1c (β=0.02 [0.01; 0.02]), non-fasting glucose (β=0.57 
      [0.31; 0.83]), and inversely associated with HDL-cholesterol (β=-0.73 
      [-0.91; -0.54]). Furthermore, NC showed associations with diabetes 
      (OR=1.08 [1.02; 1.15]), heart failure (OR=1.12 [1.02; 1.23]) and gout 
      (OR=1.09 [1.01; 1.17]). Association with ‘clinical CVD’ did not remain 
      statistically significant after BMI adjustment.ConclusionsNC
       was associated with several cardiometabolic risk factors, including 
      glycemic and lipid traits and self-reported cardiometabolic diseases. 
      These observations suggest that NC may be a useful surrogate marker for 
      cardiometabolic risk.
AU  - Strathmann, E.A.*
AU  - Ratjen, I.*
AU  - Willrodt, K.*
AU  - Enderle, J.*
AU  - Schlesinger, S.*
AU  - Fischer, B.*
AU  - Weber, K.*
AU  - Cara Övermöhle,*
AU  - Greiser, K.H.*
AU  - Sedlmeier, A.M.*
AU  - Heier, M.
AU  - Köttgen, A.*
AU  - Günther, K.*
AU  - Nauck, M.*
AU  - Lieb, W.*
C1  - 75830
C2  - 58095
CY  - 2055 L St Nw, Suite 600, Washington, Dc 20036 Usa
TI  - Association of neck circumference with cardiometabolic risk factors and diseases in the German National Cohort.
JO  - J. Endocr. Soc.
VL  - 9
IS  - 12
PB  - Endocrine Soc
PY  - 2025
SN  - 2472-1972
ER  - 

TY  - JOUR
AB  - CONTEXT: The 2 peaks of type 1 diabetes incidence occur during early childhood and puberty. OBJECTIVE: We sought to better understand the relationship between puberty, islet autoimmunity, and type 1 diabetes. METHODS: The relationships between puberty, islet autoimmunity, and progression to type 1 diabetes were investigated prospectively in children followed in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Onset of puberty was determined by subject self-assessment of Tanner stages. Associations between speed of pubertal progression, pubertal growth, weight gain, homeostasis model assessment of insulin resistance (HOMA-IR), islet autoimmunity, and progression to type 1 diabetes were assessed. The influence of individual factors was analyzed using Cox proportional hazard ratios. RESULTS: Out of 5677 children who were still in the study at age 8 years, 95% reported at least 1 Tanner Stage score and were included in the study. Children at puberty (Tanner Stage ≥2) had a lower risk (HR 0.65, 95% CI 0.45-0.93; P = .019) for incident autoimmunity than prepubertal children (Tanner Stage 1). An increase of body mass index Z-score was associated with a higher risk (HR 2.88, 95% CI 1.61-5.15; P < .001) of incident insulin autoantibodies. In children with multiple autoantibodies, neither HOMA-IR nor rate of progression to Tanner Stage 4 were associated with progression to type 1 diabetes. CONCLUSION: Rapid weight gain during puberty is associated with development of islet autoimmunity. Puberty itself had no significant influence on the appearance of autoantibodies or type 1 diabetes. Further studies are needed to better understand the underlying mechanisms.
AU  - Warncke, K.
AU  - Tamura, R.*
AU  - Schatz, D.A.*
AU  - Veijola, R.*
AU  - Steck, A.K.*
AU  - Akolkar, B.*
AU  - Hagopian, W.*
AU  - Krischer, J.P.*
AU  - Lernmark, Å.*
AU  - Rewers, M.J.*
AU  - Toppari, J.*
AU  - McIndoe, R.*
AU  - Ziegler, A.-G.
AU  - Vehik, K.*
AU  - Haller, M.J.*
AU  - Elding Larsson, H.*
C1  - 70831
C2  - 55945
CY  - 2055 L St Nw, Suite 600, Washington, Dc 20036 Usa
TI  - The influence of pubertal development on autoantibody appearance and progression to type 1 diabetes in the TEDDY Study.
JO  - J. Endocr. Soc.
VL  - 8
IS  - 7
PB  - Endocrine Soc
PY  - 2024
SN  - 2472-1972
ER  - 

TY  - JOUR
AB  - CONTEXT: Behaviorally, the most pronounced effects of leptin substitution in leptin deficiency are the hunger-decreasing and postprandial satiety-prolonging effects of the adipokine. Previously, with functional magnetic resonance imaging (MRI), we and others showed that eating behavior-controlling effects are at least in part conveyed by the reward system. However, to date, it is unclear if leptin only modulates eating behavior specific brain reward action or if it also alters the reward function of the brain unrelated to eating behavior. OBJECTIVE: We investigated with functional MRI the effects of metreleptin on the reward system in a reward task unrelated to eating behavior, the monetary incentive delay task. DESIGN: Measurements in 4 patients with the very rare disease of lipodystrophy (LD), resulting in leptin deficiency, and 3 untreated healthy control persons were performed at 4 different time points: before start and over 12 weeks of metreleptin treatment. Inside the MRI scanner, participants performed the monetary incentive delay task and brain activity during the reward receipt phase of the trial was analyzed. RESULTS: We found a reward-related brain activity decrease in our 4 patients with LD over the 12 weeks of metreleptin treatment in the subgenual region, a brain area associated with the reward network, which was not observed in our 3 untreated healthy control persons. CONCLUSIONS: These results suggest that leptin replacement in LD induces changes of brain activity during reward reception processing completely unrelated to eating behavior or food stimuli. This could suggest eating behavior-unrelated functions of leptin in the human reward system. TRIAL REGISTRATION: The trial is registered as trial No. 147/10-ek at the ethics committee of the University of Leipzig and at the State Directorate of Saxony (Landesdirektion Sachsen).
AU  - Schlögl, H.
AU  - Janssen, L.*
AU  - Fasshauer, M.*
AU  - Miehle, K.*
AU  - Villringer, A.*
AU  - Stumvoll, M.
AU  - Mueller, K.*
C1  - 67803
C2  - 54281
CY  - 2055 L St Nw, Suite 600, Washington, Dc 20036 Usa
TI  - Reward processing during monetary incentive delay task after leptin substitution in lipodystrophy-an fMRI case series.
JO  - J. Endocr. Soc.
VL  - 7
IS  - 6
PB  - Endocrine Soc
PY  - 2023
SN  - 2472-1972
ER  - 

TY  - JOUR
AB  - Context: Research in lipodystrophy (LD) and its treatment with metreleptin has not only helped patients with LD but has opened new directions in investigating leptin's role in metabolism and the regulation of eating behavior. Previously, in a study with patients with LD undergoing metreleptin treatment using functional magnetic resonance imaging (MRI), we found significantly increased resting-state brain connectivity in 3 brain areas including the hypothalamus. Objective: In this study, we aimed to reproduce our functional MRI findings in an independent sample and compare results to healthy participants. Design: Measurements in 4 female patients with LD undergoing metreleptin treatment and 3 healthy untreated controls were performed at 4 different time points over 12 weeks. To identify treatment-related brain connectivity alterations, eigenvector centrality was computed from resting-state functional MRI data for each patient and each session. Thereafter, analysis aimed at detecting consistent brain connectivity changes over time across all patients. Results: In parallel to metreleptin treatment of the patients with LD, we found a significant brain connectivity increase in the hypothalamus and bilaterally in posterior cingulate gyrus. Using a 3-factorial model, a significant interaction between group and time was found in the hypothalamus. Conclusions: Investigating brain connectivity alterations with metreleptin treatment using an independent sample of patients with LD, we have reproduced an increase of brain connectivity in hedonic and homeostatic central nervous networks observed previously with metreleptin treatment. These results are an important contribution to ascertain brain leptin action and help build a foundation for further research of central nervous effects of this important metabolic hormone.
AU  - Schlögl, H.
AU  - Villringer, A.*
AU  - Miehle, K.*
AU  - Fasshauer, M.*
AU  - Stumvoll, M.
AU  - Mueller, K.*
C1  - 68379
C2  - 54629
CY  - 2055 L St Nw, Suite 600, Washington, Dc 20036 Usa
TI  - Metreleptin robustly increases resting-state brain connectivity in treatment-naïve female patients with lipodystrophy.
JO  - J. Endocr. Soc.
VL  - 7
IS  - 8
PB  - Endocrine Soc
PY  - 2023
SN  - 2472-1972
ER  -