Tuesday, June 16, 2015

ADA, Me and My MODY (Maybe) - Part 1

I recently posted an introduction to Maturity Onset Diabetes of the Young (MODY).  This is of personal interest to me as I've had a suspicion that I might have MODY for more than five years.  This last April I was shocked to actually be referred for the genetic tests for MODY.  So being able to attend the 75th ADA Scientific Sessions and learn more about MODY and have a chance to hear the worlds experts and even ask some questions was a great opportunity.  In this post I'll be talking about my attendance at an ask the expert session on MODY by Dr. Rochelle Naylor of Kovler.  In subsequent posts I'll talk about a presentation by the infamous Professor Andrew Hattersley of Exeter as well as my viewing of the film "Journey to a Miracle" a movie about MODY.

On the first day of the ADA sessions I started by attending a meet the expert session entitled "When to Suspect Monogenic Diabetes."  Dr. Rochelle Naylor gave the presentation and gave a great overview of MODY.  She highlighted the newest screening criteria for MODY and how some additional tests can be used to differentiate patients.  Obviously, antibodies and c-peptide could be used to differentiate T1 from MODY.  But she also highlighted the use of hs CRP and c-peptide/creatinine to differentiate certain forms from T1, T2 and GCK.

Dr. Naylor talked further about a MODY probability calculator which is available from Exeter.  That calculator is designed to help physicians figure out chances that a patients has MODY.  Unfortunately the calculator was designed for a cohort of patients under 35 and of European/Caucasian descent and key features of the calculator are somewhat arbitrary to treatment decisions (i.e. is the patient being treated with orals or insulin).  A further paper highlighted the limitations of this in extending the calculator to other populations.  I also found it odd that all forms of MODY were lumped together, it would have made more sense to at least separate GCK from the other forms since they present so differently.

In terms of treatment, Dr. Naylor discussed the use of sulfonylureas for MODY-1, 3 and 4.  It was also reported that GLP-1 drugs seem to work with MODY-3.  She suggested that GCK does not respond to treatment and that unless the patient was pregnant neither Exeter nor Kovler recommended and treatment except perhaps a low carb diet.  She said these were based on certain observational studies but when I looked up the reports they were from very small sample populations and the studies have a lot of limitations.  There are other reports that while microvascular complications are rare in GCK patients, some cases of proteinuria, proliferative retinopathy and proliferative neuropathy have been reported.  I find it hard to believe that if CVD risks in non-diabetics are strongly associated with HbA1c that somehow GCK patients are immune.

I actually got to ask this question of Dr. Naylor.  I asked why patients with A1cs up in the 7-8% range were somehow immune to CVD when even the non-diabetic population displayed a strong association between A1c and CVD.  She explained that because GCK is simply a higher set point that patients still respond normally to a glucose increment so that while the average is higher the patients don't experience significant time "out of range."  She did note that the higher A1c may still matter to retinopathy risks.  Personally, I am not convinced, there seems to be little data to support this and it goes against much other evidence which suggests elevated blood sugars are a CVD risk.

There was then some discussion about screening for MODY and based on the responses the screening is still quite rough.  Apparently there is some data on the specificity and sensitivity in differentiating MODY-1 but that is of limited use as most MODY is either MODY-2 (GCK) or MODY-3 (HNF1α).  If there is suspicious that a patient might have MODY about the only way to further confirm a diagnosis is to perform genetic testing.  And finally Dr. Naylor talked about the MODY Registry being run by Kovler.  They are attempting to put together a database of everyone diagnosed (or suspected) to have MODY.  The criteria for inclusion are a bit strange being all over the map.  The initial criteria from my previous contacts excluded me, but it appears that with the update criteria I might have been reconsidered.

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