Contributing authors: Iina Laitinen, Senior Director PET Imaging @ Antaros Medical, Edvin Johansson, Senior Director MR Imaging @ Antaros Medical, and Martin Schain, Director PET Imaging @ Antaros Medical
Last week, over 11,000 delegates attended the European Association for the Study of Diabetes (EASD) Congress onsite in Hamburg, Germany, or virtually. Throughout the week (October 2-6) we were able to listen to many interesting sessions, presentations, and discussions.
Antaros Medical was kept busy, speaking in a symposium, giving oral presentations, and supporting our collaborators and colleagues.
In this post we will be discussing our 3 personal highlights from the congress and reflecting on why we found them particularly interesting.
Highlight 1: Obesity heterogeneity: clinical aspects
The session on the heterogeneity of obesity stood out for us. Obesity and chronic weight management were hot topics throughout the congress, but the talks of this session that were given by Roy Taylor, Matthias Blüher, and Mikael Rydén helped put into context some potential reasons for why we often observe mixed treatment responses in obesity and obesity-related diseases.
The first presentation by Roy Taylor covered data from various trials that supported the idea that individuals have different tolerability to fat in the liver and pancreas, and that those who develop type 2 diabetes (T2D) do so because the amount of fat is more than can be accommodated by the individual. This raises questions about the utility of fixed liver fat thresholds that are being used to determine risk for developing metabolic complications.
Then Matthias Blüher discussed the concept of metabolically healthy obesity (MHO), those patients with obesity that do not have the metabolic complications. He also proposed that this is a transient condition, as the risk for complications is still elevated in MHO when compared to healthy, non-obese individuals. Linking to the ideas presented earlier in the session, he suggested that adipose tissue mechanisms such as the ‘expandability’ of what can be considered ‘safe’ fat depots, could help to explain this phenotype. The comparably favourable prognosis for MHO makes them an interesting group for future research, to help further our understanding of risk reduction of metabolic complications or potentially slowing down disease progression.
Finally, Mikael Rydén presented data supporting the idea that heterogeneity in adipocytes may also help to explain the differences in treatment responses. Research has characterised at least 3 specific adipocyte subtypes with different insulin responses. Clinical studies investigating the role of this in the heterogeneity of responses to pharmacological treatments for obesity and diabetes are ongoing, and it will be very interesting to see the results in the coming years.
What we took away from this session was the importance of looking beyond weight loss as kilograms lost when thinking about obesity. The complexity of obesity as a disease, and the range of processes and mechanisms involved needs to be further understood. One aspect of this is in understanding different treatment responses, as in the future this will help to determine which treatments will be optimal for individual patients.
Highlight 2: Survodutide-Cy7 acts through circumventricular organs in the brain and activates neural pathways associated with appetite regulation
While there was a lot of research focused on incretins presented at the congress, the short oral discussion given by Tina Zimmerman was another highlight for us. She presented data demonstrating that glucagon-like peptide-1 (GLP-1) signals to the brain via receptors outside of the blood brain barrier.
GLP-1 is a peptide hormone that is too large to cross the blood brain barrier. However, given that circulating GLP-1 has been shown to induce satiety, there is some type of communication with the central nervous system, but the underlying mechanism here is not yet well understood.
The data from this preclinical study showed that brain regions outside of the blood brain barrier were activated upon administration of a GLP-1/glucagon molecule, and that these regions signalled regions inside the brain that are known to be associated with reductions in food intake. She also presented that this effect was mediated via the GLP-1, and not the glucagon.
This was interesting to us because it may provide a partial explanation for how GLP-1 can induce satiety without crossing the blood brain barrier. It also contributes to our growing understanding of how newer pharmacotherapies, incretins in particular, are capable of modifying feelings and behaviours without entering the brain. however, it also demonstrates how much we still don’t understand about the mechanisms behind these drugs, and how they affect different organs, the brain included.
Highlight 3: Mildly elevated liver fat content is characterised by central insulin resistance: evidence from a positron emission tomography study
Discussions as to what can be considered a normal percentage of liver fat was touched on over multiple occasions throughout the week, and the oral presentations given by Mikka-Juhani Honka offered data to this effect.
Hepatic steatosis is generally defined by liver fat content equal to or above 5.56%, however recent studies have suggested that a lower threshold of 1.85% be used. In line with what was also presented during the EASD-Lilly Centennial Anniversary Prize Lecture by Gerald I. Shulman, this study investigated whether individuals with mildly elevated liver fat content (1.85% – 5.55%) have tissue-specific insulin resistance compared to participants with less liver fat.
Mikka-Juhani Honka presented results from a study that measured tissue specific insulin induced glucose uptake using [18F]-flurodeoxyglucose /FDG) Positron Emission Tomography (PET) under hyperinsulinemic clamp (HEC) and liver fat using Magnetic Resonance Spectroscopy (MRS), in non-diabetic individuals. The study showed that mildly elevated liver fat content was associated with impaired insulin sensitivity in visceral adipose tissue and elevated glucose uptake in the brain.
For us, this emphasised the importance of looking holistically at metabolic disease. Insulin resistance is linked to a range of health concerns and co-morbidities, and looking more closely at multiple organs in this group of individuals with levels of liver fat content below what is generally considered hepatic steatosis might help to further our understanding of some of the different mechanisms at play.
In summary, while there was a whole programme of interesting research at this year’s EASD Congress, we chose 3 of our personal highlights to reflect on in this post:
- Obesity heterogeneity: clinical aspects, Roy Taylor, Matthias Blüher, and Mikael Rydén
- Survodutide-Cy7 acts through circumventricular organs in the brain and activates neural pathways associated with appetite regulation, Tina Zimmerman
- Mildly elevated liver fat content is characterised by central insulin resistance: evidence from a positron emission tomography study, Miikka-Juhani Honka
We are already looking forward to attending EASD Congress 2024 next year in Madrid, Spain.
The views and opinions expressed in this article are solely those of the contributing author/s. These views and opinions do not necessarily represent those of Antaros Medical.
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