Diabetes Flashcards
What is the normal range for blood glucose?
3.5-7mmol/L
What are the typical symptoms of diabetes?
Thirst
Polyuria
Blurred vision
Polydipsia
Diabetic ketoacidosis
Hyperosmotic hyperglycaemic syndrome (HHS) - more commonly seen in type 2.
What are the complications of diabetes?
Cardiovascular death
IHD
Stroke
Angina
Renal failure
Visual loss
Neuropathy
Foot problems
Summary of the different types of diabetes:
Type 1 - Autoimmune B cell destruction
Type 2 - Disruption in insulin metabolism - resistance / deficiency.
Type 3 - Gestational DM, Steroid induced DM, Monogenic DM.
HHS stands for what and is usually seen in what diabetic patients?
Hyperosmotic hyperglycaemic syndrome - often seen in type 2 diabetic paitents.
Why does ketoacidosis occur?
- just read to refresh
The body senses there is not enough glucose in cells.
Lipolysis occurs breaking down free fatty acids which enter the krebs cycle.
Release of acetyl coa this is broken down into acetone (a ketone body).
Ketone bodies then disocciate to release H+.
= metabolic ketoacidosis
DKA symptoms and signs:
What is Kussmaul breathing?
Kussmaul breathing is a type of hyperventilation that is the lung’s emergency response to acidosis. Kussmaul breathing causes a labored, deeper breathing rate. It is most commonly associated with conditions that cause metabolic acidosis, particularly diabetes.
Pathophysiology of HHS
Signs of HHS:
How is HHS diagnosed?
- Hypovolaemia
- Marked hyperglycemia >30mmol of glucose without any ketones or acidosis.
- Hyperosmolarity (>320mosmo/kg)
What blood glucose level = hypoglycemia?
less than 4mmol (2.6-3.8mmol)
Signs and symptoms of hypoglycemia
Diabetic neuropathic ulcer characteristics
Ischemic ulcer characteristics
How are diabetic ulcers managed?
Debridement - turns a chronic non-healing ulcer into an acute healing one.
Pressure relief (sandals / insoles)
Dressings
Antibiotics if infected
What is Charcot foot?
(most often caused by diabetic neuropathy)
Charcot neuropathic osteoarthropathy (CN), commonly referred to as the Charcot foot, is a condition affecting the bones, joints, and soft tissues of the foot and ankle, characterized by inflammation in the earliest phase.
Charcot neuroarthropathy
Progressive pathological fracutres and joint dislocation / subluxation in a neuropathic foot.
How is Charcot foot managed?
Treated as an emergency - bed rest, and total contact casting.
How do Sulfonureas like glicazide work?
- when are they used?
Sulfonylureas are oral hypoglycaemic drugs used in the management of type 2 diabetes mellitus. They work by increasing pancreatic insulin secretion and hence are only effective if functional B-cells are present.
Side effects of Sulfonylureas
Hypoglycemic episodes
Weight gain
When are sulfonylureas contraindicated?
Pregnancy and breast feeding
A patient with type 2 diabetes mellitus is started on sitagliptin. What is the mechanism of action of sitagliptin?
Gliptins (DPP-4 inhibitors) reduce the peripheral breakdown of incretins such as GLP-1.
DKA pathophysiology
DKA is caused by uncontrolled lipolysis (not proteolysis) which results in an excess of free fatty acids that are ultimately converted to ketone bodies
Features of DKA
- abdominal pain
- polyuria, polydipsia, dehydration
- Kussmaul respiration (deep hyperventilation)
- Acetone-smelling breath (‘pear drops’ smell)
How is DKA managed?
Main principles of management
Fluid replacement
most patients with DKA are deplete around 5-8 litres
isotonic saline is used initially, even if the patient is severely acidotic
please see an example fluid regime below.
Insulin
An intravenous infusion should be started at 0.1 unit/kg/hour
Once blood glucose is < 15 mmol/l an infusion of 5% dextrose should be started
Correction of electrolyte disturbance
Serum potassium is often high on admission despite total body potassium being low
This often falls quickly following treatment with insulin resulting in hypokalaemia
Potassium may therefore need to be added to the replacement fluids.
If the rate of potassium infusion is greater than 20 mmol/hour then cardiac monitoring may be required.
Long-acting insulin should be continued, short-acting insulin should be stopped.
Complications of DKA
Complications may occur from DKA itself or the treatment:
- gastric stasis
- thromboembolism
- arrhythmias secondary to hyperkalaemia/iatrogenic hypokalaemia
- iatrogenic due to incorrect fluid therapy: cerebral oedema*, hypokalaemia, hypoglycaemia
- acute respiratory distress syndrome
- acute kidney injury
When administering insulin to DKA patient what electrolyte is it important to monitor and why?
Insulin normally drives potassium into cells. Without insulin potassium is not added to and stored in cells. Serum potassium can be high or normal as the kidneys continue to balance blood potassium with the potassium excreted in the urine, however total body potassium is low because no potassium is stored in the cells. When treatment with insulin starts patients can develop severe hypokalaemia (low serum potassium) very quickly and this can lead to fatal arrhythmias.
DKA Management
The most dangerous aspects of DKA are dehydration, potassium imbalance and acidosis. These are what will kill the patient. Therefore the priority is fluid resuscitation to correct the dehydration, electrolyte disturbance and acidosis. This is followed by an insulin infusion to get the cells to start taking up and using glucose and stop producing ketones.
Metformin
Increases insulin sensitivity
Decreases glucose production in the liver
Diagnosis of DKA
- Hyperglycaemia (i.e. blood glucose > 11 mmol/l)
- Ketosis (i.e. blood ketones > 3 mmol/l)
- Acidosis (i.e. pH < 7.3)
DKA Treatment mnemonic
FIG PICK
F – Fluids – IV fluid resuscitation with normal saline (e.g. 1 litre stat, then 4 litres with added potassium over the next 12 hours)
I – Insulin – Add an insulin infusion (e.g. Actrapid at 0.1 Unit/kg/hour)
G – Glucose – Closely monitor blood glucose and add a dextrose infusion if below a certain level (e.g. 14 mmol/l)
P – Potassium – Closely monitor serum potassium (e.g. 4 hourly) and correct as required
I – Infection – Treat underlying triggers such as infection
C – Chart fluid balance
K – Ketones – Monitor blood ketones (or bicarbonate if ketone monitoring is unavailable)
Long term type 1 diabetes management:
Subcutaneous insulin regimes
Monitoring dietary carbohydrate intake
Monitoring blood sugar levels on waking, at each meal and before bed
Monitoring for and managing complications, both short and long term
NICE Guideline 2015 HbA1c treatment targets:
Type 2 diabetics
Diabetics that use metformin and an additional drug
NICE Guideline 2015 recommend the following HbA1c treatment targets:
48 mmol/mol for new type 2 diabetics
53 mmol/mol for diabetics that have moved beyond metformin alone
First and second line management of diabetes:
First line: metformin titrated from initially 500mg once daily as tolerated.
Second line add: sulfonylurea, pioglitazone, DPP-4 inhibitor or SGLT-2 inhibitor. The decision should be based on individual factors and drug tolerance.
Third line management of type 2 diabetes:
Third line:
Triple therapy with metformin and two of the second line drugs combined, or;
Metformin plus insulin
In patients with cardiovascular disease what medication is recommended?
SGLT-2 inhibitors and GLP-1 mimetics (e.g. liraglutide) preferentially in patients with cardiovascular disease.
How does metformin work and what effect does it have on weight?
Metformin is a “biguanide”. It increases insulin sensitivity and decreases liver production of glucose. It is considered to be “weight neutral” and does not increase or decrease body weight.
Side effects of metformin
Diarrhoea and abdominal pain. This is dose dependent and reducing the dose often resolves the symptoms
Lactic acidosis
Pioglitazone
- class and how does it work?
Pioglitazone is a “thiazolidinedione”. It increases insulin sensitivity and decreases liver production of glucose.
Side effects of pioglitazone
- Weight gain
- Fluid retention
- Anaemia
- Heart failure
- Extended use may increase the risk of bladder cancer
- Does NOT typically cause hypoglycaemia
Most common sulfonylurea and how does it work?
The most common sulfonyluria is “gliclazide”. Sulfonylureas stimulate insulin release from the pancreas.
Side effect of sulfonylureas like glicazide?
Weight gain
Hypoglycaemia
Increased risk of cardiovascular disease and myocardial infarction when used as monotherapy
How do incretins work?
Incretins are hormones produced by the GI tract.
They are secreted in response to large meals and act to reduce blood sugar. They:
Increase insulin secretions
Inhibit glucagon production
Slow absorption by the GI tract
The main incretin is “glucagon-like peptide-1” (GLP-1). Incretins are inhibited by an enzyme called “dipeptidyl peptidase-4” (DPP-4).
The main incretin is “glucagon-like peptide-1” (GLP-1). Incretins are inhibited by an enzyme called “dipeptidyl peptidase-4” (DPP-4).
What class of drug sitagliptin and how does it work?
The most common DPP-4 inhibitor is sitagliptin. It inhibits the DPP-4 enzyme and therefore increases GLP-1 activity.
Side effects of DPP4 inhibitors like sitagliptin?
GI tract upset
Symptoms of upper respiratory tract infection
Pancreatitis
Exenatide
- what class of drug and how does it work?
These medications mimic the action of GLP-1. A common GLP-1 mimetic is “exenatide”. Exenatide is given as a subcutaneous injection either twice daily by the patient or once weekly in a modifiable-release form.
Another GLP-1 mimetic is liraglutide, which is given daily as a subcutaneous injection. They are sometimes used in combination with metformin and a sulfonylurea in overweight patients.
Side effects of GLP-1 mimetics like exenatide:
- GI tract upset
- Weight loss
- Dizziness
- Low risk of hypoglycaemia
How do SGLT-2 inhibitors work?
The SGLT-2 protein is responsible for reabsorbing glucose from the urine in to the blood in the proximal tubules of the kidneys. SGLT-2 inhibitors block the action of this protein and cause glucose to be excreted in the urine.
SGLT-2 inhibitors end with the suffix “-gliflozin”, such as empagliflozin, canagliflozin and dapagliflozin.
Side effects of SGLT-2 inhibitors:
- Glucoseuria (glucose in the urine)
- Increased rate of urinary tract infections
- Weight loss
- Diabetic ketoacidosis, notably with only moderately raised glucose. This is a rare complication
- Lower limb amputation appears to be more common in patients on canagliflozin. It is not clear if this applies to other SGLT-2 inhibitors
What diabetic treatment is contraindicated in a patient with heart failure?
Pioglitazone can cause fluid retention and is therefore contraindicated in patients with heart failure.
How many times a day should type 1 diabetics monitor their blood glucose?
In type 1 diabetics, recommend monitoring blood glucose at least 4 times a day, including before each meal and before bed.
A rare, but important, side effect of DPP4-inhibitors is what…?
A rare, but important, side effect of DPP4-inhibitors is pancreatitis
Metformin increases the risk of lactic acidosis - suspend during intercurrent illness eg. diarrhoea and vomiting
Metformin increases the risk of lactic acidosis - suspend during intercurrent illness eg. diarrhoea and vomiting
