Insulin Resistance Clinical Pearls

• People with pre-diabetes or insulin resistance also can have low or normal blood sugars, if their high circulating insulin levels are further challenged by a prolonged period of fasting or dietary restriction, e.g. food allergy/sensitivities, Paleo, Keto, Vegan, Vegetarian, etc. 
• Red Blood Cell (RBC) agglutination (stuck together, shed oxygen) has been consistently associated with insulin resistance.
• Insulin Resistance deprives all parts of the body of glucose and oxygen. Both of which are delivered through the blood.

Symptoms of Insulin Resistance

Vasomotor Autonomic Dysfunction

• Vasomotor Imbalance
  • Poor Sampling of Hormones by Hypothalamus-Pituitary Axes (HPA, HPT, HPG, HPD, Blood glucose control)
• Sleep Issues
  • Inability to stay asleep at night. (Sympathetic over-ride)
  • Excess Daytime Sleepiness (body goes into Power-Saver Mode)
• Thermogenesis (Sympathetic over-ride)
  • Also know as “Hot Flashes”.
• Hypoglycemic-Associated Autonomic Dysfunction (HAAF)
  • AD is common in Insulin Resistance / Metabolic Syndrome patients, and in those who suffer Iatrogenic Hypoglycemia, there is a Hypoglycemia-Associated Autonomic Failure (HAAF). This is a result of decreased response of adrenals and the SNS to hypoglycemia
• Hypoglycemic Unawareness (HU)
  • AD creates hypoglycemic unawareness, and therefore a vicious circle of worsening AD.

Brain fogginess

• Inability to focus. 
• Brain requires oxygen and glucose to function efficiently.
• Insulin Resistance combined with Vasomotor Autonomic Dysfunction deprives the brain of the necessary oxygen and glucose. 
• Red Blood Cells
  • 98.5% of oxygen is carried by Red Blood Cells (RBCs). ~1.5% of oxygen is free in blood. 
  • RBCs release oxygen below 7.2 blood pH. 
  • RBCs hold onto oxygen above 7.4 blood pH.
  • If not absorbed by cells immediately, free oxygen becomes Reactive Oxygen Species (ROS). ROS cause damage to interior of blood vessels.
• RBC agglutination slows blood flow to the muscles, nerves and all parts of the body. RBC agglutination causes RBCs to shed oxygen. Further depriving all of the body of oxygen and glucose. 
• See Hepatic Encephalopathy below.

Cardiovascular disease

• RBC Agglutination causes RBCs to shed oxygen. Especially in turbulent areas, i.e. heart blood vessels. Free oxygen becomes destructive Reactive Oxygen Species (free-radicals) that damage interior of blood vessels. Cholesterol is used to spackle over the damaged areas.
• Hypertension – Increased blood pressure.
  • It is a fact that most people with hypertension have too much insulin and are Insulin Resistant. It is often possible to show a direct relationship between insulin resistance and blood pressure: as insulin levels elevate, so does blood pressure. 

Depression. 

• When the brain is deprived of oxygen and glucose, brain function slows down, going into power saver mode creating the symptoms of “depression”. 
• Brain requires oxygen and glucose to function efficiently. Insulin Resistance deprives the brain of the necessary oxygen and glucose.  
• RBC agglutination slows blood flow to the brain. Further depriving the brain of oxygen and glucose. 

Dyslipidemia

Increased cholesterol and triglycerides. 

• RBC Agglutination causes RBCs to shed oxygen. Free oxygen becomes destructive Reactive Oxygen Species (free-radicals) that damage interior of blood vessels. Cholesterol is used to spackle over the damaged areas.
• When triglycerides are equal to or greater than cholesterol suspect Diabetes.
• High Cholesterol, LDL increase the stickiness of Red Blood Cells – RBC Agglutination.
• Hypoxia (Low Oxygen):
  • High Cholesterol, LDL decreases the delivery and availability of oxygen to the tissues of the body.
• RBC Agglutination causes RBCs to shed oxygen. Free oxygen becomes destructive Reactive Oxygen Species (free-radicals) that damage interior of blood vessels. Cholesterol is used to spackle over the damaged areas.
• When triglycerides are equal to or greater than cholesterol suspect Diabetes.

Eye – Floaters, Cataracts, Declining Vision

• Retinal hemorrhages, floaters (soft exudates, hard exudates),
• Changes in blood vessels of the eyes (intraretinal microvascular abnormalities or venous beading)
• Reversible cataracts  

Excessive Daytime Sleepiness

Insulin Resistance is connected with circadian misalignment and elevations of blood pressure.^,  Excessive sleep is associated with the metabolic dysfunction – Insulin Resistance.

• Sleep Apnea – diminished ventilatory response during nocturnal sleep, hence increased hypoxemia, and the associated hypercapnia.
• Metabolic Syndrome is considered a clinical manifestation of Insulin Resistance.  

Fatigue.

• Sometimes the fatigue is physical, but often it is mental. 
• Muscles, nerves, brain, and all other parts of the body require oxygen and glucose to function efficiently. Insulin Resistance deprives all of them of the necessary oxygen and glucose. 
• RBC agglutination slows blood flow to the muscles, nerves and all parts of the body. RBC agglutination causes RBCs to shed oxygen. Further depriving all of the body of oxygen and glucose. 

Fibromyalgia

• Metabolic Syndrome or Insulin Resistance is associated with an increased risk of Fibromyalgia.
• Fibromyalgia patients have a greater glycemic response to a glucose load than do healthy people.
• The difference in the glycemic response is explained by Insulin Resistance and Metabolic Conditions.

Fluid Retention

• Failure of normal lymphatic function results in a build-up of interstitial fluid and can lead to the clinical manifestations such as lymphedema and ascites.
• This results in weight gain that is difficult to loose.

Portal Hypertension

Insulin resistance (IR) is an important driver for the development of Hepatic Portal Hypertension and nonalcoholic fatty liver. During Insulin resistance and non-alcoholic fatty liver (NAFL) progression, abnormal angiogenesis in the splanchnic system further aggravates portal inflow resulting in Internal/External Hemorrhoids.

Hepatic Portal Hypertension is a multi-organ condition.

• Internal Hemorrhoids: Esophageal varices/GERD, stomach varicies, small intestine, large intestine, diaphragm, umbilical, Pelvic Congestion Syndrome, gallbladder, and spider/varicose veins in legs.   
• External Hemorrhoids: Vaginal/uterine,  Rectal
• Disc Bulges: 96% of disc bulges seen on MRI images are Epidural Varices.
  • Cauda Equina Syndrome (CES) by means of direct mechanical compression or congested flow-induced ischemia.^,,,,  
  • Brain and Spinal Cord Myelopathy causing changes in the central nervous system blood flow and neural degeneration.^,,,  

Hepatic Encephalopathy

Hepatic encephalopathy can arise from portal-systemic shunting in the absence of intrinsic liver disease. Several metabolic syndrome clinical manifestations such as non-alcoholic fatty liver disease (NAFLD) and Insulin Resistance are associated with brain fog, cognitive impairment. Insulin Resistance treatment for patients with insulin resistance/metabolic syndrome protects against Hepatic Encephalopathy.

Hepatic Encephalopathy Symptoms

Unfortunately, it is often under-diagnosed, likely related to the notion that highly specialized personnel concentrate all their efforts on the brain and Central Nervous System.

Symptoms may begin slowly and slowly get worse. They may also begin suddenly and be severe from the start. Early symptoms may be mild and include:

• Breath with a musty or sweet odor
• Change in sleep patterns
• Changes in thinking
• Confusion that is mild
• Forgetfulness
• Mental fogginess
• Personality or mood changes

• Poor concentration
• Poor judgment
• Worsening of handwriting or loss of other small hand movements

More severe symptoms may include:

• Abnormal movements or shaking of hands or arms
• Agitation, excitement, or seizures (occur rarely)
• Disorientation
• Drowsiness or confusion
• Strange behavior or severe personality changes
• Slurred speech
• Slowed or sluggish movement

Minimal Hepatic Encephalopathy (MHE)

• Several comorbidities, such as Metabolic Syndrome and Insulin Resistance, contribute to the development of MHE.
• Minimal Hepatic Encephalopathy effects areas of attention, alertness, response inhibition, and decision making functions and sleep disorders.  Moreover, the brain fog and cognitive impairment results in the use of more healthcare resources focused on treating only the brain while ignoring the causative liver dysfunction.

High blood sugar.

Mild, brief periods of low blood sugar are normal during the day, especially if meals are not eaten on a regular schedule. But prolonged hyperglycemia with some of the symptoms listed here, especially physical and mental fatigue, are not normal. 

• Feeling agitated, jittery, moody, nauseated, or having a headache is common in Insulin Resistance, without immediate relief once food is eaten. 

Intestinal bloating.

• Most intestinal gas is produced from food fermenting and putrefying due to inadequate production of digestive chemistry.
• Insulin Resistance sufferers who eat carbohydrates suffer from gas, lots of it. 

Thyroid / Hypothyroid

• Everything the body does is defensive in nature.
• Supply vs. Demand
• Thyroid Hormones stimulate the metabolic rate. 
• Insulin Resistance slows the metabolic rate. 
• Thyroid will slow production of thyroid hormones to compensate for insulin resistance.
• Reduced levels of oxidative stress accompany hypothyroidism (low thyroid) 
• Hypothyroidism reduces production of reactive oxygen species generation, lipid peroxidation, and NAFL.

Thyroid Antibodies

• Thyroid TPO Antibodies and TAA Antibodies are increased in those with Insulin Resistance.

Nerve Pain – Blood / Nerve Reciprocity

• Nerves and all other parts of the body require oxygen and glucose to function efficiently. Insulin Resistance deprives all of them of the necessary oxygen and glucose. 
• All nerves depend wholly upon the arterial system for their oxygen and glucose and the quality of their function, such as sensation, signal transmission and motion.
• A loss of blood flow results in nerve cell deterioration and ultimately in nerve death starting within minutes. A deteriorating nerve send pain signals to the brain.
• RBC agglutination slows blood flow to the nerves and all parts of the body. 

Nonalcoholic Fatty Liver (NAFL)

• A condition marked by elevated liver enzymes, abnormally high levels of fat in the liver, and enlargement of the organ, the severity of nonalcoholic fatty liver disease increases with obesity and abdominal fat and may develop as a result of Insulin Resistance.

Obstructive Sleep Apnea

Sleep apnea is a breathing disorder in which you stop breathing for very short periods of time while sleeping.

• Red Blood Cell (RBCs) become sticky with Insulin Resistance. RBCs deliver 98.5% of oxygen to the tissues of the body.
• Movement during daily activities prevents clumping of RBCs.
• Lack of movement during sleep allows RBCs to stick together causing oxygen release far away from the tissues that need it.
• Oxygen deprivation triggers alarm signals causing a person to wake and move. Temporarily dispersing RBCs from each other and allowing diminished oxygen delivery.

Poor Sleep

• Self-perceived insufficient, poor or short sleep is also associated with Insulin Resistance metabolic impairments such as elevated glucose and insulin levels, elevated HBA1c or whole-body insulin resistance.
• Moreover, inadequate sleep has been shown to worsen glucose control in patients with Insulin Resistance.
• Interestingly, the affliction is stronger in women than men.

Sleepiness.

Many people with Insulin Resistance get sleepy immediately after eating a meal exceeding their Carbohydrate Tolerance. Body is going into power-saver mode like your electronic device.

• Fatigue after meals, craving sugar after meals, must have dessert: 
• Cut back on carbs until you are no longer sleepy after meals and/or do not crave sugar after eating.

Sleep Hypoxia

• Insulin Resistance induces intermittent hypoxia (low oxygen levels in blood).
• There is a higher prevalence of sleep apnoea-hypopnea syndrome (SAHS) in patients with persistant Insulin Resistance up to 85%, with 70% for the range of moderate SAHS.
• Intermittent nocturnal hypoxia is associated with poorer glycemic control and an increase in cardiovascular risk.
• Intermittent hypoxia has been shown to result in neuronal damage in wake promoting structures or disturbance in sleep architecture.

Weight Gain

Fat storage, difficulty losing weight. The fat in IR is generally stored around the midsection in both males and females. 

Supply vs. Demand

• Thyroid Hormones stimulate the metabolic rate.
  • Insulin Resistance slows the metabolic rate. 
  • Thyroid will slow production of thyroid hormones to compensate for insulin resistance.
• Reduced levels of oxidative stress accompany hypothyroidism (low thyroid) 
• Hypothyroidism reduces production of reactive oxygen species generation, lipid peroxidation (Thyroid Under-Conversion), and NAFL.  

Symptoms of Red Blood Cell Aggregation

• Fatigue 
• Brain fogginess and inability to focus
• Nerve pain
• Cold hands and feet
• Numbness and tingling in arms and legs
• Muscle cramping

Insulin resistance is also known as “Prediabetes”, they are both considered the same thing, just in case you didn’t know. The Medical Doctors are trained to wait until a person develops full Diabetes. Then convince people that it is not reversible, making the people life-long drug-dependent patients. 

Insulin resistance is often present for up to 10 years or more before an “official” diagnosis. Many never develop Type 2 Diabetes but suffer for years from insulin resistance. Especially, those with long-term dietary restrictions. That’s a long time for you to do something about it. People with pre-diabetes or insulin resistance also can have low or normal blood sugars, if their high circulating insulin levels are further challenged by a prolonged period of fasting or dietary restriction.

Recommended Labs For Metabolic Health

• Preferred Lab Test is Comprehensive BioScreen Panel (LC) LabCorp.
• Use (QD) if no LabCorp facility is near where you live.