Endocrine - Type 2 Diabetes Flashcards
What is the pathophysiology of type 2 diabetes?
Repeated exposure to glucose and insulin cause cells to become insulin resistant
More insulin is therefore needed to uptake glucose
Over time the pancreas cannot keep up with this demand and produces less insulin
This leads to insulin resistance and reduced insulin production causing chronic hyperglycaemia
What are the risk factors of diabetes type 2?
Non-modifiable
Age
Ethnicity (Black African or Caribbean and South Asian)
Family history
Modifiable
Obesity
Sedentary lifestyle
Diet
How does T2DM present?
Tiredness
Polyuria and polydipsia
Unintentional weight loss
Opportunistic infections
Slow wound healing
Glucosuria
Acanthosis nigricans
What is pre-diabetes?
Indication that patient is heading towards diabetes, reversible
HbA1c 42-47 mmol/mol
48mmol/mol or above indicates type 2 diabetes
Sample repeated after 1 month to confirm diagnosis
What causes acanthosis nigricans?
Insulin-mediated activation of IGF receptors on keratinocytes
Result of hyperinsulinaemia or insulin resistance
What are the HbA1c treatment targets?
48 mmol/mol- new type 2 diabetics
53 mmol/mol- patients that need more than 1 medication
HbA1c measured every 3-6 months until under control and stable
What is the medical management of T2DM?
First-line
Metformin
If the patient has existing CVD or HF add an SGLT-2 inhibitor (dapagliflozin)
Consider if QRISK over 10%
Second-line
Add one :
- Sulfonylurea
- Pioglitazone
- DPP-4 inhibitor
- SGLT-2 inhibitor
Third-line
- Triple therapy- add another second-line drug
- Insulin therapy
When triple therapy fails what can be done?
Switch one of the drugs to a GLP-1 mimetic
What is a potential risk of using SGLT-2 inhibitors?
DKA
Outline metformin
Biguanide
Increases insulin sensitivity and decreases glucose synthesis by liver
May cause GI symptoms
Lactic acidosis secondary to AKI
If GI symptoms try modified-release
Outline SGLT-2 inhibitors
Dapagliflozin
Blocks SG co-transporter in proximal tubule reducing glucose reabsorption
Lowers HbA1c
Lowers BP
Weight loss
Improves HF
Can cause hypoglycaemia
Reduce CVD risk
Dapagliflozin can be used for CKD and HF
- Increased frequency of UTI and genital thrush due to lots of sugar passing out
- DKA
- Fournier’s gangrene
Outline pioglitazone
Thiazolidinedione
Increases insulin sensitivity and decreases liver production of glucose
Does not cause hypoglycaemia
Side effects
- Weight gain
- HF
- Bone fractures
- Bladder cancer
Outline sulfonylureas
Gliclazide
Stimulate insulin release from pancreas
- Weight gain
- Hypoglycaemia
Outline DPP-4 inhibitors
Incretins are produced by GI tract to reduce blood sugar
- Increases insulin secretion
- Inhibits glucagon production
- Slows absorption
Main incretin is glucagon-like peptide-1 (GLP-1)
Incretins are inhibited by dipeptidyl peptidase-4 (DPP-4)
DPP-4 inhibitors prevent incretins from being inhibited
Sitagliptin
- Headaches
- Low risk of acute pancreatitis
Outline GLP-1 mimetics
Imitate action of glucagon-like peptide-1
Mimics incretins
Exenatide
Liraglutide (can be used for weight loss in non-diabetics)
Subcut injections
- Reduced appetite
- Weight loss
- GI symptoms
