Chapter 6: Endocrine system Flashcards
What is the advice from the DVLA regarding insulin dependent diabetic drivers?
- Should always carry a glucose meter and blood-glucose test strips when driving
- Check blood glucose no more than 2 hours before driving and then every 2 hours during driving
- More frequent monitoring if necessary e.g. after physical activity, altered meal routine
- Blood glucose should always be above 5 mmol/L whilst driving
- Falls <5mmol/L - eat a snack
- Should always ensure a fast-acting carbohydrate is available in the vehicle
- If blood glucose is <4 mmol/L, should NOT drive, eat/drink source of sugar, wait until 45 mins after blood-glucose has returned to normal before continuing journey
This may also be the case in patients taking oral antidiabetic drugs, in particular those that cause hypoglycaemia e.g. sulphonlyureas, nateglinide, repaglinide
Must not drive if hypoglycaemia awareness is lost and must inform DVLA
True or false:
Alcohol can cause delayed hyperglycaemia
False- can cause delayed HYPOglycaemia
Can make the signs of hypoglycaemia less clear
Only drink alcohol in mod and when accompanied by food
Do you have to fast before a HbA1c test?
No
Yes for an oral glucose tolerance test
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
6.5%
How often should blood glucose be measured in Type 1 diabetes?
At least 4 times a day, including before each meal and before bed
What are the blood glucose aims in Type 1 diabetes for:
a) Waking
b) Before meals
c) 90 minutes after eating
d) Driving
a) 5-7 on waking
b) 4-7 before meals
c) 5-9 at least 90 mins after eating
d) at least 5 when driving
all in mmol/L
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; alongside multiple bolus injections of short-acting insulin before meals
What is a mixed (biphasic) insulin regimen?
One, two, or three insulin injections per day of short-acting insulin mixed with intermediate-acting insulin
Can be mixed by the patient at the time or a pre-mixed product can be used.
What insulin regimen is first choice for Type 1 diabetics?
Basal bolus
In a basal bolus regimen for Type 1 diabetes, what basal insulin would be first choice?
What would be the second choice?
Insulin determir BD - can also be offered as once daily
Once daily insulin glargine
Are non-basal bolus regimens recommended in newly diagnosed Type 1 diabetics?
No
Non-basal bolus regimens - BD mixed (biphasic), basal-only, bolus-only
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 analogue
(Rather than soluble human insulin or animal insulin (rarely used))
Rapid-acting insulin analogue should be injected before meals. Routine use after meals is discouraged.
Pts who have a strong preference for an alternative mealtime insulin should be offered their preferred insulin.
Continuous subcut insulin infusion (insulin pump) therapy should only be offered to what group of people?
- Suffer from disabling hypoglycaemia
- High HbA1c of 69mmol/mol (8.5%) or above with multiple daily injection therapy
Should be initiated by a specialist.
What situations can cause an INCREASE in required insulin dose?
therefore what can cause/predispose to hyperglycaemia
- Infection
- Stress
- Accidental/surgical trauma
What situations can cause an DECREASE in required insulin dose?
- Physical activity
- Intercurrent illness - a disease that intervenes during the course of another disease.
- Reduced food intake
- Impaired renal function
- Certain endocrine disorders
When insulin requirements decrease, susceptibility to hypoglycaemia is increased.
Physical activity lowers glucose
How does impaired awareness of hypoglycaemia occur?
Patients’ awareness of hypoglycaemia should be assessed annually using what score tools?
When the ability to recognise usual symptoms is lost or when the symptoms are blunted or no longer present.
Gold or Clarke score
What cardiac class of drug can blunt hypoglycaemia awareness?
Beta blockers
Will 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 insulin - produced by recombinant DNA technology and have the same amino acid sequence as endogenous human insulin
Human insulin analogues - produced in the same way as human insulins but the insulin is modified to produce a desired kinetic characteristic, such s an extend duration of action, or faster absorption and onset of action
Animal insulin - extracted and purified from animal sources (bovine or porcine insulin).
Which area of the body has the fastest absorption rate for insulin?
And slower absorption?
Abdomen - where there is plenty of subcutaenous fat
and maybe inner thighs
outer thighs and buttocks
What can occur if you repeatedly inject insulin into the same area without rotating? How does it affect insulin/glucose?
How can you prevent it?
Lipohypertrophy
Can cause erratic absorption of insulin + poor glycaemic control
- use different injection sites in rotation
- injection sites should be checked for infection, swelling, bruising and lipohypertrophy before administration
How much time before meals do you administer short acting soluble insulin?
Onset and duration of action of s/c and IV soluble insulin?
15-30 minutes before
Depends on insulin preparation used
S/C
- 30-60 mins onset of action
- 9 hr duration
IV
- short half life - a few minutes
- onset of action is instantaneous
What is the most appropriate form of insulin to use in diabetic emergencies e.g. DKA & peri-operatively
Soluble insulin IV
What are the 3 types of rapid acting insulin?
Insulin aspart
Insulin glulisine
Insulin lispro
How much time before meals do you administer rapid acting insulin?
Onset of action and duration of action?
Immediately before
onset of action - within 15 minutes
duration of action - 2-5 hours
What are the advantages of rapid acting insulin over short acting soluble insulin?
- Can be given immediately before meals
- Improved glucose control, reduction of HbA1c, and reduction in the incidence of severe hypoglycaemia, including nocturnal hypoglycaemia.
Is injecting short acting (BNF states rapid acting??) insulins post meals recommended?
No avoid
When given during or after meals –
- poorer glucose control
- increased risk of high postprandial (during or after meal) - glucose conc and subsequent hypoglycaemia
What type of insulin is isophane?
Onset of action?
Maximal effect at?
Duration of action?
Intermediate - designed to mimic the effect of endogenous basal insulin
- 1-2 hrs
- 3-12 hrs
- 11-24 hrs
What are biphasic insulins?
Give examples of pre-mixed versions
Pre-mixed insulin preparations containing various combinations of short-acting insulin (soluble insulin or rapid-acting analogue insulin) and an intermediate-acting insulin.
- biphasic isophane insulin
- biphasic insulin aspart
- biphasic insulin lispro
What are the long acting insulins?
Duration of action?
Time to steady-state level?
Insulin detemir - BD or OD
Insulin glargine - OD
Insulin degludec - OD
Rarely prescribed:
Protamine zinc insulin
Insulin zinc suspension
Designed to mimic endogenous basal insulin secretion.
Duration of action - 36 hours
Steady state level achieved - 2-4 days — to produce a constant level of insulin
Does metformin cause hypoglycaemia?
No
Because it does not stimulate insulin secretion.
Has an anti-hyperglycaemic effect lowering both basal and postprandial blood-glucose concentrations
If standard release metformin is not tolerated e.g. GI side effects, what should be given?
Modified release metformin
Give examples of sulfonylureas
Glibenclamide (long-acting) Gliclazide Tolbutamide Glipizide Glimepiride
Give examples of meglitinides
Duration and onset of action?
When can they be used?
Nateglinide
Repaglinide
Rapid onset of action
Short duration of action
Can be used flexibly around mealtimes to find around individual eating habits which may be beneficial for some patients but are generally less preferred than sulphonylureas
Give examples of DPP-4 inhibitors
Incidence of weight gain and hypoglycaemia?
Alogliptin Linagliptin Sitagliptin Saxagliptin Vildagliptin
Does not appear to be associated with weight gain.
Less incidence of hypoglycaemia compared to sulphonylureas.
What is an advantage of DPP-4 inhibitors over sulphonylureas in terms of side effects?
Not associated with weight gain and have less incidence of hypoglycaemia
Give examples of SGLT2 inhibitors
When are they suitable to use?
Increased risk of?
Canaglifozin
Dapaglifozin
Empaglifozin
When first line options fail.
Canagliflozin + empagliflozin can be beneficial in those with T2DM and established cardiovascular disease
Increase risk of DKA
Give examples of GLP-1 receptor agonists
when can they be used?
What is liraglutide good for?
Glucagon - like peptide-1 receptor agonists
Dulaglutide
Exenatide
Liraglutide - proven cardiovascular benefit and should be considered in those with T2DM and established cardiovascular disease
Lixisenatide
Reserved for combination therapy when other treatment options have failed.
What should be the target HbA1c in a Type 2 diabetic that is managed by lifestyle/ a single antidiabetic agent that is NOT associated with hypoglycaemia?
48 mmol/mol
What should be the target HbA1c in a Type 2 diabetic that is managed with one associated with hypoglycaemia OR two or more antidiabetic drugs in combination?
53 mmol/mol (7%)
In terms of HbA1c, when should treatment in a Type 2 diabetic on ONE antidiabetic drug be intensified?
58 mmol/mol or higher
What should be the target HbA1c in a Type 2 diabetic that is managed with 2 or more antidiabetic drugs?
53 mmol/mol
What is first line drug treatment in Type 2 diabetes and why?
Metformin
- Positive effect on weight loss
- Reduced risk of hypoglycaemia
- Long term cardiovascular benefits
If a sulphonylurea is indicated in one of the following:
- Elderly patients
- Renal impairment
- Particular risk of hypoglycaemia
What sulphonylurea should you opt for?
Short acting one e.g. gliclazide or tolbutamide
If a Type 2 diabetic is not been adequately controlled on metformin and requires intensification of treatment, what are the add in options?
- Sulphonylurea
- Pioglitazone
- DPP-4 inhibitor
SGLT-2 inhibitor - only when sulphonylureas are contraindicated or if patient is at significant risk of hypoglycaemia
Type 2 diabetes:
Dapagliflozin is not recommended in a triple therapy regimen with what drug?
Pioglitazone
Type 2 diabetes:
If dual therapy is unsuccessful, what are the triple therapy combination options?
- Metformin + DPP-4 + sulphonylurea
- Metformin + pioglitazone + sulphonylurea
- Metformin + sulphonylurea + SGLT-2 inhibitor
- Metformin + pioglitazone + SGLT-2 inhibitor (not dapaglifozin)
May be appropriate to start insulin at this stage
When is GLP-1 receptor agonists indicated in Type 2 diabetes?
- If triple therapy with metformin and 2 other oral drugs are tried
- BMI of 35 kg/m2 or above (adjusted for ethnicity) and who also have specific psychological or medical problems associated with obesity; or for those who have a BMI lower than 35 kg/m2 but for whom insulin therapy would have significant occupational implications or if the weight loss associated with glucagon-like peptide-1 receptor agonists would benefit other significant obesity-related comorbidities.
If started on a GLP-1 receptor agonist for Type 2 diabetes, when should this be reviewed and how do you know it is okay to continue?
After 6 months, the drug should be reviewed and only continued if there has been a beneficial metabolic response (a reduction of at least 11 mmol/mol [1.0%] in HbA1c and a weight loss of at least 3% of initial body-weight).
If metformin is contraindicated or not tolerated, what should be used for initial treatment?
Sulphonylurea or DPP-4 inhibitor or pioglitazone monotherapy
SGLT2 inhibitor monotherapy can be used only if the above are not appropriate
Repaglinide can be used as monotherapy however cannot be used in combination with anything else other than metformin
What is the problem with using repaglinide monotherapy in Type 2 diabetes?
An effective alternative option for single theraoy
If intensification of treatment is required, can only be given with metformin
It is NOT licensed in combination with any other antidiabetic drugs
In patients where metformin is contraindicated/not tolerated:
If a patient is on a non-metformin single therapy however requires intensification of treatment, what dual combinations can be prescribed?
- DPP-4 inhibitor and pioglitazone
- DPP-4 inhibitor and sulfonylurea
- Pioglitazone and sulfonylurea
If dual therapy does not provide control, consider insulin
If a patient is on dual therapy for Type 2 diabetes, and metformin is contraindicated/not tolerated, what should be considered?
Insulin
In Type 2 diabetes, if insulin therapy is required, what should happen to their other antidiabetic drugs?
- Continue metformin if not contraindicated or tolerated
- Review all others and stop if necessary
In Type 2 diabetics, what insulin regimens can you use?
- Isophane (NPH) OD/BD
- Isophane + short acting (either separate or pre-mixed) - particularly appropriate if HbA1c is 75 or higher
- Insulin detemir or glargine can be an alternative to isophane
In Type 2 diabetics, at what HbA1c would the following insulin regimen be particularly appropriate:
Isophane + short acting insulin (separate or pre-mixed)
75 or higher (9%)
In type 2 diabetics requiring insulin therapy, when would long acting insulin (glargine or detemir) be preferable?
- If once daily injection is beneficial e.g. assistance is needed to inject, trouble with the device
- If recurrent symptomatic hypoglycaemic episodes are a problem
- If BD isophane would still require oral antidiabetics
When starting insulin therapy in Type 2 diabetes, when should the first basal insulin be given and how do you adjust the dose?
Bedtime basal insulin should be initiated and the dose titrated against fasting glucose in the morning
Providing there are no contraindications, what should you give for diabetic nephropathy that is causing proteinuria or established microalbuminuria?
Blood pressure should be reduced to the lowest achievable level to slow the rate of decline of the glomerular filtration rate and reduce proteinuria
ARB or ACEi to be started even if the blood pressure is normal
What is the potential problem with ACEis in diabetics if the patient is on insulin or oral antidiabetic drugs?
Can potentiate the hypoglycaemic effect
More likely in the first few weeks of combined treatment and in patients with renal impairment
The management of DKA involves what?
What should happen to their basal insulin?
What should be monitored and how often?
Replacement of fluid and electrolytes
Include potassium chloride in the fluids unless anuria is suspected
Administration of soluble insulin in sodium chloride 0.1 units/kg/hr
Long acting insulin (basal) should be continued in the background
If blood glucose falls below 14, give glucose 10%
Monitor ketones and glucose hourly
Monitor BP
Blood pH
During DKA treatment when the patient is on an insulin infusion, when should you recommence the short acting subcut insulin and stop the infusion and how is this done?
Continue insulin infusion until blood-ketone concentration is below 0.3 mmol/litre, blood pH is above 7.3 and the patient is able to eat and drink; ideally give subcutaneous fast-acting insulin and a meal, and stop the insulin infusion 1 hour later.
In the management of HHS, are lower or higher rates of insulin infusion usually required compared to DKA?
HHS - hyperosmolar hyperglycaemic state
Lower rates usually required
During DKA management, what rate should you give the insulin infusion?
0.1 units/kg/hr
Diabetic women who are planning on becoming pregnant should aim to keep their HbA1c to what?
Below 48 if possible without causing any problematic hypoglycaemia
any reduction towards this target is likely to reduce the risk of congenital malformations in the newborn
What is the folic acid supplementation recommendation in diabetic patients planning on becoming pregnant?
High dose - 5mg daily as classed in the high risk group of neural tube defects
What is the treatment recommendation for diabetic patients when they become pregnant?
What about during breastfeeding?
All antidiabetic drugs APART from metformin should be stopped and substituted with insulin therapy
For breastfeeding, the options are:
- Insulin continued
- Metformin continued
- Glibenclamide is fine to restart if originally on it
However, all other antidiabetic agents should be avoided during breastfeeding
What is the first choice for long acting insulin therapy during pregnancy?
Isophane insulin
However in women who have good blood-glucose control before pregnancy with the long-acting insulin analogues (insulin detemir or insulin glargine), it may be appropriate to continue using them throughout pregnancy.
What is the patient advice regarding insulin therapy during pregnancy?
Should be aware of the risk of hypoglycaemia (particularly in the first trimester) and should always carry a fast-acting form of glucose e.g. dextrose tablets, glucose-containing drink
It is recommended that pregnant women with Type 1 diabetes should be prescribed what just in case of hypoglycaemia?
Glucagon
Women with pre-existing diabetes treated with insulin during pregnancy are at an increased risk of what?
Hypoglycaemia during the postnatal period
Should reduce their insulin immediately after birth and blood glucose levels monitored
If a diabetic patient is on an ACEi or ARB for diabetic complications, however wishes to become pregnant, what would be the most appropriate action?
ACEi or ARB should be discontinued and an alternative antihypertensive suitable in pregnancy should be used
(Preferably before conception if pregnancy is planned)
If a diabetic patient becomes pregnant but is on a statin, what would be the most appropriate action?
Discontinue the statin during pregnancy (Preferably before conception if pregnancy is planned)
True or false:
A patient with gestational diabetes should continue their hypoglycaemic treatment after birth
False - should discontinue hypoglycaemic treatment immediately after giving birth
How would you manage an insulin dependent diabetic patient with good glycaemic control due for an elective minor procedure?
(Day before surgery and during the operative period)
On the day before surgery, give the usual insulin dose
However, once daily long acting insulins should be given at 80% of normal dose
Then their usual insulin regimen can be adjusted accordingly during the operative period
On the day before a minor op in an insulin dependent diabetic with good glycaemic control, you can give their usual insulin dose as normal. With what insulin would you not give the full dose?
Long acting insulin
You give 80% of normal dose
How would you manage an insulin dependent diabetic due for major elective surgery or in patients pre-op who have poor glycaemic control?
(Day before surgery, day of surgery, during the operative period)
VRII - Continued until the patient is eating/drinking and stabilised on their previous diabetes medication
Day before surgery - Give normal insulin dose (Apart from once daily long acting insulin is given at 80% usual dose)
Day of surgery and during the operative period:
- Once daily insulin given at 80% usual dose. All of the other patient’s insulin should be stopped until the patient is eating and drinking again
- Start IV infusion of potassium chloride with glucose and sodium chloride AND a variable rate insulin infusion of soluble human insulin in 0.9% sodium chloride
Blood glucose monitored hourly for at least the first 12 hours
In patients that are on VRII during an operative period, what would you do if their blood glucose drops below 6?
What about if it drops before 4?
<6 - Give IV glucose 20% and check blood glucose hourly
<4 - Give IV glucose 20% and check blood glucose every 15 mins
After surgery, if a patient is on VRII, they must not restart their subcut insulin until when?
They are eating/drinking without nausea or vomiting
Note- their insulin dose may need adjusting due to altered food intake/post-op stress/infection
After surgery, a patient is ready to stop their VRII and go back to their BASAL-BOLUS regimen when would you stop the VRII and restart their subcut insulin?
Should be restarted when the first post-op meal is due
Give the first short-acting insulin first and then stop VRII 30-60 mins after
Note- the long acting insulin is continued in the background of VRII at 80% dose - should continue at that dose until the patient leaves hospital
After surgery, a patient is ready to stop their VRII and go back to their TWICE DAILY MIXED insulin regimen when would you stop the VRII and restart their subcut insulin?
Should be restarted before breakfast or evening meal (not at any other time)
Stop VRII 30-60 mins after
In type 2 diabetes, when would you consider VRII for surgery?
- When the fasting period requires more than one missed meal - major elective surgery
- Patients with poor glycaemic control
- Risk of renal injury
- If on insulin as part of their treatment anyway
-
If VRII is required for surgery in a type 2 diabetic, what antidiabetic drugs should be stopped?
When should they be restarted?
- Acarbose
- Sulfonylureas
- DPP-4 inhibitors
- Pioglitazone
- Meglitinides
- SGLT-2 inhibitors
Should be stopped once VRII has commenced
Should not be restarted until the patient is eating and drinking normally