4.8: An introduction to diabetes mellitus (part 1 of 2)

Question 1

Insulin action on glucose (2)

Answer 1

Decreases hepatic glucose output
Increases muscle uptake of glucose

Question 2

Insulin action on fats (2)

Answer 2

Decreased lipolysis
Decreased ketogenesis

Question 3

What two tissues is GLUT-4 commonly found in

Answer 3

Myocytes and adipocytes

Question 4

Do GLUT-4 transporter proteins responds to insulin?

Answer 4

Yes

Question 5

How does insulin affect

Question 6

Insulin effects on proteins

Answer 6

Decreases proteolysis

Question 7

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

Answer 7

Stimulates it

Question 8

What effect does cortisol have on proteolysis in myocytes?

Answer 8

Stimulates it

Question 9

What is a gluconeogenic amino acid?

Answer 9

An amino acid that can be converted into glucose through gluconeogenesis

Question 10

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

Answer 10

Glucagon

Question 11

What role does glucagon have in the liver?

Answer 11

Stimulates proteolysis to produce more gluconeogenic amino acids (converted to glucose)

Question 12

What effect does insulin have on the hepatic glucose output in the fed state?

Answer 12

Reduces hepatic glucose output as gluconeogenesis is inhibited, so less glucose synthesised

Question 13

What does lipoprotein lipase break triglycerides down into and what hormone stimulates this process?

Answer 13

Glycerol and non-esterified fatty acids (NEFA)
Insulin

Question 14

2 effects of insulin in adipocytes?

Answer 14

Increases uptake of glucose via GLUT-4

converts glycerol and NEFA into triglycerides- when required

Question 15

Why does insulin use glucose instead of NEFA as a substrate for triglyceride re-synthesis

Answer 15

To reduce glucose levels
And Inhibit breakdown of triglycerides in adipocytes back into glycerol and NEFA

Question 16

What effects do GH and cortisol have on triglycerides in adipocytes in the fasting state?

Answer 16

Stimulates break down of triglycerides into glycerol and NEFA
Used as an alternative energy source once in liver -lipolysis stimulation

Question 17

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

Answer 17

Converted into glucose (gluconeogenesis)
Increasing hepatic glucose output

Question 18

I’m the fed state what happens to glycerol taken up by liver?

Answer 18

Converted into triglycerides

Question 19

What can the brain use as fuel?

Answer 19

Glucose
Ketone bodies

Question 20

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

Answer 20

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

Question 21

In the fasting state, what does insulin do once NEFA is uptake by liver?

Answer 21

NEFA converted into fatty Acyl-CoA
Converted into ketone bodies

Question 22

What does a high level of ketones and glucose indicate?

Answer 22

Issue with insulin secretion

Question 23

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

Answer 23

Converted into glucose-6-P
Then converted to glycogen (stimulated by insulin)

Question 24

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

Answer 24

Glycogen broken down (stimulated by glucagon) - glycogenolysis

Question 25

In the fed state what happens to glucose in myocytes?

Answer 25

Glucose converted into glycogen and stored Used when: myocytes require energy Aerobic respiration

Question 26

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

Answer 26

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

Question 27

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

Answer 27

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

Question 28

What is the insulin spike after a meal called?

Answer 28

First phase insulin release

Question 29

What 4 tests can be carried out to make a diagnosis of diabetes?

Answer 29

Fasting glucose > 7.0mmol/L Random glucose > 11.1 mmol/L Oral glucose tolerance test HbA1c >48mmol/L

Question 30

How many tests are required to diagnose diabetes?

Answer 30

2 positive tests Or 1 positive test and symptoms

Question 31

Desribe the pathophysiology of Type 1 Diabetes Mellitus (T1DM)

Answer 31

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

Question 32

How does T1DM lead to osmotic diuresis?

Answer 32

Increased glucose in blood so more glucose in urine Lowering water potential of urine, water enters urine via osmosis, leading to major water loss

Question 33

How does diabetic ketoacidosis occur ?

Answer 33

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

Question 34

4 symptoms present in patients with T1DM

Answer 34

Weight loss Hyperglycaemia Glycosuria → polyuria, nocturia, polydipsia Ketones in blood and urine -

Question 35

3 diagnostic tests for T1DM over T2DM

Answer 35

Antibodies: GAD, IA2 C-Peptide (usually not present) Presence of ketone bodies

Question 36

What 4 hormones induce a counterregulatory response to hypoglycaemia?

Answer 36

Glucagon Catecholamines Cortisol Growth hormone

Question 37

What is the counterregulatory response to hypoglycaemia?

Answer 37

Increased HGO with glycogenolysis and gluconeogenesis Increased lipolysis

Question 38

4 autonomic signs and symptoms of hypoglycaemia

Answer 38

Sweating Pallor Palpitations Shaking

Question 39

5 neuroglycopenic symptoms of hypoglycaemia?

Answer 39

Slurred speech Poor vision Confusion Seizures Loss of consciousness

Question 40

What is severe hypoglycaemia?

Answer 40

Episode where a person needs third party assistance for treatment

Question 41

After insulin binds to its receptor, in which pathway does insulin resistance reside?

Answer 41

PI3K-Akt pathway which leads to metabolic actions

Question 42

Which pathway is followed alternatively since insulin resistance prevents the other?

Answer 42

MARK Pathway, leading to growth and proliferation of structures such as arterioles → increasing blood pressure -

Question 43

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

Answer 43

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 44

3 consequences of insulin resistance?

Answer 44

Hypertension Weight gain High fasting glucose (>6.0mmol/L)

Question 45

6 signs and symptoms of T2DM

Answer 45

Hyperglycaemia Overweight Dyslipidaemia Less osmotic symptoms Insulin resistance Later insulin deficiency

Question 46

5 risk factors of T2DM

Answer 46

Age High BMI Ethnicity Family History Inactivity

Question 47

5 dietary recommendations could be given to a patient with T2DM?

Answer 47

Reduce calories as fat or refined carbohydrate Increase calories as complex carbohydrate Increase soluble fibre Decrease sodium Total calories control

Question 48

4 management strategies made for patients with T1DM

Answer 48

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

Question 49

4 management strategies for patients with T2DM

Answer 49

Diet Oral medication Education May need insulin later - if loss of B cell function later on in life

Question 50

4 long term diabetes complications that can be avoided through certain management strategies

Answer 50

Retinopathy Neuropathy Nephropathy Cardiovascular