BNF - Chapter 6 - Endocrine system - (Part 1) Flashcards
What is diabetes insipidus?
It is a rare condition where you produce a large amount of urine and often feel thirsty
Which two drugs can be used in the management of diabetes insipidus?
Vasopressin (antidiuretic hormone) + Desmopressin
What is used in the treatment of ‘cranial’ diabetes insipidus?
Vasopressin also can use desmopressin (analogue of vasopressin)
Is treatment required life long after diabetes insipidus following trauma or pituitary surgery?
No may be required for a limited period of time
Which is more potent - desmopressin or vasopressin?
Desmopressin is more potent and has a longer duration of action than vasopressin
Does desmopressin have vasoconstrictor effect?
No, unlike vasopressin it has no vasoconstrictor effect
Which one of the two is used in the differential diagnosis of diabetes insipidus?
Desmopressin
How is desmopressin used in the differential diagnosis of diabetes insipidus?
Following a dose intramuscularly or intranasally, restoration of the ability to concentrate urine after water deprivation confirms a diagnosis of cranial diabetes insipidus.
Failure to respond occurs in nephrogenic diabetes insipidus.
In nephrogenic and partial pituitary diabetes insipidus what use of drug may be of benefit?
benefit may be gained from the paradoxical antidiuretic effect of thiazides.
What are some other uses of desmopressin?
Desmopressin is also used to boost factor VIII concentration in mild to moderate haemophilia and in von Willebrand’s disease; it is also used to test fibrinolytic response. Desmopressin may also have a role in nocturnal enuresis.
Which drug can be used in the treatment of hyponatraemia resulting from inappropriate secretion of antidiuretic hormone?
- Democlocycline, if fluid restriction alone does not restore sodium concentration or is not tolerable
How is democlocycline thought to work?
By directly blocking the renal tubular effect of antidiuretic hormone
Which vassopressin V2 receptor antagonist is licensed for the treatment of hyponatraemia secondary to syndrome of inappropriate antidiuretic hormone secretion?
- Tolvaptan
What can rapid correction of hyponatraemia during tolvaptan therapy cause?
osmotic demyelination, leading to serious neurological events; close monitoring of serum sodium concentration and fluid balance is essential.
What is dosage of vasopressin/ desmopressin tailored to?
The dosage is tailored to produce a diuresis every 24 hours to avoid water intoxication
What is nephrogenic diabetes insipidus treated with?
Thiazides
What should patients taking desmopressin be warned about regarding hyponatraemic convulsions?
patients being treated for primary nocturnal enuresis (bedwetting) should be warned to avoid fluid overload (including during swimming) and to stop taking desmopressin during an episode of vomiting or diarrhoea (until fluid balance normal)
In healthy individuals what does the adrenal cortex secrete?
- Secretes Cortisol (glucocorticoid) and aldosterone (mineralocorticoid)
Is cortisol a glucocorticoid or a mineralocorticoid?
Glucocorticoid
Is aldosterone a glucocorticoid or a mineralocorticoid?
Mineralocorticoid
Is corticosteroids used in psoriasis?
Corticosteroids should be avoided or used only under specialist supervision in psoriasis.
Is fludrocortisone gluco or mineralocorticoid?
Mineralocorticoid
What is a use of fludrocortisone acetate?
Can be used to treat postural hypotension in autonomic neuropathy
Can high dose corticosteroids be used for septic shock?
No high doses should be avoided in septic shock
However, there is evidence that administration of lower doses of hydrocortisone and fludrocortisone acetate is of benefit in adrenal insufficiency resulting from septic shock.
Does dexamethasone and betamethasone have a great or little mineralocorticoid action?
Dexamethasone and betamethasone have little if any mineralocorticoid action and their long duration of action makes them particularly suitable for suppressing corticotropin secretion in congenital adrenal hyperplasia
In common with all glucocorticoids when are their suppressive action on the hypothalamic pituitary adrenal axis the greatest and most prolonged - when they are given in the morning or night?
When given at night
In most individuals a single dose of dexamethasone at night, is sufficient to inhibit corticotropin secretion for how many hours?
For 24 hours
Betamethasone and dexamethasone are also appropriate for conditions that produce which symptom?
for conditions where water retention would be a disadvantage.
Can a corticosteroid be used for the management of head injury or stroke?
No because it is unlikely to be of benefit and may even be harmful.
Are corticosteroids recommended for the routine emergency treatment of anaphylaxis?
No
What is central serious chorioretinopathy?
It is a retinal disorder that has been linked to the systemic use of corticosteroids
Patients should be advised to report any blurred vision or other visual disturbances with corticosteroid treatment given by any route
What are the mineralocorticoid side effects?
hypertension sodium retention water retention potassium loss calcium loss
Which corticosteroids show more mineralocorticoid activity?
Mineralocorticoid side effects are most marked with fludrocortisone, but are significant with hydrocortisone, corticotropin, and tetracosactide. Mineralocorticoid actions are negligible with the high potency glucocorticoids, betamethasone and dexamethasone, and occur only slightly with methylprednisolone, prednisolone, and triamcinolone.
What are the glucocorticoid side effects?
diabetes
osteoporosis, which is a danger, particularly in the elderly, as it can result in osteoporotic fractures for example of the hip or vertebrae
in addition high doses are associated with avascular necrosis of the femoral head
muscle wasting (proximal myopathy) can also occur
corticosteroid therapy is also weakly linked with peptic ulceration and perforation
psychiatric reactions may also occur
When is the suppressive action of a corticosteroid on cortisol secretion the least?
When given as a single dose in the morning
In an attempt to reduce pituitary-adrenal suppression further what can be done about doses?
the total dose for two days can sometimes be taken as a single dose on alternate days;
alternate-day administration has not been very successful in the management of asthma.
For which patients may a steroid emergency card help?
A patient-held Steroid Emergency Card has been developed for patients with adrenal insufficiency and steroid dependence who are at risk of adrenal crisis.
What is the aim of the steroid emergency card?
It aims to support healthcare staff with the early recognition of patients at risk of adrenal crisis and the emergency treatment of adrenal crisis
Which corticosteroid is cortisol also known as?
Hydrocortisone
Does hydrocortisone have glucocorticoid or mineralocorticoid activity?
Glucocorticoid activity with weak mineralocorticoid activity.
In deficiency states of the adrenal cortex, physiological replacement is best achieved with a combination of which two corticosteroids?
Hydrocortisone and the mineralocorticoid fludrocortisone
In Addison’s disease or following adrenalectomy, hydrocortisone is usually required via which route?
Via - oral route. by mouth
How many doses per day is given of oral hydrocortisone in Addison’s disease?
2 doses - the larger in the morning and the smaller dose in the evening - mimicking the normal diurnal rhythm or cortisol secretion
Also given fludrocortisone
In adrenal crisis what is given and which route?
Hydrocortisone intravenously
What’s the difference in hypopituitarism and adrenal insufficiency?
In hypopituitarism, hydrocortisone should be given as in adrenal insufficiency.
But since production of aldosterone is also regulated by the renin-angiotensin system a mineralocorticoid is not usually required.
When comparing the relative potencies of corticosteroids in terms of their anti-inflammatory (glucocorticoid) effect what should be borne in mind about mineralocorticoid activity?
it should be borne in mind that high glucocorticoid activity in itself is of no advantage unless it is accompanied by relatively low mineralocorticoid activity
Does fludrocortisone acetate have much anti-inflammatory activity?
The mineralocorticoid activity of fludrocortisone acetate is so high that its anti-inflammatory activity is of no clinical relevance.
Why is hydrocortisone unsuitable for disease suppression on a long term basis?
Hydrocortisone has a relatively high mineralocorticoid activity, and results in fluid retention making it unsuitable.
Can hydrocortisone be used for adrenal replacement therapy?
Yes
Do prednisolone and prednisone have predominantly glucocorticoid activity or mineralocorticoid activity?
Predominantly glucocorticoid activity
Which corticosteroid is used most commonly by mouth for long term disease suppresion?
- Prednisolone
Do betamethasone and dexamethasone have long or short duration of action?
Long duration of action
What properties make betamethasone and dexamethasone suitable for conditions which require suppression of corticotropin (corticotrophin)?
Betamethasone and dexamethasone also have a long duration of action and this, coupled with their lack of mineralocorticoid action makes them particularly suitable for conditions which require suppression of corticotropin (corticotrophin) secretion (e.g. congenital adrenal hyperplasia).
Does deflazacort have a high or low glucocorticoid activity?
A high glucocorticoid activity; it is derived from prednisolone
Can live virus vaccines be given in those receiving immunosuppressive doses of corticosteroids?
No - it is listed on the Contraindications
What are the common side effects of systemic corticosteroids?
Anxiety; behaviour abnormal; cataract subcapsular; cognitive impairment; Cushing’s syndrome; electrolyte imbalance; fatigue; fluid retention; gastrointestinal discomfort; headache; healing impaired; hirsutism; hypertension; increased risk of infection; menstrual cycle irregularities; mood altered; nausea; osteoporosis; peptic ulcer; psychotic disorder; skin reactions; sleep disorders; weight increased
During prolonged therapy with corticosteroids, particularly with systemic use, what may develop and can persist for years after stopping?
Adrenal atrophy
During adrenal suppression therapy, what can abrupt withdrawal after a prolonged period lead to?
- acute adrenal insufficiency
- hypotension
- death
To compensate for a diminished adrenocortical response caused by prolonged corticosteroid treatment what do any significant intercurrent illness, trauma or surgical procedure require?
A temporary increase in corticosteroid dose, or if already stopped, a temporary reintroduction of corticosteroid treatment.
Prolonged courses of corticosteroids increase susceptibility to what?
To infections and severity of infections
clinical presentation of infections may also be atypical. Serious infections e.g. septicaemia and tuberculosis may reach an advanced stage before being recognised, and amoebiasis or strongyloidiasis may be activated or exacerbated (exclude before initiating a corticosteroid in those at risk or with suggestive symptoms).
What effect can prolonged courses of corticosteroids have on fungal or viral ocular infections?
They may also be exacerbated
What is the effect of chickenpox and corticosteroid use?
Unless they have had chickenpox, patients receiving oral or parenteral corticosteroids for purposes other than replacement should be regarded as being at risk of severe chickenpox
Should corticosteroids if chickenpox is contracted - should they be stopped?
Corticosteroids should not be stopped and dosage may need to be increased
What advice should be given to patients taking corticosteroids about measles?
Patients taking corticosteroids should be advised to take particular care to avoid exposure to measles and to seek immediate medical advice if exposure occurs. Prophylaxis with intramuscular normal immunoglobulin may be needed.
System corticosteroids, particularly in high does have been linked to what neurological reactions?
Psychiatric reactions including euphoria, insomnia, irritability, mood liability, suicidal thoughts, psychotic reactions and behavioural disturbances,
Does the benefit of treatment with corticosteroid during pregnancy outweigh the risk?
Yes it does
When administration is prolonged or repeated during pregnancy, systemic corticosteroids increase the risk of intra-uterine growth restriction; there is no evidence of intra-uterine growth restriction following short-term treatment (e.g. prophylactic treatment for neonatal respiratory distress syndrome).
Any adrenal suppression in the neonate following prenatal exposure usually resolves spontaneously after birth and is rarely clinically important.
What monitoring is important if corticosteroids are used in children?
The height and weight of children receiving prolonged treatment with corticosteroids should be monitored annually; if growth is slowed, referral to a paediatrician should be considered.
gradual withdrawal of systemic corticosteroids should be considered in which patients?
received more than 40 mg prednisolone (or equivalent) daily for more than 1 week;
been given repeat doses in the evening;
received more than 3 weeks’ treatment;
recently received repeated courses (particularly if taken for longer than 3 weeks);
taken a short course within 1 year of stopping long-term therapy;
other possible causes of adrenal suppression.
In which patients may systemic corticosteroids be stopped abruptly?
Systemic corticosteroids may be stopped abruptly in those whose disease is unlikely to relapse and who have received treatment for 3 weeks or less and who are not included in the patient groups described above
During corticosteroid withdrawal the dose may be reduced rapidly down to physiological doses (what dose is this equivalent to)? then it can be reduced slowly?
Equivalent to prednisolone 7.5mg daily
In children when should gradual withdrawal of corticosteroid be considered?
Gradual withdrawal of systemic corticosteroids should be considered in those whose disease is unlikely to relapse and have:
received more than 40 mg prednisolone (or equivalent) daily for more than 1 week or 2 mg/kg daily for 1 week or 1 mg/kg daily for 1 month;
been given repeat doses in the evening;
received more than 3 weeks’ treatment;
recently received repeated courses (particularly if taken for longer than 3 weeks);
taken a short course within 1 year of stopping long-term therapy;
other possible causes of adrenal suppression.
In children what dose of prednisolone is equivalent to physiological doses?
Prednisolone 2-2.5mg/m2 daily
What is the purpose of a steroid treatment card?
to support communication of the risks associated with treatment and to record details of the prescriber, drug, dosage, and duration of treatment.
In which adults can steroid emergency cards be issued to?
Steroid Emergency Cards should be issued to patients with adrenal insufficiency and steroid dependence for whom missed doses, illness, or surgery puts them at risk of adrenal crisis.
List patients in which it may be appropriate to issue a steroid emergency card?
those with primary adrenal insufficiency;
those with adrenal insufficiency due to hypopituitarism requiring corticosteroid replacement;
those taking corticosteroids at doses equivalent to, or exceeding, prednisolone 5 mg daily for 4 weeks or longer across all routes of administration (oral, topical, inhaled, intranasal, or intra-articular);
those taking corticosteroids at doses equivalent to, or exceeding, prednisolone 40 mg daily for longer than 1 week, or repeated short oral courses;
those taking a course of oral corticosteroids within 1 year of stopping long-term therapy.
What does the steroid emergency card also include?
The card includes a management summary for the emergency treatment of adrenal crisis and can be issued by any healthcare professional managing patients with adrenal insufficiency or prescribing steroids.
Does hydrocortisone have more gluco or mineralocorticoid activity?
Equal activity of both
What does crushing syndrome result from?
It results from chronic exposure to excess cortisol
What is the most common cause of cushing syndrome?
Exogenous corticosteroid use is the most common cause.
What are some of the endogenous causes of Cushing syndrome?
adrenocorticotrophic hormone (ACTH)-secreting pituitary tumours (Cushing’s disease), cortisol-secreting adrenal tumours, and rarely, ectopic ACTH-secreting tumours
How are most types of endogenous Cushing’s syndrome treated?
Surgically
Which drug is licensed for the management of Cushing syndrome?
Metyrapone
Which drug is licensed for the treatment of endogenous Cushing’s syndrome?
- Ketoconazole
What type of antifungal does ketoconazole belong to?
Imidazole derivative which acts a potent inhibitor of cortisol and aldosterone synthesis
Is oral ketoconazole marketing as being available and used for fungal infection?
The CHMP recommended that the marketing authorisation for oral ketoconazole to treat fungal infections should be suspended.
The CHMP concluded that the risk of hepatoxicity associated with oral ketoconazole is greater than the benefit in treating fungal infections.
Can oral ketoconazole be used for endogenous Cushing’s syndrome?
Yes
What is the uses of metyrapone?
Used to treat Cushing’s syndrome
Also can be used to test anterior pituitary function
To summarise, what is used in adrenal replacement therapy?
In replacement therapy, hydrocortisone (cortisol) (a glucocorticoid) and
fludrocortisone (aldosterone) (a mineralocorticoid) is used
Why is prednisolone still remained as the drug of choice for most oral corticosteroid treatments?
Since it has a larger margin of safety
Abrupt withdrawal of long term treatment of corticoids can leaf to adrenal insufficiency, hypotension or death. what other symptoms are associated with withdrawal?
cold and flu like symptoms, itching and weight loss
Why should steroids be used with caution in children?
Due to possible growth restrictions
What effect may steroids have on warfarin?
corticosteroids may enhance the anticoagulant effects of warfarin at high-doses
At low doses they may reduce the anticoagulant effect of warfarin
What are the side effects of mineralocorticoid?
- hypertension
- sodium retention
- potassium loss
- water retention
- calcium loss
Aldosterone is a mineralocorticoid involved in the rennin- angiotensin system – hence increased sodium and decreased potassium and hydrogen ions.
HINT - in ACEi / ARBs - angiotensin-renin system is blocked - meaning less aldosterone meaning opposite - potassium retention
What are the glucocorticoids side effects?
include diabetes and osteoporosis; also potentially peptic ulceration. Hydrocortisone is a glucocorticoid, it has anti- inflammatory and immunosuppressive effects (hence ulceration); they increase blood glucose levels (hence diabetes) and mobilise calcium (hence osteoporosis).
How does type 1 diabetes occur?
Occurs due to a lack of insulin following autoimmune destruction of the pancreatic beta cells.
What about type 2 diabetes?
- reduced insulin release or resistance to insulin or both
How is diabetes diagnosed?
By measuring fasting or random blood-glucose levels
What’s the difference in what treatment is required for type 1 and 2 diabetes?
• Type 1 diabetics require insulin, Type 2 diabetics can be managed with diet, but may require antidiabetic drugs, insulin or both. Type
How can type 2 diabetes in overweight patients be prevented?
By losing weight and increasing physical activity
What is the purpose of diabetes treatment?
It is to optimise blood glucose and minimise the risk of long term complications
What is diabetes a risk factor for?
- Cardiovascular disease - to reduce this risk diabetic patients are also on ramipril, low dose aspirin and simvastatin (R.A.S)
Which CVD prevention drugs should be discontinued before pregnancy in diabetic patients
Ramipril + Simvastatin
What is diabetes mellitus?
Diabetes mellitus is a group of metabolic disorders in which persistent hyperglycaemia is caused by deficient insulin secretion or by resistance to the action of insulin
What does persistent hyperglycaemia in diabetes mellitus lead to?
Leads to the abnormalities of carbohydrate, fat and protein metabolism that are characteristic of diabetes mellitus
What are the classifications of diabetes?
Type 1 diabetes and Type 2 diabetes are the two most common classifications of diabetes. Other common types of diabetes are gestational diabetes (develops during pregnancy and resolves after delivery, see Diabetes, pregnancy and breast-feeding) and secondary diabetes (may be caused by pancreatic damage, hepatic cirrhosis, or endocrine disease). Treatment with endocrine, antiviral, or antipsychotic drugs may also cause secondary diabetes.
All drivers being treated with which diabetic medication must inform DVLA?
- Insulin
With some exceptions for temporary treatment
What must drivers being treated with insulin always carry?
Carry a glucose meter and blood-glucose strip when driving
How often should drivers on insulin check their blood glucose concentration?
- no more than 2 hours before (within 2 hours before driving)
- then every 2 hours while driving.
While driving what must blood glucose always be above?
Above 5mmol/L while driving.
If blood glucose falls to 5mmol/L or below then a snack should be taken.
Drivers treated with insulin should also ensure that there is a supply of what else?
A fast-acting carbohydrate is always available in the vehicle
If a driver is treated usually with insulin for diabetes and their blood-glucose concentration is less than 4mmol/L, or warning signs of hypoglycaemia develop, can the patient drive?
The patient should not drive
What if the patient is already driving?
the driver should:
stop the vehicle in a safe place;
switch off the engine, remove keys from the ignition, and move from the driver’s seat;
eat or drink a suitable source of sugar;
wait until 45 minutes after blood-glucose has returned to normal, before continuing journey.
Can patients drive if hypoglycaemia awareness has been lost?
No and the DVLA must be notified; drivers may resume if a medical report confirms that awareness has been regained.
What is the effect of alcohol on signs of hypoglycaemia?
Alcohol can make the signs of hypoglycaemia less clear, and can cause delayed hypoglycaemia
What do specialist sources recommend about patients with diabetes who want alcohol?
- should drink alcohol in moderation, and when accompanied by food.
When is the oral glucose tolerance test mainly used?
It is used mainly for diagnosis of impaired glucose tolerance - it is not recommended for necessary for routine diagnostic use when severe symptoms of hyperglycaemia are present.
In patients who have less severe symptoms and a blood-glucose concentration that does not establish or exclude diabetes (e.g. impaired fasting glycaemia), an oral glucose tolerance test may be required.
When else is an oral glucose tolerance test used?
To establish the presence of gestational diabetes
What does an oral glucose tolerance test involve?
An oral glucose tolerance test involves measuring the blood-glucose concentration after fasting, and then 2 hours after drinking a standard anhydrous glucose drink. Anhydrous glucose may alternatively be given as the appropriate amount of Polycal® or as Rapilose® OGTT oral solution.
What is HbA1c?
Glycated haemoglobin (HbA1c) forms when red blood cells are exposed to glucose in the plasma.
What indicator is HbA1c used for?
The HbA1c test reflects average plasma glucose over the previous 2 to 3 months and provides a good indicator of glycaemic control
Like oral glucose tolerance test does HbA1c test require fasting?
Unlike the oral glucose tolerance test, an HbA1c test can be performed at any time of the day and does not require any special preparation such as fasting.
What is the value expressed for HbA1c values?
HbA1c values are expressed in mmol of glycated haemoglobin per mol of haemoglobin (mmol/mol), a standardised unit specific for HbA1c created by the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC)
What are the equivalence values of HbA1c mmol/mol to HbA1c expressed as percentages?
IFCC-HbA1c (mmol/mol) DCCT-HbA1c (%) 42 6.0 48 6.5 53 7.0 59 7.5 64 8.0 69 8.5 75 9.0
When is the HbA1c test used?
For monitoring glycaemic control in both Type 1 and 2 diabetes and is also now used for the diagnosis of type 2 diabetes
In which patients should HbA1C not be used for?
HbA1c should not be used for diagnosis in those with suspected type 1 diabetes, in children, during pregnancy, or in women who are up to two months postpartum. It should also not be used for patients who have:
- had symptoms of diabetes for less than 2 months;
- a high diabetes risk and are acutely ill;
- treatment with medication that may cause hyperglycaemia;
- acute pancreatic damage;
- end-stage chronic kidney disease;
- HIV infection.
HbA1c used for diagnosis of diabetes should be interpreted with caution in which patients?
with abnormal haemoglobin, anaemia, altered red cell lifespan, or who have had a recent blood transfusion.
What is HbA1c also a reliable predictor of?
microvascular and macrovascular complications and mortality.
Is a higher or lower HbA1c better?
Lower HbA1c is associated with a lower risk of long term vascular complications and patients should be supported to aim for an individualised HbA1c target
What is the recommendations of how often HbA1C should be measured for type 1 and type 2 daibetes?
HbA1c should usually be measured in patients with type 1 diabetes every 3 to 6 months, and more frequently if blood-glucose control is thought to be changing rapidly.
Patients with type 2 diabetes should be monitored every 3 to 6 months until HbA1c and medication are stable when monitoring can be reduced to every 6 months.
When is HbA1c monitoring invalid?
invalid for patients with disturbed erythrocyte turnover or for patients with a lack of, or abnormal haemoglobin. In these cases, quality-controlled plasma glucose profiles, total glycated haemoglobin estimation (if there is abnormal haemoglobin), or fructosamine estimation can be used.
What does fructosamine concentration measure?
Laboratory measurement of fructosamine concentration measures the glycated fraction of all plasma proteins over the previous 14 to 21 days but is a less accurate measure of glycaemic control than HbA1c.
What is type 1 diabetes?
Type 1 diabetes describes an absolute insulin deficiency in which there is little or no endogenous insulin secretory capacity due to destruction of insulin-producing beta-cells in the pancreatic islets of Langerhans. This form of the disease has an auto-immune basis in most cases, and it can occur at any age, but most commonly before adulthood.
What does the loss of insulin secretion result in?
- In hyperglycaemia and other metabolic abnormalities
What are the typical features in adult patients presenting with type 1 diabetes?
- Hyperglycaemia (random plasma-glucose concentration above 11mmol/L)
- ketosis
- rapid weight loss
- a body max index below 25kg/m2
- age younger than 50 years
- and a personal/family history of autoimmune disease (though not all features may be present
What is the treatment aims of type 1 diabetes?
- using insulin regimens to achieve as optimum a level of blood glucose control as is feasible
while avoiding or reducing the frequency of hypoglycaemic episodes, in order to minimise the risk of long-term microvascular and macrovascular complications
What is the aim of HbA1c concentration or lower in patients with type 1 diabetes?
48 mmol/mol (6.5%) or lower in patients with type 1 diabetes
How often should blood glucose concentration be monitored for someone with type 1 diabetes?
At least four times a day, including before each meal and before bed
For type one diabetes what blood glucose concentration is recommended on waking?
a fasting blood-glucose concentration of 5–7 mmol/litre on waking
For type one diabetes what blood glucose concentration is recommended before meals at other times of the day?
4–7 mmol/litre before meals at other times of the day
For type one diabetes what blood glucose concentration is recommended at least 90 minutes after eating?
5-9mmol/L at least 90 minutes after
For type one diabetes what blood glucose concentration is recommended when driving?
above 5 mmol/litre when driving, as recommended by the Driver and Vehicle Licensing Agency (DVLA)
What replacement does type 1 diabetes require?
- insulin replacement
In addition to insulin therapy which tablet may be used unlicensed?
In patients who have a BMI of 25 kg/m2 or above (23 kg/m2 or above for patients of South Asian or related ethnicity) who wish to improve their blood-glucose control while minimising their effective insulin dose, consider metformin hydrochloride [unlicensed indication] as an addition to insulin therapy.
Is dietary control only important for type 2 diabetes?
No it is important for both type 1 and type 2 diabetes
What should patients with type-1 diabetes be offered - for diet?
Patients with type 1 diabetes should be offered carbohydrate-counting training as part of a structured education programme.
Do all patients with type 1 diabetes require insulin therapy?
Yes
List the different types of insulin therapy regimens for type 1 diabetes?
- Multiple daily injection basal-bolus insulin regimens
- Mixed (biphasic) regimen
- Continuous subcutaneous insulin infusion (insulin pump)
What is multiple daily injection basal-bolus insulin regimens used for type 1 diabetes?
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. This regimen offers flexibility to tailor insulin therapy with the carbohydrate load of each meal.
What is mixed (biphasic) regimen used for type 1 diabetes?
One, two, or three insulin injections per day of short-acting insulin mixed with intermediate-acting insulin.
The insulin preparations may be mixed by the patient at the time of injection, or a premixed product can be used.
What is continuous subcutaneous insulin infusion (insulin pump)?
A regular or continuous amount of insulin (usually in the form of a rapid-acting insulin analogue or soluble insulin), delivered by a programmable pump and insulin storage reservoir via a subcutaneous needle or cannula
Which regimen is first-line choice for patients with type 1 diabetes?
multiple daily injection basal-bolus insulin regimens
For the basal-bolus regimen which insulin should be given as the long-acting insulin?
- Insulin detemir (Levemir)
Twice daily administration
What should be given as an alternative if insulin detemir is not tolerated, or if a twice-daily regimen is not acceptable?
Insulin Glargine (100units/ml)
(Lantus)
(Once Daily Administration)
If there is a concern about nocturnal hypoglycaemia then which other insulin is an alternative to the previous two mentioned as the basal part of the basal-bolus regimen?
Insulin degludec
(Tresiba)
(Ultra-long acting_
For patients who need help with injection administration from a carer or healthcare professional a once daily ultra-long acting insulin may be given - which ones are ultra long acting?
Insulin degludec (Tresiba)
Insulin Glargine (300units/ml) (Touejo)
Are non-basal-bolus regimens (e.g. twice-daily mixed [biphasic], basal-only, or bolus-only regimens) recommended for adults with newly diagnosed type 1 diabetes?
No they are not
What acting insulin is recommended as the mealtime insulin replacement for the basal-bolus regimen?
A rapid acting insulin analogue
Rather than soluble human insulin or animal insulin (rarely used).
When should the rapid-acting insulin analogue be injected?
Should be injected before meals - routine use after meals should be discouraged
If the first-line choice of going for a basal-bolus regimen is not possible or not preferred then what regimen may be offered next?
(Biphasic)
a twice-daily mixed insulin regimen should be considered if it is preferred.
In patients who are using a twice-daily human mixed insulin regimen and have hypoglycaemia that affects their quality of life what should be trialled?
a trial of a twice-daily analogue mixed insulin regimen should be considered.
Who should continuous subcutaneous insulin infusions be offered to?
should only be offered to patients who suffer disabling hypoglycaemia while attempting to achieve their target HbA1c concentration, or, who have high HbA1c concentrations (69 mmol/mol [8.5%] or above) with multiple daily injection therapy (including, if appropriate, the use of long-acting insulin analogues) despite a high level of care. Insulin pump therapy should be initiated by a specialist team.
When may insulin requirements decrease and therefore susceptibility to hypoglycaemia increase?
by physical activity, intercurrent illness, reduced food intake, impaired renal function, and in certain endocrine disorders.
What should patients’ awareness of hypoglycaemia be assessed using and how often?
Should be assessed annually using the Gold score or the Clarke score.
Impaired awareness of symptoms below what mmol of glucose concentration is associated with a significantly increased risk of severe hypoglycaemia?
Below 3mmol/L
Which class of drugs may blunt/ mask hypoglycaemia awareness?
Beta blockers
reducing warning signs such as tremor
Can relaxation of individualised blood glucose targets be used as a strategy to improve hypoglycaemia awareness?
This should be avoided
Do clinical studies confirm if human insulin decreases hypoglycaemia awareness?
No they do not confirm this
What is insulin and its role?
Insulin is a polypeptide hormone secreted by pancreatic beta-cells. Insulin increases glucose uptake by adipose tissue and muscles, and suppresses hepatic glucose release. The role of insulin is to lower blood-glucose concentrations in order to prevent hyperglycaemia and its associated microvascular, macrovascular and metabolic complications.
What is the natural profile of insulin secretion in the body?
(a low and steady secretion of background insulin that controls the glucose continuously released from the liver) and meal-time bolus insulin (secreted in response to glucose absorbed from food and drink).
How many types (sources) of insulin are available in the UK?
Three types
- human insulin
- human insulin analogues
- animal insulin
What are animal insulins extracted from?
Animal insulins are extracted and purified from animal sources (bovine or porcine insulin)
Are animal insulins still used?
No longer initiated but still used in patients who do not wish to change to human insulins
What are human insulins produced by?
Human insulins are produced by recombinant DNA technology and have the same amino acid sequence as endogenous human insulin.
What about human insulin analogues?
Human insulin analogues are produced in the same way as human insulins, but the insulin is modified to produce a desired kinetic characteristic, such as an extended duration of action or faster absorption and onset of action.
Why must insulin be given by injection?
As it is inactivated by gastro-intestinal enzymes and must therefor be given by injection
Where should insulin be injected?
Into a body area with plenty of subcutaneous fat - usually the abdomen (fastest absorption rate) or outer thighs/buttocks (Slower absorption compared with the abdomen or inner thighs)
What else can affect the absorption rate of insulin?
Absorption from a limb site can vary considerably (by as much as 20–40%) day-to-day, particularly in children. Local tissue reactions, changes in insulin sensitivity, injection site, blood flow, depth of injection, and the amount of insulin injected can all affect the rate of absorption.
Increased blood flow around the injection site due to exercise can also increase insulin absorption.
When can lipohypertrophy occur?
Lipohypertrophy can occur due to repeatedly injecting into the same small area, and can cause erratic absorption of insulin, and contribute to poor glycaemic control.
Patients should be advised not to use affected areas for further injection until the skin has recovered.
How can lipohypertrophy be minimised?
By using different injection sites in rotation
What should injection sites be checked for?
- signs of infection
- Swelling
- Bruising
- Lipohypertrophy
all before adminstration
What are the two types of short-acting insulin?
- Soluble insulin (human and, bovine or porcine - both rarely used)
- Rapid-acting insulin analgoues
List the rapid-acting insulin analogues?
- Insulin Aspart
- Insulin Glulisine
- Insulin Lispro
What routes can soluble insulin be given?
- usually given subcutaneously but some preparations can be given intravenously and intramuscularly
When injected subcutaneously what is the onset of action for soluble insulin?
Rapid onset of action
30-60 minutes
A peak action between 1 and 4 hours and a duration of action up to 9 hours
What about when soluble insulin is given intravenously?
soluble insulin has a short half-life of only a few minutes and its onset of action is instantaneous.
What is the most appropriate insulin and route for use in diabetic emergencies such as diabetic ketoacidosis?
Soluble insulin administered intravenously
What is the list of rapid-acting insulins?
Insulin Aspart
Insulin Glulisine
- Insulin Lispro
Do rapid-acting insulin have a longer or shorter duration of action and onset of action?
Faster onset of action (within 15 minutes) and shorter duration of action (approximately 2-5 hours) than soluble insulin and are usually given subcutaneously
When rapid-acting insulin is used as maintenance regimens, ideally when should it be injected?
Immediately before meals
