24 results on '"Bódis, K."'
Search Results
2. Dataset for multidimensional assessment to incentivise decentralised energy investments in Sub-Saharan Africa
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Bender, A., primary, Moner-Girona, M., additional, Becker, W., additional, Bódis, K., additional, Szabó, S., additional, Kararach, A.G., additional, and Anadon, L.D., additional
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- 2021
- Full Text
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3. Universal access to electricity in Burkina Faso: scaling-up renewable energy technologies
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Moner-Girona, M, primary, Bódis, K, additional, Huld, T, additional, Kougias, I, additional, and Szabó, S, additional
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- 2016
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4. Energy solutions in rural Africa: mapping electrification costs of distributed solar and diesel generation versus grid extension
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Szabó, S, primary, Bódis, K, additional, Huld, T, additional, and Moner-Girona, M, additional
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- 2011
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5. Evaluating the benefits of adapting to changing flood hazard in Europe
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Feyen, Luc, primary, Bankers, R, additional, and Bódis, K, additional
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- 2009
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6. Impact of Peripheral Angioplasty on Wound Oxygenation and Healing in Patients with Chronic Limb-Threatening Ischemia Measured by Near-Infrared Spectroscopy.
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Schremmer J, Stern M, Baasen S, Wischmann P, Foerster R, Schillings M, Bódis K, Sansone R, Heiss C, Kelm M, and Busch L
- Abstract
Managing chronic limb-threatening ischemia (CLTI) is challenging due to difficulties in assessing tissue oxygen saturation in ulcers. Near-infrared spectroscopy (NIRS) is a non-invasive method for measuring tissue oxygen saturation (StO
2 ). This study evaluated the effects of endovascular treatment (EVT) on StO2 and wound healing in CLTI patients, comparing NIRS to standard ankle-brachial index (ABI) measurements. Using the Duesseldorf PTA Registry, 43 CLTI patients were analyzed: 27 underwent EVT, and 16 received conservative treatment. ABI assessed macrocirculation, while NIRS measured wound, wound area, and mean foot StO2 at baseline, post-EVT, and four-month follow-up. Wound severity was classified by wound area and wound, ischemia, and foot infection (WIfI) score. Wound StO2 increased significantly (median (interquartile range (IQR)), 38 (49.3) to 60 (34.5)%, p = 0.004), as did wound area StO2 (median (IQR), 70.9 (21.6) to 72.8 (18.3)%, p < 0.001), with no significant changes in the control group by four-month follow-up. Wound area decreased significantly after EVT (mean ± SD, 343.1 ± 267.8 to 178.1 ± 268.5 mm2 , p = 0.01) but not in the control group. Changes in wound StO2 , wound area StO2 , and WIfI score correlated with wound area reduction, unlike ABI. This small exploratory study shows that NIRS-measured StO2 improvements after EVT correlate with reduced wound area and WIfI scores, highlighting NIRS as a potential enhancement for CLTI wound management in addition to ABI.- Published
- 2024
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7. Reduced Insulin Clearance Differently Relates to Increased Liver Lipid Content and Worse Glycemic Control in Recent-Onset Type 2 and Type 1 Diabetes.
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Zaharia OP, Antoniou S, Bobrov P, Karusheva Y, Bódis K, Kupriyanova Y, Schrauwen-Hinderling V, Gastaldelli A, Szendroedi J, Wagner R, Burkart V, and Roden M
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- Humans, Insulin metabolism, Glycemic Control, Liver metabolism, Insulin, Regular, Human, Lipids, Diabetes Mellitus, Type 1 drug therapy, Diabetes Mellitus, Type 1 metabolism, Diabetes Mellitus, Type 2 metabolism, Insulin Resistance
- Abstract
Objective: Diabetes may feature impaired insulin kinetics, which could be aggravated by altered hepatic metabolism and glycemic control. Thus, we examined insulin clearance and its possible determinants in individuals with recent-onset diabetes., Research Design and Methods: Participants of the German Diabetes Study (GDS) with type 1 diabetes (T1D) (n = 306), type 2 diabetes (T2D) (n = 489), or normal glucose tolerance (control [CON]) (n = 167) underwent hyperinsulinemic-euglycemic clamps for assessment of whole-body insulin sensitivity (M value) and insulin clearance (ICCLAMP). Insulin clearance rates were further calculated during intravenous glucose tolerance tests (ICIVGTT) and mixed-meal tests (ICMMT). Hepatocellular lipid content (HCL) was quantified with 1H-MRS., Results: Both T1D and T2D groups had lower ICCLAMP (0.12 ± 0.07 and 0.21 ± 0.06 vs. 0.28 ± 0.14 arbitrary units [a.u.], respectively, all P < 0.05) and ICMMT (0.71 ± 0.35 and 0.99 ± 0.33 vs. 1.20 ± 0.36 a.u., all P < 0.05) than CON. In T1D, ICCLAMP, ICIVGTT, and ICMMT correlated negatively with HbA1c (all P < 0.05). M value correlated positively with ICIVGTT in CON and T2D (r = 0.199 and r = 0.178, P < 0.05) and with ICMMT in CON (r = 0.176, P < 0.05). HCL negatively associated with ICIVGTT and ICMMT in T2D (r = -0.005 and r = -0.037) and CON (r = -0.127 and r = -0.058, all P < 0.05). In line, T2D or CON subjects with steatosis featured lower ICMMT than those without steatosis (both P < 0.05)., Conclusions: Insulin clearance is reduced in both T1D and T2D within the first year after diagnosis but correlates negatively with liver lipid content rather in T2D. Moreover, insulin clearance differently associates with glycemic control and insulin sensitivity in each diabetes type, which may suggest specific mechanisms affecting insulin kinetics., (© 2023 by the American Diabetes Association.)
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- 2023
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8. 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).
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Stahl-Pehe A, Bächle C, Bódis K, Zaharia OP, Lange K, Holl RW, Roden M, and Rosenbauer J
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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. The 18-30-year-old participants had an age at onset either before the age of 5 years (childhood-onset long-term T1D study group, N = 749) or during adulthood (adult-onset short-term T1D study group from the German Diabetes Study (GDS), N = 163). Diabetes distress and depression screening were analysed by means of the 20-item Problem Areas in Diabetes (PAID-20) scale and the nine-item depression module from the Patient Health Questionnaire (PHQ-9). The average causal effect of age at onset was estimated by a doubly robust causal inference method., Results: The PAID-20 total scores were increased in the adult-onset study group [potential outcome mean (POM) 32.1 (95% confidence interval 28.0; 36.1) points] compared to the childhood-onset study group [POM 21.0 (19.6; 22.4) points, difference 11.1 (6.9; 15.3) points, p<0.001] adjusted for age, sex and haemoglobin A1c (HbA1c) levels. Moreover, more participants in the adult-onset group [POM 34.5 (24.9; 44.2) %] than in the childhood-onset group [POM 16.3 (13.3; 19.2) %] screened positive for diabetes distress [adjusted difference 18.3 (8.3; 28.2) %, p<0.001]. The PHQ-9 total score [difference 0.3 (-1.1; 1.7) points, p=0.660] and the proportion of participants with a positive screening result for depression [difference 0.0 (-12.7; 12.8) %, p=0.994] did not differ between the groups in the adjusted analyses., Conclusions: Emerging adults with short-term type 1 diabetes screened positive for diabetes distress more often than adults with type 1 diabetes onset during early childhood when age, sex and HbA1c values were considered confounding factors. Accounting for age at onset or the duration of diabetes may help explain the heterogeneity in the data when psychological factors are examined., (© 2023. The Author(s).)
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- 2023
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9. Metabolic Factors Predict Changes in Endothelial Function During the Early Course of Type 1 and Type 2 Diabetes.
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Zaharia OP, Schön M, Löffler L, Strassburger K, Möser C, Yurchenko I, Bódis K, Antoniou S, Karusheva Y, Szendroedi J, Burkart V, and Roden M
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- Brachial Artery, Endothelium, Vascular, Glucose, Glycated Hemoglobin, Humans, Nitroglycerin, Prospective Studies, Vasodilation, Diabetes Mellitus, Type 2 complications, Insulin Resistance
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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). Whole-body insulin sensitivity (M-value) was assessed by hyperinsulinemic-euglycemic clamps and physical fitness (VO2max) by spiroergometry. A subset of individuals with type 1 or type 2 diabetes (n = 108) was re-evaluated after 5 years., Results: At baseline, neither FMD nor NMD differed between people with diabetes and the matched glucose-tolerant groups. At the 5-year follow-up, decline in FMD (-13.9%, P = .013) of persons with type 2 diabetes was independent of age, sex, and BMI, but associated with baseline adipose tissue insulin resistance and indices of liver fibrosis. The M-value decreased in both type 1 and type 2 diabetes groups by 24% and 15% (both P < .001, respectively) over 5 years. Higher HbA1c, lower M-value, and lower VO2max at baseline was associated with lower FMD in both type 1 and type 2 diabetes., Conclusion: Endothelial function decreases during the early course of type 2 diabetes. In addition to age and BMI, insulin sensitivity at diagnosis was the best predictor of progressive impairment in endothelial function in type 2 diabetes., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.)
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- 2022
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10. NDUFB6 Polymorphism Is Associated With Physical Activity-Mediated Metabolic Changes in Type 2 Diabetes.
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Pesta D, Jelenik T, Zaharia OP, Bobrov P, Görgens S, Bódis K, Karusheva Y, Krako Jakovljevic N, Lalic NM, Markgraf DF, Burkart V, Müssig K, Knebel B, Kotzka J, Eckel J, Strassburger K, Szendroedi J, and Roden M
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- Adult, Animals, Body Composition genetics, Case-Control Studies, Cells, Cultured, Female, Follow-Up Studies, Genetic Association Studies, Germany, Glucose Clamp Technique, Humans, Longitudinal Studies, Male, Mice, Middle Aged, Muscle, Skeletal metabolism, Polymorphism, Single Nucleotide, Young Adult, Diabetes Mellitus, Type 2 genetics, Diabetes Mellitus, Type 2 metabolism, Electron Transport Complex I genetics, Exercise physiology
- Abstract
The rs540467 SNP in the NDUFB6 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. Volunteers with type 2 (n=242), type 1 diabetes (n=250) or normal glucose tolerance (control; n=139) were studied at diagnosis and subgroups with type 1 (n=96) and type 2 diabetes (n=95) after 5 years. Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamps, oxygen uptake at the ventilator threshold (VO
2 AT) by spiroergometry and PA by questionnaires. Translational studies investigated insulin signaling and mitochondrial function in Ndufb6 siRNA-treated C2C12 myotubes, with electronic pulse stimulation (EPS) to simulate exercising. PA levels were 10 and 6%, VO2 AT was 31% and 8% lower in type 2 and type 1 diabetes compared to control. Within 5 years, 36% of people with type 2 diabetes did not improve their insulin sensitivity despite increasing PA levels. The NDUFB6 rs540467 SNP modifies PA-mediated changes in insulin sensitivity, body composition and liver fat estimates in type 2 diabetes. Silencing Ndufb6 in myotubes reduced mitochondrial respiration and prevented rescue from palmitate-induced insulin resistance after EPS. A substantial proportion of humans with type 2 diabetes fails to respond to rising PA with increasing insulin sensitivity. This may at least partly relate to a polymorphism of the NDUFB6 gene, which may contribute to modulating mitochondrial function., Clinical Trial Registration: ClinicalTrials.gov, identifier NCT01055093. The trial was retrospectively registered on 25th of January 2010., Competing Interests: MR receives research support by the Ministry of Culture and Science of the State of North Rhine-Westphalia and the German Federal Ministry of Health, serves as investigator of studies supported by Boehringer-Ingelheim Pharma, Nutriticia/Danone and Sanofi and has served as advisor/consultant for Bristol-Myers Squibb, Eli Lilly, Gilead, Intercept Pharma, Novo Nordisk, Novartis, Poxel, Prosciento, Sanofi, Servier and TARGET NASH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest., (Copyright © 2021 Pesta, Jelenik, Zaharia, Bobrov, Görgens, Bódis, Karusheva, Krako Jakovljevic, Lalic, Markgraf, Burkart, Müssig, Knebel, Kotzka, Eckel, Strassburger, Szendroedi and Roden.)- Published
- 2021
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11. Impact of mixed meal tolerance test composition on measures of beta-cell function in type 2 diabetes.
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Kössler T, Bobrov P, Strassburger K, Kuss O, Zaharia OP, Karusheva Y, Möser C, Bódis K, Burkart V, Roden M, and Szendroedi J
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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 30.0 ± 4.9 kg/m
2 ) received Boost® high Protein 20 g protein three times. For comparing different meals, another 10 persons with T2DM (58 ± 5 years, 31.9 ± 5.3 kg/m2 ) ingested either Boost® high Protein 20 g protein or the isocaloric Boost® high Protein 15 g protein containing 35% less protein and 18% more carbohydrates. C-peptide, insulin and glucose release were assessed from the incremental area under the concentration time curve (iAUC) and the intra- and inter-individual variation of these parameters from the coefficients of variations (CV)., Results: Repetitive ingestion of one meal revealed intra-individual CVs for the iAUCs of C-peptide, insulin and glucose, which were at least 3-times lower than the inter-individual variation of these parameters (18.2%, 19.7% and 18.9% vs. 74.2%, 70.5% and 207.7%) indicating a good reliability. Ingestion of two different meals resulted in comparable intra-individual CVs of the iAUCs of C-peptide and insulin (16.9%, 20.5%)., Conclusion: MMTTs provide reliable estimation of beta-cell function in people with T2DM. Furthermore, moderate differences in the protein and carbohydrate contents in a standardized liquid meal do not result in relevant changes of C-peptide and insulin responses., Trial Registration: Clinicaltrials.gov, Identifier number: NCT01055093. Registered 22 January 2010 - Retrospectively registered, https://www.clinicaltrials.gov/ct2/show/study/NCT01055093.- Published
- 2021
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12. Differences in Biomarkers of Inflammation Between Novel Subgroups of Recent-Onset Diabetes.
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Herder C, Maalmi H, Strassburger K, Zaharia OP, Ratter JM, Karusheva Y, Elhadad MA, Bódis K, Bongaerts BWC, Rathmann W, Trenkamp S, Waldenberger M, Burkart V, Szendroedi J, and Roden M
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- Humans, Insulin Resistance physiology, Interleukin-6 metabolism, Male, S100A12 Protein metabolism, Biomarkers metabolism, Diabetes Mellitus, Type 1 metabolism, Inflammation metabolism
- Abstract
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. Pairwise differences between subgroups for biomarkers were assessed with generalized linear mixed models before (model 1) and after (model 2) adjustment for the clustering variables. Participants were assigned to five subgroups: severe autoimmune diabetes (21%), severe insulin-deficient diabetes (SIDD) (3%), severe insulin-resistant diabetes (SIRD) (9%), mild obesity-related diabetes (32%), and mild age-related diabetes (35%). In model 1, 23 biomarkers showed one or more pairwise differences between subgroups (Bonferroni-corrected P < 0.0007). Biomarker levels were generally highest in SIRD and lowest in SIDD. All 23 biomarkers correlated with one or more of the clustering variables. In model 2, three biomarkers (CASP-8, EN-RAGE, IL-6) showed at least one pairwise difference between subgroups (e.g., lower CASP8, EN-RAGE, and IL-6 in SIDD vs. all other subgroups, all P < 0.0007). Thus, novel diabetes subgroups show multiple differences in biomarkers of inflammation, underlining a prominent role of inflammatory pathways in particular in SIRD., (© 2021 by the American Diabetes Association.)
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- 2021
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13. Branched-Chain Amino Acids Associate Negatively With Postprandial Insulin Secretion in Recent-Onset Diabetes.
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Karusheva Y, Strassburger K, Markgraf DF, Zaharia OP, Bódis K, Kössler T, Tura A, Pacini G, Burkart V, Roden M, and Szendroedi J
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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. Plasma BCAA levels were quantified by gas chromatography-mass spectrometry, postprandial β-cell function was assessed from serum C-peptide levels, and insulin sensitivity was determined from PREDIM index (PREDIcted M-value)., Results: In type 1 diabetes, postprandial total BCAA, valine, and leucine levels were 25%, 18%, and 19% higher vs control, and total as well as individual postprandial BCAA were related inversely to C-peptide levels. In type 2 diabetes, postprandial isoleucine was 16% higher vs the respective controls, while neither total nor individual BCAA correlated with C-peptide levels. Whole-body insulin sensitivity was lower in both diabetes groups than in corresponding controls., Conclusion: Insulin deficiency associates with sustained high BCAA concentrations, which could contribute to exhausting the insulin secretory reserve in early type 1 diabetes., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)
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- 2021
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14. Reduced Muscle Strength Is Associated With Insulin Resistance in Type 2 Diabetes Patients With Osteoarthritis.
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Zaharia OP, Pesta DH, Bobrov P, Kupriyanova Y, Herder C, Karusheva Y, Bódis K, Bönhof GJ, Knitza J, Simon D, Kleyer A, Hwang JH, Müssig K, Ziegler D, Burkart V, Schett G, Roden M, and Szendroedi J
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- Adult, Aged, Case-Control Studies, Diabetes Mellitus, Type 2 metabolism, Diabetes Mellitus, Type 2 physiopathology, Female, Germany, Glucose Clamp Technique, Humans, Insulin metabolism, Male, Middle Aged, Muscle Strength physiology, Muscle Weakness metabolism, Muscle Weakness physiopathology, Osteoarthritis metabolism, Osteoarthritis physiopathology, Osteoarthritis, Knee complications, Osteoarthritis, Knee metabolism, Osteoarthritis, Knee physiopathology, Surveys and Questionnaires, Diabetes Mellitus, Type 2 complications, Insulin Resistance physiology, Muscle Weakness etiology, Osteoarthritis complications
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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. Musculoskeletal function was assessed by isometric knee extension strength (KES), grip strength, range of motion (ROM), and balance skills, while neural function was measured by nerve conductance velocity (NCV). Arthritis-related symptoms were quantified using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire, serum arthritis-related microRNA using quantitative polymerase chain reaction., Results: Insulin sensitivity was lower in T2D+OA vs T2D-OA (4.4 ± 2.0 vs 5.7 ± 3.0 mg* kg-1*min-1) and in CON+OA vs CON-OA (8.1 ± 2.0 vs 12.0 ± 2.6 mg*kg-1,*min-1, both P < .05). In T2D+OA, KES and ROM were 60% and 22% lower than in CON+OA, respectively (both P < .05). Insulin sensitivity correlated positively with KES (r = 0.41, P < .05) among T2D, and negatively with symptom severity in CON and T2D (r = -0.60 and r = -0.46, respectively, P < .05). CON+OA and T2D+OA had inferior balance skills than CON-OA, whereas NCV was comparable in T2D+OA and T2D-OA. Expression of arthritis-related microRNAs was upregulated in T2D compared to CON, but downregulated in CON+OA compared to CON-OA (P < .05), and did not differ between T2D+OA and T2D-OA., Conclusion: Musculoskeletal impairment and osteoarthritis-related symptoms are associated with insulin resistance. Type 2 diabetes can mask changes in arthritis-related microRNA profiles., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society.)
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- 2021
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15. Role of Patatin-Like Phospholipase Domain-Containing 3 Gene for Hepatic Lipid Content and Insulin Resistance in Diabetes.
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Zaharia OP, Strassburger K, Knebel B, Kupriyanova Y, Karusheva Y, Wolkersdorfer M, Bódis K, Markgraf DF, Burkart V, Hwang JH, Kotzka J, Al-Hasani H, Szendroedi J, and Roden M
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- Adult, Aged, Alleles, Case-Control Studies, Cross-Sectional Studies, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 epidemiology, Diabetes Mellitus, Type 2 metabolism, Female, Gene Frequency, Genetic Association Studies, Genetic Predisposition to Disease, Germany epidemiology, Glucose Clamp Technique, Humans, Insulin genetics, Insulin metabolism, Lipase genetics, Male, Membrane Proteins genetics, Middle Aged, Non-alcoholic Fatty Liver Disease complications, Non-alcoholic Fatty Liver Disease metabolism, Obesity complications, Obesity epidemiology, Obesity genetics, Obesity metabolism, Polymorphism, Single Nucleotide, Diabetes Mellitus, Type 2 genetics, Insulin Resistance genetics, Lipase physiology, Lipid Metabolism genetics, Liver metabolism, Membrane Proteins physiology, Non-alcoholic Fatty Liver Disease genetics
- Abstract
Objective: The rs738409(G) single nucleotide polymorphism (SNP) in the patatin-like phospholipase domain-containing 3 ( PNPLA3 ) 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., Results: The G allele associated positively with HCL (β = 0.36, P < 0.01), independent of age, sex, and BMI across the whole cohort, but not in the individual clusters. Those with SIRD exhibited lowest whole-body insulin sensitivity compared with those with severe insulin-deficient (SIDD), moderate obesity-related (MOD), moderate age-related (MARD), and severe autoimmune diabetes (SAID) clusters (all P < 0.001). Interestingly, the SIRD group presented with higher prevalence of the rs738409(G) SNP compared with other clusters and the glucose-tolerant control group ( P < 0.05). HCL was higher in the SIRD group (median 13.6% [1st quartile 5.8; 3rd quartile 19.1] compared with the MOD (6.4 % [2.1; 12.4], P < 0.05), MARD (3.0% [1.0; 7.9], P < 0.001), SAID (0.4% [0.0; 1.5], P < 0.001), and glucose-tolerant (0.9% [0.4; 4.9), P < 0.001) group. Although the PNPLA3 polymorphism did not directly associate with whole-body insulin sensitivity in SIRD, the G-allele carriers had higher circulating free fatty acid concentrations and greater adipose tissue insulin resistance compared with noncarriers (both P < 0.001)., Conclusions: Members of the SIRD cluster are more frequently carriers of the rs738409(G) variant. The SNP-associated adipose tissue insulin resistance and excessive lipolysis may contribute to their NAFLD., (© 2020 by the American Diabetes Association.)
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- 2020
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16. Expansion and Impaired Mitochondrial Efficiency of Deep Subcutaneous Adipose Tissue in Recent-Onset Type 2 Diabetes.
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Bódis K, Jelenik T, Lundbom J, Markgraf DF, Strom A, Zaharia OP, Karusheva Y, Burkart V, Müssig K, Kupriyanova Y, Ouni M, Wolkersdorfer M, Hwang JH, Ziegler D, Schürmann A, Roden M, and Szendroedi J
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- Age of Onset, Follow-Up Studies, Humans, Male, Middle Aged, Mitochondria metabolism, Prognosis, Prospective Studies, Subcutaneous Fat, Abdominal metabolism, Biomarkers metabolism, Diabetes Mellitus, Type 2 physiopathology, Mitochondria pathology, Subcutaneous Fat, Abdominal pathology
- Abstract
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. We assessed mitochondrial efficiency (coupling: state 3/4o; proton leak: state 4o/u) via high-resolution respirometry in superficial (SSAT) and deep (DSAT) SAT-biopsies, hepatocellular lipids (HCL) and fat mass by proton-magnetic-resonance-spectroscopy and -imaging., Results: T2D patients (known diabetes duration: 2.5 [0.1; 5.0] years) had 43%, 44%, and 63% lower muscle insulin sensitivity (IS), metabolic flexibility (P < 0.01) and AT IS (P < 0.05), 73% and 31% higher HCL (P < 0.05), and DSAT-thickness (P < 0.001), but similar hepatic IS compared with CON. Mitochondrial efficiency was ~22% lower in SSAT and DSAT of T2D patients (P < 0.001) and ~8% lower in SSAT vs DSAT (P < 0.05). In both fat depots, mitochondrial coupling correlated positively with muscle IS and metabolic flexibility (r ≥ 0.40; P < 0.05), proton leak correlated positively (r ≥ 0.51; P < 0.01) and oxidative capacity negatively (r ≤ -0.47; P < 0.05) with fasting free fatty acids (FFA). Metabolic flexibility correlated positively with SAT-oxidative capacity (r ≥ 0.48; P < 0.05) and negatively with DSAT-thickness (r = -0.48; P < 0.05). DSAT-thickness correlated negatively with mitochondrial coupling in both depots (r ≤ -0.50; P < 0.01) and muscle IS (r = -0.59; P < 0.01), positively with FFA during clamp (r = 0.63; P < 0.001) and HCL (r = 0.49; P < 0.01)., Conclusions: Impaired mitochondrial function, insulin resistance, and DSAT expansion are AT abnormalities in recent-onset T2D that might promote whole-body insulin resistance and increased substrate flux to the liver., (© Endocrine Society 2019.)
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- 2020
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17. 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.
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Karusheva Y, Koessler T, Strassburger K, Markgraf D, Mastrototaro L, Jelenik T, Simon MC, Pesta D, Zaharia OP, Bódis K, Bärenz F, Schmoll D, Wolkersdorfer M, Tura A, Pacini G, Burkart V, Müssig K, Szendroedi J, and Roden M
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- Adipose Tissue, White metabolism, Cross-Over Studies, Double-Blind Method, Female, Humans, Male, Meals, Middle Aged, Mitochondria physiology, Muscle, Skeletal metabolism, Amino Acids, Branched-Chain administration & dosage, Diabetes Mellitus, Type 2 microbiology, Gastrointestinal Microbiome, Insulin Secretion
- Abstract
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., Methods: This randomized, placebo-controlled, double-blinded, crossover trial examined well-controlled T2D patients receiving isocaloric diets (protein: 1 g/kg body weight) for 4 wk. Protein requirements were covered by commercially available food supplemented ≤60% by an AA mixture either containing all AAs or lacking BCAAs. The dietary intervention ensured sufficient BCAA supply above the recommended minimum daily intake. The patients underwent the mixed meal tolerance test (MMT), hyperinsulinemic-euglycemic clamps (HECs), and skeletal muscle and white adipose tissue biopsies to assess insulin signaling., Results: After the BCAA- diet, BCAAs were reduced by 17% during fasting (P < 0.001), by 13% during HEC (P < 0.01), and by 62% during the MMT (P < 0.001). Under clamp conditions, whole-body and hepatic insulin sensitivity did not differ between diets. After the BCAA- diet, however, the oral glucose sensitivity index was 24% (P < 0.01) and circulating fibroblast-growth factor 21 was 21% higher (P < 0.05), whereas meal-derived insulin secretion was 28% lower (P < 0.05). Adipose tissue expression of the mechanistic target of rapamycin was 13% lower, whereas the mitochondrial respiratory control ratio was 1.7-fold higher (both P < 0.05). The fecal microbiome was enriched in Bacteroidetes but depleted of Firmicutes., Conclusions: Short-term dietary reduction of BCAAs decreases postprandial insulin secretion and improves white adipose tissue metabolism and gut microbiome composition. Longer-term studies will be needed to evaluate the safety and metabolic efficacy in diabetes patients.This trial was registered at clinicaltrials.gov as NCT03261362., (Copyright © American Society for Nutrition 2019.)
- Published
- 2019
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18. A New Targeted Lipidomics Approach Reveals Lipid Droplets in Liver, Muscle and Heart as a Repository for Diacylglycerol and Ceramide Species in Non-Alcoholic Fatty Liver.
- Author
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Preuss C, Jelenik T, Bódis K, Müssig K, Burkart V, Szendroedi J, Roden M, and Markgraf DF
- Subjects
- Adult, Animals, Calibration, Disease Models, Animal, Humans, Limit of Detection, Male, Mice, Inbred C57BL, Mice, Transgenic, Ceramides metabolism, Diglycerides metabolism, Lipid Droplets metabolism, Lipid Metabolism, Liver metabolism, Muscle, Skeletal metabolism, Myocardium metabolism, Non-alcoholic Fatty Liver Disease metabolism
- Abstract
Obesity is frequently associated with excessive accumulation of lipids in ectopic tissue and presents a major risk factor for type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD). Diacylglycerols (DAGs) and ceramides (CERs) were identified as key players in lipid-induced insulin resistance, typical for such diseases. Recent results suggest that the subcellular distribution of these lipids affects their lipotoxic properties. However, the subcellular dynamics of these lipids and the role of lipid droplets (LDs) as a potential storage site is not understood. Here, we developed a liquid chromatography triple quadrupole mass spectrometry (LC-MS/MS)-method for the rapid and simultaneous quantification of DAG and CER species in tissue sample fractions. The assay is characterized by excellent recovery of analytes, limit of quantification, accuracy and precision. We established a fractionation protocol that allows the separation of subcellular tissue fractions. This method was subsequently tested to measure the concentration of DAGs and CERs in subcellular fractions of human muscle and several mouse tissues. In a mouse model of NAFLD, application of this method revealed a prominent role for LDs as repository for lipotoxic DAG and CER species. In conclusion, the new method proved as a valuable tool to analyse the subcellular dynamics of lipotoxins, related to the pathogenesis of insulin resistance, T2D and NAFLD., Competing Interests: The authors declare no conflict of interest.
- Published
- 2019
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19. Mechanosensing by β1 integrin induces angiocrine signals for liver growth and survival.
- Author
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Lorenz L, Axnick J, Buschmann T, Henning C, Urner S, Fang S, Nurmi H, Eichhorst N, Holtmeier R, Bódis K, Hwang JH, Müssig K, Eberhard D, Stypmann J, Kuss O, Roden M, Alitalo K, Häussinger D, and Lammert E
- Subjects
- Animals, Cells, Cultured, Endothelial Cells physiology, Female, Hepatocyte Growth Factor metabolism, Hepatocytes cytology, Hepatocytes physiology, Humans, Liver blood supply, Liver cytology, Male, Mice, Mice, Inbred C57BL, Middle Aged, Vascular Endothelial Growth Factor Receptor-3 metabolism, Autocrine Communication, Integrin beta1 metabolism, Liver growth & development, Liver physiology, Mechanotransduction, Cellular physiology, Signal Transduction
- Abstract
Angiocrine signals derived from endothelial cells are an important component of intercellular communication and have a key role in organ growth, regeneration and disease
1-4 . These signals have been identified and studied in multiple organs, including the liver, pancreas, lung, heart, bone, bone marrow, central nervous system, retina and some cancers1-4 . Here we use the developing liver as a model organ to study angiocrine signals5,6 , and show that the growth rate of the liver correlates both spatially and temporally with blood perfusion to this organ. By manipulating blood flow through the liver vasculature, we demonstrate that vessel perfusion activates β1 integrin and vascular endothelial growth factor receptor 3 (VEGFR3). Notably, both β1 integrin and VEGFR3 are strictly required for normal production of hepatocyte growth factor, survival of hepatocytes and liver growth. Ex vivo perfusion of adult mouse liver and in vitro mechanical stretching of human hepatic endothelial cells illustrate that mechanotransduction alone is sufficient to turn on angiocrine signals. When the endothelial cells are mechanically stretched, angiocrine signals trigger in vitro proliferation and survival of primary human hepatocytes. Our findings uncover a signalling pathway in vascular endothelial cells that translates blood perfusion and mechanotransduction into organ growth and maintenance.- Published
- 2018
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20. Reduced expression of stearoyl-CoA desaturase-1, but not free fatty acid receptor 2 or 4 in subcutaneous adipose tissue of patients with newly diagnosed type 2 diabetes mellitus.
- Author
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Bódis K, Kahl S, Simon MC, Zhou Z, Sell H, Knebel B, Tura A, Strassburger K, Burkart V, Müssig K, Markgraf D, Al-Hasani H, Szendroedi J, and Roden M
- Subjects
- Adult, Cross-Sectional Studies, Diabetes Mellitus, Type 2 diagnosis, Female, Humans, Insulin Resistance physiology, Male, Middle Aged, Diabetes Mellitus, Type 2 metabolism, Receptors, Cell Surface metabolism, Receptors, G-Protein-Coupled metabolism, Stearoyl-CoA Desaturase metabolism, Subcutaneous Fat metabolism
- Abstract
Background: In subcutaneous adipose tissue (SAT), higher stearoyl-CoA desaturase-1 (SCD1) expression has been related to improved insulin sensitivity in thiazolidinedione-treated type 2 diabetes mellitus patients. In animal models, deficiency of the free fatty acid receptor (FFAR) 2 associated with higher and FFAR4-deficiency with lower insulin sensitivity. We hypothesized that increased FFAR2 expression and reductions in FFAR4 and SCD1 expression in SAT of type 2 diabetes mellitus patients associate positively with insulin resistance and impaired beta cell function., Methods: Twenty-five type 2 diabetes mellitus patients and 25 glucose-tolerant humans (CON) matched for sex, age, and BMI underwent mixed-meal tests to assess insulin sensitivity (OGIS) and beta cell function (ΔAUC(C-peptide)
0-180 min /ΔAUC(glucose)0-180 min ) in a cross-sectional study. Gene and protein expression of SCD1 and FFAR2/4 were quantified in SAT biopsies., Results: Insulin sensitivity was 14% and beta cell function 71% (both p < 0.001) lower in type 2 diabetes mellitus patients. In type 2 diabetes mellitus, SCD1 mRNA was fivefold (p < 0.001) and protein expression twofold (p < 0.01) lower. While FFAR2/4 mRNA and protein expression did not differ between groups, FFAR2 protein levels correlated negatively with beta cell function only in CON (r = -0.74, p < 0.01). However, neither SCD1 nor FFAR2/4 protein expression correlated with insulin sensitivity in both groups., Conclusions: Type 2 diabetes patients have lower SCD1, which does not associate with insulin resistance. Only in non-diabetic humans, FFAR2 associated with impaired beta cell function.- Published
- 2018
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21. Association of Lower Cardiovagal Tone and Baroreflex Sensitivity With Higher Liver Fat Content Early in Type 2 Diabetes.
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Ziegler D, Strom A, Kupriyanova Y, Bierwagen A, Bönhof GJ, Bódis K, Müssig K, Szendroedi J, Bobrov P, Markgraf DF, Hwang JH, and Roden M
- Subjects
- Autonomic Nervous System Diseases etiology, Case-Control Studies, Cross-Sectional Studies, Diabetes Mellitus, Type 1 complications, Diabetes Mellitus, Type 1 pathology, Diabetes Mellitus, Type 1 physiopathology, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 pathology, Female, Glucose Clamp Technique, Humans, Liver pathology, Magnetic Resonance Spectroscopy, Male, Autonomic Nervous System physiopathology, Baroreflex physiology, Diabetes Mellitus, Type 2 physiopathology, Fatty Liver etiology, Heart Rate physiology
- Abstract
Context: Cardiovascular autonomic neuropathy (CAN) diagnosed by diminished heart rate variability (HRV) is prevalent and carries an increased risk of mortality in patients with diabetes and chronic liver diseases., Objective: To determine whether lower HRV is associated with increased liver fat content in recent-onset diabetes., Design: Cross-sectional study., Setting: German Diabetes Study (GDS), Düsseldorf, Germany., Participants: Individuals with type 1 diabetes (n = 97) or type 2 diabetes (n = 109) with known diabetes duration ≤1 year and two age- and sex-matched glucose-tolerant control groups from the GDS baseline cohort., Main Outcome Measures: Four time and frequency domain HRV indices each were measured over 3 hours during a hyperinsulinemic-euglycemic clamp, whereas spontaneous cross-correlation baroreflex sensitivity (xBRS) was computed over 5 minutes. Hepatic fat content was determined by 1H magnetic resonance spectroscopy, and values >5.56% were defined as hepatic steatosis., Results: Hepatic steatosis was observed in 52% and 5% of patients with type 2 and type 1 diabetes, respectively. After adjustment for sex, age, body mass index, smoking, diabetes duration, hemoglobin A1c, M-value, and triglycerides, all four vagus-mediated time domain HRV indices, three of four frequency domain indices, and xBRS were inversely associated with liver fat content in participants with type 2 diabetes (all P < 0.05) but not in the group with type 1 diabetes., Conclusions: Both lower cardiovagal tone and baroreflex sensitivity are strongly associated with prevalent hepatic steatosis in patients with recent-onset type 2 as opposed to type 1 diabetes, suggesting a role for hepatic steatosis in the early development of parasympathetic CAN in type 2 diabetes.
- Published
- 2018
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22. Metabolic Characteristics of Recently Diagnosed Adult-Onset Autoimmune Diabetes Mellitus.
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Zaharia OP, Bobrov P, Strassburger K, Bódis K, Karusheva Y, Scholz M, Markgraf DF, Burkart V, Schloot NC, Müssig K, Szendroedi J, and Roden M
- Subjects
- Adult, Age of Onset, Autoantibodies blood, Case-Control Studies, Diabetes Mellitus, Type 1 blood, Diabetes Mellitus, Type 1 diagnosis, Diabetes Mellitus, Type 2 diagnosis, Diagnostic Errors, Female, Humans, Insulin metabolism, Insulin Resistance, Insulin Secretion, Islets of Langerhans physiopathology, Male, Middle Aged, Diabetes Mellitus, Type 1 epidemiology, Diabetes Mellitus, Type 1 metabolism
- Abstract
Context and Objective: Among patients diagnosed with type 2 diabetes, autoimmune diabetes often remains undetected. Metabolic features of these patients are insufficiently characterized at present., Design, Setting, and Patients: This study compared age- and sex-matched adult (aged 41 to 62 years) humans with recent-onset diabetes: patients positive for antibodies against glutamic acid decarboxylase (GAD) and/or cytoplasmic islet-cell antigen with an insulin-free period of >6 months [antibody positive/insulin negative (ab+/ins-); previously termed latent autoimmune diabetes of adults], type 1 diabetes [antibody positive/insulin positive (ab+/ins+)], and type 2 diabetes [antibody negative/insulin negative (ab-/ins-)], as well as glucose-tolerant humans (controls) of the German Diabetes Study (n = 41/group). β-Cell function was assessed from glucagon tests and intravenous glucose tolerance tests (IVGTTs), and insulin sensitivity was determined from hyperinsulinemic-euglycemic clamps., Results: Of the ab+/ins- patients, 33 (81%) were initially diagnosed as having type 2 diabetes. In ab+/ins-, body mass index (BMI) was higher than in ab+/ins+ (27.8 ± 5.3 kg/m2 vs 25.0 ± 3.5 kg/m2, P < 0.05), lower than in ab-/ins- (31.9 ± 5.8 kg/m2, P < 0.05), and similar to controls (29.4 ± 6.6 kg/m2). In ab+/ins-, GAD antibody titers correlated negatively with BMI (r = -0.40, P < 0.05) and with C-peptide secretion in glucagon stimulation tests (r = -0.33, P < 0.05). β-Cell function from IVGTT was 228% higher in ab+/ins- than in ab+/ins+ but 35% lower than in ab-/ins- and 61% lower than in controls (all P < 0.05). Insulin sensitivity in ab+/ins- was comparable to ab+/ins+ and controls but 41% higher than in ab-/ins- (P < 0.05) after adjustment for BMI and fasting blood glucose or hemoglobin A1c., Conclusion: Even shortly after diagnosis, ab+/ins- patients feature partly preserved β-cell function and chronic hyperglycemia, which possibly contributes to the observed impairment of whole-body insulin sensitivity., (Copyright © 2017 Endocrine Society)
- Published
- 2018
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23. Patterns of cutaneous nerve fibre loss and regeneration in type 2 diabetes with painful and painless polyneuropathy.
- Author
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Bönhof GJ, Strom A, Püttgen S, Ringel B, Brüggemann J, Bódis K, Müssig K, Szendroedi J, Roden M, and Ziegler D
- Subjects
- Adult, Aged, Cross-Sectional Studies, Female, Humans, Male, Middle Aged, Diabetes Mellitus, Type 2 pathology, Diabetic Neuropathies pathology, Nerve Fibers pathology, Skin innervation, Skin pathology
- Abstract
Aims/hypothesis: The determinants and mechanisms of the development of diabetic sensorimotor polyneuropathy as a painful (DSPN+p) or painless (DSPN-p) entity remain unclear. We examined the degree of cutaneous nerve fibre loss and regeneration in individuals with type 2 diabetes with DSPN+p or DSPN-p compared with individuals with recent-onset type 2 diabetes and corresponding healthy volunteers., Methods: In this cross-sectional study, skin biopsies taken from the distal lateral calf were obtained from individuals with recent-onset type 2 diabetes (n = 32) from the German Diabetes Study, with DSPN+p (n = 34) and DSPN-p (n = 32) from the PROPANE study, and volunteers with normal glucose tolerance (n = 50). Double immunofluorescence staining for protein gene product 9.5 (PGP9.5) (pan-neuronal marker) and growth-associated protein 43 (GAP-43) (nerve regeneration marker) was applied to assess intraepidermal nerve fibre density (IENFD) and length (IENFL) and dermal nerve fibre length (DNFL). DSPN was diagnosed using the modified Toronto Consensus (2011) criteria, while neuropathic pain was assessed using an 11-point Numerical Rating Scale., Results: After adjustment for age, sex, BMI and HbA
1c , IENFD and IENFL were reduced for both markers in individuals with recent-onset diabetes and both DSPN groups compared with control participants (all p < 0.05), but did not differ between the DSPN groups. The DNFL GAP-43/PGP9.5 ratio was higher in the DSPN+p and DSPN-p groups compared with control participants (1.18 ± 0.28 and 1.07 ± 0.10 vs 1.02 ± 0.10; p ≤ 0.05) and in the DSPN + p group compared with DSPN-p (p < 0.05). Correlation analyses showed distinct inverse associations between the DNFL GAP-43/PGP9.5 ratio and PGP9.5 positive IENFD as well as DNFL (IENFD: β = -0.569, DNFL: β = -0.639; both p < 0.0001) in individuals with type 2 diabetes, but not in the control group. A similar pattern was found for correlations between the DNFL GAP-43/PGP9.5 ratio and peripheral nerve function tests., Conclusions/interpretation: Dermal nerve fibre regeneration is enhanced in DSPN, particularly in DSPN+p, and increases with advancing intraepidermal nerve fibre loss. These data suggest that, despite progressive epidermal fibre loss, dermal nerve repair is preserved, particularly in DSPN+p, but fails to adequately counteract epidermal neurodegenerative processes.- Published
- 2017
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24. Differential Patterns of Impaired Cardiorespiratory Fitness and Cardiac Autonomic Dysfunction in Recently Diagnosed Type 1 and Type 2 Diabetes.
- Author
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Röhling M, Strom A, Bönhof G, Püttgen S, Bódis K, Müssig K, Szendrödi J, Markgraf D, Lehr S, Roden M, and Ziegler D
- Subjects
- Adolescent, Adult, Aged, Autonomic Nervous System Diseases complications, Creatinine blood, Cross-Sectional Studies, Diabetes Mellitus, Type 1 complications, Diabetes Mellitus, Type 2 complications, Electric Impedance, Female, Germany, Glycated Hemoglobin, Heart Diseases complications, Heart Rate, Humans, Insulin Resistance, Male, Middle Aged, Prospective Studies, Young Adult, Autonomic Nervous System physiopathology, Autonomic Nervous System Diseases diagnosis, Cardiorespiratory Fitness, Diabetes Mellitus, Type 1 diagnosis, Diabetes Mellitus, Type 2 diagnosis, Heart Diseases diagnosis
- Abstract
Objective: Both impaired cardiorespiratory fitness (CRF) and heart rate variability (HRV) are predictors of mortality, but their relative roles in recent-onset diabetes are unknown. We determined to which extent CRF and HRV are reduced and interrelated in recent-onset diabetes., Research Design and Methods: Participants from the German Diabetes Study with type 1 (n = 163) or type 2 (n = 188) diabetes with known diabetes duration <1 year and two age-matched glucose-tolerant control groups (n = 40 each) underwent spiroergometry and HRV assessment during a hyperinsulinemic-euglycemic clamp., Results: Compared with control subjects, patients with type 2 diabetes showed reduced VO
2max (median [1st-3rd quartiles] 19.3 [16.5-22.9] vs. 25.6 [20.7-29.9] mL/kg body weight/min; P < 0.05), diminished VCO2max (23.0 [19.1-26.8] vs. 30.9 [24.5-34.4] mL/kg body weight/min; P < 0.05), blunted heart rate recovery after 2 min (-29.0 [-35.0 to -23.0] vs. -36.0 [-42.8 to -28.0] beats/min; P < 0.05), and reduced HRV in four of nine indices, whereas patients with type 1 diabetes had unaltered CRF but reduced HRV in three of nine indices (P < 0.05), indicating diminished vagal and sympathetic HRV modulation. HRV measures correlated with VO2max in patients with type 1 diabetes (r >0.34; P < 0.05) but not in those with type 2 diabetes., Conclusions: CRF is reduced in recently diagnosed type 2 diabetes but preserved in type 1 diabetes, whereas cardiac autonomic function is reduced in both diabetes types but is strongly associated with CRF only in type 1 diabetes. These results support the therapeutic concept of promoting physical fitness in the early course of diabetes., (© 2017 by the American Diabetes Association.)- Published
- 2017
- Full Text
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