Good afternoon. My name is Fernando Gomez Peralta. I'm the coordinator for the uh diabetes area of the Spanish Society of Endocrinology and Nutrition. And let me uh give you a warm welcome to this uh symposium from uh Abbott diabetes Care for the ATTD 2026 edition. And This is the. Uh, well, I would like, in fact, to, to, uh, present, um, uh, to recognize that as a clinical endocrinologist I had to refresh, uh, my knowledge on ketone bodies in the last months or years after starting to hear about the promise of a continuous ketone monitoring sensor. I even recovered. Some books from my degree or um my studies to obtain a physiological description of the basics of ketones. You will see in my presentation some really vintage figures and references, many published more than 50 years ago. Latest one, however, it's also a way to explain how scarce the research on this topic has been in the last decades. I hope you will enjoy reading or rereading these ancient pearls of knowledge and reminding you of the basic of this topic could be of some help. But I will also try to present recent data and even share a view of the future I foresee after this technology. Opens an unknown reality. The term ketone bodies refers to 3 molecules acetocetate, 3 beta hydroxybutyrate, and acetone. The two predominant kitten bodies measured in urine or blood over the last few decades. Are mainly energy fields. Produced by the liver from fatty acid metabolism under low carbohydrate conditions. In healthy adults, the liver can produce up to 185 g of ketone bodies per day. In healthy adults it's that figure 3 big oxybutyrate is formed from the reduction of acetocetate in the mitochondria, and these two opposing opposing arrows. In every picture. Describe a continuous conversion between them. Pathologic production in diabetic ketoacidosis causes an hydrogen ion overload which quickly exceeds buffering capacity and results in high anion gap metabolic acidosis. The 3rd ketone body is acetone. It's formed via the spontaneous decarboxylation of acetocetate in pasted with DKA. Acetone, while present in abnormally high concentration during uh uh DKA does not contribute to metabolic acidosis. Acetone is slowly excreted. Through the lungs, it generates a distinctive aromatic. A smell on patient's breath in DKA and it may have been the molecule used as clinical detection method for DKA for centuries somehow. Acetone smell, keto ketosic smell, um, has been the former monitoring for us, clinically monitoring for us of ketosis in the past. During fasting, free fatty acids released from adipocytes undergo ketogenesis in the liver, generating beta hydroxybutyrate and acetylcystate. Beta hydroxybutyrate acetocystate is transported into circulation by monocarboxylate transporters 1 and 2 and used via ketolysis as an energy fuel. Sears in various organs including the brain, heart, kidneys, and skeletal muscle. In fact, ketone bodies provide nearly 2/3 of the brain's energy needs during periods of prolonged fasting of starvation. Going beyond uh technical considerations, beta hydroxybutyrate is preferred over acetoxytate because beta hydroxybutyrate more dynamically reflects the metabolic state. This, um, a nice, uh, picture from this old, um, um, article reflects the dynamics of glucose insulin and, um, ketone bodies during, um, hyperglycemic crisis in two patients. Administration of insulin causes blood beta oxybutase levels to fall earlier and more rapidly than acetocytase levels. During the treatment of ketoidesis in the left side of, of the slide you can see a case described. There's typically an initial rise in this acetocytate which may remain elevated for several hours despite clinical improvement and declining of beta deoxybuterase and glu glucose levels. Then betadioxybutyrate is the uh ketonbo uh body prefer to describe dynamically, continuously, the, uh, clinical situation. In starvation and diabetic ketoacidosis. Let's come to the present. This recently published article assess continuous ketone monitoring profiles in adults with type one diabetes. As expected, a lower daily carbohydrate intake is associated with higher continuous ketone monitoring ketone readings. Ketone levels were predominant, predominantly um elevated during uh dawn and evening hours rather than exclusively during fastings, fasting. More than 30 years ago, it was shown that stress hormones such as cortisol or. Uh, adrenaline, in addition to insulin deficiency or in a setting of insulin deficiencies, deficiency influence ketone body levels according to a circadian rhythm. That's very interesting for type 1 diabetes patients. That's also very interesting in the last years for describing hyperglycemia and the rela relationship with hypercortisolemia in type 2 diabetes as well. This clear illustrative, I, I, I find it very nice graphic summarizes how counterregulatory hormones, stress hormones stimulate ketone body metabolism primarily at the uh adipocyte. In the setting of a low insulin to glu glucagon ratio in the liver or in the, uh, or any insulin deficiency uh situation, this provides the main framework for understanding how ketone body levels in the blood can offer additional insight into. Actual tissue insulin action and the concomitant also and the concomitant stressed state. This is only a personal insight, but probably ketone bodies could also be used to assess. The actual tissue level effects of insulin this is an earlier study showed that minor differences in free insulin blood levels are or reflects in bigger changes in ketone bodies. Providing a more precise information of actual insulin action. Then this information, this additional information from uh kitten bodies can feed, for example, the algorithm for um um um closed loop uh integrated system and pumps for insulin delivery or anyway, adding information on glucose levels um alone. Several physiological and pathological conditions have been associated with ketosis. Particularly important are diabetic ketosidosis and the more recently described form of glycemic DKA related or linked to SLT2 inhibitors use. DKA and keto monitoring will be covered by Professor Datarila shortly. I would just like to introduce his talk and highlighting how critical this condition is, as well as the changes we have seen in epidemiology of DKA in the recent years. The latest ADASD consensus report on hyperglycemic crisis in adults. With diabetes, stated that global data clearly show an increase in the number of DKA and hyperglycemic crisis admissions over the past decade, with recent evidence reporting a 55 55% increase in the rate of DKA hospitalizations, admissions. This paper in the uh right side of the of the slide. Um, published just a a few days ago showed a plateau or even a slight upward trend in mortality rates among type one diabetes patients with EKA from 2016 to 2019. Obviously, the COVID-19 uh pandemic has a half mired. Impact on mortality, but it's clear that we need to improve outcomes in this potentially fatal diabetes complication. Despite thera therapeutic advances in the uh last years, DKA hospitalizations continue to increase and to uh obtain bad outcomes in our practice. Let me advise to uh give your attention to this um uh presentations and communication that will be presented uh in this topic during this uh ATTD 2026 uh um conference. Sedu and colleagues will present. Uh, that rising, the rising burden of diabetic ketosis in the UK, they conclude that decay rates have increased and confirmed previous results in both diabetes types and personalized education acts and access to real-time keto monitoring are warranted in their opinion. They will also present how mm previous DKA is the, the, the, the first uh risk factor uh to uh um another DKA event and also some risk factors includes female sex. Several international studies have confirmed a clear reduction in these DKA events following the initiation of CGM. The relief program in France showed these amazing results in people with type 1 diabetes, general type 2 diabetes population, type 2 diabetes treated just or only with basal insulin, and even in those treated only with oral agents. The Swedish study showed a similar reduction when compared with the population using capillary fingert testing. Our data in Spain, and let me show you some very, very recently analyzed um by us uh data from Spain, indicated a clear reaction also in both type 1 diabetes and type 2 diabetes. However, the addition of continuous keto monitoring can lead to an even greater reduction and an improvement in the outcomes of these DKA events. Uh, Manuel Cozon, and colleagues will present in this ATTD 2026 conference then. Patients knowledge and various took it on self-monitoring um perspective. And they conclude that high interest in dual glucose ketone sensors highlights limitation of current methods and the need for accessible patient-centric solutions to support decay prevention. And also we some and colleagues. will present the provide the pers perspective on how hyperkeonemia, DKA burden. And keton monitoring in type 1 and type 2 diabetes, they conclude these insights will highlight needs around ketone management, which could include increased awareness and access to ketone monitoring tools to help fill the current gaps in ketone management for patients with diabetes. Regarding them, um, unequally, uh, termed glycemic diabetic ketoidosis because you already know that, in fact, uh, this situation. Um, uh, presents with, uh, hyperglycemia, not reaching the, the highest um glucose levels seen in classical DKA but in hyperglycemia anyway, but this case published some years ago illustrates how management of this frequently underdiagnosed condition could be optimized. Through access to dynamic ketone level data, in this case, if we would have access to ketone levels at that, at this point, at this moment, probably we will approach the situation um uh before or earlier and treat the patient uh in an optimized way. And we should bear in mind that the off-label use of SLT2s in type one diabetes is increasing worldwide and SLT2s uh use in type 2s is also increasing, um, um, and, and rocketing in the, um, in the, uh, last years. These are data from the USA. Uh, confirming that in the population with type one diabetes, the use of SLT2s and then explaining the rising of, uh, hyperglycemic crisis and DKA in this population is, uh, warranted and this increase in, in the use of SLT2s is not only, um, um. Uh, uh, limited to the population with obesity, uh, within the type one diabetes population. The range of potential kitten body actions is extremely broad. Intracellular signaling mediated by beta-droxybutyrate can trigger numerous processes related to mediators of long-term diabetes complications. Thus, the role of ketone bodies is not limited to type 1 diabetes and DKA, and it may also provide information about complications associated with type 2 diabetes. Of particular interest is the possibility. That ketone bodies serve as an additional fuel source for the myocardium in people with heart failure, which may at least partially explain the benefits of served with SLT2 inhibitor therapy. Shown here graphically is a brief history of ketone body research outlining the discovery mechanistic characterization and importance of ketone bodies in human human phys physiology and disease. This can serve as my summary. It's particularly interesting that in recent years the focus. Has been on the role on ketone bodies in type 2 diabetes, inflammation, NFLD or MALD, and heart failure. Therefore, continuous ketone monitoring can also be complementary to the topic of CGM in earlier stages of type 2 diabetes that Doctor Bilmot will discuss shortly. Thank you very much for your attention, mucha gracias.
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