Maturity-Onset Diabetes of the Young, Type 2

All human beings are genetically very similar, sharing approx. 99.9% of the DNA code. The remaining 0.1% explains the natural differences between people, including our predisposition to hereditary diseases. Although sequencing of our genetic material is becoming a routine diagnostic analysis, it is unfortunately far from simple to determine whether specific small differences in our DNA affect our risk of developing disease. The usefulness of DNA sequencing is therefore often limited to the few cases where it is already known if a gene variant increases the risk of disease. Researchers at the Department of Biology, University of Copenhagen, have now contributed to solving this problem for a specific gene called GCK. The study has just been published in Genome Biology. Figure: GCK gene Rasmus Hartmann-Petersen, Professor at the Department of Biology, explains: - “The GCK gene, which codes for the enzyme glucokinase, regulates the secretion of insulin in the pancreas. GCK gene variants can therefore cause a form of hereditary diabetes. Although the connection between GCKand diabetes has been known for several years, we have, until now, only known the effect of a few percent of the possible variants of this gene”. Together with colleagues at the PRISM centre, UCPH, who are currently studying the effects of genetic variations, the researchers measured the effect of all of the possible variants of GCK. PhD student Sarah Gersing, who is the first author of the article, explains: - “We used yeast cells to measure the activity of over 9000 different GCK variants. In this way, we were able to generate a list of the effects — both of already known variants, but also of variants that patients might carry, but that have not yet been discovered. This provides us with a reference for future GCK diagnostics”.  Prof. Kresten Lindorff-Larsen, who heads the PRISM centre, continues: - “Our results are quite unique; not only have we measured the effect of several thousand variants, but for many of the variants, we can now explain what they do to the glucokinase protein. In our centre, we have gathered researchers working across a range of research fields, bridging from data analysis and biophysics to cell biology and medicine, and it is now clear how this broad approach pays off in explaining how diseases arise”. Gene variants of GCK can, among other things, cause a form of hereditary diabetes called "GCK maturity onset diabetes of the young" (GCK-MODY). Professor of genetics, dr. med. Torben Hansen, who is also a member of the PRISM centre, says: - "Although GCK-MODY patients exhibit elevated blood glucose levels, this is often not associated with complications. Hence, unlike other forms of diabetes, most GCK-MODY patients might therefore not need to be treated with medication. However, due to missing or inaccurate genetic data, more than half of the GCK-MODY patients are classified with having either type 1 or type 2 diabetes – and are therefore unnecessarily medicated. We estimate that approx. 1% of those who have recently been diagnosed with type 2 diabetes in Denmark have a variant in the GCK gene, meaning that they don’t need treatment, or need to be treated differently. Our new map of GCK variants can hopefully help give these patients a more correct diagnosis.” The next step for PRISM is to transfer these methods to other genes and diseases. - "We are already well underway with genes involved in e.g., neurodegenerative diseases, and we are trying to develop precise methods that can provide us with insights on disease mechanisms", says Rasmus Hartmann-Petersen.  Kresten Lindorff-Larsen continues: - "Our data gives us the opportunity to test and develop computational models for variant effects, which will then be transferable to other genes and diseases." - “Now, we have measured the effects of almost all variants of GCK, giving us knowledge on which variants that function, and which that do not. The next step is to understand why, and how the same underlying molecular mechanisms can give rise to a wide range of different diseases", concludes Sarah Gersing.

ARLINGTON, Va., Oct. 5, 2022 /PRNewswire/ -- The American Diabetes Association® (ADA) has launched new requests for applications (RFAs) for the Fall 2022 Grant Cycle to research and expand the field of knowledge to improve the lives of those living with diabetes. The critical topics for research include supporting the behavioral and mental health of people with diabetes, tackling the epidemic of youth onset type 2 diabetes, and improving the lives of women living with diabetes. Each topic offers multiple award mechanisms including—postdoctoral fellowships, junior faculty development, innovative basic, and innovative clinical or translational science awards. Continue Reading New Research Funding Opportunities in Youth Onset Type 2 Diabetes, Mental & Behavioral Health, and Women’s Health in Diabetes "We're looking for impactful projects that can usher in the next generation of scientific breakthroughs and improvements in diabetes care," said Robert Gabbay, MD, PhD, chief scientific and medical officer for the ADA. "These RFAs directly align with ADA's mission to cure and prevent diabetes and improve the lives of all people living with diabetes." "We are excited to be launching these very timely RFAs and look forward to competitively reviewing and funding the most promising research proposals," said Marlon Pragnell, PhD, vice president of research at the ADA. "We are following a two-stage process, with the exception of postdoctoral fellowship applications, to facilitate the application process. The first stage will be a relatively short letter of intent. The most promising proposals will then be invited to submit a full application. Please share with your colleagues!" Brief descriptions of each priority: Supporting the Psychological and Emotional Needs of People with Diabetes Solicits proposals to fund translational research to more effectively deliver personalized, patient-centered psychological and emotional care that considers the context of the person with diabetes, as well as their individual values and preferences. Research areas may include, but are not limited to, strategies for improving patient communications and interactions, problem identification, psychosocial screening, diagnostic evaluation, intervention, and intervention scalability. For the purposes of this RFA, research proposals focusing on potential physiological and biological underpinnings of psychological conditions are out of scope. Tackling the Epidemic of Youth-Onset Type 2 Diabetes Solicits proposals to address key knowledge gaps in youth-onset type 2 diabetes in order to better understand, prevent, treat, and ultimately induce remission for the rapidly increasing numbers of affected individuals. Applications that focus on disadvantaged lower socioeconomic level families where the burden of disease is greatest are strongly encouraged. Emphasis will be placed on clinical and translational research. Improving the Lives of Women with Diabetes across the Lifespan Soliciting proposals for research to better understand clinically important sex and gender differences to optimally inform prevention, diagnosis, and treatment strategies for women across the lifespan and the development of sex-specific clinical guidelines where warranted. While this call is broad in scope and encompasses basic clinical research, significant emphasis will be placed on diabetes clinical research and translation. For questions or more information, please contact Research Programs at [email protected]. About the American Diabetes Association The American Diabetes Association (ADA) is the nation's leading voluntary health organization fighting to bend the curve on the diabetes epidemic and help people living with diabetes thrive. For 82 years, the ADA has driven discovery and research to treat, manage, and prevent diabetes while working relentlessly for a cure. Through advocacy, program development, and education we aim to improve the quality of life for the over 133 million Americans living with diabetes or prediabetes. Diabetes has brought us together. What we do next will make us Connected for Life. To learn more or to get involved, visit us at diabetes.org or call 1-800-DIABETES (1-800-342-2383). Join the fight with us on Facebook (American Diabetes Association), Spanish Facebook (Asociación Americana de la Diabetes), LinkedIn (American Diabetes Association), Twitter (@AmDiabetesAssn), and Instagram (@AmDiabetesAssn). Contact: Daisy Diaz, 703-253-4807, [email protected] SOURCE American Diabetes Association