Introduction to Diabetes Flashcards
What can the actions of glucose be split into?
glucose
protein
fat
What action does insulin take on glucose?
Decrease HGO (hepatic glucose output)
Increase muscle uptake of glucose
What action does insulin take on protein?
decrease proteolysis
What action does insulin take on fat?
decrease lipolysis
decrease ketogenesis
In the fasted and fed state
What is GLUT4?
Common in myocytes (muscle) and adipocytes (fat)
Highly insulin-responsive
Lies in vesicles
Recruited and enhanced by insulin
7-fold increase glucose uptake
What does insulin do to AA?
Insulin stops oxidation of AA
Because it doesn’t need protein or AA as an alternative fuel source
Insulin promotes AA conversion to protein in fed state for storage
If there are any additional Aa lingering around then they leave the muscle cell and they are gluconeogenic (aka they can be taken up by the liver to be converted into glucose at a later stage= gluconeogenesis)
What is an example of a gluconeogenic amino acid?
Alanine
What are the effects of insulin on cell metabolism (myocyte)?
Inhibits respiration in mitochondria
Insulin, IGF-1, GH= promote AA-> protein
Insulin inhibits protein-> AA
What does cortisol promote in cell metabolism to do with AA?
promote protein to AA
Describe the process of gluconeogenesis.
How do AA enter the liver for gluconeogenesis?
pyruvate lactate
What promotes pyruvate lactate?
glucagon
In the liver what promotes and what inhibits gluconeogenesis?
promote=
glucagon
cortisol
inhibit=
insulin
In the liver what promotes which part of protein and AA conversion?
protein to AA= glucagon
AA to protein= insulin
What are our fuel stores?
carbs
protein
fat
What is the mass (kg), energy (Kj/kg), time of carb stores?
0.5kg
16 KJ/kg
16 hours (depletable within a day fast)
What is the mass (kg), energy (Kj/kg), time of protein stores?
8-9kg
17KJ/kg
15 days
What is the mass (kg), energy (Kj/kg), time of fat stores?
9-10kg
37KJ/kg
30-40 days
How much of our E store is protein?
20%
What breaks down triglycerides that would otherwise be unable to leave the circulation?
Lipoprotein lipase (LPL)
How do triglycerides leave and enter adipocytes?
NEFA= fatty acids (non-esterified)
What does the hepatoportal circulation allow?
Allows blood to to go to the digestive tract to pick up any nutrients which is then directly taken to the liver for processing
When insulin is released, it goes straight into the hepatic portal circulation
- that’s why insulin secretion in body acts very rapidly
Why do injections of insulin take longer than endogenous insulin?
with injections it takes longer because it has to go through adipose tissue and more before entering circulation
What happens to glycerol for gluconeogenesis?
Gly enters liver and turns in Gly-3P
Hepatic gluconeogenesis 25% HGO after 10 hour fast
What can the brain use for energy/ what are the cerebral energy requirements?
Glucose (preferred)
Ketones (emergency)
- the brain’s inability to use fatty acids as a fuel makes it unique among body tissues
Where are ketone bodies produced?
in the liver
What happens to ketone bodies, glucose and insulin during fasting?
ketone bodies increase
glucose and insulin decrease
What happens during type 1 diabetes to the number of ketone bodies, insulin and glucose?
glucose levels are high
insulin levels are low
ketone bodies is high
What promotes and what inhibits ketone body formation?
glucagon promotes
Insulin inhibits
How are ketone bodies formed in the liver?
Fatty acyl-CoA–>
Acetyl CoA-> acetoacetate-> acetone + 3 OH-B (Beta-hydroxybutyrate)–>
ketone bodies
What is hepatic glycogenolysis?
generation of glucose from stored glycogen in the liver
Describe the process of hepatic glycogenolysis.
What hormone(s) increase blood glucose?
growth hormone and glucagon
What happens once glucose enters a muscle cell?
Glucose can be taken up into muscle cells and can be stored as glycogen
But the muscle cells can’t release glucose out of the cells as they lack glucose-6-phosphatase
It is used for respiration
What is the glucose transporter to bring glucose into muscle cells?
GLUT4
What promotes and inhibits GLUT4?
insulin= promotes
Glucagon and GH= inhibit
Diagram for what happens to glucose inside a myocyte.
What happens during the fasted state?
Low insulin-to-glucagon ratio
[Glucose] 3.0-5.5mmol/l
Increased [NEFA]
Decreased [amino acid] when prolonged
Increased Proteolysis
Increased Lipolysis
Increased HGO from glycogen and gluconeogenesis
Muscle to use lipid
Brain to use glucose, later ketones
Increased Ketogenesis when prolonged
What is the body’s response to fasting?
Pancreas decreases insulin
Leading to…
Proteinolysis (forming AA) in muscles
Hepatic glucose output increases in liver
Lipolysis to form glycerol and NEFA in adipose cells
What happens during the fed state?
Stored insulin released then 2nd phase
High [insulin] to [glucagon] ratio
Stop HGO
↑ Glycogen
↓ gluconeogenesis
↑ protein synthesis
↓ proteolysis
↑ Lipogenesis
What are the tests for diabetes?
oral glucose tolerance test
fasting glucose
random glucose
HbA1c
A diagnosis requires 2 positive tests or 1 positive test and symptoms
What are the levels for…
oral glucose tolerance test
fasting glucose
random glucose
HbA1c
In a patient with diabetes?
Fasting glucose >7.0 mmol/L
Random glucose >11.1 mmol/L
Oral glucose tolerance test
Fasting glucose
75g glucose load
2-hour glucose
HbA1c (>48mmol/mol)
What is HbA1c?
average of what your glucose has been over the past 3 months
What are osmotic symptoms and which diabetes are they most likely linked to?
Typical symptoms such as thirst or polyuria are classed as ‘osmotic’ based but these are not always present. Atypical symptoms might include a fall, a change in vision, or a change in memory.
Type 1 diabetes
What is the pathophysiology of type 1 diabetes?
Autoimmune condition
- destruction of B cells
- leading to absolute insulin deficiency
No insulin means…
proteinlysis
increase HGO
lipolysis
What happens in diabetic ketoacidosis?
pH <7.3, ketones +3, HCO3- <15, gluc >11
Serious acute complication
What is the presentation of T1DM?
Weight loss
Hyperglycemia
Glycosuria with osmotic symptoms (polyuria, nocturia, polydipsia)
Ketones in blood and urine
What are useful diagnostic tests for T1DM?
Antibodies: GAD, IA2 (both are specific to T1DM)
C-peptide- gives indication if pancreas is still making insulin
Presence of ketones
What happens during insulin induced hypoglycaemia?
less glucose leaving liver
more glucose entering muscle
levels in blood drop significantly
What is impaired awareness of hypoglycaemia and how does it occur?
Reduced ability to recognise symptoms of hypoglycaemia
Due to loss of counterregulatory response
Recurrent hypoglycaemia
What are counterregulatory responses to hypoglycaemia?
What are the 2 types of signs and symptoms of hypoglycaemia?
autonomic and neuroglycopenic
What are autonomic signs of hypoglycaemia?
Sweating
Pallor
Palpitations
Shaking
What are neuroglycopenic signs and symptoms of hypoglycaemia?
Slurred speech
Poor vision
Confusion
Seizures
Loss of consciousness
What is severe hypoglycaemia?
Defined as an episode where a person needs third party assistance to treat
Why are there not extreme presentation in type 2 like there is in type 1?
There is enough insulin circulating around to suppress ketone production and breakdown of fat (so no extreme presentations)
Where does insulin resistance reside?
liver, muscle, adipose tissue
All metabolic sites and all arms of intermediary metabolism
Glucose
Fatty acids
In type 2 diabetes there is enough insulin the to suppress what?
ketogenesis
proteolysis
What are the possible pathways when insulin binds to a receptor?
MAPK pathway
- growth, proliferation
PI3K-Akt pathway
- metabolic actions
What pathway is involved in insulin resistance?
PI3k-Akt pathway
- metabolic actions
What is dyslipidemia and what does it cause?
Abnormal lipid levels in the blood
This causes your body to be in an inflammatory state
What are the symptoms of insulin resistance?
TG= triglycerides
HDL= high density lipoproteins
What are the presentations of T2DM?
Hyperglycaemia
Overweight
Dyslipidaemia
Less osmotic symptoms
With complications
Insulin resistance
Later insulin deficiency (destruction of B cells- so may need injections)
hat are risk factors of T2DM?
Age
PCOS
High BMI
Family Hx
Ethnicity
Inactivity
What are dietary recommendation for T2DM?
Healthy eating or diet
Total calories control
Reduce calories as fat
Reduce calories as refined carbohydrate
Increase calories as complex carbohydrate
Increase soluble fibre
Decrease sodium
What are reading recommendations for diabetes?
DAFNE course workbook
Then Meet DESMOND
What are some long term diabetes related complication that have to be monitored to prevent?
retinopathy
neuropathy
nephropathy
cardiovascular
How do you manage type 1 diabetes?
Exogenous insulin (basal-bolus regime)
Self-monitoring of glucose
Structured education
Technology
How do you manage type 2 diabetes?
Diet
Oral medication
Structured education
May need insulin later
