T2DM Flashcards
What is the pathophysiology of T2DM?
Insulin resistance leading to hyperinsulinaemia then beta cell impairment resulting in decreased insulin secretion and hyperglycaemia (Impaired insulin action + Deficient insulin secretion)
What are symptoms of T2DM?
- Polydipsia
- Polyuria
- Weight loss
- Blurry vision
- Urogenital infections
- Fatigue
What are 2 macrovascular complications of T2DM?
- Stroke
- IHD
What are 3 microvascular complications of T2DM?
- Retinopathy
- Neuropathy
- Nephropathy
What are the risk factors for T2DM?
- Inactivity
- Family history
- Metabolic syndrome
- PCOS
- Poor diet
What is metabolic syndrome?
Group of conditions that collectively increase risk of heart disease, stroke & T2DM:
- HTN
- DM
- Obesity
- Dyslipidaemia
What investigations are used for a patient with suspected T2DM?
- FBC, U&Es, Lipid profile
- Urine dipstick
- HbA1c
- Fasting plasma glucose
- Random plasma glucose (If symptomatic)
What are the diagnostic criteria categorised by WHO?
If the patient is symptomatic:
- Fasting glucose >= 7.0 mmol/l
- Random glucose >= 11.1 mmol/l (or after 75g oral glucose tolerance test)
-
HbA1c >= 6.5% (48 mmol/mol)
- Value of less than 6.5% does not exclude diabetes
If the patient is asymptomatic
Above criteria must be demonstrated on two separate occasions.
What can cause misleading HbA1c results
Increased red cell turnover
What is the HbA1c?
Amount of glucose covalently bonded to RBCs - Average blood glucose over last 2-3 months
When should HbA1c not be used?
- Under 18 years old
- Pregnancy
- End stage kidney disease
- HIV +ve
What is the target HbA1c for patient’s managed with lifestyle changes and a single drug?
48 mmol/L (6.5%)
What is the target HbA1c for patients managed with multiple drug therapy?
53 mmol/L (7%)
What is the NICE guidance of T2DM?
What is the mechanism of action of metformin?
- Increases insulin sensitivity
- Reduces hepatic gluconeogenesis
- Reduces CVS events and limits weight gain
What is the mechanism of action of sulfonylureas?
Stimulate beta cells to release insulin
What’s the mechanism of action of SGLT2 inhibitors (Gliflozins) ?
Selectively inhibits Sodium-Glucose Co-Transporter 2 in renal prox. tubule so glucose excreted in urine
What is the action of piglitazone?
Increases insulin sensitivity in muscle and adipose tissue & reduces hepatic glucose output by acting on PPARs
What is the action of DDP-4i (Gliptins) ?
- Inhibits DPP-4 (enzyme that destroys incretin), increasing incretin levels, stimulating increased GLP-1 secretion from intestinal L cells
- Action of GLP-1:
- Increases glucose uptake
- Increases insulin secretion
- Decreases glucose production
What are the contra-indications of metformin?
eGFR < 30
What are the contra-indications for piaglitazones?
- DKA
- HF
- Bladder cancer
- Haematuria
- Hepatic impairment
What advice on “Sick Day Rules” would you give to patients who are commencing treatment for diabetes mellitus?
- Increase frequency of blood glucose monitoring to four hourly or more frequently
- Encourage fluid intake aiming for at least 3 litres in 24hrs
- If unable to take struggling to eat may need sugary drinks to maintain carbohydrate intake
- It is useful to educate patients so that they have a box of ‘sick day supplies’ that they can access if they become unwell
- Access to a mobile phone has been shown to reduce progression of ketosis to diabetic ketoacidosis
What are 2 common side-effects of metformin?
- Gastrointestinal side-effects
- Lactic acidosis
What are 4 common side-effects of sulfonylureas?
- Hypoglycaemic episodes
- Increased appetite & weight gain
- Syndrome of inappropriate ADH secretion (SIADH)
- Liver dysfunction (cholestatic)
What are 4 common side-effects of glitazones?
- Weight gain
- Fluid retention (Worsening HF)
- Liver dysfunction
- Fractures
What is a common side effect of gliptins?
Pancreatitis
What are typical C-Peptide levels in T2DM?
How does this compare to C-peptide levels in T1DM?
Why?
Normal / High in T2DM
C-peptide levels are low in T1DM
Because pancreas not creating enough insulin precursor (which is broken down into C-peptide & insulin)
Which second intensification drug (sulfonylureas / gliptins / pioglitazone) is best to commence in a patient who is obese and why?
Gliptins/DPP-4 inhibitors (e.g. Sitagliptin) because they can induce weight loss.
The other two options (Sulfonylureas & Pioglitazone) can both cause weight gain.
What is the best choice for a second intensification drug in non-obese patients?
Sulfonylurea (e.g. gliclazide or glibenclamide) because most effective at reducing blood glucose (with risk of sever/prolonged hypoglycaemia)
Why are sulfonylureas not recommended for patient’s that are professional drivers?
Due to increased risk of severe/prolonged hypoglycaemia
What oral-hypoglycaemic is safe to use for pregnant/breastfeeding women with T2DM?
Metformin
What is the consequence of metformin causing increased risk of lactic acidosis?
Should be suspended when there is risk
eg. dehydration, sepsis, CT with contrast, renal failure, heart failure; particularly if the patient is frail or elderly.
What is the target BP for a patient with T2DM and no end-organ damage?
< 140/90 mmHg
What HbA1c result should make you consider adding a second intensification drug ?
> 58 mmol/L (7.5%)
