Endocrine (Diabetes) Flashcards
T1DM pathophysiology
Autoimmune condition characterised by prolonged hyperglycaemia caused by destruction of Beta cells i the islets of Langerhans in the pancreas
- Beta cells produce insulin, therefore if they are destroyed blood glucose levels rise
RF for T1DM
- Family history
- Some environmental factors are thought to play a role (e.g. some viral infections)
presentation of T1DM
symptoms tend to start more acutely than type 2
- Polyuria – excessive thirst
- Polyuria – excessive passage of urine
- Weight loss
- Fatigue – often seen in children/young people
key acute complication of T1DM
DKA
Diabetic ketoacidosis (DKA) presentation
- Abdominal pain
- Vomiting
- Clinical features of dehydration
- Tachypnoea
- Altered consciousness or coma
T1DM investigations
- urine dipstic e.g. glucose, ketones
- blood tests suggesting raised blood glucose
- coeliac screening
Specific
- C-pepide levels
- Autoantibodies e.g. anti-GAD
blood glucose tests for T1DM
A helpful way to remember the thresholds for fasting and random blood glucose in diabetes is ‘7-11 fr (For Real)’ for Fasting blood glucose and Random respectively
Fasting blood glucose:
- ≥7.0 mmol/L
Random blood glucose:
- ≥11.1 mmol/ L – see Diagnosis section on diagnosing T1DM
HbA1c:
- ≥48 mmol/mol
- Not as useful as it reflects hyperglycaemia over the last 3 months and does not show quick fluctuations in blood glucose
fasting blood glucose
> 7.00 mmol/L
random blood glucose
> 11.1 mmol/L
HbA1C
> 48 mmol/mol
C-peptide in someone with T1DM
Low or undetectable
Pro-insulin is cleaved to form insulin and C-peptide.
main autoantibody for T1DM
Glutamic acid decarboxylase antibodies (anti-GAD): may be positive
World Health Organisation (WHO) criteria for T1DM
T1DM is diagnosed if:
SYMPTOMATIC +
one of the following on one occasion:
- Raised fasting glucose (≥7.0 mmol/L)
- Raised random glucose (≥11.1 mmol/L)
ASYMPTOMATIC but one of the above criteria has been demonstrated on two separate occasions.
T1DM monitoring
- HbA1c measured every 3-6 months - aim to be kept below 48mmol/mol
- Blood glucose should be self-monitored at least x4 a day including before each meal and before bed
Optimal blood glucose targets
- 5-7 mmol/L on waking
- 4-7 mmol/L before meals at other times of the day
Screening
- Screen for eye disease annually from 12 years of age
- Screen for diabetic nephropathy annually from 12 years of age
- Screen blood pressure annually from 12 years of age
Insulins can broadly be categorised based on their time-action profiles:
-
Rapid- and short-acting insulins: quick onset and short duration of action
* This is to mimic an ‘insulin spike’ that normally occurs in response to glucose absorbed from a meal or sugary drink -
Intermediate- and long-acting insulins: slow onset and long duration of action
* This is to mimic the effect of endogenous basal insulin (insulin that is released continuously throughout the day)
basal bolus regimes
One of the main advantages of a basal-bolus regimen is that it allows you to fairly closely match how your own body would release insulin if it was able to.
Basal
- Background insulin- keeps blood glucose levels at a consistent levels whilst fasting
- Given once a day - long acting or intermediate insulin
Bolus
- dose taken at meal times
- short acting or rapid acting insulin
Examples of long-acting basal insulin for people with diabetes include:
- glargine (Basaglar or Toujeo, which is ultra long-acting)
- detemir (Levemir)
- degludec (Tresiba}
Rapid-acting insulins include:
- aspart (Novolog)
- lispro (Humalog)
- glulisine (Apidra)
microvascular complications of T1DM
- Diabetic retinopathy – due to damage to small blood vessels in the kidney
- Diabetic retinopathy – due to damage to small blood vessels in the retina
- Diabetic neuropathy – due to direct damage due to hyperglycaemia and decreased blood flow due to damage to small blood vessels supplying the nerves.
diabetic neuropathy can lead to
- Painful diabetic neuropathy
- Diabetic foot disease
- Autonomic neuropathy – late-stage complication where there is autonomic nervous system dysfunction. This can lead to reduced hypoglycaemia awareness.
Macrovascular complications
Atherosclerosis and increased risk of cardiovascular diseases such as
* myocardial infarction
* stroke
* heart failure
* peripheral arterial disease
DKA is a characterised by a triad of
- Hyperglycaemia (i.e. blood glucose > 11 mmol/l)
- Ketosis (i.e. blood ketones > 3 mmol/l)
- Acidosis (i.e. pH < 7.3)- low bicarbonate
ketoacidosis is caused by
The lack of insulin in the body leads to the release of fatty acids from adipose tissue which are then metabolised into ketones, leading to ketosis.
- Ketones ordinarily act as a source of energy in states of energy deficiency (e.g. starvation), however, in DKA, they can lead to acidosis.
- The body initially resists the change in pH using the bicarbonate buffering system but becomes overwhelmed, leading to other compensatory mechanisms to combat the acidosis (e.g. hyperventilation to lower the blood CO2 levels, known as Kussmaul respiration if severe).
potasium imbalance in DKA
Insulin normally causes cells to take up potassium. Without insulin, potassium remains in the blood, leading to high serum potassium, but low total body potassium as none is stored in the cells. This is important because treatment with insulin can lead to hypokalaemia which carries complications such as arrhythmia.
Dehydration and DKA
Hyperglycaemia can lead to glucose being filtered out in the urine, taking water along with it via osmotic diuresis. This leads to polyuria, polydipsia, and dehydration.
Factors that may precipitate a DKA
often physical stresses:
- Infection
- Discontinuation of insulin
- Inadequate insulin treatment
- Stroke
- Myocardial infarction
features of DKA
Features may be:
- Abdominal pain – may be the presenting complaint
- Nausea and/or vomiting
- Altered consciousness
- Hyperventilation (Kussmal breathing- deep sighing breaths at a slow rate)
- Polyuria
- Polydipsia
- Dehydration
- Acetone-like breath smell:
- Similar in smell to pear drops or nail varnish remover
- Features of a precipitant (e.g. infection or discontinuation of insulin)
DD for DKA
Hyperosmolar hyperglycaemic state (HHS)
- Patients are generally older and have a history of type 2 diabetes
- The onset of symptoms is usually over days to weeks
- Focal neurological signs may be seen
- Ketones are normal, urinary ketones are normal/slightly raised
- On an arterial blood gas, the pH is usually >7.30
T2DM presentation
The presentation of T2DM tends to be milder and more subacute. T2DM is often incidentally picked up on routine tests. Features may be:
- Asymptomatic
- Polyuria
- Polydipsia
- Recurrent urinary tract infections
- Recurrent skin infections
- Candida infections
- Fatigue
- Acanthosis nigricans – a sign of insulin resistance: Velvety dark skin usually on the neck, underarms, or groin
management of T2DM in patients where Metformin is not contraindicated
First line
Metformin + check cardiovascular disease (CVD) status:
- If they have heart failure, established CVD, or are at high risk for CVD (QRISK >10%): add an SGLT-2 inhibitorafter the metformin has been established and titrated up
- If metformin is not tolerated, switch to a modified-release form
- If the patient develops heart failure, or CVD, or becomes at high risk for CVD at any point: add an SGLT-2 inhibitor regardless of HbA1c
Second line
Dual therapy – if the HbA1c has risen to 58 mmol/mol, then another drug is indicated, which may be one of the following:
- Metformin + DPP-4 inhibitor
- Metformin + pioglitazone
- Metformin + sulfonylurea
- Metformin + SGLT-2 inhibitor if a sulfonylurea is contraindicated/not tolerated, or the person is at risk of hypoglycaemia or its consequences
Third line:
Triple therapy – one of the following:
- Metformin + DPP-4 inhibitor + sulfonylurea
- Metformin + pioglitazone + sulfonylurea
- Metformin + pioglitazone or sulfonylurea + canagliflozin or empagliflozin (specific SGLT-2 inhibitors)
- Metformin + DPP-4 inhibitor + ertugliflozin (SGLT-2 inhibitor) if sulfonylurea or pioglitazone is inappropriate
- Start insulin-based treatment
which hypoglycaemic agents can cause hypoglycaemia
- Sulphonylures such as glicazide -> increased panceeatic insulin secretion
- Glitazones such as pioglitazone -> enhances insulin sensitivity and glucose utilisation
Biguanides
Metformin
- no hypoglycaemia risk
- suppresses appetides
- oral
MOA: reduces hepatic glucose output
