Blood Sugar Regulation (week 2) Flashcards
Incidence of type 2 diabetes
in the US:
-top 10 leading cause of death
-37.2 million (11.3% of total population)
-48.8% in adults 65+
-96 million with prediabetes
-1 in 2 adults with diabetes or prediabetes
global incidence:
-increased from 108 million in 1980 to 422 million in 2014 (4x increase in 34 years)
-in 2019, ~463 million adults with diabetes
-estimated to rise to 700 million by 2045
changing names:
-type 1 diabetes historically called “juvenile diabetes”
-type 2 diabetes historically called “adult onset diabetes”
-age based names are no longer accurate due to the rising incidence of type 2 diabetes in children
insulin resistance
insulin resistance = a condition in which cells in the body become less responsive to the effects of insulin
-insulin receptors on target cells lose sensitivity to insulins signals
-pancreas produces more insulin to compensate
over time, results in:
-hyperglycemia (chronically elevated blood sugar levels)
-hyperinsulinemia (chronically elevated blood insulin levels)
-pancreatic beta cells may not produce sufficient insulin
associated with:
-high blood pressure
-weight gain (excess abdominal or visceral fat)
-hormonal dysregulation
-inflammation
-fatigue
glucose intolerance
related to insulin resistance, but is a broader term
refers to the body’s inability to process and metabolize glucose effectively, including:
-prediabetes
-diabetes
insulin resistance is a key factor in developing glucose intolerance
to summarize:
-insulin resistance = decreased responsiveness of cells to insulin
-glucose intolerance = body’s inability to process and metabolize glucose
glycation
chemical reaction - glucose molecules in the bloodstream bind to proteins or lipids
forms “advanced glycation end products” (AGEs) which accumulate in tissues over time
-AGEs cause damage to cells by reacting to essential proteins
considered to be irreversible
accelerates the aging process
promotes inflammation and oxidative stress
note that BOTH chronically elevated glucose AND sharp glucose spikes contribute to the glycation process
HbA1c measures glycation of red blood cells
Glucose ranges
healthy blood sugar range:
-fasting blood glucose: (8hr after eating) below 100 mg/dL
-lower risk at 70-90 mg/dL
-postprandial blood glucose: (2 hrs after eating): below 140 mg/dL
Prediabetes:
-impaired fasting glucose (IFG): fasting blood glucose levels between 100 to 125 mg/dL
-impaired glucose tolerance (IGT): two hour postprandial blood glucose levels between 140 to 199 mg/dL
Diabetes:
-fasting blood glucose: above 125 mg/dL on more than one occasion
-post prandial blood glucose: equal to or above 200 mg/dL on more than one occasion
-oral glucose tolerance test (OGTT): two hour postprandial blood glucose equal to or above 200 mg/dL during an oral glucose tolerance test
-HbA1c: equal to or above 6.5% on more than one occasion
Stages of Dysglycemia
- reactive hypoglycemia
- insulin resistance & hyperinsulinemia
- metabolic syndrome & pre-diabetes
- type 2 diabetes
healthy glucose regulation
insulin (+incretins) help limit upper range “use & store”
glucagon and adrenal hormones help limit lower range “release storage”
key characteristics: glucose stays within range, smooth curves, metabolic flexibility, and stable energy
Stage 1: reactive hypoglycemia
in the early stages of dysglycemia, we begin to see sharp swings in blood glucose.
When we consume a high glycemic meal, our blood glucose shoots up past normal, healthy upper ranges.
It is moving so fast that the body produces excessive amounts of insulin to protect you from the damages of hyperglycemia.
The body does not know when this rapid increase in glucose will end, so it basically overcorrects by producing excessive amounts of insulin.
Once the glucose consumption stops, the high insulin levels continue to do their work, shuttling glucose into cells.
This causes a sharp drop in blood glucose, called reactive hypoglycemia.
Stage 1: reactive hypoglycemia
With these early stages of dysglycemia, our cellular insulin response is still working well, and so
our fasting glucose levels are still returning to normal most days.
This is more of a rollercoaster ride, with sugar highs and crashes rather than constantly elevated glucose, but over the long term, it can contribute to the progression of later stages of dysglycemia.
One of the things that make the rollercoaster so taxing is that the adrenal glands are required
to help keep the floor from falling out below us.
The increased levels of stress hormones can
cause jittery feelings and anxiety, commonly referred to as being “hangry.”
So, when we talk about low blood sugar being a form of biochemical stress, this kind of reactive hypoglycemic
spell is exactly what we are talking about.
Hypoglycemia signs and symptoms
- Increased cravings for sugar and refined carbohydrates
- Increased blood pressure
- Unstable energy levels
- Headaches
- Mood swings
- Anxiety
- Disrupted sleeping
- Ravenous hunger
- Feeling light-headed if meals are missed
- Feeling jittery or shaky between meals
- Sweating
- Rapid or irregular heartbeat
- Reduced cognitive performance
Stage 2: Insulin Resistance & Hyperinsulinemia
decreased response to insulins signal
sugar highs: crashes may become less frequent
accumulation of glucose and insulin = hyperglycemia and compensatory hyperinsulinemia
chronically elevated glucose leads to glycation
chronically elevated insulin contributes to:
-elevated blood pressure
-dyslipidemia
-inflammatory conditions
-hormonal dysregulation
-fatigue
-weight gain
Stage 2: Insulin Resistance & Hyperinsulinemia
fatigue & weight gain:
-two of the most common complaints
-signs that blood glucose regulation is not optimal
weight gain:
-lipolysis is inhibited, lipogenesis is stimulated
-lipid overflow hypothesis = when body fat stores are maxed, lipids are stored as visceral fat around organs
fatigue:
-glucose uptake is impaired = cells do not receive adequate energy supply = fatigue and low energy levels
-low energy can lead to reduced activity
Stage 2: Insulin Resistance & Hyperinsulinemia
insulin resistance may be seen as a protective mechanism for cells:
-glycolysis in mitochondria produces oxidative stress, a normal cost of producing energy
-insulin resistance could be considered as an antioxidant defense mechanism to prevent cells from excessive oxidative damage
Stage 2: Insulin Resistance & Hyperinsulinemia
Common signs and symptoms of insulin resistance include:
- Increased hunger
- Increased fatigue and lethargy
- Increased brain fog and difficulty focusing
- Increased weight gain, especially in the abdomen
- Increased blood sugar
- Increased triglycerides and cholesterol levels
- Increased blood pressure
- Hyperpigmentation of the skin, especially around the neck and in the armpits
- Depression and mood disorders
- Endocrine imbalances, including thyroid and fertility issues
- Slow healing
- Premature aging
Stage 3: Metabolic Syndrome and Prediabetes
share common features and often coexist, but have distinct characteristics
metabolic syndrome = a set of specific biometrics
prediabetes = elevated blood glucose levels below the diagnostic criteria for diabetes
Prediabetes is diagnosed when either of the following criteria is met:
* Impaired fasting glucose (IFG): Fasting blood glucose levels between 100 mg/dL and 125 mg/dL.
* Impaired glucose tolerance (IGT): Blood glucose levels measured two hours after
an oral glucose tolerance test (OGTT) between 140 mg/dL and 199
mg/dL
Metabolic syndrom
a cluster of interconnected metabolic abnormalities
an increased risk of cardiovascular disease and type 2 diabetes
criteria for diagnosis:
* Abdominal obesity: Waste Circumference > 40” male / 35” female
* Elevated triglycerides (>150mg/dL)
* Blood Pressure (>130/85 mm/Hg)
* Elevated fasting glucose (> 100mg/dL)
* HDL below 50 mg/dL
additional signs include:
-systemic inflammation
-reproductive hormone dysregulation
Stage 4: Type 2 Diabetes
persistent hyperglycemia
insulin production insufficient to compensate for insulin resistance
impaired insulin secretion from pancreas
in some cases, exogenous insulin is required, or medication to:
-potenize insulin signaling
-lower glucose absorption in the intestines
-increase glucose excretion
Diagnostic criteria:
-Elevated blood glucose levels (at least one reading above 200 mg/dl in 24 hours)
-Hemoglobin A1c (HbA1c) above 6.4
Stage 4: Type 2 Diabetes
Common signs and symptoms of Type 2 Diabetes include:
- Extreme hunger or thirst
- Persistent hunger, even after a meal
- Frequent or increased urination
- Tingling sensations in the hands or feet
- Chronic, persistent fatigue
- Frequent infections
a chronic condition:
-effects can be mitigates through diet and lifestyle
-some individuals can achieve remission or reversal
-clients on glucose lowering medications need to work with prescribing physician to manage medication and prevent hypoglycemia
Type 1 diabetes
autoimmune condition
destruction of pancreatic beta cells (insulin)
uncontrolled elevations of blood sugar
requires insulin medications
permanent condition with no known cure
diet and lifestyle modifications can help manage disease and reduce complications
influencing factors:
-genetic predisposition (HLA class II genes)
-environmental factors include early life nutrition
-A1 beta-casein in cows milk
increasing rates:
-2% ride in T1D in youth (<20 per year)
-28% more US citizens compared to 2017
glycemic index (GI)
measures how quickly a carbohydrate containing food raises blood glucose levels, compared to a reference food
reference food = pure glucose or white bread
how is it obtained?
-blood glucose after consuming enough of the food to equal 50g of available carbohydrate (sugar and starch)
-GI number = a comparison between the glycemic response to a specific food vs the reference food on a scale of 0-100
-reference food = GI of 100
glycemic index (GI)
high GI = 70 or above
-rapidly digested and absorbed = quick and significant increase in blood sugar levels
ex: white bread, white rice, sugary beverages, most processed snacks
Low GI = 55 or below
-digested and absorbed more slowly = slower and smaller rise in blood sugar levels
Ex: meat, fermented dairy, most tart fruits and veggies, whole grain, legumes, nuts
glycemic index limitations
GI values do show:
-the speed at which glucose enters the bloodstream from 50g available carbohydrate
GI values don’t show:
-how many grams of carbohydrates are found in a serving
why is this a problem?
-GI can wrongly malign foods which require extremely large servings to reach 50g of available carbohydrates:
-1.5 pounds of carrots (one large bag) = 50g of carbohydrates (much more than one serving)
-one large single carrot weighs about 0.2 pounds (low glycemic impact)
glycemic load (GL)
what is it:
-a more contextualized rating of a food’s impact on blood glucose
-multiplies a given foods GI by the number of non-fiber carbohydrates (in grams) contained in a single serving size
-low GL = 10 or less
-moderate GL = 11-19
-high GL = 20 or more
ex: carrots (peeled and boiled in salt water) = GI of 92, but GL is only 9 (considered low)
Refined vs Whole Grain
the more processed a food is, the higher its GI will be
ex: “quick oats” vs steel cut or old fashioned rolled oats
refined cereal grain flours have a higher GI
-lack the bran and endosperm (vitamins, minerals, phytochemicals, and healthy fats)
reducing/avoiding products made from refined flour is a powerful way to improve blood glucose management
fermentation
sourdough: lactic acid bacteria and yeast transform sugars and starches into:
-carbon dioxide (causes bread to rise)
-lactic acid
-acetic acid
reduces the amount of available starch
organic acids slow absorption:
-lactic acid = inhibition of amylase enzymes
-acetic acid = delays gastric emptying rate
regular white bread = GI of 100 and GL of 10
sourdough whole wheat bread = GI of 54 and GL of 8
GI < 55 is defined as low, 56-69 is moderate, and >70 is high
glycemic index: cooking methods
boiled sweet potato vs baked sweet potato
moisture content:
boiled sweet potato = cooked in water, water softens and gelatinizes the starch, lower GI
baked sweet potato = cooked in dry air, reduces the water content, higher GI
cooking time:
boiled sweet potato = shorter cooking time, preserves structural integrity of carbohydrates, lower GI
-baked sweet potato = longer cooking time, breaks down the starch further, higher GI
note: most foods have a lower GI when consumed raw
GI & GL practical tips
carbohydrates eaten with fats = lower GI
fiber content = lower GI (eat whole foods)
the more cooked or processed the food, the higher the GI
foods high in fructose and artificial sweeteners may have misleadingly moderate GI:
-fructose must first be converted to glucose to be ,easured
-fructose still enters the bloodstream and causes glycation
response to carbohydrates is highly bioindividual based on:
-microbiome
-hormones
-activity levels
GL is more useful tool than GI alone
Total vs Net carbohydrates
total carbohydrates:
-the sum of all types of carbs present
-includes sugars (naturally occurring and added), fiber, and starch
-lumps together glycemic and non-glycemic carbs
-listed on nutrition labels
net carbohydrates:
-SUBTRACTS the fiber from the total carbohydrates
-more accurate number
-not always listed on food labels
The formula for calculating net carbs is usually:
Net Carbs = Total Carbohydrates - Dietary Fiber
microbiome profiles
exact microbial profile in patients with blood glucose dysregulation is not fully understood
distinct differences do exist
“metabolic endotoxemia” = increased adiposity and systemic inflammation result from chronic exposure to lipopolysaccharide
studies show alterations in the gut microbiome in T2DM, T1DM, and those on the brink of developing T1DM
microbiome and insulin resistance
dysbiosis contributes to:
inflammation: lipopolysaccharide impairs insulin signaling and promotes systemic inflammation
barrier dysfunction: increased passage of harmful substances into bloodstream
elevated zonulin: found in patients with T1D preceding/during disease
short chain fatty acids: dysbiosis disrupts production of butyrate
disrupted bile acid metabolism: dysbiosis alters secondary bile acid metabolism by bacteria
impaired gut hormone regulation: reduced production of GLP1 and PYY can impair insulin secretion and reduce insulin sensitivity
production of metabolites: elevated levels of metabolites some associated with insulin resistance (trimethylamine N-oxide, TMAO)
firmicutes to bacteroidetes ratio
two major phyla of bacteria
mixed research results in GI disorders and metabolic disorders
firmicutes extract more energy from food = hypothesis that elevated firmicutes to bacteroidetes ratio is marker of metabolic disorders
in contrast:
-several studies have not observed significant changes in ratio
-some show decreased firmicutes/bacteroidetes ratio associated
-bacteroides includes largest group of gram negative bacteria, conflicting with the elevated firmicutes hypothesis
microbiome takeaways
relevance of firmicutes and bacteroidetes is unclear
loss of diversity and high levels of gram negative bacteria can contribute to insulin resistance and blood sugar dysregulation
anything that contributes to alterations in the microbiome could potentially contribute to disturbance in metabolism and glucose regulation
clinical trials using some probiotics show benefits to glucose, lipids, blood pressure, and inflammatory markers in metabolic syndrome and T2D
A1 vs A2 beta-casein
A1:
-most cows produce both A1 and A2 beta-casein
-contains histidine at position 67
-histidine allows cleavage by proteolytic enzymes
-releases the peptide beta-casomorphin 7 (BCM-7)
-BCM-7 binds/activates opiois receptors in CNS, GI tract, and some immune cells
-may inhibit immune function or trigger inflammatory immune reactions
-increased absorption of BCM-7 in infants
A2:
-sheep and goat milk. certain herds of cows of african, asian, and european descent
-human breastmilk
-contains proline at position 67
-proline resists hydrolysis and cleavage of enzymes
A1 beta-casein milk and risk of T1D
Mu-opioid receptors found in islets of langerhans (pancreas - insulin)
BCM-7 from A1 beta casein can disrupt pancreas function
differences in dietary intake of cow dairy among populations = primary factor associated with varying rates of T1D
19 country study:
-finland and sweden = highest incidence of T1D and highest rate of A1 beta-casein consumption per person
-venezuela and japan = lowest incidence of T1D and lowest rate of A1 beta-casein consumption per person
systemic review and meta-analysis of 96 studies: what dietary factors reduced the risk of T1D?
-breastfeeding for 6-12 months
-avoiding dairy and gluten for the first 3 months of life
-reducing exposure to cows milk in early childhood
population based cohort studies:
-children who were never breastfed = 2x risk of T1D compared to children breastfed for 12 months
-children with mild-moderate dairy intolerance: acute GI symptoms, markers of inflammation, markers of immunity increased with A1 but not A2 beta-casein
-in adults aged 25-68, A1 beta-casein was associated with more GI symptoms, stomach inflammation, discomfort, levels of BCM-7, reduced transit time, cognitive functioning, and levels of short chain fatty acids
T1D vs T2D Prevalance
CDC estimates that in the US:
-T1DM = ~0.55% representing 1.6 to 1.9 million
-T2DM = ~11.3% representing 37.2 million, not counting millions with other stages
circadian rhythms
24 hour internal clocks
central control in hypothalamus, peripheral clocks in other organs
influenced by environmental factors like light and temperature
circadian rhythm genes influence glucose regulation. production of melatonin in the evenings causes insulin resistance and impairs the release of insulin by the pancreas
melatonin
synthesized and secreted by the pineal gland
one of the most reliable markers of circadian rhythms
regulated by the hypothalamus
main types of melatonin receptors:
-MT1 and MT2 receptors: found in the islets of langerhans of the pancreas (insulin and glucagon)
melatonin inhibits the cAMP pathway in the pancreas:
-blocks insulin secretion from pancreas in later part of the day and evening
eat in line with the circadian rhythms of metabolism
having a late dinner is associated with an increased risk for diabetes
chrononutrition
chrononutrition = how meal timing, metabolism, and circadian rhythms interact to influence health
before the industrial revolution:
-moderate breakfast
-dinner was main meal in the midday
-supper was light or option in evening
-snacking was far less common
after the industrial revolution, people worked away from home as more career opportunities arose, and electric lights made staying up late more compelling
-breakfast became an optional meal, often skipped
-midday meal became lunch and was lighter fare
-in the evening, dinner became the main/largest
modern trends:
-carb heavy breakfast on the go, large evenings meals, late night snacking
chrononutrition
studies show:
=when comparing identical meals given in evening or morning, evening meal resulted in higher glycemic response in blood sugar
making breakfast the largest meal of the day and dinner the smallest meal is linked to:
-improved glucose tolerance and insulin function
-lower BMI
-decreased change of become overweight/obese
-reduced inflammation
meal frequency
metabolic benefit in consuming 2-3 meals per day vs many small meals or snacks:
-greater insulin sensitivity
-reduction in BMI
-reduction in fat accumulation in the liver
fewer meals = give the body a window of low insulin exposure so we can utilize stored glucose for energy
intermittent fasting: extend fasting window in evening rather than morning aligns more with circadian rhythms
eat breakfast like a king, lunch like a prince, and dinner like a pauper
inadequate sleep
inadequate sleep, late sleep timing, artificial exposure to light, and shift work are associated with metabolic dysfunctions such as type 2 diabetes
as sleep duration decreases, stress hormones increase, which contributes to blood sugar dysregulation
studies show:
-one week of 4-5 hours of sleep a night, cells became unresponsive to insulins signals
-animal studies: mice experience increase in adiposity and diabetes when kept awake during sleep window
irregular sleep patterns
shift work increasingly common in the US (15-20% of workforce):
-irregular and prolonged hours
-exposure to artifical light
-abnormal sleeping patterns
overnight shift work:
-dysregulation of circadian rhythms
-reduced glucose tolerance
-increased risk of diabetes
meta-analysis that included 12 studies and 226,652 participants found that shift work
is strongly associated with an increased risk of developing type 2 diabetes.
One study included in this meta-analysis followed a large number of nurses for 20 years and kept track of their frequency of working night shifts. Having this kind of long-term research study adds a lot of strength to the findings since many of these metabolic impacts play out over time. And there are other large studies that back up this finding.
One study in the UK that looked at 272,214
participants also found that night shift workers were more likely to have type 2 diabetes than day workers.
chronic stress
activation of the sympathetic nervous system (stress) activates cortisol, adrenaline, noradrenaline
cortisol triggers gluconeogenesis, raises glucose
cells of muscles and liver become insulin resistant in times of stress
-muscle cells can overcome this through insulin independent glucose transport stimulated by exercise
modern stress is not accompanied by exercise to counteract increase in glucose
studies show:
-moderate to high stress levels associated with 2.3x increase in developing T2D
elevated cortisol associated with:
-increased glucose levels
-decreased insulin sensitivity
-development of chronic disease including T2D
hyperinsulinemia and stress response
high blood glucose and high insulin stimulate the sympathetic branch of ANS
excess simple carbohydrate ingestion = increased sympathetic nerve activity
changes linked to hyperinsulinemia
dose dependent relationship between insulin and noradrenaline in hyerinsulinemic state
not all carbohydrate consumption causes this reaction
physical activity
physical activity = muscles use glucose for energy = improved glucose regulation
muscle contractions during exercise help transport glucose to skeletal muscles through insulin independent activation of GLUT4, even with insulin resistance
sedentary lifestyle
physical inactivity linked to insulin resistance due to:
-gene expression
-reduced functioning of pancreatic beta cells
-reduced energy expenditure
-increased free radicals and oxidative stress
-increased low-
grade inflammation
-changes in sex steroid expression
-impairment in mitochondrial function.
endocrine disrupting chemicals
rise in use of toxic chemicals
contributes to blood sugar dysregulation
“diabetogens”
* Bisphenol A (BPA)
* Persistent Organic Pollutants (POPs)
* Phthalates
* Perfluorinated Chemicals (PFCs)
* Glyphosate
* Arsenic & Heavy Metals
* Air Pollution
chemicals of concern
Bisphenol A (BPA) - BPAs have been shown to alter insulin secretion, block insulin receptor sites.
POPs - Persistent Organic Pollutants (POPs) have also been shown to disrupt
blood glucose regulation48. Studies have found that individuals with the highest levels of POPs have a 12 times increased risk of developing Type 2 Diabetes.
Phthalates - Phthalates have been shown to disrupt blood glucose control and increase the risk of developing Type 2 Diabetes as well.
Perfluorinated Chemicals (PFCs) – Similar associations have been found with
higher levels of PFCs.
chemicals of concern
Glyphosate - Recent studies in mice found that animals exposed to glyphosate experienced alterations in their carbohydrate and glucose metabolizing enzymes and a rise in proinflammatory biomarkers. Researchers found that glyphosate decreased the expression of
insulin receptors and GLUT2 glucose transporter in cell membranes.
Arsenic: There is also a strong link between arsenic levels in the body and the risk of diabetes. This is thought to be due to arsenic’s ability to damage beta cells of the pancreas, which results in a decreased production of insulin.
Heavy Metals: Similarly, heavy metals like lead, mercury, and cadmium are environmental pollutants that can accumulate in the body and adversely affect
glucose metabolism by a variety of mechanisms.
Air Pollution: Exposure to air pollution, particularly fine particulate matter
(PM2.5) and traffic-related pollutants, has been linked to insulin resistance and an increased risk of Type 2 Diabetes.
thyroid conditions
association between hypothyroidism (low levels of thyroid hormones) and insulin resistance
thyroid hormones:
-help maintain viability and growth of beta cells (insulin)
-regulate insulin receptor expression and function
-influence lipid metabolism in the liver and peripheral tissues
-in hypothyroidism, circulating lipids increase and can interfere with insulin signaling = insulin resistance
leptin:
-tells the brain we have adequate energy stores and reduces the appetite
-hypothyroidism promotes leptin resistance
reduced thyroid hormone levels negatively affect mitochondrial activity = decreased cellular energy production and insulin resistance
genetics
over 120 genetic variants linked to T2D
peroxisome proliferator-activated receptor gamma (PPARg gene)
pro12la variant of PPARg influences T2D susceptibility
diets higher in PUFAs that SFAs = Pro 12Ala expression is protective against T2DM
diets higher in SFAs than PUFAs = variant not considered protective
diet + genes = epigenetics
over expression of certain genes in the liver can lead to abnormally high levels of gluconeogenesis
