Prof. Dr. Julia Szendrödi on type 2 diabetes comorbidities and guideline-based therapy

How can fatty liver, heart, and kidney failure be prevented as type-2 diabetes comorbidities? This interview by Dr. Petra Sandow tackles the issue.

This article is a translation from the original German interview.

Interview takeaways

How to proceed with comorbidities such as non-alcoholic fatty liver, heart failure or renal insufficiency? Screening should be standard when there is an increased risk of diabetes. Pre-diabetes does not necessarily lead to diabetes, but pre-stage is already associated with various comorbidities. Patients with pre-diabetes or manifest diabetes may develop renal failure, steatosis or heart failure. Preventive measures are available to prevent this:

  1. Steatosis: In diabetic patients, the probability of developing non-alcoholic fatty liver is about 70 percent. Established markers are: the FIB-4 score, which calculates the probability from the blood values, while a liver sonography can determine a density change. 
  2. Renal insufficiency: Check kidney values, for any deviation from the normal range in the excretion of proteins.
  3. Heart failure: If there is shortness of breath, especially on exertion, do a cardiac echo. If someone has a normal ejection fraction, but still have shortness of breath, a closer look should be taken. This is where treating physicians can intervene preventively or therapeutically.

The most important thing is good physician-patient communication. The patient should know: What are my target values? What is my personal risk? What can we do to prevent the manifestation of these comorbidities without worsening the quality of life? Here, the patient has to be brought on board, and cooperate with themselves.

Prof. Dr. med. Julia Szendrödi in interview

In the context of the 2023 German Society of Diabetes (German acronym: DDG) congress in Berlin, Dr. Petra Sandow met with Prof. Szendrödi in our esanum TV studio for an exchange on the state-of-the-art guidelines on the issue. 

Our interviewing partner, Dr. Petra Sandow, is is a specialist in general medicine with a focus on infectiology. She studied human medicine in Berlin and Münster. After clinical work in gynaecology and internal medicine, she has been practising as a general practitioner in her own practice in Berlin for more than 30 years.

Prof. Dr. Julia Szendrödi is the Medical Director of the Clinic for Endocrinology Diabetology Metabolic Diseases and Clinical Chemistry at Heidelberg University Hospital (Universitätsklinikum Heidelberg), Germany.

Dr Sandow: What should we pay attention to in the treatment of our patients with diabetes mellitus when mobilities are present, such as non-alcoholic fatty liver, heart failure, renal insufficiency? What should we pay attention to?

Prof. Szendrödi: We have to screen as soon as there is an increased risk of diabetes, i.e. so-called prediabetes. This does not always have to lead to diabetes. In the meantime, however, we know that this pre-stage alone is associated with these comorbidities. We have to screen our patients with pre-diabetes or those that already manifest diabetes. We have to look at whether there is an increased risk that these patients will develop renal insufficiency, steatosis or cardiac insufficiency. And that is already half the battle, namely to determine that.

It is not only a question of establishing whether this disease is already present, but also of establishing whether something is currently developing in this direction. Because then we can take preventive measures. In the case of steatosis, we know that we cannot screen all patients. But we do know: With diabetes, the probability that someone will develop a non-alcoholic fatty liver is about 70 percent. We can screen here.

There are established markers that are now slowly becoming a standard, for example FIB4, which is a marker that can be calculated very easily from blood values that we normally also take. That is one possibility. Or simply hold the ultrasound probe on the liver and see if the density changes. And then to talk to the patient. In the case of the kidneys, of course the kidney values, but also the excretion of proteins or whether we see a drop in the normal range. And that we pay very individual attention to this, because we know that it is very heterogeneous how quickly someone develops such comorbidities. And heart failure. We know that if someone has shortness of breath, especially during exertion, we have to do a cardiac echo to clarify the issue. And even if it's normal, we now know that good function does not mean that someone's heart is healthy.

There is HFrEF and HFpEF, i.e. slightly reduced ejection fraction or normal ejection function - if someone has this but still has shortness of breath, then we have to take a closer look, and this is where preventive or therapeutic measures can be taken. And the most important thing is that we talk to the patient. So that they know: Where are my target values? What is my personal risk? We to define this individually. What can we do to prevent the manifestation of these comorbidities without worsening the quality of life? We simply have to get the patients on board. Because it depends to a large extent on them to do something about it.

Dr Sandow: So look for comorbidities in advance. What about the therapy of diabetes now? Are there antidiabetic drugs that we should avoid at all costs or are there those that we should recommend, that we should use?

Prof. Szendrödi: Yes, that is definitely the case. We now have very flexible guidelines that are rewritten quasi annually because more and more data is added. We have a lot of possibilities to intervene in order to stop this. Or also a resolution, a remission of the comorbidities or also of the diabetes. I think that is the most important thing. We have to address the issue of self-medication. And as you say, there are also antidiabetic drugs that we should avoid.

We are now moving away from a step-by-step approach. Especially in the case of heart failure, we have reached the point where we have data and we decide to start immediately, with at least 50% of the target dose during the first hospital stay and then quickly increase the dose. But the limiting factor is simply the blood pressure, but there are data on that in any case.

There is not yet any data however, for kidneys. With steatosis, we still have relatively little evidence. But the most important thing is of course the life goal intervention. We know that with those who have an increased weight, with steatosis for example, a 10% weight loss = 100% resolution of steatosis: we absolutely have to communicate these figures to the patients. This is not not just a conversation about how you have to pay more attention to your health, but that you really put the numbers on the table. Because it is very motivating to know that I now have a diagnosis, I have diabetes and a comorbidity, but I will get out of it. And then initiate the drug therapy.

What do you have to watch out for? If there is already severe renal insufficiency, we have to be careful with the SGLT2 inhibitors. Because there is a downward dip at the beginning. But most patients can be treated in time and benefit greatly from them, even across the entire class of SGLT2 inhibitors. In type 1 diabetes we are not allowed to write them down, we know that. Neither for the kidneys nor for heart failure, which is a pity because of the risk of ketoacidosis. We give pioglitazone for non-alcoholic fatty liver. There, the efficacy is also determined histologically. But we have to be careful with heart failure: It is positive for CHD, but we are not allowed to give it for heart failure, and we are also not allowed to give saxagliptin. Basically, however, it is usually the case that we are too hesitant with prescriptions.

Dr Sandow: You have already mentioned the guidelines, that they are very much undergoing change at the moment. Do you think it would be useful to focus more on the therapeutic approach indicated in the guidelines for these multimorbid diabetic patients?

Prof. Szendrödi: Yes. Basically, the guidelines are very much geared towards the risk of cardiovascular diseases and nephropathy. It's a bit divided into two parts. Neuropathy is somewhat neglected. But basically most patients have both. Because steatosis is predetermined for cardiovascular diseases. That is the real problem: not so much the liver-related mortality, but really the cardiovascular mortality, which is increased by the steatosis. That is, they go hand in hand, and we know that the cardiovascular risk is also significantly increased in patients with nephropathy.

But there is actually an overlap between the therapeutic approaches, and you just have to break it down one by one. But the most important thing is to think multidisciplinary. So the cardiologists are now thinking a lot about diabetes, which is good. And the nephrologists are actually always very multidisciplinary from the outset. To a certain extent, the general practitioner simply has to keep an eye on this and can do a lot, especially in prevention, and must then consider at what point do I continue to give the patient to a specialist?

Dr Sandow: Let's look again at the concomitant diseases, which we have already talked about in great detail. If our patients with diabetes have already developed comorbidities, does that also have a negative impact on their further prognosis?

Prof. Szendrödi: Yes and no. Of course, the comorbidities are what limit the life expectancy of our patients with diabetes. But it doesn't have to be, because we know that if someone is very well adjusted according to the guidelines and all the risk factors are well adjusted, then I, as a patient with diabetes, even have a survival advantage if I manage everything well, because very few patients receive as much attention as patients with diabetes. This is because of all the things you need to do and follow up on: losing weight, exercising, not smoking, adjusting your cholesterol. The vast majority of patients don't know their target values very well. I always ask my patients and discipline myself to think about it carefully and to find out whether I am already on target or not. In the end, patients can actually benefit from this and for us as diabetologists, who are multidisciplinary, it is also very helpful to have these guidelines.

Dr Sandow: Lastly, most people with type 2 diabetes in the German context are cared for in GP practices. If the comorbidities are now added, is that still sufficient or would you say, that is not the case? Should they also be seen by specialist colleagues, by cardiologists, nephrologists, and if so, how often?

Prof. Szendrödi: Most patients first go to their family doctor and that is good, if there is a relationship of trust and the general practitioner has always known his/her patients and that is actually the most important thing: that you know what the patient needs, what he/she is willing to do and where do I pick him/her up? Do they respond more to numbers that you have to achieve or to things that you can do again. So the most important thing is to define goals together and then, as you say, when it gets more complicated, to assign them. But there has to be someone who notices this. Because patients can't judge that well themselves. Some are more motivated and let themselves be referred, others wait and compensate a lot and are prepared to give up a lot of quality of life. Because they think to themselves, "I just have this diabetes and it is associated with a reduction in quality of life".

So there has to be someone who accompanies the patients, refers them and then also implements what the specialists recommend. It also often happens that patients come to hospital with a diabetic metabolic derailment, then an extensive medication and therapy plan is written down, and patients in an extreme situation can't really cope with that either. Then someone has to be there to go through it point by point and then make sure that it is continued and that the annual check-up takes place in any case. So an annual check becomes relevant in any case, and there are GPs who have additional training and are confident enough to do this. I think this can be managed very well.