Saturday, September 03, 2016

Autoimmune Disease Symptoms, Diagnosis and Treatments

Autoimmune Disease Symptoms

Symptoms of autoimmune disease vary and depend on the type of autoimmune disease. Here is a quick overview of some of the symptoms of the most common autoimmune diseases:

Celiac disease: Inflammation and pain in the abdomen, chest burning, tiredness, weight loss, vomiting, and diarrhea.

Rheumatoid arthritis: Painful swelling and stiffness of the joints, particularly in the hands and feet.

Psoriasis: Joint pain, dry skin, skin rashes, and itchiness.

Inflammatory bowel disease: Stomach cramps, bloating, bloody diarrhea, nausea, and constipation.

Addison's disease: Tiredness, low blood pressure, low blood sugar, dizziness, dehydration, and loss of appetite.

Type 1 diabetes: Frequent urination, increased thirst, loss of energy, blurred vision, hunger, and nausea.

Vitiligo: Loss of skin color (especially noticeable in darker-skinned patients).

Hashimoto's disease: Weight gain, tiredness, depression, joint stiffness, and increased sensitivity to cold.

Graves' disease: Weight loss, anxiety, shaky hands, high blood pressure, and sweating.

Lupus: Muscle and joint pain, rash, tiredness, and fever.
Since many autoimmune diseases share similar symptoms, diagnosis is often challenging.

For example, lupus affects the joints in a similar way to RA but tends to be less severe. Lyme disease also causes joint stiffness and inflammation similarly to RA but is caused by a tick.

IBD has similar symptoms to celiac disease but is not typically caused by eating foods containing gluten.

Symptoms and Signs of an Autoimmune Disease

If you are experiencing any of these symptoms, especially a combination of several of them, you may have an autoimmune disease:

  • Uncontrolled blood sugar, especially as a child or young adult
  • Joint pain, muscle pain or weakness or a tremor
  • Weight loss, insomnia, heat intolerance or rapid heartbeat
  • Recurrent rashes or hives, sun-sensitivity, a butterfly-shaped rash across your nose and cheeks.
  • Difficulty concentrating or focusing
  • Feeling tired or fatigued, weight gain or cold intolerance
  • Hair loss or white patches on your skin or inside your mouth
  • Abdominal pain, blood or mucus in your stool, diarrhea or mouth ulcers
  • Dry eyes, mouth or skin
  • Numbness or tingling in the hands or feet
  • Multiple miscarriages or blood clots

Diagnosis of Autoimmune Diseases

The following are some of the medical tests used to diagnose an autoimmune disease:

  • Autoantibody tests: any of several tests that look for specific antibodies to your own tissues
  • Antinuclear antibody tests: a type of autoantibody test that looks for antinuclear antibodies, which attack the nuclei of cells in your body
  • Complete blood count: measures the numbers of red and white cells in your blood; when your immune system is actively fighting something, these numbers will vary from the normal
  • C-reactive protein (CRP): elevated CRP is an indication of inflammation throughout your body
  • Erythrocyte sedimentation rate: this test indirectly measures how much inflammation is in your body

Diagnosis Differences
The diagnosis of autoimmune disease differs based on the specific disease. Rheumatoid arthritis, for example, may be diagnosed after a physical exam, blood test, or X-ray. These tests can determine the type of arthritis as well as how severe it is.

Diseases can sometimes take years to diagnose because many symptoms of autoimmune disorders mimic other diseases. Conditions like lupus and celiac disease may be misdiagnosed in their early stages because their symptoms are so similar to other diseases.

Hashimoto's disease and Graves' disease are a bit simpler to diagnose as they usually rely on a simple thyroid test. This test determines levels of thyroid hormone.

An autoimmune disease usually centers around the immune system and the antibodies produced by this system. As a result, diagnosis often involves testing for specific antibodies.

A complete blood count may be ordered to measure the amount of white and red blood cells. When the immune system is fighting something, the number of white and red blood cells will differ from normal levels.

Other tests can determine if there is any unusual inflammation in the body. Inflammation is a symptom that is fairly common among all autoimmune diseases. These tests include a C-reactive protein test and an erythrocyte sedimentation rate test.

A doctor should be seen right away as soon as symptoms begin. While symptoms may not always be caused by an autoimmune disease, it's best to tackle any issues right away than wait for them to get worse.

Medical Treatment Strategies
Unfortunately, conventional doctors only treat the symptoms of autoimmune diseases; they don't look to find the root cause. Often, they prescribe medications such as anti-inflammatory drugs, steroids, or immunosuppressants.

All of these treatments fail to address the underlying cause of the autoimmune condition in the first place and, while they may be effective in the short term, they are not a long-term solution. Treatments involving immunosuppressant drugs increase the risk of severe infections and cancer when taken for long periods of time.

Medical treatments include:

  • Hormone replacement therapy, if necessary
  • Blood transfusions, if blood is affected
  • Anti-inflammatory medication, if joints are affected
  • Pain medication
  • Immunosuppressive medication
  • Physical therapy

Alternative Treatment Strategies
If you suspect that you have an autoimmune disease, the most important steps to stopping and reversing your disease and symptoms are to identify and then to treat the underlying root cause.

Identifying which autoimmune disease is affecting you can be a difficult process. Symptoms may be vague, and autoimmune diseases can present themselves in so many different ways, affecting the thyroid, the brain, the skin, or other organs.

Work closely with a functional medicine physician or naturopathic doctor to help you with a proper diagnosis. A proper diagnosis is key to getting well.

Ensure that they review your family medical history, and understand your risk factors for infections, food sensitivities and toxins, as well as listen to your body closely to discover how all of your symptoms are related. And, you should keep a food diary to track how you're feeling and when you have a specific flareup,

All of this is an essential part of diagnosing your problem and getting well. A functional medicine physician, naturopathic doctor or similar alternative health professional will help to narrow down which labs they recommend in order to help find the root cause of your condition.

Then, they can help you design a nutritional and overall wellness program to treat your disease.

The following alternative therapies have provided relief for some people:

  • Nutritional therapy
  • Raw Juicing therapy
  • Detox therapy
  • Herbal therapy
  • Chiropractic therapy
  • Acupuncture
  • Naturopathy
  • Homeopathy
  • Hypnosis

References: (American Autoimmune Related Diseases Association)

Thursday, September 01, 2016

Types of Autoimmune Diseases

There are several different types of autoimmune disease that may affect different organs and systems in the body.

There are nearly 80 different types of autoimmune disorders. While some like Hashimoto’s thyroiditis are quite common, some are rarer.

Autoimmune diseases that affect multiple organ systems

  • Systemic Lupus Erythematosus (SLE) – this is a chronic auto-inflammatory disease. It is seen more commonly among females. The diagnostic tests are usually positive for antibodies against nuclear proteins including nucleic DNA and RNA. Some of triggers for flare ups include UV radiation, viral infections and stress.
  • Acquired Autoimmune Disorders caused by Human Immunodeficiency Virus (HIV) infection is also seen. Infection with HIV causes destruction of the immune system leading to damage to several organ systems and tissues.

Autoimmune diseases that affect the eyes

  • Acute anterior uveitis – this is the commonest inflammatory disease of the iris of the eyes. There is a strong genetic association with HLA-B27.
  • Sjögren's Syndrome – an autoimmune disease in which the immune system damages the glands that make moisture, such as tears and saliva.


  • Ankylosing Spondylitis – this is a common form of chronic, inflammatory arthritis that is caused by autoimmune pathology. It affects the joints in the spine and the sacroiliac joints of the pelvis leading to severe pain, deformity and disability.
  • Reactive Arthritis or Reiter's Syndrome – this is usually triggered by an infection. There are three classic symptoms of this condition including inflammatory arthritis of large joints (commonly knees and lower back), inflammation of the eyes with either  conjunctivitis or  uveitis and presence of urethritis in men (urethral inflammation) or cervicitis (cervical inflammation) in women.
  • Rheumatoid arthritis – this is an autoimmune disorder affecting the tissues in the joints. It leads to severe damage of cartilage in the joints leading to inflammation. Other organs such as lungs, pericardium, pleura, and sclera of the eyes may also be affected.

Autoimmune diseases affecting hormone producing organs

  • Diabetes Mellitus Type 1 – here the autoantibodies affect and target the insulin-producing beta cells of the pancreas leading to their severe deficiency. The lack of insulin leads to increased blood and urine glucose.
  • Autoimmune Pancreatitis – this is an inflammatory condition that affects the pancreas.
  • 21 - Hydroxylase Deficiency – this condition affects the adrenal glands. This condition leads to excess production of androgens, which are male sex hormones.
  • Autoimmune Thyroiditis – this condition leads to inflammatory cells targeting cells of the thyroid causing them to be destroyed leading to an underactive thyroid gland. Chronic thyroiditis or Hashimoto's disease may being at any age are is often common among middle-aged women.
  • Graves’ disease is an autoimmune disease of the thyroid gland that leads to an overactive thyroid gland.

Autoimmune diseases affecting the skin

  • Scleroderma – this type of autoimmune disorder commonly affects the connective tissues of skin and blood vessels, muscles, and internal organs. The disease usually affects women more commonly between ages 30 and 50 years.
  • Dermatomyositis – this condition results in inflammation of muscles and a skin rash. It may affect persons with cancers of the lungs, abdomen or other organs.
  • Psoriasis – this is an autoimmune skin disease. There is excessive growth of the new cells underneath the layers of skin.
  • Vitiligo – in this condition the cells that give pigment to the skin are destroyed leading to formation of white de-pigmented patches.
  • Alopecia areata is seen when the immune system attacks hair follicles or the roots of the hair.

Autoimmune diseases affecting the nerves

  • Multiple sclerosis – this is an autoimmune disease that affects the brain and the nerves. The autoimmune cells cause damage to the myelin sheath that normally acts as the protective covering that surrounds nerve cells.
  • Myasthenia gravis – in this condition the immune system attacks the nerves and muscles leading to severe weakness

Autoimmune diseases affecting the blood and blood vessels

  • Polyarteritis nodosa – this is a severe autoimmune disease affecting the small and medium-sized arteries that become inflamed and damaged. The risk of this condition rises with hepatitis b and C infections.
  • Antiphospholipid antibody syndrome leading to damage to blood vessels
  • Hemolytic anemia – this type of anemia is caused when the immunological cells damage the blood cells.
  • Idiopathic thrombocytopenic purpura (ITP) – this causes damage to the blood platelets that are essential to formation of blood clots.

Autoimmune diseases affecting the gastrointestinal system

  • Autoimmune Hepatitis – this type affects the liver when the body’s immune cells attack cells of the liver. There is a genetic predisposition to this condition. Autoimmune hepatitis affects 1-2 people per 100,000 per year and affects women much more often than men (70%). 
  • Celiac disease – this is caused when the intestines react to foods containing gluten (e.g. wheat).
  • Inflammatory bowel disease (IBD) – this condition leads to severe and chronic inflammation of the digestive tract. Crohn’s disease and ulcerative colitis are the commonest forms of IBD.
  • Primary biliary cirrhosis – in this condition the immune system slowly destroys the liver’s bile ducts.

Tuesday, August 30, 2016

What Causes Blood Sugar to Rise

The key elemnts that cause blood sugar to rise include:

  • Food
  • Drugs
  • Lifestyle

The following is a more detailed breakdown of these key elements that can cause your blood sugar to rise. This is important to understand because it's not just the food that may cause your blood sugar to rise.

By understanding this, you won't become frustrated when you eat properly and notice that your blood sugar is not coming down. This is why it's so important to maintain a daily journal of your meals, exercise regimen, activities, events, stress level, etc.

Normally, the liver releases glucose to maintain blood sugar levels. But when alcohol is consumed, the liver is busy breaking the alcohol down, and it reduces its output of glucose into the bloodstream.

This can lead to a drop in blood sugar levels if the alcohol was consumed on an empty stomach.

However, alcoholic drinks with carbohydrate-rich mixers (e.g., orange juice) can also raise blood sugar because they have plenty of carbs. But your levels may drop for as long as 12 hours after drinking.

Some people with allergies have been known to have higher glucose levels, primarily due to the stress hormone cortisol and the specific medications.

Artifical Sweeteners
An interesting new Israeli study suggests that artificial sweeteners can raise blood sugar levels! In a follow-up study of 400 people, the research team found that long-term users of artificial sweeteners were more likely to have higher fasting blood sugar levels, reported by HealthDay.

Birth Control Pills
Birth control pills with estrogen can affect the way your body handles insulin and cause your blood sugar levels to rise.

Many studies have suggested that caffeine in coffee increases insulin resistance and stimulates the release of adrenaline.

The same goes for black tea, green tea, and energy drinks. But, since each person with diabetes reacts to foods and drinks differently, it's best to keep track of your own blood glucose readings.


Of course, everyone is aware that carbohydrates raise your blood sugar. However, you should still eat carbohydrates, especially the high quality carbohydrates such as vegetables and some fruits.

It isn't just the carbs in rice, bread, pasta, etc. that cause your blood sugar to rise. It's the high amount of fat in foods such as sesame beef or sweet and sour chicken, which can make your blood sugar stay up longer. The same is true for pizza, French fries, and other foods that have a lot of carbs and fat. Check your blood sugar about 2 hours after you eat to know how a food affects you.

Dawn Phenomenon
The “Dawn Phenomenon” raises your blood sugar due to the body’s daily production of hormones around 4:00-5:00 AM. During this time, the body makes less insulin and produces more glucagon, which raises blood glucose.

Corticosteroids, such as prednisone, which are used to control asthma, arthritis, MS, and other health conditions, can raise blood sugar levels. In fact, steroids may even trigger diabetes in some people. !

In addition, common drugs such as statins to lower cholesterol levels, and diuretics to lower blood pressure, can raise blood sugar levels. Again, statins have been shown to trigger diabetes in some people!

Some antidepressants can also raise blood sugar.

Decongestants that have pseudoephedrine or phenylephrine can raise blood sugar. Cold medicines also sometimes have a little sugar or alcohol in them, so look for products that don't have those ingredients.

Being dehydrated may raise your blood sugar, especially if you're not eating foods that contain water, e.g. vegetables, while eating foods that dehydrate you, e.g. coffee, soda, fried foods, processed meats, alcohol, soy sauce, popcorn, sugary drinks.

Anger, anxiety, fear, etc. cause our bodies to produce hormones such as cortisol that can raise blood glucose even if we haven’t eaten.  These hormones are known as the “fight or flight” hormones.

Modern day stresses can be anything from starting a new job to fighting an illness to getting ready for that big birthday party. These hormones release our body’s emergency stores of sugar into the bloodstream for use as energy.  Sometimes the influx of sugar is too much for the body to use when someone has diabetes and it can cause blood sugars to rise too high.

High-intensity and moderate exercise such as sprinting or weight lifting, can sometimes raise blood glucose. This stems from the adrenaline response, which tells the body to release stored glucose. But this is not a reason to avoid high intensity exercise – studies show it can improve blood glucose for one to three days post-exercise!

Female Hormones 
When a woman's hormones change, so does her blood sugar. Keep a monthly record of your levels to get a better idea of how your menstrual cycle affects you. Hormone changes during menopause may make blood sugar even harder to control.

Heat makes your blood sugar harder to control. You should test it often and drink plenty of water to avoid dehydration. High temperatures can affect your medications, glucose meter, and test strips, too. Don't leave them in a hot car.

When you're sick, your body produces stress-related hormones that help your body fight the illness, but they can also raise your blood sugar level.

Whether it’s a cold, flu, or even a urinary tract infection, your immune system releases germ-fighting chemicals that can raise your blood sugar. Illness can cause the body to release epinephrine (adrenaline), glucagon, growth hormone, and cortisol. As a result, more glucose is released from the liver (glucagon, adrenaline) and the body can become less sensitive to insulin (growth hormone, cortisol).

Illness also causes the liver to increase glucose production to provide more energy. At the same time, stress hormones are released that make cells more insulin resistant. The net result is that blood sugar can rise dramatically when you’re ill.

Meals: Frequency, Timing
Eating less than 3 meals a day leads to larger meals which leads to higher blood glucose levels. Eating 4 to 6 smaller meals spaced out across the day and at the same time every day will help keep your blood glucose levels more consistent.

Meals: Order In Which Food Is Eaten 
A small new study from researchers at Weill Cornell Medical College suggests that the order in which diabetics eat their food may cause blood glucose to rise.

The researchers found that, when carbohydrates were eaten last, the participants’ blood sugar levels were significantly lower at the 30-, 60-, and 120-minute after-meal checks (29%, 37%, and 17%, respectively), and insulin levels were substantially lower as well, compared to when the carbohydrates were eaten first.

However, the study investigators agreed that they need to do follow-up work and conduct more studies.

Meals: Proportion Sizes
If meals are not balanced and contain too many carbs or too little fat or protein, this will raise your blood sugar.

Too much food in proportion to your diabetes medications — especially insulin — may cause your blood sugar level to climb too high (hyperglycemia).

If possible, it is also important to eat about the same amount of carbohydrates at each meal or snack to keep your blood glucose levels within target range, or to have your medication match your carbohydrate intake.

Menstruation and Menopause
Many women report having higher blood sugar levels a few days prior to their period starting, but some women notice a sharp drop in sugar levels. To figure out how you respond, your best bet is to test your blood glucose often during this time of month.

Changes in hormone levels the week before and during menstruation can result in significant fluctuations in blood sugar levels. And in the few years before and during menopause, hormone changes may result in unpredictable variations in blood sugar levels that complicate diabetes management.

Many studies have found that not getting enough sleep leads to high glucose levels and poor diabetes control, insulin resistance, weight gain, and increased food intake.

A Dutch study of patients with type 1 diabetes found that when they got just four hours of sleep a night, their insulin sensitivity dropped 20 percent compared to when they got a full night’s sleep, according to

Not getting enough sleep is a form of chronic stress on the body, and any time you have added stress, you're going to have higher blood sugar levels.

A 2006 study in the Archives of Internal Medicine found that those who report poor sleep quality have higher A1Cs. This finding is of concern because of the prevalence of obstructive sleep apnea (OSA) in people with diabetes.

Caution: Blood sugar can dip dangerously low during sleep for some people with diabetes, especially if they take insulin. It's best to check your levels at bedtime and when you wake up.

Sugar-Free Foods
Many sugar-free foods will raise your blood sugar levels, because they can still have plenty of carbs from starches. Check the total carbohydrates on the Nutrition Facts label. You should also pay attention to sugar alcohols such as sorbitol and xylitol. They add sweetness with fewer carbs than sugar (sucrose), but they may still have enough to raise your sugar levels.

Some studies suggest that smoking can increase insulin resistance, and people with diabetes who smoke are more likely than non-smokers to have trouble with insulin dosing and managing their diabetes.

A 2011 study from California State Polytechnic University found that the more nicotine samples of human blood were exposed to, the higher the A1C level (a measure of blood sugar control).

Ref: CDC
Ref: American Society for Clinical Nutrition

In people with diabetes, stress can alter blood glucose levels in two ways:

1. People under stress may not take good care of themselves. They may drink more alcohol or exercise less. They may forget, or not have time, to check their glucose levels or plan good meals.

2. Stress hormones such as cortisol can raise blood glucose levels directly. Stress can cause the body to release epinephrine (adrenaline), glucagon, growth hormone, and cortisol.

As a result, more glucose is released from the liver (glucagon, adrenaline) and the body can become less sensitive to insulin (growth hormone, cortisol).

Job Stress: Being overwhelmed, overworked or unhappy at work takes a toll. When you're under stress, your body releases hormones that can make your blood sugar rise. Learn to relax with deep breathing and exercise. Also, try to change the things that are stressing you out, if that's possible.

Stress Monitoring Tip: It's easy to find out whether mental stress affects your glucose levels. Before checking your glucose levels, write down a number rating your mental stress level on a scale of 1 to 10. Then write down your glucose level next to it. After a week or two, look for a pattern. Drawing a graph may help you see trends better. Do high stress levels often occur with high glucose levels, and low stress levels with low glucose levels? If so, stress may affect your glucose control.

Believe it or not, negative thoughts, a negative talk-track of self-blame, self-hate, anger, etc. trigger the release of cortisol and other hormones that can raise your blood sugar. Use positive affirmations, mantras, etc. and replace bad thoughts with good ones.

Each time you notice a bad thought, purposefully think of something that makes you happy or proud. Or memorize a poem, prayer, or quote and use it to replace a bad thought.

Whatever method you choose to relax, practice it. Just as it takes weeks or months of practice to learn a new sport, it takes practice to learn how to relax.

Why Blood Glucose Levels Change During The Day

Your blood glucose levels vary (up or down) due to a number of factors such as those listed below:

1. Eating food. As the carbs in food break down, glucose is released into the bloodstream ready to be absorbed by cells. Increased glucose in the bloodstream = higher blood sugar level.

2. Exercise. Exercise provides many benefits to your body, including burning excess sugar and reducing insulin resistance (by making cells more receptive to insulin, so rather than requiring more insulin to facilitate glucose uptake, the insulin you already have becomes a bit more effective). However the effect on blood sugar depends on the type of exercise, the duration of exercise, glucose and insulin levels before you start exercising.
During long, intense workouts the body may release adrenaline which counteracts the efforts of insulin. The normal process for blood sugar would be to be absorbed by cells (via insulin) for utilization or storage. Adrenaline causes the glucose to be redirected to where it is required for use immediately rather than for storage. 

3. Your physiology. The fitter you are the better. More specifically, if you have a greater muscle to fat ratio, you will burn energy at a faster rate and therefore be more effective at reducing your blood glucose level. Also, muscles do not rely on insulin to absorb/use blood glucose - same goes for the brain.

4. Emotions. Stress increases your blood glucose level. It also causes some people to forget to take their medication, turn to comfort foods, overeat and therefore introduce a higher than normal amount of glucose in the blood.

5. Sleeping. People often talk about the "dawn phenomenon" with regard to diabetes, where your blood sugar level spikes in the mornings as a result of the body releasing hormones which increase insulin resistance. However, another explanation could be a slow metabolism of dinner from the night before. Some research also suggests that not getting enough sleep causes the liver to produce/release more glucose, hence increasing your blood sugar levels.

6. Medications. Obviously, the medication you take regulates your blood sugar level and therefore your readings during the day, depending on when you took the medication. But, the medications don't get rid of your diabetes!

Note: Read Chapter 11 of Death to Diabetes for more information.

Friday, August 26, 2016

Meal Delivery Plans eDiets Diet-to-Go Nutrisystem BistroMD

Why Meal Delivery Diet Plans?

Because of work schedules, family life, travel, and other lifestyle issues, some of us (including diabetics) rely on junk food and fast food restaurants because of time and convenience.

Because of our busy lives, we don't have the time to prepare healthy meals every day.

However, we want to eat healthy -- if only there was a way to eat healthy but not have to spend a lot of time in the kitchen or shopping in the crowded grocery stores.

And, there are some of us who just can't cook!

But the good news is that there are ways to eat healthy, and not spend a lot of time in the kitchen or in the grocery store.

One of the most effective and cost-effective ways is to have your meals prepared and delivered to your home. Online meal delivery programs have grown and come a long way; and, provide a lot more options for all of us -- especially for those of us who are very busy, but still need to lose some weight or get our diabetes under control.

In addition, these types of online meal delivery programs prevent us from giving in to the fast foods and junk food.

By the way, there is another reason why we choose fast foods -- the perceived cheaper cost. It appears on the surface that fast food is a lot cheaper that healthy foods such as extra virgin olive oil and wild salmon.

However, fast food is actually NOT cheaper, when you take into account the detrimental health impact of eating too much fast food.

Once we realize that eating healthy is not as expensive as eating fast food and junk food, then, the challenge becomes finding a service that will address the areas of time and convenience -- and, not be more expensive than preparing healthy meals every day.

That service is called Meal Delivery Diet Plan or Meal Plan Delivery.

For more information about the different types of plans refer to the following website:

Can't Afford Meal Delivery?

If you can't afford meal delivery, Mr. McCulley has developed several meal planning tools to help you with meal planning.

FYI: Mr. McCulley admits that it was very intimidating when he realized everything that he would have to do to manage his diabetes and plan his meals. So, he developed acookbook and a set of meal planning diagrams and charts  that would make it easier for diabetics to perform proper meal planning.

Meal Delivery Plan Ads

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Bistro MD


Death to Obesity Weight Loss Ebook

Proper weight loss, in the context of health or physical fitness, is a reduction of your total body weight, due to a loss of fluid and body fat but not the loss of lean muscle tissue. This is key!

Many weight loss programs produce weight loss, but they lose the lean muscle tissue that your body needs to burn the fat! That’s why a lot of people on weight loss program look like “death warmed over”. They have lost lean muscle tissue, which also affects your body composition.

Weight gain is due to 3 reasons for most people:
1. Biochemical and hormonal imbalances
2. Poor nutrition and lifestyle choices that lead to low physical activity
3. Emotional issues that trigger poor eating habits

Consequently, the strategy to overcome weight gain and achieve weight loss requires the following:
1. Rebalance biochemically and hormonally.
2. Proper nutrition and lifestyle choices that lead to increased physical activity
3. Addressing the emotional issues that trigger poor eating habits.
Of course, there are other reasons such as environment, age, culture, and overall health, but these three fuel the obesity epidemic more than any other factor.

In order to increase your probability of success, you must prepare yourself physically, emotionally, and spiritually to embrace making the necessary lifestyle changes to improve your health. You must make yourself a priority and set aside the time to improve your health if you really want to lose weight.

You must establish and implement goals to increase the frequency of your (super) meals and snacks to enable proper blood glucose stabilization. You should also establish goals to increase the frequency of your exercise, cleansing/detox, and other key activities. This will prevent the blood glucose highs and lows that many people experience, and help to reduce the excess insulin production, which fuels Type 2 diabetes and obesity.

This weight loss program will also help you to reduce the belly fat, lower your blood pressure, lower your blood glucose level, and lower your cholesterol.
Implementing the Death to Obesity® Weight Loss Program includes the following activities:
• Meal Planning
• Blood Glucose Testing/Analysis (for Type 2 diabetics only)
• Exercise
• Cleansing/Detox
• Nutritional Supplementation
• Support and Relaxation Sleep
• Health Coaching & Planning
• Doctor Visits, Medical Blood Tests & Exams
• Drug Weaning

You should implement one new activity at the start of a new week until you have implemented all the activities into your daily life and lifestyle.  If one-week increments are too much for you, then, slow down and use two-week or 1-month increments.

Ebook Content & Description:
Explains how to lose weight and reduce the belly fat -- primarily for non-diabetics, but also for Type 2 diabetics. Defines the key steps to burn the fat and achieve permanent weight loss.Provides specific steps to reduce that hard-to-get-rid-of belly fat. Also, identifies the top 10 weight-loss foods and how they help to reduce weight and belly fat. Discusses the emotional and motivational factors for successful weight loss, including how to fuel motivation, discipline, and will power to achieve your weight loss goals.
Key topics include: The Weight Loss 10 Steps Program; The 10 Myths about Weight Loss, Obesity Pathophysiology, Leptin/Insulin Resistance, Lipolysis: Fat Burning, Calorie-Planning, The Role of Hormones in Losing Weight, Weight Loss Timeline, Optional Weight Loss Strategies, Exercise Regimen for Losing Weight, Cleanse/Detox Guidelines, Tips for a Better Fast, The Most Important Motivator, Limitations of Drugs/Medications, Meal Planning Tips, How to Lose That Belly Fat, BMI Chart, etc.

Note: For more information, get the Weight Loss ebook PDF at this link:

Death to Obesity Weight Loss Program
Are you tired of being fat? 
Are you tired of being tired? Are you tired of all the anxiety, despair, and hopelessness?

Would you like to enjoy life the way it was before you gained all the weight?

Then, start your journey "from fatness to thinness" today -- and get theDeath to Obesity Weight Loss ebook.

Size of Ebook:
 200+ pages

Document Format: PDF (Adobe Acrobat)

Retail Price: $19.95

Delivery: The ebook will be delivered within 1 hour to you via email, so please ensure your email address is correct.

Contact Information: Email: admin(at)deathtodiabetes(dot)com
Toll-free Phone: 800-813-1927 

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 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 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.


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.
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.


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

Monday, July 11, 2016

Beta Cell Dysfunction Five Stages

There are five stages in the progression of diabetes, each of which is characterized by different changes in ß-cell mass, phenotype, and function.

Stage 1 is compensation: insulin secretion increases to maintain normoglycemia in the face of insulin resistance and/or decreasing ß-cell mass. This stage is characterized by maintenance of differentiated function with intact acute glucose-stimulated insulin secretion (GSIS).

Stage 2 occurs when glucose levels start to rise, reaching ~5.0–6.5 mmol/l; this is a stable state of ß-cell adaptation with loss of ß-cell mass and disruption of function as evidenced by diminished GSIS and ß-cell dedifferentiation.

Stage 3 is a transient unstable period of early decompensation in which glucose levels rise relatively rapidly to the frank diabetes of stage 4.

Stage 4 is characterized as stable decompensation with more severe ß-cell dedifferentiation. 

Finally, Stage 5 is characterized by severe decompensation representing a profound reduction in ß-cell mass with progression to ketosis.

Movement across stages 1–4 can be in either direction. For example, individuals with treated type 2 diabetes can move from stage 4 to stage 1 or stage 2. For type 1 diabetes, as remission develops, progression from stage 4 to stage 2 is typically found. Delineation of these stages provides insight into the pathophysiology of both progression and remission of diabetes.


The most common example of compensation is found with the insulin resistance due to obesity, which is accompanied by higher overall rates of insulin secretion  and increased acute glucose-stimulated insulin secretion (GSIS) following an intravenous glucose challenge. Much of the increase in insulin secretion undoubtedly results from an increase in ß-cell mass, as has been found in autopsy studies in humans and numerous rodent models. Beta-Cell mass is normally tightly maintained through a balance of ß-cell birth (ß-cell replication and islet neogenesis) and ß-cell death through apoptosis.
Most of the increase in ß-cell mass with insulin resistance is probably due to increased ß-cell number, but ß-cell hypertrophy may also contribute. It is not yet clear if the higher plasma insulin levels can be entirely explained by the larger ß-cell mass or whether there is also increased secretion per given unit of ß-cell mass. Although compensation is usually thought of in the situation of insulin resistance, similar changes presumably occur in the early stages of autoimmune destruction. As ß-cell mass falls, there must be a signal to increase mass and secretion, which presumably prolong the prediabetic period, which can last for years.
There is much interest in the signal leading to increased ß-cell mass in this situation. The facile, but probably correct, explanation is that there is a feedback loop with insulin resistance producing increased glucose levels that stimulate ß-cell secretion and growth. However, concerns are raised about how this can be compatible with seemingly normal glucose levels. One explanation is that the feedback loop is tightly regulated, like a thermostat that can maintain temperatures within a very narrow range. A molecular mechanism that could facilitate this control is activation of glucokinase in ß-cells, the enzyme that controls the rate of glycolysis, thereby determining insulin secretory rates. Thus, very small elevations in glucose levels could lead to a change in the set point in GSIS that allows maintenance of “normal” plasma glucose levels.

The importance of ß-cell differentiation.

The unique differentiation of ß-cells is responsible for the extraordinary efficiency of these cells in storing and secreting insulin to provide precise regulation of metabolism. With successful compensation for insulin resistance, little change in ß-cell phenotype for the secretory machinery would be expected. The unique specialization of ß-cells is presumably necessary for optimal GSIS; the impressively large acute insulin responses to glucose challenge seen in obesity strongly suggest the phenotype is maintained.
The complexity of this differentiation is far from being understood, but some key features are apparent. The glucose transporter GLUT2 allows rapid equilibration between extra- and intracellular glucose levels. Glucose is phosphorylated by glucokinase with aKm of ~8 mmol/l that allows it to function efficiently within the normal range of plasma glucose concentrations. Glucose metabolism is dominated by glycolysis with pyruvate directed to mitochondria for oxidation. There is little if any gluconeogenesis or lactate production , which should be helpful for maximizing the efficiency of aerobic glycolysis.
The ß-cell also has specialized mitochondrial shuttles. The glycerol phosphate shuttle allows reduced nicotinamide dinucleotide (NADH) to be oxidized by mitochondria, thereby contributing to adenosine triphosphate (ATP) formation. The oxidation of NADH should also enhance glycolytic flux. In ß-cells the malate/pyruvate shuttle may facilitate the generation of NADPH, which could somehow enhance secretion. The need for these shuttles probably explains why ß-cells have very high levels of mitochondrial glycerol phosphate dehydrogenase (mGPDH) and pyruvate carboxylase.
To maintain this degree of specialization, the genes that are highly expressed in ß-cells include those of the secretory products (insulin and islet amyloid polypeptide [IAPP]), key genes for glucose metabolism (GLUT2 and glucokinase), key enzymes for the mitochondrial shuttles (glycerol phosphate dehydrogenase [mGPDH]) and pyruvate carboxylase, and critical transcription factors (PDX-1 and Nkx-6.1). Yet, enzymes that participate in unwanted pathways such as gluconeogenesis and lactate production are expected to be suppressed.
Some of these include phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase and fructose-1,6-bisphosphatase, and lactate dehydrogenase. Hexokinase would also be unneeded, so its expression could also be suppressed. Clearly these changes in gene expression are just the tip of the iceberg, and a full picture of ß-cell phenotype awaits gene array studies, which should emerge in the near future.

Maintenance of ß-cell differentiation during stage 1 compensation.

Some experimental data support the concept that much of the ß-cell phenotype is kept intact during successful compensation for insulin resistance. When glucose was infused into rats for 4 days, compensation occurred and glucose levels remained normal during the latter stages of the infusion because of increases in insulin secretion that were accompanied by increased ß-cell mass.
While responding to the increased demand, the ß-cell phenotype, as determined by analysis of a selected group of genes, remained remarkably similar to the control profile. There must have been induction of some genes required for ß-cell replication, but the genes responsible for maintaining the machinery allowing GSIS did not seem to be perturbed. This preservation of phenotype, coupled with an increase in ß-cell mass, is consistent with the exuberant GSIS seen in obesity.


It is not possible to assign a precise glucose range for this stage of ß-cell adaptation, but fasting levels between 5.0 and 7.3 mmol/l (89–130 mg/dl) are reasonable approximations. In stage 2, ß-cells can no longer be considered to be compensating because truly normal glucose levels can no longer be maintained. However, this stage can be considered stable because, as shown in the Diabetes Prevention Program, individuals at the upper end of stage 2 with IGT progressed to diabetes at the rate of ~11% per year while those who adhered to a diet and exercise regimen progressed at a rate of only 5% per year.
Thus, unless some process, such as autoimmunity, is producing rapid ß-cell destruction, individuals in stage 2 usually evade progression to diabetes for years.
Nonetheless, as glucose levels rise to stage 2, important changes in ß-cell function and differentiation occur. The most striking and best studied is the loss of acute GSIS. The acute phase of secretion occurs ~3–10 min after the start of the glucose infusion and represents the first phase of GSIS. This experimental assessment has the pathophysiological correlate of impaired early insulin release during an oral glucose challenge, which contributes to glucose intolerance. An important study published in 1976 showed that subjects maintained normal acute GSIS as long as fasting plasma glucose levels remained <5 .6="" dl="" l="" mg="" mmol="" p="">
However, acute GSIS dropped drastically when fasting plasma glucose values were above this level and disappeared completely once fasting glucose levels increased to only 6.4 mmol/l (114 mg/dl). This pattern has now been confirmed in countless studies in humans and animals. In contrast to this loss of acute GSIS, the second phase of insulin secretion is partially preserved, and acute insulin responses to nonglucose secretagogues, such as isoproterenol and arginine, remain largely intact.

Loss of GSIS in stage 2: the glucotoxicity hypothesis.

The concept of glucose toxicity is that ß-cells normally function within a narrow range of plasma glucose levels and that even modestly higher glucose levels create an unnatural environment, which leads to alteration in function and most notably a loss of acute GSIS. On the molecular level, the exact mechanisms responsible for this loss of GSIS are not known; however, we postulate that a loss of specialized gene expression leads to complete disruption of the acute phase of GSIS. In contrast, the agents that stimulate insulin release through depolarization (arginine) or cyclic AMP (isoproterenol) work through more ubiquitous and less fragile mechanisms that are maintained.
Although some have proposed that increased free fatty acid (FFA) levels are important for the ß-cell dysfunction of diabetes, these levels correlate poorly with the loss of acute GSIS, whereas the correlation with glucose levels is very precise. This interpretation does not rule out important glucose-driven derangements of lipid pathways in ß-cells that could justify use of the term “lipotoxicity.”

Changes in ß-cell differentiation in stage 2.

The loss of acute GSIS seen in the diabetic state is accompanied by marked changes in ß-cell phenotype demonstrated by changes in gene and protein expression. These changes have been found in islets from both diabetic ZDF rats and rats following partial pancreatectomy in which residual ß-cells are exposed to varying degrees of hyperglycemia The alterations may be thought of as dedifferentiation, or loss of phenotype, in that the highly expressed genes in ß-cells (mentioned above) are downregulated while those that are normally suppressed are upregulated in their expression.
Some of the upregulated genes include glucose-6-phosphatase, fructose-1,6-bisphosphatase, lactate dehydrogenase, and hexokinase. In addition, a stress response is found with a variety of antioxidant, apoptotic, and proapoptotic genes being activated. These are accompanied by a marked increase in the expression of c-myc and activation of nuclear factor (NF)-?B. These changes are consistent with a recent report that interleukin (IL)-1 expression in ß-cells is activated by high glucose levels. Another interesting facet is the presence of ß-cell hypertrophy, which may be a glucose-driven growth response stopping short of replication. Strengthening the hypothesis that these changes are secondary to chronic hyperglycemia are data showing that lowering of the elevated glucose levels with phlorizin, which inhibits renal glucose reabsorption, leads to reversal of virtually all of the changes in gene expression and hypertrophy.
It should be emphasized that some changes of gene expression occur in stage 2, when glucose levels might be considered “normal.” In some rats following a 90% partial pancreatectomy, fed plasma glucose levels of 6.9 mmol/l (124 mg/dl) were maintained over a 14-week period, whereas control rats maintained levels at 5.8 mmol/l (104 mg/dl) over the same time period. When considered in human terms, this increase of only 1.1 mmol/l (20 mg/dl) would probably not have reached the designation of IGT and therefore would be categorized as normal. However, the islets isolated from the pancreatic remnant of these rats 14 weeks after surgery had similar, albeit less marked, changes in gene expression as those of partially pancreatectomized rats with more severe hyperglycemia.
Despite the minimal degree of hyperglycemia, these changes in gene expression correlate with the losses of GSIS seen in this and similar rodent models and in humans, supporting the hypothesis that changes in ß-cell phenotype are responsible for the disruption of GSIS. We recognize that blaming the loss of GSIS on altered phenotype may be an oversimplification. Certainly there could be important changes in signal transduction pathways that could be unrelated to changes in protein levels, but we expect that the changes in phenotype are of fundamental importance. In the future it should be possible to dissect out the many candidates that could contribute to ß-cell dysfunction, such as mitochondrial shuttles, lactate dehydrogenase, glucose-6-phosphatase, uncoupling protein-2, peroxisome proliferator–activated receptor (PPAR)-a, and c-myc.


We postulate that during progression toward diabetes, stable stage 2 ends and glucose levels rise relatively rapidly from the range of 7.3 mmol/l (130 mg/dl), through an unstable transient stage 3 of decompensation, to a more stable stage 4 at ~16–20 mmol/l (285–350 mg/dl). Thus, individuals headed to type 2 diabetes can remain in stage 2 for many years, but when ß-cell mass becomes inadequate at some critical point, glucose levels rise over a relatively short period of time to stage 4, which may or may not be associated with noticeable symptoms, such as polyuria and weight loss. A similar progression occurs in type 1 diabetes, but stage 2 does not last as long because autoimmune destruction of ß-cells occurs much more rapidly than whatever process is responsible for the ß-cell attrition in type 2 diabetes.
Thus, a child nearing adolescence might be in stage 2, whereupon flu or some other stress might push glucose levels rapidly through stage 3 to stage 4. While in stage 4, the precipitating stress may recede, allowing the child to fall back through stage 3 to stage 2 for a remission, which would only last until further ß-cell destruction results in a return to stage 3 and then stage 4. Stage 4 might not be long lasting because continued ß-cell loss will usually lead to the severe decompensation of stage 5, with propensity to ketoacidosis.
The same pathophysiology probably occurs with pancreas and islet transplantation, in that loss of ß-cells in the grafts would lead to progression through the above stages. While a successful pancreas transplant will typically bring a recipient to stage 1, an islet transplant performed according to the Edmonton approach will usually place recipients in stage 2, where they will remain at risk for later decompensation.

Experimental evidence for the instability of stage 3.

When transplanting islets contained in immunoprotective devices into mice, we noted that a marginal number of islets produced either success with normal blood glucose levels or failure with glucose levels >15 mmol/l (280 mg/dl), with almost no glucose levels in between. A marginal number of syngeneic islets transplanted under the kidney capsule of streptozocin diabetic mice produced a similar pattern of either failure or success, with only a few glucose levels in the stage 3 range (data not shown). This concept was examined again in rats with a marginal reduction of ß-cell mass following a 90% partial pancreatectomy.
Although a spectrum of glucose levels was seen at 4 weeks, the rats showed two distinct outcomes by 14 weeks: they were either near normal (glucose levels of 6.9 mmol/l [124 mg/dl] and 5.8 mmol/l [104 mg/dl] in fed and control rats, respectively) or unequivocally hyperglycemic. Somehow there were forces pushing these rodents to either stage 2 or 4, with their time in stage 3 being only transient.
Support is also provided by studies of islet transplantation in which canine islets were transplanted into the livers of young diabetic dogs. As the recipients matured, rapid decompensation to marked hyperglycemia was seen, presumably a result of the ß-cell mass becoming inadequate to meet the insulin requirements of larger dogs. A recent study in humans also supports the concept that decompensation is not a continuum but can occur in a relatively short period of time.
In studies on a population from the Mexico City Diabetes Study, it was concluded that within a 3-year timeframe the development of diabetes was often rapid rather than gradual. The investigators also thought the rapidity might have been underestimated because some of the subjects were receiving diabetes treatment.

Why is stage 3 unstable?

At some point in stage 2, ß-cells are no longer able to keep glucose levels in the prediabetic range. This failure presumably occurs because of a critical decline of ß-cell mass and/or increase in insulin resistance. We postulate that there is a conspiracy of forces that push glucose levels upward, which include the insulin resistance associated with the diabetic state with its complex gluco- and lipotoxicity influencing the key insulin target tissues (i.e, liver, muscle, and fat). The increases in glucose concentration probably also worsen glucotoxic effects on ß-cells, leading to less efficient insulin secretion.
For example, as insulin mRNA falls with increasing hyperglycemia, there is evidence that insulin biosynthesis becomes rate limiting for secretion. With these factors working synchronously, glucose levels rise to stage 4 but do not immediately progress to stage 5 because enough insulin production continues to prevent severe ketosis. By treating type 2 diabetes with diet, exercise, and drugs, individuals can quickly return to stage 2 and remain in that stable range for a considerable period of time as long as they continue the treatment and have no further decline in ß-cell mass.

Why is the instability of stage 3 not more clinically apparent?

Clinicians often see patients who are asymptomatic and have unremarkable glucose levels at one point and then present with glucose levels in the range of >16 mmol/l (285 mg/dl) with the absence or presence of symptoms. Certainly individuals progressing to type 1 diabetes often rapidly progress to very high glucose levels, but clearly many people with diabetes have glucose levels within the stage 3 range. The most obvious explanation is that external forces can overwhelm the processes that make stage 3 transient (in particular, treatment with oral medications and/or insulin). Even changes in caloric intake and exercise should allow individuals to move in and out of stage 3. Another point is that the transition from stage 2 to stage 4 is not instantaneous; even in our rodent studies progression took a few weeks. Nonetheless, we postulate that stage 3 is by nature transient.


Once individuals progress through stage 3 to the unambiguous diabetes of stage 4, they typically have enough insulin secretion to remain in this stage rather than progressing to ketoacidosis. In most cases this stage lasts a lifetime for people with type 2 diabetes, while the rapid progressive autoimmune destruction of ß-cells in type 1 diabetes can lead to stage 5 relatively quickly. Individuals with failing islet transplants can probably stay in stage 4 for relatively long periods of time if the immunosuppression regimens allow sufficient ß-cell survival.

Changes in ß-cell mass, function, and differentiation in stage 4.

Morphometric studies on postmortem pancreases of people with type 2 diabetes provide convincing evidence that ß-cell mass is reduced to ~50% of that of control subjects. Data generated in rodents suggest ß-cell dedifferentiation is more severe at higher glucose levels, which should result in less efficient insulin secretion. This lack of efficiency fits with insulin secretion studies in type 2 diabetes that have indicated that the capacity for secretion is considerably less than the 50% reduction in ß-cell mass.
Important questions are raised by the finding that a stress response is induced by chronic hyperglycemia. Because the stress response is characterized by the expression of a mixture of proapoptotic, antiapoptotic, and antioxidant genes, it is difficult to know if ß-cells in this situation would be more or less susceptible to the apoptosis. For destruction by autoimmunity and/or transplant rejection, the stress response could make ß-cells either more vulnerable or provide protection.
For type 2 diabetes, this phenotypic change may accelerate ß-cell loss. Even if accelerated, the rate of ß-cell apoptosis in type 2 diabetes is certainly very slow, given the assumption that the ß-cell death rate must be similar to ß-cell birth rate, which is probably considerably less than 1% per day. Even less is known about the rate of neogenesis, which is probably very slow as well. Somehow, regardless of ß-cell loss in typical type 2 diabetes, apoptosis rarely progresses to near-complete loss, which leads to ketosis, even after decades of the disease.
Although it is often assumed that accelerated apoptosis of ß-cells is important for the pathogenesis of type 2 diabetes, limitations in ß-cell replication and/or neogenesis could be just as important. Although some rodent models of diabetes exhibit increased rates of apoptosis, in rats following 90% partial pancreatectomy with glucose levels in the stage 4 range of diabetes, rates of ß-cell replication and the incidence of apoptotic bodies were no different than in control rats.


In this last stage of diabetes, the marked loss of ß-cells is so severe that people become ketotic and truly dependent on insulin for survival. Glucose levels are typically >22 mmol/l (350 mg/dl) but will vary with eating and hydration. This situation is typically found with type 1 diabetes or patients with pancreas or islet transplants when ß-cells have been mostly destroyed by the immune system. It can also occur in unusual situations, such as exposure to certain toxins or very severe pancreatitis, but it rarely occurs in typical type 2 diabetes.

Alternative Treatment for Insulin Resistance
Given the pathology of insulin resistance, the best alternative strategy is a plant-based diet that reduces your body's production of excess insulin and blood glucose. Ideally, you also want the diet to address the cellular inflammation and weight gain issues.

Such a diet is the Death to Diabetes diet, which addresses the excess insulin, blood glucose, cellular inflammation, and weight gain.