Diabetology

1) Functions of pancreas
i) Islet A cells - release glucagon
ii) Islet B cells - release insulin, C-peptide, amylin, GABA
iii) Islet D cells - release somatostatin
iv) Islet F cells - release pancreatic polypeptide

2) GLUT receptor
i) GLUT-2 receptors : found in pancreas, small intestine,
kidney
: In pancreas, it helps in sensing glucose
and promote insulin release
ii) GLUT-4 receptor : only GLUT transporter that responds to
circulating insulin
: found in adipocytes, myocytes and
cardiomyocytes

3) Metabolic syndrome
a) Definition
- BMI more than 30 or waist circumference more than 94 for
European men and 80 for European women + 2 of the
following
- HDL less than 1.03 for male and 1.29 for female
- LDL more than 1.7
- Glucose more than 5.6 or existing DM
- BP equal or more than 135/85mmHg

b) Management -> diet & orlistat

4) Prediabetes
1) Impaired fasting glucose - decreased hepatic sensitivity but
peripheral sensitivity to insulin is intact
- only fasting glucose is impaired
2) Impaired glucose tolerance - decreased peripheral
sensitivity but intact hepatic sensitivity to insulin
- OGTT is impaired +/- impaired
fasting glucose
**EVERY PREDIABETES : Random blood glucose less than
11.1 + HbA1c = less than 42 mmol**

**The risk of progressing from IGT to diabetes in 5 years is 30-

40%, in 6 years is 60%**
**Drugs that are associated with IGT are atypical
antipsychotics, beta agonist and thiazide diuretics - MORE
SEEN IN RISPERIDONE THAN B2 AGONIST/THIAZIDE**
**Factors that affect HbA1c level -

>

3) Management of prediabetes
- High fibre low fat diet + 150minutes exercise/week
- If resistant -> metformin

5) Antidiabetic medications
a) Metformin
i) Actions : Increases insulin sensitivity and decreases hepatic
gluconeogenesis
ii) Metformin is the only medication that is responsible to
reduce macrovascular complications and improve mortality
iii) Directions : Start off by 500mg, dose increase should be
made every 1 week -> maximum dose is 1g BD
: If experience GI discomfort, try modified
release
: Once dose is more than 2g/24 hours -> most
likely to affect enterohepatic circulation and cause bile salt
malabsorption -> chronic diarrhea
iv) Side effects : Abdominal cramps, nausea and vomitting,
lactic acidosis, acute kidney injury
: Vitamin B12 deficiency
v) NICE guidelines on suspension of metformin
- Stop when eGFR is 30
- When doing any angiographic procedure, stop on day of
procedure and continue 48 hours after that
- Suspend metformin when there is sepsis, dehydration or AKI
- BNF suggest to have 6 weeks cooling off period of metformin
post MI before recommencement (hyperglycaemia during MI
best treated with IV insulin)
vi) Metformin overdose - presents with gastrointestinal upset +
lactic acidosis
- treat with activated charcoal or
gastric decontamination +/- sodium bicarbonate 8.4% when
there is severe lactic acidosis

b) Sulfonylureas
i) Actions : blocks K+ pump of B cells, causes membrane
depolarisation and insulin release
ii) Sulfonylureas are able to reduce the microvascular
complications of diabetes but not macrovascular
iii) Side effects : hypoglycaemia, weight gain, SIADH
iv) Contraindication : pregnancy & breastfeeding
v) Glibenclamide - reduce dose in CKD 1,2, do not use in CKD
3 and more
Gliclazide - can use in CKD stage 1,2,3
Glipizide is the best choice of sulphonylurea in renal
impairment
c) Meglitinides
i) Action : same function as sulfonylureas; binds to K+ channel
but with weaker affinity hence it is short acting
ii) Mostly used in patients with erratic eating pattern (doses
can be missed if patient skips meals)
iii) Kidney friendly as well

d) Pioglitazones
i) Actions : PPAR gamma agonist, reduces peripheral insulin
resistance by increasing the breakdown of free fatty acids
ii) Side effects : Weight gain, fluid retention, osteoporosis,
deranged LFT, bladder cancer
iii) Aim : to reduce 0.5% of HbA1c in 6 months -> if not
achieved can switch to DPP4 inhibitor

e) GLP 1 analogue (liraglutide, exenatide)

i) Actions : They are incretin, hence they increase insulin
secretion, inhibit glucagon secretion, delay gastric emptying
and suppreses appetite
ii) Administered by S/C
iii) Powerful agent for weight loss + improve glycaemic control
without hypoglycaemic events
iv) Side effects : Reduced appetitie, nausea and vomitting,
pancreatitis
v) Used as triple therapy when:
- BMI >35 and will help in medical and psychological issues
of the patient
- BMI <35 and will help with other weight related
comorbidities / insulin therapy is not appropriate due to
occupational implications
vi) NICE suggest to continue GLP 1 if there is 1% reduction in
HbA1c + 3% weight loss in 6 months
vii) Liraglutide can be used in severe renal impairment, not
exenatide

f) DPP4 inhibitor (gliptins)

i) Actions : DPP4 are enzymes that breakdown incretin - DPP4
inhibitor will increase the level of incretin + glucose dependent
glucagon suppresion
ii) Can be used in all CKD with dose adjustment (only
linagliptin does not need dose adjustment)
iii) NICE justified its continuous use if there is 0.5% reduction
in HbA1c in 6 months
iv) Side effects : Reduced appetitie, nausea and vomitting,
pancreatitis

g) SGLT-2 inhibitors
i) Actions : block the SGLT-2 transporter at proximal
convoluted tubule -> glycosuria with calorie dump
ii) Good agent for weight control + improved glycaemic control
+ good BP control (due to Na+ dump)
iii) Side effects : Increased events of UTI, risk of Fournier's
gangrene, Increased risk of bone fracture due to increased
PTH, Increased risk of DKA

6) Insulin (starting an insulin in someone who is insulin

naive - 0.5 to 0.75 x body weight for the total daily units of
insulin)
a) Types of insulin

b) Blood glucose and C-peptide levels

c) Insulin regime in Type 1 Diabetes Mellitus
i) First line : Basal bolus regime
ii) Second line : Mixed insulin (Isophane + rapid acting) given
twice daily (for those who cannot tolerate multiple injections
daily)
iii) Third line : Continuous insulin infusion + bolus on meals
(For those who have disabling hypoglycaemia, persistent
hyperglycaemia)

d) Insulin regime in Type 2 Diabetes Mellitus (metformin is

continued, with the review of need for other anti-diabetic
medications)
i) First line : Intermediate acting NPH insulin given once or
twice daily, with the addition of short acting insulin if HbA1c is
more than 75mmol
ii) Second line : Long acting insulin (If patient needs carers for
insulin, If patient only knows how to administer long acting
insulin, Disabling hypoglycaemia)
iii) Third line : Basal bolus regime
e) Counselling on insulin use in patients who are unwell

7) Type 1 Diabetes Mellitus

a) Features
- BMI <25
- Age less than 50 years old
- Rapid weight loss
- Ketosis
- Presence of autoimmune antibodies (Anti-GAD, Anti-ICA) or
presence of autoimmune disease in family history

b) HLA DR4 is affected more than HLA DR3

c) The risk of T1DM developing in patients with one affected

parent is 3-6%
with two affected
parent is ~40%
with one affected
twin is 30-50%
d) Indications for pancreatic or islet cell transplantation in
T1DM
- Severe hypoglycaemia not responded to any treatment
- Patient with RCC that has received transplant and under
immunosuppresion hence having suboptimal diabetes control

e) Self-monitoring and follow up for T1DM

8) Type 2 Diabetes Mellitus

a) Management

b) Self-monitoring and follow up for T2DM

9) Diabetic retinopathy
a) Can be divided into :
i) Background - microaneurysm, dot and blot haemorrhage
ii) Pre-proliferative - venous beading, haemorrhage, cotton
wool spots
iii) Proliferative - new vessel formation with haemorrhage

b) All diaebetic patient should be referred to ophtalmologist

and they should be seen within 3 months, if no urgent needs
then can be reviewed annually
Urgent referrel should be made for -> Proliferative or
macular edema
-> Rubeosis iridis, retinal
detachment, vitreous haemorrhage, acute reduction in visual
acuity
** Acute changes in visual acuity in patient who is newly
diagnosed with diabetes is due to changes in osmotic
pressure in lens**

10) Diabetic nephropathy

a) Mechanism : Non enzymatic glycosylation of the basement
membrane as well as stiffening of efferent arteriole ->
increased eGFR -> Glomerulosclerosis -> falling eGFR with
proteinuria
b) Biopsy : Kimmelstiel Wilson nodule seen
c) Management : ACE-inhibitor +/- Non-DHP Calcium channel
blocker (Diltiazem)

11) Hypertension and statins in diabetes

12) Diabetic neuropathy

a) Non enzymatic glycosylation of the axon bodies leads to
sensorimotor neuropathies
b) Symptoms : paraesthesia in extremities in glove and
stocking pattern + dyaesthesia especially in night + decreased
pain sensation + decreased proprioreception and vibration
sense + muscle weakness + hyporeflexia
c) Management
i) Duloxetine is first line - contraindicated in glaucoma, use of
other serotonergic agent such as tramadol
ii) Amitryptilline - contraindicated in glaucoma, urinary
retention, LBBB
iii) Pregabalin - most suitable in patients having glaucoma /
renal impairment / urinary retention / using any other
serotonergic agent

*Diabetic mononeuropathy*
- Carpal tunnel syndrome (median nerve)
- Meralgia paraesthetica (lateral cutaneous nerve of thigh)
- Foot drop (common peroneal nerve)
- Diplopia (CN 3 palsy with intact pupillary response)

*Diabetic amyotrophy*
- Patient presents with extreme pain of proximal muscle with
paraesthesia, tender to touch, anorexia and weight loss,
areflexia, also having difficulty sleeping at night due to pain
- Management : analgesia + conversion to insulin

*Charcot foot*
- Presents with acutely swollen feet + tender + erythema +
unable to weight bear (need to rule out cellulitis!) -> DONE BY
INDIUM LABELLED WHITE CELL SCAN
- Mechanism : symphatetic dysfunction causing excessive
blood flow to feet and increasing osteoclast activity
- Management : Immobilisation casting for 3-6 months ->
Removable casting for 4-6 months (during this period patient
may take bisphosphonates to reduce bone resorption)

*Neuropathic vs Ischaemic foot (based on tenderness, pulse,

pain)

Difference between arterial ulcer and neuropathic ulcer

*Diabetic foot*
i) If only calluses present -> glycemic control + foot care +
modifiable risk control (GFM)
ii) If 2 of callus, deformity or loss of protective sensation ->
GFM + statins and antiplatelets + supervised exercise
programme
iii) If all 3 present or previous ulceration/ampuatation -> GFM
+ statins and antiplatelets + supervised exercise programme +
foot protection service for nail care and callus debridement +/-
wound debridement or amputation

13) Diabetic autonomic neuropathy

- Causes gastroparesis (best managed by domperidone or
erythromycin)
- Postural hypotension (best managed by fludrocortisone or
compression stockings)
- Erectile dysfunction -> If DM + hypogonatrophic
hypogonadism (Low testosterone + Low FSH) : THINK OF
HEMOCHROMATOSIS (PLEASE DO FERRITIN &
TRANSFERRIN SATURATION)
-> If just hypotestosteronism (low
testosterone normal + normal FSH) : transdermal testosterone
-> PDE-5 inhibitor

14) Diabetes mellitus & Ramadan

i) Should take long acting carbs on Suhoor
ii) If taking metformin, 1/3 dose in Suhoor and 2/3 dose in Iftar
iii) If taking sulphonylurea, take larger dose during Iftar (if
possible switch to once daily dose after Iftar)
iv) No changes to pioglitazones

15) Diabetes mellitus & DVLA

i) Group 2 drivers can drive with insulin if
- They possess good hypoglycaemic awareness
- They do not have hypoglycaemic episode in the last 12
months
- They have good glycaemic control
- They have good vision
- They maintain good glucose monitoring

ii) Group 1 driver if they are taking oral medications or GLP -

no need to inform DVLA
iii) Group 1 driver on taking insulin can drive without informing
DVLA if they:
- Have not more than 1 episode of hypoglycaemia
- Possess good hypoglycaemic awareness
- No visual impairment

*If had two or more hypoglycaemic episodes -> need to inform

DVLA and stop driving*
*If had two or more hypoglycaemic episodes that requires help
-> surrender licence*
16) Hypoglycaemia
a) If conscious and able to swallow -> Glucotab 3x
b) If conscious but unable to swallow -> Glucogel 3x
c) If unconscious or incooperative -> IM Glucagon 1mg or
10% 200mL glycose or 20% 100ml glucose STAT
d) Once blood glucose more than 4mmol -> give long acting
carbohydrate

*Factitious hypoglycaemia - Abuse of insulin (Measure C-

peptide level : Synthesised insulin do not have C-peptide)

17) Diabetic ketoacidosis

a) Causes (6 I)
i) Infection
ii) Inflammation (Pancreatitis, cholecystitis)
iii) Intoxication (Alcohol, Cocaine, Amphetamine)
iv) Infarction (Myocardial infarction, stroke)
v) Iatrogenic (Drugs such as steroids, thiazides, atypical
antipsychotics, beta symphatomimetics / surgery )
vi) Reduced insulin intake

b) Pathophysiology (2 mechanisms: Reduced insulin OR

Increased Stress)
c) Symptoms (based on combination of 2 factors : Increased
ketone that precipitate acidemia + Dehydration )
d) Diagnosis of DKA (must fulfill all 3)
i) Glucose of more than 11.1 mmol
ii) Ketones more or equal to 3, urine ketones 2+ or more
iii) Acidosis evidenced by pH less than 7.3 or bicarb less than
15
3) High severity that may need ITU/HDU support
- pH less than 7
- Bicarbonate less than 5
- Ketones more than 6
- Anion gap more than 16
- K+ less than 3.5
- Tachycardia + Hypotension
- Altered mental status or GCS less than 12
- SpO2 less than 92%

4) Investigation (make sure patient have 2 large bore cannula

+ catheter)
- ECG + Urinalysis with MSU
- FBC, U&E, LFT, CRP, ABG, blood culture
- CXR

5) Management
i) IV fluids (if in shock then bolus 500mL first) + Potassium
replacement if needed in second bag onwards
ii) Fixed rate insulin infusion (0.5 units/kg/hour of 50 units
atrapid made up to 50ml of NaCL solution) -> Once blood
glucose less than 14, start glucose infusion 10% at
125ml/hour
iii) Cathetrise and strictly monitor the urine output
iv) Thromboprophylaxis
vi) Continue all long acting insulin at regular dose & time

6) Aim of treatment
- Aim to lose 3mmol of glucose with 0.5 mmmol of ketone loss
or 3 mmol of bicarb rise (Guidelines suggest that insulin
infusion rate should only be increased if
blood ketones are not falling at >0.5 mmol/h)

18) Hyperosmolar Hyperglycaemic state

a) Definition
- Hyperglycaemia (Blood glucose of more than 30mmol but
without significant ketonemia (3mmol or less) or acidemia (pH
more than 7.3 or bicarb more than 15)
- Hyperosmolar (more or equal to 320mosm/kg)
- Hypovolemia

b) Typically this patient is very largely fluid deficit (almost 10l)

hence the management is fluid replacement with potassium
supplement if needed + thromboprophylaxis + continue any
long acting insulin
(IV 0.9% sodium chloride is first line -> if plasma osmolarity is
no longer declining or high glucose still -> 0.45% sodium
chloride infusion)
- Only add insulin 0.05 unit/kg/hour if ketonemia more than 1
or urine ketone 2+ or more / blood glucose not falling with IV
fluid alone (OTHERWISE DO NOT START IV INSULIN)