Monday, September 3, 2012

Fasting Blood Glucose, PCOS, hormones and the gut….

So it’s been a little over a month since I’ve been on the cycloset.  And what an interesting month it has been.  As I’ve tracked my FBG across my cycle I’ve discovered a correlation between my FBG levels and my Progesterone levels.  What?  How is insulin connected to hormones you ask?  “Insulin is a hormone, produced by the pancreas, which is central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen inside these tissues.”[1]
How does insulin work?   “Insulin stops the use of fat as an energy source by inhibiting the release of glucagon. With the exception of the metabolic disorder diabetes mellitus and metabolic syndrome, insulin is provided within the body in a constant proportion to remove excess glucose from the blood, which otherwise would be toxic. When blood glucose levels fall below a certain level, the body begins to use stored sugar as an energy source through glycogenolysis, which breaks down the glycogen stored in the liver and muscles into glucose, which can then be utilized as an energy source.”[2]
 So how does insulin impact in women who have PCOS?    Let’s investigate.
Remember PCOS is a dis-regulation of a woman’s hormones.  But how does that dis-regulation cause insulin resistance?  First off, PCOS develops when the ovaries overproduce androgens (e.g., testosterone).[3]  What does this mean?  This means my ovaries produce more testosterone, than they should. Why is this important to women with PCOS?  “Research also suggests that when insulin levels in the blood are high enough, the ovary can be stimulated to produce more testosterone. That is, the combination of having ovaries that are responsive to insulin and high insulin levels in the blood can result in the overproduction of testosterone.”[4] 

Whoa Nellie!  This means that my ovaries are super sensitive to insulin, which in turn causes them to make more testosterone.  What I’m trying to figure out is how did I become so sensitive to insulin.  Here’s what I think happens, with me.  My ovaries produce extra testosterone, beyond what they normally should for a woman.  This drives insulin sensitivity.  So it seems that through out my cycle, when Progesterone drops, Testosterone and Estrogen spike.  When Testosterone spikes, my Fasting Blood Glucose spikes.  Crazy huh?
 I made this observation after tracking my FBG and my cycle for the past month. I've been on the cycloset since 26 July. The following are the readings I've been taking right before eating 30min after waking.  My normal wake up time is approximately 515-530 am
Here are my FBG across the time period:
7/26 98mg/dl,
7/27 90mg/dl,
7/28 83mg/dl,
7/29 93mg/dl,
7/30 94mg/dl,
8/1 - didn't test – forgot,
8/2 89mg/dl,
8/3 didn't test forgot,
8/4 85 mg/dl,
8/5 89 mg/dl,
8/6 91mg/dl,
8/7 92mg/dl
8/8 75mg/dl I was up about 1hr earlier than normal to be at work early for an early morning meeting.
8/9 87mg/dl,
8/10 88mg/dl,
8/11 87mg/dl,
8/12 91mg/dl,
8/13 73mg/dl - I was up about 1hr earlier to get ready for a business trip w/an early morning flight - don't think this is part of my normal pattern,
8/14 91mg/dl,
8/15 didn't test forgot,
8/16 97mg/dl,
8/17 98 mg/dl,
8/18 87mg/dl,
8/19, 101mg/dl,
8/20 92mg/dl,
8/21 104mg/dl,
8/22 101 mg/dl,
8/23 109mg/dl,
8/24 94mg/dl,
8/25 97mg/dl,
8/26 95mg/dl,
8/27 92mg/dl,
8/28 89mg/dl,
8/29 90mg/dl,
8/30 104 mg/dl,
8/31 109mg/dl,
9/1 92mg/dl,
9/2 92mg/dl.

An initial look at these numbers they’re ok, but not great.  By conventional medicine I’m not quite pre-diabetic so everything is A OK. However my PCP took a look at these numbers and is in agreement that they’re not good. But the question is why aren’t they good?  Given I eat low carb, Epi-Paleo diet my FBG shouldn’t be above 85mg/dl.  But they are. What’s going on?  Lets look at the numbers again – based upon where they fit within my cycle, we might find something.  Remember, I’m using Bio-identical Hormone Replacement Therapy, to help control my migraines, and address my upside down Pg:E2 ratio.

7/26 98mg/dl, cd 26, day 1 cycloset, Pg 1.0ml, felt left over effects of a migraine on cd 24 – indicative of a drop in progesterone
7/27 90mg/dl, cd 27, day 2 cycloset, Pg 1.0ml, felt left over effects of migraine on cd 24, not sleeping well – indicative of a drop in progesterone
7/28 83mg/dl, cd 1, day 3 cycloset, Pg .4ml, normal ickyness associated w/beginning of time of the month (TOTM)
7/29 93mg/dl, cd 2, day 4 cycloset, Pg .4ml, TOTM
7/30 94mg/dl, cd 3, day 5 cycloset, Pg .4ml, TOTM
7/31 didn’t test – forgot, cd 4, day 6 cycloset, Pg .4ml, TOTM
8/1 - didn't test – forgot, cd 5, day 7 cycloset, Pg .4 ml, TOTM ends
8/2 89mg/dl, cd 6, day 8 cycloset, Pg .8ml, TriEst .1ml, some intermittent spotting
8/3 didn't test forgot, cd 7 day 9 cycloset, Pg .8 mL TriEst .1ml, some intermittent spotting
8/4 85 mg/dl, cd 8, day 10 cycloset, Pg .8 ml, TriEst .1ml,
8/5 89 mg/dl, cd 9, day 11 cycloset, Pg .8ml, TriEst .1 ml
8/6 91mg/dl, cd 10, Day 12 cycloset, Pg .8ml, TriEst .1ml
8/7 92mg/dl cd 11, day 13 cycloset, Pg.8ml, TriEst .1ml
8/8 75mg/dl I was up about 1hr earlier than normal to be at work early for an early morning meeting. cd 12, day 14 cycloset, Pg .8ml, TriEst .1ml
8/9 87mg/dl, cd 13, day 15 cycloset, Pg .8ml, TriEst .1ml
8/10 88mg/dl, cd 14, day 16 cycloset, Pg .8ml, TriEst .1ml
8/11 87mg/dl, cd 15, day 17 cycloset, Pg 1.0ml
8/12 91mg/dl, cd16, day 18 cycloset, Pg 1.0ml
8/13 73mg/dl - I was up about 1hr earlier to get ready for a business trip w/an early morning flight - don't think this is part of my normal pattern, cd 17, day 19 cycloset, Pg 1.0ml
8/14 91mg/dl, cd 18, day 20 cycloset, Pg 1.0ml
8/15 didn't test forgot, cd 19, day 21 cycloset, Pg 1.0ml
8/16 97mg/dl, cd 20, day 22 cycloset, Pg 1.0ml
8/17 98 mg/dl, cd 21, day 23 cycloset, Pg 1.0ml
8/18 87mg/dl, cd 22, day 24 cycloset, Pg 1.0ml
8/19, 101mg/dl, cd 23, day 25 cycloset, Pg 1.0ml
8/20 92mg/dl, cd 24, day 26 cycloset, Pg 1.0ml, hard time falling asleep, not sleeping well – in past had migraine on this cd, progesterone is dropping, Think I need more at the end of my cycle
8/21 104mg/dl, cd 25, day 27 cycloset, Pg 1.0ml, harder to get to sleep, - not sleeping well, Pg dropping
8/22 101 mg/dl, cd 26, day 28 cycloset, Pg 1.0ml, harder to get to sleep, not sleeping well, slight head pressure feels like I’m going to get a migraine, definite Pg drop
8/23 109mg/dl, cd 27, day 29 cycloset, Pg 1.0ml, migraine right before bed, think TOTM getting ready to start, hard time falling asleep, didn’t sleep well,
8/24 94mg/dl, cd 1, day 30 cycloset, TOTM started, Pg .4ml, not sleeping well, not enough Pg to balance Estrogen or Testosterone
8/25 97mg/dl, cd 2, day 31 cycloset, TOTM, Pg .4ml, not sleeping well, not enough Pg to balance Estrogen or Testosterone
8/26 95mg/dl, cd 3, day 31 cycloset, TOTM ended in evening, Pg .4 ml, not sleeping well, not enough Pg to balance Estrogen or Testosterone
8/27 92mg/dl, cd 4, day 32 cycloset, Pg .8ml, TriEst .1ml, some spotting midday, started to sleep better but not as good as mid cycle
8/28 89mg/dl, cd 5, day 33 cycloset, Pg .8ml, TriEst .1ml, sleeping better but not as good as mid cycle
8/29 90mg/dl, cd 6 , day 34 cycloset, Pg .8ml, TriEst .1ml, sleeping better but not as good as mid cycle
8/30 104 mg/dl, cd 7, day 35 cycloset, Pg .8ml, TriEst .1ml, spotting through out day, didn’t sleep well at all that night, not enough PG, as Estrogen begins to rise w/in cycle
8/31 109mg/dl, cd 8, day 36 cycloset, Pg .8ml, TriEst .1ml, spotting again throughout day, didn’t sleep well, not enough Pg – thinking estrogen and testosterone are rising together as ovaries prepare for ovulation.
9/1 92mg/dl, cd 9, day 37 cycloset, Pg. 8ml, TriEst .1ml, didn’t sleep well at all, hard time getting to sleep, definitely not enough Pg. at this point in cycle
9/2 92mg/dl. Cd 10, day 38 cycloset, Pg .8ml, TriEst .1ml, slept like crap again, total hormonal bitch on wheels during the day, definitely not enough progesterone at this point in my cycle.

Wow that’s a lot of detailed information.  Probably a bit TMI, but I’m trying to figure out what’s going on, and if I don’t keep track of details I can’t help my PCP and BHRT Docs decide where I need to go next.  I analyze data for a living. I look at number and causal relationship and identify potential outcomes.  So, as I began analyzing my own data I noticed, that as Progesterone dropped at the end of my cycle, my Fasting Blood glucose went up.  Why?  I also noticed that across my cycle, when I have a hard time sleeping, I don’t have enough Progesterone either.  This happens in two points, the last 5 days of my cycle, through TOTM, and as Estrogen begins to rise starting around cycle day 5/6.

So, I asked a question of Dr Jack Kruse on his forum:

His answer led me back to the Testosterone, and Estrogen surges and low Pg at certain points in the cycle.  I am a Textbook case of PCOS.  Excess testosterone and estrogen production by the ovaries, drives an increase in insulin, which creates insulin resistance, and higher FBG because of the imbalance in Progesterone production. Which in-turn impacts gut micro-flora, causing more FBG issues, because my body doesn’t respond to insulin the way it should. Wow.  Is this the Brain Gut Series or what! Check out BrainGut7 for a refresher.

Ok, so now that we’ve gotten closer to pinpointing the driving factor in everything going on with my health how are we going to fix it?  We’ll in a discussion on FaceBook lead me down the rabbit hole of metformin (Hey Dr Kruse I spelled it right for once!).  That discussion led to the following thread on Dr Kruse’s forum:
In this thread Dr Kruse posted the following: "Metformin is only a relatively weak inhibitor of mitochondrail complex I, (For Morley Robbins: the incidence of life threatening lactic acidosis is very low.) Metformin generate huge amounts of superoxide at the mitochondrial membrane. Pay attn to the fact that in T2D we have IR which also produces SO. So how it works for longevity is counter intuitive to all those who dont get biochemistry. Annexin V is a marker of of bad cellular function in IR. Metformin does not stop oxphos at complex one, but it decrease our leakiness there. I believe it does this by reversing flow of electrons there and makes them go to complex two which offers a major organic chemical advantage. We produce more ATP but create less ROS. this means we age less. We reverse neolithic disease. This is how metformin works. So metformin poisons visceral fat cells and makes them burn their fat at complex two. Now here is the irony that confuses Morley. Metformin on the surfaces causes IR in fat cells. And many think that is why it ia poison and should be avoided. I dont. because they dont understand how it works totally, just partially. Metformin's correlation with low carb diet: since glucose generates 5 times more NADH+ (cytochrome one) then at cytochrome two (FADH2) it increases complex 1 activity. By the way Morley, more Mag is required too at cytochrome 1 so metformin is still win to your dogma too. Now from Nick Lane's masterpiece, Power Sex and Suicide, he reports, it looks like balanced utilization of C1-C4 leads to healthy and happy mitochondria." What is bad in low T3 states, T2D, or IR? ALL suffer from bad mitochondria. The giant circle of life!Terry L. Wahls would probably love this because she is all over minding her mitochondria. I put all my MS patients on metformin because of these intricate biochemical factors. People who do consults with me have known about this for years. The rest of the world is just waking up to it. Anti-Aging medicine being the leaders. metformin appears to correct the changes in adipocytes which lead to systemic insulin resistance. There will come a point where, as adipocytes shrink, they will become functional again and generate appropriate levels of fatty acids for the metabolic conditions prevailing and release an appropriate mix of saturated and monounsaturated fats for normal body energy homeostasis."  

Which I followed up with the question - "how does metaformin work at the brain for Insulin Resistance???"  to  which he responded "it down regulates mTore in the brain just like the sirtuins....another levee I haven not hit yet.  The giant circle of life continues."

WOW. Ok that’s a lot to take in!  So basically, a woman who has PCOS her body’s mitochondria act like they are T2D.  So, I have bad mitochondria that are directly impacted by the overproduction of Testosterone, Estrogen at the ovaries, which drives an increase in insulin.  Talk about a vicious cycle.  This means I can’t fix the insulin issue, unless I fix my mitochondria issue.  So, that’s the next step.  Tomorrow I’m going to see my PCP and we’re going to be adding metformin to the arsenal to fix my mitochondria, and my FBG issues associated with my ovaries overproduction of Testosterone and Estrogen. 

However, its just one thing in the effort to fix my hormonal issues which are driving disease.  Metformin will help the mitochondria, but things won’t fully come around until we address the gut issues that are keeping everything from falling into place. I’ve got to address the gut issues. And that’s going to mean I finally need to kick the candida I’ve been harboring to the curb.   So, I’ll also be talking with my PCP about a 12-week course of diflucan to address the candida.  Add that to daily consumption of good bugs from my home made sauerkraut, and daily consumption of Kevita, and lots of raw seafood and a diet focused solely on Epi-Paleo Rx, lots of K2, and sublingual transreversitol my gut should get back on track.  I’ll keep you posted as I continue to progress towards Optimal health.