Diabetes Mellitus

Question 1

Where are GLUT4 normally found?

Answer 1

Myocytes and adipocytes

Question 2

Describe the structure and properties of GLUT4

Answer 2

Highly insulin responsive

Lies in vesicles

Recruited and enhanced by insulin

7 fold glucose uptake

Has outer hydrophobic chain and inner hydrophilic chains

Question 3

How does insulin affects gluconeogenesis in the fed state?

Answer 3

Inhibits gluconeogenesis

Inhibits break down of proteins to gluconeogenic amino acids

Question 4

What hormones are active in the starving state and what do they do

Answer 4

Cortisol- stimulates gluconeogenesis

Glucagon- stimulates gluconeogenesis and breaking down of proteins to gluconeogenic amino acids.

This all increase HEPATIC glucose output

Question 5

What are the 3 fuel stores and list them in order of mass and energy per kg. What is their respective time in order to deplete

Answer 5

Carbs- 16 HOURS

Protein- 15 days

Fats - 30-40 days

Question 6

What enzyme is responsible for breakdown of triglycerides in plasma so that they can enter adipocytes? What hormone stimulates this enzyme

Answer 6

Lipoprotein lipase

Breaks TG down into glycerol and NEFA

They enter adipocytes

Insulin stimulates the lipoprotein lipase

Question 7

Once glycerol and NEFA are in adipocytes; describe the role of insulin intracellularly

Answer 7

Stimulates uptake of glucose into cell which can be converted to NEFA

Stimulates lipogenesis in adipocyte to make Trig

Inhibits break down of Trig in adipocyte

Question 8

In adipocytes what describe the role of GH and cortisol intracellularly

Answer 8

Stimulate lipolysis

Question 9

What is the significance of the hepatic portal system?

Answer 9

Quick flow of blood from heart to gut and liver. Hence quicker response time

Question 10

When are glycogen storage used up?

Answer 10

10 hour fast

Question 11

What can the brain can or cannot metabolise?

Answer 11

CANNOT- NEFA (fats) Can- ketone bodies and glucose(preferred)

Question 12

What hormones affect formation of ketone bodies?

Answer 12

Insulin- inhibits formation of ketone bodies by inhibiting lipolysis

Glucagon- stimulate formation of ketone bodies

More NEFA uptake

Question 13

Describe how glycogen is formed and hormones that affect hepatic glycogenolysis?

Answer 13

Glucose taken up by cell and converted to glucose 6- phosphate

Then converted to glycogen

Insulin stimulates formation of glycogen

Glucagon stimulates glycogenolysis- which can lead to secretion of glucose from LIVER

Question 14

Describe what hormones affect muscle cell uptake of glucose

Answer 14

Insulin stimulate uptake

Glucagon and GH- inhibit uptake of glucose‘

Muscle cell DO NOT RELEASE glucose into bloodstream

Question 15

Describe what happens in fasting sate

Answer 15

LOW insulin: glucagon ratio

Increased hepatic glcuose output

Increased lipolysis; hence more ketone bodies

More proteinolysis- gluconeogenic amino acids

Question 16

Describe what happens in the fed state?

Answer 16

Stored insulin released; high insulin to glucagon ratio

NO hepatic glucose output

Increased protein SYNTHESIS

LIPOGENESIS

Glycogenesis

Question 17

What are the tests required to diagnose diabetes mellitus

Answer 17

Fasting glucose levels- more than 7mmol/L

HbA1c

Random glucose test- more than 11.1mmol/L

Oral glucose tolerance test: fasting then 75g glucose load with jelly babies. check glucose 2 hours later

Urine test- for ketone bodies; or blood for ketone bodies

Question 18

What is needed to confirm diagnosis of diabetes mellitus

Answer 18

A diagnosis requires 2 positive tests OR 1 positive test +osmotic symptoms

Question 19

Describe the pathophysiology of type 1 diabetes

Answer 19

Autoimmune condition.
Absolute insulin deficiency

So increased lipolysis, proteinolysis and hepatic glucose output and ketone bodies

Can lead to ketoacidosis

Question 20

What are the presentations of type 1 diabetes

Answer 20

Weight loss

Hyperglycaemia

Glycosuria, nocturia, polyuria, polydipsia

Ketones in blood and urine

Question 21

What are the useful diagnostic test to confirm type 1 diabetes ?

Answer 21

C-peptide; it should be lower. C peptide amount can be used to figure dosage of insulin required Autoantibodies

Presence of ketone bodies

Question 22

What is the problem of administering too much insulin. Explain why?

Answer 22

Will lead to hypoglycaemia

Less hepatic glucose output and MORE glucose enter into muscle cell

Question 23

What are the body’s counterregulatory response to hypoglycaemia? What will it lead to?

Answer 23

Increased glucagon, catechoalmines, cortisol, growth hormone

Lead to increased lipolysis and HGO due to increased glycogenolysis and gluconeogenesis

Question 24

Despite the body’s counter regulatory response to hypoglycaemia; why might insulin induced hypoglycaemia still present in those with Type 1 diabetes

Answer 24

Too much insulin to overpower counters

Impaired awareness of hypoglycaemia- the body can’t recognise it’s symptoms

Question 25

What are the autonomic symptoms of hypoglycaemia

Answer 25

Sweating Pallor Shaking Palpitations

Question 26

What are the Neuroglycopenic symptoms of hypoglycaemia?

Answer 26

Slurred speech Poor vision Confusion Seizures Loss of consciousness - ALL AFFECT BRAIN

Question 27

What is severe hypoglycaemia

Answer 27

When person needs 3rd party asssiatnce to treat the episodE

Question 28

Describe the pathophysiology in type 2 diabetes?

Answer 28

INSULIN resistance residing in LIVER, MUSCLE and adipose tissue

Question 29

Why doesn’t ketogenesis occur in type 2

Answer 29

There’s enough insulin to suppress ketogenesis and proteolysis

Question 30

What intermediate pathways are affected in type 2?

Answer 30

Glucose and fatty acids.

Question 31

What are the 2 pathways that occur when insulin binds to insulin receptor? What are their roles? Which one can be insulin resistant?

Answer 31

P13k-Akt pathway - metabolic actions MAPK pathway- growth and proliferation PI3k-Akt pathway can be insulin resistance ; lead to increased insulin secretion for it to work

Question 32

What can insulin resistance lead to?

Answer 32

* High Trig * Low HDL * Hypertension * Increased waist circumference- more than 102cm in men; due to increased deposits of fats * Increased fasting glucose * Increased adipokines

Question 33

What are the presentation of Type 2?

Answer 33

Hyperglycaemia Overweight- some people Abnormal lipids Less osmotic symptoms Insulin resistance - may lead to insulin deficiency

Question 34

What’s are the risk factors for type 2?

Answer 34

Age; Increased BMI Polycystic ovary syndrome Family History Ethnicity Inactivity

Question 35

What are the dietary requirements for people with type 2?

Answer 35

* Control total calories * Reduce calories as fat and refined carb * Increase calories as complex carb; to lower glycaemic index * Increase soluble fibre * Decrease sodium

Question 36

What are the management options for type 1

Answer 36

Exogenous insulin Self monitoring of glucose levels Structured education Technology- insulin pump

Question 37

What are the management options for type 2

Answer 37

Diet and exercise Oral medication: Metformin Structured education May need insulin later

Question 38

What are the complications if diabetes isn’t managed properly?

Answer 38

Retinopathy Neuropathy- lead to amputation Nephropathy CVD

Question 39

In fasting state after 10 hours what is the contribution of hepatic gluconeogenesis to overall HGO

Answer 39

25%

Question 40

In myocyte describe the roles of the following hormones: IGF-1, GH, cortisol

Answer 40

IGF1-1- stimulate protein synthesis GH- stimulate protein synthesis from gluconeogenic amino acid Cortisol; stimulate proteinolysis to form gluconeogenic amino acids

Question 41

Describe the role of insulin in myocyte

Answer 41

Inhibit proteinolysis Stimulate protein synthesis Inhibit oxidation of amino acids

Question 42

In type 1, explain why there’s osmotic symptoms

Answer 42

Renal threshold passed; more glucose in urine, water follow urine to create a lot of urine. Blood is still very concentrated; hyperglycaemia. Sends signal to brain to dilute blood hence makes you thirsty-polydipsia

Question 43

Is family history important in diagnosis type 1

Answer 43

Yes, type 1 is autoimmune disease; may have a genetic predisposition. Having an autoimmune disorder or gene increase change of developing another one

Question 44

What is diabetes incipitus? How can it be treated? What may be the cause?

Answer 44

Lack of vasopressin; too much urine Can be treated by given AVP or drink too much fluid May be caused by head trauma or autoimmunity

Question 45

Describe the whole process of how insulin and cortisol and GH affects adipocytes. Draw it

Answer 45

Question 46

Draw the axis of what different factors affects hepatic gluconeogenesis? What hormones are present in fed and starving state

Answer 46

Question 47

Draw the axis of how insulin and other hormones affects muscle cells

Answer 47