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Diabetes
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Diabetes is a common metabolic disease, Sx: hyperglycaemia, polyuria, polydipsia,
polyphagia
Two groups:
➢ Type 1 Diabetes: caused by insulin deficiency (𝛽 cells destruction, can be Type
1A or 1B)
➢ Type 2 Diabetes: caused by inadequate response to insulin
T1DM

T2DM

𝛽 cells destruction

No 𝛽 cells destruction

Islet cells antibodies present

No islet cells antibodies present

Strong genetic link

Very strong genetic link

Onset age usually <30

Onset age usually > 40

Faster onset of Sx

Slower onset of Sx

Insulin MUST be administered

Diet control and oral hypoglycemic agents

Bodyweight: normal or low

Bodyweight: usually obese

Extreme hyperglycemia can cause DKA

Extreme hyperglycemia can cause hyperosmolar
non-ketotic hyperglycemia

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Complications:
➢ Microvascular/ neuropathic:
✓ Retinopathy, nephropathy, peripheral neuropathy (sensory loss, motor
weakness), autonomic neuropathy (postural hypotension, GIT problems),
foot disease (ulcerations, arthropathy)
➢ Macrovascular:
✓ Coronary circulation (MI), Cerebral circulation (TIA, stroke), Peripheral
circulation (Claudication, ischemia)

Gestational Diabetes
- Etiology is thought to be related to the excess hormone production during pregnancy
which results in insulin resistance
- Risks: macrosomia, microsomia, neonatal hypoglycemia, polycythemia, electrolyte
disorders, respiratory distress syndrome
- Once the child is delivered the diabetic effect goes away immediately
...
T cells react against 𝛽 cells antigens resulting in cell damage
➢ T-helper activates macrophages directed at 𝛽 cells
➢ Cytotoxic T cells directly kill 𝛽 cells
2
...
Autoantibodies against 𝛽 cells and insulin are detected in 70-80% of patients
Assessment and Diagnosis

Monitoring Recommendations and Targets
-

-

Clinical monitoring:
➢ HbA1c levels
✓ Aim for < 48 mmol/mol (6
...


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-

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First line:
➢ Basal bolus insulin regimen: Long acting + rapid acting (MDI)
✓ Long acting:
○ Insulin detemir BD
○ Or glargine OD if not tolerated or acceptable
✓ Rapid acting insulin analogues before meals
If MDI not possible, use BD mixed insulin regimen
If patients using BD HUMAN mixed insulin regimen, can consider giving trials of BD
ANALOGUE mixed insulin regimen
Non basal bolus (eg: basal only or bolus only) regimens are not recommended for newly
diagnosed T1DM patients
CSII only be offered to adults who suffer disabling hypoglycaemia or who have HbA1c
of 69 mmol/mol (8
...
Only initiated by specialists
...
5%)
➢ Patients on drug-associated with hypoglycemia
- HbA1c: 53 mmol/mol (7
...
5%) or higher, should reinforce advice on diet, lifestyle, and
adherence to antidiabetic drug Tx, should intensify antidiabetic drug Tx
...
(max 2g daily)

Sulphonylureas (SU) - stimulatesSUR1 and EPAC2 of 𝛽
cells of the Islet of Langerhans in
Eg: Gliclazide
pancreas to release insulin
(therefore ineffective if no insulin
t​1/2​ : 10 hrs
production, eg: T1DM, post
pancreatomy)
- Gliclazide does not interact with
EPAC2, less hypoglycaemia

Dose: Initially 40-80 mg OD, increase if
necessary up to 160 mg OD
...
Dose > 160 mg to give in divided
doses
...

- metabolized in liver (P450-CYP2C9)
- can cause weight gain
- ↑ risk of hypoglycaemia in renal/ hepatic
impairment
- SE: n&v, diarrhoea, constipation,
hypoglycaemia (most common in long acting/
excessive dosage)

Glitazones (3rd line)

Dose: 15 - 30 mg OD, adjusted according to
response to 45 mg daily

Eg: Pioglitazone
t​1/2​: 5-6 hrs
Duration: 16-24 hrs

Gliptins
(Eg: sitagliptin,
saxagliptin )
t​1/2​: 10-12 hr
Duration: 12-24 hr

- Increase cellular sensitivity to
insulin (insulin sensitizers)
- Increase glucose uptake
1
...
↑ GLUT (1&4) expression > ↑
peripheral tissues glucose uptake
- Binds directly to DPP4 enzymes
- Reduce inactivation of GLP-1 and
GIP
- Prolongs GLP-1 and GIP activity

- Initial dose are low as GI related SE are often
transient (diarrhoea, dyspepsia)
- Risk of lactic acidosis
- Stop immediately if eGFR < 30, not Rx if
eGFR< 45
- not metabolised, 100% renally eliminated
- can suppress appetite, will not cause weight
gain

-↑ risk of HF (do not Rx if Hx of HF)
- ↑ risk of bladder cancer (ask pt to report
haematuria, dysuria or urinary urgency)
- ↑ fracture risk (avoid in elderly)
- SE: weight gain, liver dysfunction (rare), fluid
retentions
- metabolised in the liver
...
8 hrs
Dipeptidyl
Peptidase-4
inhibitors (DPP4i)
(Eg: linagliptin)

- DPP4 inactivates and degrades
incretin, therefore need its inhibitor

Meglitinides
(Eg: repaglinide,
nateglinide)

- binds to SUR1 receptor on 𝛽
cells and stimulates insulin release

t​1/2​: 1-2 hrs

- more rapid and shorter duration
than SU

- ↑ risk of DKA
- not recommend if eGFR <60, insufficient if
eGFR< 30
-↑ UTI risk (as they increase glucose excretion in
urine)
- can be used in T1DM who x respond well to
insulin
- can cause rapid weight loss

- take 30 mins before meal
- Advantages in pt with poor renal function &
irregular eating habits
- SE: hypoglycaemia, visual disturbances,
diarrhoea, vomiting
- metabolised by liver (CypC28 & CYP3A4)

Intestinal
𝛂-glucosidase
inhibitors (eg:
acarbose)

- slows intestinal glucose
absorption
- competes with dietary
oligosaccharides for 𝛂-glucosidase,
therefore reduce postprandial peak
of blood glucose and stabilize
blood glucose conc throughout the
day

- no effect on insulin action
- SE: diarrhoea, flatulence (undigested
carbohydrates in colon)

GLP-1 Agonists

- protein mimics of incretins
- increase insulin, decrease
glucagon

- 3rd line, in place of glitazone, DPP4i or insulin
- SE: acute pancreatitis
- exenatide excreted by kidney, not for eGFR
<30

Eg: exenatide,
Liraglutide

Diabetic Emergencies and Advices
Hypoglycemia
- It can occur in those treated with insulin and occasionally with a sulfonylurea
drug
...
5 mmol/l or 63 mg/dl)
- Sx:
Autonomic
Sweating
Trembling ​发抖
Tachycardia
Palpitations
Pallor 苍白
-

Neuroglycopenic

Others

Faintness, Loss of concentration,
Hunger
Drowsiness, Visual disturbances,
Headache
Abnormal behavior (agitation,
Tiredness
aggressiveness), Confusion, Coma

Increase alcohol consumption can lead to this due to impaired gluconeogenesis
Tx:
➢ Early Tx: carbohydrate meal (10-20g of rapidly absorbing carbohydrate
...
2g/kg dextrose
➢ Buccal cavity: can apply commercial viscous glucose gel (can also use
jam or honey)- NOT TO USE IF PATIENT UNCONSCIOUS
➢ As soon as the patient is able to swallow, give glucose orally

Diabetic Ketoacidosis (DKA) - arise from poorly controlled T1DM
- A serious problem
...
0 mmol/L or significant ketonuria
➢ Blood glucose > 11
...
3
- Cardinal biochemical features: Hyperglycemia, hyperketonemia, metabolic
acidosis

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Signs and Sx:
➢ Polyuria, thirst (dehydration), weight loss, hypotension, weakness, cold
extremities (hypothermia), nausea, vomiting, tachycardia, leg cramps, air
hunger, blurred vision, the smell of acetone, abdominal pain, confusion,
drowsiness, coma
Management:
➢ Fluid replacement: 0
...
1units/kg : correction of
hyperglycemia and presence of ketones
➢ Potassium: to prevent hypokalemia (none in the first hour unless K level
<3
...
Usually
when blood glucose < 14 mmol/L
...
5 mmol/l)
➢ Mild acidosis but no ketone production
➢ Slight confusion to coma
➢ Sometimes can cause seizures
➢ Plasma Na and K usually normal
➢ Creatinine is high
➢ The fluid deficit is 10L, can lead to circulatory collapse
- Synergistic factors
➢ Insulin deficiency
➢ Increased levels of counter-regulatory or stress hormones
➢ Increase gluconeogenesis and glycogenolysis
➢ Inadequate use of glucose by peripheral tissue

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Tx:
➢ Fluid replacement: to stabilize BP, improve circulation and urine output
(NaCl 0
...
45%) add K if needed
➢ Insulin: given but not aggressive (as the fluid replacement also lowers
plasma glucose levels)
➢ Prophylaxis Tx for thromboembolism

Diabetic CVD Risk
BP Targets:
- T1DM:
➢ No albuminuria: 135/85 mmHg
➢ Albuminuria or features of metabolic syndrome: 130/80 mmHg
- T2DM:
➢ Most ppl: < 140/80 mmHg
➢ High risk: < 130/80 mHg

Cholesterol
- All diabetic patient are assume to have high CVD unless assessed as low using QRISK2
- Start statin (Atorvastatin 20mg)
Antithrombotic therapy
- Aspirin 75 mg OD
- Not for primary due to likelihood to cause GI disorders
Kidney Damage ​(2 or more raised in ACR, >2
...
5 female)
- Start ACEi (or ARB) if confirmed diabetic nephropathy

General Lifestyle Advice
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Balanced diet: low carbohydrates, low fat dairy/ oily fish, high fibre
Control saturated and trans fatty acids
Reduce alcohol intake (max 14 units)
Suitable exercise
Foot care
Smoking cessation
Eye check annually
Maintain good dental hygiene
Consult doctor if infections like UTI, thrushs occur as this can be a sign of worsening
diabetes
Consult pharmacist before buying OTC medications
Diarrhoea could be a s/e of metformin if it is titrated too quickly/ due to autonomic
nervous system damage
Be aware of signs of low blood sugar such as confusions, tiredness, excessive hungers



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