Tuesday, 10 April 2012

Is there really a link between Diabetes and Dupuytren's and Ledderhose disease?

Relationship between Diabetes and Ledderhose Disease (Plantar Fibromatosis) and Dupuytren’s Disease.
I am looking today at some of the information behind this link to see if we can find out if it is real and if it is real why is it real?

So firstly as I said yesterday I was led to a paper where this is briefly discussed and so thought I would make it the topic for today. Firstly I do not have diabetes and none of the people whom I have spoken to have mentioned having it but then I haven’t asked that many people whether or not they have diabetes so maybe it is something I should go back and ask them.

Still part of my curiosity behind whether this is fact or fiction is based on the fact that most of the people I am coming across do not display many of the predisposing factors such as diabetes, smoking, drinking and epilepsy. This lack of a correlation behind the literature and my experience is probably purely down to the small numbers of people that I have spoken to and I am sure that if you speak to the people in the know over at the International Dupuytren’s Society of the British Dupuytren’s Society they will tell you that they have seen the higher incidence in diabetes suffers (I will ask).

 So I will try and take us on a journey of the literature to see if this link exists which after a quick glance I think it does but I lets how I feel by the time I finish this post and the research. From what I have seen though I can say that there appears to be no or little understanding of the molecular mechanism which may underlie this predisposition.  

(1) Elhadd et al, 2007, Plantar Fibromatosis and Dupuytren’s disease: an association to remember in patients with diabetes, Diabetic Medicine, 24, p1305:

 So this is the paper that was referenced in yesterday’s paper and I will probably be using a lot of the references this paper to work my way back through the data. Here they, through a past paper, comment that the link between DD and diabetes maybe oxidative stress. Oxidative stress is a type of cellular stress and it will result in the production of reactive oxygen species (ROS) which can then in turn cause damage including DNA damage etc which then causes problems with the cell. ROS being a factor towards the occurrence of Dupuytren’s would also make sense of the link to smoking.

They then go on to mention the link between Dupuytren’s and other hyperproliferative disorders such as Ledderhose. They mention a case where a lady had long term Dupuytren’s in both hands and had recently started to show Ledderhose in both feet and she is a diabetic. I think the main purpose of this article though is to raise awareness that in diabetic individuals with Dupuytren’s or indeed anyone with Dupuytren’s or diabetes that you should keep an eye out for the lesser known Ledderhose disease.

Ok so I cannot say a lot from this abstract and I get the impression that the full article is in French. Still here they discuss 42 diabetic patients with Dupuytren’s and say that there it is usually not that bad in diabetic patients and often due to age the requirement for surgery is minimal.  Although they say that if you have one disease you should check for the other they do not give any stats as to frequency other than to say it is 5 to 10 times greater than in the rest of the population.

Right so at this point I decided that things were not going to plan as I hadn’t found any facts or figures that were actually showing me that this link existed. Then however with a bit more perseverance and some time on PubMed I stumbled across a couple of useful papers. Here I am only able to discuss the abstracts as they are both in foreign languages and are too old for me to be able to easily plonk them somewhere on the internet to get them translated. So...

So here they are looking at 100 randomised diabetic patients for the occurrence of Dupuytren’s contracture and found that there were 42 (therefore 42%) cases of Dupuytren’s disease which is clearly higher than what you would expect in the normal population. Further to this they also say that the rate of Dupuytren’s increased with age and length of time with diabetes though of course these things are interlinked so the only thing they would say is that it is also linked with age.

In this paper they are looking at nearly 1000 patients with diabetes and 1400 without diabetes though apart from this I am unable to determine other background such as male / female, smoker / non-smoker etc etc. Still here they find that nearly 18% of diabetic patients have Dupuytren’s disease whilst less than 1% of the non-diabetic patients have Dupuytren’s disease. Further to this again there was an increase in DD cases with age and that it was rarely found in patients under 40 years old.

I think that the above 2 papers in particular indicate that there is in all likelihood a link between diabetes and Dupuytren’s although I am unable to see information linking this to Ledderhose but I guess due to the similar nature of Dupuytren’s and Ledderhose it would make since.

This all got me thinking about how can the 2 be connected and my mind instantly jumped to IGF2. For those that have not seen it before see the picture below.

The reason that my mind went here is because IGF2 is short for insulin like growth factor and I know that the maybe some interplay between the two pathways and perhaps IGF2 gets up-regulated and this leads to a predisposition to Dupuytren’s and related disorders. So I did a Pubmed search for IGF2 and diabetes and not a lot has popped up, I think I saw one that suggested that IGF2 is actually down in diabetic patients so this route is probably not correct but I imagine that it has to be something along this way.

So at the end of the day I have to agree with the data that supports this link and was unable to further expand my knowledge about the cause of this link as I could not find any supporting information.

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