Alzheimer's and insulin resistance

This is an old article from Time Health but it raises interesting points about insulin's effect on Alzheimer's and I thought it was worth sharing.

When the body refuses to make insulin, the condition is called type 1 diabetes; when the body mismanages the hormone, it's known as type 2. Now, scientists report new evidence linking insulin to a disorder of the brain: when the brain prevents the hormone from acting properly, the ensuing chemical imbalance may help trigger Alzheimer's disease. The correlation is so strong that some researchers are calling Alzheimer's disease "type 3" diabetes.

In the body, insulin helps convert food into cellular energy. But the brain has other uses for insulin, namely as a means to learn and make new memories. Here's how it works: At synapses, the spaces across which brain cells communicate and where memories are conceived, neurons reserve special parking spots just for insulin. When the hormone pulls in, a connection is made that enables new memories to form. Since new memory formation is one of the first things to go awry in people with early stages of the disease, this insulin-initiated process may hold the key to decoding the mystery of Alzheimer's.

In August, a team of scientists at Northwestern University were the first to show why the brain's "memory function" fails in the face of an insulin shortage. The group's prior research had already pinpointed the culprit: toxic proteins called amyloid beta-derived diffusible ligands (ADDLs, for short), which are known to pile up in the brains of people with Alzheimer's. Scientists also knew that Alzheimer's patients' brains have lower levels of insulin and are insulin resistant. But what the Northwestern team discovered is the molecular mechanism behind that resistance: when ADDLs bind to neurons at synapses, they obliterate the receptors that are normally reserved for insulin. Without those parking spaces on the brain cells' surface, insulin has no place to connect, and memory fails.

"We now understand that the function of insulin at those synapses is to modulate and influence the underlying cellular structure of memories," says William Klein, professor of neurobiology and physiology at Northwestern University and a co-author of the study published online by the FASEB Journal. "What we have here is a striking phenomenon that may ultimately explain why the brains of people with Alzheimer's disease are insulin resistant and how that ties into memory."

Researchers hope these findings will help shape future research in Alzheimer's therapy — perhaps in the development of drugs that can make brain cells' insulin receptors more responsive to the hormone, or in the application of type 2 diabetes drugs, which address insulin resistance, to Alzheimer's.

The notion that Alzheimer's disease might be a neuroendocrine disorder, akin to diabetes, isn't entirely new; it first showed up in the scientific literature roughly 20 years ago, but the idea petered out. In 2005, Suzanne la Monte, a neuropathologist at Brown University Medical School, revisited the idea. Based on two of her discoveries — that the brain makes its own insulin and that Alzheimer's disease depletes insulin — she coined the disease process "type 3" diabetes.

Still, referring to Alzheimer's disease as "type 3" diabetes is controversial, especially within the diabetes community. Alzheimer's disease is a complication of diabetes, not a unique form of the disease, says Dr. Sue Kirkman, vice president of clinical affairs for the American Diabetes Association. "Nevertheless," she says, "this is primarily a semantic argument."

The terminology aside, both diseases share many traits and risk factors, including high cholesterol, high blood pressure, and metabolic disorders. So, de la Monte sees the semantic "splitting of hairs" as a good thing. "People are arguing about small parts of the bigger story," she says. "At the end of the day, these conversations will help us to better understand both diabetes and Alzheimer's disease."

Basal the spike away

Standard Disclaimer: I'm not a doctor, please read the disclaimer at the bottom of the page. Always speak to your doctor, especially before trying something that came to me while I was in the shower. 

Stubborn Highs: Arden's blood glucose can rise and at times be resistant to returning to 'normal'. Happens to all of us. I bolus and wait but nothing, so I bolus again and sometimes again. It's around the second bolus when I begin to wonder, "is the site bad", "maybe the pump has been on too long", "did I grossly miscalculate carbs", a person can go batty trying to decide what has happened. It's likely that before you (or I) can ever come to a conclusion, the BG in question will return to 'normal' or head in the complete opposite direction. Either way, the whole unsightly mess is forgotten becasue you're busy chasing the next problem which leaves you no closer to understanding why this happened or figuring out how to avoid it next time.

Sound familiar? 

This type of BG struggle isn't just associated with stubborn highs: Breakfast or meal time spikes can also lead to an urge to bang your head on a nearby firm surface. Over the last few months I've been experimenting with an idea that came to me in the shower one day and I'm seeing a lot of positive results. I'm going to do my best to explain without being boring or confusing... Please note that what follows will only work for pumpers because it involves manipulating basal rates... sorry MDI and pen users!

Using increased temp basal rates in place of a portion of your bolus

Arden is a really good eater, that is that she eats healthy foods most of the time and in acceptable portions. If the kid has one 'vice' it's that she likes a bowl of Fruit Loops in the morning - just one cup. The BG devastation that this handful of cereal visits unto Arden was, in the past,  terrible. Her BG would rocket to 400 or more after a bowel of the colorful rings. The Loops would seem to laugh in the face of a pre bolus and administering more insulin before the meal or an extra bolus after could not penetrate their sugarific force field. Once I even thought that I saw Toucan Sam give me the finger as I put the cereal box back in the pantry.

I hate this song and dance. I hate that Arden can't have a flippin' bowl of cereal once and a while and I double hate the feeling that I live with when she eats cereal and her BG goes crazy. Foods like this don't just send her BG too high, they ruin most of the rest of her day. I'm full aware that cereal isn't a good choice for my diabetic daughter but I'm not writing about that today. Today I am talking about how, with the help of an insulin pump, we can all fight meal time spikes associated with not so great food choices and manipulate stubborn high blood glucose values more easily and smoothly.

My formula

Things you need to know to follow along: 

• Arden's basal rate is .30 in the morning and much of the day.
• For a serving of Fruit Loops she requires 2 units of insulin.
• Giving say 2.5 units for the cereal does not change the trajectory of her BG.
• If I go higher (say 3 units) the spike is not effected enough, topping out at 350 and Arden's BG will plummet between the three and four hour mark.

Time to visit me in the shower where I am apparently about 20 IQ points smarter then I am anywhere else. (I've heard that the hot water on the back of your neck may be the reason why).

I was in the shower one day pondering life and Arden's breakfast BG spikes when I first began putting the pieces together. Overnight Arden's basal rate is .20, if she's high I have to put her basal back to .30 for a bolus to have the desired effect... I wondered what would happen "if I increased the basal beyond .30", could I bring a high BG down in a safer way, steadier perhaps (because she's sleeping) then if I just bolused? I tested my idea at the next opportunity and not only did a significant temp basal bring down the high overnight BG but it did it with less insulin then a bolus would have required and the drop was smoother, it's 'landing' less erratic. My inner mad scientist was intrigued and I had just unknowingly found a big piece to the puzzle that is stopping mealtime spikes.

Proof of concept: Arden sits down and begins eating on a school day at 8:20 am. Today at 7:45 am her bg was 140, I bolused for the first 15 carbs of her upcoming breakfast, which was 1 unit or half of what a serving of Fruit Loops requires. This is a pre-pre bolus, I find that after a long night of no boluses and a decreased basal rate it can take a little longer for insulin to begin working (maybe this is part of the morning insulin resistance many experience?). At 8:10 am I bolused again this time for the remaining 15 carbs but I reduced the 1 unit of insulin by .30 (the equivalent of an hour of Arden's basal rate). Last, I increased her basal by 95% for one hour. (OmniPod won't do 100%), giving the last .30 of the 2 units via an increased basal rate. The temp basal in conjunction with a significant pre bolus seems to be the key to eliminating a BG spike. Pre bolusing alone won't effect a severe spike enough because you can't perfectly sync the insulin peak with the food spike so the BG rises quickly, drops suddenly and often bounces back up. However, when you add a pre bolus to a significant temp basal, the basal acts as a constant drag on the spike and the two together win out.

Breakdown

15 carbs or 1 unit, 40 minutes before breakfast - 7:45am

I can prebolus that far off in this situation without an issue because her basal was .20 all night and she's resistant in the AM, so the insulin is a bit slower to respond first thing in the morning. Plus, with Apidra, Arden rarely experiences significant BG falls so prebolusing this far out feels safe. Additionally, I have 70 points in her BG to play with and the cereal will be releasing sugar into her blood far before she gets too low... (having a DexCom CGM doesn't hurt either).

Another 15 carbs 15 minutes before the meal (withholding the equivalent of an hour's worth of basal)- 8:10

This insulin won't begin working until after Arden begins to eat, so I'm not worried about stacking. Two boluses also mean two insulin peaks while the Fruit Loops are trying to spike her BG. 

Double the basal rate for an hour to complete second 15 carb bolus.

This .30 will work better then if it was given as part of the bolus, why? I don't know, I told you, I'm not a doctor... it just does - Maybe I know this because hot water in the shower makes me smarter. btw, more then an hour of the temp basal is too much and results in a fall in the 3-4 hour range. Doubling for an hour is perfect.

Result: At 9:30 am Arden's nurse called... Arden was 240 by her CGM. The CGM indicated 2 arrows up (which was why she was with the nurse) but the double arrows only lasted for about 4 minutes. So my little science experiment took a double arrow up event that in the past would have sky-rocketed to 400 (or more) and held it to a 4 minute double arrow that never went above 250!

Arden's BG (by the CGM) at 11 am (pre recess) was 145 diagonal down, she drank 2 ounces of juice (7 carbs) and went outside to play. When she returned her BG at 11:30 am (post recess, pre lunch) was 129 by a finger stick, 140 and steady via the CGM. 

I choose and extended bolus for lunch because she was having a bagel. 60% of the 2.20 units at 11:30 am the balance over an hour (to combat the slow breakdown of the bagel). Her BG was 145 three hours later before snack time.

Summation

It goes without saying that what works for Arden won't work for everyone but after months of using this method I am 100% comfortable telling you that what I wrote here is well worth speaking to your endo about. The concept of using a temp basal to complete a bolus holds many possibilities beyond what I wrote about here today. Slow to break down foods and high carb meals for example are also good places to try this method. I'm using a temp basal as part of Arden's bolus on almost a daily basis. It is also invaluable in bringing down stubborn high BGs and getting a BG lower during sleep, avoiding the fear of a sudden drop and without going too low.

I wish you all good health, luck and steady BGs. I'll do my best to answer any question if you have them.

Apidra SoloStar supply news

Looks like Sanofi will have the supply of their Apidra SoloStar pen back to normal levels in the second quarter of 2012. Sanofi has made the FDA aware of their timetable and SoloStar users should be happy again in just a short time.

The company has produced a web page that can help a SoloStar user navigate the supply issues and they've also extended their free Apidra offer as a way to help soften the sting of this inconvenience. We've taken advantage of the free offer even though Arden doesn't use the SoloStar pen... Nothing better then free insulin, right?

Arden's A1c is at it's lowest ever since we switched to Apidra so I'm more then excited and happy to let you all know that it's out there and for a while longer, free. 

Trusted my instincts

 

Last night before bed, Arden's BG unexpectedly spiked up. I resisted the urge to play it safe and trusted my instincts to bolus. I covered the high BG and encouraged a small snack that I did not cover. We had an early dinner and while I didn't understand the spike I knew that the insulin without anything in her stomach would likely cause a low later. So I popped some corn and Arden had a few (of her) handfuls with melted butter to get some fat into the mix.

I must have been a bit unsure initially because I posted on FaceBook that I just bolused and didn't know what to expect. Two hours later her BG was in a good place and drifting gently to where she woke this morning, 85.

This morning she woke up in such a pleasant mood and immediately began talking about all sorts of funny stuff. She hopped out of bed when I asked her to, didn't linger in the bathroom or mess around while she ate... she didn't even complain about brushing her teeth! All of that makes me wonder just how much varied and fluctuating blood glucose levels effect her personality, mood and feelings.

Free* Apidra from now until 4/30/12

I just got my card. It only took a few minutes...

All you have to do is go to this link and answer a few simple check box questions. The system will then generate a printable card for you to take into your Pharmacy and just like that your Apidra is free! Visit the link to get your card now and for more details. There is a bit of fine print... I've included some of it below.

If you want to know about more offers in the future please follow me on Twitter, FaceBook and Subscribe to Arden's Day - links are in the sidebar to the right.

Follow @ArdensDay

Please use the "share article" link just below to spread the word.

From now until April 30, 2012, Apidra® vials are free for patients with commercial insurance*. ACCESS also provides Certified Diabetes Educators for on-demand support and counseling.

 *Offer is not valid for patients participating in Medicare, Medicaid, or any other federal- or state-funded benefit programs. Offer not valid in MA (except for cash-paying patients). Void where prohibited by law. Cards are the property of sanofi-aventis, and must be returned upon request. Both parties reserve the right to rescind, revoke, or amend this program without notice. Maximum offer value $250 per prescription. Cards valid through April 30, 2012.

I have not been compensated in any way for this post. Just good information for our fellow insulin users.