Type 2 Diabetes Flashcards
What is diabetes
It is a group of conditions, which are all characterised by an abnormally raised levels of blood glucose
What is the normal blood glucose concentration
4.4 - 6.1 mmol/L
What is the most common form of diabetes
T2DM
90% of cases
How would you describe T2DM
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
Which diabetic emergency can be a first presentation of T2DM
Hyperosmolar hyperglycaemic state (HHS)
Describe the pathogenesis of T2DM
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
What causes T2DM
Combination of genetic predisposition and environmental factors
Name some of the non-modifiable risk factors of T2DM
Older age
Ethnicity (Black, Chinese, South Asian)
Family history of diabetes i.e. the genetic predisposition
Polycystic ovary syndrome
Hypertension
Dyslipidaemia
Known cardiovascular disease
Name some of the modifiable risk factors of T2DM
Overweight/Obesity – main risk factor
Sedentary lifestyles
High carbohydrate (particularly refined carbohydrate) diet
Presence of pre-diabetes
What is the biggest risk factor for T2DM
Overweight/Obesity
T2DM commonly present with a triad of symptoms.
Name these symptoms
Polyuria
Polydipsia
Weight loss
Diabetes often present with a triad of symptoms: Polyuria, polydipsia and weight loss.
Symptoms are more noticeable in which diabetes
a) T1
b) T2
a) T1
Not T2 as it is a more gradual process.
What investigations can be used to diagnosis T2DM
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)
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?
One
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?
Two
What is the cut off for the diangosis of T2DM in fasting glucose test
Greater than or equal to 7 mmol/L
What is the cut off for the diagnosis of T2DM in random plasma glucose test
Greater than or equal to 11 mmol/L
HbA1c greater than what is diagnostic of T2DM
Greater than or equal to 48 mmol/L
Oral glucose tolerance test (OGTT) greater than what is diagnostic of T2DM
Greater than or equal to 11 mmol/L
What is the gold standard investigation for T2DM
HbA1c
What is HbA1c
Glycated haemoglobin
The average blood glucose concentration over a 3 month period i.e. average life span of an erythrocyte
Why does glycated haemoglobin levels increase with blood glucose levels (as evident on HbA1c)
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.
A fasting plasma glucose should be tested after a minimum of how much time fasting
Minimum of 8 hours fasting
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
a) Metformin
e) SGLT2 inhibitor
f) GLP-1 agonist
c) Thiazolidinedione - probable
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
b) Sulphonylurea
g) Basal insulin
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
b) Sulphonylurea
c) Thiazolidinedione
g) Basal insulin
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
a) Metformin
e) SGLT2 inhibitor
f) GLP-1 agonist
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
d) DPP-4 Inhibitor
What is the 1st line management option in T2DM
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.
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
3 months
What are the choices in the 1st line medical management of T2DM
Metformin or sulfonylurea if metformin is not tolerated.
Metformin:
a) CV benefit?
b) Hypoglycaemia risk?
c) Weight?
a) Yes is CV benefit
b) Low risk of hypoglycaemia
c) Weight loss
Sulphonylurea:
a) CV benefit?
b) Hypoglycaemia risk?
c) Weight?
a) No
b) High hypoglycaemic risk
c) Weight gain
What is the main adverse effect of metformin
GI upset
What is the main adverse effect of sulphonylurea
Risk of hypoglycaemia
What is the second line medical management of T2DM
1st therapy (Metformin OR Sulfonylurea)
AND
Sulfonylurea (if not 1st line) OR Pioglitazone OR DPP-4 inhibitor OR SGLT-2 inhibitor
What is the third line medical management of T2DM
Triple therapy with (metformin + 2x oral agents)
OR
Injectable agent
Which diabetic drug increases insulin sensitivity
Thiazolidinediones i.e. Piglitazone
Name the two injectible drugs that may be used in the treatment of T2DM
GLP-1 agonist
Basal insulin
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
BMI ≥30Kg/m2
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
BMI < 30 Kg/m2
Give an example of a Biguanide
Metformin
What drug class does Metformin belong to
Biguanide
What is the mechanism of action of Biguanide e.g. metformin
Increase the activity of AMP-dependent protein kinase (AMPK)
This inhibits hepatic gluconeogenesis (production of glucose from certain non-carbohydrate substrates)
Reduces insulin resistance
What is the main side effect of metformin
GI upset e.g. diarrhoea
In what patient groups is Biguanide e.g. metformin not recommended in
Not recommended in pregnancy and renal failure (eGFR <30 mls/min)
Give an example of a Sulphonylureas
Gliclazide
What is the mechanism of action of Sulphonylureas
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.)
Give an example of a Thiazolidinedione
Pioglitazone
What is the mechanism of action of Thiazolidinedione
Reduces peripheral insulin resistance, leading to a reduction of blood-glucose concentration.
Name some of the side effects of Thiazolidinedione
Bone fracture
Increased risk of infection
Numbness
Visual impairment
Weight gain
Fluid retention – oedema
Thiazolidinedione are excreted?
a) by the kidneys
b) by the liver
a) by the kidneys
Sulphonylureas are excreted?
a) by the kidneys
b) by the liver
a) by the kidneys
Biguanide are excreted?
a) by the kidneys
b) by the liver
a) by the kidneys
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
Glucagon-like peptide 1 (GLP-1)
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
Dipeptidyl peptidase-4 (DPP-4)
Give an example of a SGLT-2 Inhibitors
End with the suffix “-gliflozin” e.g. empagliflozin, canagliflozin and dapagliflozin
What is the mechanism of action of SGLT-2 Inhibitors
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.
Name some of the side effects of SGLT-2 inhibitors
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
Hyperosmolar hyperglycaemic state (HHS) can be a first presentation of what kind of diabetes
T2DM
Which glucose test is less accurate:
a) Random
b) Fasting
Random glucose test is less accurate
For that reason is not usually a good first choice for diagnosing diagnosis
What is the difference between the fasting glucose test and the random glucose test
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
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
2 hours
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?
Required where there is a diagnostic uncertainty
Required for diagnosis of gestational diabetes.
What investigation is used to monitor glycaemic control
HbA1c
