hello. i'm new to the board and will save all my nice words for you in a later post, cuz you folks are truly great but i don't want a super long message (hindsight, i've failed). i'm long a couple years, cost basis like 6.50ish fyi. also i don't know stocks like you do, but i'm an emergency medicine physician who with diabetic emergencies daily.

over the past few days i have been reading through every post since march 19, save for some of the uvxy stuff that is way over my head, and i didn't have to see james' posts- thank you for deleting. i came across opc's reference on july 4 to the .gov site containing the trial info. something jumped out at me and i wanted to share with you before i read on. i think it's good news so keep reading mm56. this is all just IMO of course.

in mkc 171, an inclusion criterion is a BMI = 38. i kept reading then did a dbl take.... whaaaa!!?? a type 1 diabetic with a bmi of 38?? it says age = 18, so i'm assuming BMI = 38 means at least 38. folks T1s are universally not overweight due to their perpetual catabolic state, and a BMI of 38 is pretty much morbidly obesity. usually when something surprises me like that in healthcare, something's up (like when my "seizure" patient is "seizing" with his eyes shut and squinting- c'mon you can do better than that buddy! if you ask nicely i'll prob just give you the ativan).

ok back to my point. question- are we going to define type 1 diabetes as the following ADA statement?: "Type 1 diabetes is usually diagnosed in children and young adults, and was previously known as juvenile diabetes....Only 5% of people with diabetes have this form of the disease." you all know this and believe this to be the definition of T1. but let me tell you, those type 1s DO NOT have BMIs near 38. they also do not have another mkc 171 criterion of c-peptide levels of 0.3 pmol/mL, which is what NON T1s would have if we use the ADA definition of a T1. they don't have insulin and so they don't have appreciable c-peptide floating around in the serum. T2s do have that level of c-peptide though. you might find an exception or two (just like 2% of all seizures do seize with their eyes closed) but you will never fill a study of 300 plus T1s(using the above ADA definition) with those BMI and c-peptide numbers.

let me play a little game where i'm mannkind and i define type 1 DM and you try to refute me. i'm going to state that a type 1 is anyone who a doctor has made a diagnosis of type 1 diabetes (haha if i say ur T1 then that's what you are!). i'm also going to to define T1 as someone who requires some degree of insulin. i'm going to define a type 2 diabetic as anyone who is a diabetic who does not require insulin, but obviously has insulin resistance. with that definition, the percentage of type 1s of total diabetics is at least 25%, probably more. historically this later definition has been a way to differentiate the two types, but it has been largely rejected on laboratory and academic level. From a clinical standpoint however, when i'm talking to patients i make little/no distinction as to whether or not a patient has has functioning islet cells in their pancreas. they can both go into DKA, hypo, and have the same complicated barrage of end-organ damage. all i usually want to know is if they take pills or shots. that's it. and to me as an emergency physician, it doesn't matter the reason behind either of those. granted, i am not an endocrinologist nor a family practitioner and therefore am not dealing with the patients' diabetic problems on a daily basis. "to inject or not to inject"- that is the question. and to me that defines type 1 and 2 well enough, albeit in a somewhat crude and disreputable fashion by academics standards. but that is how my profession in the ED basically draws the distinction. it's from a functional, common sense standpoint- and it is how i believe mkc 171 is defining them as well.

i'm going to state that mkc 171 is not a trial of type 1 diabetics as defined strictly by the ADA. instead, mkc 171 is broadening the diagnosis of type1 to include what most endocrinologists would classify as a type 2. simply do a google search for 15 minutes or less and ask questions like, "define type 1 diabetes" or "can a type 2 become a type 1". read some of the posts about type 1.5 and LADA. i believe a paradigm shift has been in the making for a few years, resorting back to a previous model of looking at T1 vs T2. it has to do partially with awareness and for people to know they better wake up are in trouble if they don't act now with their DM. on a similar healthcare note back in ~'03 the joint commission lowered it's hypertension values to where 140 was htn and 120 was prehypertension and i think 160 was severe htn or something stupid like that. before you know it there will be pre-pre htn. did you hear on the news about 3rd hand smoke (not kidding)? you now hear ppl say "i'm prediabetic". that term didn't exist 15 years ago like it does today. when i was in med school, there was type1 where the pts required insulin to live and would die without it, then there was type2 and hardly anyone who was type2 was on insulin. in fact we learned it that way- no T2 took insulin (i went to UC davis med school). to see how things have changed, look at this little blog survey from 2008:

http://www.diabetesdaily.com/forum/type-2-diabetes/12265-what-percentage-type-2-diabetics-insulin

paradigm shifts my friends, and thus definitions... or vice versa maybe? think of it like this- we don't care why your glucose-insulin system doesn't work right and therefore don't care as much what we label you as- we just want to fix it. keep the serum glucose down to normal fluctuating levels and you won't have bad things happen. that works for t1 and t2. shades of grey abound in medicine and i believe this is no exception.

what this all means is that when the open label results from mkc 171 start coming in, BP knows we are NOT talking about the traditional ADA 5% type 1 juvenile onset diabetics- we are talking about a whole heck of a lot higher proportion of the diabetic population who have been classified as T2s. i'd bet that at least 30% of T2s are insulin dependent to some degree or should be, and thus can also be classified as type 1 AS LONG AS A DOCTOR WRITES THAT DOWN AS A DIAGNOSIS.

so a while back when you guys were talking about the NDA with just mkc 171- that could definitely work. but more importantly we would get a good set of partnership terms mid year or sooner and the dilution to get there might not be as severe. let's say al believes strongly that BP will start vying for position once they see the initial open label results. in oct/nov he dilutes us enough to get to july. by march '13, BP is looking at the T1 study early results and saying "holy chit these aren't T1s they are really T2s that are wrapped and packaged like T1s!! this thing is going to explode!" mind you the label based on mkc 171 would still look like it's limited to the "5% type 1s" to an untrained eye but boy oh boy when 175 finishes up look out label! 171 gets their attention and then WHAMM 175 empties the bases walk-off series over world champs thank you all for playing... BP provides the rest of financing thru PDUFA with some sort of contingency plan and al has room to negotiate for a little cash upfront but more ownership/control down the line when this thing really shows it's colors. and by that time approval is done and after we will all have met up somewhere to see how nerdy we all really are. on that note i was thinking there should be a printed book of posts and have a few readings on the victory vacation. sorry for the super long mssg. i also think we should have a pool with bets wagered on who we partner with. i think dale or swing should head that up.

i will reserve the right to say that if the BMI or c-peptide is a typo/mistake, then i'm off the hook and take back everything. i don't think it is though. this could be why it's been hard to enroll- those criteria are very tough. also i don't think this is "pulling over a fast one" on the fda. i would think the fda is in agreement as to the inc/exclusion criteria. i just think it's funny they are calling it a T1 trial when i just don't see it that way. feel free to critique. liahall your thoughts? does anyone know and endo doc well?

one more thing though, i can't figure out why the use of oral meds are not mentioned at all in the in/exclusion criteria for 171 if i'm right about it being more about the T2s than T1s....

chad