3 Blood Sugar Imbalances That Affect Your Ability to Manage Leaky Gut and Autoimmunity

3 Blood Sugar Imbalances That Affect Your Ability to Manage Leaky Gut and Autoimmunity

Blood cells and glucose in the vein. 3D illustration

Datis Kharrazian

Datis Kharrazian


Updated: 2/11/2024

It’s almost impossible to manage autoimmunity or improve a chronic health condition if your blood sugar is chronically dysregulated. In my more than 20 years of working with chronically ill patients worldwide, many have not improved simply because their blood sugar imbalances went ignored.
Patients and practitioners alike are eager to jump into protocols for the gut, parasites, heavy metals, the brain, hormones, etc. Meanwhile, their blood sugar dysregulation and sedentary lifestyle feed into each other in a downward spiral that holds their bodies hostage.
A blood sugar imbalance robs your cells of the ability to produce sufficient adenosine triphosphate (ATP), our primary energy source. Think of ATP as trillions of tiny batteries. We can store enough ATP to power cells for only a few seconds at any given time. This means we must constantly produce ATP through pathways that convert food into energy. When your diet has you on constant peaks and crashes of blood sugar, you sabotage these energy-production pathways. This means you don’t produce enough energy to heal.
Research shows that 88 percent of Americans suffer from blood-sugar-related metabolic disorders, thanks to the Standard American Diet high in simple carbohydrates and sugars and low in nutrition. In other words, Americans are in a cellular energy crisis.
Whether your blood sugar is consistently too high, too low, or a combination of both, the result is the same: Not enough glucose gets into the cells to produce energy. Low blood sugar starves cells, while high blood sugar blunts glucose receptors. Both leave cells hungry for energy.
Unfortunately, the longer a person is in a dysregulated blood sugar state—a lifetime for most Westerners—the more difficult it is to repair. Most people need to significantly lower their consumption of carbohydrates and increase their physical activity to unwind the cravings that drive them to overeat. Reversing insulin resistance can take many months, if not a year or more, of steadfast adherence to an anti-inflammatory diet and regular physical activity.
When these people walk into the conventional health care model, they are told to “eat right and exercise.” They probably have tried and failed multiple times. That’s because people with longstanding insulin resistance or Type 2 diabetes often experience chronic injuries or an inability to recover when they try to exercise. This is due to systemic inflammation these conditions cause. Many of the doctors and nurses treating these patients struggle with the same problems.
In this article, I’ll discuss the three primary forms of blood sugar imbalances that can affect your ability to successfully manage leaky gut and autoimmunity: Low blood sugar, high blood sugar, and a mix of both.

1. Functional Hypoglycemia

Although low blood sugar is less common than high blood sugar, it is still inflammatory and can hinder healing. Also, people can suffer symptoms of low blood sugar due to extreme blood sugar fluctuations that come with eating a higher-carbohydrate diet, even though their blood sugar is not technically low.
Throughout this article, when I refer to hypoglycemia or low blood sugar, I’m referring primarily to functional hypoglycemia. This differs from pathological hypoglycemia, with dangerously low blood sugar levels (below 65–70 mg/dL). Functional hypoglycemia falls below the bottom of the functional range. Also, lactate dehydrogenase (LDH), an enzyme important for producing cellular energy, is typically below 140 U/L (units per liter) in functional hypoglycemia.
Another common term is reactive hypoglycemia—a drop in blood sugar four hours after eating due to excessive insulin release. Reactive hypoglycemia is an early stage of insulin resistance.

Symptoms of Functional or Reactive Hypoglycemia (Low Blood Sugar):

  • Increased energy after meals (your energy should be consistent before and after meals).
  • Craving for sweets between meals.
  • Irritability if meals are missed.
  • Dependency on coffee and sugar for energy.
  • Becoming lightheaded if meals are missed.
  • Eating to relieve fatigue.
  • Feeling shaky, jittery, or tremulous.
  • Feeling agitated and nervous.
  • Becoming easily upset.
  • Poor memory, forgetfulness.
  • Blurred vision.
  • May not feel hungry despite needing to eat.
Hypoglycemic patients frequently eat sparingly. They live on salads and smoothies and become shaky, lightheaded, and irritable if they miss meals, which they do regularly. They suffer from anxiety and are prone to sleep problems. They often crash in the middle of the day, feeling revived and energetic after they eat.
They crave sugar daily, especially when their energy is low. If they snack, it’s typically something sweet or stimulating, like dried fruit, a smoothie, caffeine, or an energy drink. They bolt awake at 3 or 4 a.m. because their glycogen reserves can’t last through the night.
It’s paradoxical, but people with functional hypoglycemia often skip meals because of appetite loss. This happens because a constant flood of stress hormones from low blood sugar dysregulates the brain’s appetite center. They rarely feel hungry, and sometimes the idea of eating—particularly in the morning—makes them feel nauseous.
They may not realize they need to eat until their brain starts glitching, their energy crashes, or they become irritable, depressed, or anxious. In fact, the number-one cause of mood disorders I see in my practice is a blood sugar imbalance. While intermittent fasting is popular and has benefits, for the person with low blood sugar, it can perpetuate this unhealthy scenario.
When blood sugar drops, the brain triggers the pancreas to release glucagon, the adrenal glands to release cortisol and catecholamines, and the pituitary gland to release growth hormone. Together, these mechanisms ensure the brain stays fueled.
The reason people feel anxious, shaky, and irritable when blood sugar drops is due to the initial release of epinephrine and norepinephrine from the adrenal medulla (the innermost part of the adrenal gland). These are the catecholamine hormones released by an autonomic response from the central nervous system.
About an hour later, cortisol is released from the adrenal gland’s outer part, the adrenal cortex. When people continually blame cortisol for those “hangry” episodes, they’re more likely referring to catecholamines, which can cause “adrenalized” symptoms even in individuals with low cortisol. We often see low cortisol, as indicated on an adrenal salivary panel, accompany hypoglycemia.
Poor blood sugar handling means not enough glucose gets to the brain. This is when you see a loss of brain function. For instance, hand tremors result from insufficient fuel to the brain’s motor systems. Lack of fuel to the frontal lobes causes poor focus, concentration, or even depression. Catecholamine spikes may cause irritability, anxiety, or even rage.
Another mechanism of hypoglycemia is postprandial (the period after eating) hypoglycemia from an exaggerated insulin response. Normally, blood glucose rises after you eat, and insulin is released to escort glucose into cells. However, in postprandial hypoglycemia, the insulin release is excessive, causing a rapid drop in blood sugar levels after eating and symptoms of low blood sugar. This can be a stepping stone to developing insulin resistance.
You can test how well these mechanisms function with an oral glucose tolerance test (OGTT), typically used to diagnose prediabetes, diabetes, and gestational diabetes.
If your postprandial blood glucose level is between 140-199 mg/dL (milligrams per deciliter) and insulin is normal or high, it may indicate prediabetes. In general, a diagnosis of diabetes is made if your blood glucose level is higher than 200 mg/dL after two hours and insulin is normal or low. If you are pregnant and your blood glucose level is above 140 mg/dL after two hours, you may be diagnosed with gestational diabetes.

2. High Blood Sugar and Insulin Resistance

Many people slide from reactive hypoglycemia into high blood sugar or hyperglycemia, and insulin resistance. Insulin escorts glucose into the cells, where it is made into energy. The chronic insulin release to battle high blood sugar exhausts the cells until they refuse entry to insulin and become insulin resistant. This person feels like they need a nap after every meal, and if they eat a carb-rich meal, may nod off. Insulin resistance also causes intense sugar cravings and constant hunger.
Many women with insulin resistance carry excess belly fat and struggle with insomnia and hormonal imbalances that cause PCOS (polycystic ovary syndrome), hair loss, and facial hair growth. It also manifests with excess belly fat in men, but men develop male breasts and hips and find they cry more easily. Insulin resistance triggers enzymes that raise testosterone in women and estrogen in men. It can also promote early puberty in girls and boys, particularly if they are overweight.
Insulin resistance contributes to diabetes, heart disease, sleep apnea, hormonal disorders, obesity, and multiple other diseases. The damage starts early in our society—nearly 20 percent of children today are obese, which is usually accompanied by insulin resistance.

Symptoms of insulin resistance (high blood sugar):

  • Fatigue after meals.
  • General fatigue.
  • Constant hunger.
  • Craving for sweets not relieved by eating them.
  • Must have sweets after meals.
  • Waist girth equal to or larger than hip girth.
  • Frequent urination.
  • Increased appetite and thirst.
  • Difficulty losing weight.
  • Migrating aches and pains.
Insulin resistance is identified with fasting blood sugar over 99 mg/dL (blood sugar 126 mg/dL and above indicates diabetes). When glucose can’t enter the cell, it is converted to triglycerides through lipogenesis. This process requires ATP, one reason people with insulin resistance feel tired after eating. Instead of glucose going into their cells to produce ATP, it siphons energy to convert it into fat, package it into triglycerides, and store it in adipose tissue. Insulin resistance also inhibits the body’s ability to burn fat.
When glucose fails to enter cells and excess amounts are circulating in the bloodstream, the pancreas releases more insulin, perpetuating insulin resistance.

The Inflammatory Cascade of High Blood Sugar and Insulin Resistance

Chronically high blood sugar and insulin resistance trigger various inflammatory responses, making managing chronic health issues more difficult.
For starters, both trigger the production of advanced glycosylated end products (AGEs)—when sugars combine with protein or fats. AGEs are inflammatory compounds that promote the breakdown of intestinal tight junctions and promote leaky gut. Leaky gut allows bacterial byproducts called lipopolysaccharides (LPS) to enter the bloodstream, causing endotoxemia.
Endotoxemia is one of the most potent inflammatory conditions and contributes to multiple diseases. This is why when people with endotoxemia begin an exercise program, they become injured easily, experience significant joint and muscle pain, and have difficulty recovering.
Chronic blood sugar dysregulation inflames the brain, alters neurochemistry, and depletes the brain’s energy production. Brain research has shown that as insulin resistance progresses into diabetes, the neurotransmitter activity and shape of the brain change to be much different from that of a healthy person.
Those with insulin resistance are constantly looking for their next dopamine surge, with food becoming an addiction that often overrides willpower. This makes it more difficult for people to “eat right and exercise” when they’re trapped in a vicious cycle of pain, inflammation, lethargy, and never-ending hunger and cravings.
Additionally, high blood sugar triggers the liver and the fat cells to produce inflammatory compounds.
Combined, these multiple channels of inflammation impair energy production in the muscles to the point where it’s difficult to exercise without significant muscle and joint pain and fatigue. Brain changes caused by insulin resistance sap them of energy and motivation, so they’re chronically exhausted and tipped into overtraining syndrome very easily if they do exercise.
As a result, regular exercise continually falls to the bottom of the to-do list, perpetuating an already dire vicious cycle. They become understandably discouraged.
Patients with high blood sugar, insulin resistance, obesity, and chronic illness are accused of being lazy and told to “eat right and exercise,” but in reality, they are up against multiple metabolic hurdles.
To start turning things around, you need to understand where you fall on the blood sugar scale of severity and how to begin reversing that progression while adding in appropriate physical activity.

Moving Along the Blood Sugar Scale of Severity

It takes about 10 to 15 years for insulin resistance to progress to insulin-dependent Type 2 diabetes, significantly raising the risk of hypertension, dementia, cardiovascular disease, and stroke.
In early insulin resistance, fasting glucose is above 100, and triglycerides are elevated. Fasting glucose, HbA1c (measurement of average blood glucose over the past two to three months), and a lipid panel are often normal. However, an OGTT often shows elevated glucose or insulin. If glucose levels are high in the postprandial stage, this is a red flag that the blood sugar handling system is starting to deteriorate. The primary complaint at this stage is fatigue after meals.
A more advanced form of insulin resistance is called metabolic syndrome. The criteria for a diagnosis of metabolic syndrome are three of the following:
  • Blood pressure higher than 130/85.
  • Fasting blood sugar over 100.
  • Waist is larger than 40 inches for men and 35 inches for women.
  • HDL cholesterol under 40 for men and under 50 for women.
  • Triglycerides over 150.
Once you’re at this stage, your risk of stroke, dementia, and cardiovascular disease becomes more serious. CRP (c-reactive protein) and ferritin, markers of inflammation, may be elevated but aren’t necessarily.
As the condition progresses towards Type 2 diabetes, HbA1c, goes up, along with AGEs (advanced glycation end-product). AGEs also promote the development of receptors for advanced glycation end-products (RAGEs). RAGEs create a systemic inflammatory response, devastating blood vessels, organs, and the brain. The kidneys help clear out RAGEs but at a cost. Kidney disease develops while uncleared AGEs build up in the body, causing damage and disease progression.
Eventually, this process damages nerves and blood vessels, leading to retinopathy, nephropathy, neuropathy, microvascular disease, strokes, peripheral arterial disease, and other lifestyle diseases.

3. Mixed High and Low Blood Sugar

Many people show both high and low blood sugar patterns and symptoms. They have low blood sugar symptoms before meals (even though blood sugar is not low) but feel sleepy after they eat. They may have insulin resistance but still crash at 4 p.m. or bolt awake at 3 a.m., which are symptoms of low blood sugar. I more commonly see people on a rollercoaster ride with their blood sugar swinging back and forth between high and low symptoms. This leads to issues with energy, fatigue, sleep, mood, and brain function.
In these scenarios, I like to measure fasting glucose, fasting insulin, HbA1c, and postprandial glucose and insulin to gauge how advanced the insulin resistance is.
The HOMA-IR (homeostasis model assessment of insulin resistance) scale can help you determine your level of insulin resistance.

Advanced Blood Sugar Severity

If left unchecked, metabolic syndrome progresses to Type 2 diabetes, in which fasting blood sugar exceeds 126 mg/dL and HbA1c 6.5 percent. This is when serious complications become highly likely, including early dementia, peripheral neuropathy, and kidney disease.

Reversing Out of Insulin Resistance Is a Long Game

The further along the scale you are, the more diligently you must work to reverse insulin resistance. The older you are, the more patience and persistence you must have. Some people have been insulin resistant for decades—it can take many months, if not a couple of years, to restore insulin sensitivity.
Weight loss may be slow and stubborn during this period, do not let that derail you. It’s more important that you stay the course to preserve your brain health and lower your risk of dementia than it is to lose weight quickly (although some people, particularly men, lose weight quickly and easily). As we age, we lose some resilience, so older people will likely need to be stricter for the best results. The good news is that most people feel so much better so quickly that this motivates them to stay on track with a whole-foods, low-carb, or ketogenic diet, and their daily exercise plan.

Dietary Tips for Stabilizing Blood Sugar

Managing blood sugar, especially after decades of blood sugar instability and insulin resistance, becomes a life’s work. But don’t see it as something negative or punitive. People find a new lease on life when they begin regaining their health and brain function. It becomes a feed-forward cycle that continually increases their motivation, energy, activity levels, and vitality.
Here are some basic principles to start moving back down the scale of severity into insulin sensitivity:
  • Do not skip breakfast. Eat a breakfast of high-quality protein and fats that is also low in sugars.
  • If you have low blood sugar, eat a small amount of protein and/or healthy fat every two to three hours. Avoid snacks that are sugar- or carb-only.
  • Find your carbohydrate tolerance and stick to it. If you feel sleepy or crave sugar after you eat, you have eaten too many carbohydrates. You can use a glucometer to check your fasting blood glucose, which should be between 80–100.
  • Never eat high-carb foods without some fiber, fat, or protein. These will slow down the rate at which the glucose is absorbed into the bloodstream and help prevent “insulin shock.” However, it is best to avoid high-carb foods when stabilizing your blood sugar. These include bread, pasta, rice, grains, potatoes, and anything sweet, including natural, so-called “low-glycemic” sweeteners such as agave or coconut sugar. These are still sugars that cause blood sugar to spike and crash.
  • Do not eat sweets or starchy foods before bed. This is one of the worst things a hypoglycemic person can do. Your blood sugar will crash during the night, long before your next meal is due. Chances are your adrenals will kick into action, creating restless sleep or that 3 a.m. wake up with anxiety.
  • Avoid all fruit juices and carrot juice. These can be more sugary than soda and will quickly have you crashing. Also, avoid dried fruits for the same reason: they are concentrated sugar.
  • Avoid or limit caffeine, which spikes blood sugar.
  • Eat a well-balanced diet consisting primarily of vegetables, quality meats, and fats.
  • Eliminate food allergens and intolerances. The immune reactions spike blood sugar.
The key concept to remember with autoimmunity and blood sugar control is that insulin spikes activate the TH-17 system and perpetuate autoimmune activity. Constantly spiking your insulin levels will continue to activate your autoimmune response. If you get tired after you eat, you have just activated an insulin spike and promoted autoimmune activity. If you are more hypoglycemic, your body produces an insulin surge every time your blood sugar crashes to get any available glucose into the cells. This can also activate autoimmunity.
When you have autoimmunity, dietary management is about avoiding gluten or other reactive foods and stabilizing your blood sugar with proper meal timing and food selection.
Datis Kharrazian

Datis Kharrazian


Datis Kharrazian, Ph.D., DHSc, DC, MS, MMSc, FACN, is a Harvard Medical School trained, award-winning clinical research scientist, academic professor, and world-renowned functional medicine health care provider. He develops patient and practitioner education and resources in the areas of autoimmune, neurological, and unidentified chronic diseases using non-pharmaceutical applications.

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