Diabetes Flashcards
Describe the normal profile of plasma insulin throughout the day
Peaks at mealtimes with basal levels inbetween
In a normal person, what triggers an increase in insulin?
- increased glucose
- incretins (GLP-1, GIP)
- glucagon
- parasympathetic activity (M3)
In a normal person, what triggers a decrease in insulin?
- decreased glucose
- cortisol
- sympathetic activity (alpha 2)
What is the role of insulin?
- Decreased hepatic glucose output by inhibiting gluconeogenesis
- Inhibits glycogenolysis
- Promotes uptake of fats
What level of glucose in a random plasma glucose test would suggest diabetes?
plasma glucose _>_11 mmol/L
What are some of the symptoms of diabetes?
- polyuria
- polydipsia
- weight loss
- fatigue/ lethargy
What are some risk factors for developing type 2 diabetes?
- Obesity - 80/85% risk
- Family history
- Ethnicity
- Poor diet
- Drugs - thiazide/ thiazide like diuretics, glucocorticoids, Beta blockers
- Low birth weight (some evidence)
What 2 blood measurements are usually taken when monitoring diabetics?
- Blood glucose - immediate measure of glucose
- HbA1c- glycated Hb, reflets the average blood sugar over last 10-12 weeks
Why must insulin be given parenterally?
Insulin is a protein so would be digested in the gut if given orally
What form of insulin is given to patients in the UK today?
Recombinant form of human insulin (bacteria/ yeast)
or, enzymatic modification of porcine
What is the usual formulation of insulin given?
100 U/ mL
(although 300 and 500 U/mL are available)
How do you administer insulin?
- Routinely delivered by subcutaneus injection
- To; upper arms, thighs, buttocks, abdomen
- Can be given intravenously for emergency treatment
When is concentration of insulin in plasma highest after meals?
When would you administer insulin around meal times?
Greatest 2-3 hours post meals
Administer 15-30 mins prior to meals
Why must you change the site of administration of insulin injections?
Repeated injection at the same site can cause lipdystrophy
(atrophy/ hypertrophy of lipid profile around the site changes absorption)
What are the different preparations of insulin?
(onset of action, peak of action, duration, class)
In which patients would you avoid giving insulin to?
- Hypoglycaemic patients
- Lipohypertrophic patients
- Lipoatrophic patients
- Patients with renal impairment
All have a risk of hypoglycaemia
In which patients do you have to use insulin with caution?
- increased doses on patients with steroids
- use with caution if on other hypoglycaemic agents
What is the benefit of delivering insulin via a pump?
- reduces long term cost
- less errors in dosing
- less change of hypoglycaemia
What is basal bolus dosing for insulin?
A bolus dose is given around mealtimes- rapid acting e.g. aspart
A long acting (basal) dose is given to maintain basal levels - long acting e.g. glargine
When would you suspect diabetic ketoacidosis?
Blood glucose >11 mmol/L AND
- infection
- stress/ trauma
- poor insulin adherance
- adverse drug reaction
- ketosis
What is the primary treatment for treating diabetic ketoacidosis?
Fluids are the priority, followed by insulin
What is the secondary treatment for DKA
After fluids and insulin give…
Glucose and potassium
Why do you need to give potassium in DKA?
Due to acidosis there is reciprocal movement of H+(into cells) and K+ (out of cells)
K+ movement out of cells causes eventual loss that will need to be replaced
Always monitor with an ECG due to changes in potassium
What pathological changes happen in type 2 diabetes?
- A reduction in sensitivity to insulin into cells
- Insulin resistance initally overcome by an increase in pancreatic insulin secretion
- Eventual decrease in insulin receptors and decrease in GLP-1 secretion
- Glucotoxicity from fatty acids and ROS can cause Beta cell dysfunction
How can you treat type II diabetes non-pharmacologically?
- Lifestyle (can be reversed!)
- Surgery (bariatric)
- Education
What is the first line pharmacological of treatment for type II diabetics?
Metformin (Biguanide)
How does metformin work?
- Decreases hepatic glucose output but reducing gluconeogenesis and glycogenolysis
- Increase glucose utilisation in skeletal muscle
- Suppresses appetite to limit weight gain
What are the side effects of metformin.
When would you not prescribe metformin?
Side effects:
- GI upset
- Nausea
- Vomiting
- Diarrhoea
- Lactic acidosis (rare)
- Excreted unchanged by kidneys so stop if eGFR <30mL/min
When would you be careful about prescribing metformin due to drug-drug interactions?
Patients on:
- ACEi
- Diuretics
- NSAIDs
- Any drug that may impair renal function e.g. thiazide like diuretics
- Drugs that increase glucose may limit effectiveness
What is the mechanism of action of sulfonylureas? (SU)
Stimulates Beta cell pancreas insulin secretion by blocking ATP K+ channels
- blocking K+ channel causes membrane depolarisation
- VOCC open → Ca2+ influx into cell causes insulin vesicle secretion
(needs some residual pancreatic function)
What is the name of the most commonly used sulfonylurea?
Gliclazide
What are the side effects of sulfonylureas?
- Weight gain due to anabolic effect of insulin (not suitable for all patients)
-
GI upset
- Nausea and vomiting
- diarrhoea
- Hypoglycaemia if given with other agents
- Hypersensitivity reactions (rare)
When should you prescribe sulfonylureas with caution?
- Other hypoglycaemic agents
- Hepatic impairment
- Renal impairment
- Thiazide like diuretics increase glucose so can reduce SU action
What is the mechanism of action of thiazolinediones (glitazones) in treating type II diabetes?
- Insulin sensitisation in muscle and adipose decreases hepatic glucose output
- Activate PPAR-y causing changes in gene transcription
- Turns glucose to triacylglyceride
- Causes weight gain
Used less frequently than other agents
Name the most common glitazones?
- Pioglitazone
- Rosiglitazone
When are some of the risks of glitazones and when should they be used with caution?
Risks:
- GI upset
- fluid retention
- fracture risk
- CVD concerns
- Bladder cancer
Use with caution: other hypoglycaemics
What is the mechanism of action of SGLT-2 inhibitors (gliflozins)
- Inhibit SGLT2 in PCT causing decreased glucose absorption from tubular filtrate
- Increases glucose excretion in urine
- Causes modest weight loss
- Risk of hypoglycaemia is low
Name the 2 most common SGLT2 inhibitors?
Dapagliflozin
Canagliflozin
Which patients do you use SGLT2 inhibitors in?
When should you prescribe with caution?
Used in Type 1 diabetics at risk of DKA
Used in Type 2 diabetics as an add on therapy
Prescribe with caution in:
- prescribed other antihypertensives
- other hypoglycaemic agents
What are some of the side effects of SGLT2 inhibitors?
- UTI and genital infection
- Thirst and polyuria (due to diuretic effect)
What are some of the physiological effects of GLP-1 (Glucagon like peptide)
What is the mechanism of action of DPP-4 inhibitors (gliptins)?
- Prevent incretin degredation → increases plasma incretin
- Incretins are glucose dependent so only act post-prandially (don’t stimulate insulin at normal blood glucose levels) therefore have low hypoglycaemic risk
- Suppress appetite - good for weight control
What are some of the side effects/ risks of DDP-4 inhibitors?
- GI upset
- Small risk of pancreatitis
- Avoid use in pregnancy
When should you prescribe DDP-4 inhibitors ( gliptins) with caution?
- other hypoglycaemic agents
- drugs that increase glucose (thiazides, loop diuretics) can oppose effects of gliptins
Name 2 commonly used DDP-4 inhibitors (gliptins)
- Sitagliptin
- Saxagliptin
Explain how GLP-1 receptor agonists work
- Mimick effects of incretins (GLP-1)
- Activates GLP-1 receptors (not degraded by DPP-4)
- Promotes satiety and weight loss
Name two GLP-1 receptor agonists
- Exenatide
- Liraglutide
What are some side effects of GLP-1 agonists, when would you use with caution?
Side effects:
- GI upset
- GORD
- Stop if eGFR <30mL/min
Use with caution with other hypoglycaemics
What is diabulimia?
A problem with diabetics not using insulin to control their weight
Eating disorder
Why swallow tablets whole when giving modified release preparations?
Coating of tablets causes modified release
Chewing tablet will stop modified release effect
