Diabetes Mellitus Flashcards
What are insulins’ major actions?
Glucose:
decrease HGO
increase muscle uptake
Protein:
decrease proteolysis
Fat:
decrease lipolysis
decrease ketogenesis
In the fasted and fed state
What is the purpose of the GLUT-4 transporter and outline its structure
Transports glucose into muscle tissue
-One side is hydrophobic
-One side is hydrophilic
What is insulins’ effect regarding GLUT-4 and roughly how much does insulin increase its uptake?
GLUT-4 is recruited and enhanced with insulin
-Has 7x the glucose uptake with insulin
What are insulins’ effects on muscle cellular metabolism?
-Enhances conversion of glucogenic amino acids(AA’s) to proteins
-Inhibits conversion of protein to AA’s
-Inhibits mitochondrial metabolism
What are insulins’ effects on hepatocytes?
-Enhances conversion of glucogenic amino acids(AA’s) to proteins
-Inhibits gluconeogenesis
Outline the usage of bodily fuel stores in terms of time to depletion, mass and energy present
Carbs are depletable within 1 day
What are the effects of insulin on adipose cells
-Promotes vascular conversion of triglycerides into NEFAs and glycerol, allowing them to be uptaken into adipocytes
-Inhibits triglyceride breakdown into glycerol+NEFAs
-Promotes conversion of glycerol+NEFAs into triglycerides from bloodstream
After a 10hr fast, what proportion of hepatic glucose output(HGO) does hepatic gluconeogenesis make up?
10%
What fuel source does the brain utilise?
(Preferred: Glucose)
Ketone bodies
Cannot use fatty acids(NEFAs)
Outline the production of ketone bodies and insulins’ influence on the process
Fatty acyl CoA/Acetyl CoA->Acetoacetate->Acetone+ 3 OH-B->Ketone bodies
Insulin reduces the conversion of fatty acyl CoA to acetoacetate
How does insulin affect glucose transport in muscle cells?
Insulin increases the uptake of glucose into the cell
What is the insulin/glucagon ratio in the fasted state?
Low ratio
How do amino acid levels and NEFA levels change in the fasted state?
NEFA levels rise
Amino acid levels drop when in a prolonged fasted state
What occurs to:
proteolysis
lipolysis
HGO from glycogenolysis and gluconeogenesis
Ketogenesis
-in the fasted state
All increase
-Ketogenesis is only active when prolonged
What responses are produced by the muscles, liver and adipocytes when insulin levels decrease?
Muscles: Increase proteinolysis
HGO: Increases glucose output
Adipocytes: Lipolysis, producing NEFAs and glycerol
What is the insulin/glucagon ratio in the fed state and what occurs to HGO, gluconeogenesis, proteolysis, glycogen stores, protein synth and lipogenesis rates?
High insulin/glucagon ratio
Decreased HGO
Decreased gluconeogenesis
Decreased proteolysis
Increased glycogen stores
Increased protein synthesis
Increased lipogenesis
How do you diagnose diabetes M through fasting glucose, random glucose and HbA1c and what conditions need to be met for a diagnosis?
Fasting glucose>7mmol/L
Random glucose>11.1mmol/L
HbA1c>48mmol/L
A diagnosis requires 2 positive tests or 1 positive test + symptoms
What is administered in an oral glucose test and what does it measure?
Fasting glucose
75g glucose load
2-hour glucose
Describe the pathophysiology of T1DM
-Autoimmune condition
-Absolute insulin deficiency
-Ketoacidosis(pH <7.3, ketones +3, HCO3- <15, gluc >11, serious acute complication of T1DM)
Why does a lack of insulin produce ketoacidosis?
Insulin inhibits conversion of fatty acyl CoA to acetoacetate, leading to progression of the ketone body pathway
What would you find in the urine of a person with T1DM?
Ketones, reducing sugars
Give some symptoms of T1DM
Weight loss
Hyperglycaemia
Glycosuria with osmotic symptoms (polyuria, nocturia, polydipsia)
Ketones in blood and urine
What are 3 useful diagnostic tests for T1DM that don’t use sugar level testing
Antibodies: GAD, IA2
C-peptide
Presence of ketones
What occurs generally to muscles and the liver with insulin induced hypoglycaemia?
Liver doesn’t secrete enough glucose
Muscles uptake too much glucose
What occurs in the counterregulatory response to hypoglycaemia
Increased:
Glucagon
Catecholamines
Cortisol
Growth hormone
Leading to:
Increased HGO(gluconeogenesis, glycogenolysis)
Increased Lipolysis
What does poor hypoglycaemic counterregulatory response lead to?
Reduced ability to recognise symptoms of hypoglycaemia
Due to loss of counterregulatory response
Recurrent hypoglycaemia
(Body stops reacting to hypoglycaemia as it starts to think that it is normal, so the body enters a very dangerous positive feedback loop)
What defines severe hypoglycaemia?
Defined as an episode where a person needs third party assistance to treat
Give 5 neuroglycopenic symptoms of hypoglycaemia
Neuroglycopenic>CNS symptoms generated from direct lack of glucose
Slurred speech
Poor vision
Confusion
Seizures
Loss of consciousness
Give 4 ANS generated symptoms of hypoglycaemia
Sweating
Pallor
Palpitations
Shaking
PSPS
Describe the pathophysiology of T2DM
Insulin resistance resides in liver, muscle and adipose tissue
-Still enough insulin to inhibit ketogenesis and proteolysis
What 2 intracellular pathways are triggered by insulin action and outline the mechanism for insulin resistance?
MAPK pathway responsible for growth+proliferation
Pl3K-Akt pathway responsible for metabolic actions
(Pl3K-Akt pathway contains all of the resistance)
Body starts producing insulin++ due to lesser effect caused by resistance, the MAPK pathway isn’t resistant so T2DM causes excess proliferation of various tissue e.g vasculature
Give some of the symptoms of insulin resistance
Give some symptoms and risk factors of T2DM
Symptoms:
Hyperglycaemia
Overweight
Dyslipidaemia
Less osmotic symptoms
With complications
Insulin resistance
Later insulin deficiency
Risk factors:
Age
PCOS
Increased BMI
Family Hx
Ethnicity Inactivity
What kind of diet is recommended for a T2 diabetic?
Total calories control
Reduce calories as fat
Reduce calories as refined carbohydrate
Increase calories as complex carbohydrate
Increase soluble fibre
Decrease sodium
How is the treatment of T1 and T2 diabetes different?
When might a T2DM patient need insulin?
When hyperglycaemia is constant/symptoms are too severe/ B cells are diminished and can no longer produce insulin
