Diabetes Flashcards
What is the value for hypoglycaemia?
<2.5mmol/L
What is the value for hyperglycaemia?
> 10mmol/L
What are the values for normoglycaemia?
3-5mmol/L - healthy fasting value
7-8mmol/L - post prandial
Describes the events of hyperglycaemia
Rise in blood sugar from eating carbohydrate rich food
Insulin release from beta cells in pancreas
Insulin exerts an effect on different tissues in the body
As a result of insulin release, blood sugar reduces
Describe the events of hypoglycaemia
Low blood sugar levels from overnight or deliberate fasting
Glucagon is released
Glucagon promotes endogenous glucose production, increasing availability of glucose in the blood
Raises blood sugar levels
What is insulin?
A protein hormone derived from pro-insulin
Where is insulin synthesised?
Beta cells - in the islets of Langerhans
When would insulin be complexed with zinc?
When used for slow release formulations
What is insulins half life?
3-5 mins
How does insulin lower blood sugar?
Binds to insulin receptors on tissues
Insulin receptor is a dimer - insulin binding triggers a conformation change
Endogenous kinase protein is switched on
Receptor becomes active and has kinase activity
Transport protein switched on - becomes active and transports glucose across cell membrane
Signalling cascade leads to more transporters in the cell membrane
How does insulin promote hypoglycaemia?
Increases transport of glucose into cells Converts glucose to glycogen Decreases glycogen breakdown Increases fat stores increases protein production
Glucose levels lean towards hyperglycaemia when…
Food intake is increased
Glucose is produced
Glucose is reabsorbed
Glucose levels lean towards hypoglycaemia when…
Glucose is utilised
Food intake decreases
Glucose is stored
Glucose is lost
What is diabetes?
A chronic disease which occurs when the pancreas doesn’t produce enough insulin OR when the body can’t used insulin produced effectively.
What are the non-medical causes of hypoglycaemia?
Inadequate, irregular food intake
Insulin overdose
Sulphonylurea overdose
What are the medical causes of hypoglycaemia?
Insulinoma Hyperinsulinism T1DM Post-gastric bypass hypoglycaemia Transient neonatal hypoglycaemia
What is glucagon used for?
Severe hypoglycaemia when oral glucose is not possible / desired
Given by injection
What is diazoxide therapy used for?
Recurrent hypoglycaemia
Inhibit glucose action on beta cells to stop insulin release
- Eudemine 50mg tablets (Proglychem brand)
What are the presenting symptoms of T1DM?
Polyuria Polydipsia Fatigue/lethargic Weight loss DKA
What happens in response to the absence of insulin in T1DM diabetic ketoacidosis?
Increase in glycogenesis and gluconeogenesis and reduced glucose uptake by tissues
Increased urine output
Suppressed lipolysis
What are the symptoms of DKA?
Tachypnoea
Altered mental state
N&V
Abdominal pain
What needs to be done in the first 4 hours of someone presenting with DKA?
Fluid resuscitation - isotonic fluids only and given slowly
Insulin infusion
Maintenance fluid
Reintroduce food and drink
When should a DKA patient be switched to maintenance fluid?
Once cBG is <15mmol/L
At what point should a DKA patient be given s/c insulin?
30 mins before stopping insulin infusion
When should insulin be started in a child with DKA?
cBG <14mmol/L
Ketones <3mmol/L
Resolved acidosis
Oral fluids are tolerated
Basal bolus insulin regime:
Long acting in the evening or BD
3 doses of short/rapid acting during the day before meals (based on carb intake)
Biphasic insulin regime:
2 biphasic doses, morning and tea time
Dose split depends on biggest meal
Describe rapid acting insulin and give examples
Mimics pancreases
Onset 5-15 mins, peak 30-90min, duration 4-6 hours
Novorapid - Insulin Aspart
Humalog - Insulin lispro
Apidra - Insulin glulisine
Describe short acting insulin and give examples
Soluble
Onset 30mins-1hour, peak 2-3 hours, duration 8-10 hours
Human Actrapid - human insulin
Humulin S - human insulin
Insuman rapid - human insulin
Describe intermediate acting insulin and give examples
Isophane insulin
Onset 2-4 hours, peak 4-10 hours, duration 12-18 hours
Human insulatard
Humulin I
Inusman Basal
Describe long acting insulin and give examples
Flat insulin profile
Onset 2-4 hours, duration 20-24 hours, no peak as it mirrors basal insulin out put in non-diabetics
Lantus & Abasaglar - Insulin glargine
Levemir - Determir
Describe ultra long acting insulin and give examples
3rd line use. OD administration fives flattest insulin profile. Up to 42 hours duration
Tresiba - Insulin degludec
Toujeo - Insulin glargine 300 units/ml
What are the symptoms of hypoglycaemia in medication controlled diabetes?
<4mmol/L cBG
Hunger, tremor, sweating, palpitation
Odd behaviour drowsiness, visual disturbance, seizures
Headache and nausea
What is used to replace glucose in hospitalised patients?
Conscious - dextrose tabs/glucogel
Unconscious - glucagon IM followed by 10% glucose 100ml/hr
When should insulin be injected? What are the exceptions to this?
Half an hour before meals
Except: insulin lispro, aspart or glulisine - these can be given 5 mins before eating
Define disabling hypoglycaemia
Repeated and unpredictable occurrence of hypos that results in persistent anxiety about recurrence and is associated with adverse effects on quality of life
What is used in the treatment of disabling hypoglycaemia?
Continuous s/c insulin infusion
When should continuous insulin infusion be considered?
Attempts to achieve HbA1c with daily injections results in disabling hypoglycaemia
HbA1c is still high (>69mmol/L) on multiple daily injections despite high level of care
Patient has commitment and competence to use
What is classed as good diabetes management?
Low cBG Low HbA1c Reduced episodes of hypoglycaemia Reduced episodes of hyperglycaemia No hospitalisations Reduces complications and mortality
When is tight control needed?
Benefits outweigh risk
Long term benefits outweigh short term side effects
When is less tight control needed?
Risk outweighs benefits
Little change of long term benefit
What is HbA1c?
The amount of glucose attached to Hb in RBC.
It is a good measure of average blood glucose for the last <6 months and it is a good predictor of heart attack, amputation and microvascular complications.
What is HbA1c a poor predictor of?
Early death, other heart disease, stroke or foot ulcers
What is the normal HbA1c value?
<42 mmol/ml - normal
What is the HbA1c value for pre diabetes?
42-47 mmol/ml
What is the HbA1c value for good diabetes control?
<58 mmol/ml
What is the HbA1c value for moderate diabetes control?
58-70 mmol/ml
What is the HbA1c value for poor diabetes control?
> 70 mmol/ml
Which drug is first line for diabetes?
Metformin
Describe the MoA of biguanides
Inhibit gluceoneogenesis in the liver, results in lower hepatic glucose production
Increases insulin mediated glucose utilisation in peripheral tissues
Give an example of a biguanide and its dosage regime
Metformin
Start dose 500mg OD
Max dose 1g TDS
When is metformin contraindicated and used with caution?
C/I if eGFR <30ml/min/1.73m2
Caution if eGFR <45ml/min/1.73m2
What can a patient do to avoid the severe GI side effects that come with metformin?
Take with meals
What are the advantages biguanides?
Cheap
Weight neutral
Low risk of hypos
What are the disadvantages biguanides?
Can cause GI side effects
Rarely causes lactic acidosis
Short half life - take TDS
Need reasonable renal function
Describe the MoA of sulfonylureas
Directly stimulate insulin release from beta cells by stimulating ATP sensitive potassium channels
Give examples of short and long acting sulfonylureas
Short acting: gliclazide, glipizide, toltubamide, glimepride
Long acting: glibenclamide
What needs to be monitored when a patient is on sulfonylureas?
Liver function - can lead to hepatitis
What are the advantages sulfonyureas?
OD or BD
Quickly lowers cBG
Fewer GI side effects
What are the disadvantages sulfonylureas?
Can cause hypos
Weight gain
Needs residual pancreatic function
Unpredictable in renal impairment and in the elderly
Describe the MoA of thiazolidinediones
Increase insulin sensitivity and reduce glucose production from the liver. They act on adipose and muscle tissues to increase glucose utilisation
Give an example of a thiazolidinedione
Pioglitazone
Starting dose 15mg
What are the advantages of tiazolidindiones?
OD
Low hypo risk
Suitable in renal impairment
What are the disadvantages of tiazolidindiones?
Associated with heart failure, increased risk of bladder cancer and fractures
Causes weight gain
Liver toxicity
3-6 months to show benefit
How do meglitanides differ from sulfonylureas?
Work in the same way but on different beta cells
Give 2 examples of meglitanides
Repaglinide an nareglinide
Describe the MoA of alpha glucosidase inhibitors
Inhibit enzymes that convert complex polysaccharide carbohydrates into monosaccarides. They have a dose dependent effect.
Give an example of an alpha glucosidase inhibitor
Acarbose
Describe the MoA of GLP 1 agonists
Stimulate insulin release from pancreas and suppresses glucagon secretion. Also inhibit gastric emptying and reduce appetite
Give examples of daily and weekly GLP 1 agonists
Daily: exenatide, liraglutide, lixisenatide
Weekly: albiglutide, dugladtide, long acting exenatide
Describe the MoA of DPP-4 inhibitors
Block rapid degradation of GLP 1
Give examples of DPP-4 inhibitors
Sitagliptin
Vildagliptin
Saxagliptin
Alogliptin
Give advantages of DPP-4 inhibitors
OD
No weight gain
Can be used in renal impairment
Give disadvantages of DPP-4 inhibitors
Cause GI side effects, rash and UTIs
Rarely causes pancreatic inflammation
Describe the MoA of SGLT-2 inhibitors
Block active transport of glucose from glomerular filtrate.
When should SGLT-2 inhibitors be stopped?
when eGFR <45ml/min
Give examples of SGLT-2 inhibitors
Canagliflozin
Empagliflozin
Dapagliflozin
What are the advantages of SGLT-2 inhibitors?
Can cause weight loss
Reduces blood pressure (1-3mmHg)
Low risk of hypos
What are the disadvantages of SGLT-2 inhibitors?
Thrush and UTIs when starting Needs reason renal function Lower BP can increase fall risk Risk of DKA Risk of KI and foot ulcers
What type of insulin is first line and why?
Basal insulin
Needs less frequent blood testing, lower hypo risk, and no carb counting. Give as OD or BD injections which are immediate or long acting
What drug combinations can be used in poor diabetes control?
Metformin, DPP-4 inhibitor & sulfonylurea
Metformin, pioglitazone & sulfonyurea
Metformin, sulfonylurea & SGLT-2 (not dapaligflozin)
Metformin, pioglitazone & SGLT-2 (not dapaligflozin)
What are the diabetic microvascular complications?
Retinopathy (proliferative or non-proliferative)
Neuropathy
Nephropathy
What causes diabetic retinopathy? How can it be treated?
High blood sugar makes blood more coagulable - this is an issue in retina due to fine blood vessels. Capiliaries become blocked.
Proliferative: new vessels form & leak blood
Non-proliferative: no new vessels form
No drug treatment but laser therapy burns leakages
What causes diabetic neuropathy? How can it be treated?
Increased blood sugar leads to reduced blood flow and death of nerves. Peripheral neuropathy is most common.
Topical: capsaicin
Antidepressants: duloxetine or amitriptyline/nortriptyline
Anticonvulsants: gabapentin or prcegablin
What causes diabetic foot ulcers?
It is a complication of neuropathy, lack of sensation increases risk of damage to feet.
Increased blood sugars increase infection risk and decrease healing
What causes diabetic nephropathy? How can it be treated?
Nephrons are thickened and scarred making them less effective. Kidney function deteriorates.
Treatment involves good BP control with ACE or ARBs
How can macrovascular complications be prevented?
Control cholesterol - atorvastatin
Control BP - Aspirin 75mg, CCB, ACEI
Control blood sugar
What is T2DM?
Chronic hyperglycaemia due to insulin resistance and impairment of insulin secretion relative to requirements
What are the T2DM risk factors?
Genetics Ethnic background Increased age Female Obesity Poor food choices/sedentary lifestyle Smokers
What are the presenting symptoms of T2DM?
Always hungry Vaginal infections Numbness and tingling of feet Frequent urination Wounds that won't heal Unexplained weight loss Blurred vision Always tired Increased thirst
How can T2DM be treated with diet?
Eat foods: high in fibre, low GI sources of carbs, low fat dairy products, oily fish
Avoid: saturates and trans fatty acids, simple carbs and food aimed at diabetics
How can T2DM be treated with exercise?
Active daily 150 mins a week of moderate activity and 75mins intense activity Muscle strengthening 2x a week Stop smoking Avoid sitting for long periods of time
Which drugs reduce sugar through enhanced insulin secretion?
Sulfonylureas and Meglitanides
Which drugs reduce peripheral insulin resistance?
Metformin and pioglitazone
Which drugs delay carbohydrate absorption?
Acarbose and GLP 1 agonists
Which drugs reduce hepatic glucose output?
Metformin, pioglitazone, DPP-4 inhibitors and GLP 1 agonists
Which drugs reduce glucose rey-take from glomerular filtrate?
SGLT 1 inhibitors
Which drugs enhance the action of incretin?
GLP 1 agonists and DPP-4 inhibitors
