Diabetes Flashcards
What does insulin do?
Glyconeogenesis in liver
Enhances fat deposition within cell
Glucose incorporation into cell
What is Type 1 diabetes?
Autoimmune metabolic disorder. Everyone is insulin-dependent
Often diagnosed in childhood
Not associated with excess body weight
Often associated with higher than normal ketone levels at diagnosis
Treated with insulin injections or insulin pump
Cannot be controlled without taking insulin
What is Type 2 diabetes?
→ Insulin resistance
→ Hyperglycaemia (progressive) leading to polyuria or polydipsia
→ Weight loss and fatigue due to poor utilisation of glucose by cells
Why might Type 2 DM need insulin injections?
Due to low sensitivity to insulin (which increases with excess body weight) or due to beta cell failure (more insulin production leads to cell damage)
What is HbA1c?
Glycated haemoglobin which is the average plasma glucose concentration.
Gives an overall picture of average blood sugar level over a period of weeks/months.
42-48 : pre diabetic
Above 48 - diabetes
Why is testing HbA1c better than blood glucose level?
As RBCs survive for 8-12 weeks, HbA1c can reflect blood glucose levels over that duration.
This is different to blood glucose level which can be measured using fasting plasma glucose test but this gives an indication of current glucose levels only.
Diabetic target is 48mmol/mol (6.5%).
The most common causative agent of osteomyelitis?
Staph. aureus is the most common cause except in patients with sickle-cell anaemia where Salmonella species predominate.
How does ethanol lead to polyuria?
Ethanol reduces the calcium-dependent secretion of anti-diuretic hormone (ADH) by blocking channels in the neurohypophyseal nerve terminal.
What is hyperosmolar hyperglycaemic state (HHS)?
HHS is characterised by:
- ) Severe hyperglycaemia
- ) Hypovolaemia and renal failure
- ) Mild/absent ketonuria
Mortality of 50%
Seem more in T2DM, usually with an infecton and in elderly
What are the complications of HHS?
Rhabdomyolysis, venous thromboembolism, lactic acidosis, hypertriglyceridaemia, renal failure, stroke and cerebral oedema.
Biguanides:
o Metformin - best primary treatment for T2DM.
o It activates the enzyme AMP kinase, which is involved in the regulation of cellular energy metabolism
o Reduces the rate of gluconeogenesis, and hepatic glucose output and increases insulin sensitivity
o Common SE: anorexia, GI discomfort and diarrhoea.
Uncommon SE: pruritis, urticaria, b12 malabsorption, erythema
o Risk of accumulation (and lactic acidosis) if eGFR <30
Sulphonylurea:
o Act on the beta cells to promote insulin secretion (ineffective in patients without a functional beta cell mass)
o Cheap and very effective at first but their effect wears off over time as the beta-cell mass declines.
o Weight gain and hypoglycaemia (should be cautious to use in the elderly, pregnant and patients with liver or kidney disease)
o Need multiple daily dosing
Thiazolidinediones (glitazones):
o Pioglitazones (PPARα)
o Reduce insulin resistance by binding with transcription factor PPARγ. It is a receptor involved in lipid and glucose metabolism, insulin transduction and adipocyte differentiation. Increased expression of GLUT4 increasing cell glucose uptake.
o SE: weight gain, oedema, heart failure (esp with insulin), bone fractures, increased risk of bladder cancer
Dipeptidyl peptidase-4 (DPP-4) inhibitors
o Sitagliptin, saxagliptin - dose adjustment needed for renal impairment.
Linagliptin - no dose adjustment needed
o These enhance the incretin effect inactivating inhibition of GLP-1 and GIP –> increased insulin secretion and lower glucagon release
o Weight neutral, no hypoglycaemia, low potency
o Most effective in the early stages of T2DM, when insulin secretion is relatively preserved
o Main side effect is nausea
SGLT-2 inhibitors:
Examples: Empagliflozin, Canagliflozin, Dapagliflozin
o The sodium/glucose transporter 2 (located in the PCT) reabsorbs 90% glucose from the renal filtrate.
The drug increases renal excretion of glucose and calories in the urine = lowers blood glucose and facilitates weight loss.
o SE: a small increase in genital candidiasis and UTIs. Hypovolaemia, Fournier’s gangrene (penis gangrene). Don’t give to elderly
GLP1 agonists
Example: liraglutide
o This is an injection which is long-acting in its effects.
o 1. They increase the secretion of insulin 2. inhibit glucagon secretion 3. delay gastric emptying 4. suppress appetite
effects on appetite
o Long-acting, subcutaneous injection. SE: Risk of pancreatitis.
What is meant by latent
autoimmune diabetes in adults (LADA)
Slower progression of insulin deficiency therapy
Clinical clues are leaner build, rapid progression to insulin therapy, following an initial response to other
therapies, the presence of circulating islet autoantibodies.
What is diabetic kidney disease
DKD - macroalbuminuria, or microalbuminuria associated with retinopathy and/or >10
years’ duration of type 1 diabetes mellitus.
Leading cause of premature death in diabetics
Overdose of what drug will show elevated C-peptide and insulin?
Gliclazide overdose causes hyperinsulinemia and high C-peptide levels
What can artificially lower or increase HbA1c levels?
Sickle-cell anaemia, Haemoglobinopathies G6PD deficiency Splenectomy Iron-deficiency anaemia B12 deficiency Alcoholism CKD Children HIV Steroid use
Examples of rapid-acting analogue insulins
Novorapid (aspart)
Humalog (lispro)
Apidra
Lower risk of hypoglycaemia
What to check before starting patient
o It is important to warn the patient before starting them on metformin about the GI upset as it can be bad for 1-2 weeks but then go away.
o Renal function - avoid if eGFR is <30 (risk of accumulation and lactic acidosis)
How to diagnose DKA?
Ketonaemia > 3.0mmol/L or significant ketonuria (more than 2+ on standard urine sticks)
Blood glucose > 11.0mmol/L or known diabetes mellitus
Bicarbonate (HCO3-) < 15.0mmol/L and/or venous pH < 7.3
How to manage DKA
- Commence IV 0.9% sodium chloride solution
- Commence a Fixed Rate IV Insulin Infusion (FRIII) but only after fluid therapy has been commenced
- Continue normal LA insulin but stop SA insulin
How to treat patients with hypoglycaemia
Give 15-20g quick acting carbohydrate of the patient’s choice where possible. (for conscious patients)
Some examples are:
-5-7 Dextrosol® tablets
-1 bottle (60ml) Glucojuice®
-150-200ml pure fruit juice e.g. orange
-3-4 heaped teaspoons of sugar dissolved in water
Adults who are unconscious or having seizures or are very aggressive:
- If IV access available, give 75-100ml of 20% glucose over 15 minutes, (e.g. 300-400ml/hr).
- If no IV access is available then give 1mg Glucagon IM. (not gonna work for people with liver dysfunction)
How does intravenous insulin work in treating DKA?
Reduction in blood glucose and even more importantly suppression of lipolysis and resolution of ketonaemia
What to do if blood glucose in between 10-13mmol/L in patients with DKA?
Increase usual insulin by 10%
Check every 4 hours
If no improvement in 24h increase by another 10%
What to do if blood glucose in above 13 mmol/L?
Increase insulin by 10% and give quick acting insulin, repeat every 2-4 hours
Test for urine ketones
Try drink 2 litres a day of fluid
What are the main CVD complications of diabetes and how can the risk be reduced?
Atherosclerosis due to dyslipidaemia
Risk reduced by ace inhibitors and statins
