Endocrinologist Orville Kolterman discusses Type 2 diabetes
... as well as the gut microbiome and Pendulum Glucose Control
What about Pendulum Glucose Control’s 5 probiotics and 1 inulin prebiotic is so game changing for the management of Type 2 diabetes?
In people with Type 2 diabetes, there are certain bacteria that have gone missing in the gut microbiome. As a result of these bacteria going missing, certain important gut health functions are either decreased—or gone altogether.
Pendulum Glucose Control and its 5 probiotics and inulin prebiotic contain those missing bacteria, and put them back into your gut microbiome.
One important function is that these bacteria ferment dietary fiber to produce the short-chain fatty acid butyrate, which is an important signaling molecule for both metabolic function, as well as for other important things.
For eons, the foundation/cornerstone of Type 2 diabetes treatment has been diet and exercise. How is Pendulum Glucose Control now a companion to diet and exercise?
If you look at the dietary recommendations that are made, what they in essence do is increase the content of dietary fiber in the diet. So, those are the building blocks for activating this pathway that is responsible for producing butyrate.
However, if you don’t have the appropriate bacterial strains in the gut to metabolize that fiber—and produce that important butyrate—your dietary impact is being somewhat limited.
While I can’t prove it today, I think that over time we’ll come to understand that this is one of the reasons why diet and exercise haven’t had the anticipated impact on Type 2 diabetes. Diet and exercise is always where we start, but it usually falls short of the goal. Healthcare professionals will often write that off as poor compliance on the part of the patient.
How does a sedentary lifestyle—coupled with poor dietary choices—decrease beneficial bacteria in the gut microbiome?
A poor dietary lifestyle deprives the important microbes within your gut microbiome of their primary dietary fiber-nutrient source.
If you look at poor dietary lifestyles, it usually involves not getting enough fruits, nuts, and fresh vegetables.
“Westernized” diets have replaced fruits, veggies, and nuts with highly refined carbohydrates, sugars, and fat
For as long as humans have been around, we have come by fiber honestly. Are you saying that following “Westernized” diets puts us in a position where we don’t give ourselves those sources of fiber anymore, which then affects our Type 2 diabetes management?
I think that’s true.
It’s like the Pima Indian story. You go back 200-300 years ago. Our ancestors were fit and healthy because they had to run all day to catch whatever it was they were going to eat. Or, they foraged around for nuts and berries.
Then, we took the Pima Indians and we confined them to this reservation where they were no longer running around for their food. We also gave them food that was low in fiber and high in refined sugars and carbohydrates, as well as excess fats from processed foods.
Since they had selected “thrifty genes” to survive in a food-restrained environment, they quickly gained large amounts of weight in the presence of excess calories. And, the low fiber content of their new diet disrupted their gut microbiome.
Do these beneficial bacteria in the gut microbiome eventually just “give up” when—over time—the body is inundated with sugars and fat and denied fiber?
Like you said: Before the adoption of "Westernized" diets, we always came by our fiber honestly. But now, we are putting ourselves in a position where we don’t want to give ourselves those types of fibers anymore.
Is there a genetic component that factors into the levels of Akkermansia muciniphila in the gut microbiome?
Within the gut microbiome, there is over 11 times more genetic material than what there is in the human genome, and we don't totally understand all the aspects of how the human genome interacts with itself. However, we now have this big mass of additional genetic material, and it’s clear that those two are interacting.
It’s my expectation that—over time—the microbiome is going to provide the answer to a number of things that we just don’t yet understand about ourselves.
So, if a 9th-grade biology student asked, “Why is the microbiome a crucial part of my health, and how does it somehow play a role in me developing Type 2 diabetes?” What would you tell that 9th grader?
I’d tell her or him that if you read through the material that has been written and you have been given about the various organ systems in the human body, you will not read about the microbiome today. And that’s a major oversight, because—in reality—the gut microbiome is an organ that we didn’t know that we have.
We know the role that the pancreas and kidney play in Type 2 diabetes. What would you tell that high school student about the role the microbiome plays in Type diabetes?
I think you can look at the microbiome as playing a role that is as important as the pancreas when it comes to diabetes.
Take any of the endocrine organs you learn about in biology. About how it’s an organ that produces these hormones that are secreted into the bloodstream. They then exert effects on distant parts of the body.
The microbiome does the same thing.
The microbiome produces metabolites that either act locally in the gut, or they hit the bloodstream and they go throughout the body and impact distant targets.
There is even strong evidence that there are neurotransmitters that are produced by the microbiome that enter the bloodstream and exert effects on the brain.
In relation to Pendulum Glucose Control, butyrate is a key product which functions in this way. Butyrate is a fuel source for the cells that line the gut. Butyrate also interacts with receptors on the L cells that produce GLP-1 and PYY. Equally as important to all of that, it appears that butyrate made in the gut is an important regulator for the immune system, and it just keeps going and going.
If that high-school biology student had a mom or dad with Type 2 diabetes, what would tell him or her about Akkermansia or PGC?
I would tell them that PGC would likely give their mom or dad back strains—or add strains—to their microbiome that will digest the healthy fiber that the dietitians have talked to their parents about needing to include in their diet for healthy living. It will sort of activate that fiber to make it really have a greater impact upon the aspects of metabolism that will help them improve their glucose control.
As far as Akkermansia is concerned: I would tell them that Akkermansia is not indicated for the management of. Type 2 diabetes. Akkermansia improves the health of the gut lining. It maintains the protective mucin layer that overlays the gut lining. This mucin also serves an important energy source for the cells that line the gut.
Can you speak to the inulin prebiotic of the Pendulum Glucose Control capsule? What does it bring to the game of managing Type 2 diabetes?
The inulin prebiotic is included in the Pendulum Glucose Control formulation because—for the strains that are contained in Pendulum Glucose Control—inulin seems to be a preferred fiber source. The bugs that we have in Pendulum Glucose Control use inulin as a source to drive the things that they do.
It’s like we’re sending these beneficial bacteria strains in a Pendulum Glucose Control capsule out for a picnic within the gut. The 5 probiotics are going down the gut to have a picnic, but the inulin is there so that when they arrive at their picnic they have something to eat right away to help them get established and get the party going.
So, are we at a point now in the history of Type 2 management where we can say to a a person with Type 2 diabetes, “Hey... you have deficits of beneficial bacteria in your gut microbiome because of your Type 2 diabetes, but there’s now a ‘companion’ to growing beneficial bacteria back into your gut?”
And the beneficial bacteria are there as long as you take the Pendulum Glucose Control product. The data that we have so far—after 3 months of administration—says that if you stop using Pendulum Glucose Control, the beneficial strains that you get from taking PGC disappear again.
I can make a theoretical argument that if you continue to take PGC for longer, say18 months as an example, the favorable strains in PGC will be able to set up housekeeping so that they can persist without a continued influx of the strains.
Orville Kolterman, MD, is the Chief Medical Officer at Pendulum.
Dr. Kolterman received his MD and did his postgraduate training in Endocrinology and Metabolism at Stanford University.
Dr. Kolterman has held leadership roles in regulatory, research, development, clinical, and medical affairs departments—many of which were officer-level positions.
During his 20-year tenure at Amylin, Dr. Kolterman led teams that developed four novel, first-in-class drugs that are currently used by patients with both Type 1 and Type 2 diabetes.
Dr. Kolterman came out of retirement because of his fascination with exploring the microbiome in an effort to improve the lives of individuals struggling to restore metabolic balance.
Dr. Kolterman feels that the interactions between the microbiome and the human genome has the potential to both better understand and address many abnormalities that are not adequately addressed today.
We recently sat down with Dr. Kolterman to discuss the gut microbiome and Type 2 diabetes