Intro To Doabetes

Question 1

GLUT 4

Answer 1

Found in myocytes and adipocytes
Respond to insulin
Recruited and enhanced by insulin

Question 2

How does insulin affect proteolysis and protein synthesis respectively in myocytes in the fed state?

Answer 2

Inhibits proteolysis as protein is not needed as a fuel source

Stimulates protein synthesis to use the proteins for storage

Question 3

What effect does GH and IGF-1 have on protein synthesis in myocytes

Answer 3

Stimulates it as it converts amino acids into protein for storage

Question 4

• What effect does cortisol have on proteolysis in myoctes?

Answer 4

Stimulates it

Question 5

What hormone leads to an increase in uptake of gluconeogenic amino acids in the liver?

Answer 5

Glucagon

Question 6

What is the effect of glucagon on the liver in the fasting state?

Answer 6

• Gluconeogenic amino acids released from myocytes enter liver which glucagon helps
• Glucagon stimulates proteolysis to produce more gluconeogenic amino acids
• Glucagon increases gluconeogenesis (to form glucose) to increase hepatic glucose output (HGO) → cortisol also does this

Question 7

What is the effect of insulin on the liver in the fed state?

Answer 7

• Insulin inhibits gluconeogenesis in liver to reduce hepatic glucose output
• Stimulates protein synthesis

Question 8

How long do carb, protein and fat stores in the body last?

Answer 8

• Carb- 16 hours → are depletable within a 1 day fast
• Protein- 15 days
• Fat- 30 to 40 days

Question 9

What does Lipoprotein Lipase break Triglycerides (in the blood stream) down into and what hormone is this process stimulated by?

Answer 9

Glycerol and non esteriged fatty acids
Stimulated by insulin

Question 10

How does insulin interact with adipocytes in a fed state? (2 things)

Answer 10

Increases uptake of glucose via GLUT-4

Converts Glycerol and NEFA into triglycerides again for later use when needed - lipogenesis

• Insulin also inhibits breakdown of triglycerides in adipocytes as you don’t need alternative energy source

Question 11

What happens to adipocytes in fasting state (recall the two hormones involved)?

Answer 11

• Blood glucose and insulin is low so GH and cortisol secretedThese stimulate breakdown of triglycerides into Glycerol and NEFA to be used as an alternative energy source once transported into the liver - stimulates lipolysis

Question 12

In the fasting state what happens to the glycerol taken up by the liver?

Answer 12

It is converted into glucose in process, gluconeogenesis

Increasing hepatic glucose output

-

Question 13

In the fed state what happens to the glycerol taken up by the liver

Answer 13

Converted into triglycerides

Question 14

What fuel can the brain use?

Answer 14

• Glucose- preferred energy source
• Ketone bodies
  Can’t use NEFA as a fuel

Question 15

• How are ketone bodies produced?
  -

Answer 15

• NEFA released from adipocytes are taken up by liver
• In fasting state, glucagon is released which promotes conversion of NEFA into ketone bodies to be used as alternative energy source

Question 16

In the fed state, what does insulin do once NEFA is uptaken by the liver?

Answer 16

NEFA converted into fatty Acyl-CoA

Insulin inhibits the conversion of Fatty Acyl-CoA into ketone bodies

This prevents it from being used as an alternative metabolic substrate to glucose

The opposite happens in the fasting state where ketone bodies are produced

Question 17

In the fed state what happens to glucose in the liver?

Answer 17

It is converted into Glucose-6-P

This is then converted into Glycogen (stimulated by insulin)

Question 18

In the fasting state what happens to glycogen in the liver?

Answer 18

is broken down into glucose-6-p which gets turned into glucose and outputted from liver (process stimulated by glucagon) - Glycogenolysis

Question 19

What does it mean if there is a high level of ketones and glucose?

Answer 19

There is an issue with insulin secretion

Question 20

In the fed state what happens to Glucose in myocytes?

Answer 20

It is converted into glycogen to be stored and used only when the myocyte needs energy

It is also used in aerobic respiration

Question 21

What effect does Glucagon and GH have on the GLUT-4 transporters in myocytes?

Answer 21

Inhibits uptake of glucose via GLUT-4 to allow more glucose to remain in circulation and increase the blood glucose levels

Question 22

In the fasting state why is amino acid concentration increased initially and then decreased when prolonged?

Answer 22

Increased due to increased proteolysis and then decreased due to more gluconeogenesis to increase hepatic glucose output

Question 23

What is the spike in insulin when you eat referred to as?

Answer 23

First Phase Insulin Release

Question 24

What overall happens in body in fasted state?

Answer 24

• Low insulin-to-glucagon ratio
• (normal glucose is maintained at 3-5.5 mmol/L)
• Increased NEFA from increased lipolysis
• Increased proteolysis so increased amino acids but they decrease when prolonged fast
• Increase in HGO from glycogen and gluconeogenesis
• Muscles use lipids and brain uses glucose and later ketones
• Increased ketogenesis when prolonged

Question 25

What overall happens in body in fed state?

Answer 25

• Stored insulin released in 1st phase then slow release in 2nd phase
• High insulin-to-glucagon ratio
• Stop HGO
• Increased glycogen storage, lipogenesis and protein synthesis
• Decrease gluconeogenesis and proteolysis

Question 26

Describe the pathophysiology of Type 1 Diabetes Mellitus (T1DM)

Answer 26

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

• Leads to protein lysis into AAs, increased HGO

Question 27

How does T1DM lead to osmotic diuresis?

Answer 27

Increased glucose in blood (hyperglycemia) so more glucose in urine

Lowering water potential of the urine, so water enters urine via osmosis, leading to a lot of water loss

Question 28

How does diabetic ketoacidosis occur? (explain the mechanism, involving one of the pancreatic hormones)

Answer 28

Less insulin is there 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

Question 29

What do patients with T1DM usually present with?

Answer 29

• Weight loss
• Hyperglycaemia
• Glycosuria (glucose in urine) with osmotic symptoms:
  
  • Polyurialots of urine made
  • Polydipsiafeeling very thirsty due to losing so much fluids
  • Nocturiapassing of urine in night
• Ketones in blood and urine

Question 30

• What (4) useful diagnostic tests help distinguish between t1 and t2?

Answer 30

• Antibodies: GAD, IA2
• Low c-peptide
• Presence of ketone bodies
• GAD (glutamic acid decarboxylase), IA2 (islet antigen 2)

Question 31

Which (4) hormones induce a counterregulatory response to hypoglycemias

Answer 31

Glucagon

Catecholamines

Cortisol

Growth Hormone

Question 32

• What is the counterregulatory response to hypoglycaemia?

Answer 32

Increased HGO with glycogenolysis and gluconeogenesis

Increased lipolysis

Question 33

Why is it important to avoid hypoglycaemia?

Answer 33

• Makes people feel awful and lethargic
• Recurrent episodes of hypoglycaemia can lead to impaired awareness of hypoglycaemia where our body gets used to being hypoglycaemic so we have a reduced ability to recognise symptoms until glucose is much lowe

Question 34

Signs of hypoglycemia

Answer 34

Shaking

Sweating

Pallor

Palpitations

Seizures

Slurred speech

Poor vision

Confusion

Loss of consciousness

Question 35

What is the management for t1dm like?

Answer 35

• Exogenous insulin (basal-bolus regime) → multiple daily injections (long acting injection once a day and short acting ones before you eat)
• Self-monitoring of glucose e.g. finger prick test
• Structured education
• Technology like insulin pumps and continuous glucose monitoring tech
• Monitoring and prevention of long term diabetes complications like retinopathy, neuropathy, nephropathy etc

Question 36

Type 2 diabetes

Answer 36

Insulin resistance in liver muscle and adipose tissue however there is enough insulin to suppress ketogenesis and proteolysis

Question 37

What tests can be carried out to make a diagnosis of Type 2 diabetes?

Answer 37

Fasting glucose > 7.0mmol/L

Random glucose > 11.1mmol/L

Oral glucose tolerance test

HbA1c (>48mmol/L) (haemoglobin becomes glycated due to persistent hyperglycaemia in T2DM)

-
Red two positive test or one positive test and symptoms

Question 38

How do T2DM patients present?

Answer 38

Insidious onset

Dyslipidaemia

Hyperglycaemia

Overweight

Less osmotic symptoms than t1

Insulin resistance

Later insulin deficiency

Question 39

• What effect does insulin resistance have on Triglyceride and HDL concentration?

Answer 39

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

Question 40

Type 2 diabetes treatment

Answer 40

• Total calories control
• Reduce calories as fat and refined carbs
• Increase calories as complex carb and soluble fibre
• Decrease sodium
• Oral medication
• Structured education
• May need insulin later if beta cells stop working
• Monitoring and prevention of long term complications

Question 41

What are some of the long-term diabetes complications that can be avoided through certain management strategies

Answer 41

Retinopathy (microvascular)

Neuropathy (microvascular)

Nephropathy (microvascular)

Cardiovascular (macrovascular)