Tuesday, April 5, 2016

Blood Glucose, Leaky Gut, and Potatoes Part 2

I am exploring a possible third arm of blood glucose (BG) dysfunction and why the potato hack causes a lowering of BG levels in some people. I think that "leaky gut" is responsible for elevated BG in some people with type 2 diabetes (T2D).

Type 1 diabetes is a condition in which the pancreas secretes too little insulin to clear glucose from the blood leading to chronically elevated blood glucose. From Wikipedia on T1D (highlights mine):

Diabetes mellitus type 1 (also known as type 1 diabetes, or T1D; formerly insulin-dependent diabetes or juvenile diabetes) is a form of diabetes mellitus that results from the autoimmune destruction of the insulin-producing beta cells in the pancreas.[2] The subsequent lack of insulin leads to increased glucose in blood and urine. The classical symptoms are polyuria (frequent urination), polydipsia (increased thirst), polyphagia (increased hunger) and weight loss.[3]

The cause of diabetes mellitus type 1 is unknown.[4] Type 1 diabetes can be distinguished from type 2 by autoantibody testing. The C-peptide assay, which measures endogenous insulin production, can also be used. Administration of insulin is essential for survival.

Type 2 diabetes (T2D) is quite a bit different:

Type 2 diabetes is due to insufficient insulin production from beta cells in the setting of insulin resistance.[7] Insulin resistance, which is the inability of cells to respond adequately to normal levels of insulin, occurs primarily within the muscles, liver, and fat tissue.[39] In the liver, insulin normally suppresses glucose release. However, in the setting of insulin resistance, the liver inappropriately releases glucose into the blood.[16] The proportion of insulin resistance versus beta cell dysfunction differs among individuals, with some having primarily insulin resistance and only a minor defect in insulin secretion and others with slight insulin resistance and primarily a lack of insulin secretion.[7]

Other potentially important mechanisms associated with type 2 diabetes and insulin resistance include: increased breakdown of lipids within fat cells, resistance to and lack of incretin, high glucagon levels in the blood, increased retention of salt and water by the kidneys, and inappropriate regulation of metabolism by the central nervous system.[16] However, not all people with insulin resistance develop diabetes, since an impairment of insulin secretion by pancreatic beta cells is also required.[7]

While medical researchers, nutritionists, and health writers go to great lengths to explain diabetes by looking at insulin resistance, lack of insulin, and other factors no one describes what I think seems to be an even bigger problem, and quite possibly the root cause of T2D: a leaky gut.

Leaky Gut

It's not quite like it sounds. Leaky gut is not a perforated gut, but a malfunctioning gut. All guts are leaky, by design. The leakiness is referred to as "intestinal permeability." The small intestine has two important jobs:
  • Bring nutrients into the body
  • Keep toxic substances out of the body
To do this, the small intestine relies on permeable membranes. The permeability is created by changing the electron structure of cells which line the small intestine. There are also some specific channels inside of these cells which allow passage of some things and not others. Things can and do go wrong with this system. Leaky gut is a condition which describes incorrect intestinal permeability.

A good review of gut permeability can be found here:  Alterations in intestinal permeability (Arrietta, 2006).

From the lower oesophageal sphincter to the anus, the gastrointestinal tract has a single contiguous layer of cells that separates the inside of the body from the external environment. Separation is important as there are a wide variety of environmental agents in the lumen of the bowel that can initiate or perpetuate mucosal inflammation if they cross the epithelial barrier. While the epithelial lining of the intestine plays a critical role in preventing access of these agents, it is not the only component of what is termed barrier function. Also important are secreted products such as immunoglobulin, mucous, defensins, and other antimicrobial products.

Tight Junctions

One mechanism that controls the passage and blockage of nutrients or toxins between the small intestine and the bloodstream are tight junctions (TJ). Often shown as a very simplistic structure, as this discussion on celiac disease and TJs:

Tight Junctions are not quite as simple as shown in the graphic above, they involve some complex protein structures and permeable membranes:

From: Nature

A description of the figure above explains:

The main barrier function of the epithelium is thought to depend on tight junctions, which are connected with the actin cytoskeleton (left panel). Three types of transmembrane proteins are part of tight junctions: occludin, claudins and junctional adhesion molecules (JAMs), and they are connected to adaptor proteins such as zona occludens 1 (ZO1), ZO2 and ZO3. Many additional proteins are also essential, including PAR6, atypic Ca2+- and diacylglycerol-independent protein kinase C (aPKC), and PAR3. This complex, which is important for cell polarity, is regulated by Cdc42, as is the CRUMBS3–PALS1–PATJ-complex, which is essential for tight junction assembly. The precise role of RhoA and Rac in tight junction regulation has still to be elucidated. Recently, it was suggested that RhoA-dependent phosphorylation of occludin is crucial for tight junction function.

Tight Junctions communicate with each other, with the body, bacteria, fungi, and with the foods or toxins they come into contact with. It's an immensely elaborate biological marvel that scientists are just beginning to understand.  The important takeaways here are:
  • Tight Junctions can and do malfunction
  • Things get into our blood that should not be there
  • Tight Junctions allow the passage of glucose from food to bloodstream.
The topic of "Leaky Gut" as a disease state in human health is very controversial, and I do not intend to tackle this topic at the moment. But some well-known foods are shown to cause transient leakiness. From the Autoimmunity Reviews journal (2015), "Changes in intestinal tight junction permeability associated with industrial food additives explain the rising incidence of autoimmune disease." :

Glucose, salt, emulsifiers, organic solvents, gluten, [Microbial transglutaminase] mTG, and nanoparticles are extensively and increasingly used by these industries to improve the qualities of the food (as claimed by manufacturers and some consumers). However, all these food additives increase intestinal permeability by bringing about TJ paracellular transfer. In fact, TJ dysfunction is common in multiple [auto-immune disease] AD and the central part played by the TJ in AD pathogenesis has been extensively described. It is hypothesized that commonly used industrial food additives abrogate human epithelial barrier function, thus, increasing intestinal permeability through the opened TJ, resulting in entry of foreign immunogenic antigens and activation of the autoimmune cascade.

Conclusion to Part 2:

I am not trying to solve the Leaky Gut disease phenomenon, I am just laying the groundwork to show that malfunctioning TJs can result in high blood glucose. There are lots of papers, like the two or three linked above, that explore leaky gut if you are interested.

T2D is a disease in which chronically elevated blood glucose leads to loss of insulin sensitivity. The elevated blood glucose then damages cells and entire organs as it circulates through the body. The usual explanation is that we simply eat too much glucose-containing foods, ie. sugar, potatoes, and this leads to chronically high gluocose levels and/or a worn-out pancreas. Yet, a high carb diet can cure some cases of diabetes. How can this be?

Next...a description of how glucose gets from food to blood, and blood to cells, under normal circumstances. Also, why high blood glucose is so dangerous.


  1. "T2D is a disease in which chronically elevated blood glucose leads to loss of insulin sensitivity."

    I always thought chronic elevated blood glucose levels were the effect of being insulin resistant rather than the cause. And that the causes were a set of different possible things, most importantly having excess adipose tissue and the resultant inflammation this creates.

    1. Kind of chicken and egg, eh? In reading, there does not seem to be a consensus on what starts the cascade into metabolic syndrome.

      One of the leading theories is simply that we eat too much sugar, our blood glucose continually "spikes" and all this excess glucose causes insulin resistance.

      This theory has led to low carb dieting, intermittent fasting, and many other diet plans that avoid any spike in BG.

      In avoiding foods that might (gasp) cause a rise in blood sugar, we also avoid good, real, wholesome foods like whole grains, fruit, and POTATOES.

    2. I believe this is one of those cases where it may not be as simple as one causing the other.

      I know a fair amount about PCOS because I have it and have read about it extensively, so I will use PCOS as an example. PCOS is very strongly correlated with insulin resistance, overweight/obesity, dyslipidemia, inflammation, type 2 diabetes, elevated androgen levels, and a host of other things. It's part of such a complex feedback loop that you can enter the vicious cycle from just about any point.

      You can be thin and wind up with the full-blown syndrome, yet it's clear that obesity can lead to PCOS. You can have normal androgen levels and wind up with it, yet it's clear that excessive androgens can throw your glucose tolerance out of whack. You can have insulin resistance and *not* wind up with PCOS, and you can have PCOS without being insulin resistant.

      The point of my saying all of that is, maybe (going back to T2D now): either chronically elevated blood glucose AND/OR excess body fat are capable of leading to the full-blown T2DM syndrome, depending on the individual and on a whole lot of other factors we haven't even thought to mention or measure.

      --(Sidenote: As someone with dysautonomia, I'd like to suggest this as another of those "cause and/or effect?" symptoms, but it seems to be very common in both PCOS and T2D.)

    3. Tara - This is why I have pretty much dropped this subject. Glucose/insulin metabolism is very well studied, but hardly understood by anyone. When researching, it's like chasing a rabbit around a briar patch.

      As soon as I think I get it, something like PCOS comes along to make me realize there is always more to the story.

      Thanks for reading and commenting!

    4. Thanks for replying to me!

      Yes, it's all a very complicated entanglement with dozens (if not hundreds!) of factors. In fact, that's why I get so frustrated when people refuse to consider complex feedback loops and individual differences. They can really add up, and I think most of us can agree that this is precisely why there aren't really any "one-size-fits-all" solutions.

    5. Yep. ie., in the news today: http://medicalxpress.com/news/2016-08-gene-variant-differences-diabetes-drug.html

      I like writing about these things, but people must realize there is usually more to the story than meets the eye.

  2. I think I really need that physiology review. :-) I guess from the Diabetes article I linked to last post and read, I saw it as if diabetes starts (as you say) before the pancreas and cellular level and at the GI tract. Which the Diabetes article suggests can be for various reasons which could go along with all this "alternative" stuff of leaky gut/dysbiosis/macronutrient alteration/fiber ingestion, etc. The cells which line our GI tract are amazing, and I was thinking that any disruption that would go hand-in-hand with what we like to call "leaky gut syndrome" (not necessarily only the tight junction route) would also lead to disruption of the whole early encounter of carbohydrates/glucose metabolism. (Here's that article again: http://diabetes.diabetesjournals.org/content/62/9/3005.full ) My apologies if none of this makes sense and I'm talking in left field. Have a great day! Terri

    1. This makes sense where Paleo types have been noshing biggie time on coconut oil and other fats. Then they get blood glucose regulation issues when they start to eat carbs. Which means they've reregulated their gut microbiome for their diet and so long as they stick with that diet, they won't be running into trouble. Change it up and there's a temporary glitch with glucsoe regulation. Also certain micronutrients are missing in a meat based diet. So possibly this factors in as well. Low magnesium for example. Type 2 diabetics are encouraged to supplement with magnesium.

      But if lipids provide a negative feedback loup for ceasing eating, then for sure this is disabled in people who can down a 3 pound ribeye steak. That is obesogenic behaviour.

    2. Great article, Terri - I just read a few times. Even though they give numerous routes to diabetes, it seems they are saying that the excess glucose is simply a result of insulin resistance.

      Stated in the article:

      "Within 2 days, DJB [gastric bypass surgery] lowers blood glucose concentrations independent of lowering food intake/body weight or increasing insulin secretion in both uncontrolled diabetic models."

      This can also be seen with the potato hack. I'd love to see a controlled study comparing a potato intervention with bypass surgery.

      The paper implies that bypass surgery works by bypassing the duodenum (first section of the small intestine). They believe it has to do with nutrient sensing and feedback loops/glucose absorbtion.

      Maybe it really works because the duodenums's of these patients are extremely leaky. Bypass surgery removes the leaky section, the potato hack repairs the leaky section (for a short time).

      Long term diabetes remission after bypass surgery is not that great. 27% according to this paper: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110959/

      So what happens? Does the leakiness move to the previously non-leaky section of the small intestine?

      Here's another diet that cures diabetes: http://www.ncbi.nlm.nih.gov/pubmed/24532293

      No potatoes, but all veggie, no meat, no fat. Kempner Rice diet cured diabetes. An all-potato diet described in an 1800's medical journal cured diabetes.

  3. Tim, Here is a similar article to my last. I'll probably not make it back so no worries on replies.


    I hate putting my theories on the internet because I'm more the person who likes to read everything everyone else writes and then try to synthesize it and digest it and put it together--but let's say that the duodenum of "today's person" is leaky/dysbiotic/the brush border is damaged and moderately dysfunctional/the hormonal and chemical system which starts with even thinking about food is disrupted/and so on and so forth with all these alternative ideas. In one case removing the duodenum "cures" the diabetes. In the potato case, does removing the need for all those things to be intact remove the diabetes? So the potato doesn't need so much of an intact duodenal environment and yet provides appropriate nourishment, yet gut rest, to maybe promote healing? Well, that's about all I have. I wish I had time to read the articles you linked to. But I've got a future research team to train up, and they are BUSY kids. :-) All the best to you and Gabriella too! Terri

  4. Here's the final piece in a series of posts written by the estimable Stephan Guyenet on the causes of insulin resistance. He creates a list in order of importance:

    1.Cellular energy excess

    2.Physical inactivity (related to #1)

    3.Inflammation (related to #1 and others)

    4.Very low carbohydrate intake (less than 10%)


    6.Insulin resistance in the brain

    7.Low birth weight/size

    8.Inappropriate micronutrient status and insufficient protective phytochemical intake

    9.Smoking tobacco

    10.High heat cooking

    11.Excessive physical or psychological stress


    1. Thanks. Great list. What I see missing is "excess glucose." The general thoughts are that the insulin resistance itself leads to excess glucose in the blood, and perpetuates itself. Others see it as too much glucose from sugary/starchy foods leads to excess glucose and in turn insulin resistance.

      No one sees it as excess glucose leaked into the blood via a damaged, or mis-signalled gut. The excess glucose then causing insulin resistance, or mimicking insulin resistance, but overtaxing the pancreas nonetheless.

    2. Although, maybe his #1 "Cellular excess energy" is a way of saying too much glucose in the blood.