@article{BirukovPolemitiJaegeretal.2022, author = {Birukov, Anna and Polemiti, Elli and Jaeger, Susanne and Stefan, Norbert and Schulze, Matthias B.}, title = {Fetuin-A and risk of diabetes-related vascular complications}, series = {Cardiovascular diabetology}, volume = {21}, journal = {Cardiovascular diabetology}, number = {1}, publisher = {BMC}, address = {London}, issn = {1475-2840}, doi = {10.1186/s12933-021-01439-8}, pages = {11}, year = {2022}, abstract = {Background Fetuin-A is a hepatokine which has the capacity to prevent vascular calcification. Moreover, it is linked to the induction of metabolic dysfunction, insulin resistance and associated with increased risk of diabetes. It has not been clarified whether fetuin-A associates with risk of vascular, specifically microvascular, complications in patients with diabetes. We aimed to investigate whether pre-diagnostic plasma fetuin-A is associated with risk of complications once diabetes develops. Methods Participants with incident type 2 diabetes and free of micro- and macrovascular disease from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort (n = 587) were followed for microvascular and macrovascular complications (n = 203 and n = 60, respectively, median follow-up: 13 years). Plasma fetuin-A was measured approximately 4 years prior to diabetes diagnosis. Prospective associations between baseline fetuin-A and risk of complications were assessed with Cox regression. Results In multivariable models, fetuin-A was linearly inversely associated with incident total and microvascular complications, hazard ratio (HR, 95\% CI) per standard deviation (SD) increase: 0.86 (0.74; 0.99) for total, 0.84 (0.71; 0.98) for microvascular and 0.92 (0.68; 1.24) for macrovascular complications. After additional adjustment for cardiometabolic plasma biomarkers, including triglycerides and high-density lipoprotein, the associations were slightly attenuated: 0.88 (0.75; 1.02) for total, 0.85 (0.72; 1.01) for microvascular and 0.95 (0.67; 1.34) for macrovascular complications. No interaction by sex could be observed (p > 0.10 for all endpoints). Conclusions Our data show that lower plasma fetuin-A levels measured prior to the diagnosis of diabetes may be etiologically implicated in the development of diabetes-associated microvascular disease.}, language = {en} } @article{SeidelJacobsKohlTamayoetal.2022, author = {Seidel-Jacobs, Esther and Kohl, Fiona and Tamayo, Miguel and Rosenbauer, Joachim and Schulze, Matthias Bernd and Kuss, Oliver and Rathmann, Wolfgang}, title = {Impact of applying a diabetes risk score in primary care on change in physical activity}, series = {Acta diabetologica}, volume = {59}, journal = {Acta diabetologica}, number = {8}, publisher = {Springer}, address = {Mailand}, issn = {0940-5429}, doi = {10.1007/s00592-022-01895-y}, pages = {1031 -- 1040}, year = {2022}, abstract = {Aim There is little evidence of the impact of diabetes risk scores on individual diabetes risk factors, motivation for behaviour changes and mental health. The aim of this study was to investigate the effect of applying a noninvasive diabetes risk score in primary care as component of routine health checks on physical activity and secondary outcomes. Methods Cluster randomised trial, in which primary care physicians (PCPs), randomised (1:1) by minimisation, enrolled participants with statutory health insurance without known diabetes, >= 35 years of age with a body mass index >= 27.0 kg/m(2). The German Diabetes Risk Score was applied as add-on to the standard routine health check, conducted in the controls. Primary outcome was the difference in participants' physical activity (International Physical Activity Questionnaire) after 12 months. Secondary outcomes included body mass index, perceived health, anxiety, depression, and motivation for lifestyle change. Analysis was by intention-to-treat principle using mixed models. Results 36 PCPs were randomised; remaining 30 PCPs (intervention: n = 16; control: n = 14) recruited 315 participants (intervention: n = 153; controls: n = 162). A slight increase in physical activity was observed in the intervention group with an adjusted mean change of 388 (95\% confidence interval: - 235; 1011) metabolic equivalents minutes per week. There were no relevant changes in secondary outcomes. Conclusions The application of a noninvasive diabetes risk score alone is not effective in promoting physical activity in primary care. Clinical Trial Registration: ClinicalTrials.gov (NCT03234322, registration date: July 31, 2017).}, language = {en} } @article{WiggerSchumacherSchneiderSchauliesetal.2021, author = {Wigger, Dominik and Schumacher, Fabian and Schneider-Schaulies, Sibylle and Kleuser, Burkhard}, title = {Sphingosine 1-phosphate metabolism and insulin signaling}, series = {Cellular signalling}, volume = {82}, journal = {Cellular signalling}, publisher = {Elsevier Science}, address = {Amsterdam [u.a.]}, issn = {0898-6568}, doi = {10.1016/j.cellsig.2021.109959}, pages = {16}, year = {2021}, abstract = {Insulin is the main anabolic hormone secreted by 13-cells of the pancreas stimulating the assimilation and storage of glucose in muscle and fat cells. It modulates the postprandial balance of carbohydrates, lipids and proteins via enhancing lipogenesis, glycogen and protein synthesis and suppressing glucose generation and its release from the liver. Resistance to insulin is a severe metabolic disorder related to a diminished response of peripheral tissues to the insulin action and signaling. This leads to a disturbed glucose homeostasis that precedes the onset of type 2 diabetes (T2D), a disease reaching epidemic proportions. A large number of studies reported an association between elevated circulating fatty acids and the development of insulin resistance. The increased fatty acid lipid flux results in the accumulation of lipid droplets in a variety of tissues. However, lipid intermediates such as diacylglycerols and ceramides are also formed in response to elevated fatty acid levels. These bioactive lipids have been associated with the pathogenesis of insulin resistance. More recently, sphingosine 1-phosphate (S1P), another bioactive sphingolipid derivative, has also been shown to increase in T2D and obesity. Although many studies propose a protective role of S1P metabolism on insulin signaling in peripheral tissues, other studies suggest a causal role of S1P on insulin resistance. In this review, we critically summarize the current state of knowledge of S1P metabolism and its modulating role on insulin resistance. A particular emphasis is placed on S1P and insulin signaling in hepatocytes, skeletal muscle cells, adipocytes and pancreatic 13-cells. In particular, modulation of receptors and enzymes that regulate S1P metabolism can be considered as a new therapeutic option for the treatment of insulin resistance and T2D.}, language = {en} } @article{SchibornSchulze2020, author = {Schiborn, Catarina and Schulze, Matthias Bernd}, title = {Diabetes risk scores}, series = {Der Diabetologe}, volume = {16}, journal = {Der Diabetologe}, number = {3}, publisher = {Springer}, address = {Heidelberg}, issn = {1860-9716}, doi = {10.1007/s11428-020-00592-0}, pages = {226 -- 233}, year = {2020}, abstract = {Risk scores are used to identify high-risk individuals for type 2 diabetes (T2DM) who benefit from preventive measures. The DIfE-DEUTSCHER DIABETES-RISIKO-TEST (R) (DRT) is used to determine the absolute 5-year risk for T2DM. Since the calculation is based on non-clinical information, the test can be used independently of a doctor's visit. Data from prospective population-based long-term studies serve as the basis for the development of risk scores. As in the case of the DRT, the very good predictive quality of a score should be confirmed in independent populations. In addition to the use by doctors and for individual self-anamnesis, non-clinical risk scores can be used in the context of broader, population-based prevention concepts and information offers to reduce the risk of disease. Prevention services billable by health insurance companies should support the integration of health-promoting behavior into everyday life within the meaning of the German Prevention Act. Although obesity and diet are relevant lifestyle risk factors for T2DM, the proportion of preventive courses taken on this topic is only 3\% of the courses billed. Appropriate recommendations in medical examinations could promote more extensive use. The use of risk scores as the basis for systematic and targeted recommendations for behavioral prevention could also support this, as is already established in guidelines for cardiovascular prevention. The further development of implementation research is also important for the efficient use of risk scores.}, language = {de} } @article{KwanbunjanPanprathipPhosatetal.2018, author = {Kwanbunjan, Karunee and Panprathip, Pornpimol and Phosat, Chanchira and Chumpathat, Noppanath and Wechjakwen, Naruemon and Puduang, Somchai and Auyyuenyong, Ratchada and Henkel, Ina and Schweigert, Florian J.}, title = {Association of retinol binding protein 4 and transthyretin with triglyceride levels and insulin resistance in rural thais with high type 2 diabetes risk}, series = {BMC Endocrine Disorders}, volume = {18}, journal = {BMC Endocrine Disorders}, publisher = {BMC}, address = {London}, issn = {1472-6823}, doi = {10.1186/s12902-018-0254-2}, pages = {7}, year = {2018}, abstract = {Background: Retinol binding protein 4 (RBP4), a protein secreted by adipocytes and bound in plasma to transthyretin (TTR), has been associated with obesity, the early phase of insulin resistance, metabolic syndrome, and type 2 diabetes mellitus. The objective of this study was to elucidate the relationship between RBP4, TTR, triglyceride (TG) and type 2 diabetes risk in rural Thailand. Results: RBP4 and TTR levels, as well as homeostatic model assessment of insulin resistance (HOMA-IR) values, were significantly elevated among subjects with high triglyceride levels (p < 0.01, p < 0.05, p < 0.05, respectively). Triglyceride levels correlated with RBP4 (r = 0.34, p < 0.001) and TTR (r= 0.26, p < 0.01) levels, as well as HOMA-IR values (r= 0.16, p < 0.05). After adjustment for age and gender, the risk of hypertriglyceridemia was 3.7 times greater (95\% Cl =1.42 -9.73, p = 0.008) in the highest RBP4 tertile as compared to the lowest tertile. Similarly, the highest TTR and HOMA-IR tertiles had greater risk of hypertriglyceridemia at 3.5 (95\% Cl = 1.30-9.20, p = 0.01) and 3.6 (95\% CI = 1.33- 9.58, p = 0.01) times higher than the respective lowest tertiles. The correlation between TTR and blood glucose was statistically significant (r 0.18, p < 0.05), but not found this relationship in RBP4. Conclusions: The associations of RBP4 and TTR with hypertriglyceridemia and insulin resistance may have important implications for the risk of heart disease and stroke.}, language = {en} } @article{SaussenthalerOuniBaumeieretal.2019, author = {Saussenthaler, Sophie and Ouni, Meriem and Baumeier, Christian and Schwerbel, Kristin and Gottmann, Pascal and Christmann, Sabrina and Laeger, Thomas and Sch{\"u}rmann, Annette}, title = {Epigenetic regulation of hepatic Dpp4 expression in response to dietary protein}, series = {The journal of nutritional biochemistry}, volume = {63}, journal = {The journal of nutritional biochemistry}, publisher = {Elsevier}, address = {New York}, issn = {0955-2863}, doi = {10.1016/j.jnutbio.2018.09.025}, pages = {109 -- 116}, year = {2019}, abstract = {Dipeptidyl peptidase 4 (DPP4) is known to be elevated in metabolic disturbances such as obesity, type 2 diabetes and fatty liver disease. Lowering DPP4 concentration by pharmacological inhibition improves glucose homeostasis and exhibits beneficial effects to reduce hepatic fat content. As factors regulating the endogenous expression of Dpp4 are unknown, the aim of this study was to examine whether the Dpp4 expression is epigenetically regulated in response to dietary components. Primary hepatocytes were treated with different macronutrients, and Dpp4 mRNA levels and DPP4 activity were evaluated. Moreover, dietary low-protein intervention was conducted in New Zealand obese (NZO) mice, and subsequently, effects on Dpp4 expression, methylation as well as plasma concentration and activity were determined. Our results indicate that Dpp4 mRNA expression is mediated by DNA methylation in several tissues. We therefore consider the Dpp4 southern shore as tissue differentially methylated region. Amino acids increased Dpp4 expression in primary hepatocytes, whereas glucose and fatty acids were without effect. Dietary protein restriction in NZO mice increased Dpp4 DNA methylation in liver leading to diminished Dpp4 expression and consequently to lowered plasma DPP4 activity. We conclude that protein restriction in the adolescent and adult states is a sufficient strategy to reduce DPP4 which in turn contributes to improve glucose homeostasis. (C) 2018 Published by Elsevier Inc.}, language = {en} }