Wednesday, August 24, 2016

Insulin Resistance, Inflammation, Oxidation and Glycation

There are many biological, biochemical and hormonal processes that fuel diseases such as Type 2 diabetes, heart disease, obesity, arthritis, Alzheimer's and cancer.
Five of the key processes that fuel these diseases are:
  • Insulin Resistance
  • Inflammation
  • Oxidation
  • Glycation
  • Toxicity

Insulin Resistance (IR)

Insulin resistance is a physiological condition in which cells fail to respond to the hormone insulin. The pancreas produces insulin, but the cells in the body become resistant to insulin and are unable to use it as effectively, leading to hyperglycemia.
Subsequently, the pancreas increases its production of insulin, further contributing to hyperinsulinemia. This often remains undetected and can lead to the development of Type 2 diabetes.
One of insulin's functions is to regulate delivery of glucose into cells to provide them with energy. Insulin resistant cells cannot take in glucose, amino acids and fatty acids. Thus, glucose, fatty acids and amino acids 'leak' out of the cells.
A decrease in insulin/glucagon ratio inhibits glycolysis which in turn decreases energy production. The resulting increase in blood glucose may raise levels outside the normal range and cause adverse health effects, depending on dietary conditions.
As depicted in the diagram below, certain cell types such as fat and muscle cells require insulin to absorb glucose from the bloodstream. When these cells fail to respond adequately to circulating insulin, blood glucose levels rise.
The liver helps regulate glucose levels by reducing its secretion of glucose in the presence of insulin. This normal reduction in the liver’s glucose production may not occur in people with insulin resistance.
Insulin resistance in fat and muscle cells reduces glucose uptake (and also local storage of glucose as glycogen and triglycerides, respectively), whereas insulin resistance in liver cells results in reduced glycogen synthesis and storage and also a failure to suppress glucose production and release into the blood. 
Elevated blood fatty-acid concentrations, reduced muscle glucose uptake, and increased liver glucose production all contribute to elevated blood glucose levels. High levels of insulin and glucose due to insulin resistance are a major component of the Metabolic Syndrome. 

Inflammation

Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. In other words, inflammation is the body’s attempt to heal itself.
Inflammation is a protective immune response that involves macrophages, white blood cells and other immune cells. These cells work together to eliminate the initial cause of cell damage/injury, clear out necrotic cells and tissues damaged from the original injury, and to initiate cell/tissue repair.
The classical signs of acute inflammation are pain, heat, redness, swelling, and loss of function until the cells/tissues are repaired.
Inflammation is tightly regulated by the body. Too little inflammation could lead to progressive tissue destruction by the harmful stimulus (e.g. bacteria) and compromise the survival of the organism. In contrast, chronic inflammation may lead to a host of diseases, such as atherosclerosis, rheumatoid arthritis, periodontitis, and even cancer.
Inflammation can be classified as either acute or chronic. Acute inflammation is the initial response of the body to harmful stimuli and is achieved by the increased movement of plasma and leukocytes (especially granulocytes) from the blood into the injured tissues.
A series of biochemical events occur, involving the local vascular system, the immune system, and various cells within the injured tissue.
As depicted in the diagram above, prolonged inflammation, known as chronic inflammation, leads to a progressive shift in the type of cells present at the site of inflammation and is characterized by simultaneous destruction and healing of the tissue from the inflammatory process.
Over time, this type of prolonged inflammation can lead to diseases such as heart disease, Type 2 diabetic complications, Parkinson's and Alzheimer's. 

Oxidation

Oxidation is a process where there is the loss of at least one electron when two or more atoms or molecular compounds interact. An apple turning brown or a nail rusting are examples of oxidation.
If you recall what you learned in your high school chemistry class, most molecules are stable when they have 2 electrons in the outer “shell” or orbit. But, when one of the electrons is removed, the molecule becomes unstable. This is known as a "free radical".
Free radicals are atoms or molecules which have at least one unpaired valence electron in the outer orbital.
Free Radical Molecule: Cause of Oxidation
In our modern world, our bodies are exposed to elevated levels of free radicals from external sources such as exposure to X-rays, ozone, cigarette smoking, air pollutants, and industrial chemicals.
The mitochondria in our cells are the main source of free radicals under normal conditions. Free radicals can react with any biological molecule (proteins, lipids, sugars, DNA) altering its structure and often its function. Therefore living organisms are provided with a rich system of antioxidant defenses whose main purpose is to prevent the free radicals attack to other molecules.
The DNA in the nucleus of our cells is one of the major targets of oxidation and free radicals. Free radicals damage our DNA, which may lead to a cell mutation and trigger the development of diseases such as cancer.
Free radicals also cause damage to other cells and tissues in the body, which may lead to other diseases such as atherosclerosis, heart disease, and arthritis.

When free radicals increase significantly, this can cause oxidative stress. Oxidative stress (chronic oxidation) is an imbalance between oxidants and antioxidants in favor of the oxidants, potentially leading to cell/tissue damage.
Oxidative stress occurs when our exposure to, or our body’s production of, free radicals exceeds our body’s ability to counteract or detoxify their harmful effects through neutralization by the body's internal antioxidants.
However, similar to inflammation, oxidation is not harmful as long as it doesn't get out of control. For example, free radicals are normally used by the immune system to attack and kill invading germs and some pre-cancer cells. 
As shown in the diagram below, when oxidation gets out of control (oxidative stress), it is involved in accelerated biological aging as well as in the pathogenesis of several diseases, including atherosclerosis, cancer, Type 2 diabetes, Alzheimer's, and heart disease.

Glycation

Red blood cells contain a small amount of glucose molecules attached (glycated) to the protein portion of the red blood cells. This is considered normal.
However, when there is an excess amount of glucose molecules in the bloodstream (i.e. hyperglycemia), this increases the amount of glucose molecules that are attached to the red blood cells. This process is known as glycation.
As depicted in the following diagram of a red blood cell, in a diabetic's body, there are a lot more glucose molecules attached to the hemoglobin within the red blood cell.
Red-Blood-Cells-Hemoglobin-and-Glucose-Molecules
Glycation is a process where glucose molecules attach themselves to red blood cells, forming a crystalline (coarse) crust and creating advanced glycation end products (AGEs). See diagram below of a glycated red blood cell.
As these coarse red blood cells circulate throughout the body, they cause damage throughout the circulatory system to arteries and capillaries.
As you can see from the diagram (below), a glycated red blood cell has "jagged" edges, which cause damage to the linings of your blood vessels.
In response to this damage, your immune system triggers various white blood cells and other cells to release various enzymes and repair agents to try to repair the damage caused by the diabetes.
But, the immune system lacks the resources (e.g. vitamins and minerals) to repair the damage, so it becomes overwhelmed and ill-equipped to deal with the scope of this disease.
Glycated Red Blood Cell
This damage is repaired by the cholesterol produced by the liver, leading to arterial plaque formation -- all triggered by an inflammatory response. These coarse red blood cells cause greater damage in dense capillary areas such as the hands and feet, and fragile capillaries such as those that feed the kidneys and the eyes.
These advanced glycation end products (AGEs) form at a constant but slow rate in the normal body, starting in early embryonic development, and accumulate with time. However, their formation is accelerated in diabetes because of the increased availability of glucose.
As a result, an increase in AGEs can be found in vascular tissues, retinal vessels, nerve cells (myelin sheath damage) and glomeruli membranes of diabetic patients, which can lead to atherosclerosis, retinopathy, neuropathy and nephropathy.
Increased AGE accumulation in the diabetic vascular tissues has been associated with changes in endothelial cell, macrophage, and smooth muscle cell function.
In addition, AGEs can modify LDL cholesterol in such a way that it tends to become easily oxidized and deposited within vessel walls, causing streak formation and, in time, atheroma. AGE-crosslink formation results in arterial stiffening with loss of elasticity of large vessels, which, over time, can lead to high blood pressure, atherosclerosis and heart disease.
Studies in animals have demonstrated an important relationship between high dietary AGE intake (e.g. fried foods, fast foods) and the development or progression of diabetes-related tissue damage, e.g., vascular and renal.
This can be prevented by following a diet designed to be low in AGEs (such as the Death to Diabetes Diet). This type of diet can decrease AGE intake by more than 50% and reduce circulating AGEs by ∼30% within 2-3 months, reducing fasting blood glucose and hemoglobin A1C levels. 

Formation of Red Blood Cells

Red blood cells (erythrocytes) are produced through a process called erythropoiesis. Erythropoiesis is the development process in which new erythrocytes are produced in the bone marrow, through which each cell matures in about seven days.
Through this process, erythrocytes are continuously produced in the red bone marrow of large bones, at a rate of about 2 million cells per second in a healthy adult. 
Within the bone marrow, all blood cells originate from a single type of unspecialized cell called a stem cell. When a stem cell divides, it first becomes an immature red blood cell, white blood cell, or platelet-producing cell. The immature cell then divides, matures further, and ultimately becomes a mature red blood cell, white blood cell, or platelet.
The rate of blood cell production is controlled by the body's needs. Normal blood cells last for a limited time (ranging from a few hours to a few days for white blood cells, to about 10 days for platelets, to about 120 days for red blood cells) and must be replaced constantly.
Key Point About Your Red Blood Cells: When new red blood cells are created, they are "virgin" and have no glucose attached to them. When the new red blood cells leave the bone marrow and enter your bloodstream, some of them become glycated because of the high amount of glucose (molecules) in your bloodstream. These red blood cells cannot become unglycated.
However, since your red blood cells have a limited life span (90-120 days), the body eventually gets rid of the glycated red blood cells and replaces them with new "virgin" red blood cells. But, since you're diabetic, the new virgin red blood cells eventually become glycated also.
However, if you start eating a plant-based diet, the amount of glucose molecules in your bloodstream begin to decrease and the amount of red blood cells that become overly glycated start to go down. Then, eventually, your blood glucose level will start to come down within 3 to 4 weeks, sometimes sooner.
As a result, you will notice your day-to-day blood glucose readings start to go down; although, on some days, it will still go up. But, as long you continue eating and exercising properly and consistently, eventually, after 3-4 months (or longer), your hemoglobin A1C will also start to come down.
Please keep in mind that, depending on the amount of glycation and how long you've been diabetic, it may take several months (or longer) to get your blood glucose back to the normal range.
Why is this a key point to understand? Because there are a lot of websites, videos, etc. claiming that they can cure your diabetes in 30 days or sooner! These websites are either lying to you or they're just ignorant when it comes to understanding cell biology, hematology, and biological processes such as erythropoiesis, specifically the life cycle of erythrocytes.
Since you now realize that it takes 90-120 days to turn over your red blood cells, you can't reverse or cure your diabetes in 30 days. So, although our program will begin to lower your blood glucose within 7 to 10 days, it takes a lot longer for your blood glucose to stabilize and be consistent.

Toxicity

We expose our bodies to toxins every day via food, water, air and the environment. Pesticides and chemical solvents are obvious toxins that most of us are aware of; but, there are thousands of other toxins that we may overlook.
For example, toxins from food (artificial sweeteners, food dye, trans fats, MSG) and water (fluoride, chlorine, arsenic) can cause serious damage to our cells and tissues, especially if we don't eat the right foods to help our organs remove these toxins from our bodies.
This constant exposure to these toxins every day puts a tremendous load on our liver, kidneys, colon and lungs to remove these toxins.
These toxins cause oxidative stress and inflammation, which cause cell and tissue damage. And, over a period of years, a toxic overload can lead to diseases such as cancer, diabetes, obesity, thyroid disease, autoimmune disease, and Alzheimer's.
Refer to the Cleanse-Detox web page for more information about these toxins and how to get rid of them.

Cells Affected and Damaged

As depicted in the following flowchart, there are many cells that are affected and damaged from long-term insulin resistance, chronic inflammation, excess  oxidation and glycation.
These cells include red blood cells, white blood cells, fat cells, liver cells, muscle cells, kidney cells, endothelial (blood vessel inner lining) cells, epithelial (skin)cells, nerve cells, brain cells, and cells associated with the eyes (e.g. retina) -- just to name a few.
Cells Affected and Damaged From Type 2 Diabetes
As depicted in the flowchart (above) and in the  following diagram, when these cells are damaged, this leads to a multitude ofdiabetic complications such as blindness, amputation and kidney failure. In addition, these processes fuel other diseases such as heart disease, arthritis, obesity, Alzheimer's and even some cancers.
Diabetic Complications Created From Damaged Cells

No comments: