German Center For Infection Research

People with prediabetes are advised to reduce their weight in order to prevent manifest diabetes. Researchers have now been able to show that people achieve the best diabetes protection when they reduce their weight and at the same time normalize blood sugar regulation. People with prediabetes are advised to reduce their weight in order to prevent manifest diabetes. Researchers from the Institute for Diabetes Research and Metabolic Diseases of Helmholtz Munich at the University of Tübingen, a partner in the German Center for Diabetes Research (DZD), together with US colleagues in the "Diabetes Prevention Program (DPP)," have now been able to show for the first time that people achieve the best diabetes protection when they reduce their weight and at the same time normalize blood sugar regulation. In the specialist journal Diabetologia, the authors argue that the normalization of blood sugar levels in prediabetes should be included as a therapeutic goal in the guidelines in order to improve the prevention of type 2 diabetes. Diabetes is widespread and is associated with an increased risk of a number of life-threatening complications such as stroke, heart attack and kidney failure. "In order to prevent the development of the disease, early therapies are already important in the prediabetes stage, a preliminary stage of type 2 diabetes. Our results can be used to change the goals of these early lifestyle interventions in order to reduce the overall development rates of diabetes," explains first author Reiner Jumpertz-von Schwartzenberg. Prediabetes drastically increases the risk of diabetes Prediabetes is diagnosed when there is no manifest type 2 diabetes yet, but the fasting blood sugar is already elevated and glucose tolerance is impaired. To prevent prediabetes from becoming diabetes, affected patients are advised to reduce their weight. US guidelines from the American Diabetes Association (ADA), for example, recommend reducing body weight by at least 7 percent. This recommendation is based on the DPP study. The research team from the Department of Internal Medicine IV, Diabetology, Endocrinology and Nephrology at the Medical University Hospital of Tübingen, the Institute for Diabetes Research and Metabolic Diseases of Helmholtz Munich in Tübingen and the Phoenix Epidemiology and Clinical Research Branch at the National Institute of Diabetes and Digestive and Kidney Diseases in Phoenix, USA, investigated whether this weight loss is sufficient, or whether it is not better to prevent diabetes by also reducing blood sugar levels such that prediabetes goes into remission. Prevention through one-year lifestyle intervention They analyzed data from 480 people with prediabetes who participated in the US Diabetes Prevention Program (DPP) and had lost at least 7 percent of their body weight through a one-year lifestyle intervention. In 114 of them, prediabetes also went into remission during the intervention, meaning that their fasting blood sugar, glucose tolerance and HbA1c had normalized. However, the majority of the 366 study participants had not managed to significantly improve their blood sugar regulation despite successfully losing weight. Their prediabetes was not in remission at the end of the intervention. The researchers found that significantly fewer people in the group that had lost weight and achieved prediabetes remission developed manifest diabetes thereafter. The additional remission of prediabetes resulted in a relative risk reduction for the development of diabetes of 76 percent compared to those who had not achieved normalization of their blood sugar levels. The absolute risk reduction was higher than 10%. "In the group with additional remission of prediabetes, there was even no type 2 diabetes at all in the first 4 years after the lifestyle intervention," reports last author Andreas Birkenfeld. "In the group that had 'only' lost weight, however, some study participants did develop manifest diabetes during that period." Jumpertz-von Schwartzenberg and Birkenfeld draw a clear conclusion: "Our results show that remission of prediabetes brings a further significant benefit in addition to weight reduction. We therefore advocate that the goal of prediabetes remission should be included in the objectives of the practice guidelines in order to significantly improve the prevention of type 2 diabetes."

Many bacteria produce substances to gain an advantage over competitors in their highly competitive natural environment. Researchers have discovered a new so-called lantibiotic, namely epilancin A37. It is produced by staphylococci that colonize the skin and acts specifically against their main competitors there, the corynebacteria. This specificity is presumably mediated by a very special mechanism of action, which the researchers were able to decipher in detail. Many bacteria produce substances to gain an advantage over competitors in their highly competitive natural environment. Researchers at the University Hospital Bonn (UKB), the University of Bonn and the German Center for Infection Research (DZIF) have discovered a new so-called lantibiotic, namely epilancin A37. It is produced by staphylococci that colonize the skin and acts specifically against their main competitors there, the corynebacteria. This specificity is presumably mediated by a very special mechanism of action, which the researchers were able to decipher in detail. Their results have now been published in the ISME Journal. Due to increasing antibiotic resistance in pathogens causing infections, the development of new antibacterial substances is important. Hopes are pinned on a new group of substances produced by gram-positive bacteria, the lantibiotics. These are antimicrobial peptides that often have a very narrow spectrum of activity. "Such compounds are highly interesting from a medical point of view, as they could specifically attack individual groups of organisms without affecting the entire bacterial flora, as is the case with broad-spectrum antibiotics, for example," says corresponding author Dr. Fabian Grein, until recently head of the DZIF research group "Bacterial Interference" at the Institute of Pharmaceutical Microbiology at the UKB and member of the Transdisciplinary Research Area (TRA) "Life & Health" at the University of Bonn. Essential competitive advantage over corynebacteria The UKB research team led by Fabian Grein and Tanja Schneider, together with the team led by Ulrich Kubitscheck, Professor of Biophysical Chemistry at the University of Bonn, have now discovered a new lantibiotic, namely epilancin A37. It is produced by staphylococci, which are typical colonizers of the skin and mucous membranes. Little is known about these antimicrobial peptides. "We were able to show that epilancins are widespread in staphylococci, which underlines their ecological importance," says first author Jan-Samuel Puls, a doctoral student from the University of Bonn at the Institute of Pharmaceutical Microbiology at the UKB. This is because staphylococci and corynebacteria are important genera of the human microbiota -- i.e. the totality of all microorganisms such as bacteria and viruses -- in the nose and skin, which are closely linked to health and disease. The need to produce such a compound indicates a pronounced competition between the species. The researchers were able to show that the newly discovered epilancin A37 acts very specifically against corynebacteria, which are among the main competitors of staphylococci within the skin microbiome. New mode of action in the "bacterial war" decoded "This specificity is presumably mediated by a very special mechanism of action that we were able to decipher in detail," says Grein. Epilancin A37 penetrates the corynebacterial cell, initially without destroying it. The antimicrobial peptides accumulate in the cell and then dissolve the cell membrane from the inside, thus killing the corynebacterium. Co-author Dr. Thomas Fließwasser from the Institute of Pharmaceutical Microbiology at the UKB, postdoctoral researcher at the University of Bonn and acting head of the DZIF research group "Bacterial Interference" adds: "Our study shows how a specific mechanism of action can be used to specifically combat a single bacterial species. It therefore serves us as a 'proof of concept'."

After weight loss, people with overweight and obesity express more of the protein Kallistatin in subcutaneous white adipose tissue. Kallistatin improves metabolism and could open up new therapeutic options for people with obesity and type 2 diabetes in future. After weight loss, people with overweight and obesity express more of the protein Kallistatin* in subcutaneous white adipose tissue. This was demonstrated by researchers from the DZD in a recent study. In addition, Kallistatin improves metabolism and could open up new therapeutic options for people with obesity and type 2 diabetes in future. The results have now been published in Molecular Metabolism. An increasing number of people are developing type 2 diabetes and obesity. These are highly complex and multifaceted diseases. In order to treat them sustainably, new approaches to therapy are needed. Clinical studies on humans have shown that heavily overweight individuals produce less Kallistatin. Kallistatin is a protein that has various effects in the body. Among other things, it is involved in counteracting inflammation and healing wounds. The role that Kallistatin plays in glucose metabolism and its potential suitability as a therapeutic target are currently being investigated by researchers from the German Center for Diabetes Research (DZD), the Institute for Diabetes Research and Metabolic Diseases (IDM) of Helmholtz Munich at the Eberhard-Karls-University of Tübingen, and the Department of Diabetology, Endocrinology and Nephrology at the University Hospital Tübingen. Kallistatin Expression Increases After Weight Loss To this end, they measured Kallistatin expression in subcutaneous white adipose tissue in 47 individuals with overweight to obesity before and after weight loss. The result: Kallistatin expression increases after weight loss. Kallistatin Improves Hepatic Insulin Sensitivity Additionally, the researchers examined the effect of the protein in an animal model. In the process, they observed that human Kallistatin improves hepatic insulin sensitivity in diet-induced obese mice. "Our results suggest that Kallistatin may be an interesting, yet challenging, therapeutic target for people with obesity and insulin resistance," says lead author Leontine Sandforth. "Because Kallistatin has insulin-sensitizing effects in the liver, it should be investigated as a potential liver-specific target for emulating the beneficial effects of weight loss and potentially treating type 2 diabetes and obesity," adds last author Prof. Andreas Birkenfeld.