4.8: An introduction to diabetes mellitus (part 1 of 2) Flashcards
Insulin action on glucose (2)
Decreases hepatic glucose output
Increases muscle uptake of glucose
Insulin action on fats (2)
Decreased lipolysis
Decreased ketogenesis
What two tissues is GLUT-4 commonly found in
Myocytes and adipocytes
Do GLUT-4 transporter proteins responds to insulin?
Yes
How does insulin affect
Insulin effects on proteins
Decreases proteolysis
What effect does GH and IGF-1 have on protein synthesis in myocytes?
Stimulates it
What effect does cortisol have on proteolysis in myocytes?
Stimulates it
What is a gluconeogenic amino acid?
An amino acid that can be converted into glucose through gluconeogenesis
What hormone leads to an increase in uptake of gluconeogenic amino acids in the liver?
Glucagon
What role does glucagon have in the liver?
Stimulates proteolysis to produce more gluconeogenic amino acids (converted to glucose)
What effect does insulin have on the hepatic glucose output in the fed state?
Reduces hepatic glucose output as gluconeogenesis is inhibited, so less glucose synthesised
What does lipoprotein lipase break triglycerides down into and what hormone stimulates this process?
Glycerol and non-esterified fatty acids (NEFA)
Insulin
2 effects of insulin in adipocytes?
Increases uptake of glucose via GLUT-4
converts glycerol and NEFA into triglycerides- when required
Why does insulin use glucose instead of NEFA as a substrate for triglyceride re-synthesis
To reduce glucose levels
And Inhibit breakdown of triglycerides in adipocytes back into glycerol and NEFA
What effects do GH and cortisol have on triglycerides in adipocytes in the fasting state?
Stimulates break down of triglycerides into glycerol and NEFA
Used as an alternative energy source once in liver -lipolysis stimulation
In the fasting state what happens to glycerol taken up by liver?
Converted into glucose (gluconeogenesis)
Increasing hepatic glucose output
I’m the fed state what happens to glycerol taken up by liver?
Converted into triglycerides
What can the brain use as fuel?
Glucose
Ketone bodies
In the fed state, what does insulin do once NEFA is uptake by liver?
NEFA converted into Acyl-CoA
Insulin inhibits conversion of fatty Acyl-CoA into ketone bodies, preventing it from being used as an alternative metabolic substrate to glucose
In the fasting state, what does insulin do once NEFA is uptake by liver?
NEFA converted into fatty Acyl-CoA
Converted into ketone bodies
What does a high level of ketones and glucose indicate?
Issue with insulin secretion
In the fed state what happens to glucose in the liver?
Converted into glucose-6-P
Then converted to glycogen (stimulated by insulin)
In the fasting state what happens to glycogen in the liver?
Glycogen broken down (stimulated by glucagon) - glycogenolysis
In the fed state what happens to glucose in myocytes?
Glucose converted into glycogen and stored
Used when:
myocytes require energy
Aerobic respiration
What effect does glucagon and GH have on the GLUT-4 transporters in myocytes?
Inhibits uptake of glucose via GLUT-4 to allow more glucose to remain in circulation and increase the blood glucose levels
In the fasting state why is amino acid concentration increased initially and then decreased when prolonged?
Increased due to increased proteolysis and then decreased due to more gluconeogenesis to increase hepatic glucose output
What is the insulin spike after a meal called?
First phase insulin release
What 4 tests can be carried out to make a diagnosis of diabetes?
Fasting glucose > 7.0mmol/L
Random glucose > 11.1 mmol/L
Oral glucose tolerance test
HbA1c >48mmol/L
How many tests are required to diagnose diabetes?
2 positive tests
Or 1 positive test and symptoms
Desribe the pathophysiology of Type 1 Diabetes Mellitus (T1DM)
Autoimmune condition that eventually leads to a T-Cell mediated destruction of the insulin-producing beta cells in the pancreas, leading to absolute insulin deficiency
How does T1DM lead to osmotic diuresis?
Increased glucose in blood so more glucose in urine
Lowering water potential of urine, water enters urine via osmosis, leading to major water loss
How does diabetic ketoacidosis occur ?
Less insulin present to down-regulate the breakdown of triglycerides in adipocytes
So more triglycerides are broken down into NEFA and Glycerol
NEFA are then converted into ketone bodies in the liver (which would also normally be inhibited by insulin), leading to a build up of ketones
4 symptoms present in patients with T1DM
Weight loss
Hyperglycaemia
Glycosuria → polyuria, nocturia, polydipsia
Ketones in blood and urine
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3 diagnostic tests for T1DM over T2DM
Antibodies: GAD, IA2
C-Peptide (usually not present)
Presence of ketone bodies
What 4 hormones induce a counterregulatory response to hypoglycaemia?
Glucagon
Catecholamines
Cortisol
Growth hormone
What is the counterregulatory response to hypoglycaemia?
Increased HGO with glycogenolysis and gluconeogenesis
Increased lipolysis
4 autonomic signs and symptoms of hypoglycaemia
Sweating
Pallor
Palpitations
Shaking
5 neuroglycopenic symptoms of hypoglycaemia?
Slurred speech
Poor vision
Confusion
Seizures
Loss of consciousness
What is severe hypoglycaemia?
Episode where a person needs third party assistance for treatment
After insulin binds to its receptor, in which pathway does insulin resistance reside?
PI3K-Akt pathway which leads to metabolic actions
Which pathway is followed alternatively since insulin resistance prevents the other?
MARK Pathway, leading to growth and proliferation of structures such as arterioles → increasing blood pressure
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What effect does insulin resistance have on Triglyceride and HDL concentration?
High Triglyceride concentration in plasma as insulin function is lacking and so LPL cannot breakdown TG into Glycerol and NEFA
Low HDL concentration - overproduction of VLDL leading to increased TG plasma levels which results in lower levels of HDL
3 consequences of insulin resistance?
Hypertension
Weight gain
High fasting glucose (>6.0mmol/L)
6 signs and symptoms of T2DM
Hyperglycaemia
Overweight
Dyslipidaemia
Less osmotic symptoms
Insulin resistance
Later insulin deficiency
5 risk factors of T2DM
Age
High BMI
Ethnicity
Family History
Inactivity
5 dietary recommendations could be given to a patient with T2DM?
Reduce calories as fat or refined carbohydrate
Increase calories as complex carbohydrate
Increase soluble fibre
Decrease sodium
Total calories control
4 management strategies made for patients with T1DM
Exogenous insulin (basal-bolus regime) - 1 long acting insulin injection once or twice a day and then quick injections just before meals
Self-monitoring of glucose - fingerprick testing
Structured education
Technology
4 management strategies for patients with T2DM
Diet
Oral medication
Education
May need insulin later - if loss of B cell function later on in life
4 long term diabetes complications that can be avoided through certain management strategies
Retinopathy
Neuropathy
Nephropathy
Cardiovascular
