Friday, November 8, 2013

Carnitine As Newborn Marker for Type-1 and Speculative Cure


Carnitine As Newborn Marker for Type-1 and Speculative Cure

A team in Italy has been storing blood samples taken the day a baby is born.  Another team performed the following experiment:  If a child was diagnosed with type-1 diabetes at age 6 or less, they tested the stored blood for Carnitine and a variety of closely related chemicals.  These chemicals occur naturally and are biologically active, in your body.  They are vaguely related to B vitamins, but are not technically vitamins themselves.  The team then compared the levels of these chemicals to the levels in the newborn blood taken from babies who had not been diagnosed with type-1 diabetes, but were born within one day of those that were.  (These children formed a control group.)

The results were striking: the children who would later get type-1 diabetes had statistically significantly lower levels of many of these Carnitine related chemicals.  Now, they did not find a clear line, where carnitine levels below X singled type-1 diabetes, and over Y was safe.  There was significant overlap.  What they found was that on average lower levels predicted higher type-1 rates. [d1]

This study could be the first step towards predicting type-1 diabetes.  Obviously, being able to predict type-1 diabetes at birth, even if not perfect, would still be very helpful, both in terms of extra vigilance for earlier diagnoses [d2], and for early intervention and prevention.

Speculation About A Cure

This brings up the issue of "cause vs. association".   Specifically, the study did not show that low levels of Carnitine cause type-1 diabetes, but only that low levels are associated with type-1.   From an early detection point of view, this doesn't matter.  As long as something can be measured early, it doesn't really matter if it is a cause or an association.  But for prevention the "cause vs. association" question is critical.

The researchers [d3] who ran this experiment, think that low levels of Carnitine (and/or related compounds) during the first day or two of life, causes type-1 diabetes later in life.  It's a unique theory.  I've never heard any other researcher who believes anything similar.  The theory is low Carnitine triggers a failure when the body is starting up it's immune system, that it never recovers from, and that manifests itself as type-1 diabetes later in life.  Their full paper is on-line (link below), so you can read their explanation yourself.

If low Carnitine during the first few days of life does cause type-1 diabetes, then perhaps it could be prevented by giving Carnitine supplements to pregnant women, or to newborns.  Neither of these interventions is impossible.  Today it is recommended that pregnant women (and even those trying to get pregnant) take folic acid, to prevent a specific type of birth defect.  And also, newborns are often given vitamin K (and a Hep B vaccine) within hours of birth.  So similar could be done for Carnitine, if it mattered.

Obviously, the next step would be an intervention study, where people are given Carnitine, and then tracked to see if it lowers the chance they will get type-1 diabetes.  Such studies require a lot of people, and a long time, so I would not expect a quick answer.  The study reported on here, is a retrospective, population based study, and so is much less persuasive than an intervention study. The good news is that L-carnitine is available now as a "dietary supplement" so setting up an intervention study should not be that complicated.

News article:
http://www.gazzettadelsud.it/news/66934/Possible-cause-of-juvenile-diabetes-found-in-Italy.html
Full paper:  http://www.nature.com/nutd/journal/v3/n10/full/nutd201333a.html

Extra Discussion

[d1] In more detail: what they found was that, for a whole group of Carnitine related chemicals, people who later got type-1 diabetes had -- on average -- lower levels, than those who would not get type-1.  None of these chemicals could be used alone to predict type-1 diabetes.    None of them had a line which separated type-1 diabetics from everyone else.  Instead, at higher levels very few people got type-1 diabetes, at the middle levels it gradually shifted from few type-1s to more and more of them.  And then at lower levels the number of type-1 diabetics were higher.  But you could never say "level X means type-1" or "level Y means you will not get type-1".

This brings up a critical question: even if none of the chemicals gave a yes/no answer to the question of future type-1 diabetes, maybe by combining data for all the chemicals we could give a yes/no answer.  There is no discussion in the paper of the authors' attempt to use mathematical analysis to see if a combination of different chemical levels could be used to predict type-1 diabetes.

[d2] For example, diabetic ketoacidosis at the time of diagnosis might become much more rare, than it is now, if people were on the lookout for type-1 from birth.  Obviously, there is a downside in terms of hypervigilance, and over protectiveness, etc.  But the only way we can get to prevention is through early intervention, and the only way to get to early intervention is to predict who is going to get the disease.

[d3] This group of researchers was led by Gian Franco Bottazzo, who is generally credited with discovering (in 1974) that type-1 diabetes was an autoimmune disease.  Obviously, this was a huge breakthrough in type-1 research.  He has won the Banting medal, and several other international honors.

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.

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