PBL 2: T2DM Flashcards
(55 cards)
1
Q
Define type 2 diabetes mellitus
A
- T2DM is a progressive disorder. Characterised initially by the diminished sensitivity of the metabolic tissue to insulin. The decrease in insulin sensitivity impairs glucose uptake into the cells, raising blood glucose levels (hyperglycaemia). In a compensatory effort, beta cells produce more insulin, resulting in a rise in plasma insulin levels, hyperinsulinemia. This cannot be sustained and eventually leads to a relative insulin deficiency. This reduces the amount of insulin produce and prevents the body from regulating blood glucose levels.
2
Q
The insulin resistance is aggrevated by 3 factors. What are they?
A
- Age
- Physical inactivity
- Obesity
3
Q
Describe the aetiology of Type 2 diabetes mellitus
A
- Often presents with a genetic predisposition
- Insulin resistance is aggravated by ageing, physical inactivity, and overweight
4
Q
What are the 4 major risk factors for type 2 diabetes mellitus?
A
- Obesity
- Age
- Ethnicity
- Family history
5
Q
Name some non-modifiable risk factors for type 2 diabetes mellitus?
A
- Older age- onset approx. 50 years old
- Ethnicity - Black, Chinese and South Asian are at a higher risk
- Family history
6
Q
Name some of the modifiable risk factors for type 2 diabetes mellitus
A
- Obesity!!!
- Sedentary lifestyles
- High carbohydrate diet
7
Q
Describe the clinical presentation of type 2 diabetes mellitus
A
- Presents with the classic triad of symptoms
- Polyuria
- Polydipsia
- Unexplained weight loss
- Symptoms are less likely to be noticeable than those with T1DM as it is a more gradual process.
- Other symptoms include:
- Fatigue
- Blurred vision
- Acanthosis nigricans (brown to black, poorly defined, velvety hyperpigmentation of the skin. It is usually found in body folds)
8
Q
What are the 4 investigations that can be done to establish a firm diagnosis of type 2 diabetes mellitus
A
o Fasting plasma glucose
- >6.9 mmol/L (>125 mg/dL)
o Random plasma glucose
- ≥11.1 mmol/L (≥200 mg/dL) + diabetes symptoms such as polyuria, polydipsia, fatigue, or weight loss
o 2-hour post-load glucose
- Glucose tolerance test
- ≥11.1 mmol/L (≥200 mg/dL)
o HbA1c
§ ≥48 mmol/mol (≥6.5%)
9
Q
Name some of the other metabolic syndrome conditions that increase the risk of type 2 diabetes mellitus
A
- Polycystic ovary syndrome
- Cardiovascular diseases such as hypertension
10
Q
What is the aim of type 2 diabetes mellitus treatment
A
Aims of T2DM treatment are to prevent diabetes-related complications
11
Q
Describe the lifestyle changes that is used in the treatment of type 2 diabetes mellitus
A
- T2DM can be effectively treated, at least in the early stages, with exercise, caloric restriction, and weight reduction
- Patient education about their condition and the lifestyle changes they need to make is essential. It is important to advise the patient that it is possible to cure type 2 diabetes.
- T2DM is reversible
12
Q
Describe the dietary modifications that is used in the treatment of type 2 diabetes mellitus
A
- Vegetables and oily fish
- Typical advice is low glycaemic, high fibre diet
- A low carbohydrate may in fact be more effective in treating and preventing diabetes but is not yet mainstream advice
13
Q
What is the first line medication used to treat type 2 diabetes mellitus
A
Metformin
14
Q
If metaformin alone is not working in treating the type 2 diabetes mellitus, what is the 2nd line treatment
A
Give metformin and add: sulfonylurea, pioglitazone, DPP-4 inhibitor or SGLT-2 inhibitor.
The decision should be based on individual factors and drug tolerance.
15
Q
What are the 3rd line treatments for type 2 diabetes mellitus
A
- Triple therapy with metformin and two of the second line drugs combined, or
- Injectable agent
16
Q
Name the second line drugs for treating type 2 diabetes mellitus
A
- Sulfonylurea
- Pioglitazone
- DPP-4 inhibitor
- SGLT-2 inhibitor.
17
Q
What injectable agents are used in the treatment of type 2 diabetes and how do we decide which to give
A
- BMI ≥30Kg/m2 = GLP-1 agonist
- BMI < 30 Kg/m2 = Basal insulin
18
Q
SIGN Guidelines suggest the use of ____ and _______ preferentially in type 2 diabete patients with cardiovascular disease.
A
A) SGLT-2 inhibitors
B) GLP-1 inhibitors
19
Q
Describe the mode of action for biguanide
A
- aka metformin
- Primary treatment for T2DM.
- It activates the enzyme adenosine monophosphate (AMP) kinase, which is involved in regulation of cellular energy metabolism, but its precise mechanism of action remains unclear.
- Its effect increases insulin sensitivity and decreases gluconeogenesis.
- It is considered to be “weight neutral” and does not increase or decrease body weight.
20
Q
What are the notable side effects of biguanide
A
- Diarrhoea and abdominal pain. This is dose dependent and reducing the dose often resolves the symptoms
- Lactic acidosis
- Does NOT typically cause hypoglycaemia
21
Q
Describe the mode of action for thiazolidinedione
A
- It increases insulin sensitivity and decreases liver production of glucose.
22
Q
Give an example of a biguanide
A
Metformin
23
Q
Give an example of a thiazolidinedione
A
Pioglitazone
24
Q
What are the notable side effects of thiazolidinedione
A
- Weight gain
- Fluid retention
- Anaemia
- Heart failure
- Extended use may increase the risk of bladder cancer
- Does NOT typically cause hypoglycaemia
25
Describe the mode of action for sulfonylurea
* Sulfonylureas stimulate insulin release from the pancreas.
26
Give an example of a sulfonylurea
Gliclazide
27
What are the notable side effects of sulfonylurea
* Weight gain
* Hypoglycaemia
* **Increased risk** of *cardiovascular disease* and *myocardial infarction* when used as monotherapy
28
What are the two intestinal peptide hormones that cause the incretin effect
* Glucose-dependent insulinotropic peptide (GIP)
* Glucagon-like peptide-1 (GLP-1)
29
Glucose-dependent insulinotropic peptide (GIP) causes \_\_\_% of the incretin effect.
Glucagon-like peptide-1 (GLP-1) causes \_\_\_%, of the incretin effect
GIP = **30%**
GLP-1 = **70%**
30
Both GIP and GLP-1 have _____ half-lives in the circulation, being degraded predominantly by the enzyme \_\_\_\_
A) Very short
B) Dipeptidyl peptidase-4 (DPP4)
31
Glucose-dependent insulinotropic peptide (GIP) is secreted by which cells and where?
K cells in the duodenum
32
Glucagon-like peptide-1 (GLP-1) is secreted by which cells and where?
L cells in the ileum
33
Glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotrophic peptide (GIP) are secreted in response to what stimuli?
In response to food
34
Define the incretin effect
Incretin effect is that insulin response to oral glucose is greater than the response to intravenous glucose.
This is because of the intestinal peptide hormones:GIP and GLP-1. They are produced in the small intestine in response to food. They have a potentiating effect on pancreatic secretion of insulin
35
What is the effect of glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1)?
Both have a potentiating effect on pancreatic secretion of insulin
36
Describe the mode of action for DPP-4 inhibitors
* It inhibits the **DPP-4 enzyme** and therefore increases **GLP-1** activity.
* GLP-1 is important in the incretin effect (increases the insulin response to oral glucose)
37
Give an example of a DPP-4 inhibitor
Sitagliptin
38
What are the notable side effects of DPP-4 inhibitor
* GI tract upset
* Symptoms of upper respiratory tract infection
* Pancreatitis
39
Describe the mode of action for GLP-1 agonist?
* These medications mimic the action of GLP-1.
* GLP-1 is important in the incretin effect (increases the insulin response to oral glucose)
40
Give an example of a GLP-1 agonist
Exenatide- subcutaneous injection either twice daily by the patient or once weekly in a modifiable-release form.
41
What are the notable side effects of GLP-1 agonist
* GI tract upset
* Weight loss
* Dizziness
* Low risk of hypoglycaemia
42
Describe the mode of action for SGLT-2 inhibitors
* The SGLT-2 protein is responsible for reabsorbing glucose from the urine in to the blood in the **proximal tubules** of the **kidneys**.
* SGLT-2 inhibitors block the action of this protein and cause glucose to be excreted in the urine.
43
Give an example of a SGLT-2 inhibitor
* SGLT-2 inhibitors end with the suffix “**-gliflozin**”, such as empagliflozin, canagliflozin and **dapagliflozin**.
44
What are the notable side effects of SGLT-2 inhibitors
* **Glucosuria** (glucose in the urine)
* Increased rate of urinary tract infections
* Weight loss
45
Connect the drug type to their effect
**Thiazolidinediones –** Increase insulin sensitivity.
**Metformin** – suppress liver glucose production.
**Sulfonylureas** – cause additional release of insulin by the beta cells.
46
Type 2 diabetes is far more common than type 1, accounting for about ____ percent of all cases of diabetes mellitus.
90 to 95 percent of all cases of diabetes mellitus.
47
Fill in the blanks
48
Describe the epidemiological trend that is occuring for type 2 diabetes mellitus
In recent years, there has been a steady increase in the number of younger individuals, some younger than 20 years old, with type 2 diabetes. This trend appears to be related mainly to the increasing prevalence of **obesity, the most important risk factor for type 2 diabetes.**
49
Which ethnicities are at a higher risk of type 2 diabetes mellitus
Black, Chinese, South Asian
50
Define dyslipidaemia
Characterised by elevated levels of small dense low-density lipoprotein (LDL) cholesterol and triglycerides, and a low level of high-density lipoprotein (HDL) cholesterol
51
Metabolic syndrome is characterised by what?
* Hyper-insulinaemia
* Low glucose tolerance
* Dyslipidaemia (high TG in the blood)
* Hypertension
* Obesity.
52
What does metabolic syndrome refer to
This refers to a cluster of biochemical and physiological abnormalities associated with the development of cardiovascular diseases and T2DM.
53
What are the clinical signs of metabolic syndrome
* Obesity, especially accumulation of abdominal fat
* Insulin resistance
* Fasting hyperglycaemia
* Hypertension
* Dyslipidaemia (characterised by elevated levels of small dense low-density lipoprotein (LDL) cholesterol and triglycerides, and a low level of high-density lipoprotein (HDL) cholesterol
* Other conditions such as non-alcoholic fatty liver disease and polycystic ovarian syndrome.
54
Fill in the blanks to compare T1 and T2 diabetes
55
What causes the cells to become insulin resistant in type 2 diabetes
The cause of T2DM is complex and includes many factors
Thought that multiple factors work together to cause the T2DM.
These factors include: genetics, obesity, hypertension, increasing age etc
