Friday, October 24, 2014

Type-1 and Obstructive Sleep Apnea


A reader of this blog asked me what I knew about the relationship between Obstructive Sleep Apnea (OSA) and Type-1 Diabetes.  I didn't know anything, but over the last few weeks, I've been looking through the research.  There is not a lot, but what there is, I've summarized here.

The sound track for this posting is Bon Jovi's I'll Sleep When I'm Dead:
http://grooveshark.com/#!/s/I+ll+Sleep+When+I+m+Dead/wu1oT

This is an area where it is important not to mix up type-2 and type-1 diabetes, and to remember that people who say "diabetes" almost always mean "type-2 diabetes".  One of the more common causes of OSA is being overweight, and this is also one of the more common causes of type-2 diabetes (although in neither case is it the only cause).  The result is that OSA is highly correlated with type-2 diabetes.

However, there has been a little research on type-1 diabetes and Obstructive Sleep Apnea (OSA), and that is what I'm focusing on here.

But first, a little background on OSA:
http://en.wikipedia.org/wiki/Obstructive_sleep_apnea
http://www.webmd.com/sleep-disorders/guide/understanding-obstructive-sleep-apnea-syndrome

Question 1: How common is OSA?

Simple Answer: about 5% of the general population, and about twice that in people with T1D.

Detailed Answer: The overall rate is about 4% [r2] or 5.7% [r4] of the population, but the rate for people who have T1D is about 10% [r3] or 12.7% [r4].  One study [r6] found that sleep apneas were much more common in type-1 diabetics, than in type-2 diabetics.  Study [r8] found high levels of sleep apneas in people with type-1 diabetes, but had no comparison group.

Question 2: Is OSA a danger sign for people who have T1D?

The [r4] study found no connection between sleep issues and HbA1c numbers.  But [r5] found that patients' poor glycemic control and worse apneas were correlated (but no way to tell which caused the other, or if they were both caused by something else entirely). The "Sleep and Glucose Regulation in Youth With Type 1 Diabetes Mellitus" study [r7] is clearly based on the idea that bad sleep results in worse BG control.  Their data shows a clear correlation, but again,I don't see a causal direction.  Although it seems reasonable to me to think that if you BG was out of range, that would cause sleeping problems, rather than the other way around.

Question 3: Is OSA an early warning signal of T1D?

While there is no question that OSA can be an early warning sign of type-2 diabetes, I was not able to find any studies suggesting that it was an early warning sign for type-1.

Question 4: Does OSA cause T1D?
Question 5: Does T1D cause OSA?

I could not find any research on these questions.

Ongoing Studies

There is only one related clinical trial currently running.  They are comparing people who have type-1 diabetes to those without, and are investigating relative rates of OSA, type-1 issues which might cause OSA, and OSA impacts on complications of type-1.  The study includes 145 people, and is expected to be completed in Sept. 2016.  They are recruiting in Paris, France.
Clinical Trial Record: http://clinicaltrials.gov/ct2/show/NCT01935765

There is another small study at the University of Arizona, where students with type-1 will be asked to extend their sleeping hours.
Clinical Trial Record: http://clinicaltrials.gov/ct2/show/NCT01739712

My Summary

My basic conclusion from all this, is that there is very little research in this area.  Based on what we have, it looks like OSA is much more common in people who have type-1 diabetes than in others, and maybe even more common in people with type-1 than type-2 diabetes.   This is a major change in perspective, since OSA is traditionally associated (in people's minds) with type-2 diabetes. Unfortunately, almost nothing else is known about the causality or effects of OSA in people who have type-1 diabetes.

References

[r1] http://en.wikipedia.org/wiki/Obstructive_sleep_apnea
[r2] http://www.webmd.com/sleep-disorders/guide/understanding-obstructive-sleep-apnea-syndrome
[r3] http://www.ncbi.nlm.nih.gov/pubmed/21679352
[r4] http://www.ncbi.nlm.nih.gov/pubmed/21573904
[r5] http://www.ncbi.nlm.nih.gov/pubmed/10907113 (this study uses the term "insulin dependant diabetes", but they are clearly studying children, so I'm assuming they are type-1)
[r6] http://www.ncbi.nlm.nih.gov/pubmed/4004160
[r7] http://www.ncbi.nlm.nih.gov/pubmed/22215921  mass media report here:
http://www.medpagetoday.com/Endocrinology/Diabetes/30460 and clinical trial record here:
http://clinicaltrials.gov/ct2/show/NCT00848822
[r8] http://www.endocrinology.dk/index.php/spor-24-blandet-endokrinologi/488-96-prevalence-of-sleep-apnea-in-danish-type-1-diabetes-patients



Joshua Levy 
http://cureresearch4type1diabetes.blogspot.com 
publicjoshualevy at gmail dot com 
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF, JDCA, or Tidepool news, views, policies or opinions. My daughter has type-1 diabetes and participates in clinical trials, which might be discussed here. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog.

Thursday, October 16, 2014

Three Unsuccessful Trials


This blog posting summarizes several clinical trials aimed at curing type-1 diabetes which have failed.  These are never fun, happy blog postings, but they are important.  One of the big problems with trying to understand research based on mass media reporting is that failures are rarely covered at all.  The soundtrack for this posting is "Down" by Melissa Lambert:
http://grooveshark.com/#!/s/Down/4BHhwn

Sitagliptin and Lansoprazole Unsuccessful in Phase-II Trial

This was a combination therapy.  The researchers were attempting to combine a drug to stop the autoimmune attack and another drug to trigger beta cell growth.  Both drugs were approved for other purposes, and commonly used.  Unfortunately, it didn't work.  Summary from abstract:
At 12 months, the mean change in C-peptide area under curve was −229 pmol/L for the treatment group and −253 pmol/L for the placebo group; this difference was not significant (p=0·77).
Abstract: http://www.sciencedirect.com/science/article/pii/S2213858714701159
Blog at start of trial: http://cureresearch4type1diabetes.blogspot.com/2010/08/possible-cures-for-type-1-in-news-mid.html

Pioglitazone Unsuccessful in Phase-I Trial

Pioglitazone has been approved for use in type-2 diabetes for over 10 years. It is part of a larger drug family called thiazolidinediones which have been shown to preserve beta cells in animals with type-1 diabetes, and to reduce death of beta cells in petri dishes.  It was being tested as a honeymoon cure, but did not pan out:
Conclusion: In this pilot study, pioglitazone did not preserve ╬▓ cell function when compared to placebo.
Article: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3890222/
Previous blogging: http://cureresearch4type1diabetes.blogspot.com/search/label/Pioglitazone

Stop Covering Lisofylline

As far as I can tell, no one has done human trials of this treatment for over two years, so I'm going to stop considering it as a possible cure, unless something new comes to light.  Lisofylline is an anti-inflammatory.

Previous coverage (one blog posting) is here:
http://cureresearch4type1diabetes.blogspot.com/search/label/Lisofylline


Joshua Levy
http://cureresearch4type1diabetes.blogspot.com 
publicjoshualevy at gmail dot com
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF, JDCA, or Tidepool news, views, policies or opinions. My daughter has type-1 diabetes and participates in clinical trials, which might be discussed here. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog.