Center for Diabetes Research

Wake Forest, NC, United States

Center for Diabetes Research

Wake Forest, NC, United States
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Sink K.M.,Section on Gerontology and Geriatric Medicine | Whitlow C.T.,Advanced Neuroscience Imaging Research Laboratory | Palmer N.D.,Center for Diabetes Research | Hugenschmidt C.E.,Section on Gerontology and Geriatric Medicine | And 5 more authors.
Diabetes Care | Year: 2015

OBJECTIVE: Albuminuria and reduced kidney function are associated with cognitive impairment. Relationships between nephropathy and cerebral structural changes remain poorly defined, particularly in African Americans (AAs), a population at higher risk for both cognitive impairment and diabetes than European Americans. We examined the relationship between urine albumin:creatinine ratio (UACR), estimated glomerular filtration rate (eGFR), and cerebral MRI volumes in 263 AAs with type 2 diabetes. RESEARCH DESIGN AND METHODS: Cross-sectional associations between renal parameters and white matter (WM), gray matter (GM), hippocampal, and WM lesion (WML) volumes were assessed using generalized linearmodels adjusted for age, education, sex, BMI, hemoglobin A1c (HbA1c) level, and hypertension. RESULTS: Participants had a mean (SD) age of 60.2 years (9.7 years), and 62.7%were female. Mean diabetes duration was 14.3 years (8.9 years), HbA1c level was 8.2% (2.2%; 66 mmol/mol), eGFR was 86.0 mL/min/1.73 m2 (23.2 mL/min/1.73 m2), and UACR was 155.8 mg/g (542.1mg/g;median 8.1mg/g). Those with chronic kidney disease (CKD) (eGFR <60 mL/min/1.73 m2 or UACR >30 mg/g) had smaller GM and higher WML volumes. Higher UACR was significantly associatedwith higherWML volume and greater atrophy (larger cerebrospinal fluid volumes), and smaller GM and hippocampal WM volumes. A higher eGFR was associated with larger hippocampalWMvolumes. Consistentwith higherWML volumes, participants with CKD had significantly poorer processing speed and working memory. These findings were independent of glycemic control. CONCLUSIONS: We found albuminuria to be a better marker of cerebral structural changes than eGFR in AAs with type 2 diabetes. Relationships between albuminuria and brain pathology may contribute to poorer cognitive performance in patients with mild CKD. © 2015 by the American Diabetes Association.


Cox A.J.,Center for Human Genomics | Cox A.J.,Center for Diabetes Research | Ng M.C.Y.,Center for Human Genomics | Ng M.C.Y.,Center for Diabetes Research | And 2 more authors.
Diabetes Care | Year: 2014

OBJECTIVE: Given the high rates of cardiovascular disease (CVD) and associated mortality in individuals with type 2 diabetes, identifying and understanding predictors of CVD events and mortality could help inform clinical management in this high-risk group. Recent large-scale genetic studies may provide additional tools in this regard. RESEARCH DESIGN AND METHODS: Genetic risk scores (GRSs) were constructed in 1,175 self-identified European American (EA) individuals comprising the family-based Diabetes Heart Study based on 1) 13 single nucleotide polymorphisms (SNPs) and 2) 30 SNPs with previously documented associations with CVD in genome-wide association studies. Associations between each GRS and a self-reported history of CVD, coronary artery calcified plaque (CAC) determined by noncontrast computed tomography scan, all-cause mortality, and CVD mortality were examined using marginal models with generalized estimating equations and Cox proportional hazards models. RESULTS: The weighted 13-SNP GRS was associated with prior CVD (odds ratio [OR] 1.51 [95% CI 1.22-1.86]; P = 0.0002), CAC (β-coefficient [β] 0.22 [0.02-0.43]; P = 0.04) and CVD mortality (hazard ratio [HR] 1.35 [1.10-1.81]; P = 0.04) when adjusting for the other known CVD risk factors: age, sex, type 2 diabetes affection status, BMI, current smoking status, hypertension, and dyslipidemia. The weighted 30-SNP GRS was also associated with prior CVD (OR 1.33 [1.08-1.65]; P = 0.008), CAC (β 0.29 [0.08-0.50]; P = 0.006), all-cause mortality (HR 1.28 [1.05-1.56]; P = 0.01), and CVD mortality (HR 1.46 [1.08-1.96]; P = 0.01). CONCLUSIONS: These findings support the utility of two simple GRSs in examining genetic associations for adverse outcomes in EAs with type 2 diabetes. © 2014 by the American Diabetes Association.


Cox A.J.,Center for Diabetes Research | Cox A.J.,Center for Genomics and Personalized Medicine Research | Bowden D.W.,Center for Diabetes Research | Bowden D.W.,Center for Genomics and Personalized Medicine Research
Diabetes Care | Year: 2014

OBJECTIVE: Heart rate-corrected QT (QTc) interval is associated with mortality in the general population, but this association is less clear in individuals with type 2 diabetes. We assessed the association of QTc interval with all-cause and cardiovascular disease (CVD) mortality in the Diabetes Heart Study. RESEARCH DESIGN AND METHODS: We studied 1,020 participants with type 2 diabetes (83% European Americans; 55% women; mean age 61.4 years) who were free of atrial fibrillation, major ventricular conduction defects, and antiarrhythmic therapy at baseline. QT duration was automatically calculated from a standard 12-lead electrocardiogram (ECG). Following American Heart Association/American College of Cardiology Foundation recommendations, a linear scale was used to correct the QT for heart rate. Using Cox regression, risk was estimated per 1-SD increase in QTc interval as well as prolonged QTc interval (>450 ms) vs. normal QTc interval for mortality. RESULTS: At baseline, the mean (SD) QTc duration was 414.9 ms (18.1), and 3.0% of participants had prolonged QTc. After a median follow-up time of 8.5 years (maximum follow-up time 13.9 years), 204 participants were deceased. In adjusted multivariate models, a 1-SD increase in QTc interval was associated with an 18% higher risk for all-cause mortality (hazard ratio 1.18 [95% CI 1.03-1.36]) and 29% increased risk for CVD mortality (1.29 [1.05-1.59]). Similar results were obtained when QTc interval was used as a categorical variable (prolonged vs. normal) (all-cause mortality 1.73 [0.95-3.15]; CVD mortality 2.86 [1.35-6.08]). CONCLUSIONS: Heart rate QTc interval is an independent predictor of all-cause and CVD mortality in this population with type 2 diabetes, suggesting that additional prognostic information may be available from this simple ECG measure. © 2014 by the American Diabetes Association.


Cox A.J.,Center for Human Genomics | Cox A.J.,Center for Diabetes Research | Agarwal S.,Oakwood | Bowden D.W.,Center for Human Genomics | Bowden D.W.,Center for Diabetes Research
Diabetic Medicine | Year: 2012

Aims Although current American Heart Association guidelines address C-reactive protein concentration and cardiovascular disease risk, it remains unclear whether this paradigm is consistent across populations with differing disease burdens. Individuals with Type 2 diabetes mellitus represent one group at increased risk of cardiovascular disease and subsequent mortality. This study aimed to examine the relationship between C-reactive protein concentrations and risk for all-cause mortality in European Americans with Type 2 diabetes from the Diabetes Heart Study. Methods A total of 846 European Americans with Type 2 diabetes and baseline measures of C-reactive protein were evaluated. Vital status was determined after a follow-up period of 7.3±2.1years (mean±SD). C-reactive protein concentrations were compared between living and deceased subgroups along with other known risk factors for cardiovascular disease, including blood lipids. Logistic regression was performed to determine risk for mortality associated with increasing C-reactive protein concentrations. Results At follow-up 160 individuals (18.7%) were deceased. No significant differences in baseline serum glucose or lipid measures were observed between living and deceased subgroups. Baseline C-reactive protein concentrations were significantly higher in the deceased subgroup (9.37±15.94) compared with the living subgroup (5.36±7.91mg/l; P<0.0001). Participants with C-reactive protein concentrations of 3-10mg/l were approximately two times more likely to be deceased at follow-up (OR 2.06; 95% CI 1.17-3.62); those with C-reactive protein >10mg/l were more than five times more likely to be deceased (OR 5.24; CI 2.80-9.38). Conclusions This study documents the utility of C-reactive protein in predicting risk for all-cause mortality in European Americans with Type 2 diabetes and supports its use as a screening tool in risk prediction models. © 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.


Cox A.J.,Center for Diabetes Research | Cox A.J.,Center for Genomics and Personalized Medicine Research | Criqui M.H.,University of California at San Diego | Bowden D.W.,Center for Diabetes Research | Bowden D.W.,Center for Genomics and Personalized Medicine Research
Diabetes Care | Year: 2014

OBJECTIVE Not all individualswith type 2 diabetes and high coronary artery calcified plaque (CAC) experience the same risk for adverse outcomes. This study examined a subset of high-risk individuals based on CAC >1,000 mg (using a total mass score) and evaluated whether differences in a range of modifiable cardiovascular disease (CVD) risk factors provided further insights into risk for mortality.RESEARCH DESIGN AND METHODS We assessed contributors to all-cause mortality among 371 European American individuals with type 2 diabetes and CAC >1,000 from the Diabetes Heart Study (DHS) after 8.2 ± 3.0 years (mean ± SD) of follow-up. Differences in known CVD risk factors, including modifiable CVD risk factors, were compared between living (n = 218) and deceased (n = 153) participants. Cox proportional hazards regression models were used to quantify risk for all-cause mortality.RESULTS Deceased participants had a longer duration of type 2 diabetes (P = 0.02) and reduced use of cholesterol-lowering medications (P = 0.004). Adjusted analyses revealed that vascular calcified plaque scores were associated with increased risk for mortality (hazard ratio 1.31-1.63; 3.89 × 1025 < P < 0.03). Higher HbA1c, lipids, and C-reactive protein and reduced kidney function also were associated with a 1.1- To 1.5-fold increased risk for mortality (3.45 3 1026 < P < 0.03) after adjusting for confounding factors.CONCLUSIONS Even in this high-risk group, vascular calcification and known CVD risk factors provide useful information for ongoing assessment. The use of cholesterol lowering medication seemed to be protective for mortality. © 2014 by the American Diabetes Association.


News Article | February 16, 2017
Site: www.eurekalert.org

The global proliferation of overweight and obese people and people with type 2 diabetes is often associated with the consumption of saturated fats. Scientists at the German Diabetes Center (Deutsches Diabetes-Zentrum, DDZ) and the Helmholtz Center in Munich (HMGU) have found that even the one-off consumption of a greater amount of palm oil reduces the body's sensitivity to insulin and causes increased fat deposits as well as changes in the energy metabolism of the liver. The results of the study provide information on the earliest changes in the metabolism of the liver that in the long term lead to fatty liver disease in overweight persons as well as in those with type 2 diabetes. In the current issue of the "Journal of Clinical Investigation", DZD researchers working at the German Diabetes Center, in conjunction with the Helmholtz Center in Munich and colleagues from Portugal, published a scientific investigation conducted on healthy, slim men, who were given at random a flavored palm oil drink or a glass of clear water in a control experiment. The palm oil drink contained a similar amount of saturated fat as two cheeseburgers with bacon and a large portion of French fries or two salami pizzas. The scientists showed that this single high-fat meal sufficed to reduce the insulin action, e.g. cause insulin resistance and increase the fat content of the liver. In addition, changes in the energy balance of the liver were proven. The observed metabolic changes were similar to changes observed in persons with type 2 diabetes or non-alcoholic fatty liver disease (NAFLD). NAFLD is the most common liver disease in the industrial nations and associated with obesity, the so-called "metabolic syndrome," and is associated with an increased risk in developing type 2 diabetes. Furthermore, NAFLD in advanced stages can result in severe liver damage. "The surprise was that a single dosage of palm oil has such a rapid and direct impact on the liver of a healthy person and that the amount of fat administered already triggered insulin resistance", explained Prof. Dr. Michael Roden, scientist, Managing Director and Chairman at the DDZ and the German Center for Diabetes Research (Deutsches Zentrum für Diabetesforschung, DZD). "A special feature of our study is that we monitored the liver metabolism of people with a predominantly non-invasive technology, e.g. by magnetic resonance spectroscopy. This allows us to track the storage of sugar and fat as well as the energy metabolism of the mitochondria (power plants of the cell)." Thanks to the new methods of investigation, the scientists were able to verify that the intake of palm oil affects the metabolic activity of muscles, liver and fatty tissue. The induced insulin resistance leads to an increased new formation of sugar in the liver with a concomitant decreased sugar absorption in the skeletal muscles - a mechanism that makes the glucose level rise in persons afflicted with type 2 diabetes and its pre-stages. In addition, the insulin resistance of the fatty tissue causes an increased release of fats into the blood stream, which in turn continues to foster the insulin resistance. The increased availability of fat leads to an increased workload for the mitochondria, which can in the long term overtax these cellular power plants and contribute to the emergence of a liver disease. The team of Prof. Roden suspects that healthy people, depending on genetic predisposition, can easily manage this direct impact of fatty food on the metabolism. The long-term consequences for regular eaters of such high-fat meals can be far more problematic, however. This paper is promoted by the Federal Ministry of Health, the Ministry for Innovation, Science and Research of the state of North Rhine-Westphalia, the Federal Ministry for Education and Research (Deutsches Zentrum für Diabetesforschung e.V.), as well as the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG), the German Diabetes Society (DDG) and the Schmutzler Foundation. Elisa Álvarez Hernández, Sabine Kahl, Anett Seelig, Paul Begovatz, Martin Irmler, Yuliya Kupriyanova, Bettina Nowotny, Peter Nowotny, Christian Herder, Cristina Barosa, Filipa Carvalho, Jan Rozman, Susanne Neschen, John G. Jones, Johannes Beckers, Martin Hrab? de Angelis and Michael Roden, Acute dietary fat intake initiates alterations in energy metabolism and insulin resistance, J Clin Invest. 2017, January 23, 2017. doi:10.1172/JCI89444. The German Diabetes Center (DDZ) is the German reference center for diabetes. The goal is to contribute to the prevention, early detection, diagnosis and treatment of diabetes mellitus. At the same time, the research center aims at improving the epidemiological data situation in Germany. DDZ is in charge of the multi-center German Diabetes Study. It is the point of contact for all players in the health sector. In addition, it prepares scientific information on diabetes mellitus and makes it available to the public. DDZ is part of "Wissenschaftsgemeinschaft Gottfried Wilhelm Leibniz" (WGL) and is a partner of the German Center for Diabetes Research (DZD e.V.). The German Center for Diabetes Research (DZD) is a national association that brings together experts in the field of diabetes research and combines basic research, translational research, epidemiology and clinical applications. The aim is to develop novel strategies for personalized prevention and treatment of diabetes. Members are Helmholtz Zentrum München - German Research Center for Environmental Health, the German Diabetes Center in Düsseldorf, the German Institute of Human Nutrition in Potsdam-Rehbrücke, the Paul Langerhans Institute Dresden of the Helmholtz Zentrum München at the University Medical Center Carl Gustav Carus of the TU Dresden and the Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Zentrum München at the Eberhard-Karls-University of Tuebingen together with associated partners at the Universities in Heidelberg, Cologne, Leipzig, Lübeck and Munich. The Helmholtz Zentrum München, the German Research Center for Environmental Health, pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München is headquartered in Neuherberg in the north of Munich and has about 2,300 staff members. It is a member of the Helmholtz Association, a community of 18 scientific-technical and medical-biological research centers with a total of about 37,000 staff members


News Article | December 22, 2016
Site: www.eurekalert.org

The extra pounds you gain during the holidays will not only show up on your hips but will also affect your DNA. This is the result of a large-scale international study coordinated by Helmholtz Zentrum München, a partner in the German Center for Diabetes Research, which has now been published in 'Nature'. The study shows that a high BMI leads to epigenetic changes at nearly 200 loci of the genome - with effects on gene expression. While our genes do not change in the course of life, our lifestyle can directly influence their surroundings. Scientists speak here of the epigenome (Greek epi: over, outside of, around), which refers to everything that happens on or around the genes. Up to now there has not been much research on how the epigenome is altered as a result of being overweight. "This issue is particularly relevant because an estimated one and a half billion people throughout the world are overweight," said first author Dr. Simone Wahl of the Research Unit Molecular Epidemiology (AME) at Helmholtz Zentrum München, "especially considering that being overweight can have adverse consequences and lead to diabetes and diseases of the cardiovascular and metabolic systems." For this reason, the international research team led by Dr. Christian Gieger and Dr. Harald Grallert of the AME (as well as Jaspal Kooner and John Chambers of Imperial College London) examined possible correlations between body mass index (BMI) and epigenetic changes.* Using state-of-the-art technology, the team carried out the world's largest study so far on the subject. The scientists examined the blood samples of over 10,000 women and men from Europe. A large proportion of these were inhabitants of London of Indian ancestry, who according to the authors are at high risk for obesity and metabolic diseases. In a first step with 5,387 samples **, the research team identified 207 gene loci that were epigenetically altered dependent on the BMI. They then tested these candidate loci in blood samples of an additional 4,874 subjects and were able to confirm 187 of these***. Further studies and long-term observations also indicated that the changes were predominantly a consequence of being overweight - not the cause. "In particular, significant changes were found in the expression of genes responsible for lipid metabolism and substrate transport, but inflammation-related gene loci were also affected," said group leader Harald Grallert. From the data, the team was also able to identify epigenetic markers that could predict the risk of type 2 diabetes. "Our results allow new insights into which signaling pathways are influenced by obesity", said Christian Gieger, head of the AME. "We hope that this will lead to new strategies for predicting and possibly preventing type 2 diabetes and other consequences of being overweight." Next, within the framework of translational research in the German Center for Diabetes Research, the researchers want to investigate in detail how the epigenetic changes affect the expression of the underlying genes. * Specifically, the team investigated the methylation patterns, i.e. the presence or absence of methyl groups on the DNA. By means of high-throughput measurements, these methylation patterns can now be investigated relatively quickly and on a large scale. ** Among others from the Augsburg KORA study, the London LOLIPOP study and a part of the EPICOR study population from Italy *** Some of these have also been confirmed in adipose tissue, indicating that changes in gene regulation in disease-relevant tissues are also visible in the blood. Helmholtz Zentrum München has extensive expertise in the field of genetic and epigenetic causal research on metabolic diseases: As recently as July 2016, the researchers were involved in the world's largest genetic study on type 2 diabetes, which was likewise published in the renowned journal Nature. Link to press release: https:/ Furthermore, already in March 2016 scientists of Helmholtz München showed that diet-induced obesity and diabetes can be passed on epigenetically to the offspring via both oocytes and sperm. Link to related press release: https:/ Wahl, S. et al. (2016): Epigenome-wide association study of body mass index, and the adverse outcomes of adiposity. Nature, doi:10.1038/nature20784 http://www. The Helmholtz Zentrum München, the German Research Center for Environmental Health, pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München is headquartered in Neuherberg in the north of Munich and has about 2,300 staff members. It is a member of the Helmholtz Association, a community of 18 scientific-technical and medical-biological research centers with a total of about 37,000 staff members. http://www. The Research Unit of Molecular Epidemiology (AME) analyses population-based cohorts and case studies for specific diseases, using genomics, epigenomics, transcriptomics, proteomics, metabolomics and functional analyses. The aim of this research unit is to decipher the molecular mechanisms of complex diseases like type 2 diabetes or obesity. The unit administers the biological specimen repository of the Department of Epidemiology and stores the samples for national and international projects. http://www. The Institute of Epidemiology II (EPI II) focuses on the assessment of environmental and lifestyle risk factors which jointly affect major chronic diseases such as diabetes, heart disease and mental health. Research builds on the unique resources of the KORA cohort, the KORA myocardial infarction registry, and the KORA aerosol measurement station. Aging-related phenotypes have been added to the KORA research portfolio within the frame of the Research Consortium KORA-Age. The institute's contributions are specifically relevant for the population as modifiable personal risk factors are being researched that could be influenced by the individual or by improving legislation for the protection of public health. http://www. Research at the Institute of Genetic Epidemiology (IGE) focuses on planning, realization and analysis of projects regarding the identification of genetic factors responsible for complex traits. This involves application, further development and implementation of a variety of statistical methods to address specific aspects such as rare genetic variants, mitochondrial DNA, gene-gene and gene-environment interactions, family studies, and the handling of population structures. The elucidation of disease-relevant genetic factors as well as their inclusion into models of disease risk provides the basis of individualized approaches to treatment or prevention. http://www. The Institute of Human Genetics (IHG) at the Helmholtz Zentrum München and the Technical University of Munich: The Institute is concerned with identifying genes associated with disease and characterizing their functions. The main aim of the research projects is to develop disease-related genetic variation in humans and mice as well as to develop chromosome analysis techniques and new methods for dealing with specific issues in the sphere of pre- and post-natal diagnostics and tumor cytogenetics. http://www. The German Center for Diabetes Research (DZD) is a national association that brings together experts in the field of diabetes research and combines basic research, translational research, epidemiology and clinical applications. The aim is to develop novel strategies for personalized prevention and treatment of diabetes. Members are Helmholtz Zentrum München - German Research Center for Environmental Health, the German Diabetes Center in Düsseldorf, the German Institute of Human Nutrition in Potsdam-Rehbrücke, the Paul Langerhans Institute Dresden of the Helmholtz Zentrum München at the University Medical Center Carl Gustav Carus of the TU Dresden and the Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Zentrum München at the Eberhard-Karls-University of Tuebingen together with associated partners at the Universities in Heidelberg, Cologne, Leipzig, Lübeck and Munich. http://www.


News Article | November 7, 2016
Site: www.eurekalert.org

Certain proteins in the blood of children can predict incipient type 1 diabetes, even before the first symptoms appear. A team of scientists at the Helmholtz Zentrum München, partners in the German Center for Diabetes Research (DZD), reported these findings in the Diabetologia journal. The work was based on two large studies that are intended to explain the mechanisms behind the development of type 1 diabetes (BABYDIAB and BABYDIET*). The study participants are children who have a first-degree relative with type 1 diabetes and who consequently have an increased risk of developing the disease due to the familial predisposition. This autoimmune process does not develop from one day to the next, however: Often the young patients go through longer asymptomatic preliminary stages that see the formation of the first antibodies against the child's own insulin-producing cells in the pancreas; these are the so-called autoantibodies. Biomarkers that indicate whether and when this is the case and how quickly the clinical symptoms will appear could significantly improve the treatment of patients at-risk. A team of scientists, led by Dr. Stefanie Hauck, head of the Research Unit Protein Science and the Core Facility Proteomics, and Prof. Dr. Anette-G. Ziegler, Director of the Institute of Diabetes Research (IDF) at the Helmholtz Zentrum München, analyzed blood samples from 30 children with autoantibodies who had developed type 1 diabetes either very rapidly or with a very long delay. The researchers compared the data with data on children who displayed neither autoantibodies nor diabetes symptoms. In a second step with samples from another 140 children, the researchers confirmed the protein composition differences that they found in this approach. "Altogether, we were able to identify 41 peptides** from 26 proteins that distinguish children with autoantibodies from those without," reports Dr. Christine von Toerne, a scientist in the Research Unit Protein Science who shared first authorship of the work with Michael Laimighofer, a doctoral candidate in Jan Krumsiek's junior research group at the Institute of Computational Biology. Striking in their evaluations: A large number of these proteins are associated with lipid metabolism. "Two peptides -- from the proteins apolipoprotein M and apolipoprotein C-IV -- were particularly conspicuous and were especially differently expressed in the two groups," von Toerne adds. In autoantibody-positive children, it was furthermore possible to reach a better estimate of the speed of the diabetes development using the peptide concentrations of three proteins (hepatocyte growth factor activator, complement factor H and ceruloplasmin) in combination with the age of the particular child. The researchers are confident that the protein signatures they have discovered will be helpful as biomarkers for future diagnostics. "The progression of type 1 diabetes into a clinical disease takes place over a period of time that varies from individual to individual and that at this time is insufficiently predictable," explains Prof. Ziegler. "The biomarkers that we have identified allow a more precise classification of this presymptomatic stage and they are relatively simple to acquire from blood samples." * The BABYDIAB study, which was established in 1989 as the world's first diabetes prospective birth cohort, is a pioneering study in the field of type 1 diabetes pathogenesis research. More than 1650 children of parents with type 1 diabetes have been observed since their birth, or for a period of 25 years. The objective of the BABYDIAB study is to determine when islet autoantibodies first appear, which genetic factors and environmental factors influence their development, and which characteristics of the autoantibodies are most strongly associated with the development of type 1 diabetes. The participants in the study are reexamined every three years by means of blood samples and questionnaires. The BABYDIET is examining the influence of food containing gluten on the development of type 1 diabetes. Of the 2,441 children included in the two studies, so far 124 have developed a precursor to diabetes. 82 of these meanwhile display a clinical disease (as of November 2014). ** Peptides are molecules that, like proteins, are constructed from amino acids. However, they are smaller and to some extent result as fragments during protein breakdown. The transition is therefore relatively fluid. The study was financed by the Juvenile Diabetes Research Foundation (JDRF), which has headquarters in the USA. The number of new cases of type 1 diabetes each year continues to rise. New immunotherapeutic approaches aim at stopping this development. A precise assessment of the individual stage of disease development is an important criterion for the targeted use of new treatments. The described study shows that children already display proteomic changes in the blood during the presymptomatic stage. This information allows a better assessment of the time until clinical manifestation of the disease. Recently scientists in the Protein Science Research Unit were also able to identify biomarkers for the precursor to type 2 diabetes: https:/ Von Toerne, C. & Laimighofer, M. et al. (2016): Peptide serum markers in islet autoantibody-positive children. Diabetologia, doi: 10.1007/s00125-016-4150-x http://link. The presence of certain proteins in blood samples can predict incipient type 1 diabetes. The researchers identify these in their measurements using so-called peptide peaks (see selection in red). Source: Helmholtz Zentrum München The Helmholtz Zentrum München, the German Research Center for Environmental Health, pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München is headquartered in Neuherberg in the north of Munich and has about 2,300 staff members. It is a member of the Helmholtz Association, a community of 18 scientific-technical and medical-biological research centers with a total of about 37,000 staff members. http://www. The independent Research Unit Protein Science (PROT) investigates the composition of protein complexes and their integration into cellular processes and protein networks. One focus is the analysis of the interaction of genetic variance and environmental factors in neurodegenerative and metabolic diseases. The aim of this research is to identify biological systems and disease-associated disorders on a systemic level, thus contributing to a molecular understanding of diseases. http://www. The Core Facility Proteomics is an instrumental analysis platform at the Helmholtz Zentrum München. It provides interested research groups with access to comprehensive proteome analyses conducted with highly sensitive mass spectrometers. The portfolio ranges from technical and scientific consultation during project design and sample preparation to the development of optimized analysis methods to actual sample measurement and data evaluation. The Institute of Diabetes Research (IDF) focuses on the pathogenesis and prevention of type 1 diabetes and type 2 diabetes and the long-term effects of gestational diabetes. A major project is the development of an insulin vaccination against type 1 diabetes. The IDF conducts long-term studies to examine the link between genes, environmental factors and the immune system for the pathogenesis of type 1 diabetes. Findings of the BABYDIAB study, which was established in 1989 as the world's first prospective birth cohort study, identified risk genes and antibody profiles. These permit predictions to be made about the pathogenesis and onset of type 1 diabetes and will lead to changes in the classification and the time of diagnosis. The IDF is part of the Helmholtz Diabetes Center (HDC). http://www. The German Center for Diabetes Research (DZD) is a national association that brings together experts in the field of diabetes research and combines basic research, translational research, epidemiology and clinical applications. The aim is to develop novel strategies for personalized prevention and treatment of diabetes. Members are Helmholtz Zentrum München - German Research Center for Environmental Health, the German Diabetes Center in Düsseldorf, the German Institute of Human Nutrition in Potsdam-Rehbrücke, the Paul Langerhans Institute Dresden of the Helmholtz Zentrum München at the University Medical Center Carl Gustav Carus of the TU Dresden and the Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Zentrum München at the Eberhard-Karls-University of Tuebingen together with associated partners at the Universities in Heidelberg, Cologne, Leipzig, Lübeck and Munich. https:/


Dillon L.W.,Medical Center Boulevard | Pierce L.C.T.,University of California at San Diego | Ng M.C.Y.,Center for Genomics and Personalized Medicine Research | Ng M.C.Y.,Center for Diabetes Research | Wang Y.-H.,Medical Center Boulevard
Human Molecular Genetics | Year: 2013

The formation of alternative DNA secondary structures can result in DNA breakage leading to cancer and other diseases. Chromosomal fragile sites, which are regions of the genome that exhibit chromosomal breakage under conditions of mild replication stress, are predicted to form stable DNA secondary structures. DNA breakage at fragile sites is associated with regions that are deleted, amplified or rearranged in cancer. Despite the correlation, unbiased examination of the ability to form secondary structures has not been evaluated in fragile sites. Here, using the Mfold program, we predict potential DNA secondary structure formation on the human chromosome 10 sequence, and utilize this analysis to compare fragile and non-fragile DNA. We found that aphidicolin (APH)-induced common fragile sites contain more sequence segments with potential high secondary structure-forming ability, and these segments clustered more densely than those in non-fragile DNA. Additionally, using a threshold of secondary structure-forming ability, we refined legitimate fragile sites within the cytogenetically defined boundaries, and identified potential fragile regions within non-fragile DNA. In vitro detection of alternative DNA structure formation and a DNA breakage cell assay were used to validate the computational predictions. Many of the regions identified by our analysis coincide with genes mutated in various diseases and regions of copy number alteration in cancer. This study supports the role of DNA secondary structures in common fragile site instability, provides a systematic method for their identification and suggests a mechanism by which DNA secondary structures can lead to human disease. © The Author 2013. Published by Oxford University Press.


Ng M.C.Y.,Center for Genomics and Personalized Medicine Research | Ng M.C.Y.,Center for Diabetes Research
Current Diabetes Reports | Year: 2015

Type 2 diabetes (T2D) is a global health problem showing substantial ethnic disparity in disease prevalence. African Americans have one of the highest prevalence of T2D in the USA but little is known about their genetic risks. This review summarizes the findings of genetic regions and loci associated with T2D and related glycemic traits using linkage, admixture, and association approaches in populations of African ancestry. In particular, findings from genome-wide association and exome chip studies suggest the presence of both ancestry-specific and shared loci for T2D and glycemic traits. Among the European-identified loci that are transferable to individuals of African ancestry, allelic heterogeneity as well as differential linkage disequilibrium and risk allele frequencies pose challenges and opportunities for fine mapping and identification of causal variant(s) by trans-ancestry meta-analysis. More genetic research is needed in African ancestry populations including the next-generation sequencing to improve the understanding of genetic architecture of T2D. © 2015, The Author(s).

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