Interview with FinnDiane study Part 1: Predicting type 1 diabetes complications with urine metabolites

While type 2 diabetes, a chronic disease that typically occurs at later stages in life and is more common, type 1 diabetes affects individuals at an early age. Due to the early development of the disease, linked complications — such as kidney disease — have a higher probability of developing during an individual's lifetime. Moreover, the person becomes dependent on insulin from the very beginning, which also affects their quality of life.

In a two-part interview (read part two here), Nightingale sat down with Stefan Mutter and Erkka Valo — researchers from the world-leading Finnish Diabetic Nephropathy (FinnDiane) Study Group lead by Prof. Per-Henrik Groop — to discuss how one of the most extensive studies on type 1 diabetes in the world is tackling this chronic disease.

In this first part of a two-part interview, the two researchers shed light on FinnDiane’s mission, the group’s patient-study methods, how they are trying to predict and prevent complications related to type 1 diabetes and about introducing the newly available urine metabolites data in their latest research work. Excerpts:

FinnDiane is one of the leading studies on type 1 diabetes. What’s its main objective?

Mutter: The FinnDiane study looks at complications arising in individuals with type 1 diabetes, that is, individuals who typically have diabetes from a very young age because of an autoimmune reaction in their body. These patients are unable to produce insulin and need external insulin throughout their life. These individuals have a lifelong risk of developing complications related to their diabetes. The FinnDiane study focuses on complications, specifically on diabetic kidney disease.

For type 1 diabetes, FinnDiane is one of the largest cohorts in the world. Could you tell us more about how you study the patients?

Mutter: It’s an ongoing study that began in 1997. Currently, we have over 6,000 study participants and are constantly recruiting new ones who come back for follow-ups every five years. I think we just had the first batch of patients who came back for their fifth visit. This means we get a complete picture of their health every time they come for follow-up visits.

That said, we also continuously follow the patients’ electronic health records. Therefore, we are aware when they develop, for example, cardiovascular disease or start showing signs of kidney disease. We also get to see their outpatient medication records from KELA, the Social Insurance Institution of Finland — additional information that’s not directly captured during an official study visit.

The study is spread across Finland and we have multiple centres all over the country that collect these data for us. And that’s why, although it’s not a population study, it comes very close to one.

So, what happens during these study visits?

Mutter: The participants fill in a questionnaire about their health as well as share their family’s health history. Then we collect their blood and urine samples (24-hour urine or overnight urine). Recently, we started scanning the participants’ bodies to measure body fat distribution and bone density. We have scanned around 700 people so far. Now, that’s also a part of the standard checks. Apart from this, the participants are also invited to maintain a food diary. For some of them, we take a stool sample and measure their 24-hour blood pressure. We have participants who also took part in the breath analysis and got their ECG done.

Valo: At times, we also look at the pulse velocities and stiffness of the veins. So, it's quite detailed.

From what you tell, it’s an extremely detailed study. So, what’s your role in it?

Valo: I've been working as a bioinformatician in FinnDiane for five years, currently I am analysing the urine metabolite data from Nightingale together with Stefan. I also participate in the genetic projects, where we've been looking at the association of genetic variance with diabetic kidney disease or diabetic nephropathy to be more specific.

Mutter: We’ve been trying to identify people with a high risk of developing complications as early as possible. This can help avert their illness or at least slow down the disease development process. It’ll also help in preventing other complications related to the illness. That’s our main job.

So, what’s the big picture? If you could briefly share how your research improves the lives of people with diabetes?

Mutter: Even today, prevention of complications is hard. For now, early detection is the best chance we have against them. This way, we can at least slow down their development with interventions.

Valo: We are still quite far from using genetics clinically to be able to classify people into groups and identify the ones at high risk of diabetic kidney disease. Someday, if we find enough genetic variants that are associated with diabetic nephropathy, it might be possible. But that's quite far down the line.

Mutter: We know that one-third of the population who have type 1 diabetes develop kidney disease. This segment of the population has a much shorter lifespan and lower quality of life. However, we don't know what makes them more vulnerable to kidney diseases than the rest of the population. Solving this mystery is also a big part of our research.

What are your plans for upcoming studies?

Mutter: Recently, we started looking at NMR-based blood measures and urine measures and how they correlate. We are interested in specific markers, like TMAO (Trimethylamine N-oxide) and want to examine how it relates to other blood markers. In the future, we will surely examine the associations between urine metabolites and all the other hundreds of blood metabolites that we have. It will be interesting to find out the associations between urine and blood.

Fully quantitative urine metabolite data are quite new. Do you have a favourite urine marker?

Mutter: I quite like glycine because in our study it showed a different behaviour between the early and late progression of diabetic kidney disease. That was exciting. But I also like branched-chain amino acids because in studies using blood, they already show associations with insulin sensitivity and can predict the risk of type 2 diabetes.

Valo: Glycine showed an association in the genetic study too. So, I would have to say glycine is my top pick as well.

Mutter: Also, our colleague is looking at the gut microbiome and she was happy to see 2-hydroxybutyrate among the metabolites in the urine platform.

Since data from urine are new, some researchers who have these samples may not know how to utilise them. What would you like to tell them?

Mutter: If they're interested in kidney disease, hopefully, I wouldn't even have to convince them to study the urine data. After all, urine is a product of the kidney. Also, for researchers doing non-kidney related research, like the gut microbiota, I would encourage them to look at the urine since gut microbiota influences the urine.

About practicalities, urine is non-invasive and the study participants may be more willing to give a urine sample than a stool sample. So, it’d be easier to measure, and studies might get more patients.

In short, it's a new area, there are possibilities of many new findings and it’s a big plus that urine is so easy to measure.