Type 2 Diabetes Mellitus Flashcards
Pathophysiology of type 2 diabetes mellitus
High insulin levels over a prolonged period of time leads to insulin resistance.
Beta cells progressively become impaired leading to decreased levels of insulin. This is a relative insulin deficiency.
Epidemiology of T2DM
- 3.5 million people with T2DM in the UK
- 90% of patients are adults
- 80% of total cases of diabetes
Risk factors for T2DM
- Age: 45-64 years old
- Family history: strong genetic predisposition
- Ethnicity
- Obesity
- Drugs: cortiocosteroids
- PCOS
Symptoms of T2DM
- Polyuria
- Polydipsia
- Polyphagia
- Weight loss
- Fatigue
Signs of T2DM
- Neuropathy
- Glove and stocking sensory loss
- Retinopathy
- Diabetic foot disease
- Peripheral vascular disease
- Calluses
- Tissue loss
- Acanthosis nigricans (area of hyperpigmentation in axilla or skin folds - occurs due to high circulating levels of insulin)
Primary investigations for T2DM
Asymptomatic: 2 separate positive investigations
Symptomatic: 1 positive investigation
- Random blood glucose: ≥ 11.1 mmol/L
- Fasting blood glucose: ≥7.0 mmol/L
- Oral glucose tolerance test: ≥ 11.1 mmol/L two hours after a 75g oral glucose load
- HbA1c: ≥ 48 mmol/mol suggests hyperglycaemia over 3 months
Investigations to consider:
- U&Es: screen for renal failure
- Urine albumin:creatinine ratio: screen for renal failure
- Fasting lipids: screen for dyslipidaemia
Normal results for:
Random glucose (mmol/L)
Fasting glucose (mmol/L)
OGTT (mmol/L)
HbA1c (mmol/mol)
- Random glucose < 11.1 mmol/L
- Fasting glucose < 6.1 mmol/L
- OGTT < 7.8 mmol/L
- HbA1c < 42 mmol/mol
Management of T2DM
- Lifestyle (Target HbA1c = 48)
Step up therapy if HbA1c >48
- Metformin (Target HbA1c = 48)
Step up therapy if HbA1c >58
- Dual therapy - add in:
- DPP4i
- Sulfonylurea
- Pioglitazone
- SGLT2i
- (Target HbA1c = 53)
Step up therapy if HbA1c > 58
- Insulin + metformin
Or
- Triple therapy
Step up if triple therapy is not effective and BMI >35
- Metformin + sulfonylurea + GLP-1 mimetic
Metformin is in which drug class?
Mechaism of action of metformin?
Biguanides
Reduces gluconeogenesis and increases insulin sensitvity
Side effects of metformin
- Nausea and vomiting
- GI discomfort
- AKI (should be avoided in patients with significant renal impairment)
- Lactic acidosis
Examples of sulfonylureas
Mechanism of action
Gliclazide + Glibenclamide
Inhibits ATP-K+ channel on beta cells causing depolarisation and insulin release
Sulfonylurea side effects
- Weight gain
- Hypoglycaemia
SGLT-2 inhibitor examples
Mechanism of action
Dapagliflozin + Empagliflozin
Inhibit SGLT-2 in the proximal tubule causing urinary glucose excretion
SGLT-2 side effects
Increases risk of UTI
Pioglitazone mechanism of action
Side effects
PPAR gamma agonist reduce peripheral insulin resistance
Can cause fluid retention (contraindicated in heart failure)
DDP-4 inhibitors examples
Mechanism of action
Linagliptin + Sitagliptin
Prevent degradation of incretins hence promoting insulin secretion
GLP-1 mimetics examples
Mechanism of action
Liraglutide + Exanetide
Incretin mimetic which stimulates insulin secretion
GLP-1 mimetics side effects
GI upset
Reduced appetite and weight loss
Monitoring in T2DM
- Glucose
- HbA1c: measured every 3-6 months with a target or ≤48 mmol/mol
- Self monitoring: only advised if on insulin
- Retinopathy
- Immediate ophthalmology referral upon diagnosis and annually thereafter
- Diabetic foot
- Should be assessed at least annually, refer urgently to foot protection service if at risk
- Diabetic nephropathy
- Annual measurement of eGFR and urinary albumin:creatinine ration
When would an urgent opthalmology referral be required?
- Acute reduction in acuity
- Pre-proliferation or proliferative retinopathy
- Diabetic maculopathy
Complications of T2DM
- Cardiovascular
- Ischaemic heart disease
- Heart failure
- PVD
- Neurological
- Stroke
- Carpal tunnel syndrome
- Neuropathy
- Endocrine
- HHS
- Renal
- Diabetic nephropathy and CKD
- Opthalology
- Diabetic retinopathy
- Macular degeneration
- Open-angle glaucoma
- Cataracts
