Of Automobiles and Insulin Delivery

I applaud the New York Times for caring to write about type 1 technology. I would encourage them to take a little more time to better understand the subject next time. I'll try to help. Since we are all Americans here, lets use a metaphor we all understand - cars. Fuel efficient small foreign cars, so maybe not something we all understand.

In the 1970s I drove a VW Beatle. It had been my mom’s. It would go anywhere, including places my friend Ric broke his jeep. One year for Christmas I got a hand full of Craftsman tools and rebuilt the engine and clutch. Bugs were easy enough to fix anyone with tools could do it.  

Coming home from college one weekend, I was cut off on a highway and skidded into a gas station sign. The car was totaled. I was nearly so too. The impact of my face cracked the steering wheel and popped the windshield out. The Glass flew across the service station and landed unbroken. I remember the gas station guys talking about seeing the glass fly and marveling that it didn’t break, from my semi conscious state waiting for the ambulance. 

I still like small cars. I have a Mini. It has a host of features my Bug lacked; anti lock breaks, a host of front and side air bags, crumple zone construction, good seat belts, power steering and much more.

I bring all this up to point out the value of current automotive technology verses 1970s technology. It would be easy to say that both the Beatle and the Mini do the same job. They get me from point A to point B in relatively the same mix of shifting, steering, breaking and being a little weary of bigger vehicles. In that context the newer car’s significantly higher cost could be seen an extravagance. 

Modern cars are significantly safer (even if they don’t go up Jeep trails like a Bug.) 

I think there is a parallel to diabetes technology. Modern diabetes technology looks like it is doing the same job as the 70s stuff. 

It isn’t.

Modern insulins allow a better if not perfect parallel of physiologic insulin. Pumps provide a better delivery system and allow delivery to be programed to daily rhythms. Continuous sensing can alert patients to changes and prevent dangerous lows and highs. 

Yes, this stuff cost more than 1970’s stuff. Cost isn’t the question, value is. Air bags are mandated because some cars are gonna crash. Antilock breaks, crumple zone construction, side impact doors, safe fuel systems etc all cost more. The value is in safer roads, lives saved. 

See where I am goin’ here? 

The story of technology is the value it brings. Computers cost more than pencils, ruled notebooks and movable type presses. The New York Times assembles the paper with computers, because they bring value. We drive safer cars for the value. People with type 1 diabetes can be more productive members of society due to the value of effective technology.

Sent via email to: Elisabeth Rosenthal NYT. (without the cool images, what can ya do.) 

ps. Neither my Bug of Mini looked the good but the colors are right. 

Meth. or Insulin

“This is rather startling.” 

That was the opening paragraph of an email I received yesterday from Jeff Hitchcock. He’s not easily startled. What had caught his attention was a JAMA paper titled, “National Estimates of Insulin-Related Hypoglycemia and Errors Leading to Emergency Department Visits and Hospitalizations.”

Just like the title says, the paper estimates Emergency Room visits for what is called IHEs or insulin-related hypoglycemia and errors. The authors’ figure is 97,648 IFEs annually, of which 29% result in hospitalization. 

Jeff had started totaling up the costs of all those visits. Emails like this make me think he likes to spin me up. Like I need help?

I found an article that puts the prices on these in another journal. The American Journal of Managed Care. There is a group that is going to be super geeky about costs, right? In, "The Incidence and Costs of Hypoglycemia in Type 2 Diabetes" they say, “costs for hypoglycemia visits were $17,564 for an inpatient admission, $1387 for an ED visit.” (remember ED here being Emergency Department, not the blue pill problem.) 

Easy enough to take the number of visits and multiply it out by the costs and - Son-Of-A... -  hypos are estimated to cost about $640 million a year. 

The JAMA piece goes on to say these IHEs are far more likely to be the elderly. “Insulin-treated patients 80 years or older were more than twice as likely to visit the ED and nearly 5 times as likely to be subsequently hospitalized for IHEs than those 45 to 64 years.” These are they very people who can’t get continuous glucose monitors (CGM) to help warn of hypos, because Medicare says CGMs are not medically necessary. 

I can think of over half a billion reasons why maybe they are needed.

Beyond the money, the JAMA piece says, “Severe neurologic sequelae* were documented in an estimated 60.6% of ED visits for IHEs, and blood glucose levels of 50 mg/dL or less were recorded in more than half of cases (53.4%).” (*I had to look sequelae up too. Thanks wikipedia, “Typically, a sequela is a chronic condition that is a complication of an acute condition that begins during that acute condition.”) So translating that here: Chronic neurologic conditions as a result of the acute event, aka hypos are, disproportionally hitting American seniors. 

That just ain’t right.  

Look at it this way, Drugabuse.gov (I swear this is the citation I’ll drag out) says, “stimulants, including amphetamines and methamphetamine, were involved in 93,562 ED visits.”

Diabetes beats Breaking Bad.

97.8K ED visits for Team Insulin over 93.5k for Meth. et al.  

This is "rather startling." 

YDMV - so your term for what "This is ____" may be more colorful. I trust they will show up in the comments. 

Sources: 

https://archinte.jamanetwork.com/article.aspx?articleid=1835360

http://www.ajmc.com/publications/issue/2011/2011-10-Vol17-n10/AJMC_11oct_Quilliam_673to680

http://www.drugabuse.gov/publications/drugfacts/drug-related-hospital-emergency-room-visits

Of Beer and Insulin

I was pretty psyched to see Lilly’s insulin factory. I had no idea how the stuff got into those little bottles. I had seen the picture of pork pancreas stacked 10,000 pounds high that was used in the old days to make one pound of insulin crystals. It is in Breakthrough, the book about the discovery of insulin by Thea Copper and Arthur Ainsberg. I knew that pork piles aren’t the means of making insulin now. I did not know much more.

Much to my delight I found making insulin is a lot like brewing beer. The folks at Lilly may not have been delighted by my comparison but they were good sports about it. While I can brew an acceptable ale at home, I am sure I can't cook up a batch of insulin.

Some of the finer Belgian beers are crafted by Trappists Monks and fermented with wild yeast that happens to float into the brewery. Wild bugs may be great for a Belgian Lambic but are not so great for insulin. A multitude of little microorganism would love to grow up in a big old vat of glucose. So Lilly goes to great lengths to keep them out. Just like home brewing (only more so) sterilization is a big deal for insulin production.

Beer is made by putting water and sugar from malted grain and some yeast in a clean sealed bucket. The yeast eats the sugar, excretes CO2 and alcohol, while multiplying like crazy. At some point the yeast can’t grow any more and it dies off. The brewer separates the beer from the mass of dead yeast and put the beer in a bottle with a pinch of extra sugar to carbonate it.

Lilly has some little tiny critters that eat glucose, replicate and in the process sequence a DNA string that just happens to be insulin (and by ‘just happens’ I mean is very carefully engineered). They start with a teeny amount of these critters, like about an ounce, and end up with 50 tons of glucose water in bunch of (very clean) vats fermenting the little guys. Unlike beer Lilly are after the bugs and filter out the water. They filter, wash, spin and process and end up with less than 50 pounds of insulin crystals. A pinch of those 50 pounds will be mixed with sterile solution to fill a bottle. All told a batch makes around a half billion ‘units’ of insulin.

   Photo courtesy of Lilly

About clean: To see the bottling room, from the other side of glass, the tour had to put on hair nets, smocks, booties and for the facially haired, beard masks. That was to look though said piece of glass into the clean room. The guys in the room (or girls it was not really clear their gender for all the garb they were wearing) apparently spend a half hour dressed up. Nothing human exposed, breathing through respirators they were more suited up that what you see in a bio scare flick. The room was beyond surgically clean and 8 vials at a time filled as they looked on. Eight at a time, all day, to the tune of more than a million vials week.

So let review: Like beer insulin is fermented filtered processed and bottled. Like brewing beer sterilization really matters. Unlike beer the process of insulin is not so easy you can do it in the kitchen.

My friends Scott and Scott have posts about the tour that dose not involve beer
here: http://scottsdiabetes.com/2013/05/lilly-diabetes-making-insulin/  and
here: http://www.ardensday.com/main/2013/5/9/tears-of-insulin.html

But for those still with me here is a handy graphic to help with my comparison.

Lilly Diabetes invited and paid for me to attend the 2013 summit. Airfare, lodging, food and transportation was all covered by Lilly. They did not ask me to write about my experience. My comments are my own.  I did check the numbers in the info graphic with them. 

FDA Asks for More Study of Degludec

Good friend of the blog Scott Strumello sent me a link to Pharmalot that says the FDA is looking for more studies and will reject the application to market insulin degludec pending those studies. http://www.pharmalot.com/2013/02/sticking-point-fda-rejects-novo-nordisk-insulin/

I applaud safety and scrutiny on cardio risks is part of safety. However it is not the only safety issues with insulin.

I wonder if the current basal insulins would pass the same level of safety and long term risk for cardio issues. The FDA panel IMHO seemed any potential benefits of the insulin the benefits saying there was already an approved drug so we can be tougher on cardio here. One benefit seemed to be fewer hypos. Hypos have risks and the benefit of a reduction of those risks appeared to me, as non physician lay observer who clearly could be missing the mark, to be brushed over.

It is hard to balance all that out but there should be a conversation about it.

My comments at the hearing are here:
http://www.ydmv.net/2012/11/fda-endocrinologic-and-metabolic-drugs.html

The Spanish Inquisition, Children With Diabetes and Surgery.

File this in the I wish I had know this better before folder. In my case that folder is a file cabinet but what the heck.

I didn't spend a ton of time thinking that the kids may need surgery.  Health, active kids seem to have a myriad of issues most of which involved looking forward to school, sports, a camp, a play or some other interest. Typically we didn't think about them needing surgery.

Spending a few minutes thinking about it is would have been a solid idea. I am reminded of this by a great article with some useful links that I just read. I wish I had read it years ago: Pamela Wilson's, Surgery and Children with Diabetes.

Our experience has been that even routine dental surgery can wreck havoc on diabetes balance. One of the issues was steroids. They were routinely prescribed for recovery. They totally screw up Blood Glucose (BG) balance. How routine? Well so routine that even when we have had a agreed not to have them given to the kids, the post dental surgery process handed them out as a matter of course. The result was a festival of whacky BG that left the poor kid feeling a lot worse. His recovery to get back into the swing of things was significantly impared.

If Monty Python has taught us anything it is that Nobody expects the Spanish Inquisition!

Not a lot of people expect appendicitis either. Should you happen to have a case of appendicitis and choose not to turn over BG management to the hospital, who in our case were going to change insulins and use a "sliding scale" they couldn't or maybe wouldn't define, you can expect the equivalent of the inquisition.  Without the comfy chair.

I think the dental experience helped us anticipate the issues with the appendicitis. So maybe that file cabinet of things we learned the hard way payed off.

So here is today's YDMV school of hard knocks top tip: Next time you are at the endo have a conversation about, steroids, going off your regular insulin program and other emergencies medicine treatments. Prepare to advocate for your best interest when what is least expected happens.

UPDATE: A friend of the blog sent  this link about insulin and hospitalization:
http://www.ashp.org/s_ashp/docs/files/Safe_Use_of_Insulin.pdf



Related YDMV posts:
Speaking Up for Yourself with Health Professionals.
Not that I was planning to be here
Of the ER, the Web and Perfection
The Boy's Oratorical

Damn Mice.

Apparently mice can now turn their gut cells into insulin producers. Seriously is it possible to spit on a mouse in a lab without curing diabetes? I think these diabetic mice just spontaneously cure themselves to stay in the media. Kinda like Charlie Sheen. 

Anyway here is the article and I notice the picture they ran is not a mouse. New Approach to Treating Type 1 Diabetes? Transforming Gut Cells Into Insulin Factories 

Not only do mice get cured at the drop of a hat they also have kick ass abs. Only way that is a mouse is if she was one of the dancers who work the Mickey suit at Disney World...

... get to hang out at Disney too. 

Damn mice 

Required Reading - JDRF on GRI in Countdown

Back in September JDRF Launched a prize to encourage people outside of diabetes research to join the hunt for a Glucose Responsive Insulin (GRI.) I wrote briefly about it in the post Know a Smart Chemist? JDRF's current edition of Countdown, their online magazine has a great story with more information about GRI and the JDRF initiative.

This is a fascinating approach to living with type 1. It is not a cure in the pure sense but if they can find ways to make Glucose Responsive Insulin work it is a Game Changer. In fact The Game Changer is the title of the piece and because of that potential, years down the way, the articles gets my vote for this weeks reading assignment.

The Game Changer: Treating type 1 diabetes with glucose-responsive insulins.
http://countdown.jdrf.org/Features.aspx?id=8589934727