Weight-loss medications, commonly referred to as “weight-loss injections”, have significantly expanded treatment options for people with obesity in recent years. At the same time, their increasing use raises important medical and societal questions: Who may benefit from these therapies? What health effects can be achieved? What are their limitations – and what role could these medications play in the long-term treatment of obesity?

A recent episode of the ZDF documentary series 37° explores these questions from different perspectives. The documentary follows one patient on her personal journey with obesity and pharmacological weight management.

Scientific Perspective from Andreas Birkenfeld

Alongside the patient’s personal experience, the programme also explores the scientific and clinical perspective. Prof. Dr. Andreas L. Birkenfeld contributes as an expert, explaining the medical background of these new treatment options.

The discussion goes beyond weight reduction itself and considers how these medications can be meaningfully integrated into obesity treatment. Recent developments also illustrate how significantly therapeutic options in this field have evolved in recent years.

The 37° documentary highlights that the discussion surrounding weight-loss injections extends far beyond the number on the scale. It touches on obesity as a chronic disease, individual treatment decisions, and the opportunities and limitations of new pharmacological approaches.

Watch the documentary:

The episode is available on the 37° YouTube channel:
www.youtube.com/37Grad

The project focuses on the mechanisms underlying modern incretin-based therapies. In particular, Sandforth aims to investigate how tirzepatide affects communication between the brain and the body and influences energy metabolism. The research will also address why individuals may respond differently to treatment and explore potential sex-specific differences.

With the DZD Young Talent Program, the German Center for Diabetes Research (DZD) supports innovative research ideas at an early career stage and strengthens the next generation of researchers in diabetes and metabolism research. The program is intended to provide new impetus for the prevention, diagnosis, and treatment of diabetes and its complications.

We are delighted that Leontine Sandforth, a young scientist from the IDM in Tübingen, has been selected for this funding and congratulate her on this achievement.

Further information on the DZD Young Talent Program and the funded projects is available on the DZD website DZD website.

Prevention begins long before disease onset

The authors propose a so-called life-course approach. Rather than viewing diabetes prevention as a single intervention in adulthood, this approach treats it as a continuous effort throughout life. Six life stages are particularly important: the period before pregnancy, pregnancy, early childhood, adolescence and young adulthood, and midlife.

“Many people think of diabetes prevention mainly in terms of diet and exercise in adulthood,” says first author Yiying Wang, a medical doctoral researcher at University Hospital Tübingen. “However, the risk of developing the disease later in life is shaped much earlier. The metabolic health of both the mother and the father before pregnancy can influence the future metabolic health of their child. Pregnancy and breastfeeding provide further important opportunities to positively shape the health of both generations.”

Restoring health rather than merely slowing disease

A central concept of the publication is remission. According to the authors, prevention should not only aim to slow the progression of disease. Instead, the goal should be to restore metabolic health as early as possible and preserve it over the long term.

This is particularly relevant for prediabetes. At this stage preceding type 2 diabetes, blood glucose levels are already elevated but remain below the diagnostic threshold for diabetes. Studies show that targeted lifestyle interventions can often restore normal blood glucose regulation. People who achieve this have a substantially lower long-term risk of developing type 2 diabetes.

“Prediabetes is not an irreversible condition,” says senior author Birkenfeld. “Prediabetes remission—meaning a return to normal blood glucose levels—should therefore become a central goal of prevention. The aim is not merely to stop disease progression, but to restore metabolic health as early and as durably as possible.”

Ten priorities for the future of diabetes prevention

Beyond summarizing the current state of knowledge, the international panel of experts presents the first jointly developed ten-point framework for the future of diabetes prevention. In it, the authors identify what they consider the most important next steps for making prevention more effective—from life-course risk assessment and personalized prevention strategies to the use of digital and AI-supported tools, as well as new approaches that place greater emphasis on remission as a prevention target and aim to reduce health inequities.

With their ten-point framework, the authors establish the first international expert consensus on the key priorities for the future of diabetes prevention. The aim is to identify risks earlier, establish prediabetes remission as a central prevention target, and help people maintain metabolic health for as long as possible.

Original publication: Wang Y. et al. Type 2 diabetes prevention across the life course. Nature Medicine (2026). 

Please find the paper here:  https://rdcu.be/fyX8B 

Scientific contact:
Prof. Dr. Andreas Birkenfeld
Medical Director
Clinic for Diabetology, Endocrinology, and Nephrology
University Hospital Tübingen
Director of the Institute of Diabetes Research and Metabolic Diseases (IDM) of Helmholtz Munich at University of Tübingen

Not all fat is the same. While body weight has long been considered a key indicator of metabolic health, researchers are increasingly asking a more specific question: Where does the body store fat – and what does this mean for our health?

A new study by researchers from the Institute of Diabetes Research and Metabolic Diseases (IDM) of Helmholtz Munich at the University of Tübingen shows that the distribution of body fat is not only important for metabolic health but is also linked to changes in brain insulin responsiveness in a sex-specific manner.

The findings have been published in Diabetologia.

The hippocampus: a metabolism-related brain region

The hippocampus is well known for its role in learning and memory. However, this brain region is much more than a memory center: it also interacts closely with metabolic processes and responds to insulin.

Reduced sensitivity to insulin in the brain may disrupt communication between metabolism and the brain. Brain insulin resistance is increasingly recognized as a potential link between metabolic disorders and age-related changes in cognitive health.

Visceral fat and liver fat as metabolic warning signs

The researchers studied 260 adults without type 2 diabetes, combining advanced imaging techniques with detailed metabolic assessments.

The findings revealed that fat distribution matters in a sex-specific manner. Higher levels of visceral adipose tissue and liver fat were associated with reduced hippocampal insulin responsiveness.

These results highlight that metabolic health cannot be fully captured by body weight alone. The location of stored fat are crucial factors.

Women show stronger associations

One of the most striking findings was the difference between women and men.

Women with increasing age and unhealthy fat distribution showed a stronger decline in hippocampal insulin sensitivity. Women with increased metabolic risk also demonstrated reduced hippocampal insulin responses and the results differed between pre- and postmenopausal women.

These sex-specific differences provide new insights into why metabolic and brain health trajectories may differ between women and men across the lifespan.

Towards more personalized prevention strategies

The study deepens our understanding of the close relationship between metabolism and brain insulin responsiveness. It demonstrates that metabolic alterations may interact with the brain even without and long before the onset of diabetes.

The findings highlight the need for personalized prevention strategies that consider not only body weight and glucose levels, but also fat distribution, sex, and individual metabolic risk profiles.

Publication:
Sandforth L, Veit R, Machann J et al. Unhealthy fat distribution as a sex-specific predictor of declining hippocampus insulin sensitivity. Diabetologia (2026).
DOI: 10.1007/s00125-026-06787-2

Cancer prevention has long focused on reducing exposure to well-established risk factors such as smoking, alcohol consumption, physical inactivity, and obesity. However, Birkenfeld and Heikenwälder argue that many of these factors ultimately converge on common biological pathways. These include elevated blood glucose levels, insulin resistance, chronic inflammation, and altered metabolic processes—conditions that may also contribute to tumor initiation and progression.

The authors therefore advocate for a shift in perspective. In addition to addressing individual risk factors, future prevention strategies could place greater emphasis on improving overall metabolic health.

Prediabetes Remission as a Measurable Prevention Target

At the center of the commentary is the concept of prediabetes remission, defined as the sustained return from prediabetes to normal glucose regulation. While this state has already been associated with a lower risk of type 2 diabetes and cardiovascular disease, its potential role in cancer prevention has received little attention to date.

Large population-based studies from South Korea involving several million participants provide intriguing epidemiological evidence. These analyses found that individuals with persistent prediabetes had an increased risk of developing pancreatic and gallbladder cancer. By contrast, people whose glucose levels returned to the normal range showed no statistically significant increase in cancer risk compared with individuals who remained normoglycemic.

New Perspectives for Prevention Research

The authors emphasize that these findings do not establish a causal relationship between prediabetes remission and reduced cancer risk. Nevertheless, they offer a biologically plausible hypothesis: long-term disturbances in glucose metabolism may create conditions that favor cancer development, whereas remission of prediabetes could potentially mitigate these processes.

Importantly, returning to normoglycemia appears to be an achievable goal. In the cohorts analyzed, more individuals transitioned from prediabetes back to normal glucose regulation than remained in a persistent prediabetic state. According to the authors, this makes prediabetes remission a realistic and measurable target for future prevention strategies.

Original publication

Birkenfeld AL, Heikenwälder M. Cancer Prevention Through Metabolic Remission. Nature Reviews Endocrinology (2026). DOI: 10.1038/s41574-026-01268-3.

https://www.nature.com/articles/s41574-026-01268-3

Metabolism Junior Faculty Award

The “Metabolism Junior Faculty Award” has been presented annually by the journal Metabolism since 2012 and honors outstanding publications that appeared in the previous year and whose first authors are in the early stages of their careers. An international jury of experts evaluates the contributions in terms of their innovative strength, scientific quality, and significance for the further development of metabolic research. With this award, Metabolism aims to specifically promote the next generation of academic leaders.

About the person

Anja Schork completed her medical training and doctorate at the University Hospital of Tübingen. She currently works as a senior physician and clinical scientist in the Department of Diabetology, Endocrinology, and Nephrology and at the Institute for Diabetes Research and Metabolic Diseases (IDM) of Helmholtz Munich at the University of Tübingen and the German Center for Diabetes Research (DZD). Her research work lies at the interface of nephrology and diabetes/prediabetes, investigating the mechanisms underlying kidney and metabolic diseases and translating experimental and molecular findings into personalized treatment strategies.

Original Publication

Schork et al., 2025: Differential risk assessment in persons at risk of type 2 diabetes using urinary peptidomics. Metabolism. DOI: https://doi.org/10.1016/j.metabol.2025.156174
 

What happens in the body when there is too much sugar? 

Starting at minute 7:28, the program impressively shows how unhealthy eating affected Eckart von Hirschhausen's body. After just one week of high sugar and fat intake, tests conducted at the Tübingen site revealed more fat in the liver and between the organs in the abdomen (visceral fat). This was shown in an experiment conducted in 2024.  

A year and a half later, after losing several kilos, Hirschhausen underwent another examination – with positive news: the dangerous abdominal fat and liver fat had been significantly reduced. 

How do sweeteners affect the brain and appetite? 

In another experiment at the IDM, Prof. Kullmann shows how the brain reacts to sweeteners. These can trigger a “start signal” in the brain that increases appetite. Hirschhausen's conclusion: “I would like to write a package insert: Sweeteners change your brain and trick your perception.” 

"Hirschhausen and the Sugar" is available in the ARD media library until February 20, 2031.
 Hirschhausen und der Zucker - watch here (German only)

Press release from the DZD.

Breakthrough in Prevention Research 

A joint analysis of two of the world’s largest diabetes prevention studies, from the United States and China, now provides clarity. Together with colleagues in the U.S. and China, researchers from Helmholtz Munich, the DZD, and University Hospital Tübingen were able to show that the decisive factor is apparently not the lifestyle change itself, but whether people with prediabetes manage to bring their blood glucose back into the normal range – in other words, whether they achieve remission of prediabetes.

Risk to Heart and Vessels Cut In Half

Long-term data from more than 2,400 people with prediabetes show that those who succeed in normalizing their blood glucose have a significantly lower risk of dying from cardiovascular disease or being hospitalized for heart failure than those whose glucose levels remain elevated, even when both groups lose a similar amount of weight. In both studies, participants’ risk of cardiovascular death was reduced by roughly 50%, and overall mortality also fell significantly. The U.S. study followed its participants for 20 years, while its Chinese counterpart tracked participants for 30 years. Under the leadership of the Tübingen team, these datasets were harmonized and reanalyzed to compare rates of cardiovascular death and hospitalization for heart failure in people with and without prediabetes remission.

A New, Measurable Target for Medicine

Cardiovascular prevention has so far rested on three pillars: blood pressure control, lowering LDL cholesterol, and smoking cessation. With these new findings, a fourth pillar could be added: sustained normalization of blood glucose in prediabetes.

“Our results suggest that remission of prediabetes not only delays or prevents the onset of type 2 diabetes, as already known, but also protects people from serious cardiovascular diseases in the long term, over the span of decades,” says Prof. Dr. Andreas Birkenfeld, Director of the Institute of Diabetes Research and Metabolic Diseases (IDM) at Helmholtz Munich, board member of the DZD and Medical Director of Department of Medicine IV at University Hospital Tübingen.

A fasting blood glucose value of ≤ 97 mg/dL proved to be a simple marker for a persistently lower risk of heart disease, regardless of age, weight, or ethnic background. This threshold could be applied in primary care practices worldwide, making prevention more tangible.

Germany Lagging in International Comparison

Germany is lagging behind when it comes to preventive health care. According to the current Public Health Index, the country ranks second to last among 18 European nations in implementing evidence-based prevention measures. As a result, the risk of dying from cardiovascular disease is significantly higher in Germany than in many neighboring European countries. The new study highlights the untapped potential and shows how concrete target values can substantially improve public health.

“We see a clear therapeutic window: If glucose levels are normalized already at the prediabetes stage, the long-term risk of heart attack, heart failure, and premature death can be markedly reduced. Our data support explicitly anchoring remission as a primary treatment goal in guidelines for the prevention of diabetes and cardiovascular disease,” urges Birkenfeld.

Original Publication

Vazquez Arreola et al., 2025: Prediabetes Remission and Cardiovascular Morbidity and Mortality: A post-hoc analysis from DPPOS and DaQingDPOS. The Lancet. DOI: 10.1016/ S2213-8587(25)00366-3
 

Breakthrough in prevention research 

A joint analysis of two of the world’s largest diabetes prevention studies, from the United States and China, now provides clarity. Together with colleagues in the U.S. and China, researchers from the DZD, University Hospital Tübingen, and Helmholtz Munich were able to show that the decisive factor is apparently not the lifestyle change itself, but whether people with prediabetes manage to bring their blood glucose back into the normal range – in other words, whether they achieve remission of prediabetes.

Risk to heart and vessels cut in half 

Long-term data from more than 2,400 people with prediabetes show that those who succeed in normalizing their blood glucose have a significantly lower risk of dying from cardiovascular disease or being hospitalized for heart failure than those whose glucose levels remain elevated, even when both groups lose a similar amount of weight. In both studies, participants’ risk of cardiovascular death was reduced by roughly 50%, and overall mortality also fell significantly. The U.S. study followed its participants for 20 years, while its Chinese counterpart tracked participants for 30 years. Under the leadership of the Tübingen team, these datasets were harmonized and reanalyzed to compare rates of cardiovascular death and hospitalization for heart failure in people with and without prediabetes remission.

A new, measurable target for medicine 

Cardiovascular prevention has so far rested on three pillars: blood pressure control, lowering LDL cholesterol, and smoking cessation. With these new findings, a fourth pillar could be added: sustained normalization of blood glucose in prediabetes. “Our results suggest that remission of prediabetes not only delays or prevents the onset of type 2 diabetes, as already known, but also protects people from serious cardiovascular diseases in the long term, over the span of decades,” says Professor Dr. Andreas Birkenfeld, a board member of the DZD and Medical Director of Department of Medicine IV at University Hospital Tübingen. A fasting blood glucose value of ≤ 97 mg/dL proved to be a simple marker for a persistently lower risk of heart disease, regardless of age, weight, or ethnic background. This threshold could be applied in primary care practices worldwide, making prevention more tangible.

Germany lagging in international comparison 

Germany is lagging behind when it comes to preventive health care. According to the current Public Health Index, the country ranks second to last among 18 European nations in implementing evidence-based prevention measures. As a result, the risk of dying from cardiovascular disease is significantly higher in Germany than in many neighboring European countries. The new study highlights the untapped potential and shows how concrete target values can substantially improve public health. “We see a clear therapeutic window: If glucose levels are normalized already at the prediabetes stage, the long-term risk of heart attack, heart failure, and premature death can be markedly reduced. Our data support explicitly anchoring remission as a primary treatment goal in guidelines for the prevention of diabetes and cardiovascular disease,” urges Professor Birkenfeld.

Title: Elsa Vazquez Arreola et al.: Prediabetes remission and cardiovascular morbidity and mortality: post-hoc analyses from the Diabetes Prevention Program Outcome study and the DaQing Diabetes Prevention Outcome study. 

The Lancet Diabetes & Endocrinology. DOI: doi.org/10.1016/S2213-8587(25)00295-5 Link to publication: www.thelancet.com/journals/landia/article/PIIS2213- 8587(25)00295-5/fulltext University Hospital Tübingen Corporate Communications Department Hoppe-Seyler-Straße 6, 72076 Tübingen Tel. 07071 29-88548, Fax 07071 29-25024 pressespam prevention@med.uni-tuebingen.de

Media coverage:

New York Times: https://www.nytimes.com/2025/12/15/well/blood-sugar-heart-disease-risk.html

Chinese news report: https://mp.weixin.qq.com/s/EZyc3B5xEsUUe09dJ5pYgQ

Tagesschau: https://www.tagesschau.de/wissen/gesundheit/praediabetes-blutzucker-herz-100.html

Der Spiegel: www.spiegel.de/gesundheit/praediabetes-blutzuckerwerte-sind-offenbar-wichtiger-als-abnehmen-a-14348b88-df9d-49ac-a46d-85fab95985dd

Expert: Prof. Dr. Andreas Birkenfeld Medical Director Clinic for Diabetology, Endocrinology, and Nephrology University Hospital Tübingen 

Director of the Institute of Diabetes Research and Metabolic Diseases (IDM) of Helmholtz Munich at University of Tübingen

A Closer Look at the Early Stage of the Metabolic Disorder

To find answers to this question, researchers have been searching for more precise markers. The one-hour plasma glucose concentration (1h-PG) in the oral glucose tolerance test (OGTT) seemed particularly relevant to them. This is the blood glucose level that doctors determine exactly one hour after the patient has ingested a glucose solution.
According to the International Diabetes Federation (IDF), a value of ≥ 155 mg/dl is considered an early indicator of impaired glucose regulation – often before fasting or two-hour values become abnormal. The hope is that this measurement could offer opportunities to identify at-risk individuals early and treat them in a targeted manner.

Lifestyle Intervention with a Significant Effect

To test their hypothesis, researchers in the Tübingen Lifestyle Intervention Program (TULIP)* intensively monitored 317 individuals with varying levels of glucose tolerance for nine months. The goal of the lifestyle intervention was a weight loss of at least five percent through a balanced diet and regular exercise.
Participants were assigned to three groups based on metabolic parameters:
• with normal glucose regulation,
• with isolated elevated 1-hour prostaglandin (other values, such as fasting glucose and 2-hour prostaglandin, were still normal),
• with classic impaired glucose regulation (prediabetes).
At the beginning of the study, it became apparent that individuals with high 1-hour prostaglandin levels were metabolically intermediate between healthy and unhealthy. Their insulin sensitivity and beta-cell function were impaired, and their liver and abdominal fat levels were elevated, although still reversible.
After nine months of intervention, insulin sensitivity and beta-cell function improved significantly in the 1h-PG group, restoring to levels comparable to those of metabolically healthy individuals. At the same time, liver fat levels normalized. These improvements were considerably less pronounced in the prediabetes group.

Long-Term Benefits: 80 Percent Lower Risk

Over a period of up to twelve years, an impressive effect was observed: Individuals with elevated 1-hour glucose levels who participated in the intervention were 80 percent less likely to develop type 2 diabetes than people with prediabetes. Almost half even achieved normal blood glucose levels (normoglycemia) – twice as many as in the prediabetes group.
“Weight loss and reduced liver fat improved both insulin sensitivity and the ability of beta cells to respond to glucose. This normalization of key metabolic processes could be crucial for enabling the transition to stable, healthy glucose metabolism.” says Yiying Wang, the first author of the study and a MD student in the Department of Diabetology, Endocrinology and Nephrology of the University Hospital Tübingen and a Clinician Scientist in the DZD. 

New Prevention Strategy With Practical Potential

The one-hour glucose value proved to be the most sensitive marker for the early detection of impaired glucose tolerance. It was significantly more informative than the HbA1c value, fasting glucose, or two-hour glucose. “This value apparently marks the optimal point in time to normalize metabolism,” comments Prof. Dr. Andreas Birkenfeld. He is the senior author of the study, spokesperson for the German Center for Diabetes Research (DZD), and director of the Institute for Diabetes Research and Metabolic Diseases of Helmholtz Munich at the University of Tübingen.
According to Birkenfeld, the test could potentially enable the early identification and effective treatment of at-risk individuals, long before prediabetes is diagnosed. This could establish the 1-hour post-load glucose (1h-PG) as a new, clinically relevant biomarker.

*About the Tübingen Lifestyle Intervention Program

The Tübingen Lifestyle Intervention Program (TULIP) is a scientifically developed program at the University of Tübingen for the prevention and treatment of type 2 diabetes and obesity. It was developed at the Institute for Diabetes Research and Metabolic Diseases (IDM) of Helmholtz Munich in collaboration with the Medical Clinic of the University of Tübingen.
TULIP aims to reduce the risk of metabolic diseases or improve existing conditions such as insulin resistance, prediabetes, or fatty liver through targeted lifestyle changes—especially healthy eating, regular physical activity, and behavioral adjustments.

Original Publication 

Wang et al., 2025: Lifestyle intervention is more effective in high 1-hour post-load glucose than in prediabetes for restoring β-cell function, reducing ectopic fat, and preventing type 2 diabetes. Metabolism. DOI: 10.1016/j.metabol.2025.156430

Unhealthy fat distribution and ongoing weight gain are linked to the brain’s response to insulin. In a healthy person, insulin helps control appetite in the brain. However, in people with obesity, insulin loses its ability to regulate eating habits, leading to insulin resistance. Insulin plays many roles in the body, including helping sugar, or glucose, reach muscle cells to be used for energy after a meal. In the brain, insulin also signals the body to eat less.

Not every brain responds the same

But not every brain responds equally to insulin. Many people have a weak or absent insulin response in the brain, known as “brain insulin resistance”. People with brain insulin resistance experience more food cravings and have more belly fat. Fat can promote obesity and so contribute significantly to insulin resistance.

The more fat cells there are, especially in the belly, the less effective insulin is. Fat re- leases messenger substances that promote insulin resistance. However, the signs of reduced insulin sensitivity in the brain can already be seen way before we speak of obesity, which is defined as a body mass index (BMI) above 30. This is calculated as weight (in kilograms) divided by the square of height (in meters), but has its limitations. So it is recommended that excess obesity needs to be confirmed by measuring body fat.

After just five days of consuming an extra 1,500 calories consisting of chocolate bars and crisps, the insulin sensitivity in the brains of the study participants drastically dropped. Symptoms that, until now, have mostly been seen in obese people. Even one week after resuming a normal diet, MRI scans showed a persistently low insulin sensitivity in the brain. Although no significant weight gain was seen, the short period was long enough to let liver fat rise significantly.

It seems that obesity is not only a matter of poor diet and insufficient exercise. It also has a lot to do with the adaptation of the brain’s insulin response to short-term changes in diet before any weight gain occurs. But is insulin resistance in the brain a permanent issue? In the past, exercising regularly over a period of time has been shown to restore brain insulin sensitivity in overweight and obese people. The assumption can be made that this also could apply to people of normal weight. The number of obese people worldwide has more than doubled in the past two decades. And there is little evidence that this trend will shortly come to an end. It is clear that the role of the brain has to be taken into account since the mechanisms in the body that lead to obesity are more complex than just a poor diet and lack of exercise.

Professor Stephanie Kullmann researches neurobiological mechanisms associated with obesity and diabetes in humans. 

She is deputy head of the Metabolic Neuroimaging Department at the Institute for Diabetes Research and Metabolic Diseases (IDM) at the Helmholtz Center Munich at the University of Tübingen

For more information see News and publications of the University Clinic Tübingen. 

¹ Stephanie Kullmann et al, „A short-term, high-caloric diet has prolonged effects on brain insulin action in men”, Nature Metabolism, 21 February 2025, https://www.nature.com/articles/s42255-025-01226-9 

Text: Stephanie Kullmann

"Greater weight loss is usually accompanied by an adjustment in muscle mass [...]. Overall, the evidence – including evidence from imaging and animal studies - suggests that muscle changes under incretin RA therapy are primarily adaptive: the lower muscle volume is in line with expectations depending on age, disease burden, and extent of weight loss - and is comparable to the effects of diets or bariatric surgery."

At the same time, Prof. Dr. Birkenfeld emphasizes that sufficient protein intake and regular physical activity remain essential. Combination therapies with anabolic substances should be reserved for special situations and remain the exception.

You can read the full article from Deutsches Ärzteblatt here.

The experiment was based on a scientific study published in Nature Metabolism (Kullmann et al., 2025). Researchers at the IDM demonstrated that just five days of a high-calorie diet—an additional 1,500 kcal from snacks such as chocolate or chips—significantly impaired insulin action in the brain. Remarkably, this reduced insulin sensitivity persisted even one week after returning to a normal diet. For the first time, it was shown that even short-term dietary changes can disrupt the brain’s reward system, potentially contributing to the development of obesity and type 2 diabetes (link to the study).

For further context, Prof. Andreas Birkenfeld provides a fact check of key claims about weight loss injections and obesity in a dedicated thesis check (link to the fact check).

The program is available in the ARD media library until April 8, 2029.

Further information about the award (Link to Stiftung Gesundheit)

Precise Classification Thanks to Machine Learning 

In order to identify epigenetic markers, the research team used a machine learning method to analyze DNA methylation patterns (small chemical modifications in DNA) in the blood. They studied people without type 2 diabetes (T2D) who differed in terms of their brain’s response to insulin but had similar peripheral insulin sensitivity values. Imaging data, metabolic data, and epigenetic data were integrated into the machine learning workflow. 

In a first study cohort with 167 participants, the researchers identified 540 so-called CpG sites with methylation patterns that made it possible to reliably distinguish between people with and without insulin resistance in the brain. 

“It is noteworthy that many of these methylation sites were associated with an elevated risk of T2D,” reports Meriem Ouni of DIfE, last author of the study. “This suggests a mutual influence between insulin resistance in the brain and metabolic disease.”

The findings were subsequently confirmed in two independent replication cohorts with 33 and 24 people – and with a high degree of accuracy (83% to 94%). “We were able to show that these signatures are reliable independent of age or BMI,” emphasizes Schürmann.  

Blood as a Reflection of the Brain 

All 540 examined CpG sites exhibited changed methylation patterns. For 98 of the identified CpG sites, the researchers found a correlation between blood methylation and brain methylation in a publicly available dataset. Many of the corresponding genes play a role in neuronal development, synapse formation, and signal transmission. “Our findings suggest that the epigenetic profile in the blood can reflect key processes in the brain,” explains Ouni. 

Great Relevance for Prevention and Therapy 

Previous work had already shown that people with insulin resistance in the brain respond less well to lifestyle interventions, store more visceral fat, and experience more frequent cravings – all risk factors for the development of T2D. 

“In future, the newly identified epigenetic markers could serve as a screening instrument in order to detect risk patients early on and provide them with targeted treatment – such as through more intensified lifestyle changes or new active substances ,” states Ouni with conviction. “If we know who is insulin resistant in the brain, we can make interventions much more targeted and effective.” The team’s goal is now to develop a standardized test panel on the basis of the 540 identified CpG sites that can be used in clinical practice. 

Whether epigenetic signatures in the blood can also be used for the early detection of neurodegenerative diseases such as Alzheimer’s disease remains a question for future studies.  

Interdisciplinary Collaboration

The current research findings were enabled by close interdisciplinary collaboration between various institutions. The interplay between the DZD’s two main research topics; “Metabolic Control by the Brain” (Brain Academy) and “The Influence of Genetics and Epigenetics on the Development of Diabetes” (Epigenetic Academy) played a key role in this. Scientists from the Center of Brain, Behavior and Metabolism (CBBM) of the University of Lübeck and from the Ulm University Hospital were also involved. This interdisciplinary expertise was instrumental in gaining new insights into the complex relationships between metabolism, epigenetics, and the brain. 

Background information: 
Epigenetics
Epigenetics is the study of changes in gene activity that are not caused by modifications to the DNA sequence itself. Instead, chemical modifications to the DNA (e.g. methylations) or histone proteins – the packaging units of DNA – regulate the accessibility and readability of genes. Epigenetic changes are mediated by environmental factors, such as diet, stress, or harmful substances. They are reversible in some cases and, among other factors, play a role in the development of diseases such as cancer, diabetes, or Alzheimer’s disease.

CpG sites
CpG sites are DNA sequences in which a cytosine (C) is immediately followed by a guanine (G) on the same strand of DNA – the “p” stands for the phosphate group that binds the nucleotides. CpG sites are important, as cytosine is often methylated at these locations. 

Original publication: 
Stephanie Kullmann, Amandeep Singh, Ratika Sehgal, Fabian Eichelmann, Leontine Sandforth, Britta Wilms, Markus Jähnert, Andreas Peter, Svenja Meyhöfer, Dirk Walther, Hubert Preissl, Hans-Ulrich Häring, Matthias B. Schulze, Martin Heni, Andreas L. Birkenfeld, Annette Schürmann, Meriem Ouni: Circulating Epigenetic Signatures Classifying Brain Insulin Resistance in Humans. Science Translational Medicine, DOI: 10.1126/scitranslmed.adv7834

Scientific contact
Dr. Meriem Ouni
German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE)
Phone: +49 33200 88-2505
E-Mail: meriem.ouni@dife.de

Prof. Dr. Annette Schürmann
German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE)
Phone: +49 33 200 88 - 2368
E-Mail: schuermann@dife.de

Prof. Dr. Stephanie Kullmann
Institute for Diabetes Research and Metabolic Diseases (IDM) at Helmholtz Munich at the University of Tübingen
Universitätsklinikum Tübingen, Innere Medizin IV
Phone: +49 7071 29-87703
E-Mail: stephanie.kullmann@med.uni-tuebingen.de

German Institute of Human Nutrition Potsdam-Rehbruecke 
The DIfE is a member of the Leibniz Association. It investigates the causes of diet-related diseases in order to develop new strategies for prevention and therapy and to provide dietary recommendations. Its research focus includes the causes and consequences of the metabolic syndrome, which is a combination of obesity, high blood pressure, insulin resistance and lipid metabolism disorder, as well as the role of diet in healthy aging and the biological basis of food choices and eating habits. www.dife.de/en

Founded in 1805, Tübingen University Hospital is one of the leading centers of university medicine in Germany. Being one of the 33 university hospitals in Germany, it contributes to the successful combination of high-performance medicine, research and teaching. More than 400,000 inpatients and outpatients from all over the world benefit from this combination of science and practice every year. The clinics, institutes and centers bring together specialists from a wide range of disciplines under one roof. 
The experts work together on an interdisciplinary basis and offer each patient the best possible treatment based on the latest research findings. The University Hospital of Tübingen is researching for better diagnoses, therapies, and chances of recovery. Many new treatment methods are being clinically tested and applied here. In addition to diabetology, research in Tübingen focuses on neurosciences, oncology, immunology, infection research and vascular medicine. Over the past 25 years, the Chair of Diabetology / Endocrinology has been a center of interdisciplinary research, particularly involving surgery, radiology, and laboratory medicine. 
The discovery of prediabetes subtypes was only possible thanks to interdisciplinary collaboration. The University Hospital is a reliable partner of four of the six German Centers for Health Research initiated by the federal government. www.medizin.uni-tuebingen.de   

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 Munich – 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 Helmholtz Munich at the University Medical Center Carl Gustav Carus of the TU Dresden and the Institute for Diabetes Research and Metabolic Diseases of Helmholtz Munich at the Eberhard-Karls-University of Tuebingen together with associated partners at the Universities in Heidelberg, Cologne, Leipzig, Lübeck and Munich. www.dzd-ev.de/en

Chronic conditions such as obesity, type 2 diabetes, and cardiovascular disease can often be managed through medication. However, many individuals face barriers to staying on treatment – ranging from social stigma and lack of support to financial challenges. CarePath, funded by the European Union, aims to close this gap by developing a flexible toolbox that empowers people to manage their treatments in ways that fit their needs, values, and daily routines.

Putting People First

The project takes a person-centered approach, co-developing solutions with patients, healthcare professionals, and other stakeholders. The toolbox will include mobile apps that support communication and self-management, tools to track symptoms and patient experiences, and short questionnaires that help detect when additional support may be needed. By combining digital tools with human care, the solutions can be tailored to various healthcare environments.

Testing Across Europe

To ensure broad relevance and impact, the CarePath toolbox will be piloted in six countries: Germany, Israel, the Netherlands, Poland, Spain, and Sweden. These pilot sites were chosen to reflect a wide range of healthcare systems and population needs. A dedicated proof-of-concept study will also take place in Germany, focusing on people managing type 2 diabetes in outpatient clinics.

Helmholtz Munich’s Role in CarePath

Helmholtz Munich is a central research partner in the five-year project. Principal investigator Prof. Andreas Birkenfeld (Institute of Diabetes Research and Metabolic Diseases), together with Prof. Matthias Blüher (HI-MAG) and Prof. Nikolaos Perakakis (Institute for Pancreatic Islet Research), contribute extensive expertise in metabolic diseases and chronic care. They will test new ways to help people with type 2 diabetes and obesity consistently take essential glucose- and lipid-lowering medications – including the incretin receptor agonists semaglutide and tirzepatide – using a suite of digital tools developed within the consortium. The approach will be evaluated in randomized controlled trials. Helmholtz Munich will receive €980,000 in funding for its participation. The overall project is supported by €11.3 million in EU funding and €8.5 million in in-kind contributions from industry partners.

“This year’s agenda showcases our dedication to pushing the boundaries of research, encouraging innovation, and ultimately enhancing the lives of people living with diabetes and obesity,” said Rita Rastogi Kalyani, ADA President of Medicine & Science.

We are proud that our researchers (from left to right: Prof. Dr. Andreas Birkenfeld, Arvid Sandforth, Leontine Sandforth, Prof. Dr. Reiner Jumpertz-von Schwartzenberg) contributed to this important international conference with their latest research presented in talks and scientific posters.

About the ADA: The ADA is a major voluntary health organization dedicated to the prevention and cure of diabetes. For more information, visit diabetes.org

We congratulate Leontine Sandforth on this important recognition and are delighted about the acknowledgement of her innovative research.

Recognize Earlier, Act more Purposefully 

Background: More than 800 million people worldwide live with diabetes – most of them in low- and middle-income countries. There is often a lack of resources, access to modern therapies and research data. The Copenhagen Declaration aims at improving this situation. It calls for the development of precise early detection and prevention measures and the implementation of culturally and economically appropriate programs. 

Intention: The long-term effects of remission strategies, such as lifestyle changes or new, innovative drugs, are to be systematically investigated. According to the authors, it is crucial to focus not only on achieving normoglycemic values in the short term, but also on preventing disease progression in the long term. 

“We have to understand how stable a diabetes remission is, which groups particularly benefit from it and how we can also achieve these effects under real conditions,” explains Birkenfeld. “The potential is huge, but we need evidence-based concepts and international cooperation.” 
 

Precision Medicine: Phenotyping of Prediabetes is the Key

Another central focus of the declaration is precision medicine. The experts recommend differentiating between prediabetes phenotypes in order to develop risk-based, personalized prevention strategies. Genetic, epigenetic, behavioral and environmental factors should be taken into account. “The idea of a uniform prediabetes stage is outdated,” says Birkenfeld. “Only if we understand the biological diversity of the early stages can we really specifically prevent prediabetes from becoming type 2 diabetes.” 
 

Seven Fields of Action, one Global Mission 

The Copenhagen Declaration defines seven fields of action: 

1. Prevention, early detection and remission: development of low-threshold programs and assessment of the long-term effectiveness of intervention strategies. 
2. Precision medicine: subtyping of forms of diabetes by using AI-assisted decision-making aids. 
3. Equitable access to care: development of infrastructure, especially in regions with few resources. 
4. Innovative treatment models: integration of real-time data, digital tools and biomarker-based decision-making aids. 
5. Integrated care for comorbidities: focus on cardiovascular, renal and oncological concomitant diseases, among others. 
6. Psychosocial support: digital peer-to-peer programs and AI-assisted psychological tools. 
7. Global cooperation and research: focus on LMICs (low- and middle-income countries). 

Particular attention is paid to cost-effective solutions: Artificial intelligence, mobile health applications and telemedicine are to be made accessible to people worldwide. 

Appeal to Politics and Society 

The declaration is not merely a vision, but a concrete call to action – to governments, health organizations, research institutions and industry. It calls for targeted investments, standardized monitoring systems and the development of global data platforms. 
 
“The Copenhagen Declaration is a roadmap for fairer, more effective and smarter care for people with type 2 diabetes,” says Birkenfeld. “If we set the right course now, we can prevent millions of illnesses – and improve the lives of hundreds of millions of people.” 
 

„Wir stehen an einem Wendepunkt“, erklärt Prof. Andreas Birkenfeld, Koautor der Erklärung. Er ist Direktor der Inneren Medizin IV am Universitätsklinikum Tübingen und Leiter des Instituts für Diabetesforschung und Metabolische Erkrankungen (IDM) von Helmholtz Munich am Standort Tübingen des Deutschen Zentrums für Diabetesforschung (DZD). „Wenn wir die Dynamik der globalen Diabetes-Epidemie stoppen wollen, müssen wir deutlich früher ansetzen – mit präziser Vorhersage, personalisierten Strategien und neuen Präventionskonzepten, wie der Prädiabetes Remission“ , betont Birkenfeld.

Früher erkennen, gezielter handeln 

Zum Hintergrund: Weltweit leben mehr als 800 Millionen Menschen mit Diabetes – die meisten in Ländern mit niedrigen und mittleren Einkommen. Dort fehlt es häufig an Ressourcen, an Zugang zu modernen Therapien und an Forschungsdaten. Die Copenhagen Declaration will die Situation verbessern. Sie ruft dazu auf, präzise Früherkennungs- und Präventionsmaßnahmen zu entwickeln und kulturell wie ökonomisch angepasste Programme in die Praxis umzusetzen. 

Eine Forderung: Die langfristigen Effekte von Remissions-Strategien, etwa durch Lebensstiländerungen oder durch neue, innovative Medikamente, sollen systematisch untersucht werden. Entscheidend sei, so die Autorinnen und Autoren, nicht nur das kurzfristige Erreichen normoglykämischer Werte, sondern das dauerhafte Verhindern der Krankheitsprogression im Blick zu haben. 

„Es geht darum, zu verstehen, wie stabil eine Diabetes-Remission ist, welche Gruppen davon besonders profitieren und wie wir diese Effekte auch unter realen Bedingungen erzielen“, erklärt Birkenfeld. „Das Potenzial ist riesig, aber wir brauchen evidenzbasierte Konzepte und eine internationale Zusammenarbeit.“ 

Präzisionsmedizin: Phänotypisierung von Prädiabetes als Schlüssel 

Ein weiterer zentraler Schwerpunkt der Erklärung liegt auf der Präzisionsmedizin. Hier empfehlen die Expertinnen und Experten, Prädiabetes-Phänotypen differenziert zu erfassen, um risikobasierte, personalisierte Präventionsstrategien zu entwickeln. Dabei sollen genetische, epigenetische, verhaltensbezogene und umweltbedingte Faktoren berücksichtigt werden. „Die Idee eines einheitlichen Prädiabetes-Stadiums ist überholt“, so Birkenfeld. „Nur wenn wir die biologische Vielfalt der Frühstadien verstehen, können wir wirklich zielgerichtet verhindern, dass aus Prädiabetes Typ-2-Diabetes wird.“ 

Sieben Handlungsfelder, ein globaler Auftrag 

Die Copenhagen Declaration definiert dabei sieben Aktionsfelder:

1. Prävention, Früherkennung und Remission: Entwicklung niederschwelliger Programme und Beurteilung der langfristigen Effektivität von Interventionsstrategien.

2. Präzisionsmedizin: Subtypisierung von Diabetesformen und durch den Einsatz KI-gestützter Entscheidungshilfen.

3. Gerechter Zugang zur Versorgung: Aufbau von Infrastruktur, insbesondere in ressourcenschwachen Regionen.

4. Innovative Behandlungsmodelle: Integration von Echtzeitdaten, digitalen Tools und Biomarker-basierten Entscheidungshilfen.

5. Integrierte Versorgung bei Komorbiditäten: Augenmerk unter anderem auf kardiovaskuläre, renale und onkologische Begleiterkrankungen.

6. Psychosoziale Unterstützung: digitale Peer-to-Peer-Programme und KI-gestützte psychologische Tools.

7. Globale Kooperation und Forschung mit Fokus auf LMICs (Low- and Middle-Income Countries). 

Ein besonderes Augenmerk liegt auf kosteneffektiven Lösungen: Künstliche Intelligenz, mobile Gesundheitsanwendungen und Telemedizin sollen Menschen weltweit zugänglich gemacht werden. 

Appell an Politik und Gesellschaft 

Die Erklärung versteht sich nicht als bloße Vision, sondern als konkreter Aufruf zum Handeln – an Regierungen, Gesundheitsorganisationen, Forschungseinrichtungen und an die Industrie. Sie fordert gezielte Investitionen, einheitliche Monitoring-Systeme und den Aufbau globaler Datenplattformen. 

„Die Copenhagen Declaration ist ein Fahrplan für eine gerechtere, effektivere und intelligentere Versorgung von Menschen mit Typ-2-Diabetes“, so Birkenfeld. „Wenn wir jetzt die richtigen Weichen stellen, können wir Millionen Erkrankungen verhindern – und das Leben von Hunderten Millionen Menschen verbessern.“ 

Original-Publikation: 

Venkat Narayan KM, Global Diabetes Forum (2024): Copenhagen Declaration: a transformative vision for global diabetes. Lancet Diabetes Endocrinol 2025, 23. Mai, 2025, doi.org/10.1016/S2213-8587(25)00137-8 

This year’s cohort includes 13 exceptional postdoctoral researchers from across Helmholtz Munich, each contributing their unique expertise to this interdisciplinary initiative.

The High Potentials Program is a structured career development program tailored to support postdocs on their path to scientific leadership. It combines in-person workshops, online modules, and blended learning formats. Core components include group and individual training, annual retreats, peer group exchange, and networking opportunities.

Key topics range from career planning, leadership, and team management to third-party funding, communication, mentoring, and outreach. Fellows also take on active roles in the scientific community, such as moderating the ENABLE Seminar Series.

We congratulate Yurong on this outstanding achievement and wish her every success in the program.

Learn more about the program and meet the full cohort on the HPP website.

Looking Ahead:
While the third cohort begins their training, the first HPP Fellows are completing the program this spring. The next call for applications is planned for autumn 2025. More information on eligibility and application details can be found on the Application Website.

Obesity and the role of insulin in the brain 

Unhealthy body fat distribution and chronic weight gain are linked to the brain's sensitivity to insulin. What specific functions does insulin perform in the brain, and how does it affect individuals of normal weight? In their study, Prof. Dr. Stephanie Kullmann and her colleagues at the Tübingen University Hospital for Diabetology, Endocrinology, and Nephrology found the answer to this query. "Our findings demonstrate for the first time that even a brief consumption of highly processed, unhealthy foods (such as chocolate bars and potato chips) causes a significant alteration in the brain of healthy individuals, which may be the initial cause of obesity and type 2 diabetes," says Prof. Kullmann, the study's leader.  In a healthy state, insulin has an appetite-suppressing effect in the brain. However, in people with obesity in particular, insulin no longer regulates eating behavior properly, resulting in insulin resistance. “Interestingly, in our healthy study participants, the brain shows a similar decrease in sensitivity to insulin after a short-term high calorie intake as in people with obesity,” says Ms. Kullmann.  

“This effect can even be observed one week after returning to a balanced diet,” she adds. She is also deputy head of the Metabolic Neuroimaging department at the DZD partner Institute for Diabetes Research and Metabolic Diseases (IDM) of Helmholtz Munich at the University of Tübingen.

Focus on the brain

Prof. Dr. Andreas Birkenfeld, Medical Director of Internal Medicine IV, Director of the IDM and DZD Board Member, and the study's final author, concludes, "We assume that the brain's insulin response adapts to short-term changes in diet before any weight gain occurs and thus promotes the development of obesity and other secondary diseases." He urges more research on how the brain contributes to the development of obesity and other metabolic illnesses in light of the current findings.

Short period with far-reaching effects

29 male volunteers of average weight participated in the study and were split into two groups. For five days in a row, the first group had to supplement their regular diet with 1500 kcal from highly processed, high-calorie snacks. The extra calories were not consumed by the control group. Both groups underwent two separate examinations following an initial evaluation. One examination was conducted immediately following the five-day period, and another was conducted seven days after the first group had resumed their regular diet. The researchers used magnetic resonance imaging (MRI) to look at the liver's fat content and the brain's insulin sensitivity. Not only did the fat content of the liver of the first group increase significantly after five days of increased calorie intake. Surprisingly, the significantly lower insulin sensitivity in the brain compared to the control group also persisted one week after returning to a normal diet. This effect had previously only been observed in obese people.
 

Original publication:
Kullmann, S., …, Birkenfeld, A.L. et al. A short-term, high-caloric diet has prolonged effects on brain insulin action in men. Nat Metab (2025).
DOI: doi.org/10.1038/s42255-025-01226-9

Press contact:
University Hospital of Tübingen
Corporate Communications Department
Hoppe-Seyler-Straße 6, 72076 Tübingen
Tel. 07071 29-88548, Fax 07071 29-25024
presse(at)med.uni-tuebingen.de

Scientific contact:
Prof. Dr. Stephanie Kullmann
Medical Clinic – Inner Medicine IV
University Hospital of Tübingen
Institute for Diabetes Research and Metabolic Diseases (IDM) of Helmholtz Munich at the University of Tübingen
 

Founded in 1805, Tübingen University Hospital is one of the leading centers of German university medicine. As one of the 33 university hospitals in Germany, it contributes to the successful combination of high-performance medicine, research and teaching. Well over 400,000 inpatients and outpatients from all over the world benefit annually from this combination of science and practice. The clinics, institutes and centers unite all specialists under one roof. The experts work together across disciplines and offer each patient the best possible treatment based on the latest research findings. Tübingen University Hospital conducts research for better diagnoses, therapies and healing chances; many new treatment methods are clinically tested and applied here. In addition to diabetology, neuroscience, oncology, immunology, infection research and vascular medicine are research priorities in Tübingen. The Department of Diabetology /Endocrinology has been the center of interdisciplinary research over the past 25 years, especially with the participation of surgery, radiology and laboratory medicine. This important discovery of the prediabetes subtypes was only possible due to the interdisciplinary collaboration between the hospital’s various departments. Tübingen University Hospital is a reliable partner in four of the six German Centers for Health Research initiated by the German Federal Government. www.medizin.uni-tuebingen.de

Helmholtz Munich is a leading biomedical research center. Its mission is to develop breakthrough solutions for better health in a rapidly changing world. Interdisciplinary research teams focus on environmentally triggered diseases, especially the therapy and prevention of diabetes, obesity, allergies and chronic lung diseases. With the power of artificial intelligence and bioengineering, the researchers accelerate the translation to patients. Helmholtz Munich has more than 2,500 employees and is headquartered in Munich/Neuherberg. It is a member of the Helmholtz Association, with more than 43,000 employees and 18 research centers the largest scientific organization in Germany. More about Helmholtz Munich (Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt GmbH): www.helmholtz-munich.de/en    

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 Munich – 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 Helmholtz Munich at the University Medical Center Carl Gustav Carus of the TU Dresden and the Institute for Diabetes Research and Metabolic Diseases of Helmholtz Munich at the Eberhard-Karls-University of Tuebingen together with associated partners at the Universities in Heidelberg, Cologne, Leipzig, Lübeck and Munich. www.dzd-ev.de/en  ;

Obesity and the role of insulin in the brain 

Unhealthy body fat distribution and chronic weight gain are linked to the brain's sensitivity to insulin. What specific functions does insulin perform in the brain, and how does it affect individuals of normal weight? In their study, Prof. Dr. Stephanie Kullmann and her colleagues at the Tübingen University Hospital for Diabetology, Endocrinology, and Nephrology found the answer to this query. "Our findings demonstrate for the first time that even a brief consumption of highly processed, unhealthy foods (such as chocolate bars and potato chips) causes a significant alteration in the brain of healthy individuals, which may be the initial cause of obesity and type 2 diabetes," says Prof. Kullmann, the study's leader.  In a healthy state, insulin has an appetite-suppressing effect in the brain. However, in people with obesity in particular, insulin no longer regulates eating behavior properly, resulting in insulin resistance. “Interestingly, in our healthy study participants, the brain shows a similar decrease in sensitivity to insulin after a short-term high calorie intake as in people with obesity,” says Ms. Kullmann.

“This effect can even be observed one week after returning to a balanced diet,” she adds.

She is also deputy head of the Metabolic Neuroimaging department at the DZD partner Institute for Diabetes Research and Metabolic Diseases (IDM) of Helmholtz Munich at the University of Tübingen.

Focus on the brain

Prof. Dr. Andreas Birkenfeld, Medical Director of Internal Medicine IV, Director of the IDM and DZD Board Member, and the study's final author, concludes, "We assume that the brain's insulin response adapts to short-term changes in diet before any weight gain occurs and thus promotes the development of obesity and other secondary diseases." He urges more research on how the brain contributes to the development of obesity and other metabolic illnesses in light of the current findings.

Short period with far-reaching effects

29 male volunteers of average weight participated in the study and were split into two groups. For five days in a row, the first group had to supplement their regular diet with 1500 kcal from highly processed, high-calorie snacks. The extra calories were not consumed by the control group. Both groups underwent two separate examinations following an initial evaluation. One examination was conducted immediately following the five-day period, and another was conducted seven days after the first group had resumed their regular diet. The researchers used magnetic resonance imaging (MRI) to look at the liver's fat content and the brain's insulin sensitivity. Not only did the fat content of the liver of the first group increase significantly after five days of increased calorie intake. Surprisingly, the significantly lower insulin sensitivity in the brain compared to the control group also persisted one week after returning to a normal diet. This effect had previously only been observed in obese people.

Typ-2-Diabetes frühzeitig vermeiden

„Angesichts der Tatsache, dass die Diagnose Prädiabetes bereits auf signifikante pathophysiologische Veränderungen, wie z.B. Insulinresistenz und/oder Betazelldysfunktion, hinweist, ist es entscheidend, diese Veränderungen so früh wie möglich rückgängig zu machen, um die Betazellfunktion frühzeitig und nachhaltig zu erhalten und Folgen einer langjährigen Insulinresistenz zu verhindern“, sagt Erst-Autorin Leontine Sandforth, Ärztin, Clinician Scientist-Stipendiatin der DFG an der Medizinischen Klinik IV der Universität Tübingen und DZD-Forscherin.

Normalisierung der Blutzuckerwerte senkt Risiko für Typ-2-Diabetes

Doch wie kann das gelingen? Um der Entwicklung eines Typ-2-Diabetes sowie Schäden an Blutgefäßen und Organen vorzubeugen, wird zur Bekämpfung von Prädiabetes meist auf Lebensstiländerungen wie gesunde Ernährung und mehr Bewegung gesetzt. Aktuelle Studien zeigen, dass zusätzlich zum Gewichtsverlust vor allem die Normalisierung der Blutzuckerwerte (Prädiabetes-Remission) das Risiko für Typ-2-Diabetes deutlich senkt. Weitere Studien sollen zukünftig zeigen, ob die Remission von Prädiabetes auch vor dem Auftreten von diabetesbedingten Komorbiditäten wie Herz-Kreislauf- und/oder chronischer Nierenerkrankung schützen kann.

Prädiabetes-Remission und Gewichtsabnahme

„Um das Risiko für schwerwiegende Folgeerkrankungen und Typ-2-Diabetes zu senken, sollte in Zukunft eine gezielte Prädiabetes-Remission in Verbindung mit einer leitliniengerechten Gewichtsabnahme das primäre Therapieziel sein“, betont der Ärztliche Direktor der Medizinischen Klinik IV der Universität Tübingen und DZD-Vorstand Prof. Andreas Birkenfeld. Dies könnte künftig helfen, Typ-2-Diabetes zu verhindern, die Lebensqualität der betroffenen Personen zu verbessern und die weltweite Krankheitslast zu reduzieren.

Wichtige Punkte des Übersichtsartikels

• Die Remission von Prädiabetes zu einer normalen Glukoseregulation senkt, zusätzlich zum Standard-Gewichtsverlust, das Risiko für Typ-2-Diabetes mehr als der Standard-Gewichtsverlust allein.
• Die Remission vom Prädiabetes zur normalen Glukoseregulation sollte in Richtlinien und Empfehlungen zur Verzögerung und Prävention von Typ-2-Diabetes berücksichtigt werden.
• Zukünftige Studien werden zeigen, ob die Remission von Prädiabetes auch vor dem Auftreten von diabetesbedingten Komorbiditäten wie Herz-Kreislauf- und/oder chronischer Nierenerkrankung schützen kann.

Original-Publikation:
Leontine Sandforth, Stephanie Kullmann, Arvid Sandforth, Andreas Fritsche, Reiner Jumpertz-von Schwartzenberg, Norbert Stefan, Andreas L. Birkenfeld: Prediabetes remission to reduce the global burden of type 2 diabetes, Trends in Endocrinology & Metabolism, 2025, ISSN 1043-2760, doi.org/10.1016/j.tem.2025.01.004.

Das 1805 gegründete Universitätsklinikum Tübingen gehört zu den führenden Zentren der deutschen Hochschulmedizin. Als eines der 33 Universitätsklinika in Deutschland trägt es zum erfolgreichen Verbund von Hochleistungsmedizin, Forschung und Lehre bei. Weit über 400 000 stationäre und ambulante Patienten aus aller Welt profitieren jährlich von dieser Verbindung aus Wissenschaft und Praxis. Die Kliniken, Institute und Zentren vereinen alle Spezialisten unter einem Dach. Die Experten arbeiten fachübergreifend zusammen und bieten jedem Patienten die optimale Behandlung ausgerichtet an den neuesten Forschungsergebnissen. Das Universitätsklinikum Tübingen forscht für bessere Diagnosen, Therapien und Heilungschancen, viele neue Behandlungsmethoden werden hier klinisch erprobt und angewandt. Neben der Diabetologie sind die Neurowissenschaften, Onkologie, Immunologie, Infektionsforschung und Vaskuläre Medizin Forschungsschwerpunkte in Tübingen. Der Lehrstuhl für Diabetologie /Endokrinologie war in den letzten 25 Jahren Zentrum interdisziplinärer Forschung insbesondere unter Beteiligung der Chirurgie, Radiologie und Labormedizin. Diese ausgezeichnete Entdeckung der Prädiabetes-Subtypen war nur durch die interdisziplinäre Zusammenarbeit hat die Entdeckung der Prädiabetes Subtypen am Universitätsklinikum ermöglicht. Das Universitätsklinikum ist in vier der sechs von der Bundesregierung initiierten Deutschen Zentren für Gesundheitsforschung verlässlicher Partner. www.medizin.uni-tuebingen.de 

Helmholtz Munich ist ein biomedizinisches Spitzenforschungszentrum. Seine Mission ist, bahnbrechende Lösungen für eine gesündere Gesellschaft in einer sich schnell verändernden Welt zu entwickeln. Interdisziplinäre Forschungsteams fokussieren umweltbedingte Krankheiten, insbesondere die Therapie und die Prävention von Diabetes, Adipositas, Allergien und chronischen Lungenerkrankungen. www.helmholtz-munich.de

Das Deutsche Zentrum für Diabetesforschung (DZD) e.V. ist eines der acht Deutschen Zentren der Gesundheitsforschung. Es bündelt Experten auf dem Gebiet der Diabetesforschung und verzahnt Grundlagenforschung, Epidemiologie und klinische Anwendung. Ziel des DZD ist es, über einen neuartigen, integrativen Forschungsansatz einen wesentlichen Beitrag zur erfolgreichen, maßgeschneiderten Prävention, Diagnose und Therapie des Diabetes mellitus zu leisten. Mitglieder des Verbunds sind Helmholtz Munich – Deutsches Forschungszentrum für Gesundheit und Umwelt, das Deutsche Diabetes-Zentrum DDZ in Düsseldorf, das Deutsche Institut für Ernährungsforschung DIfE in Potsdam-Rehbrücke, das Institut für Diabetesforschung und Metabolische Erkrankungen von Helmholtz Munich an der Eberhard-Karls-Universität Tübingen und das Paul-Langerhans-Institut Dresden von Helmholtz Munich am Universitätsklinikum Carl Gustav Carus der TU Dresden, assoziierte Partner an den Universitäten in Heidelberg, Köln, Leipzig, Lübeck und München sowie weitere Projektpartner www.dzd-ev.de;

Mehr Informationen finden Sie auf der DZD Seite.

The next step is the development of non-invasive glucose measurement methods that do without needles. To this end, optical and optoacoustic methods are being investigated. One highly promising technology is Raman spectroscopy, which identifies molecules such as glucose based on their vibrations after interacting with light. Until now, it has been a problem that this method mixes signals from all skin layers, which impairs accuracy. Another key method that has already existed for a long time is the optoacoustic technology termed depth-gated mid-infrared optoacoustic sensor (DIROS)¹. It enables blood sugar to be measured by time-gating optoacoustic signals so that only measurements in the capillary-rich subcutaneous layers are recorded.

Improved Raman Spectroscopy for Glucose Monitoring
A new study by Zhang et al. in Nature Metabolism ² shows that Raman spectroscopy can be improved by focusing on vessel-rich layers of the skin. The researchers used multiple μ-spatially offset Raman spectroscopy (mμSORS). This method makes it possible to detect signals from deeper skin layers where the capillaries are located. The researchers compared the results of their method with the plasma glucose levels of 230 participants. The new technology demonstrated a high degree of accuracy and could represent a promising method for non-invasive glucose monitoring.

Further Challenges Must Be Resolved
The authors Birkenfeld and Ntziachristos point out that, despite the promising results, a number of challenges still need to be resolved before widespread use among people with diabetes is possible. The current measurement time of around eight minutes makes it difficult to capture rapid blood sugar fluctuations, which are important for precise hypoglycemia monitoring. In addition, the current device is as big as a desktop computer, which hinders use at home.

“Nevertheless, this technology is a step towards a needle-free future for glucose monitoring. On the whole, the mμSORS technology appears to be taking non-invasive glucose monitoring to the next level by providing a proof of concept for its applicability for people with and without diabetes,” says Prof. Andreas Birkenfeld. “Although some aspects need to be further optimized, such as accuracy in the hypoglycemic range, the measurement time, and the size of the device, the presented data are a convincing step towards a needle-free and non-invasive future for millions of patients.”

¹Uluc, N. et al. Non-invasive measurements of blood glucose levels by time-gating mid-infrared optoacoustic signals. Nat Metab 6, 678-686, doi:10.1038/s42255-024-01016-9 (2024).

²Zhang, Y., Zhang, L., Wang, L. et al. Subcutaneous depth-selective spectral imaging with mμSORS enables noninvasive glucose monitoring. Nat Metab (2025). https://doi.org/10.1038/s42255-025-01217-w

Original publication:
Birkenfeld, A.L., Ntziachristos, V.: A future without needles: non-invasive glucose measurements in patients with diabetes. Nat Metab (2025). https://doi.org/10.1038/s42255-025-01221-0

About the researchers:
Prof. Dr. med. Andreas Birkenfeld
Andreas Birkenfeld is the Medical Director and Chairman of the Department of Diabetology, Endocrinology and Nephrology at the University Clinic Tübingen as well as Director of the Institute for Diabetes Research and Metabolic Diseases (IDM), Helmholtz Munich. He is a member of the executive board and one of the five speakers of the German Center for Diabetes Research (DZD).

Prof. Vasilis Ntziachristos
Vasilis Ntziachristos is Director of the Institute of Biological and Medical Imaging as well as Director of the Bioengineering Center at Helmholtz Munich. He holds the Chair of Biological Imaging, Central Institute for Translational Cancer Research (TranslaTUM), School of Medicine and Health & School of Computation, Information and Technology, Technical University of Munich. He is the inventor of the DIROS technology¹.

More information can be found at the DZD webpage.

Higher cognitive performance, such as initial memory formation or prenatal learning, can be examined in this way. This provides interesting insights into the world of fetal perception. How does the fetal brain react to stimuli from the outside world such as light and sound or even the maternal speech?

Research shows that the fetal brain is able to distinguish repeated stimuli from new ones. The brain activity is lower in response to repeated stimuli than to new ones. Additionally, Prof. Dr. Hubert Preißl explains, “ We have many indications that language and the recognition of language are processes that take place in the maternal womb. There is evidence that the fetus is able to distinguish its maternal voice from that of a stranger”.

The documentary offers valuable scientific insights into the earliest developmental stages of human life and fetal perception. The documentary is available on the ZDF media library (link) and will also be broadcast on ZDF on February 9, 2025 at 7.30 pm on ZDF.

For more information on DZD NEXT Medical Doctoral Thesis Stipends, click here.

Subtypes of Prediabetes

“With the help of data from the Tübingen Diabetes Families (TUEF) study, researchers at the German Center for Diabetes Research (DZD) led by Robert Wagner (currently DDZ Düsseldorf) and Andreas Fritsche (IDM Tübingen) have succeeded in identifying six different subtypes of prediabetes,” reports Prof. Dr. Andreas Birkenfeld, Medical Director of the Medical Clinic IV of the University of Tübingen and Scientific Director of the Institute for Diabetes Research and Metabolic Diseases (IDM) of Helmholtz Munich at Eberhard Karls University of Tübingen. The subtype (cluster) makes a big difference for people suffering from prediabetes: Three of the newly identified clusters are characterized by a low risk (clusters 1, 2 and 4) and three by an increased risk of developing diabetes, fatty liver, cardiovascular disease or kidney damage. People in cluster 5 have a significantly higher risk of T2D, ASCVD and mortality. “The early identification of high-risk individuals can enable precise prevention strategies,” emphasizes Birkenfeld.

Remission of Prediabetes

Analyses of the Prediabetes Lifestyle Intervention Study (PLIS) show that, in addition to weight reduction, normalization of glucose regulation (remission of prediabetes) in particular significantly reduces the risk of T2D. The study found that targeted remission of prediabetes to normal glucose regulation plus weight loss reduces the risk of T2D more effectively than the weight loss alone recommended by the treatment guidelines. Key factors are a significant improvement in insulin resistance and a reduction in visceral fatty tissue.

Precise Prevention for People at Particularly High Risk

The authors argue that precision prevention in individuals at high risk of diabetes and ASCVD should focus on accurately identifying those at highest risk. This could lead to early remission and thus prevent complications in the long term.

Original publication:
Birkenfeld, Andreas L. et al. : Precision Medicine in People at Risk for Diabetes and Atherosclerotic Cardiovascular Disease: A Fresh Perspective on Prevention. Circulation (2024). DOI: 10.1161/CIRCULATIONAHA.124.070463

More information can be found at the DZD webpage.

New studies show that pharmacological treatment with GLP-1-RA and dual GLP-1/glucose-dependent insulinotropic polypeptide receptor agonists (GIP-RA) cause almost as much weight loss as gastric surgery. However, there are concerns that greater weight loss could have a negative impact on muscle mass, especially in more susceptible patients. Therefore, it is important to find out whether changes in the muscles from weight loss treatments such as GLP-1 RAs are negative for the muscles (maladaptive), a normal response to weight loss (adaptive), or even improve muscle health or function. Andreas Birkenfeld, DZD spokesperson and Director of the Helmholtz Institute for Diabetes Research and Metabolic Diseases (IDM) of Helmholtz Zentrum München at the University of Tübingen, describes it as follows: “The concept of adaptive muscle adjustment is known from the heart. With high blood pressure, the heart muscle has to pump harder and the heart muscle thickens, meaning that the heart mass increases. If the blood pressure is lowered, e.g. with medication, the heart muscle becomes thinner again and the mass decreases because it no longer has to exert as much force. This process is positive for the heart muscle and is characterized as adaptive. It is also known that the muscle mass that a heavy person needs to support him- or herself decreases when the person loses weight and the muscle no longer has to carry the same weight. This process is also generally considered to be adaptive.” How this is to be classified in the context of treatment with GLP-1 RAs, such as semaglutide or tirzepatide, is discussed in the new article in 'Circulation'.

Weight loss through GLP-1 RAs has an adaptive effect on the muscles

In order to answer this question, current findings and additional studies using magnetic resonance imaging, which provide more precise findings than previous methods of measuring muscle volume, are included. These indicate that the skeletal muscle changes in GLP-1 RA treatments are a normal, adaptive process. The changes in muscle volume correspond to expectations based on age, health status and weight loss. In addition, weight loss in persons with obesity leads to improved insulin sensitivity and less fat in the muscles, thus improving muscle quality. The quality improvement of the muscles is the important criterion for judging whether a process is positive or negative for the muscles. Better muscle quality is associated with a lower risk of loss of strength and function or even increases strength and function.

However, factors such as advanced age and pre-frailty can influence the selection of patients that are eligible for these therapies. Several pharmacological treatments to maintain or improve muscle mass in combination with GLP-1-based therapies are in development for these patients.

More objective methods needed to assess muscle health

The authors emphasize that the introduction of more objective and comprehensive methods to assess muscle health is crucial for the future development of GLP-1-based and other weight loss therapies and for patient-centered treatment optimization. This includes accurate and meaningful assessments of muscle quantity, composition, function, mobility and strength.

It is important that patients and doctors understand how the medication used affects muscle mass. With their article, the three authors therefore want to bring clarity to the current discussion. They say that this is important because it is foreseeable that many more patients will use these drugs in the future.
 

Original publication:
Jennifer Linge, Andreas L. Birkenfeld, Ian J. Neeland: Muscle Mass and Glucagon-Like Peptide-1Receptor Agonists: Adaptive or Maladaptive Response to Weight Loss? Circulation. 2024;150:00–00. DOI: 10.1161/CIRCULATIONAHA.124.067676

More information can be found at the DZD webpage.

· Prof. Birkenfeld, Director of the IDM, chaired three sessions and held a talk titled "New Insights into the Prevention of Type 2 Diabetes: Remission of Prediabetes in PLIS and DPP – The European-American Perspective."

· Dr. Simon Dreher presented his study results in his presentation about "Sex-Specific Differences of Human Skeletal Muscle: A Multi-Omics Exercise Study."

· Dr. Lorza Gil held a presentation on the "Impact of GLP-1/GIP Receptor Signaling on Human Pancreatic Adipose Tissue Organoids."

· Lorenzo Semeia spoke about the "Influence of insulin sensitivity on food cue evoked brain response in children.”

· Marlene Ganslmeier gave a presentation entitled "Reshaping the Diagnostic Algorithm to Improve Differentiation Between Type 1 and Type 2 Diabetes."

· Leontine Sandforth held a talk titled "Age-Related Decrease of Hippocampal Insulin Sensitivity is Linked to Unhealthy Fat Distribution in Women."

· Konstantinos Kantartzis spoke on the topic "Metabolic Dysfunction-Associated Steatotic Liver Disease, but Not Visceral Adiposity, is a Strong and Independent Determinant of Increased Plasminogen Activator Inhibitor-1 Levels in Humans."

The EASD continues to be an excellent forum for us to inform ourselves about relevant topics on an international stage and to exchange ideas with outstanding international scientists.

To the congress website
 

..what is the main aim of the project?  

We hypothesize that the cross-talk between lymphocytes with liver stromal cells as well as lymphocyte topography in MASLD and hepatic insulin resistance is driven by commensal bacteria. To study the role of the gut microbiota for immune zonation, we will use germ free and gnotobiotic mouse models, stool transplantation from human MASLD donors and metagenomic shot-gun sequencing and study the development of MASLD-like pathology in distinct murine models of insulin resistance and liver fibrosis. We will then use quantitative volumetric imaging, genetically modified mice and spatial transcriptomics to explore spatial topography in the hepatic immune niche. 

..how is it relevant to the public?  

The worldwide epidemic of obesity has led to an increasing prevalence of T2D and MASLD promoting the development of irreversible liver fibrosis. Our research should deepen our understanding of lymphocyte topography and immune-microbiome interactions in MASLD and liver fibrosis and may lead to disease-relevant personalized therapeutic strategies.

For me, the DZD means …  

... the opportunity to meet and (potentially) to collaborate with talented scientists across Germany to combat diabetes and its associated complications. 

More information to the DZD Young Talent Program is available at the DZD webpage.