Chapter 6: Endocrine system Flashcards
What shoud all diabetic drivers carry in their car?
Glucose strips and fast-acting carbohydrate
Do you have to fast before a HbA1c test?
No
WHO: HbA1c below 42 mmol/mol (6.0%): Non-diabetic
HbA1c between 42 and 47 mmol/mol (6.0–6.4%): Impaired glucose regulation or Prediabetes
HbA1c of 48 mmol/mol (6.5%) or over: Type 2 diabetes
Is HbA1c used for monitoring glycaemic control in Type 1 diabetes, Type 2 diabetes, or both?
Both should not be used for diagnosis of Type 1
How often should HbA1c be measured in diabetes?
Every 3-6 months If type 2 and stable, can be every 6 months
What is the recommended HbA1c target in Type 1 diabetes?
48mmol/mol or lower
How often should blood glucose be measured in Type 1 diabetes?
At least 4 times a day
What are the blood glucose aims in Type 1 diabetes for:a) Wakingb) Before meals c) 90 minutes after eatingd) Driving
a) 5-7mmol/L on waking
b) 4-7mmol/L before meals
c) 5-9mmol/L at least 90 mins after eating
d) at least 5mmol/L when driving
What is a basal bolus insulin regimen?
One or more separate daily injections of intermediate-acting insulin or long-acting insulin analogue as the basal insulin; (mimics background insulin)
alongside multiple bolus injections of short-acting insulin before meals
What insulin regimen is first choice for Type 1 diabetics?
Basal bolus
1) Insulin detemir (Levemir) BD (has a plataeu effect over 24hrs hence BD) should be offered as the long insulin therapy
2) Insulin glargine (Lantus) OD if dosing issues
3) Insuline detemir (Levemir) OD
In a basal bolus regimen for Type 1 diabetes, what basal insulin would be first choice? What would be the second choice?
Insulin determir (Levemir) BD - can also be offered as once daily
Once daily insulin glargine (Lantus)
Are non-basal bolus regimens recommended in newly diagnosed Type 1 diabetics?
No Should only be considered after trying basal bolus regimen
In basal bolus regimen in Type 1 diabetes, what type of insulin is recommended for the bolus aspect?
Rapid acting insulin (LAG - Lispro - Humalog, Aspart - novorapid, Glulisine - apidra) (Rather than soluble human or animal insulin)
Continuous subcut insulin infusion therapy should only be offered to what group of people?
- Suffer from disabling hypoglycaemia- High HbA1c of 69 or above with multiple daily injection therapy
Patients’ awareness of hypoglycaemia should be assessed annually using what score tools?
Gold or Clarke score
What cardiac class of drug can blunt hypoglycaemia awareness?
Beta blockersWill reducing warning signs such as tremor
What is an impaired awareness of hypoglcyaemia?
Can occur when the ability to recognise usual symptoms of hypoglycaemia is lost, or when the symptoms are blunted or no longer present
What are the 3 types of insulin sources?
Human insulinHuman insulin analoguesAnimal insulin
Which area of the body has the fastest absorption rate for insulin?
Abdomen
What can occur if you repeatedly inject insulin into the same area without rotating?
LipohypertrophyCan cause erratic absorption of insulin
How much time before meals do you administer short acting soluble insulin?
15-30 minutes before
What is the most appropriate form of insulin to use in diabetic emergencies e.g. DKA
Soluble insulin IV
What are the 3 types of rapid acting insulin?
Insulin aspartInsulin glulisineInsulin lispro
How much time before meals do you administer rapid acting insulin?
Immediately before
What are the advantages of rapid acting insulin over short acting insulin?
NAME?
Can you think of their brand names?
Insulin Glulisine Apidra®
Insulin Aspart Novorapid®
Insulin Lispro Humalog®
That GAL is RAPID!
Insulin Aspart
Rapid-acting
Immediately before eating
(0- 15 mins before food)
~10 - 20 minutes
around 2 - 5 hours
300 units
3ml pens containing 100 units/ ml
Less at risk of hypoglyceamia as it is only in body for a few hours and is used with meals
Short acting insulin= Soluble insulin (S S)
Can get different types of soluble insulins:
Soluble human
Soluble bovine ('neutral') Beef
Soluble porcine ('neutral') Pig
Insulin soluble (human)
Short- acting
15 - 30 mins before food
Must eat food within 30 mins of injecting to avoid hypoglyceamia
They start working after 30 mins
Duration of action: 4 - 8 hours
Peak activity: 2 - 4 hours
Intermediate acting = Isophane insulin (i,i)
Human isophane insulin usually used
Isophane insulin is a suspension of Insulin with protamine: bovine porcine or human insulin in the form of a complex obtained by the addition of protamine
Usually found in biphasic preparations
Isophane insulins:
Insulatard®
Humulin I®
(all of the i's!)
They usually need to be injected twice daily, sometime once daily in eldery
No need to inject with meals
They have a peak action at 4 - 12 hour and last for around 21 hours
Insulin Detemir Levemir®
Insulin Glargine Lantus ®
Insulin Degludec Tresiba®
around 18 - 24 hours
42 hours: Degludec (tresiba)
Soluble insulin
These are basically pre-mixed preparations of a rapid or short acting insulin plus a intermediate acting insulin (either the protamine [longer chain version of the short/ rapid acting one] or isophane insulin).
They are to be injected twice daily, and are good for patients who don't like multiple injecting regimens ( also called basal bolus- where people have to inject short acting with meals plus a long acting insulin)
Disadvantages of these are that there may be less control as proportions are fixed- if unwell and need to boost their insulin they cannot use these and would need a rapid or short acting insulin for this.
Insulin aspart (rapid acting)
Insulin aspart protamine (long acting)
Together it becomes intermediate acting- injected twice daily
Cloudy
Need to be resuspended before use- tell patient this- by rolling in their hands (not shaking)
Novomix 30 (insulin aspart+ aspart protamine)
Humalog Mix 25 / Humalog Mix 50 (Insulin Lispro + lispro protamine)
Humulin M3 (soluble insulin + isophane insulin)
Insuman Comb 50 (soluble insulin + isophane insulin)
HypoKaleamia
Think about what each one contains: short or rapid acting?
The ones containing rapid acting (NovoMix 30, Humalog Mix) should be injected 0-15 mins before a meal
Containing short acting (Humulin M3, Insuman Comb) inject 15 - 30 mins before a meal
Protamine
These will now have a 28 day expiry, as not-in-use pens need to be in the fridge to be used by their original expiry date (i.e. now follow the same rules that In-use pens have)
Fasting= over 7 mmol/L
Two hour post food/ glucose: Over 11 mmol/L
HbA1c of over 48 mmol/mol
or 6.5%
- Children/ young adults
- Suspected Type 1 diabetes
- Symptoms less than 2 months
- Medication related glucose effects e.g. steroids, antipsychotics
- Pancreas damage
- Pregnancy
- Acutely unwell/ in hospital
Intermediate acting (Isophane)
Biphasic preparations- Novomix, Humulin M3, Humalog Mix, Insuman Comb
Within 2 hours of starting their journey
Every 2 hours whilst driving
If a hypo occurs: stop, pull over, get out of drivers seat, eat sugar, wait 45 mins after BG has returned to normal to continue driving
3 months
Within 2 hours of starting to drive
every 2 hours whilst driving
at least twice daily when not
Fat hypertrophy at injection site
Local reactions at injection site
Transient oedema
Just because the patient is ill and not eating does not mean they should stop injecting their insulin
ill/ infection= stress hormones/ steroids released
steroids increase blood glucose
stay well hydrated to avoid DKA
patient should monitor their BG and urine ketones more frequently and be prepared to inject accordingly
For all insulin preparations, except rapid- and short-acting insulin and insulin glargine (Lantus), the vial or pen should be gently rolled in the palms of the hands (or shaken gently) to resuspend the insulin.
Intermediate acting: Human isophane insulin
Onset of action of 10-20 mins
Peak acivity of 1-4 hours
It is the first insulin to be available in two different strengths:
100 units/ml
200 units/ml
Increase insulin secretion from the pancreas
Short acting:
Gliclazide
Glipizide
Tolbutamide
Longer acting:
Glimepramide
Glibenclamide (longest acting)
Glibencamide (longest acting)
Avoid use in the elderly
Hypoglyceamia can persist for many hours.
It must always be treated in hospital
NB: Hypoglyceamia with sulfonylureas is uncommon and usually indicates excessive dosage
After diet/ lifestyle, then metformin alone have been tried:
Can use a sulfonylurea instead if metformin Contra-indicated, patient is NOT overweight or rapid response is needed as glucose levels very high.
If metformin alone does not work, can then add in a sulfonylurea
Weight gain
GI disturbance: Diarrhoea, constipation, nausea, vomitting
Fever (usually in first 6- 8 weeks)
Jaundice (avoid in severe liver impairment)
It is a Biguanide:
Decreases gluconeogenesis (production of new glucose) and increases peripheral utilisation of glucose
Remember: metformin produce normoglyceamia rather than hypoglyceamia
NB: It does not increase insulin secretion like other oral antidiabetics, therefore it does not cause weight gain!
GI upset- take with food, use MR if intolerable
Weight loss
Taste disturbance
risk factors such as
renal dysfunction (as metformin accumulates),
liver disease,
heavy alcohol ingestion
IV contrast media- reduces renal function therefore lactic acidosis risk
Poor tissue perfusion/ poor renal function= risk of lactic acidosis
Vitamin B12
Can lead to vitamin B12 deficient aneamia: symptoms= increased tirednes, weakness, mouth ulcers, pins and needles
In severe renal impairment
eGFR falls below 30 ml/min/ 1.73m2
In moderate impairment (eGFR under 45) a dose reduction is needed
2g a day
Alpha glucosidase inhibitor- (remember Alpha= Acarb) this enzyme breaks down starch and disaccharides to glucose, so Acarbose stops this, thereby delaying the digestion and absorption of starch and sucrose- small but significant effect in loweing blood glucose.
Acarbose= Starchy effects (potatoes!)
FLATULENCE- advise this will decrease with time
Diarrhoea/ Soft stools (as poo becomes sugary due to limited glucose absorption)
Other GI effects
Chew with first moutful of food or swallow with a little liquid immediately before food.
Interaction:
Renal function deteriorates rapidly
can then increase risk of Lactic acidosis
Sitagliptin
Vildagliptin
Saxagliptin
Inhibit an enzyme called Dipeptidylpeptidase-4
This enzyme breaks down incretins, incretins trigger insulin secretion and lower glucagon secretion, therefore they are good at helping control glucose, so by inhibiting the enzyme that breaks them down, gliptins increase incretin levels.
Gliptins.. incretins... gliptins.... incretins!
Upper respiratory tract infections
Gatro-intestinal upset
Peripheral oedema
Pancreatitis
Trigger insulin release so some weight gain?
There is less risk of Hypoglyceamia with the gliptins!
Vildagliptin
Report symptoms of liver disease: nausea, vomitting, abdominal pain, fatigue, dark urine
What are the symptoms of this?
Dipeptidylpeptidase-4 inhibitors (gliptins- sitagliptin, Linagliptin etc)
Glucagon-like peptide-1 receptor agonists (Exenatide, Liraglutide, Lixisenatide)
Exanatide especially can cause SEVERE PANCREATITIS
Symtpoms: Persistent and severe abdominal pain
Nausea and vomitting
Reduces peripheral insulin resistance
Pioglitazone
Incidence of HF increased when pioglitazone is combined with insulin
Also small risk of BLADDER cancer
Signs of bladder cancer: blood in urine, pain on urination, urinary urgency
Yes- alot of them cause a headache, particularly pioglitazone and the gliptins
Can you name them?When should they be taken?
Nateglinide
Repaglinide
Stimulate insulin secretion
Take 30 minutes before meals
Pioglitazone
The Gliptins- linagliptin, sitagliptin, vildagliptin
Glucagon-like peptide-1 receptor agonists
Examples:
Exenatide
Liraglutide
Lixisenatide
These are given by SUBCUTANEOUS INJECTION- not oral
These work by binding to the GLP-1 receptor causing:
-> Increase in insulin secretion
-> suppression of glucagon secretion (glucagon gets converted in glucose usually)
-> Slow gastric emptying
If given with sulfonylureas or insulin, their dose may need to be reduced as increased risk of hypoglyceamia!
Exenatide (GLP-1 agonist)
These are symptoms of pancreatitis- exanatide can cause severe pancreatitis- discontinue permanently
Miss that dose out and just continue with the next scheduled dose.
Usual dose is to be injected 1 hour before 2 main meals a day that are at least 6 hours apart
Do not administer the dose after a meal
Some oral med's need to be given 1 hour before or 4 hours after this drug
Sodium Glucose Co-transporter 2 inhibitors
Gliflozins
Examples:
Canagliflozin
Dapagliflozin
Empagliflozin
(DECeeeee!)
The sodium glucose transporter is found in the kidneys: by inhibiting this they stop glucose be re-absorbed in the renal tubule and therefore more glucose is excreted
What concomitant drugs/ conditions could increase the risk of this?
Volume depletion !
Think floz= flow
Think: these are inhibiting glucose rer-absorption into the renal tubules. Water usually follows the glucose- less reabsorbed= less water follows= more weeing etc
Patients need to report signs of this:
Dizzy, postural hypotension
Side effects:
Thirst
Constipation (less water in stools)
UTI's
Increased risk: things that also decrease fluid volume
Antihypertensives
Elderly
diarrhoea
0.5 percentage points
The SGLT2 inhibitors:
Dapagliflozin
Canagliflozin
Empagliflozin
Poylcystic ovary syndrome
It helps to normalise the menstrual cycle an ovulation
Symptoms of bladder cancer:
heamatruria
dysuria
urinary urgency
Also signs of liver toxicity: blood in urine, severe stomach pain/ nausea and vomiting
WITH MEALS
Reduce the dose- sulfonylureas metabolised hepatically- they will accumulate and cause hypoglyceamia
Chewed with first mouthful of food/ with a bit of water immediately before food
Diazoxide
(remember diuretics can cause hyperglyceamia)
A sulfonylurea- Gliclazide
Exenatide
This is a NICE recommendation