4. Diabetes Mellitus and hypoglycaemia Flashcards
1
Q
Diabetes mellitus
A
A metabolic disorder characterised by persistently high blood glucose levels
2
Q
Type 1 and Type 2 Diabetes mellitus
A
Type 1: Autoimmune destruction of beta islet cells
Type 2: Cells do not respond to insulin
3
Q
Diabetes Mellitus symptoms
A
- Polyuria - body’s attempt to get rid of excessve glucose from the blood
- Polydipsia
- Polyphagia - peripheral tissues cannot take up glucose from the blood to use an energy
- Poor wound healing
- Fatigue
- Weight Loss - body breaks down fat and muscle to use an alternative form of energy
- Blurred vision
- Glucosuria - predispose to cystitis vaginal thrush. (REFER DIABETES PATIENTS = POOR GLYCAEMIC CONTROL)
4
Q
Macrovascular complications of diabetes mellitus
A
- Stroke
- Heart attack/atherosclerosis
5
Q
Microvascular complications of diabetes mellitus
A
- Diabetic retinopathy
- Diabetic nephropathy
- Peripheral neuropathy —> diabetic foot, wound healing is slow in diabetes
Refer diabetics immediately, if they present with foot issues, do not treat with anything OTC
6
Q
Treatment of macrovascular complications
A
Cardiovascular disease:
Primary -
Low dose statin
(If patient is over 40, has had type 1 diabetes for over 10 years, has had type 2 diabetes for over 20 years, has target organ damage)
Secondary-
Low-dose aspirin
7
Q
Treatment of microvascular complications
A
High blood pressure and high glucose levels damage blood vessels supply the kidneys and eyes. Must reduce BP to treat retinopathy and nephropathy
Diabetic retinopathy
Treat hypertension
Diabetic nephropathy
Treat hypertension
The vessels in the kidneys, leak albumin into the urine = proteinuria. This is treated with a low-dose ACE inhibitor, which has renal protective properties.
ACE inhibitors cause hyperkalaemia. In kidney disease, you have reduced ability to excrete potassium into the urine. Therefore cannot combine this with another drug that also causes hyperkalaemia
Diabetic neuropathy
Neuropathic pain is treated with analgesics, tricyclic antidepressants, anti-epileptic drugs.
Nerves suppling penis is damaged, therefore can cause erectile dysfunction. This is treated with a phosphodiesterase type 5 inhibitor (sildenafil).
8
Q
Diabetic ketoacidosis symptoms
A
- fruity breath
- dehydration & extreme thirst
- polyuria
- High conc of ketones in blood and urine
- Blood glucose conc >11 mmol/L
- Abdominal pain
- N + V
9
Q
Diabetic ketoacidosis treatment
A
- IV infusion to replace eletcrolytes and insulin
- Short acting insulin
- Do not administer potassium if patient is anuric, as kidneys will be unable to filter it out from blood
10
Q
What is diabetic ketoacidosis
A
More common with type1 diabetics, where the body breaks down fat to use as an alternative source of energy. This process causes a build-up of ketones in the blood and urine. Ketones lower blood PH and make blood acidic.
11
Q
Risk factors for diabetic ketoacidosis
A
- surgery
- interucurrent illness
- dehydration
- restricted food intake
12
Q
What are the 3 types of insulin
A
- Human- soluble insulin (developed from recombinant technology)
- Human analogues - rapid and long-acting (modified human insulin, developed from recombinant technology)
- Beef/Pork - soluble animal
13
Q
Diabetes Mellitus
Type 1 treatment
A
- Parenteral insulin (mostly subcutaneous), adjusted according to patient’s needs.
14
Q
More insulin is needed, during:
A
- infection/illness, as cortisol increases which causes glucose to increase
- surgery, trauma
- Puberty, pregnancy (2nd/3rd timester)
15
Q
Less insulin needed, during:
A
- Reduced food intake, physical activity
- Renal impairement
- Endocrine disorders, e.g Addison’s disease
16
Q
Side effect of insulin
A
Weight gain
HypOglycaemia
17
Q
Insulin counselling
A
- Adminster subcutaenously into abdomen, thighs, buttocks, upper arm
- Rotate injection sites to prevent lipodystrophy which reduces insulin abroption, thus glycaemic control
- Check site for signs of swelling, bruising
- Avoid missing meals and strenous exercise
- Residual insulin SHOULD NOT be extracted from pen devices
- Patients should not inject themselves intravenously, route only reserved for medical personnel
- Unopened insulin should be stored 2-8 degrees and once opened, should be stored at room temperature. Can be used by <28 days. FROZEN INSULIN must be thrown away
18
Q
Prescribing insulin considerations
A
- NEVER give IV syringes for SC injections. IV syringes are in mm and SC syringes are in units
- Doses should be prescribed in UNITS of INTERNATIONAL UNITS, IU/U not acceptable
19
Q
Types of insulin preparations
A
BOLUS/Large single dose. Usally faster onset,
- Rapid-acting
- Short-acting
BASAL/Background insulin. Usually has a slow onset.
- Intermediate-acting
- Long-acting
20
Q
Short-acting insulin (soluble insulin)
A
- HUMAN OR BEEF/PORK
Route:
SC and IM
IV: surgery or emergency
Time:
15-30 min before meals. Must eat within less than 30 minutes of administering to prevent hypos
21
Q
Rapid-acting insulin (analogue)
A
- Aspart (Novorapid)
- Glulisine (Apidra)
- Lispro (Humalog)
Route: SC, IV if emergency
Time:
Just before meals, lower risk of hypo before meals as it prevents insulin levels from spiking, during meals.
Rapid-acting insulins mimic the insulin secretion profile more closely - more preferred
22
Q
Intermediate acting insulin
A
- Isophane (NPH). This is mixed with short-acting insulin and protamine, which is a protein used to extend duration of action. However, protamine associated with allergic reactions.
Route:
NOT IV - linked to thrombosis
Administration:
Take BD
23
Q
Long-acting insulin
A
- Degludec (Tresiba)
- Detemir (Levemir)
- Glargine (Lantus)
- Protamine zinc
- Zinc Insulin
Time:
Taken OD at the same time
24
Q
Type 1 diabetes Insulin Regimens
A
- Multiple Injections/Basal-bolus. This is 1st line in type 1 diabetes
- Biphasic. This is an alternative to basal-bolus.
- Subcutaenous infusion, Typically given to patients with type 1 diabetes that are under 12
25
Basal-bolus regimen
Short OR Rapid-acting (before each meal)
AND
Intermediate OR Long-acting (once or twice a day)
Pro: Flexible dosing, can match insulin dose to carb intake
Con: More injections
26
Biphasic regimen
Short OR Rapid-acting
MIXED
with intermediate acting
(e.g twice a day before meals)
Pro: Less injections
Cons: Insulin doses are fixed so less flexible, Cannot tailor doses e.g during an illness.
Patients must ensure carb intake matches fixed dose. Must also ensure insulin proportions are apropriate e.g Humlin M3 is 30/70 (30% short acting, 70% Long acting)
27
Subcuteanous Infusion Regimen
Short OR Rapid acting is a continous infeusion, using a programmabble pump
28
Type 2 diabetes insulin regimens
**Basal-only**
Human isophane injected *once/twice* daily as a basal insulin.
Alternatively, determir/glargine if lifestyle is restricted by hypo episodes or if a patient needs help injecting. Hypos are less likely with long-acting insulins as they are more steady.
**Multiple injections/biphasic**
Human isophane + short-acting (before each meal)
Alterntaively rapid acting insulin can be used as it better controls glucose levels, following a meal. Prevents nocturnal hypos.
29
Types of insulin devices
1. Insulin pen
2. Insulin pump
3. Insulin syringe (not as popular, only if the insulin is not available as a cartridge)
30
Diabetes mellitus sick-day rules
**S**- Sugar. Monitor blood glucose levels more frequently, every 3-4 hours including throughout the night and until you feel better
**I**- Insulin. Never stop taking insulin. May even require more insulin.
**C**- Carbs. Eat carbs as normal. If unable to do this, replace with high carb drink, such as apple juice or milkshake. Drink at least 3 litres of fluid a day.
Seek medical help if persistent v + n
**K** - Ketones. Patient should check for ketones every 3-4 hrs, including throughout the night.
Medical help:
Urine ketone ≥ 2 mmol/L
Blood ketone ≥ 3 mmol/L
31
Insulin interactions
**Beta blockers** - mask symptoms of hypoglycaemia
**ACE inhibitors & ARBS** - enhance the hypoglycaemic effects of oral antidiabetic drugs, through inducing hyperkalemia. Glucose and potassium are linked.
**Antipsychotics (clozapine & olanzapine), Corticosteroids, Thiazide Diuretics** cause hyperglycaemia. This antagonises insulin
32
Insulin administration during surgery
For a major procedure, during emergencies:
Done though a 'sliding scale' with human insulin. This is a variable rate infusion determined by blood glucose measured hourly.
Remember cortisol increases during surgery, therefore glucose will too
Minor procedure:
Ajust insulin
33
Metformin mechanism of action, pregnancy
Reduces glucose synthesis in the liver, to reduce glucose levels AND increases glucose uptake by peripheral tissues
Insulin sensitiser so only works if insulin is present in the body.
SAFE in pregnant women AND breastfeeding
1st line for Type 2 diabetes
34
Metformin side effects, cautions, contraindications and counselling
* Does not cause hypoglycaemia
* Causes weightloss
* Causes GI disorders: nausea, vomiting, diarrohea. These side effects can make it intolerable.
* Taste disturbance
* Reduced Vitamin B12 absoroption
To manage the GI side effects, gradually increase the dose and switch to modified release preparation
Counselling: Metformin should be taken with or just after food
* Rarely can cauce lactic acidosis: gradual build up of lactic acid, which lowers the PH of blood.
Patients should seek immediate medical atttention if the following occurs: dynpoae, abdominal pain, hypothermia, asthenia, cramps.
AVOID Metformin in severe renal impairment as metformin is cleared by the kidneys and can cause built up of lactic acid OR in conditions that cause acute kidney injury such as dehydration or infection.
Lactic acidosis more liekely to occur in codnitons where the kidneys are deprived of oxygen such as acute heart failure or recent heart attack
35
Sulphonylureas mechanism of action
Sulponylureas increase insulin secretion so can only work if insulin is being made inside the body.
Can be long-acting or short acting
Short-acting: elderely patients, renal impairement as these patient groups are at greater risk of hypoglycaemia
examples include: Gliclazide, Glipizide,
36
Sulphonylureas side effects and interactions
* Sulphonylurea induced hypoglycaemia can be **dangerous** and last for many hours, can be fatal. Treated in hospital.
* Glipizide and Gliclazide can cause hyponatraemia. This may cause falls in the elderely.
* Can cause weight gain, due to increased insulin levels
* Hypersensitivity reactions
Interactions
ACE inhibitors and ARBS potentiate the Hypoglycaemic effects of oral antidiabetic drugs, as they cause hypERkalaemia, which is linked to HypOglycaemia
37
Pioglitazone mechanism of action, examples and side effects
Reduces peripheral resistance in peripheral tissues
Side effects:
- Heart failure (monitor for signs of heart failure such as breathlessness, swelling)
- Bladder cancer (monitor for haematuria, dysuria)
- Hepatotoxicty
38
SGLT inhibitors mechansims of action, examples and side effects
Inhibits sodium-glucose transporter, therefore sodium excretion increases. Reduces Sodium and glucose reabsoprtion
* Diabetic ketoacidosis, (can present as moderately high glucose levels)
* Volume depletion (as they increase urinary sodium excretion)
* Fournier's gangrene (flesh eating bacterium of the genitals)
Examples include:
Dapaglizon
Canaglifozin (increased risk of lower limb amputation)
Empaglifozin
39
DPP inhibitors examples, mechanism of action and side effects
Inhibits dipeptidylpeptidase-4, (the enzyme breaks down incretins), incretins increases insulin secretion and suppress glucagon secretion
Side effects:
- pancreatitis (persistent, severe abdominal pain)
- hepatoxicity
examples include:
sitagliptin, aloglitpin, saxaglitpin (gliptins)
40
GLP-1 agonists examples, mechansim of action
Act on receptors peptide-1 receptors (type of increitin) to increase insulin secretion and decrease glucagon secretion
Prescribed if
* BMI ≥ 35 and patients has psychological/medical issues with obesity
* BMI<35 and if weight loss would benefit a significant obesity related co-morbidity, patient has job complications with insulin, or for weight loss
examples:
- Dulaglutide
- Liraglutide
- Exenatide
-
41
GLP-1 agonists route and side effects
- Only anti-diabetic drug given by injection. All are stored in the fridge except exenatide and lixisenatide
Side effects:
- gastrointestinal side effects as the drug delays gastric emptying so food remains in the stomach for longer
- Pancreatitis
- Diabetic ketoacidosis if insulin is rapidly reduced or discontinued
- Contraceptives mmust be taken by women of child-bearing age with exenatide and lisexenatide
42
Acarbose mechanism of action, side effect, counselling
Inhibits alpha-glucosidade to reduce starch and sucrose absorption.
Reserved for use when other antidiabetic drugs fail
- Flatulence (reduced with time)
- Diarrhoea
Counselling:
Acarbose should be chewed with the first mouthful of food or swallowed whole with a little liquid immediately before food
Glucose (NOT SUCROSE as acarbose delays absorption of sucrose) should be carried to treat hyperglycaemia
43
Meglitinides mechanism of action, side effects and counselling
Stimulate insulin secretion
Side effects:
* hypoglycaemia
* Diarrhoea
Counselling:
Should be taken shortly before each main meal
44
kidney sick day rules
During an intercurrent illness, there is an increased risk of an acute kidney injury:
Some antidiabetic drugs need to be temporarily stopped, due to this:
- Metformin
(as it is renally cleared, and increases the risk of lactic acidosis)
- SGLT inhibitors
(As they work on the kidneys and can cause volume depletion - a risk factor for acute kidney injury)
45
During surgery
**Major procedure**: all antidiabetic drugs except GLP-1 agonists should be stopped. Patients are transferred to sliding scale insulin
**Minor procedure**
Pioglitazone, DPP inhibitor, GLP-1 agonists can be continued as normal
CAUTION WITH
SGLT inhibitors: risk of diabetic ketoacidosis
Sulphonylureas: hypoglycaemia in fasted state
Metformin: renal impairement and lactic acidosis
46
Diabetes and pregnancy
To reudce risk of neural tube defects, patients should take 5mg folic acid daily before conception until week 12 (first trimester)
HBA1C targetL <48mmol/ml (6.5%)
47
Treating diabetes in pregnancy
Rapid acting + isophane insulin
Insulin requirements increase during the 2nd and 3rd trimester, so higher doses are needed. Then reduced immediately after birth.
All oral antidiabetic drugs must be stopped in pregnancy except metformin. ACE-inhibitors, ARBS, statins are also teratogenic.
48
Gestational diabetes & treatment & Breastfeeding
## Footnote
Different to women who have diabetes prior to pregnancy
Occurs when pregnant women is unable to meet the increased insulin demand
If if glucose is < 7mmol/L
1st line: Diet and exercise.
2nd line: offer metformin If blood glucose targets are not met within 1-2 weeks
If glucose is > 7mmol/L
1st line: insulin WITH OR WITHOUT Metformin
Stop treatment after birth
**Breastfeeding**
Insulin and Metformin are safe with breastfeeding
49
What is hypoglycaemia
When blood glucose levels fall below 4 mmol/L. Common with sulphonulureas
symptoms:
- tingling lips
- sweats/chills
- pale/clammy skin
- hunger
- drowsy/confused
50
Hypoglycaemia treatment
Patients must check their blood glucose levels immediately
If > 4mmol/L: small carbohydrate snack or have their next meal
If < 4mmol/L : 15-20g of fast acting sugar (up to 200ml of fruit juice, glucose oral gel between gums and check if patient is unconscious, 4-5 glucose tablets). This should be followed by a long-acting carbohydrate to sustain glucose levels and prevent it from falling again.
Hypoglycaemia caused by sulphonylureas must be treated in hospital as it may be fatal.
51
Diabetes diagnosis
HbA1c of ≥ 6.5% or 48mmol/mol warrants a diabetes diagnosis
Oral glucose tolerance test diagnosis pre-diabetes and gestational diabetes. The test measures how the body responds to the ingested glucose.
52
Diabetes Mellitus monitoring
Type 1 diabetes: 4x a day (before each meal and before bed)
Not routinely recommended for type 2 diabetics to be testing their blood glucose UNLESS:
- driving
- intercurrent illness
- medication changes
53
Blood glucose level targets
| waking, before meals, after meals, driving
Waking (fasting): 5-7mmol/L
Before meals: 4-7 mmol/L
90 minutes after meal: 5-9mmol/L
Driving: at least 5 mmol/L
Must ensure it does not fallow below 4mmol/L as this = hypoglycaemia
54
HbA1c targets
Type 1 diabetes: 6.5% (48mmol/mol)
Type 2 diabetes:
* diet controlled monotherapy: 6.5% (48mmol/mol)
* Hypoglycaemic monotherapy & combination therapy: 7.0 % (53mmol/mol)
* Intensify monotherapy if HbA1c >7.5% (58mmol/mol)
55
Hypertension targets in diabetes
Type 1: 140/90
Type 1 albumin creatnine ratio: <130/80
Type 2 under 80: <140/90
Type 2 Over 80: <150/90
56
Cholesterol targets in diabetes
Normal patients < 5mmol/L
High risk patient: <4 mmol/L
57
Diabetic patients that must notify the DVLA
* Patients taking insulin
* Patients who have had 2+ severe episodes of hypos <12 months, patients wirth imapired awareness, disabling hypos while driving
* Bus, lorry drivers
* patients with diabetic complications, e.g retinopathy
58
How should diabetic patients monitor their blood glucose whilst driving
2 hours before driving AND every 2 hours for a long journey
If blood glucose is <5 mmol/L: eat carbohydrate snack
If blood glucose is <4 mmol/L: avoid driving
During hypo, must stop vehicle, switch it off. Conduct treatment and wait for 45 minutes
