Chapter 6: Endocrine: Type 2 Diabetes Flashcards
What is T2DM characterised by?
Insulin resistance
Also causing an increase in cardiovascular risk, what is T2DM associated with?
- Obesity
- Physical inactivity
- Raised blood pressure
- Dyslipidaemia
- Tendency to thrombosis
When does T2DM usually develop?
In later life
What is the first line intervention of T2DM?
Lifestyle measures
Which lifestyle measures can be used to manage T2DM? (3)
- Smoking cessation
- Weight loss
- Exercise
Metformin does not stimulate release of insulin, therefore it has no risk of causing which adverse event?
Hypoglycaemia
What is the starting dose of metformin?
500mg OD after one meal for 1 week
500mg BD after two meals for 1 week
500mg TDS with all three meals
Why is metformin titrated gradually?
To reduce gastro-intestinal effects
If patients find metformin intolerable, what can be offered?
Modified release preparation
Which 5 drugs are in the sulfonylureas class?
- Glibenclamide
- Gliclazide
- Glimepiride
- Glipizide
- Tolbutamide
Which adverse effect can sulfonyureas cause?
Hypoglycaemia
Which sulfonylureas is hypoglycaemia more likely with? and why?
Glibenclamide
Long acting
Which oral antidiabetic has the poorest anti-hyperglycaemic effect?
Arcabose
Meglitinides are less preferred compared with sulphonylureas. Give two examples (DVLA)
- Nateglinide
2. Repaglinide
Which oral antidiabetic drug is associated with several long term risks and has 2 MHRA alerts?
Pioglitazone
What are the 2 MHRA alerts concerning pioglitazone?
- Cardiovascular safety
2. Bladder cancer
Incidence of heart failure is increased when pioglitazone is combined with which other antidiabetic drug?
Insulin
What should happen if a patient on pioglitazone has deteriorating cardiac status?
Discontinue treatment
Can pioglitazone be used in patients with heart failure or those with a history of heart failure?
No
Although pioglitazone carries a risk of bladder cancer, why is it still used?
Benefits outweigh risks
Due to its risk of bladder cancer, in which patients should pioglitazone note be used?
- Active bladder cancer
- Past history of bladder cancer
- Uninvestigated haematouria
In which group of patients should pioglitazone be used with caution, due to the risk of bladder cancer?
Elderly
After how long should the safety and efficacy of pioglitazone be reviewed?
3-6 months
If there is an inadequate response to treatment with which T2DM drug should treatment be discontinued?
Pioglitazone
Due to its risk of bladder cancer, which signs should patients promptly report?
- Haematouria
- Dysuria
- Urinary urgency
Give 5 examples of DPP-4 inhibitors
- Sitagliptin
- Vidagliptin
- Alogliptin
- Linagliptin
- Saxagliptin
Can DPP-4 inhibitors (gliptins) cause weight gain?
No
Can DPP-4 inhibitors (gliptins) cause hypoglycaemia?
No
Give 5 exampled of GLP-1 mimetics
- Exanatide
- Liraglutide
- Albiglutide
- Lixisenatide
- Dalaglutide
Give 3 examples of SGT-2 inhibitors
- Canagliflozin
- Dapaglifloxin
- Empagliflozin
What do SGT-2 inhibitors (flozins) carry a risk of?
ketoacidosis
Besides T2DM, what other indication does metformin have? (specialist initiation - unlicensed)
Insulin sensitising drug in women with polycystic ovarian syndrome who are not planning on having children
Does metformin have a hypoglycaemic effect in those without diabetes?
No
What is the HbA1c target for T2DM patients using diet and lifestyle alone or taking a single oral antidiabetic NOT associated with hypoglycaemia?
Less than 48mmol/mol
What is the HbA1c target for T2DM patients taking a single oral antidiabetic associated with hypoglycaemia or TWO oral antidiabetics?
Less than 53mmol/mol
What are the options if a single oral antidiabetic is not controlling symptoms? (3)
- Check adherence
- Reinforce diet and lifestyle advice
- Intensify treatment by adding a second drug
What is the first line oral antidiabetic for all patients?
Metformin
What are the benefits of metformin? (3)
- Encourages weight loss
- Low incidence of hypoglycaemic events
- Lowers long term cardiovascular risk
If glycaemic control is not achieved with one oral antidiabetic, which others can be added? (3)
- DPP-4 Inhibitor (Gliptin)
- Sulfonylureas
- Pioglitazone
During first intensification of T2DM oral antidiabetic treatment, which drug is an option ONLY if sulfonylureas are contraindicated, not tolerated or there is a significant risk of hypoglycaemia?
SGT-2 inhibitor (Flozin)
Which drug might it be appropriate to start at the stage of second intensification? (3 drugs)
Insulin
As well as insulin-based treatment, which class of oral antidiabetic drug may it be appropriate to consider if second intensification (3 drugs) fails?
GLP-1 mimetics (TIDES)
In which patients would it be beneficial to use GLP-1 mimetics (TIDES) for T2DM?
BMI >35
After how long must treatment with GLP-1 mimetics for T2DM be reviewed?
6 months
What are the treatment options for T2DM if metformin is contradindicated?
- DPP-4 inhibitor (GLIPTINS)
- Pioglitazone
- Sulfonylureas
In the treatment of T2DM, can metformin be continued if the patient is started on insulin?
Yes
In the treatment of T2DM, if a patient needs insulin-based treatment, metformin can be continued. What happens with the other oral antidiabetics?
They are reviewed then stopped if necessary
What are the recommended insulin regimens for T2DM> (4)
- Human isophane insulin - once or twice daily
- Human isophane insulin + short-acting insulin
- Insulin determir or glargine (BASAL)
- Biphasic preparations
As well as GI effects, what is another food-related side effect of metformin?
Taste disturbance
In which patients are we worried about lactic acidosis with metformin?
Poor renal function
At which renal function do we stop treatment with metformin?
Less than 30
Which oral antidiabetics can cause weight gain? (2)
- Sulphonylureas
2. Pioglitazone
Which oral antidiabetic can cause fluid retention?
Pioglitazone
Which oral antidiabetic should not be used in the elderly?
Sulfonylureas
Which oral antidiabetic can cause fractures?
Pioglitazone
Which oral antidiabetic should be avoided in G6DP deficiency?
Sulfonylureas
Which oral antidiabetic can cause flatulence?
Acarbose
Which oral antidiabetic can cause acute pancreatitis?
DPP-4 inhibitors (gliptins)
Which antidiabetic can lead to lower limb amputations?
SGT-2 inhibitors (FLOZIN)
As well as a risk of hypoglycaemia, which antidiabetic can cause injection site itch?
SGT-2 inhibitos (FLOZIN)
Diabetes carries a strong risk for which other disease?
Cardiovascular disease
Which non-antidiabetic drugs can be used in diabetes to reduce the risk of cardiovascular risk? (3)
- ACE inhibitor
- Low dose aspirin
- Lipid-regulating drug
To manage the risk of diabetic nephropathy, regular review of diabetic patients should include which tests? (2)
- Urinary protein
2. Serum creatinine
Even if blood pressure is normal, all diabetic patients with established microalbuminuria (3 positive tests) should be treated with which drug?
ACE inhibitor (or ARB)
Which electrolyte disturbance are T2DM patients with nephropathy more susceptible to?
Hyperkalaemia
Can an ACE inhibitor be combined with an ARB to treat diabetic nephropathy?
No - risk of hyperkalaemia
When used with insulin and/or oral antidiabetic drugs, what can ACE inhibitors potentiate? Especially in the first few weeks of treatment, especially in patients with renal impairment
Hypoglycaemic effect
Which drugs can be used to control mild-moderate diabetic neuropathic pain? (2)
- Paracetamol
2. Ibuprofen
After paracetamol and ibuprofen, what is the first line treatment for diabetic neuropathy?
Duloxetine
If duloxetine is not tolerated in diabetic neuropathy, what else can be tried?
Amitriptyline
To manage the pain of diabetic neuropathy, if amitriptyline cannot be tolerated, which drug can be tried?
Nortriptyline
To manage the pain of diabetic neuropathy, what is the next step if neither duloxetine or amitriptyline are effective? (2)
- Duloxetine + Pregabalin
2. Amitriptyline + Pregabalin
To which class of analgesics can diabetic neuropathic pain be responsive to?
Opioids
For the treatment of diabetic neuropathy, which drugs can be only initiated under specialist supervision?
- Oxycodone
- Morphine
- Tramadol
As well as pregabalin, which other anti-epileptics can be used to treat diabetic neuropathic pain? (2)
- Gabapentin
2. Carbamazepine
During pregnancy, which drug can women with pre-exiting diabetes be treated with? (unlicensed)
Metformin
During pregnancy, can women with pre-exiting diabetes be treated with both metformin and insulin?
Yes
What are the treatment options for gestational diabetes, after 11 weeks?
- Metformin
- Glibenclamide
- Glibenclamide with insulin
How long after giving birth should antidiabetic treatment be carried on?
It should be stopped after giving birth
True or false: All patients with diabetes should have emergency treatment for hypoglycamia written on their drug chart on admission
TRUE
True or false: All patients undergoing any type of surgery should be put on a continuous variable rate insulin infusion
FALSE: patients going for minor surgery with good glycaemic control, HbA1c less than 69mmol/mol, can have their usual insulin the day before surgery. Long-acting once daily preparation to be reduced by 20%
What should a continuous variable rate insulin infusion be administered with?
A glucose substrate
On the day of surgery and throughout the intra-operative period, can patients receive their regular insulin if they do not need to be on a continuous variable rate insulin infusion?
No, basal only until eating and drinking
After a patient has been on a a continuous variable rate insulin infusion, when can they be converted back to their regular insulin?
If they are eating and drinking without nausea or vomiting
At which point does the patient start taking their regular insulin after they have been on a continuous variable rate insulin infusion?
With their first post-operative meal
How long after the first dose of post-operative insulin after the patient’s first meal is the continuous variable rate insulin infusion continued?
30-60 minutes
If a diabetic patients taking insulin requires emergency surgery; blood glucose, urinary ketones, serum electrolytes and serum bicarbonate should be checked before surgery. Which state, if present, can cause delay in treatment?
Ketoacidosis
If a patient taking antidiabetic drugs requires insulin during surgery, can their regular drugs be continued?
No, all but GLP-1 mimetics (TIDES) need to be stopped
Which oral antidiabetics should always be omitted on the day of surgery and until the patient is eating and drinking as normal again? (2)
Sulfonylureas
SGT-2 inhibitors
Should metformin always omitted during surgery?
No, if they have an eGFR greater than 60mL/min and no contrast media is being used, may need to only omit the lunchtime dose if the patient is taking it TDS
Which condition are SGT-2 inhibitors associated with during periods of dehydration, stress, surgery, trauma, and acute medical illness?
Diabetic ketoacidosis
What does the management of diabetic ketoacidosis involve?
- Fluid and electrolyte replacement
2. Insulin
At which blood pressure should we administer 500mL sodium chloride 0.9% over 10-15mins in diabetic ketoacidosis?
below 90mmHg
Which electrolyte should be included in IV fluids when treating diabetic ketoacidosis?
Potassium chloride
At which times should plasma potassium be monitored in diabetic ketoacidosis when administering potassium chloride? (3)
- At 60 minutes
- At 2 hours
- Every 2 hours
Which preparation of insulin should be used in diabetic ketoacidosis
Soluble
True or false: established treatment with long-acting insulin should be continued during diabetic ketoacidosis
TRUE
With a small but significant effect on lowering blood glucose, what does arcabose delay?
Digestion and absorption of starch and sucrose
What is the metformin mechanism of action? (2)
- Decreases gluconeogensis
2. Increases peripheral utilisation of glucose
Can metformin be given to someone without any residual functioning pancreatic islet cells?
No, requires some endogenous insulin to work
What must be determined before treatment is commenced with metformin and at least annually thereafter?
Renal function
What are the symptoms of lactic acidosis that patients and carers taking metformin should be counselled on? (5)
- Dyspnoea
- Muscle cramps
- Abdominal pain
- Hypothermia
- Asthenia
What is the mechanism of action of DPP-4 inhibitors (GLIPTINS)? (2)
- Increase insulin secretion
2. Lower glucagon secretion
DPP-4 inhibitors can cause pancreatitis, what is the symptom of pancreatitis that patients should be made aware of?
Persistent, severe abdominal pain
Which DPP-4 can cause hepatotoxicity?
Vidagliptin
What is the mechnism of action of GLP-1 mimetics (TIDES)? (2)
- Augment glucose-dependent insulin secretion
2. Slow gastric emptying
What is the dose of dulaglutide?
Once weekly
As well as DPP-4 mimetics, which other class of antidiabetic drug can cause pancreatitis?
GLP-1 mimetics
If a patient misses a dose of dulaglutide, what should they do?
- More than 3 days until next dose, take and take next as normal
- Less than 3 days until next dose, don’t take and take next as normal
Women of child-bearing age should take contraception during treatment and 12 weeks after discontinuation when taking which GLP-1 mimetic?
Exenatide
What are the MHRA alerts associated with Canagliflozin? (2)
- Lower limb amputation (mainly toes)
2. Diabetic ketoacidosis
MHRA advice is to; consider stopping canagliflozin if a patient develops foot problems, monitor all patients with risk factors for diabetic foot problems and what else?
Ensure they stay well hydrated and monitor for signs of salt and water loss
What are the signs and symptoms of diabetic ketoacidosis? (8)
- Fast, deep breathing
- Rapid weight loss
- Nausea and vomiting
- Abdominal pain
- Sleepiness
- Sweet smell to breath
- Sweet metallic taste in mouth
- Different odour/colour to urine
If DKA is diagnosed or suspected in someone taking canagliflozin, what should happen to their treatment?
Discontinue