TY  - JOUR
AB  - Research on rare tumors heavily relies on suitable models for basic and translational research. Paragangliomas (PPGL) are rare neuroendocrine tumors (NET), developing from adrenal (pheochromocytoma, PCC) or extra-adrenal (PGL) chromaffin cells, with an annual incidence of 2-8 cases per million. While most PPGL cases exhibit slow growth and are primarily treated with surgery, limited systemic treatment options are available for unresectable or metastatic tumors. Scarcity of appropriate models has hindered PPGL research, preventing the translation of omics knowledge into drug and therapy development. Human PPGL cell lines are not available, and few animal models accurately replicate the disease's genetic and phenotypic characteristics. This review provides an overview of laboratory models for PPGLs, spanning cellular, tissue, organ, and organism levels. We discuss their features, advantages, and potential contributions to diagnostics and therapeutics. Interestingly, it appears that in the PPGL field, disease models already successfully implemented in other cancers have not been fully explored.
AU  - Karna, B.
AU  - Pellegata, N.S.
AU  - Mohr, H.
C1  - 69009
C2  - 55186
CY  - Rudigerstr 14, D-70469 Stuttgart, Germany
SP  - 51-64
TI  - Animal and cell culture models of PPGLs - Achievements and limitations.
JO  - Horm. Metab. Res.
VL  - 56
IS  - 1
PB  - Georg Thieme Verlag Kg
PY  - 2024
SN  - 0018-5043
ER  - 

TY  - JOUR
AB  - Intraportal islet transplantation in patients with type 1 diabetes enables restoration of glucose-regulated insulin secretion. However, several factors hamper a widespread application and long-term success: chronic hypoxia, an inappropriate microenvironment and suppression of regenerative and proliferative potential by high local levels of immunosuppressive agents. Therefore, the identification of alternative and superior transplant sites is of major scientific and clinical interest. Here, we aim to evaluate the adrenal as an alternative transplantation site. The adrenal features a particular microenvironment with extensive vascularization, anti-apoptotic and pro-proliferative, anti-inflammatory and immunosuppressive effects. To validate this novel transplantation site, an in vitro co-culture system of adrenal cells and pancreatic islets was established and viability, islet survival, functional potency and antioxidative defense capacity were evaluated. For in vivo validation, an immune-deficient diabetic mouse model for intra-adrenal islet transplantation was applied. The functional capacity of intra-adrenally grafted islets to reverse diabetes was compared to a standard islet transplant model and measures of engraftment such as vascular integration were evaluated. The presence of adrenal cells positively impacted on cell metabolism and oxidative stress. Following transplantation, we could demonstrate enhanced islet function in comparison to standard models with improved engraftment and superior re-vascularization. This experimental approach allows for novel insights into the interaction of endocrine systems and may open up novel strategies for islet transplantation augmented through the bystander effect of other endocrine cells or the active factors secreted by adrenal cells modulating the microenvironment.
AU  - Schubert, U.
AU  - Lehmann, S.
AU  - Schmid, J.
AU  - Morawietz, H.*
AU  - Bornstein, S.R.
AU  - Ludwig, B.
C1  - 70261
C2  - 55474
CY  - Rudigerstr 14, D-70469 Stuttgart, Germany
SP  - 286-293
TI  - The adrenal gland and pancreatic islets - a beneficial endocrine alliance.
JO  - Horm. Metab. Res.
VL  - 56
IS  - 4
PB  - Georg Thieme Verlag Kg
PY  - 2024
SN  - 0018-5043
ER  - 

TY  - JOUR
AB  - Ferroptosis was recently identified as a non-apoptotic, iron-dependent cell death mechanism that is involved in various pathologic conditions. There is first evidence for its significance also in the context of islet isolation and transplantation. Transplantation of pancreatic human islets is a viable treatment strategy for patients with complicated diabetes mellitus type 1 (T1D) that suffer from severe hypoglycemia. A major determinant for functional outcome is the initial islet mass transplanted. Efficient islet isolation procedures and measures to minimize islet loss are therefore of high relevance. To this end, better understanding and subsequent targeted inhibition of cell death during islet isolation and transplantation is an effective approach. In this study, we aimed to elucidate the mechanism of ferroptosis in pancreatic islets. Using a rodent model, isolated islets were characterized relating to the effects of experimental induction (RSL3) and inhibition (Fer1) of ferroptotic pathways. Besides viability, survival, and function, the study focused on characteristic ferroptosis-associated intracellular changes such as MDA level, iron concentration and the expression of ACSL4. The study demonstrates that pharmaceutical induction of ferroptosis by RSL3 causes enhancement of oxidative stress and leads to an increase of intracellular iron, zinc and MDA concentration, as well as the expression of ACSL4 protein. Consequently, a massive reduction of islet function, viability, and survival was found. Fer1 has the potential to inhibit and attenuate these cellular changes and thereby protect the islets from cell death.
AU  - Schepp, F.*
AU  - Schubert, U.
AU  - Schmid, J.
AU  - Lehmann, S.
AU  - Latunde-Dada, G.O.*
AU  - Kose, T.*
AU  - Steenblock, C.*
AU  - Bornstein, S.R.
AU  - Linkermann, A.*
AU  - Ludwig, B.
C1  - 68750
C2  - 54960
CY  - Rudigerstr 14, D-70469 Stuttgart, Germany
TI  - Mechanistic insights into ferroptotic cell death in pancreatic islets.
JO  - Horm. Metab. Res.
PB  - Georg Thieme Verlag Kg
PY  - 2023
SN  - 0018-5043
ER  - 

TY  - JOUR
AB  - Coronavirus disease 2019 (COVID-19) is characterized by a wide clinical spectrum that includes abnormalities in liver function indicative of liver damage. Conversely, people with liver diseases are at higher risk of severe COVID-19. In the current review, we summarize first the epidemiologic evidence describing the bidirectional relationship between COVID-19 and liver function/liver diseases. Additionally, we present the most frequent histologic findings as well as the most important direct and indirect mechanisms supporting a COVID-19 mediated liver injury. Furthermore, we focus on the most frequent liver disease in the general population, non-alcoholic or metabolic-associated fatty liver disease (NAFLD/MAFLD), and describe how COVID-19 may affect NAFLD/MAFLD development and progression and conversely how NAFLD/MAFLD may further aggravate a COVID-19 infection. Finally, we present the long-term consequences of the pandemic on the development and management of NAFLD.
AU  - Hoffmann, C.*
AU  - Gerber, P.A.*
AU  - Cavelti-Weder, C.*
AU  - Licht, L.*
AU  - Kotb, R.*
AU  - Al Dweik, R.*
AU  - Cherfane, M.*
AU  - Bornstein, S.R.*
AU  - Perakakis, N.
C1  - 64864
C2  - 52525
SP  - 522-531
TI  - Liver, NAFLD and COVID-19.
JO  - Horm. Metab. Res.
VL  - 54
IS  - 8
PY  - 2022
SN  - 0018-5043
ER  - 

TY  - JOUR
AB  - Recently, we proposed two pathophysiologic subtypes of type 2 diabetes mellitus (T2DM), one related and one unrelated to metabolic syndrome. To begin to understand the pathophysiology of the subtype unrelated to metabolic syndrome, we now measured selected hormones and signaling molecules in affected individuals. In this cross-sectional analysis, we examined 138 women out of the monocenter, post gestational diabetes study PPSDiab. Of these women, 73 had prediabetes or screening-diagnosed T2DM, 40 related to metabolic syndrome and 33 unrelated. The remaining 65 women were normoglycemic controls. Our analysis included medical history, anthropometrics, oral glucose tolerance testing, laboratory chemistry, and cardiopulmonary exercise testing. In addition, plasma proinsulin/insulin ratio, growth hormone (hGH) nadir during oral glucose tolerance testing, Insulin-like Growth Factor I (IGF-I), Leptin, Resistin, Adiponectin, Fetuin-a, FGF21, and myostatin were measured. Compared to controls, women with prediabetes or screening-diagnosed T2DM unrelated to metabolic syndrome depicted higher plasma Leptin [10.47(6.6-14.57) vs. 5.52(3.15-10.02); p<0.0001] and IGF-I [193.01(171.00 - 213.30) vs. 167.97(138.77- 200.64); p=0.0008], as well as a lower hGH nadir [0.07(0.05-0.15) vs. 0.14(0.08-0.22; p<0.0001]. These differences were independent of body adiposity. Women with prediabetes or T2DM related to metabolic syndrome, in comparison to controls, displayed elevated Leptin, Fetuin-a, and FGF21, as well as reduced Adiponectin and hGH nadir. Based on our study, altered Leptin and hGH/IGF-I signaling could potentially contribute to the pathophysiology of prediabetes and T2DM unrelated to metabolic syndrome. Further mechanistic investigations of these signaling pathways in the context of lean T2DM are necessary to test causal relationships.
AU  - Kern-Matschilles, S.
AU  - Gar, C.
AU  - Schilbach, K.*
AU  - Haschka, S.J.
AU  - Rauch, B.
AU  - Then, C.
AU  - Seissler, J.
AU  - Bidlingmaier, M.*
AU  - Lechner, A.
C1  - 65000
C2  - 52611
SP  - 613-619
TI  - Altered circulating leptin, hGH, and IGF-I in prediabetes and screening-diagnosed T2DM unrelated to metabolic syndrome in women post gestational diabetes.
JO  - Horm. Metab. Res.
VL  - 54
IS  - 9
PY  - 2022
SN  - 0018-5043
ER  - 

TY  - JOUR
AB  - The COVID-19 Pandemic has led to a world health crisis with major socioeconomic consequences that have deeply affected our daily lives. Until the end of May 2022, more than 500 million people have been infected by COVID-19 and more than 6 million have died from the disease. Unprecedented efforts in research, illustrated by the more than 250 000 publications in PubMed, have led to the identification of important pathophysiological mechanisms affected by SARS-CoV-2 and have resulted in the development of effective vaccines and treatment protocols for patients with COVID-19.
AU  - Perakakis, N.
AU  - Barthel, A.*
AU  - Bornstein, S.R.*
C1  - 65903
C2  - 52972
SP  - 494-495
TI  - The role of endocrine and metabolic system in COVID-19 disease - the transcampus experience and review of evidence from international collaborating groups.
JO  - Horm. Metab. Res.
VL  - 54
IS  - 8
PY  - 2022
SN  - 0018-5043
ER  - 

TY  - JOUR
AB  - Currently, we are experiencing a true pandemic of a communicable disease by the virus SARS-CoV-2 holding the whole world firmly in its grasp. Amazingly and unfortunately, this virus uses a metabolic and endocrine pathway via ACE2 to enter our cells causing damage and disease. Our international research training programme funded by the German Research Foundation has a clear mission to train the best students wherever they may come from to learn to tackle the enormous challenges of diabetes and its complications for our society. A modern training programme in diabetes and metabolism does not only involve a thorough understanding of classical physiology, biology and clinical diabetology but has to bring together an interdisciplinary team. With the arrival of the coronavirus pandemic, this prestigious and unique metabolic training programme is facing new challenges but also new opportunities. The consortium of the training programme has recognized early on the need for a guidance and for practical recommendations to cope with the COVID-19 pandemic for the community of patients with metabolic disease, obesity and diabetes. This involves the optimal management from surgical obesity programmes to medications and insulin replacement. We also established a global registry analyzing the dimension and role of metabolic disease including new onset diabetes potentially triggered by the virus. We have involved experts of infectious disease and virology to our faculty with this metabolic training programme to offer the full breadth and scope of expertise needed to meet these scientific challenges. We have all learned that this pandemic does not respect or heed any national borders and that we have to work together as a global community. We believe that this transCampus metabolic training programme provides a prime example how an international team of established experts in the field of metabolism can work together with students from all over the world to address a new pandemic.
AU  - Bornstein, S.R.
AU  - Guan, K.*
AU  - Brunßen, C.*
AU  - Mueller, G.*
AU  - Kamvissi-Lorenz, V.*
AU  - Lechler, R.*
AU  - Trembath, R.*
AU  - Mayr, M.*
AU  - Poston, L.*
AU  - Sancho, R.*
AU  - Ahmed, S.*
AU  - Alfar, E.*
AU  - Aljani, B.*
AU  - Alves, T.C.*
AU  - Amiel, S.*
AU  - Andoniadou, C.L.*
AU  - Bandral, M.
AU  - Belavgeni, A.*
AU  - Berger, I.*
AU  - Birkenfeld, A.L.
AU  - Bonifacio, E.
AU  - Chavakis, T.*
AU  - Chawla, P.
AU  - Choudhary, P.*
AU  - Cujba, A.M.*
AU  - Delgadillo Silva, L.F.
AU  - Demcollari, T.*
AU  - Drotar, D.M.
AU  - Duin, S.*
AU  - El-Agroudy, N.N.*
AU  - El-Armouche, A.*
AU  - Eugster, A.*
AU  - Gado, M.*
AU  - Gavalas, A.
AU  - Gelinsky, M.*
AU  - Guirgus, M.
AU  - Hansen, S.*
AU  - Hanton, E.*
AU  - Hasse, M.*
AU  - Henneicke, H.*
AU  - Heller, C.*
AU  - Hempel, H.*
AU  - Hogstrand, C.*
AU  - Hopkins, D.*
AU  - Jarc, L.
AU  - Jones, P.M.*
AU  - Kamel, M.
AU  - Kämmerer, S.*
AU  - King, A.J.F.*
AU  - Kurzbach, A.*
AU  - Lambert, C.*
AU  - Latunde-Dada, Y.*
AU  - Lieberam, I.*
AU  - Liers, J.*
AU  - Li, J.W.*
AU  - Linkermann, A.*
AU  - Locke, S.*
AU  - Ludwig, B.
AU  - Manea, T.*
AU  - Maremonti, F.*
AU  - Marinicova, Z.
AU  - McGowan, B.M.*
AU  - Mickunas, M.*
AU  - Mingrone, G.*
AU  - Mohanraj, K.*
AU  - Morawietz, H.*
AU  - Ninov, N.
AU  - Peakman, M.*
AU  - Persaud, S.J.*
AU  - Pietzsch, J.*
AU  - Cachorro, E.*
AU  - Pullen, T.J.*
AU  - Pyrina, I.*
AU  - Rubino, F.*
AU  - Santambrogio, A.*
AU  - Schepp, F.*
AU  - Schlinkert, P.*
AU  - Scriba, L.D.*
AU  - Siow, R.*
AU  - Solimena, M.
AU  - Spagnoli, F.M.*
AU  - Speier, S.
AU  - Stavridou, A.*
AU  - Steenblock, C.*
AU  - Strano, A.*
AU  - Taylor, P.*
AU  - Tiepner, A.*
AU  - Tonnus, W.*
AU  - Tree, T.*
AU  - Watt, F.E.*
AU  - Werdermann, M.*
AU  - Wilson, M.*
AU  - Yusuf, N.*
AU  - Ziegler, C.G.*
C1  - 61460
C2  - 50312
CY  - Rudigerstr 14, D-70469 Stuttgart, Germany
SP  - 204-206
TI  - The transCampus metabolic training programme explores the link of SARS-CoV-2 virus to metabolic disease.
JO  - Horm. Metab. Res.
VL  - 53
IS  - 3
PB  - Georg Thieme Verlag Kg
PY  - 2021
SN  - 0018-5043
ER  - 

TY  - JOUR
AB  - Cartilage oligomeric matrix protein (COMP)-Angiopoietin-1 is a potent angiopoietin-1 (Ang-1) variant that possesses therapeutic potential in angiogenesis and vascular endothelial dysfunction. Noteworthy, we have shown that COMP-Ang-1 improves hyperglycemia and neuroregeneration in ob / ob mice. However, the mechanism of the antidiabetic effect of COMP-Ang-1 is completely unknown. Therefore, we elucidated the diabetes protective molecular mechanisms of COMP-Ang-1 in diabetic db / db mouse model. COMP-Ang-1 (0.5ng/g body weight) or aqueous NaCl solution was injected intraperitoneally per day in 21 consecutive days into 3-month old, male db / db mice (n=10 per group). Blood glucose and HbA1c levels were determined at baseline and 21 days after COMP-Ang-1 or NaCl treatment. The effect of COMP-Ang-1 on glucose uptake was investigated by euglycemic-hyperinsulinemic clamp studies and key genes of glucose metabolism were studied by Western blot analysis. Our findings indicate that COMP-Ang-1 improves glucose metabolism in a tissue specific manner by regulating HIF-1 alpha transcriptional genes of GLUT-1 expression.
AU  - Baum, P.*
AU  - Paeschke, S.*
AU  - Klöting, N.
AU  - Blüher, M.*
AU  - Kern, M.*
AU  - Serke, H.*
AU  - Nowicki, M.*
AU  - Kosacka, J.*
C1  - 58783
C2  - 48401
CY  - Rudigerstr 14, D-70469 Stuttgart, Germany
SP  - 685-688
TI  - COMP-ang-1 improves glucose uptake in db/db mice with type 2 diabetes.
JO  - Horm. Metab. Res.
VL  - 52
IS  - 9
PB  - Georg Thieme Verlag Kg
PY  - 2020
SN  - 0018-5043
ER  - 

TY  - JOUR
AB  - The C57BL/6J (B6J) mouse strain has been widely used as a control strain for the study of metabolic diseases and diet induced obesity (DIO). B6J mice carry a spontaneous deletion mutation in the nicotinamide nucleotide transhydrogenase (Nnt) gene eliminating exons 7-11, resulting in expression of a truncated form of Nnt, an enzyme that pumps protons across the inner mitochondrial membrane. It has been proposed that this mutation in B6J mice is associated with epigonadal fat mass and altered sensitivity to diet induced obesity. To define the role of Nnt in the development of diet induced obesity, we generated first backcross (BC1) hybrids of wild type Nnt C57BL/6NTac and mutated Nnt C57BL/6JRj [(C57BL/6NTac×C57BL/6JRj)F1×C57BL/6NTac]. Body weight gain and specific fat-pad depot mass were measured in BC1 hybrids under high fat diet conditions. Both sexes of BC1 hybrids indicate that mice with Nnt wild type allele are highly sensitive to DIO and exhibit higher relative fat mass. In summary, our data indicate that the Nnt mutation in mice is associated with sensitivity to DIO and fat mass.
AU  - Kunath, A.*
AU  - Heiker, J.T.
AU  - Kern, M.*
AU  - Kosacka, J.*
AU  - Flehmig, G.*
AU  - Stumvoll, M.*
AU  - Kovacs, P.*
AU  - Blüher, M.
AU  - Klöting, N.
C1  - 59616
C2  - 48876
CY  - Rudigerstr 14, D-70469 Stuttgart, Germany
SP  - 877-881
TI  - Nicotinamide nucleotide transhydrogenase (Nnt) is related to obesity in mice.
JO  - Horm. Metab. Res.
VL  - 52
IS  - 12
PB  - Georg Thieme Verlag Kg
PY  - 2020
SN  - 0018-5043
ER  - 

TY  - JOUR
AB  - The adrenal gland integrates catecholamine-producing neuroendocrine cells and steroid-producing cells with mesenchymal origin in a structured manner under one capsule and is a key regulator for vital bioactivity. In addition to adrenal-specific disease, dysregulation of adrenal hormones is associated with systemic effects, leading to undesirable metabolic and cardiovascular consequences. Mass spectrometry imaging (MSI) technique can simultaneously measure a broad range of biomolecules, including metabolites and hormones, which has enabled the study of tissue metabolic and hormone alterations in adrenal and adrenal-related diseases. Furthermore, this technique coupled with labeled immunohistochemistry staining has enabled the study of the pathophysiological adaptation of the adrenal gland under normal and abnormal conditions at different molecular levels. This review discusses the recent applications of in situ MSI in the adrenal gland. For example, the combination of formalin-fixed paraffin-embedded tissue microarray and MSI to tissues from patient cohorts has facilitated the discovery of clinically relevant prognostic biomolecules and generated promising hypotheses for new sights into physiology and pathophysiology of adrenal gland. MSI also has enabled the discovery of clinically significant tissue molecular (i. e., biomarker) and pathway changes in adrenal disease, particularly in adrenal tumors. In addition, MSI has advanced the ability to optimally identify and detect adrenal gland specific molecules. Thus, as a novel analytical methodology, MSI has provided unprecedented capabilities for in situ tissue study.
AU  - Li, F.
AU  - Feuchtinger, A.
AU  - Walch, A.K.
AU  - Sun, N.
C1  - 59261
C2  - 48690
CY  - Rudigerstr 14, D-70469 Stuttgart, Germany
SP  - 435-447
TI  - In situ metabolite mass spectrometry imaging: New insights into the adrenal gland.
JO  - Horm. Metab. Res.
VL  - 52
IS  - 6
PB  - Georg Thieme Verlag Kg
PY  - 2020
SN  - 0018-5043
ER  - 

TY  - JOUR
AB  - Animal data link high circulating fetuin-A to low insulin sensitivity and observational studies identify the hepatokine as a marker of future incident type 2 diabetes mellitus in humans. However, a recent, well-powered Mendelian randomization study finds no causal role. We therefore tested in a deeply-phenotyped human cohort if circulating fetuin-A correlates independently with insulin sensitivity and how it relates to the metabolic syndrome and ectopic fat deposition. We analyzed data from 290 young women with and without recent gestational diabetes mellitus. We found that circulating fetuin-A correlates inversely with insulin sensitivity in univariate analyses, but that this correlation is lost after adjustment for markers of the metabolic syndrome and of fatty liver. Additionally, we investigated which fat compartment associates most strongly with circulating fetuin-A. In whole body MRI data from a subcohort of 152 women, this was liver fat content. We conclude that high circulating fetuin-A occurs as part of the metabolic syndrome in young women and associates most strongly with liver fat content. Its close link to the metabolic syndrome may also cause the inverse correlation of circulating fetuin-A with insulin sensitivity as we found no independent association.
AU  - Reif, S.
AU  - Moschko, S.
AU  - Gar, C.
AU  - Ferrari, U.
AU  - Hesse, N.*
AU  - Sommer, N.N.*
AU  - Seissler, J.
AU  - Lechner, A.
C1  - 59879
C2  - 49086
CY  - Rudigerstr 14, D-70469 Stuttgart, Germany
SP  - 809-814
TI  - No independent association of circulating fetuin-A with insulin sensitivity in young women.
JO  - Horm. Metab. Res.
VL  - 52
IS  - 11
PB  - Georg Thieme Verlag Kg
PY  - 2020
SN  - 0018-5043
ER  - 

TY  - JOUR
AB  - The whole world has been affected by a dramatically increasing prevalence of diabetes. Today, the etiology of both type 1 and type 2 diabetes is thought to revolve around the dysfunction of β-cells, the insulin producing cells of the body. Within the pharmaceutical industry, the evaluation of new drugs for diabetes treatment is mostly done using cell lines or rodent islets and depends solely on the assessment of static insulin secretion. However, the use of cell lines or rodent islets is limiting lack of similarity of the human islet cells, leading to a constrain of the predictive value regarding the clinical potential of newly developed drugs. To overcome this issue, we developed an Engineered Micro-Pancreas as a unique platform for drug discovery. The Engineered Micro Pancreas is composed of (i) an organ-derived micro-scaffold, specifically a decellularized porcine lung-derived micro-scaffold and (ii) cadaveric islets seeded thereon. The Engineered Micro Pancreas remained viable and maintained insulin secretion in vitro for up to three months. The quantities of insulin were comparable to those secreted by freshly isolated human islets and therefore hold the potential for real-time and metabolic physiology mimicking drug screening.
AU  - Goldman, O.*
AU  - Puchinsky, D.*
AU  - Durlacher, K.*
AU  - Sancho, R.*
AU  - Ludwig, B.
AU  - Kugelmeier, P.*
AU  - Heller, C.
AU  - Kunicher, N.*
AU  - Treves, A.J.
AU  - Bornstein, S.R.
C1  - 57607
C2  - 47859
SP  - 805-811
TI  - Lung based engineered micro-pancreas sustains human beta cell survival and functionality.
JO  - Horm. Metab. Res.
VL  - 51
IS  - 12
PY  - 2019
SN  - 0018-5043
ER  - 

TY  - JOUR
AU  - Schott, M.*
AU  - Bornstein, S.R.
AU  - A Stratakis, C.*
C1  - 55319
C2  - 46202
CY  - Rudigerstr 14, D-70469 Stuttgart, Germany
SP  - 8-10
TI  - Hormone and metabolic research: 50 years of research.
JO  - Horm. Metab. Res.
VL  - 51
IS  - 1
PB  - Georg Thieme Verlag Kg
PY  - 2019
SN  - 0018-5043
ER  - 

TY  - JOUR
AB  - Dyslipidemia and dyslipoproteinemia are common causes of metabolic and cardiovascular diseases. On the other hand, intracellular bacteria, such as Borrelia burgdorferi, utilize host lipids to survive and disseminate within the host. Recent data suggest that elevated lipids are a contributing factor to the maintenance and severity of Lyme disease and its complications. Here we review and discuss the role of lipids in Borreliosis and report on a pilot trial to examine the potential roles of circulating lipids and lipoproteins in patients with Borrelia infection. In this analysis we assessed the clinical and lipid profiles of 519 patients (319 women, 200 men) with a proven history of Lyme disease, before and after an extracorporeal double membrane filtration. Lipid profiles pre- and post-apheresis were analyzed in conjunction with clinical symptoms and parameters of inflammation. Circulating cholesterol, triglycerides, LDL, LP(a), and other inflammatory lipids were significantly reduced after the apheresis, while symptoms of the disorder and bioindexes of inflammation such as CRP improved. Further studies should be initiated to investigate the possibly causal relation between Lyme disease and circulating lipids and to design appropriate therapeutic strategies.
AU  - Straube, R.*
AU  - Voit-Bak, K.*
AU  - Gor, A.*
AU  - Steinmeier, T.*
AU  - Chrousos, G.P.*
AU  - Boehm, B.O.*
AU  - Birkenfeld, A.L.
AU  - Barbir, M.*
AU  - Balanzew, W.*
AU  - Bornstein, S.R.
C1  - 56022
C2  - 46766
CY  - Rudigerstr 14, D-70469 Stuttgart, Germany
SP  - 326-329
TI  - Lipid profiles in lyme borreliosis: A potential role for apheresis?
JO  - Horm. Metab. Res.
VL  - 51
IS  - 5
PB  - Georg Thieme Verlag Kg
PY  - 2019
SN  - 0018-5043
ER  - 

TY  - JOUR
AB  - In the above-mentioned article, the representation of the graphs in Fig. 1, 2 and 3 and the matching captions were incorrect. The correct illustrations with the correct captions are below. (Figure Presented).
AU  - Straube, R.*
AU  - Voit-Bak, K.*
AU  - Gor, A.*
AU  - Steinmeier, T.*
AU  - Chrousos, G.P.*
AU  - Boehm, B.O.*
AU  - Birkenfeld, A.L.
AU  - Barbir, M.*
AU  - Balanzew, W.*
AU  - Bornstein, S.R.
C1  - 56743
C2  - 47273
SP  - 554
TI  - Erratum: Lipid profiles in lyme borreliosis: A potential role for apheresis (Hormone and Metabolic Research (2019) 51:5 (326-329) DOI: 10.1055/a-0885-7169).
JO  - Horm. Metab. Res.
VL  - 51
IS  - 8
PY  - 2019
SN  - 0018-5043
ER  - 

TY  - JOUR
AB  - The main treatment algorithm for adrenal insufficiency is hormonal replacement, however, inadequate hormone substitution often leads to severe side effects. Adrenal cell transplantation could be a more effective alternative but would require life-long immune suppressive therapy. PreImplantation Factor (PIF) is an endogenous peptide secreted by viable human embryos that leads to maternal tolerance without immunosuppression. PIF could be effective for xenogeneic cell transplantation such as of bovine adrenocortical cells (BAC), which are used for bioartificial adrenal gland development that may more effectively restore complex adrenal functions. We report here that PIF exerts a dual regulatory effect on BAC by targeting mostly hyper-activated cells to specifically reduce adrenocorticotropic hormone (ACTH)-stimulated cortisol secretion. Reverse transcription real time PCR analysis revealed that PIF modulates the expression of two genes in the cortisol synthesis pathway, Steroidogenic Factor 1 (SF1), an activator of steroidogenesis, and the downstream steroidogenic enzyme Cytochrome P450 17A1 (CYP17A1). PIF increased basal expression of SF1 and CYP17A1 regardless of the activation level of the adrenocortical cells. In contrast, following ACTH stimulation, PIF reduced SF1 expression and induced expression of the immune suppressing anti-inflammatory cytokine IL10 only in the hyper-activated cells, suggesting both a protective and immune tolerant function. In conclusion, PIF regulates stress-induced adrenal steroidogenesis and immune tolerance in BAC, supporting a potential clinical application to reduce rejection by the host's immune response following xenotransplantation.
AU  - Balyura, M.*
AU  - Gelfgat, E.*
AU  - Ullmann, E.*
AU  - Ludwig, B.
AU  - Barnea, E.R.*
AU  - Bornstein, S.R.
C1  - 52682
C2  - 44080
CY  - Stuttgart
SP  - 168-174
TI  - PreImplantation factor (PIF*) regulates stress-induced adrenal steroidogenesis and anti-inflammatory cytokines: Potential application for bioartificial adrenal transplant.
JO  - Horm. Metab. Res.
VL  - 50
IS  - 2
PB  - Georg Thieme Verlag Kg
PY  - 2018
SN  - 0018-5043
ER  - 

TY  - JOUR
AB  - Inhibition of aldosterone synthase (CYP11B2) is an alternative treatment option to mineralocorticoid receptor antagonism to prevent harmful aldosterone effects. FAD286 is the best characterized aldosterone synthase inhibitor. However, to date, no study has used sensitive liquid chromatography-tandem mass spectrometry to characterize in detail the effect of FAD286 on the secreted steroid hormone profile of adrenocortical cells. Basal aldosterone production in NCI-H295R cells was detectable and 9-fold elevated after stimulation with angiotensin II. FAD286 inhibited this increase, showing a maximal effect at 10 nmol/l. Higher concentrations of FAD286 did not further reduce aldosterone concentrations, but showed a parallel reduction in corticosterone, cortisol and cortisone levels, reflecting additional inhibition of steroid-11 beta-hydroxylase (CYP11B1). Pregnenolone, progesterone and 17-OH-progesterone levels remained unaffected. In conclusion, the aldosterone synthase inhibitor FAD286 lowers angiotensin II-induced aldosterone concentrations in adrenocortical cells but the relative lack of selectivity over CYP11B1 is evident at higher FAD286 concentrations.
AU  - Brunssen, C.*
AU  - Hofmann, A.*
AU  - Peitzsch, M.*
AU  - Frenzel, A.*
AU  - Ziegler, C.G.
AU  - Brown, N.F.*
AU  - Weldon, S.M.*
AU  - Eisenhofer, G.*
AU  - Willenberg, H.S.*
AU  - Bornstein, S.R.*
AU  - Morawietz, H.*
C1  - 52000
C2  - 43632
CY  - Stuttgart
SP  - 701-706
TI  - Impact of aldosterone synthase inhibitor FAD286 on steroid hormone profile in human adrenocortical cells.
JO  - Horm. Metab. Res.
VL  - 49
IS  - 9
PB  - Georg Thieme Verlag Kg
PY  - 2017
SN  - 0018-5043
ER  - 

TY  - JOUR
AB  - An increased risk for type 1 diabetes can be identified using genetic and immune markers. The Freder1k study introduces genetic testing for type 1 diabetes risk within the context of the newborn screening in order to identify newborns with a high risk to develop type 1 diabetes for follow-up testing of early stage type 1 diabetes and for primary prevention trials. Consent for research-based genetic testing of type 1 diabetes risk is obtained with newborn screening. Increased risk is assessed using three single nucleotide polymorphisms for HLA DRB1*03 (DR3), HLA DRB1*04 (DR4), HLA DQB1*0302 (DQ8) alleles, and defined as 1. an HLA DR3/DR4-DQ8 or DR4-DQ8/DR4-DQ8 genotype or 2. an HLA DR4-DQ8 haplotype and a first-degree family history of type 1 diabetes. Families of infants with increased risk are asked to participate in follow-up visits at infant age 6 months, 2 years, and 4 years for autoantibody testing and early diagnosis of type 1 diabetes. After 8 months, the screening rate has reached 181 per week, with 63% coverage of newborns within Freder1k-clinics and 24% of all registered births in Saxony. Of 4178 screened, 2.6% were identified to have an increased risk, and around 80% of eligible infants were recruited to follow-up. Psychological assessment of eligible families is ongoing with none of 31 families demonstrating signs of excessive burden associated with knowledge of type 1 diabetes risk. This pilot study has shown that it is feasible to perform genetic risk testing for childhood disease within the context of newborn screening programs.
AU  - Hommel, A.*
AU  - Haupt, F.
AU  - Delivani, P.*
AU  - Winkler, C.
AU  - Stopsack, M.*
AU  - Wimberger, P.*
AU  - Nitzsche, K.*
AU  - Heinke, S.*
AU  - Naeke, A.*
AU  - Ceglarek, U.*
AU  - Thiery, J.*
AU  - Bergert, R.*
AU  - Stadthaus, D.*
AU  - Groeger, K.*
AU  - Heubner, G.*
AU  - Schramm, U.*
AU  - Dziambor, U.*
AU  - Zirkel, A.*
AU  - Kiess, W.*
AU  - Mueller, I.*
AU  - Lange, K.*
AU  - Berner, R.*
AU  - Bonifacio, E.*
AU  - Ziegler, A.-G.
C1  - 52308
C2  - 43893
CY  - Stuttgart
SP  - 44-49
TI  - Screening for type 1 diabetes risk in newborns: The Freder1k pilot study in Saxony.
JO  - Horm. Metab. Res.
VL  - 50
IS  - 1
PB  - Georg Thieme Verlag Kg
PY  - 2017
SN  - 0018-5043
ER  - 

TY  - JOUR
AB  - Insulin resistance is the underlying mechanism for the metabolic syndrome and associated dyslipidaemia that theoretically implies a practical tool for identifying individuals at risk for cardiovascular disease and type-2-diabetes. Another screening tool is the hypertriglyceremic-waist phenotype (HTW). There is important impact of the ethnic background but a lack of studied European populations for the association of the triglyceride/ high-density lipoprotein cholesterol (HDL-C) ratio and insulin resistance. This observational, retrospective study evaluated lipid ratios and the HTW for predicting the metabolic syndrome/insulin resistance in 1932 non-diabetic individuals from Germany in the fasting state and during a glucose tolerance test. The relations of triglyceride/HDL-C, total-cholesterol/HDL-C, and low-density lipoprotein cholesterol/HDL-C with 5 surrogate estimates of insulin resistance/sensitivity and metabolic syndrome were analysed by linear regression analysis and receiver operating characteristics (ROC) in participants with normal (n = 1 333) or impaired fasting glucose (n = 599), also for the impact of gender. Within the lipid ratios, triglyceride/ HDL-C had the strongest associations with insulin resistance/ sensitivity markers. In the prediction of metabolic syndrome, diagnostic accuracy was good for triglyceride/HDL-C (area under the ROC curve 0.817) with optimal cut-off points (in mg/dl units) of 2.8 for men (80 % sensitivity, 71 % specificity) and 1.9 for women (80 % sensitivity, 75 % specificity) and fair for HTW and HOMA-IR (area under the curve 0.773 and 0.761). These data suggest the triglyceride/HDL-C ratio as a physiologically relevant and practical index for predicting the concomitant presence of metabolic syndrome, insulin resistance and dyslipidaemia for therapeutic and preventive care in apparently healthy European populations.
AU  - von Bibra, H.*
AU  - Saha, S.*
AU  - Hapfelmeier, A.*
AU  - Mueller, G.*
AU  - Schwarz, P.E.
C1  - 51662
C2  - 43370
CY  - Stuttgart
SP  - 542-549
TI  - Impact of the triglyceride/high-density lipoprotein cholesterol ratio and the hypertriglyceremic-waist phenotype to predict the metabolic syndrome and insulin resistance.
JO  - Horm. Metab. Res.
VL  - 49
IS  - 7
PB  - Georg Thieme Verlag Kg
PY  - 2017
SN  - 0018-5043
ER  - 

TY  - JOUR
AB  - Angiopoietin-like protein 8 (ANGPTL8)/betatrophin expression in visceral adipose tissue and associations with circulating fatty acid profile have not yet been investigated.Forty subjects were included in a cross-sectional study, 57 in a dietary weight reduction intervention. Circulating Angiopoietin-like protein 8/betatrophin was measured in all subjects. Liver and adipose tissue were sampled and plasma fatty acids and tissue Angiopoietin-like protein 8/betatrophin expression were evaluated in the cross-sectional study. In the intervention study oral glucose testing and liver magnetic resonance scanning at baseline and after 6 months were performed. Angiopoietin-like protein 8/betatrophin mRNA was increased in visceral compared to subcutaneous adipose tissue (p<0.001). Circulating ANGPTL8/betatrophin correlated with liver steatosis (r=0.42, p=0.047), triacylglycerols (r=0.34, p=0.046), saturated (r=0.43, p=0.022), monounsaturated (r=0.51, p=0.007), and polyunsaturated fatty acids (r=-0.53, p=0.004). In the intervention study, baseline Angiopoietin-like protein 8/betatrophin correlated with age (r=0.32, p=0.010) and triacylglycerols (r=0.30, p=0.02) and was increased with hepatic steatosis (p=0.033). Weight loss reduced liver fat by 45% and circulating Angiopoietin-like protein 8/betatrophin by 11% (288±17 vs. 258±17 pg/ml; p=0.015). Angiopoietin-like protein 8/betatrophin is related to liver steatosis, while visceral adipose tissue represents an additional site of expression in humans.
AU  - von Loeffelholz, C.*
AU  - Pfeiffer, A.F.*
AU  - Lock, J.F.*
AU  - Lieske, S.*
AU  - Döcke, S.*
AU  - Murahovschi, V.*
AU  - Kriebel, J.
AU  - de Las Heras Gala, T.
AU  - Grallert, H.
AU  - Rudovich, N.N.*
AU  - Stockmann, M.*
AU  - Spranger, J.*
AU  - Jahreis, G.*
AU  - Bornstein, S.R.*
AU  - Lau, G.*
AU  - Xu, A.*
AU  - Schulz-Menger, J.*
AU  - Exner, L.*
AU  - Haufe, S.*
AU  - Jordan, J.*
AU  - Engeli, S.*
AU  - Birkenfeld, A.L.*
C1  - 50826
C2  - 42892
CY  - Stuttgart
SP  - 343-349
TI  - ANGPTL8 (Betatrophin) is expressed in visceral adipose tissue and relates to human hepatic steatosis in two independent clinical collectives.
JO  - Horm. Metab. Res.
VL  - 49
IS  - 5
PB  - Georg Thieme Verlag Kg
PY  - 2017
SN  - 0018-5043
ER  - 

TY  - JOUR
AB  - Type 1 diabetes (T1D) during pregnancy possibly affects the development of the thymus and the maturation of the immune system in the offspring. The aim of the ImmunDiabRisk study was to investigate thymus growth and maternal and fetal immune responses in pregnancies with and without T1D. The thymus circumferences of the fetuses of pregnant women with T1D (n=49) and without diabetes (n=59) were measured using ultrasound around the 29th gestational week and standardized for gestational age. Simultaneously, the frequencies and total numbers of cell markers were analyzed by flow cytometry in maternal peripheral blood, and at birth in umbilical cord blood. The standardized circumference of the thymus was similar in fetuses of mothers with and without T1D (p=0.26). We observed higher numbers of FOXP3 Tregs, memory Tregs, erythrocytes, and lymphocytes in the cord blood from T1D pregnancies (p=0.01, p=0.002, p=0.002 and p=0.02, respectively). The frequencies of CD4+/CD8+ T cells correlated positively in maternal blood and umbilical cord blood of mother-child pairs, as did the levels of neutrophils (Spearman's correlation coefficient r=0.43, p=0.02 for CD4+/CD8+ cells; r=0.46, p=0.03 for neutrophils), while no significant correlations were observed between thymus circumference and any cell markers in the child. Parts of the prenatal immune system seem to develop differently in the offspring of mothers with and without T1D. The correlation of Tregs between maternal blood and cord blood may indicate a significant cross-talk between the maternal and fetal immune system.
AU  - Warncke, K.
AU  - Lickert, R.
AU  - Eitel, S.
AU  - Gloning, K.P.*
AU  - Bonifacio, E.
AU  - Sedlmeier, E.-M.
AU  - Becker, P.
AU  - Knoop, J.
AU  - Beyerlein, A.
AU  - Ziegler, A.-G.
C1  - 52333
C2  - 43912
CY  - Stuttgart
SP  - 892-898
TI  - Thymus growth and fetal immune responses in diabetic pregnancies.
JO  - Horm. Metab. Res.
VL  - 49
IS  - 11
PB  - Georg Thieme Verlag Kg
PY  - 2017
SN  - 0018-5043
ER  - 

TY  - JOUR
AB  - The pregnancy outcomes in women with gestational diabetes mellitus (GDM) and 'overt diabetes in pregnancy' were compared and the need for further subclassification was investigated with respect to postpartum outcome risk. Data from 944 women who had been uniformly diagnosed as having GDM in Munich, Germany, between 1998 and 2010, were re-classified into GDM and 'overt diabetes in pregnancy'. Pregnancy related outcomes in the offspring were derived from Bavarian birth registry data. Classification and regression trees were used to identify further GDM sub-phenotypes. In total, 88 women (9.3%) were re-classified as having 'overt diabetes in pregnancy'. Compared to women with GDM, women with 'overt diabetes in pregnancy' used insulin more frequently, and were at increased risk for large for gestational age infants [odds ratio 2.50 (95% confidence interval 1.02, 6.13)], preterm delivery [odds ratio 3.28 (1.02, 10.50)], and low APGAR-score at 5 min [odds ratio 12.70 (1.58, 102.2)]. In the 856 women with GDM, classification and regression tree analyses provided further risk stratification in that a combination of fasting glucose>5.3 mmol/l and 1-h glucose>11.1 mmol/l at GDM diagnosis predicted insulin requirement [OR 5.57 (3.75, 8.27) compared to the rest], and maternal body mass index (BMI)≥35 kg/m(2) predicted large for gestational age status. The new differentiation between GDM and 'overt diabetes in pregnancy' is a first step towards refining classification relevant to fetal and maternal postpartum risk. A combination of glucose levels and maternal BMI at diagnosis of GDM may provide further improvement.
AU  - Much, D.
AU  - Jaschinski, H.
AU  - Lack, N.*
AU  - Hummel, S.
AU  - Füchtenbusch, M.
AU  - Hummel, M.
AU  - Ziegler, A.-G.
AU  - Beyerlein, A.
C1  - 47298
C2  - 39312
SP  - 16-19
TI  - Risk stratification in women with gestational diabetes according to and beyond current WHO criteria.
JO  - Horm. Metab. Res.
VL  - 48
IS  - 1
PY  - 2015
SN  - 0018-5043
ER  - 

TY  - JOUR
AB  - Very little is known about the role of the innate immune system in the course of human type 1 diabetes. Here we investigated neutrophil numbers along with other leukocyte populations in patients at diagnosis of type 1 diabetes and during prediabetes. Complete and differential blood counts were analyzed from 107 adult patients with newly diagnosed type 1 diabetes, 21 children with persistent islet autoantibodies and a family history of type 1 diabetes, and 1 238 age and gender matched control subjects, all individuals without any signs of acute infection.Adult patients with newly diagnosed type 1 diabetes had significantly lower total WBC (p<1×10 - 6), neutrophil (p<1×10 - 6), basophil (p<1×10 - 6), monocyte (p=4×10 - 6) and lymphocyte (p<1×10 - 6) counts compared to control subjects. Erythrocyte, eosinophil and platelet counts did not differ between groups. Similarly, children with persistent islet autoantibodies had decreased WBC (p=0.001), neutrophils (p=0.003), and lymphocytes (p=0.006) in comparison to control children. Our findings demonstrate a perturbation of leukocyte homeostasis at and prior to onset of type 1 diabetes suggesting a general involvement of the innate immune system in the pathogenesis of type 1 diabetes.
AU  - Harsunen, M.H.
AU  - Puff, R.
AU  - D'Orlando, O.
AU  - Giannopoulou, E.Z.
AU  - Lachmann, L.
AU  - Beyerlein, A.
AU  - von Meyer, A.*
AU  - Ziegler, A.-G.
C1  - 22605
C2  - 30915
SP  - 467-470
TI  - Reduced blood leukocyte and neutrophil numbers in the pathogenesis of type 1 diabetes.
JO  - Horm. Metab. Res.
VL  - 46
IS  - 6
PB  - Thieme
PY  - 2013
SN  - 0018-5043
ER  - 

TY  - JOUR
AB  - Genetic variation in the FTO gene is associated with increased body weight and reduced insulin sensitivity. We investigated whether genetic variation in FTO is associated with polycystic ovary syndrome (PCOS), a condition also characterized by insulin resistance. Furthermore, we tested whether insulin resistance is specifically associated with genetic variation in FTO in women with PCOS. Sixty-two nondiabetic patients with PCOS defined by the Rotterdam criteria were compared to BMI and age-matched women. Each PCOS case was matched to 2 controls. All participants underwent an oral glucose tolerance test and were genotyped for the single nucleotide polymorphism rs8050136 in the FTO gene. There was no difference in the frequency of FTO genotypes between the PCOS and the non-PCOS groups. In non-PCOS participants, genetic variation in FTO is associated with insulin sensitivity (p = 0.03). This association remained significant after adjustment for age and/or BMI (p < = 0.03). In subjects with PCOS, however, FTO did not associate with insulin sensitivity (p = 0.67). Genetic variation in FTO does not have an impact on insulin sensitivity in women with PCOS and is therefore not involved in the pathogenesis of the insulin resistant phenotype seen in patients with PCOS.
AU  - Hatziagelaki, E.*
AU  - Wagner, R.*
AU  - Kantartzis, K.
AU  - Heni, M.*
AU  - Linder, K.*
AU  - Ketterer, C.*
AU  - Machicao, F.
AU  - Stefan, N.
AU  - Staiger, H.
AU  - Häring, H.-U.
AU  - Fritsche, A.
C1  - 10884
C2  - 30454
SP  - 810-813
TI  - Insulin resistant phenotype of polycystic ovary syndrome does not seem to be caused by variation in FTO.
JO  - Horm. Metab. Res.
VL  - 44
IS  - 11
PB  - Thieme
PY  - 2012
SN  - 0018-5043
ER  - 

TY  - JOUR
AU  - Grallert, H.
AU  - Herder, C.*
AU  - Marzi, C.*
AU  - Meisinger, C.
AU  - Wichmann, H.-E.
AU  - Rathmann, W.*
AU  - Illig, T.
C1  - 216
C2  - 27164
CY  - Stuttgart
SP  - 149-151
TI  - Association of genetic variation in KCNQ1 with type 2 diabetes in the KORA surveys.
JO  - Horm. Metab. Res.
VL  - 42
IS  - 2
PB  - Thieme
PY  - 2010
SN  - 0018-5043
ER  - 

TY  - JOUR
AB  - The renin-angiotensin-aldosterone system plays a key role in the regulation of human blood pressure. The aldosterone-to-renin ratio (ARR) is widely accepted for screening the primary hyperaldosteronism (PAL). Various cutoffs for positive PAL screening have been defined in patient cohorts from endocrinological referral centers and primary care. However, the distribution of the ARR in the general population is largely unknown. We aim to provide reference ranges for plasma aldosterone concentration (PAC), plasma renin concentration (PRC), and the ARR for the general population of north-east Germany. A cohort of 3 300 subjects participated in the first follow-up of the longitudinal, population-based Study of Health in Pomerania (SHIP). PAC and PRC were measured by radioimmunometric procedures. The reference interval was defined as the central 95% range between the 2.5(th) and 97.5(th) percentiles. A reference population comprising 1,347 healthy subjects was selected. Sex and age-specific (25-54 and 55-74 years) reference ranges are presented. The upper reference limit for the ARR was 14.2 and 20.3 in younger, and 22.4 and 25.5 in older men and women, respectively. Time of blood sampling had no influence on the ARR, while beta blockers, and agents acting on the renin-angiotensin system were associated with higher and lower ARR, respectively. Our upper reference limit for the ARR is clearly lower than previously reported values from studies of hypertensive patients in primary care or hypertension referral centers. We confirm that PAC and PRC are associated with various factors, including sex, age, intake of estrogen, and various antihypertensive medications.
AU  - Hannemann, A.*
AU  - Friedrich, N.*
AU  - Lüdemann, J.*
AU  - Völzke, H.*
AU  - Rettig, R.*
AU  - Peters, J.*
AU  - Reincke, M.*
AU  - Döring, A.
AU  - Nauck, M.*
AU  - Wallaschofski, H.*
C1  - 2814
C2  - 27383
CY  - Stuttgart
SP  - 392-399
TI  - Reference intervals for aldosterone, renin, and the aldosterone-to-renin ratio in the population-based Study of Health in Pomerania (SHIP-1).
JO  - Horm. Metab. Res.
VL  - 42
IS  - 6
PB  - Thieme
PY  - 2010
SN  - 0018-5043
ER  - 

TY  - JOUR
AB  - Infant diet affects health and development. The aim of our study was to investigate WHO infant feeding compliance in children who have a first degree family history of type 1 diabetes (T1D). One hundred and fifty children who were first degree relatives of patients with T1D were intensively followed from birth in the BABYDIET intervention study. Infant feeding, infections, and medication were recorded daily by participating families. Weight and length of children were obtained from paediatric records. Only 5% of the families followed the WHO recommendations for infant feeding that include full breastfeeding for at least 6 months (18.8% of children) and introduction of complementary foods under continued breastfeeding thereafter (22.2% of children). Maternal age in the first quartile (<29 years; p<0.0001), and maternal smoking (p<0.0001) were associated with an earlier introduction of solid food and reduced breastfeeding. Full breastfeeding > or =6 months was associated with reduced frequency of gastrointestinal infections (12 vs. 38%, p=0.02) and antibiotic treatment (24 vs. 48%, p=0.04). Our findings indicate that WHO infant feeding recommendations were poorly followed by families with a family history of T1D. Action to improve levels of infant feeding behaviour is essential, especially among young mothers with T1D.
AU  - Pflüger, M.
AU  - Winkler, C.
AU  - Hummel, S.
AU  - Ziegler, A.-G.
C1  - 4392
C2  - 28065
CY  - Stuttgart
SP  - 143-148
TI  - Early infant diet in children at high risk for type 1 diabetes.
JO  - Horm. Metab. Res.
VL  - 42
IS  - 2
PB  - Thieme
PY  - 2010
SN  - 0018-5043
ER  - 

TY  - JOUR
AB  - Aldosterone excess in the context of primary aldosteronism (PA) has been associated with impaired glucose tolerance and diabetes mellitus. We retrospectively assessed the prevalence of diabetes mellitus in patients from the German Conn's Register and compared the data with those from hypertensive subjects of a population-based survey. In a case-control study, we have compared 638 patients with PA from the German Conn's registry who were treated in 6 German centers with 897 hypertensive control subjects from the population-based F3 survey of the Cooperative Health Research in the Region of Augsburg (KORA). The samples were matched for age, sex, and blood pressure in a 1:1 ratio. Risk factors associated with the presence of diabetes mellitus were calculated in 638 patients with PA and 897 hypertensive controls. In the case control study, the diabetes prevalence was calculated in 338 cases and controls. In patients with primary aldosteronism, age, BMI, and a higher number of antihypertensive drugs (lowest tertile vs. highest tertile) were variables associated with diabetes mellitus. In contrast, serum potassium and plasma aldosterone concentrations were not associated with higher diabetes prevalence, whereas diastolic blood pressure was inversely associated with diabetes mellitus. Diabetes mellitus was more prevalent in patients with PA than in 338 matched controls (23 vs. 10% in controls). Our data for the German population show that diabetes mellitus is more prevalent in patients with primary aldosteronism than in hypertensive controls.
AU  - Reincke, M.*
AU  - Meisinger, C.
AU  - Holle, R.
AU  - Quinkler, M.*
AU  - Hahner, S.*
AU  - Beuschlein, F.*
AU  - Bidlingmaier, M.*
AU  - Seissler, J.*
AU  - Endres, S.*
C1  - 717
C2  - 27273
CY  - Stuttgart
SP  - 435-439
TI  - Is primary aldosteronism associated with diabetes mellitus? Results of the German Conn's Registry.
JO  - Horm. Metab. Res.
VL  - 42
IS  - 6
PB  - Thieme
PY  - 2010
SN  - 0018-5043
ER  - 

TY  - JOUR
AB  - Genome-wide association (GWA) studies identified novel gene variants that are associated with type 2 diabetes. However, results were not always consistent across different populations. Thus, the aims of this study were (i) to replicate findings from previous GWA studies in mainly Northern European populations using data from the German KORA 500 K diabetes project and (ii) to assess the impact of BMI on associations between single nucleotide polymorphisms (SNPs) and type 2 diabetes. The KORA 500 K diabetes project includes 433 cases with validated type 2 diabetes and 1 438 nondiabetic controls from two population-based KORA surveys. Genotyping was performed using the Affymetrix GeneChip Human Mapping 500 K Array Set. We investigated associations between SNPs and type 2 diabetes in 10 genes that have been reported to increase the risk of type 2 diabetes or were in complete or near-complete linkage disequilibrium with these variants. SNPs in the CDKAL1 gene showed the strongest association with type 2 diabetes [range of age and sex-adjusted odds ratios (OR): 1.30-1.39, p-values 0.0008-0.0004]. In addition, we found evidence for association of SNPs in the genes PPARG, IGF2BP2, HHEX, TCF7L2, and FTO with type 2 diabetes in the same directions as previously described (p<0.05), but not for WFS1, CDKN2A/B, KCNJ11, or EXT2. Adjustment for BMI slightly strengthened the link between CDKAL1 and type 2 diabetes, but had almost no impact on the other associations. We conclude that gene variants of CDKAL1, PPARG, IGF2BP2, HHEX, TCF7L2, and FTO predispose to type 2 diabetes in the German KORA 500 K study population. These associations appear to be independent of BMI.
AU  - Herder, C.*
AU  - Rathmann, W.*
AU  - Strassburger, K.*
AU  - Finner, H.*
AU  - Grallert, H.
AU  - Huth, C.
AU  - Meisinger, C.
AU  - Gieger, C.
AU  - Martin, S.*
AU  - Giani, G.*
AU  - Scherbaum, W.A.*
AU  - Wichmann, H.-E.
AU  - Illig, T.
C1  - 1861
C2  - 26119
SP  - 722-26
TI  - Variants of the PPARG, IGF2BP2, CDKAL1, HHEX, and TCF7L2 genes confer risk of type 2 diabetes independently of BMI in the German KORA studies.
JO  - Horm. Metab. Res.
VL  - 40
IS  - 10
PY  - 2008
SN  - 0018-5043
ER  - 

TY  - JOUR
AB  - Recently, significant associations between common variants of the transcription factor 7-like 2 gene ( TCF7L2) and type 2 diabetes have been reported. This study was designed to replicate the reported associations of the two highly correlated (r (2)=0.86) TCF7L2 single nucleotide polymorphisms rs12255372 and rs7903146 with type 2 diabetes in a case-control study of 2369 MONICA/KORA participants (678 cases/1691 controls from Augsburg, Germany). To further investigate the pathogenic mechanism underlying these associations, we extended our analyses to the metabolic syndrome (IDF, NCEP definitions) and its components in a population-based study comprising 1404 male and female KORA participants aged 55-74 years. Results of our analyses strongly confirmed the minor T alleles as risk variants for type 2 diabetes (rs7903146: OR (TvsC) [95% CI]=1.36 [1.18;1.58], p=0.00003, and rs12255372: OR (TvsG) [95% CI]=1.31 [1.13;1.51], p=0.0003). Moreover, the T allele at rs7903146 was inversely associated with log-transformed, HOMA-%B (beta=-0.07, p=0.005) as a measure of basal insulin secretion, and log-transformed fasting insulin (beta=-0.06, p=0.02). No association was found with insulin resistance (HOMA-IR) and the metabolic syndrome. These findings support replication evidence that TCF7L2 variants increase type 2 diabetes risk. TCF7L2 may primarily affect pancreatic beta cell function.
AU  - Marzi, C.*
AU  - Huth, C.
AU  - Kolz, M.
AU  - Grallert, H.
AU  - Meisinger, C.
AU  - Wichmann, H.-E.
AU  - Rathmann, W.*
AU  - Herder, C.*
AU  - Illig, T.
C1  - 1518
C2  - 24394
CY  - Stuttgart
SP  - 46-52
TI  - Variants of the transcription factor 7-like 2 gene (TCF7L2) are strongly associated with type 2 diabetes but not with the metabolic syndrome in the MONICA/KORA surveys.
JO  - Horm. Metab. Res.
VL  - 39
IS  - 1
PB  - Thieme
PY  - 2007
SN  - 0018-5043
ER  - 

TY  - JOUR
AB  - The neuropeptide Y2 receptor (NPY2R) has been implicated in body weight regulation both in humans and rodents. We investigated if genetic variation in the NPY2R gene is associated with obesity in German extremely obese children and adolescents. The coding sequence and predicted promoter of the NPY2R were screened for variations. Subsequently, case-control (184 extremely obese children and adolescents: mean body mass index [BMI] 35.7 +/- 6.1 kg/m(2), 277 lean students: mean BMI 18.2 +/- 1.1kg/m(2)) and family-based (770 parental pairs with a total of 1081 obese offspring) association analyses were conducted in independent samples. We identified 14 sequence variants (seven novel variants including two coding variants c.369C > T and c.834G > A), five of which were detected once, each in the heterozygous state. In case-control analyses we did not detect association with obesity for seven common (minor allele frequency > 1%) variants (all p > 0.16); additional gender-stratified analyses employing several genetic models and haplotype analyses were also nonsignificant. Furthermore, in a family-based association study for coding synonymous SNP rs1047214 (Ile195) we found no evidence for a transmission disequilibrium in the total or in the gender-stratified PDT analyses (all p > 0.50). In conclusion, we did not find evidence for an involvement of genetic variation in the NPY2R in early onset obesity in German samples.
AU  - Wang, H.J.*
AU  - Wermter, AK.*
AU  - Nguyen, T.T.*
AU  - Scherag, A.*
AU  - Reichwald, K.*
AU  - Waldenmaier, B.*
AU  - Lichtner, P.
AU  - Bettecken, T.*
AU  - Hebebrand, J.*
AU  - Hinney, A.
C1  - 5037
C2  - 28300
CY  - Stuttgart
SP  - 840-844
TI  - No association of sequence variants in the neuropeptide Y2 receptor (NPY2R) gene with early onset obesity in Germans.
JO  - Horm. Metab. Res.
VL  - 39
IS  - 11
PB  - Thieme
PY  - 2007
SN  - 0018-5043
ER  - 

TY  - JOUR
AU  - Mostafazadeh, A.*
AU  - Herder, C.*
AU  - Haastert, B.*
AU  - Hanifi-Moghaddam, P.*
AU  - Schloot, N.*
AU  - Koenig, W.*
AU  - Illig, T.
AU  - Thorand, B.
AU  - Holle, R.
AU  - Eslami, M.-B.*
AU  - Kolb, H.
C1  - 4197
C2  - 22703
SP  - 257-263
TI  - Association of humoral immunity to human Hsp60 with the IL-6 gene polymorphism C-174G in patients with type 2 diabetes and controls.
JO  - Horm. Metab. Res.
VL  - 37
PY  - 2005
SN  - 0018-5043
ER  -