Blood Sugar Regulation (week 3) Flashcards
digestion
increased incidence of general GI complaints
-individuals with type 1 and 2 diabetes have higher incidence
-symptoms more common the less glucose is managed
vagal nerve & gastric motility
-delays in the rate of stomach emptying
-diabetic neuropathy is most common known cause of gastroparesis
migrating motor complex:
-peristaltic movement that clears the GI tract of debris
-occurs every 90-230 minutes
-when blood glucose levels remain high, the cycle length of the MMC is reduced
non-alcoholic fatty liver disease:
-high blood glucose levels can lead to non-alcoholic fatty liver disease (NAFLD)
-NAFLD = increased risk for gastroesophageal reflux disease and other digestive complaints
dysbiosis:
-can negatively impact hormonal signaling required for glucose metabolism
-bacterial products like LPS, SCFAs, and bile salts can alter glucose metabolism for better or worse
-refined sugars and starch can alter gut microbiome and promote insulin resistance
-diets high in fiber alter the microbiome in a protective way
sleep
contributors to poor sleep:
-hyperglycemia
-insulin resistance
hyperglycemia
-increased urination
-frequent awakenings throughout the evening
reactive hypoglycemia
-blood sugar below 70 mgdL while sleeping at night is “nocturnal hypoglycemia”
-skipping dinner, exercising close to sleep, alcohol or sugar before bed.
-leads to increased stress hormones which cause waking
stress
stress can impact blood sugar regulation. dysregulated blood sugar can impact HPA axis
reactive hypoglycemia:
-after high glycemic meals
-excess synthetic insulin medication
-excess secretion of insulin by the pancreas
-adrenaline and cortisol secreted in response to low glucose - helps prevent blood glucose levels from galling too low
if ongoing, reactive hypoglycemia can lead to dysregulation in HPA axis
-early stages - stress hormones may be elevated
-over time stress hormone production falls symptom is hypoglycemia
study: 20% of individuals with type 2 diabetes and severe hypoglycemia had an impaired cortisol response
hypoglycemia can also occur if:
-meal frequency is too far apart
-poor macronutrient balance for the individual
-impaired metabolic flexibility to move to other energy production pathways
stress: mental health
connection between depression, anxiety, stress and consumption of foods high on the glycemic index
biological mechanism:
-reactive hypoglycemia = elevated cortisol levels = anxiety and mood disturbances
rapid blood sugar fluctuations disrupt:
-balance of neurotransmitters in the brain (serotonin, dopamine, norepinephrine)
-brains energy supply = impaired cognitive function and mood
high glycemic diets = alterations in intestinal microbiome = mental health conditions
cardiovascular system
cardiovascular system most directly affected by blood sugar dysregulation
glycation: glucose molecules in the bloodstream bind to proteins or lipids
endothelial cells of vascular lining are vulnerable to injury and glycation
elevated glucose and hyperinsulinemia can promote
-high blood pressure
-dyslipidemia: an atherogenic lipid profile
cardiovascular: blood pressure
hyperinsulinemia leads to:
-sodium retention: increases the reabsorption of sodium in the kidneys, resulting in increased fluid volume
-activation of the sympathetic nervous system: causes blood vessels to constrict
-impaired nitric oxide production: impaired production/reduced bioavailability of nitric oxide, leading to decreased vasodilation and increased vascular resistance or rigidity
-endothelial dysfunction: increased production of vasoconstrictors and increased inflammation
what is hyperlipidemia?
hyperlipidemia: abnormally elevated levels of lipids in the blood, both cholesterol and triglycerides
dyslipidemia: indicates that there is an abnormal distribution of lipids
-elevated levels of LDL cholesterol
-reduced levels of HDL cholesterol
-elevated triglycerides
cholesterol and triglycerides are essential, but excess levels are associated with a higher risk factor for cardiovascular diseases, including atherosclerosis
lipid types
high density lipoprotein (HDL) cholesterol:
-referred to as “good” cholesterol
-helps remove excess cholesterol and transports it to the liver for recycling/elimination
-higher levels of HDL cholesterol as associated with a reduced risk of heart disease
low-density lipoprotein (LDL) cholesterol:
-referred to as “bad” cholesterol
-carries cholesterol from the liver to the cells in the body
-excess of LDL particles can increase risk of atherosclerosis (hardening and narrowing of arteries)
lipid types
more nuanced conversation to be had about LDL cholesterol:
-LDL has essential roles to play
-particle size and type changes risk
-conflicting information on reducing LDL and other health outcomes like all cause mortality
-exclusive focus on LDL for cardiovascular risk can take away from focus on other risk factors
key point for blood sugar regulation:
-the more dangerous particle types and sizes are the ones that become elevated in the context of hyperglycemia and hyperinsulinemia
elevated triglycerides - most directly connected to glucose dysregulation
cardiovascular system: dyslipiemia
hyperglycemia and hyperlipidemia can lead to:
-increased lipid production: stimulates the liver to convert more glucose into lipids, particularly triglycerides
-dysregulated lipid storage: body adipose tissue becomes less efficient at storing lipids = increasing circulating lipid levels / promotes ectopic fat deposition in non-adipose tissue like the liver, skeletal muscle, heart, and pancreas
-altered lipoprotein metabolism: increase in LDL production and a decrease in HDL production, leading to an unfavorable lipid profile
-impaired lipid oxidation: high levels of insulin can block the enzymes needed to convert lipids into energy
nervous system: glycation
glycation is linked to diabetic neuropathy
nerve tissues affected by glycation:
-both sensory and motor nerves
-all parts of nerve cells: nerve body, axions, dendrites, stromal collagen that support the function of the nerve fibers
schwann cells: glial cells that wrap around nerve fibers to create myelin
higher AGE deposition leads to reduced myelination of nerves
AGEs may contribute to neuronal cell death
glycation slows nerve conduction and causes impaired regeneration of supportive tissues
diabetic neuropathy
peripheral diabetic neuropathy - nerve damage in people with diabetes
-7% of people within one year of diagnosis
-50% of people who have had diabetes for over 25 years
occurs in peripheral nervous system:
-motor
-sensory
-autonomic
nerves in hands, fingers, feet, and toes are primarily impacted = sensation of tinging or burning
can progress to deep pain and loss of feeling
amputation occurs in 1-2%
commonly impact cardiovascular and digestive systems
vision (nervous system)
diabetic teinopathy: hyperglycemia damages blood vessels in the retina and optic nerve
early symptoms includes: blurry vision, trouble reading, difficulty seeing objects far away, floating spots and streaks, blindness
can lead to other eye conditions:
-diabetic macular edema
-glaucoma
the brain: hyperglycemia and neurodegeneration
prolonged hyperglycemia damages blood vessels that carry oxygen throughout body
brain may receive too little oxygen rich blood = brain atrophy:
-impaired functioning
-death of brain cells
-problems with memory and cognition
the brain: hyperglycemia and alzheimer’s
many studies link blood sugar dysregulation and alzheimer’s disease
study investigated association between glucose intolerance and development of dementia:
-1000 dementia free adults
-participants followed for 15 years
-findings: participants with diabetes and blood sugar dysregulation had significantly higher cases of all-cause dementia and AD compared to those with normal glucose tolerance
AD often referred to as “type 3 diabetes”
~80% of AD patients have impaired fasting glucose or type 2 diabetes
alzheimer’s disease and blood sugar dysregulation
glycotoxic AD:
caused by chronic inflammation from high blood glucose levels. a loss of nutrition support (loss of insulin sensitivity)
glucose is the brains primary and preferred fuel source:
-adult brain:
~2% of body weight
consumes ~20% of glucose derived energy
insulin receptors found in regions of the brain involved in learning and memory: hippocampus, entorhinal cortex, frontal cortex
in some people, insulin resistance may begin in the brain before the rest of the body
amyloid beta and Tau
excessive build-up of amyloid beta and tau proteins in AD
insulin helps regulate the construction and destruction of these proteins:
insulin degrading enzyme (IDE): needed to break down and clear amyloid beta. impaired during an insulin-resistant state
-expression of the tao gene and activation of tau protein is regulated by insulin stimulation
buildup of these two proteins contributes to
-increased neuroinflammation
-oxidative stress
-synaptic dysfunction = impairment of cognition, memory, and learning
brain health summary
insulin resistance:
-leaves the brain cells deprived of glucose
-impaired regulation and clearance of amyloid beta and tao
prolonged hyperglycemia:
-increases oxidative stress
-increases AGE formation
-increases damage to neurons
all these factors contribute to neurodegeneration and reduced brain functioning
immune system
metabolic syndrome and type 2 diabetes associated with low-grade inflammation: “meta inflammation”
both a driver and result of blood sugar dysregulation:
-chronic inflammation can impair metaoblism
-elevated levels of glucose and free fatty acids in circulation can increase inflammation
immune dysregulation
individuals with T2D more susceptible to infections:
-urinary tract, skin, respiratory
multifactorial: viruses manipulate glucose metabolism to promote their reproduction
compromised T cell and macrophage function: impaired ability to recognize and combat infections
reduced wound healing ability
-impaired blood flow to wound site
-reduced immune cell migration
-reduced production of growth factors needed for tissue repair
autoimmune disorders
endocrine
blood sugar regulation is regulated by endocrine hormones
relationships are multi-directional and complex
it is not within the scope to diagnose or treat a hormonal condition
helping someone find their way toward better blood sugar balance is effective and within scope
endocrine: thyroid
thyroid conditions can promote insulin resistance (and vice versa)
insulin resistance associated with alterations in thyroid hormone levels
studies show link between insulin resistance and subclinical hypothyroidism:
-significant reduction of conversion of T4 (less active) to T3 (active)
-overall deficiency in active T3
-increased conversion of T4 to reverse T3 = brake on intracellular T3 activity
endocrine: sex hormones
androgens are hormones produced by the body in greater amounts in males (testosterone)
aromatase enzyme converts androgens into estrogens
insulin resistance increases aromatase activity = higher estrogen production = imbalance between estrogen and testosterone and progesterone in both males and females
in males, insulin resistance = lower levels of testosterone
in some females, insulin resistance = excessive androgens synthesis in the ovary:
-disrupts menstrual cycles
-contributes to development of PCOS
-insulin stimulates theca cells in ovaries to produce increased testosterone
-inhibits production of sex hormone-binding globulin (SHBG)
-sex hormone binding globulin is a protein that binds to sex hormones. increase insulin = decrease SHBG = excess androgens
in PCOS, insulin resistance + lower levels of SHBG are linked to
-high androgens (testosterone)
-abnormal glucose and lipid metabolism in PCOS patients
endocrine: estrogens
estrogen helps preserve insulin sensitivity: insulin resistance more common in women after menopause
insulin resistance can alter estrogen metabolism
increase in the production of estrogens in visceral adipose tissue. excess can contribute to endometriosis and fibroids in females
blood sugar dysregulation can negatively affect gut microbiome, which can alter estrogen metabolism (estrobolome)
impairs the livers ability to metabolize and eliminate excess estrogens
urinary / kidney health
CDC - 1 in 3 adult diabetics have kidney disease
nephrons are responsible for filtering our blood:
-sort nutrients from waste
-excrete the waste from the body through the urine
-reabsorb nutrients
capillaries in nephrons receive large volumes of blood under high pressure
kidney disease:
-filtration ability is reduced
-impaired regulation of body fluid = edema
-sodium filtration is impaired = elevated blood pressure and hypertension
-reduced ability to convert vitamin D2 into D3 = lower vitamin D levels and decreased calcium absorption
skeletal / bone health
magnesium is needed for proper bone metabolism
-increased excretion of magnesium
-increased magnesium demand
-decrease serum magnesium levels
increase osteoclast (cut) formation/reduction in osteoblast (building) activity
-increase bone reabsorption/bone loss
negative impact of AGEs on collagen matrix in bone
-reduced flexibility and strength
-increase excretion of urinary calcium
-decrease bone mineral density
-risk of bone fractures
-increase joint pain
-increase pain severity
