Diabetes Metabolism Flashcards
Define dietary intake
The food we consume for metabolism and energy production
What is blood glucose mainly influenced by?
Dietary intake
Why do glucose levels need to be maintained (2)
- Glucose is an important fuel substrate
- Homeostasis
How can blood glucose be measured? In what units do we measure this and what is the conversion?
- Glucometer
- mg/dL and mmol/L
What happens when a meal is digested and absorbed?
Glucose rises
Define pre- and post-prandial
Before and after a meal
Post-prandially, when does one’s BGpeak? What is the normal value associated, in mmol/L?
- 50-60mins
- 7mmol/L
When does one experience a decline in BG levels?
Roughly 2hrs, returns to pre-praandial levels
What factors affect the magnitude of the BG spike and the time this peak lasts for?
- The type of food consumed (GI, fat, etc.)
- Type/quality of carbohydrates (processed or whole?)
- Individual’s metabolism
What procedure can we perform to ascertain BG levels?
- Measure pre-prandial BG levels
- Dietary intake (post-prandial BG rise will be expected)
- Perform a post-prandial BG test every 15 mins for 2 hours or until pre-prandial BG levels are reached again
Define post-prandial glucose test
The amount of glucose in the blood following a meal
Fill in the missing words:
1, 2, and 3 have been shown to produce exaggerated post-prandial responses?
- Processed food
- Easily digestible food
- Sugary drinks
Which of these types of carbohydrates are healthiest in terms of BG levels?
- whole meal pasta (lowest peak at 30mins post-prandially; reading = 6.25mmol/L; preprandial levels are recovered after 3 hours)
- wheat bread (highest peak at 30 mins post-prandially; reading = 6.9mmol/L; preprandial levels take longer to return to, as after 3 hours the BG level dips below inital pre-prandial levels)
What is the pattern of glucose levels throughout the day, and night, for a healthy individual who consumes 3 meals throughout the day?
- Preprandial levels are measured (within normal range)
- After 1st meal: meal intake, excursion (spike) then comes down to pre-prandial levels
- After 2nd meal: meal intake, excursion (spike) then comes down to pre-prandial levels
- After final meal: meal intake, excursion (spike) then comes down to pre-prandial levels
- During rest/”fasted” state: the pre-prandial or homeostatic level of glucose is maintained until
the next morning when the fast is broken
What is the pattern of glucose levels throughout the day, and night, for a diabetic individual who consumes 3 meals throughout the day?
- Postprandial spikes occur to a larger degree and for a longer duration.
- Diabetic #1:
starts off just a little higher than the normal person but that the blood
glucose levels is maintained at a much higher level in the blood during the day. BG comes down post-prandially but never to the pre-prandial level; it’s maintained high and then it spikes even higher during the night it returns gradually down to pre-prandial levels but the time that it takes for this response is also increased - Diabetic #2:
Slightly worse off
Pre-prandial level starts at 8mmol/L and rises quite
rapidly and quite significantly after the first meal and then that is maintained throughout the day. - You can still see this cyclical nature of the spiking, but it doesn’t quite come down to pre-prandial levels or not at all so in this individual there is high level of glucose in the blood for much longer
during the day.
What is the physiological relevance of BG excusions/spikes?
May indicate underlying health conditions
What is the correlation between post-prandial blood glucose levels, and coronary lumen diameter?
- Individuals with healthy BG levels (+-4.8mmol/L) show an increase in coronary lumen diameter = Good measure of
the functionality of the coronary artery, indicating low incidence of atherosclerosis.
*Individuals with unhealthy BG levels (6.9mmol/L+) show a decrease in coronary lumen diameter = poor coronary artery function and high possibility of CHD
What is the relationship between post-prandial blood glucose levels and coronary artery health?
HIGHER increase in post-prandial glucose levels = GREATER risk in coronary artery disease
What is the correlation between postprandial glucose and oxidative stress?
Directly proportional; higher postprandial BG levels = higher levels of oxidative stress markers
With respect to diabetes, what triggers the production of reactive oxygen species?
Exaggerated glucose levels
Describe what’s happening in this graph.
Postprandial glucose
response measured = slightly
longer.
Glucose spike (orange) increases.
TAGS upregulated and even more upregulated after return to pre-prandial levels.
Describe what’s happening in this graph.
few markers measured but
take note of red line which is nitro tyrosine (marker of ox stress which is elevated with postprandial levels)
What happens when carbohydrates are consumed with healthy fats and proteins?
Gastric emptying occurs more slowly into the duodenum –> causing a slower absorption of glucose and thus lowering the spike.
What happens when you combine eating bread with vinegar?
Decreases BG and insulin spikes, as well as increases satiety
What happens when we compare resistant starch scones and normal scones?
- Participants consumed scones with resistant starch and wheat flour
- Resistant starch = lower peak postprandial response and returned to pre-prandial levels earlier
- Composition of dietary carbohydrate intake displayed
Other than improving our diet, how else can we modulate glucose levels?
Exercise (moderate)
Explain how exercise modulates BG levels
- Exercise may sensitise tissue
- reduction in plasma glucose levels with percentage of walking hours
- exercise may sensitise tissues (specifically skeletal muscles for glucose uptake and clearance from blood)
The degree of post-prandial glucose excursion (spike) depends on what?
Meal types/quality of carbohydrates (GI)
What are repetitive, large excursions linked with?
cardio-metabolic disease onset
What are possible mediators of the process of CHD development in someone with poor BG levels?
Systemic inflammation and oxidative stress
What are the 2 states of metabolism?
Fasted state (post-absorptive) and fed state (absorptive)
How long does the absorptive state last for?
Lasts up to 4 hours
What is the main fuel source in the absorptive state?
glucose
What metabolic process is involved in the absorptive state?
Anabolic = energy is stored
3 major macromolecules contribute to metabolism. Name them.
Glucose, fatty acids and amino acids
What is the aim of the post-absorptive state?
To replace fuels
What is the main source of fuel in the post-absorptive state?
Fatty acids (ketone bodies)
What type of energy process is involved in the post-absorptive state?
Catabolic = stored energy is broken down
What is the fate of dietary glucose?
- The liver acquires 30%
- The other organs acquire 70%
What is the fate of the majority of glucose in the body’s organs?
- Readily available
- Used in ATP production - Glycolysis and CAC
What is excess glucose stored as?
- Glycogen (liver and muscle)
- Fat (adipose tissue)
What is the fate of dietary amino acids in the liver and other cells?
- Liver = Used for synthesis of lipoproteins and plasma proteins
- Other cells = Used for synthesis of structural and functional proteins
What is the fate of amino acids, when consumed in high amount with little glucose, and a high amount with plenty glucose?
- Low glucose, high amino acids = Converted to pyruvate and used as alternative energy source
- High glucose, high amino acids = Excess AAs converted to fat
What is the role of amino acids in fat linkage?
- Some amino acids are deaminated so the
amine groups are cleaved off –> can form pyruvate - pyruvate is then one of the downstream steps of glycolysis and can enter the Krebs cycle –> converted into acetylcoA
- acetyl-coA is one of the central and key metabolites and can either in the citric
acid cycle (contribute to the production of ATP) or it can be converted or used as a substrate in the conversion
into fatty acids
Where does amino acid to fat take place?
Liver and adipose tissue
What happens to carbohydrates in the def state?
Carbohydrates: glucose feeds into metabolism
with FA and Amino acids used for energy (cellular
work)
What happens to fatty acids, glucose and amino acids after a meal?
- Fatty Acids = stored in fed state
- Glucose = stored as glycogen (liver and muscle)
- Excess glucose = stored in adipose tissue as FA
- Amino acids = contribute to anabolic formation of body protein but can also be used in interconversion reactions to form glucose (gluconeogenesis)
What is lipogenesis and lipolysis?
Lipogenesis: FFA/glucose to fat stores
Lypolysis: breakdown of fat stores into FFA
What is Glycogenesis, glycogenolysis and gluconeogenesis?
Glyogenesis: glucose to glycogen stores
Glycogenolysis: breakdown of glygoen to glucose
Gluconeogenesis: production of glucose from non-carbohydrate precursor (i.e amino acids)
What is glycolysis?
Breakdown of glucose into pyruvate for ATP production
What are possible sources of gluconeogenesis?
Glycerol (Lipids)
Amino acids (Protein)
How can triglycerides be made from glucose? Describe what is happening in this diagram.
- Glycerol can be made from glucose through GLYCOLYSIS
- Two-carbon acyl units from acetyl-CoA are linked together by fatty ascid synthetase to from FAs
- One glycerol + 3 FAs –> triglyceride
What are the consequences of the following metabolic processes?
What happens to glycogen in the liver during the fasted state?
- After +/- 4hrs, glycogen stores are liberated from liver (converted to glucose)
- Some glucose remains in liver to provide the mitochondria energy
- The majority of glucose enters the blood
- The brain relies on glucose
In the fasted state, what happens to the other metabolites (fats and proteins)?
Proteins: broken down into AAs –> gluconeogenesis occurs –> AAs = converted to pyruvate which is a TCA precursor–> new glucose is formed and BG levels are maintained
Fats: Much later into the fast, fat stores are liberated and from FFAs –> glycerol is liberated
What happens to fats and proteins as a fast progresses?
As fasting prevails, these finite sources of nutrients decrease until they are depleted
What happens after prolonged starvation?
Fatty acids are liberated from adipose tissue then sent to liver –> here, beta-oxidation takes place –> ketone bodies form
What is the fate of lactic acid in the muscles formed during anaerobic respiration?
Lactic acid is cleared from the muscles to the liver, and converted into glucose by the liver (gluconeogenesis)
What is the role of adipose tissue in the fasted state?
- Triglyceride stores are broken down in the adipose tissue
- FAs and glycerol = liberated
- FAs = stored in liver for production of ketone bodies
- Glycerol = converted to glucose and sent to the liver (gluconeogenesis)
What does FA acid breakdown in the liver result in?
Formation of ketone bodies via B-oxidation (used as alternative fuel source by brain especially)
Name 3 tests one can use to test BG levels
- Fasting blood glucose levels test (stop eating at 10pm)
- Glycosylated Hb test (HbA1c)
- Oral glucose tolerance test (OGTT)
In fasting blood glucose levels, what are considered healthy, pre-diabetic and diabetic BG levels (mmol/L)?
Healthy = < 5.6mmol/L
Pre-diabetic = 5.6-6.9mmol/L
Diabetic = >7.0mmol/L
What are healthy, pre-diabetic and diabetic levels in the HbA1c test (%)?
Healthy = < 5.7%
Pre-diabetic = 5.7-6.4%
Diabetic = >6.5%
% = mean of blood sugar levels over a few months
How does the HbA1c test work?
- Snapshot of circulating glucose levels from the past 2-3 months
- Glucose has the power to modify body proteins like Hb
- Glucose readily diffuses into red blood cells
- Glucose and glucose metabolites thus act directly with the proteins –> glycation occurs
- N-terminal valine residue (alpha chain) would be available for this irreversible reaction
- Glycation is proportional to glucose concentration (more glycation of Hb = more circulating BG)
- Able to predict average blood sugar level over 120 days (then they die)
What is the oral glucose tolerance test (OGTT)?
Direct measurement of post-prandial excursion –> gold standard for diabetes testing
What is the basis/procedure of OGTT (5 steps)?
- Fast overnight
- Before the test begins a sample of blood taken
- Consume liquid with fixed amount glucose (usually 75 grams)
- Blood taken every 30 to 60 mins after this
- Test can take up to 3 hours
What are healthy, pre-diabetic and diabetic ranges fro the OGTT?
Healthy = < 7.8mmol/L
Pre-diabetic/impaired glucose tolerance = 7.8-11.1mmol/L
Diabetic = >11.1 mmol/L
