Type 2 Diabetes

Question 1

What is diabetes

Answer 1

It is a group of conditions, which are all characterised by an abnormally raised levels of blood glucose

Question 2

What is the normal blood glucose concentration

Answer 2

4.4 - 6.1 mmol/L

Question 3

What is the most common form of diabetes

Answer 3

T2DM

90% of cases

Question 4

How would you describe T2DM

Answer 4

Characterised by a combination of reduced sensitivity to the action of insulin and inadequate production of insulin by the pancreatic beta cells to overcome the insulin resistance

Question 5

Which diabetic emergency can be a first presentation of T2DM

Answer 5

Hyperosmolar hyperglycaemic state (HHS)

Question 6

Describe the pathogenesis of T2DM

Answer 6

T2DM is a progressive disorder

Repeated exposure to glucose and insulin makes the cells in the body become resistant to the effects of the insulin

One of the insulin’s functions is to tell the body cells to take up glucose therefore the decrease in insulin sensitivity impairs glucose uptake into the cells, raising blood glucose levels (hyperglycaemia).

In a compensatory effort to deal with the hyperglycaemia, the pancreatic beta cells produce more insulin, resulting in a rise in plasma insulin levels, hyperinsulinemia.

The production of hyperinsulinemia cannot be sustained and over time, the pancreatic beta cells become fatigued and damaged and eventually leads to a relative insulin deficiency.

The result is insulin resistance by the body’s cell, relative insulin deficiency due to beta cell fatigue and damage, chronic hyperglycaemia

Question 7

What causes T2DM

Answer 7

Combination of genetic predisposition and environmental factors

Question 8

Name some of the non-modifiable risk factors of T2DM

Answer 8

Older age

Ethnicity (Black, Chinese, South Asian)

Family history of diabetes i.e. the genetic predisposition

Polycystic ovary syndrome

Hypertension

Dyslipidaemia

Known cardiovascular disease

Question 9

Name some of the modifiable risk factors of T2DM

Answer 9

Overweight/Obesity – main risk factor

Sedentary lifestyles

High carbohydrate (particularly refined carbohydrate) diet

Presence of pre-diabetes

Question 10

What is the biggest risk factor for T2DM

Answer 10

Overweight/Obesity

Question 11

T2DM commonly present with a triad of symptoms.

Name these symptoms

Answer 11

Polyuria

Polydipsia

Weight loss

Question 12

Diabetes often present with a triad of symptoms: Polyuria, polydipsia and weight loss.

Symptoms are more noticeable in which diabetes

a) T1
b) T2

Answer 12

a) T1

Not T2 as it is a more gradual process.

Question 13

What investigations can be used to diagnosis T2DM

Answer 13

Fasting Glucose >= 7 mmol/l

Random plasma Glucose >= 11 mmol/l

HbA1c >= 48 mmol/mol

OGTT 2 hour result >= 11 mmol/l (2 hours after 75g glucose)

Question 14

T2DM can be diagnosed using the following tests: Fasting glucose, random plasma glucose, HbA1c and oral glucose tolerance test (OGTT).

How many diagnostic tests are required to confirm diabetes in a symptomatic patient?

Answer 14

One

Question 15

T2DM can be diagnosed using the following tests: Fasting glucose, random plasma glucose, HbA1c and oral glucose tolerance test (OGTT).

How many diagnostic tests are rquired to confirm diabetes in a asymptomatic patient?

Answer 15

Two

Question 16

What is the cut off for the diangosis of T2DM in fasting glucose test

Answer 16

Greater than or equal to 7 mmol/L

Question 17

What is the cut off for the diagnosis of T2DM in random plasma glucose test

Answer 17

Greater than or equal to 11 mmol/L

Question 18

HbA1c greater than what is diagnostic of T2DM

Answer 18

Greater than or equal to 48 mmol/L

Question 19

Oral glucose tolerance test (OGTT) greater than what is diagnostic of T2DM

Answer 19

Greater than or equal to 11 mmol/L

Question 20

What is the gold standard investigation for T2DM

Answer 20

HbA1c

Question 21

What is HbA1c

Answer 21

Glycated haemoglobin

The average blood glucose concentration over a 3 month period i.e. average life span of an erythrocyte

Question 22

Why does glycated haemoglobin levels increase with blood glucose levels (as evident on HbA1c)

Answer 22

Glycated haemoglobin occurs due to non-enzymatic irreversible modification of the beta globin chain in haemoglobin. As blood glucose levels increase the amount of glycation of haemoglobin also increases.

Question 23

A fasting plasma glucose should be tested after a minimum of how much time fasting

Answer 23

Minimum of 8 hours fasting

Question 24

Which of the diabetic drugs is known to give CV benefit:

a) Metformin
b) Sulphonylurea
c) Thiazolidinedione
d) DPP-4 Inhibitor
e) SGLT2 inhibitor
f) GLP-1 agonist
g) Basal insulin

Answer 24

a) Metformin
e) SGLT2 inhibitor
f) GLP-1 agonist
c) Thiazolidinedione - probable

Question 25

Which of the diabetic drugs is known to have a high risk of hypoglycaemia: a) Metformin b) Sulphonylurea c) Thiazolidinedione d) DPP-4 Inhibitor e) SGLT2 inhibitor f) GLP-1 agonist g) Basal insulin

Answer 25

b) Sulphonylurea g) Basal insulin

Question 26

Which of the diabetic drugs is known to cause weight gain: a) Metformin b) Sulphonylurea c) Thiazolidinedione d) DPP-4 Inhibitor e) SGLT2 inhibitor f) GLP-1 agonist g) Basal insulin

Answer 26

b) Sulphonylurea c) Thiazolidinedione g) Basal insulin

Question 27

Which of the diabetic drugs is known to cause weight loss: a) Metformin b) Sulphonylurea c) Thiazolidinedione d) DPP-4 Inhibitor e) SGLT2 inhibitor f) GLP-1 agonist g) Basal insulin

Answer 27

a) Metformin e) SGLT2 inhibitor f) GLP-1 agonist

Question 28

Which of the diabetic drugs is known to cause weight neutral: a) Metformin b) Sulphonylurea c) Thiazolidinedione d) DPP-4 Inhibitor e) SGLT2 inhibitor f) GLP-1 agonist g) Basal insulin

Answer 28

d) DPP-4 Inhibitor

Question 29

What is the 1st line management option in T2DM

Answer 29

Diet and Lifestyle changes Dietary Modification: Typical advice is low glycaemic, high fibre diet. Less refined carbohydrate e.g. white bread. Optimise Other Risk Factors: Exercise and weight loss; Stop smoking; Optimise treatment for other illnesses e.g. hypertension.

Question 30

T2DM is intially managed with diet and lifestyle changes as it can be reversible. How long would the trial period be before thinking about adding in medication

Answer 30

3 months

Question 31

What are the choices in the 1st line medical management of T2DM

Answer 31

Metformin or sulfonylurea if metformin is not tolerated.

Question 32

Metformin: a) CV benefit? b) Hypoglycaemia risk? c) Weight?

Answer 32

a) Yes is CV benefit b) Low risk of hypoglycaemia c) Weight loss

Question 33

Sulphonylurea: a) CV benefit? b) Hypoglycaemia risk? c) Weight?

Answer 33

a) No b) High hypoglycaemic risk c) Weight gain

Question 34

What is the main adverse effect of metformin

Answer 34

GI upset

Question 35

What is the main adverse effect of sulphonylurea

Answer 35

Risk of hypoglycaemia

Question 36

What is the second line medical management of T2DM

Answer 36

1st therapy (Metformin OR Sulfonylurea) AND Sulfonylurea (if not 1st line) OR Pioglitazone OR DPP-4 inhibitor OR SGLT-2 inhibitor

Question 37

What is the third line medical management of T2DM

Answer 37

Triple therapy with (metformin + 2x oral agents) OR Injectable agent

Question 38

Which diabetic drug increases insulin sensitivity

Answer 38

Thiazolidinediones i.e. Piglitazone

Question 39

Name the two injectible drugs that may be used in the treatment of T2DM

Answer 39

GLP-1 agonist Basal insulin

Question 40

The choice of injectable agent as part of the third line management of T2DM depends on BMI. At what BMI would you use GLP-1 agonist as the first option

Answer 40

BMI ≥30Kg/m2

Question 41

The choice of injectable agent as part of the third line management of T2DM depends on BMI. At what BMI would you use basal insulin as the first option

Answer 41

BMI \< 30 Kg/m2

Question 42

Give an example of a Biguanide

Answer 42

Metformin

Question 43

What drug class does Metformin belong to

Answer 43

Biguanide

Question 44

What is the mechanism of action of Biguanide e.g. metformin

Answer 44

Increase the activity of AMP-dependent protein kinase (AMPK) This inhibits hepatic gluconeogenesis (production of glucose from certain non-carbohydrate substrates) Reduces insulin resistance

Question 45

What is the main side effect of metformin

Answer 45

GI upset e.g. diarrhoea

Question 46

In what patient groups is Biguanide e.g. metformin not recommended in

Answer 46

Not recommended in pregnancy and renal failure (eGFR \<30 mls/min)

Question 47

Give an example of a Sulphonylureas

Answer 47

Gliclazide

Question 48

What is the mechanism of action of Sulphonylureas

Answer 48

Stimulates B cells of the pancreas to produce more insulin Increase cellular glucose uptake and glycogenesis; reduces gluconeogenesis Glicazide is short acting (12 hours approx.)

Question 49

Give an example of a Thiazolidinedione

Answer 49

Pioglitazone

Question 50

What is the mechanism of action of Thiazolidinedione

Answer 50

Reduces peripheral insulin resistance, leading to a reduction of blood-glucose concentration.

Question 51

Name some of the side effects of Thiazolidinedione

Answer 51

Bone fracture Increased risk of infection Numbness Visual impairment Weight gain Fluid retention – oedema

Question 52

Thiazolidinedione are excreted? a) by the kidneys b) by the liver

Answer 52

a) by the kidneys

Question 53

Sulphonylureas are excreted? a) by the kidneys b) by the liver

Answer 53

a) by the kidneys

Question 54

Biguanide are excreted? a) by the kidneys b) by the liver

Answer 54

a) by the kidneys

Question 55

Incretins are hormones produced by the GI tract. They are secreted in response to large meals and act to reduce blood sugar. Name the main incretin in the body

Answer 55

Glucagon-like peptide 1 (GLP-1)

Question 56

Incretins are hormones produced by the GI tract. They are secreted in response to large meals and act to reduce blood sugar. Incretins are inhibited by what enzyme

Answer 56

Dipeptidyl peptidase-4 (DPP-4)

Question 57

Give an example of a SGLT-2 Inhibitors

Answer 57

End with the suffix “-gliflozin” e.g. empagliflozin, canagliflozin and dapagliflozin

Question 58

What is the mechanism of action of SGLT-2 Inhibitors

Answer 58

The SGLT-2 protein is responsible for reabsorbing glucose from the urine in to the blood in the proximaltubules of the kidneys. SGLT-2 inhibitors block the action of this protein and cause glucose to be excreted in the urine.

Question 59

Name some of the side effects of SGLT-2 inhibitors

Answer 59

Glucoseuria (glucose in the urine) Increased rate of urinary tract infections Weight loss Diabetic ketoacidosis, notably with only moderately raised glucose. This is a rare complication Lower limb amputation appears to be more common in patients on canagliflozin. It is not clear if this applies to other SGLT-2 inhibitors

Question 60

Hyperosmolar hyperglycaemic state (HHS) can be a first presentation of what kind of diabetes

Answer 60

T2DM

Question 61

Which glucose test is less accurate: a) Random b) Fasting

Answer 61

Random glucose test is less accurate For that reason is not usually a good first choice for diagnosing diagnosis

Question 62

What is the difference between the fasting glucose test and the random glucose test

Answer 62

Fasting glucose test involves measuring blood glucose concentration after a minimum of an 8-hour fast. High level suggests diabetes Random glucose test does not involve fasting. Useful for rapid assessment of blood glucose

Question 63

Oral Glucose Tolerance Test (OGTT) involves fasting then measuring blood glucose and then giving a glucose drink and waiting a period of time before measuring the blood glucose again. How long do you wait until you measure the blood glucose again

Answer 63

2 hours

Question 64

Oral glucose tolerance test is not done routinely now as its time consuming as it measures the ability of the body to deal with a glucose load over a two-hour period. When would it be used?

Answer 64

Required where there is a diagnostic uncertainty Required for diagnosis of gestational diabetes.

Question 65

What investigation is used to monitor glycaemic control

Answer 65

HbA1c